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Background: Depression is a widespread disorder with severe impacts for individuals and society, especially in its chronic form. Current treatment approaches for persistent depression have focused primarily on reducing negative affect and have paid little attention to promoting positive affect. Previous studies have shown that metta meditation increases positive affect in chronically depressed patients. Results from previous trials provide evidence for the efficacy of a stand-alone metta meditation group treatment in combination with mindfulness-based approaches. Further research is needed to better understand the implementation of meditation practice into everyday life. Therefore, mindfulness and metta meditation in a group setting are combined with individual cognitive behavioral therapy (CBT) into a new, low-intensity, cost-effective treatment (“MeCBT”) for chronic depression. Methods/design: In this single-center, randomized, observer-blinded, parallel-group clinical trial we will test the efficacy of MeCBT in reducing depression compared to a wait-list control condition. Forty-eight participants in a balanced design will be allocated randomly to a treatment group or a wait-list control group. Metta-based group meditation will be offered in eight weekly sessions and one additional half-day retreat. Subsequent individual CBT will be conducted in eight fortnightly sessions. Outcome measures will be assessed at four time points: before intervention (T0); after group meditation (T1); after individual CBT (T2); and, in the treated group only, at 6-month follow-up (T3). Changes in depressive symptoms (clinician rating), assessed with the Quick Inventory of Depressive Symptoms (QIDS-C) are the primary outcome. We expect a significant decline of depressive symptoms at T2 compared to the wait-list control group. Secondary outcome measures include self-rated depression, mindfulness, benevolence, rumination, emotion regulation, social connectedness, social functioning, as well as behavioral and cognitive avoidance. We will explore changes at T1 and T2 in all these secondary outcome variables. Discussion: To our knowledge this is the first study to combine a group program focusing on Metta meditation with stateof-the art individual CBT specifically tailored to chronic depression. Implications for further refinement and examination of the treatment program are discussed. Trial registration: ISRCTN, ISRCTN97264476. Registered 29 March 2018 (applied on 14 December 2017)—retrospectively registered.
Friedauer, Lucie ; Rezny-Kasprzak, Beata ; Steinmetz, Helmuth ; Du Mesnil de Rochemont, Richard Klaus Frieder ; Förch, Christian
Background and purpose: Superficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern. Methods: In all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for “hemosiderosis” and “superficial siderosis.” Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies. Results: Forty-two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non-symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected. Conclusions: Persisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.
Friedauer, Lucie ; Rezny-Kasprzak, Beata ; Steinmetz, Helmuth ; Du Mesnil de Rochemont, Richard Klaus Frieder ; Förch, Christian
Background and purpose: Superficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern. Methods: In all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for “hemosiderosis” and “superficial siderosis.” Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies. Results: Forty-two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non-symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected. Conclusions: Persisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.
Friedmann, Franziska ; Santangelo, Philip ; Ebner-Priemer, Ulrich ; Hill, Holger ; Neubauer, Andreas B. ; Rausch, Sophie ; Steil, Regina ; Müller-Engelmann, Meike ; Kleindienst, Nikolaus ; Bohus, Martin ; Fydrich, Thomas ; Priebe, Kathlen
Early experiences of childhood sexual or physical abuse are often associated with functional impairments, reduced well-being and interpersonal problems in adulthood. Prior studies have addressed whether the traumatic experience itself or adult psychopathology is linked to these limitations. To approach this question, individuals with posttraumatic stress disorder (PTSD) and healthy individuals with and without a history of child abuse were investigated. We used global positioning system (GPS) tracking to study temporal and spatial limitations in the participants’ real-life activity space over the course of one week. The sample consisted of 228 female participants: 150 women with PTSD and emotional instability with a history of child abuse, 35 mentally healthy women with a history of child abuse (healthy trauma controls, HTC) and 43 mentally healthy women without any traumatic experiences in their past (healthy controls, HC). Both traumatized groups—i.e. the PTSD and the HTC group—had smaller movement radii than the HC group on the weekends, but neither spent significantly less time away from home than HC. Some differences between PTSD and HC in movement radius seem to be related to correlates of PTSD psychopathology, like depression and physical health. Yet group differences between HTC and HC in movement radius remained even when contextual and individual health variables were included in the model, indicating specific effects of traumatic experiences on activity space. Experiences of child abuse could limit activity space later in life, regardless of whether PTSD develops.
Muskelskelett-Erkrankungen (MSE) bei Büroangestellten sind häufig mit einer höheren Muskelspannung und einer eingeschränkten Bewegungsreichweite assoziiert. Ein hohes präventives Potential haben daher Dehntrainings, da durch eine muskuläre Relaxation die Muskelspannung reduziert werden kann und gleichzeitig auf psychischer Ebene eine Möglichkeit zur Entspannung geboten wird. Auch im Rahmen von Maßnahmen der betrieblichen Gesundheitsförderung (BGF), die im Kontext der Arbeitsmedizin immer mehr an Bedeutung gewinnt, stellen Dehntrainings einen erfolgsversprechenden Ansatz dar. Allerdings sind die bislang überprüften Ansätze sehr zeitaufwendig, was zu einem erheblichen Verlust an Arbeitszeit führt. Ein Dehnprogramm mit geringem Zeitaufwand ist das gerätegestützte „five-Business“ Dehntraining, bei dem in fünf Übungen ganze Muskelketten intensiv gedehnt werden. Da das Gerät individuell einstellbar ist, ist die Trainingsintensität standardisiert und gleichzeitig individualisiert. Ziel dieser Studie war daher das five-Business“ Dehntraining auf seine Wirksamkeit hinsichtlich einer Verbesserung der Beweglichkeit, der Lebensqualität und von MSE zu evaluieren. Im Rahmen dieser Dissertation wurde in der ersten Publikation zunächst eine konkrete Methode erarbeitet, die anschließend als 12-wöchige Intervention bei Büroangestellten (Training zwei Mal wöchentlich für je 10 Minuten) umgesetzt wurde. Für die zweite Publikation wurden Veränderungen in der Beweglichkeit im Anschluss an die Intervention und deren Abhängigkeit von soziodemographischen und anthropometrischen Faktoren analysiert. Dazu wurden fünf Beweglichkeitstests verwendet: der Finger-Boden-Abstand und die Lateralflexion wurden mit einem Maßband evaluiert, während die Gelenkwinkel beim modifizierten Schultertest nach Janda, dem modifizierten Thomas Test und der Retroflexion des Rumpfes nach Janda mit einem digitalen Inklinometer gemessen wurden. Insgesamt nahmen 216 (79w; 137m) Probanden im Alter von 44,81 ± 10,55 Jahren freiwillig an der Studie teil. Die Probanden waren 1,76 ± 0,09 m groß und wogen 78,03 ± 15,11 kg. Die mittleren Unterschiede zeigten, dass die Probanden im Schultertest (rechts: 2,1 ± 7,7°, p = 0,001; links: 2,7 ± 10,11°, p = 0,001), in der nach Janda modifizierten Retroflexion des Rumpfes (5,4 ± 8,6°, p<0,001), im Finger-Boden-Abstand (-1,9 ± 4,0 cm, p<0,001) und in der Lateralflexion relativ zur Körpergröße (rechts: -0,004 ± 0,01, p = 0,002; links: -0,004 ± 0,01, p<0,001) Zuwächse im Bewegungsausmaß erzielten. Im Thomas Test zeigten die Probanden eine Abnahme der Flexibilität (rechts: -2,1 ± 4,5°, p<0,001; links: -1,2 ± 4,7°, p = 0,001). In allen Tests zeigten die Effektstärken geringe bis mittlere Effekte (d = 0,24 - 0,62). Probanden mit unterdurchschnittlicher Beweglichkeit im Prä-Test zeigten die höchsten Beweglichkeitszuwächse. Weder Alter, Körpergröße, Gewicht, Body-Mass-Index (BMI) noch Geschlecht hatten einen signifikanten Einfluss auf die Beweglichkeitsveränderungen. Insgesamt kann für das „five-Business“ Dehntraining resümiert werden, dass es effektiv zur Beweglichkeitssteigerung beiträgt. Der vergleichsweise geringe Zeitaufwand ist ausreichend, um insbesondere bei unterdurchschnittlicher Flexibilität zu einem Gewinn an Bewegungsreichweite beizutragen. Da weder soziodemographische noch anthropometrische Faktoren die Beweglichkeitsveränderungen signifikant beeinflussten, kann das „five-Business“ Dehntraining auch bei heterogen zusammengesetzten Kollektiven angewendet werden. Somit ist es als wirksame Dehnintervention als BGF Maßnahme für schreibtischgebundenen Büroangestellte einsetzbar.
Fräulin, Laura ; Holzgreve, Fabian Christian ; Brinkbäumer, Mark ; Dziuba, Anna ; Friebe, David ; Klemz, Stefanie ; Schmitt, Marco ; Theis A., Anna-Lena ; Tenberg, Sarah ; Mark, Anke van ; Maurer-Grubinger, Christian ; Ohlendorf, Daniela Maren
Background: In clinical practice range of motion (RoM) is usually assessed with low-cost devices such as a tape measure (TM) or a digital inclinometer (DI). However, the intra- and inter-rater reliability of typical RoM tests differ, which impairs the evaluation of therapy progress. More objective and reliable kinematic data can be obtained with the inertial motion capture system (IMC) by Xsens. The aim of this study was to obtain the intra- and inter-rater reliability of the TM, DI and IMC methods in five RoM tests: modified Thomas test (DI), shoulder test modified after Janda (DI), retroflexion of the trunk modified after Janda (DI), lateral inclination (TM) and fingertip-to-floor test (TM).
Methods: Two raters executed the RoM tests (TM or DI) in a randomized order on 22 healthy individuals while, simultaneously, the IMC data (Xsens MVN) was collected. After 15 warm-up repetitions, each rater recorded five measurements.
Findings: Intra-rater reliabilities were (almost) perfect for tests in all three devices (ICCs 0.886–0.996). Inter-rater reliability was substantial to (almost) perfect in the DI (ICCs 0.71–0.87) and the IMC methods (ICCs 0.61–0.993) and (almost) perfect in the TM methods (ICCs 0.923–0.961). The measurement error (ME) for the tests measured in degree (°) was 0.9–3.3° for the DI methods and 0.5–1.2° for the IMC approaches. In the tests measured in centimeters the ME was 0.5–1.3cm for the TM methods and 0.6–2.7cm for the IMC methods. Pearson correlations between the results of the DI or the TM respectively with the IMC results were significant in all tests except for the shoulder test on the right body side (r = 0.41–0.81).
Interpretation: Measurement repetitions of either one or multiple trained raters can be considered reliable in all three devices.
Six dentin adhesives were tested in vitro regarding their cytotoxicity on human fibroblasts. The adhesives Hybrid Bond, One-up Bond F Plus, AdheSE, Clearfil SE Bond, Optibond Solo Plus and Syntac were eluted with culture medium as single or sequentially applied adhesive part for 24 h. 75 Petri dishes were produced per group. They were evaluated triangulated, comprising the quantitative evaluation (105 ones) to determine “viable”, “dead” and “debris” cells with the use of a cell-counter and the reactivity index was also identified based on the qualitative assessment (420 ones). One-up Bond F Plus, AdheSE and Clearfil SE Bond showed a statistical difference of viable cells to the cell control. For One-up Bond F Plus, statistically, differences compared to hybrid bond and Syntac were also found. All the adhesives except One-up Bond F Plus showed significant differences between single and sequentially applied adhesive part regarding the quantitative evaluation. The test material showed a moderate grade of cytotoxicity. As a result, a statistically significant difference of the cytotoxicity between the self-etch and etch-and-rinse adhesives cannot be demonstrated regarding the qualitative evaluation and the reactivity index, but the differences between sequentially applied and single applied components can be proved.
Strain localization in the lithosphere and the formation, evolution, and maintenance of resulting plate boundaries play a crucial role in plate tectonics and thermo‐chemical mantle convection. Previously activated lithospheric deformation zones often appear to maintain a “memory” of weakening, leading to tectonic inheritance within plate reorganizations including the Wilson cycle. Different mechanisms have been proposed to explain such strain localization, but it remains unclear which operates on what spatio‐temporal scales, and how to best incorporate them in large‐scale mantle convection models. Here, we analyze two candidates, (1), grain‐size sensitive rheology and, (2), damage‐style parameterizations of yield, stress which are sometimes used to approximate the former. Grain‐size reduction due to dynamic recrystallization can drive localization in the ductile domain, and grain growth provides a time‐dependent rheological hardening component potentially enabling the preservation of rheological heterogeneities. We compare the dynamic weakening and hardening effects as well as the timescales of strength evolution for a composite rheology including grain‐size dynamics with a pseudo‐plastic rheology including damage‐ (or “strain”‐) dependent weakening. We explore the implications of different proposed grain‐size evolution laws, and test to which extent strain‐dependent rheologies can mimic the weakening and hardening effects of the more complex micro‐physical behavior. Such an analysis helps to better understand the parallels and differences between various strain‐localization modeling approaches used in different tectonics and geodynamics communities. More importantly, our results contribute to efforts to identify the key ingredients of strain‐localization and damage hysteresis within plate tectonics and how to represent those in planetary‐scale modeling.
Using a structural life-cycle model, we quantify the long-term impact of school closures during the Corona crisis on children affected at different ages and coming from households with different parental characteristics. In the model, public investment through schooling is combined with parental time and resource investments in the production of child human capital at different stages in the children's development process. We quantitatively characterize both the long-term earnings consequences on children from a Covid-19 induced loss of schooling, as well as the associated welfare losses. Due to self-productivity in the human capital production function, skill attainment at a younger stage of the life cycle raises skill attainment at later stages, and thus younger children are hurt more by the school closures than older children. We find that parental reactions reduce the negative impact of the school closures, but do not fully offset it. The negative impact of the crisis on children's welfare is especially severe for those with parents with low educational attainment and low assets. The school closures themselves are primarily responsible for the negative impact of the Covid-19 shock on the long-run welfare of the children, with the pandemic-induced income shock to parents playing a secondary role.
Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis
(2020)
Fuhrmann, Dominik Christian ; Mondorf, Antonia Maria ; Beifuß, Josefine ; Jung, Michaela ; Brüne, Bernhard
Highlights
• Hypoxia decreases NCOA4 transcription in primary human macrophages.
• NCOA4 mRNA is a target of miR-6862-5p.
• Lowering NCOA4 increases FTMT abundance under hypoxia.
• FTMT and FTH protect from ferroptosis.
• Tumor cells lack the hypoxic decrease of NCOA4 and fail to stabilize FTMT.
Abstract
Cellular iron, at the physiological level, is essential to maintain several metabolic pathways, while an excess of free iron may cause oxidative damage and/or provoke cell death. Consequently, iron homeostasis has to be tightly controlled. Under hypoxia these regulatory mechanisms for human macrophages are not well understood. Hypoxic primary human macrophages reduced intracellular free iron and increased ferritin expression, including mitochondrial ferritin (FTMT), to store iron. In parallel, nuclear receptor coactivator 4 (NCOA4), a master regulator of ferritinophagy, decreased and was proven to directly regulate FTMT expression. Reduced NCOA4 expression resulted from a lower rate of hypoxic NCOA4 transcription combined with a micro RNA 6862-5p-dependent degradation of NCOA4 mRNA, the latter being regulated by c-jun N-terminal kinase (JNK). Pharmacological inhibition of JNK under hypoxia increased NCOA4 and prevented FTMT induction. FTMT and ferritin heavy chain (FTH) cooperated to protect macrophages from RSL-3-induced ferroptosis under hypoxia as this form of cell death is linked to iron metabolism. In contrast, in HT1080 fibrosarcome cells, which are sensitive to ferroptosis, NCOA4 and FTMT are not regulated. Our study helps to understand mechanisms of hypoxic FTMT regulation and to link ferritinophagy and macrophage sensitivity to ferroptosis.
The aim of this paper is to examine how Adorno's aesthetic and musicological thinking was received in Czech and Slovak musicology in the decades between the 60s and the 80s. The focus is on the Czech and Slovak translation of some of Adorno’s musicological treatises and lectures – especially those concerning his views on the Second Vienna School and the musical poetics of its immediate successors – which were published in former Czechoslovakia. The study offers an interesting perspective on Adorno’s relatively unknown lecture Form der neuen Musik (1965) and its related, although not identical, Czech version Formové princípy súčasnej hudby [Formal Principles of Contemporary Music] (1966) as well as on his discussion with some Slovak composers and musicologists published as Dnes je možné iba radikálne kritické myslenie [Today, Only Radical Critical Thinking is Possible] (1967). The study also considers other scientific texts by Adorno in relation to the above-mentioned translations of his works. The analysis, reflection, and interpretation of Adorno’s works in former Czechoslovakia, as well as their contemporary reception, turn out to be sporadic in the examined period. The purpose of this research is to revive awareness of their significance and to give a new impulse to their reassessment within the current musicological and philosophical reflection.
In the1960s, texts by the prominent German philosopher and musicologist Theodor W. Adorno were translated into the Czech and Slovak language. This was only possible due to the more relaxed social and political atmosphere of those years. The translated essays were published in professionally-oriented periodicals. This paper is aimed to map and evaluate the reception of Adorno’s translatedworks in Czechoslovakia. Although these texts embraced above all Adorno’s work in the sociology of philosophy, aesthetics of literature and musicology, this paper is mainly focused on Adorno’s musicological texts. Albeit mostly regarded as an original and extremely versatile author in Czechoslovakia, Adorno was also criticised on the background of Marxist-Leninist philosophy. In order to evaluate the reception of Adorno’s ideas in the Czech and Slovak environment, it is methodologically necessary to adopt a broader aesthetic-philosophical perspective that enables us to account for Adorno’s endorsement of the Marxist philosophy pursued at Frankfurt School of Philosophy.
This article sheds light upon the role of the audience in the construction and amendment of populist representative claims that in themselves strengthen representative-represented relationships and simultaneously strengthen ties between the represented who belong to different constituencies. I argue that changes in populist representative claims can be explained by studying the discursive relationship between a populist representative and the audience as a conversation in which both poles give and receive something. From this perspective, populist representative claims, I also argue, can be understood as acts of bonding with the intended effect of constituting ‘the people,’ and inputs from the audience can be seen as conversational exercitives. Populist appeals therefore may change when the audience enacts new permissibility facts and signals to populist representatives that there is another way to strengthen relationships between several individuals belonging to otherwise-different constituencies.
To understand the development of public health in Croatia, there are newer insights into the life and work of John the Baptist Lalangue. John the Baptist Lalangue is most valued for implementation of the imperial law on public health and promotion of midwifery in Croatia during the second half of the 18th century. Lalangue is the author of the first printed medical textbook in Croatian, published in 1776, entitled Medicina ruralis iliti Vrachtva ladanyszka, za potrebochu musev, y sziromakov Horvatczkoga orszaga y okolu nyega, blisnesseh mest, Trattnern, Varaždin. In the same period, Lalangue published the first Croatian midwifery textbook entitled Brevis institute de reobstetritia iliti kratek navuk od mestrie pupkorezne za potrebochu muskeh y sziromaskeh ladanovskaya horvatskoga orszaga y okolo nyega blisnesseh sztrankih, Trattnern, Zagreb. In 1779, Lalangue published his balneological debut in Croatian, the book Tractatus de aquis medicati Regnorum Croatiae et Slavoniae Iliti Izpiszavanye vrachtvenih vod Horvatzkoga y Slavonskoga orszaga y od nachina nye vsivati za potrebochu lyudih, Trattnern, Zagreb. Lalangue’s works were used in systematic training and education of midwives and they, as well as Lalangue, have an inevitable place in the history of Croatian midwifery. During his life and work, John the Baptist Lalangue made immeasurable contribution to the development of Croatian public health.
Background: Fingolimod is used for immune therapy in patients with multiple sclerosis. Long-term treatment is associated with a small increase in the risk of herpes virus reactivation and respiratory tract infections. Patients with coronavirus disease 2019 (COVID-19) under Fingolimod treatment have not been described.
Methods and results. We report a 57-year old female patient with a relapsing remitting multiple sclerosis under fingolimod treatment who experienced a severe COVID-19 infection in March 2020 (Extended Disability Status Scale: 2.0). Having peripheral lymphopenia typical for fingolimod treatment (total lymphocytes 0.39/nL [reference range 1.22-3.56]), the patient developed bilateral interstitial pneumonia with multiple ground-glass opacities on chest CT. Fingolimod medication was stopped. On the intensive care unit, non-invasive ventilation was used to provide oxygen and ventilation support regularly. Over the following two days, oxygenation improved, and the patient was transferred to a normal ward five days after admission.
Conclusion: The implications fingolimod has on COVID-19 are complex. As an S1P analogue, fingolimod might enhance lung endothelial cell integrity. In addition, in case of a so-called cytokine storm, immunomodulation might be beneficial to reduce mortality. Future studies are needed to explore the risks and therapeutic effects of fingolimod in COVID-19 patients.
Die in der renommierten Reihe der Göttinger Orientforschungen erschienene Arbeit ist einem Thema gewidmet, das in der ägyptologischen Forschung trotz seiner offenkundig hohen Relevanz und Bedeutung lange Zeit ziemlich vernachlässigt wurde: dem vielschichtigen und facettenreichen Phänomen des Reisens im Alten Ägypten. Wie dem Untertitel zu entnehmen ist, werden dabei neben einer Vielzahl von relevanten, unter dem weiten Begriffsfeld "Reisekultur" subsumierten Aspekten insbesondere praktische Fragen nach den Fortbewegungs- und Transportmitteln in pharaonischer Zeit in den Vordergrund gestellt, doch kommt das Spektrum der textlich belegten individuellen Reisenden selbst und ihrer verschiedenen Motivationen und Destinationen keineswegs zu kurz. In der Tat kann das schmale Niltal als langgestreckte Flussoase mitsamt den unmittelbar angrenzenden Wüstengebieten in Ost und West einerseits und dem breiten, von zahlreichen Kanälen und Verbindungswegen durchzogenen Nildelta im Norden andererseits als eine naturräumlich besonders "verkehrsträchtige" Region gelten, die durch die landschaftlichen Gegebenheiten besondere Möglichkeiten bot, aber auch spezielle, nicht zuletzt verkehrstechnische und logistische Anforderungen an Reisen und Reisende in pharaonischer Zeit stellte – vor allem, wenn das Reiseziel außerhalb der eigenen kulturellen Grenzen lag. Zudem erlaubt das außerordentlich lange Bestehen der pharaonischen Hochkultur im Verbund mit einer relativ reichen Quellenlage kulturhistorisch aufschlussreiche diachrone Betrachtungen, etwa im Hinblick auf die Entwicklung von Reise- und Transportmitteln, den Ausbau des Verkehrs- und Wegesystems oder allgemeine sozio-ökonomische Prozesse, die mit Fragen der Mobilität zusammenhängen. ...
Physical activity counseling in primary health care is regarded as a useful complementary preventive and therapeutic measure and is advocated by leading public health institutions. This integrative review summarizes the available data on physical activity counseling in primary care in Germany. A systematic literature search in various databases (peer reviewed and grey literature) was carried out for quantitative and qualitative studies on physical activity counseling and use of “Exercise on Prescription”. The 25 studies included show a very high methodological diversity and, in some cases, considerable risks of bias, with limited comparability across studies. Counseling was provided in all studies by physicians. They report frequent physical activity counseling, which is partly confirmed and partly refuted by patient data. The use of “Exercise on Prescription” is at a very low level. Information on the frequency of physical activity counseling in Germany varies depending on data source and is sometimes contradictory. Our review provides a synthesis of various perspectives on routine physical activity counseling in primary care in Germany. Future studies using standardized and validated instruments in representative samples are needed to further knowledge on counseling and to be able to establish trends in prevalence. Strengthening the topics of physical activity and health and physical activity counseling in medical curriculum is strongly recommended.
Der Erforschung der Bronzestatuetten der Frühen Neuzeit im 19. Jahrhundert wurde bisher wenig Beachtung geschenkt. Die erste umfassende stilkritische Gattungsmonographie mit dem Titel „Die Italienischen Bronzestatuetten der Renaissance“ wurde von Wilhelm von Bode (1845 - 1929) verfasst. Er veröffentlichte diese kurz nach der Eröffnung des neu gebauten Kaiser-Friedrich-Museums in Berlin 1904. Maßgeblich durch Bode geprägt, zeigte dieses Museum erstmals Bronzestatuetten der Renaissance und des Barock als eine eigenständige Skulpturengattung. Die wissenschaftshistorische Frage nach der Entstehung der stilkritischen Kleinbronzenforschung zwischen 1871 und 1904 steht daher im Kontext der Berliner Museums- und Sammlungsgeschichte, mit dem Schwerpunkt auf der Erwerbung der Kleinbronzen, deren Zuschreibung und Präsentation. Ein 1883 veröffentlichtes Konzept für ein Berliner „Renaissancemuseum“ verknüpfte mit der Sammlungspräsentation die Erwartung, der ästhetischen Selbstvergewisserung ihrer Betrachter zu dienen. Die Kunst der Renaissance, darunter auch die Bronzestatuetten, war dabei Sinnbild des modernen bürgerlichen Autonomiebestrebens. Diesem Leitbild stand die Arbeitsorganisation ihres Erforschers Wilhelm von Bode gegenüber, die seine historische Theorie und stilkritische Methode prägte. Neben dem Einfluss Jakob Burckharts und dessen „Kunstgeschichte nach Aufgaben“ geben Bodes Briefwechsel mit Theodor von Frimmel, Louis Courajod und dem Sammler Fürst Johann II. von und zu Liechtenstein Aufschluss über sein Forschungsinteresse. So fokussierte er seine Forschung auf die Statuetten des Bildhauers und Bronzemodelleurs Bertoldo di Giovannis. Hier lässt sich der Wandel von einer kulturgeschichtlichen Perspektive hin zu einer historisch-kritischen Analyse der Statuetten verfolgen. Mit der Transformation der so genannten „Kopienkritik“ aus der klassischen Archäologie und mit Hilfe der Fotografie entwickelte Wilhelm von Bode eine Methode für die stilkritische Analyse der kleinformatigen Skulpturen.
Gagl, Benjamin ; Richlan, Fabio ; Ludersdorfer, Philipp ; Sassenhagen, Jona ; Eisenhauer, Susanne ; Gregorova, Klara ; Fiebach, Christian
To characterize the left-ventral occipito-temporal cortex (lvOT) role during reading in a quantitatively explicit and testable manner, we propose the lexical categorization model (LCM). The LCM assumes that lvOT optimizes linguistic processing by allowing fast meaning access when words are familiar and filter out orthographic strings without meaning. The LCM successfully simulates benchmark results from functional brain imaging. Empirically, using functional magnetic resonance imaging, we demonstrate that quantitative LCM simulations predict lvOT activation across three studies better than alternative models. Besides, we found that word-likeness, which is assumed as input to LCM, is represented posterior to lvOT. In contrast, a dichotomous word/non-word contrast, which is assumed as the LCM’s output, could be localized to upstream frontal brain regions. Finally, we found that training lexical categorization results in more efficient reading. Thus, we propose a ventral-visual-stream processing framework for reading involving word-likeness extraction followed by lexical categorization, before meaning extraction.
Gagl, Benjamin ; Sassenhagen, Jona ; Haan, Sophia ; Gregorova, Klara ; Richlan, Fabio ; Fiebach, Christian
Most current models assume that the perceptual and cognitive processes of visual word recognition and reading operate upon neuronally coded domain-general low-level visual representations – typically oriented line representations. We here demonstrate, consistent with neurophysiological theories of Bayesian-like predictive neural computations, that prior visual knowledge of words may be utilized to ‘explain away’ redundant and highly expected parts of the visual percept. Subsequent processing stages, accordingly, operate upon an optimized representation of the visual input, the orthographic prediction error, highlighting only the visual information relevant for word identification. We show that this optimized representation is related to orthographic word characteristics, accounts for word recognition behavior, and is processed early in the visual processing stream, i.e., in V4 and before 200 ms after word-onset. Based on these findings, we propose that prior visual-orthographic knowledge is used to optimize the representation of visually presented words, which in turn allows for highly efficient reading processes.
Gagl, Benjamin ; Sassenhagen, Jona ; Haan, Sophia ; Gregorova, Klara ; Richlan, Fabio ; Fiebach, Christian
Most current models assume that the perceptual and cognitive processes of visual word recognition and reading operate upon neuronally coded domain-general low-level visual representations – typically oriented line representations. We here demonstrate, consistent with neurophysiological theories of Bayesian-like predictive neural computations, that prior visual knowledge of words may be utilized to ‘explain away’ redundant and highly expected parts of the visual percept. Subsequent processing stages, accordingly, operate upon an optimized representation of the visual input, the orthographic prediction error, highlighting only the visual information relevant for word identification. We show that this optimized representation is related to orthographic word characteristics, accounts for word recognition behavior, and is processed early in the visual processing stream, i.e., in V4 and before 200 ms after word-onset. Based on these findings, we propose that prior visual-orthographic knowledge is used to optimize the representation of visually presented words, which in turn allows for highly efficient reading processes.
Shrubs are a characteristic component of savannas, where they coexist with trees and grasses. They are often part of woody encroachment phenomena, which have been observed globally, and the determinant of shrub encroachment cases, which are particularly of concern in African savannas. In response to climate change and land use change, African savannas are vulnerable to biome shifts and shrub encroachment is a process driving and explaining this risk.
We contribute to furthering the understanding of shrubs biogeography and ecology by considering the number of stems of woody plants to characterise shrubs phenotype and strategy. We postulate that shrubs are multi-stemmed, compared to single-stemmed trees and integrate this assumption in aDGVM2 (adaptive Dynamic Global Vegetation Model 2). Modelling a trait representing the number of stems of a woody plant implies a trade-off between single-stemmed plants having higher height growth potential and multi-stemmed plants having higher hydraulic capacity but limited height growth. Multi-stemmed individuals, being shorter, are more likely to suffer severe damage from fires than tall single-stemmed trees managing to grow their crown out of the flame zone.
We simulate potential vegetation over sub-Saharan Africa at 1° spatial resolution, with aDGVM2 and compare it to simulations without our shrub model turned on. We also test the impact of fire by including or excluding it from our simulations. To assess the accuracy and relevance of our approach, we benchmark our overall model’s performance against multiple satellite derived products of above ground biomass (AGBM), and against specific field measurements of AGBM. We further benchmark our results against vegetation cover type derived from satellite data.
We demonstrate that shrubs can be modelled as multi-stemmed woody plants in African savannas based on whole-plant trait trade-off without being predefined as static functional types. Indeed, the addition of our shrub model to aDGVM2 allows for shrubs to emerge dynamically through community assembly processes without a priori categorisation. Our shrub model also improves the simulated vegetation patterns simulated by aDGVM2 in sub-Saharan Africa, particularly in savannas. The simulated pattern of stem number per woody individual broadly follows our assumptions about biogeographic patterns as it is lowest in equatorial African forests and increases in savannas and grasslands as precipitation decreases. Shrubs are more abundant in more water-stressed regions where they have a competitive advantage over trees due to their increased relative water transport potential. However, in arid and hyper-arid regions, further investigations are required. Simulated shrub prevalence is higher in more open and fire prone landscapes, where woody cover and biomass are reduced.
Adding shrubs to aDGVM2, while increasing complexity allows for greater simulated diversity. As resilience and resistance of ecosystems have been shown to be influenced by diversity, such model development is necessary to improve our ability to forecast ecosystems responses to changes. However, there are challenges to fully tap this benefit. Assessing the accuracy and relevance of our approach is challenging. Data and simulations are conceptually different which limit the possibility to conclude based on comparison. Benchmarking challenge is exacerbated by the variability existing among satellite derived products and site studies observations. In areas of extremely low biomass and vegetation cover, such as deserts and semi-deserts, the accuracy of our model is more concerning as small differences in absolute values are relatively more important.
Categorisation of life-forms shapes our understanding of their ecology and biogeography, thus, consensus about their definition is direly needed. To contribute to this debate, we investigate how vegetation distribution patterns arising from our shrub model inform our understanding of shrub biogeography. First, shrub distribution in trait space (considering stem number), relatively to environmental drivers, concurs with our assumptions. Second, shrub spatial distribution is consistent with our characterisation assumptions. Third, the role of simulated shrubs in an ecosystem supports realistic ecological dynamics. Our model allows for, shrubs to exhibit a specific phenotype, but also a specific life-strategy, which we characterise in terms of persistence strategy (shrubs are mainly resprouters, in contrast to trees, which can be either resprouters or reseeders) and in terms of resource acquisition (rooting strategy) and allocation (carbon investment). Adding stem count as a trait to aDGVM2 increase the range of simulated functional diversity.
Our shrub model allows for aDGVM2 to simulate realistic ratio of grass to woody vegetation across sub-saharan Africa. Similarly, it simulates ratio of shrubs to trees consistent with our hypotheses.
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Corporate governance is the set of rules, be they legal or self-regulatory, practices and processes pursuant to which an insurance undertaking is administrated. Good corporate governance is not only key to establishing oneself and succeeding in a competitive environment but also to safeguarding the interests of all stakeholders in an insurance undertaking. It is insofar not surprising that mandatory requirements on the administration of insurance undertakings have become rather prolific in recent years, in an attempt by regulators to protect especially policyholders against perceived risks hailing from improperly governed insurance undertakings. In Germany this has been regarded by many undertakings as an overly paternalistic approach of the legislator, especially considering that the German insurance sector has experienced for decades if not centuries a remarkably low number of insolvencies and that German insurers were neither the trigger nor the (especially) endangered actors in the financial crisis commencing in 2007. Notwithstanding the true core of this criticism, that the insurance industry was taken to a certain degree hostage by the shortcomings within the banking sector, the reform of German Insurance Supervisory Law via implementation of the Solvency II-System has brought many advances in the sense of better governance of insurance undertakings and has also brought to light many deficiencies that the administration of some insurance undertakings may have suffered from in the past, which are now more properly addressed.
Galarraga‐Vinueza, Maria Elisa ; Dohle, Eva ; Ramanauskaite, Ausra ; Maawi, Sarah al- ; Obreja, Karina Anne-Marie ; Magini, Ricardo ; Sader, Robert Alexander ; Ghanaati, Shahram Michael ; Schwarz, Frank
Background and Objective: Macrophages’ cytokine expression and polarization play a substantial role in the host's “destructive” inflammatory response to periodontal and peri‐implant pathogens. This study aimed to evaluate cell viability, anti‐inflammatory activity, and macrophage polarization properties of different cranberry concentrates.
Methods: THP‐1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB‐G cell line), osteosarcoma‐derived osteoblasts (SAOS‐2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti‐inflammatory analysis, induced macrophages exposed to cranberry concentrates (A‐type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)‐8, IL‐1 ß, IL‐6, and IL‐10 expression of LPS‐stimulated macrophages, and macrophage polarization markers were evaluated through determination of live‐cell protease activity, enzyme‐linked immunosorbent assay, and immunofluorescence staining semi‐quantification.
Results: Cranberry concentrates (A‐type PACs) did not reduce HGF, SAOS‐2, and macrophage viability after 24 hours of exposure. Pro‐inflammatory cytokine expression (ie IL‐8 and IL‐6) was downregulated in LPS‐stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti‐inflammatory IL‐10 expression was significantly upregulated in LPS‐stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS‐stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS‐stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours.
Conclusion: Cranberry‐derived proanthocyanidins may have the potential to act as an anti‐inflammatory component in the therapy of periodontal and peri‐implant diseases.
Galarraga‐Vinueza, Maria Elisa ; Obreja, Karina Anne-Marie ; Magini, Ricardo ; Sculean, Anton ; Sader, Robert Alexander ; Schwarz, Frank
Aim: To assess volumetric tissue changes at peri‐implantitis sites following combined surgical therapy of peri‐implantitis over a 6‐month follow‐up period.
Materials and Methods: Twenty patients (n = 28 implants) diagnosed with peri‐implantitis underwent access flap surgery, implantoplasty at supracrestally or bucally exposed implant surfaces and augmentation at intra‐bony components using a natural bone mineral and application of a native collagen membrane during clinical routine treatments. The peri‐implant region of interest (ROI) was intra‐orally scanned pre‐operatively (S0), and after 1 (S1) and 6 (S2) months following surgical therapy. Digital files were converted to standard tessellation language (STL) format for superimposition and assessment of peri‐implant volumetric variations between time points. The change in thickness was assessed at a standardized ROI, subdivided into three equidistant sections (i.e. marginal, medial and apical). Peri‐implant soft tissue contour area (STCA) (mm2) and its corresponding contraction rates (%) were also assessed.
Results: Peri‐implant tissues revealed a mean thickness change (loss) of −0.11 and −0.28 mm at 1 and 6 months. S0 to S1 volumetric variations pointed to a thickness change of −0.46, 0.08 and 0.4 mm at marginal, medial and apical regions, respectively. S0 to S2 analysis exhibited corresponding thickness changes of −0.61, −0.25 and −0.09 mm, respectively. The thickness differences between the areas were statistically significant at both time periods. The mean peri‐implant STCA totalled to 189.2, 175 and 158.9 mm2 at S0, S1 and S2, showing a significant STCA contraction rate of 7.9% from S0 to S1 and of 18.5% from S0 to S2. Linear regression analysis revealed a significant association between the pre‐operative width of keratinized mucosa (KM) and STCA contraction rate.
Conclusions: The peri‐implant mucosa undergoes considerable volumetric changes after combined surgical therapy. However, tissue contraction appears to be influenced by the width of KM.
Galarraga‐Vinueza, Maria Elisa ; Obreja, Karina Anne-Marie ; Ramanauskaite, Ausra ; Magini, Ricardo ; Begić, Amira ; Sader, Robert ; Schwarz, Frank
Objectives: To immunohistochemically characterize and correlate macrophage M1/M2 polarization status with disease severity at peri-implantitis sites.
Materials and methods: A total of twenty patients (n = 20 implants) diagnosed with peri-implantitis (i.e., bleeding on probing with or without suppuration, probing depths ≥ 6 mm, and radiographic marginal bone loss ≥ 3 mm) were included. The severity of peri-implantitis was classified according to established criteria (i.e., slight, moderate, and advanced). Granulation tissue biopsies were obtained during surgical therapy and prepared for immunohistological assessment and macrophage polarization characterization. Macrophages, M1, and M2 phenotypes were identified through immunohistochemical markers (i.e., CD68, CD80, and CD206) and quantified through histomorphometrical analyses.
Results: Macrophages exhibiting a positive CD68 expression occupied a mean proportion of 14.36% (95% CI 11.4–17.2) of the inflammatory connective tissue (ICT) area. Positive M1 (CD80) and M2 (CD206) macrophages occupied a mean value of 7.07% (95% CI 5.9–9.4) and 5.22% (95% CI 3.8–6.6) of the ICT, respectively. The mean M1/M2 ratio was 1.56 (95% CI 1–12–1.9). Advanced peri-implantitis cases expressed a significantly higher M1 (%) when compared with M2 (%) expression. There was a significant correlation between CD68 (%) and M1 (%) expression and probing depth (PD) values.
Conclusion: The present immunohistochemical analysis suggests that macrophages constitute a considerable proportion of the inflammatory cellular composition at peri-implantitis sites, revealing a significant higher expression for M1 inflammatory phenotype at advanced peri-implantitis sites, which could possibly play a critical role in disease progression.
Clinical relevance: Macrophages have critical functions to establish homeostasis and disease. Bacteria might induce oral dysbiosis unbalancing the host’s immunological response and triggering inflammation around dental implants. M1/M2 status could possibly reveal peri-implantitis’ underlying pathogenesis.
Galemou Yoga, Etienne ; Parey, Kristian ; Djurabekova, Amina ; Haapanen, Outi ; Siegmund, Karin ; Zwicker, Klaus ; Sharma, Vivek ; Zickermann, Volker ; Angerer, Heike
Respiratory complex I catalyzes electron transfer from NADH to ubiquinone (Q) coupled to vectorial proton translocation across the inner mitochondrial membrane. Despite recent progress in structure determination of this very large membrane protein complex, the coupling mechanism is a matter of ongoing debate and the function of accessory subunits surrounding the canonical core subunits is essentially unknown. Concerted rearrangements within a cluster of conserved loops of central subunits NDUFS2 (β1-β2S2 loop), ND1 (TMH5-6ND1 loop) and ND3 (TMH1-2ND3 loop) were suggested to be critical for its proton pumping mechanism. Here, we show that stabilization of the TMH1-2ND3 loop by accessory subunit LYRM6 (NDUFA6) is pivotal for energy conversion by mitochondrial complex I. We determined the high-resolution structure of inactive mutant F89ALYRM6 of eukaryotic complex I from the yeast Yarrowia lipolytica and found long-range structural changes affecting the entire loop cluster. In atomistic molecular dynamics simulations of the mutant, we observed conformational transitions in the loop cluster that disrupted a putative pathway for delivery of substrate protons required in Q redox chemistry. Our results elucidate in detail the essential role of accessory subunit LYRM6 for the function of eukaryotic complex I and offer clues on its redox-linked proton pumping mechanism.
The clinical and economic value of a successful shutdown during the SARS-CoV-2 pandemic in Germany
(2020)
Background and aim A shutdown of businesses enacted during the SARS-CoV-2 pandemic can serve different goals, e.g., preventing the intensive care unit (ICU) capacity from being overwhelmed (‘flattening the curve’) or keeping the reproduction number substantially below one (‘squashing the curve’). The aim of this study was to determine the clinical and economic value of a shutdown that is successful in ‘flattening’ or ‘squashing the curve’ in Germany.
Methods In the base case, the study compared a successful shutdown to a worst-case scenario with no ICU capacity left to treat COVID-19 patients. To this end, a decision model was developed using, e.g., information on age-specific fatality rates, ICU outcomes, and the herd protection threshold. The value of an additional life year was borrowed from new, innovative oncological drugs, as cancer reflects a condition with a similar morbidity and mortality burden in the general population in the short term as COVID-19.
Results A shutdown that is successful in ‘flattening the curve’ is projected to yield an average health gain between 0.02 and 0.08 life years (0.2 to 0.9 months) per capita in the German population. The corresponding economic value ranges between €1543 and €8027 per capita or, extrapolated to the total population, 4% to 19% of the gross domestic product (GDP) in 2019. A shutdown that is successful in ‘squashing the curve’ is expected to yield a minimum health gain of 0.10 life years (1.2 months) per capita, corresponding to 24% of the GDP in 2019. Results are particularly sensitive to mortality data and the prevalence of undetected cases.
Conclusion A successful shutdown is forecasted to yield a considerable gain in life years in the German population. Nevertheless, questions around the affordability and underfunding of other parts of the healthcare system emerge.
García Rosales, Francisco ; López Jury, Luciana ; González Palomares, Eugenia ; Cabral-Calderı́n, Yuranny ; Hechavarria-Cueria, Julio C.
Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the bat Carollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioral outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1–12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.
García Rosales, Francisco ; López Jury, Luciana ; González Palomares, Eugenia ; Cabral-Calderı́n, Yuranny ; Hechavarria-Cueria, Julio C.
Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the bat Carollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioural outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1-12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.
García Rosales, Francisco ; López Jury, Luciana ; González Palomares, Eugenia ; Cabral-Calderı́n, Yuranny ; Kössl, Manfred ; Hechavarria-Cueria, Julio C.
Neural oscillations are at the core of important computations in the mammalian brain. Interactions between oscillatory activities in different frequency bands, such as delta (1–4 Hz), theta (4–8 Hz) or gamma (>30 Hz), are a powerful mechanism for binding fundamentally distinct spatiotemporal scales of neural processing. Phase-amplitude coupling (PAC) is one such plausible and well-described interaction, but much is yet to be uncovered regarding how PAC dynamics contribute to sensory representations. In particular, although PAC appears to have a major role in audition, the characteristics of coupling profiles in sensory and integration (i.e. frontal) cortical areas remain obscure. Here, we address this question by studying PAC dynamics in the frontal-auditory field (FAF; an auditory area in the bat frontal cortex) and the auditory cortex (AC) of the bat Carollia perspicillata. By means of simultaneous electrophysiological recordings in frontal and auditory cortices examining local-field potentials (LFPs), we show that the amplitude of gamma-band activity couples with the phase of low-frequency LFPs in both structures. Our results demonstrate that the coupling in FAF occurs most prominently in delta/high-gamma frequencies (1-4/75-100 Hz), whereas in the AC the coupling is strongest in the delta-theta/low-gamma (2-8/25-55 Hz) range. We argue that distinct PAC profiles may represent different mechanisms for neuronal processing in frontal and auditory cortices, and might complement oscillatory interactions for sensory processing in the frontal-auditory cortex network.
García Rosales, Francisco ; López Jury, Luciana ; González Palomares, Eugenia ; Cabral-Calderı́n, Yuranny ; Kössl, Manfred ; Hechavarria-Cueria, Julio C.
Neural oscillations are at the core of important computations in the mammalian brain. Interactions between oscillatory activities in different frequency bands, such as delta (1-4 Hz), theta (4-8 Hz), or gamma (>30 Hz), are a powerful mechanism for binding fundamentally distinct spatiotemporal scales of neural processing. Phase-amplitude coupling (PAC) is one such plausible and well-described interaction, but much is yet to be uncovered regarding how PAC dynamics contribute to sensory representations. In particular, although PAC appears to have a major role in audition, the characteristics of coupling profiles in sensory and integration (i.e. frontal) cortical areas remain obscure. Here, we address this question by studying PAC dynamics in the frontal-auditory field (FAF; an auditory area in the bat frontal cortex) and the auditory cortex (AC) of the bat Carollia perspicillata. By means of simultaneous electrophysiological recordings in frontal and auditory cortices examining local-field potentials (LFPs), we show that the amplitude of gamma-band activity couples with the phase of low-frequency LFPs in both structures. Our results demonstrate that the coupling in FAF occurs most prominently in delta/high-gamma frequencies (1-4/75-100 Hz), whereas in the AC the coupling is strongest in the theta/low-gamma (2-8/25-55 Hz) range. We argue that distinct PAC profiles may represent different mechanisms for neuronal processing in frontal and auditory cortices, and might complement oscillatory interactions for sensory processing in the frontal-auditory cortex network.
Gaubatz, Jennifer ; Ernst, Leon ; Prillwitz, Conrad ; David, Bastian ; Lüchters, Guido ; Schramm, Johannes ; Weber, Bernd ; Surges, Rainer ; Hattingen, Elke ; Schlaug, Gottfried ; Elger, Christian Erich ; Rüber, Theodor
Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.
Gaubatz, Jennifer ; Prillwitz, Conrad ; Ernst, Leon ; David, Bastian ; Hoppe, Christian ; Hattingen, Elke ; Weber, Bernd ; Vatter, Hartmut ; Surges, Rainer ; Elger, Christian Erich ; Rüber, Theodor
Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.
Gavanda, Simon ; Isenmann, Eduard ; Schlöder, Yvonne ; Roth, Roland ; Freiwald, Jürgen ; Schiffer, Thorsten ; Geisler, Stephan ; Behringer, Michael
The purpose of this study was to investigate whether a six-week, twice weekly resistance training (4 sets at 30% 1-RM until failure) with practical blood flow restriction (BFR) using 7cm wide cuffs with a twist lock placed below the patella is superior to training without BFR (NoBFR) concerning muscle mass and strength gains in calf muscles.
A two-group (BFR n = 12, mean age 27.33 (7.0) years, training experience 7.3 (7.0) years; NoBFR n = 9, mean age 28.9 (7.4) years, training experience 7.1 (6.6) years) randomized matched pair design based on initial 1-RM was used to assess the effects on structural and functional adaptations in healthy males (Perometer calf volume [CV], gastrocnemius muscle thickness using ultrasound [MT], 7-maximal hopping test for leg stiffness [LS], 1-RM smith machine calf raise [1-RM], and visual analogue scale as a measure of pain intensity [VAS]).
The mean number of repetitions completed per training session across the intervention period was higher in the NoBFR group compared to the BFR group (70 (16) vs. 52 (9), p = 0.002). VAS measured during the first session increased similarly in both groups from first to fourth set (p<0.001). No group effects or time×group interactions were found for CV, MT, LS, and 1-RM. However, there were significant time effects for MT (BFR +0.07 cm; NoBFR +0.04; p = 0.008), and 1-RM (BFR +40 kg; NoBFR +34 kg; p<0.001).
LS and CV remained unchanged through training. VAS in both groups were similar, and BFR and NoBFR were equally effective for increasing 1-RM and MT in trained males. However, BFR was more time efficient, due to lesser repetition per training session.
Twenty years ago, on February 10, 2000, the CERN Director General Luciano Maiani announced: The combined data coming from the seven experiments on CERN’s Heavy Ion programme have given a clear picture of a new state of matter. This result verifies an important prediction of the present theory of fundamental forces between quarks. This report briefly reviews studies of the phase diagram of strongly interacting matter with relativistic nuclear collisions at the CERN Super Proton Synchrotron which followed the CERN’s press release on the quark-gluon plasma discovery. An attempt to formulate priorities for future measurements at the CERN SPS closes the paper. The report is dedicated to David Blaschke who celebrated his 60th birthday in 2019. David’s contribution to the studies presented here was very significant.
In this paper a new method of experimental data analysis, the Particle-Set Identification method, is presented. The method allows to reconstruct moments of multiplicity distribution of identified particles. The difficulty the method copes with is due to incomplete particle identification – a particle mass is frequently determined with a resolution which does not allow for a unique determination of the particle type. Within this method the moments of order k are calculated from mean multiplicities of k-particle sets of a given type. The Particle-Set Identification method remains valid even in the case of correlations between mass measurements for different particles. This distinguishes it from the Identity method introduced by us previously to solve the problem of incomplete particle identification in studies of particle fluctuations.
The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy.
Die vorliegende Studie befasst sich mit dem Einfluss minimalinvasiver Zugangswege zur Mitralklappe auf den Herzrhythmus, den Erfolg einer perioperativ durchgeführten Ablation und die postoperative Notwendigkeit eines Herzschrittmachers.
Mitralklappenvitien und deren herzchirurgische Versorgung sind in vielen Fällen mit präoperativ bestehendem oder postoperativ neu auftretendem Vorhofflimmern assoziiert. In den vergangenen Jahrzehnten haben sich neben der medikamentösen Therapie des Vorhofflimmerns und der durch die Mitralklappeninsuffizienz induzierten Herzinsuffizienz verschiedene minimalinvasive chirurgische Zugangswege zur Mitralklappe sowie Ablationsverfahren etabliert und einen kurativen Therapieansatz gebildet.
Die Ablation im Zuge einer Mitralklappenchirurgie ist zu einem alltäglich durchgeführten Verfahren geworden.
Neu auftretendes Vorhofflimmern im Rahmen der Mitralklappenchirurgie kann perioperativ begrenzt sein und konvertiert häufig innerhalb der ersten 6 Wochen spontan in den Sinusrhythmus. Es geht aber mit einer erhöhten Mortalität und Hospitalisierungszeit einher. Das neu auftretende Vorhofflimmern kann jedoch auch persistieren oder erst im Langzeitverlauf entstehen. Auch die Notwendigkeit eines Herzschrittmachers kann durch Mitralklappeneingriffe insbesondere mit additiver Ablation aufgrund der anatomischen Gegebenheiten erhöht sein.
In unserer Arbeit ist von Interesse, ob sich die unten genannten Zugangswege im Hinblick auf das Neuauftreten von Vorhofflimmern im Langzeitverlauf, die Vorhofflimmerrezidivrate nach Ablation und die Schrittmacherrate mit und ohne durchgeführte Ablation unterscheiden.
Die vorliegende Studie umfasst alle Mitralklappenoperationen, die zwischen 1998 und 2015 in der Klinik für Thorax-, Herz- und thorakale Gefäßchirurgie der Universitätsklinik Frankfurt am Main über die folgenden drei minimalinvasiven Zugangswege, durchgeführt wurden: Gruppe A bildeten 300 Patienten, die im genannten Zeitraum über eine anterolaterale Minithorakotomie mittels Chitwood-Klemme operiert wurden. Gruppe B bestand aus 687 Patienten, die über eine partielle obere Sternotomie mit superiorem transseptalem Zugang operiert wurden. Die 219 Patienten, bei denen eine partielle obere Sternotomie mit transcavalem Zugang angewandt wurde, bildeten Gruppe C.
Die Auswertung erfolgte anhand von Patientenakten, internen und externen Untersuchungsbefunden und eines standardisierten Fragebogens im Follow-up. Es erfolgte eine zweite Auswertung nach Propensity Matching, um präoperative signifikante Unterschiede der Gruppen zu egalisieren.
Im Ergebnis konnte in unserer Studie gezeigt werden, dass die atriale Inzision einen entscheidenden Einfluss auf den Ablationserfolg sowie auf die Schrittmacherinzidenz hat. Bekannt war dabei ein höheres Risiko für postoperatives Vorhofflimmern und Schrittmacherimplantationen aufgrund der anatomischen Gegebenheiten bei Gruppe B. Dass jedoch Gruppe C ein signifikant noch höheres Risiko für Schrittmacherimplantationen mit sich bringt, war überraschend und ist derzeit nicht in der Literatur beschrieben.
In der multivariaten Analyse nach Matching waren Gruppe C, eine additive Ablation und das Alter signifikante unabhängige Prädiktoren für Schrittmacherimplantationen. In der logistischen Regression war Gruppe A ein unabhängiger Prädiktor für den Ablationserfolg zum Zeitpunkt der Entlassung. In der Langzeitbeobachtung trat Gruppe C an Stelle von Gruppe A, möglicherweise aufgrund der bei Gruppe A vorliegenden längsten Follow-up-Zeit. Wie schon in der vorliegenden Literatur diskutiert waren auch in unserer Auswertung hohes Alter und eine präoperative linksatriale Vergrößerung unabhängige Prädiktoren für den langfristigen Ablationserfolg.
Es bedarf weiterer vergleichender Studien mit einheitlichen Follow-up-Zeiten, um die hier gezeigten Ergebnisse zu überprüfen. Insbesondere der transcavale Zugang, der sich im negativen Sinne auf die Zahl der Schrittmacherimplantationen auszuwirken scheint, gibt Anlass für weitere Untersuchungen.
Gehrke, Peter ; Abazari, Cyrus ; Schlichter, Kai ; Fischer, Carsten ; Duddeck, Dirk ; Romanos, Georgios ; Weigl, Paul
Manufacturing processes of custom implant abutments may contaminate their surfaces with micro wear deposits and generic pollutants. Such particulate debris, if not removed, might be detrimental and provoke inflammatory reactions in peri-implant tissues. Although regulatory guidelines for adequate cleaning, disinfection, or sterilization exist, there does not appear to be a consistent application and data on the amount and extent of such contaminants is lacking. The aim of the present in vitro study was to evaluate the quality and quantity of processing-related surface contamination of computer-aided design/computer-aided manufacturing (CAD/CAM) abutments in the state of delivery and after ultrasonic cleaning. A total of 28 CAD/CAM monotype and hybrid abutments were cleaned and disinfected applying a three-stage ultrasonic protocol (Finevo protocol). Before and after cleaning, the chemical composition and the contamination of the abutments were assessed using scanning electron microscopy (SEM), dispersive X-ray spectroscopy(EDX),andcomputer-aidedplanimetricmeasurement(CAPM).Inthedeliverycondition, monotype abutments showed a significantly higher amount of debris compared to hybrid abutments (4.86±6.10% vs. 0.03 ± 0.03%, p < 0.001). The polishing process applied in the laboratory after bonding the hybrid abutment components reduces the surface roughness and thus contributes substantially to their purity. The extent of contamination caused by computer-aided manufacturing of custom abutments can be substantially minimized using a three-stage ultrasonic protocol.
Hintergrund: Die chronische metabolischen Azidose (cmA) ist eine häufige Komplikation bei chronischer Niereninsuffizienz, deren Behandlung bei niereninsuffizienten Patienten mit Diabetes mellitus die Insulinresistenz verbessern kann. Um die aktuelle Therapiesituation der cmA im diabetologischen Umfeld abzubilden und mehr über die Zusammenarbeit von Diabetologen und Nephrologen zu erfahren, wurden diabetologisch tätige Haus- und Fachärzte zur cmA befragt.
Methoden An 5863 Ärzten mit diabetologischer Zusatzqualifikation wurde postalisch ein Fragebogen versandt. Alle 97 erhaltenen Antwortbögen wurden deskriptiv ausgewertet.
Ergebnisse Die meisten Teilnehmer sind Internisten mit diabetologischer Zusatzqualifikation (46 %) und behandeln im Median 50 (10; 112) Patienten mit Typ-1-Diabetes bzw. 210 (100; 450) Patienten mit Typ-2-Diabetes pro Quartal. Eine cmA wurde von 12 % der Teilnehmer in den letzten 12 Monaten bei median 4 (2; 6) Patienten mit Typ-1-Diabetes und 10 (3; 30) Patienten mit Typ-2-Diabetes beobachtet. Die cmA wird überwiegend durch Bestimmung des Serum-Bikarbonats (27; 28 %) und des Base Excess (19; 20 %) diagnostiziert. 38 (39 %) der Teilnehmer erhalten regelmäßig von Nephrologen die Empfehlung zur Behandlung der cmA. Sie wird von knapp 1 Drittel als relevant (29 %) und gut umsetzbar (27 %) betrachtet. Zur Behandlung der cmA wird vor allem orales Bikarbonat empfohlen (Bikarbonat: 39 %, Zitrat: 5 %, sonst: keine Angabe). Maßnahmen, die die Mehrheit der Diabetologen in der Verantwortung der Nephrologen sehen, sind ergänzende Diagnostik (87; 90 %) einschließlich Blutgasanalyse (59 %) sowie die Behandlung der cmA (62 %) und renalen Anämie (53 %). 34 % der Diabetologen gaben an, bisher noch keine cmA-Fälle in der Praxis behandelt zu haben. Die meisten Diabetologen überlassen die Behandlung und Überwachung der cmA dem Nephrologen (38 %). Dabei wird die Zusammenarbeit mit den Nephrologen als zufriedenstellend (81 %) bewertet. 38 % der Befragten haben in der täglichen Praxis beobachtet, dass die Einstellung der cmA auch die Insulinresistenz positiv beeinflusst. Eine CME-Fortbildung in der Diabetologie speziell zur cmA würden 76 (78 %) begrüßen.
Diskussion Bei der Behandlung der cmA wird die Kooperation zwischen Diabetologen und Nephrologen generell gut bewertet, wobei die Diagnose, Behandlung und Überwachung einer cmA in der Verantwortung des Nephrologen gesehen werden. Da die Behandlung der cmA die Insulinresistenz verringern kann, sollte der Stellenwert der cmA-Therapie im diabetologischen Umfeld nicht unterschätzt werden. Um die cmA-Behandlung bei diabetischer Nephropathie zu optimieren, wären CME-Fortbildungen zur cmA geeignet. Zudem könnten Schulungen im Rahmen einer interdisziplinären Kooperation mit Diätberatern die Umsetzbarkeit diätetischer Interventionen zur Behandlung der cmA verbessern.
Geisen, Christof ; North, Anne ; Becker, Lisa ; Brixner, Veronika ; Goetz, Melissa von ; Corash, Laurence ; Benjamin, Richard J. ; Mufti, Nina ; Seifried, Erhard
Background: The INTERCEPT™ Blood System for Red Blood Cells (RBCs) utilizes amustaline (S‐303) and glutathione (GSH) to inactivate pathogens and leukocytes in transfused RBCs. Treatment‐emergent low titer non‐hemolytic antibodies to amustaline/GSH RBC were detected in clinical trials using a prior version of the process. The amustaline/GSH process was re‐formulated to decrease S‐303 RBC adduct formation.
Study Design and Methods: A standard three‐cell antibody screening panel was modified to include reagent red cells (RRC) with high (S‐303H) or low (S‐303L) S‐303 adduct density as assessed by flow cytometry, representative of the original and current amustaline/GSH treatment processes, respectively. General hospital and RBC transfusion‐dependent patients never exposed, and clinical trial subjects exposed to amustaline/GSH RBC were screened for antibodies to amustaline/GSH RBC using a standardized agglutination assay.
Results: Twelve (0.1%) of 10,721 general hospital and 5 (0.5%) of 998 repeatedly‐transfused patients not previously exposed to amustaline/GSH RBCs expressed natural, low titer (2‐32) IgM and/or IgG (non‐IgG1 or IgG3 isotype) antibodies with acridine (a structural element of amustaline) (n = 14) or non‐acridine (n = 3) specificity. 11 of 17 sera reacted with S‐303L panel RRCs. In clinical studies 81 thalassemia and 25 cardiac surgery patients were transfused with a total of 1085 amustaline/GSH RBCs and no natural or treatment‐emergent S‐303 antibodies were detected.
Conclusion: Standardized RRC screening panels are sensitive for the detection of natural and acquired S‐303‐specific antibodies. Natural low titer antibodies to amustaline/GSH RBC are present in 0.15% of naïve patients. The clinical relevance of these antibodies appears minimal but is under further investigation.
Georg, Isabelle ; Bursch, Markus ; Stückrath, Julius B. ; Alig, Edith ; Bolte, Michael ; Lerner, Hans-Wolfram ; Grimme, Stefan ; Wagner, Matthias
The exhaustive trichlorosilylation of hexachloro-1,3-butadiene was achieved in one step by using a mixture of Si2Cl6 and [nBu4N]Cl (7:2 equiv) as the silylation reagent. The corresponding butadiene dianion salt [nBu4N]2[1] was isolated in 36 % yield after recrystallization. The negative charges of [1]2− are mainly delocalized across its two carbanionic (Cl3Si)2C termini (α-effect of silicon) such that the central bond possesses largely C=C double-bond character. Upon treatment with 4 equiv of HCl, [1]2− is converted into neutral 1,2,3,4-tetrakis(trichlorosilyl)but-2-ene, 3. The Cl− acceptor AlCl3, induces a twofold ring-closure reaction of [1]2− to form a six-membered bicycle 4 in which two silacyclobutene rings are fused along a shared C=C double bond (84 %). Compound 4, which was structurally characterized by X-ray crystallography, undergoes partial ring opening to a monocyclic silacyclobutene 2 in the presence of HCl, but is thermally stable up to at least 180 °C.
In jüngeren geschichtswissenschaftlichen Arbeiten über die römische Kaiserzeit ist ein wiederentdecktes Interesse an den vermeintlich "schlechten" Kaisern unverkennbar. Zu den umstrittensten principes des 1. Jahrhunderts n.Chr. zählt auch Domitian, der letzte Flavier auf dem Herrscherthron, der von der zeitgenössischen Literatur zum Iuppiter-gleichen Idealherrscher stilisiert, in den nach seiner Ermordung erschienenen Schriften dagegen als Tyrann gebrandmarkt wurde. ...
Shares of open-end real estate funds are typically traded directly between the investor and the fund management company. However, we provide empirical evidence for the growth of secondary market activities, i.e., the trading of shares on stock exchanges. We find high trading levels in situations where the fund management company suspends the issue or redemption of shares. Shares trade at a discount when the fund management company suspends the redemption, whereas shares trade at a premium when the fund management company suspends the issue. We also find evidence that secondary market trading activity is increasing since German regulation introduced a minimum holding period and a mandatory notice period for open-end real estate funds.
Das CBM-Experiment konzentriert sich auf die Untersuchung der Eigenschaften des Quark-Gluon-Plasmas bei hohen Netto-Baryonendichten und moderaten Temperaturen. An der zukünftigen Beschleunigeranlage FAIR an der GSI findet das Experiment, neben vielen anderen Experimenten, ihren Platz. Der TRD ist, neben dem RICH, STS und TOF, einer der zentralen Detektoren im CBM-Experiment. Der TRD nutzt dabei den physikalischen Effekt der Übergangsstrahlung, die durch ein geladenes Teilchen beim Durchqueren einer Grenze zweier Medien mit unterschiedlichen Dielektrizitätskonstanten mit einer gewissen Wahrscheinlichkeit entsteht, um Elektronen von Pionen trennen zu können. Im Jahr 2017 wurde an der DESY 4 TRD-Prototypen in einer Teststrahlzeit getestet. Dabei handelt es sich um große TRD-Module mit den Maßen 95 · 95 cm2 , was dem finalen Design sehr nahe kommt. Die Untersuchung der DESY-Daten in Kapitel 5 brachte große Problematiken in den Daten zum Vorschein. Die Hauptprobleme der DESY-Daten sind: 1) Bug des SPADIC-Chips 2.0, bei der FN-Trigger zeitlich verschoben wurden; 2) schwache und suboptimale Trigger-Bedingung, wodurch sehr viel Rauschen aufgenommen wurde. Die Daten müssen für weitere Auswertung aufbereitet werden, wobei sehr viel Information und Statistik verloren geht, da einige Daten durch diverse Probleme nicht mehr rekonstruierbar sind. Kapitel 6 beschäftigt sich mit der Simulation der Detektorantwort und geht genauer auf die einzelnen Schritte, die zur Simulation des vom SPADIC erzeugten Pulses benötigt werden, ein. Am Ende werden Ergebnisse aus beiden Datensätzen miteinander verglichen. Um einen optimalen Vergleich zu gewähren, wird die Simulation bestmöglich an die Einstellungen in der Teststrahlzeit angepasst. Hauptsächlich geht es um die Erhöhung des Gasgains und der Verschiebung der Peaking-Zeit des Pulses. Im Allgemeinen können wir in der Simulation einige Effekte, die auch in den DESY-Daten vorkommen, nachsimulieren. Wir erhalten zum Teil sehr unterschiedliche Ergebnisse in der Simulation, deren Richtigkeit nicht verifiziert werden kann, da die Daten aufgrund der Probleme unzuverlässig werden. Durch die Analyse der DESY-Daten konnten wir die Problematik in den Daten besser verstehen. Eine sinnvolle Anpassung der Simulation wird durch die Unzuverlässigkeit der DESY-Daten unmöglich. Für die Optimierung der Simulation müsste man einen Vergleich mit neueren, zuverlässigeren Daten aus zukünftigen Teststrahlzeiten nehmen.
Study design: Systematic review. Background and objectives: Preoperative neuromuscular function is predictive for knee function and return to sports (RTS) after reconstruction of the anterior cruciate ligament (ACL). The aim of this review was to examine the potential benefits of prehabilitation on pre-/postoperative objective, self-reported and RTS-specific outcomes. Methods: A systematic search was conducted within three databases. From the 1.071 studies screened, two randomized control trials (RCTs), two control trials (CTs) and two cohort studies (CS) met the inclusion criteria. Methodological quality rating adopted the PEDro- (RCT, CT) or Newcastle-Ottawa-Scale (CS). Results and conclusions: Methodological quality of the included studies was moderate (PEDro score: 6.5 ± 1.7; range 4 to 9). Two studies reported higher increases of the maximal quadriceps torque from baseline to pre-reconstruction: one study in the limb symmetry index (LSI), and one in both legs of the prehabilitation group compared to the controls. At 12-weeks post-reconstruction, one study (from two) indicated that the prehabilitation group had a lesser post-operative decline in the single-leg-hop for distance LSI (clinically meaningful). Similar findings were found in terms of quadriceps strength LSI (one study). At both pre-reconstruction (three studies) and two-year post-surgery (two studies), the prehabilitation groups reached significantly higher self-reported knee function (clinically meaningful) than the controls. RTS tended to be faster (one study). At two years post-surgery, RTS rates (one study) were higher in the prehabilitation groups. The results provide evidence for the relevance of prehabilitation prior to ACL-reconstruction to improve neuromuscular and self-reported knee function as well as RTS. More high quality confirmatory RCTs are warranted.
Historic amphibian settlements in the northwestern Nile delta - a geoarchaeological perspective
(2020)
No concise picture of the archaeological and palaeoecological evolution can be drawn for the northwestern Nile delta, and archaeological records show significant population dynamics that still need explanation and spur the need for further palaeoenvironmental research. This study delivers a set of new methods especially in the fields of remote sensing and data analytics that can be regarded as important milestones and foundations for further palaeoenvironmental research in the area. Additionally, it shows new insights for individual time slices.
This geoarchaeological project is a cooperation with the archaeological excavations of the German Archaeological Institute (DAI) in Buto and Kom el’Gir. It expands the work of Wunderlich (1989) which laid important foundations in understanding the origin of the initial landscape that was later colonized in different cultural stages showing different dynamics, settlement intensities and even long phases of abandonment or breaks in between. This forms the starting point for relating the population dynamics of the different cultural phases reaching from Predynastic (prior to 3150 before Christ) up to the Greco-Roman era (~anno Domini 650) to the environmental history and events that occurred in the area. It is very likely that environmental changes such as the shifting of major water routes, inundation or paludification of larger areas or other environmental events affected settlements and human life in the area.
In the fields of remote sensing new methods are presented to complete information on the location of ancient settlements, and complex workflows are developed that allow the tracing of subsurface structures via indirect analysis of vegetation growth in larger time series data. It was verified that a relationship exists between vegetation performance, the appearance of archaeologic material in the topsoil, and the location of former Nile river branches.
Together with a new high resolution digital elevation model (DEM) based on TanDEM-X data, new interpretations with a high spatial significance are possible. For individual time slices, namely the Late Dynastic and Greco-Roman era, this work delivers a detailed landscape description suggesting a finely ramified subdelta, with all settlements placed on alluvial levees. This explains the massive increase in settlements in the Ptolemaic, Roman and in particular late Roman periods (4th century before Christ – anno Domini 7th century).
We sampled the Nile delta clays together with the channels and the material of the archaeologic excavations in vibracores and profile walls. This geologic inspection of the subsurface together with geochemical results from a handheld portable X-ray fluorescence device (pXRF) allowed new interpretations of the landscape and environmental history. For example, we used geochemical data to distinguish between artificial and natural channels as a measure for the anthropogenic influence, a proxy for past environmental characteristics and lastly as a basis for a new dating method. Many of the channels, for instance, were dated by our own 14C datings, comparisons with the previous work ofWunderlich (1989) and application of new dating approach based on machine learning with artificial neural networks. Additionally, we run a full methodological approach, and examine the applicability of pXRF methods in general, and test the quality of the data to detect distinct geochemical differences between the main settlement phases with advanced methods in data analytics. The dating is based, for example, on the training of artificial neural networks with pXRF data from archaeological material of well-dated context to date test data of cultural layers within the vibracores. With this method the homogeneous Nile alluvium, cultural layers and channels can be dated roughly and, as a result, fundamental changes in the landscape can be linked with the settlement history of Buto and neighboring tells.
Are we creating our past?
(2020)
Urnfield Culture hilltop settlements are often associated with a predominant function in the settlement pattern. This study challenged the idea of centrality by means of density estimates and spatial inhomogeneous explanatory statistics. Reflecting on the differences in spatial trends and material culture, no conclusive evidence for a consolidation of power, economic, or cultic dominance was observed. The dataset strongly points towards the inapplicability of commonly used parametric and/or homogenous spatial algorithms in archaeology. Tracer variables as well as the methodological and theoretical limitations are critically reviewed and a methodological framework to increase the reproducibility and reusability of archaeological research is proposed.
Giroud, Jérémy ; Trébuchon, Agnès ; Schön, Daniele ; Marquis, Patrick ; Liegeois-Chauvel, Catherine ; Poeppel, David ; Morillon, Benjamin
Speech perception is mediated by both left and right auditory cortices but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex (AAC). We presented short acoustic transients to noninvasively estimate the dynamical properties of multiple functional regions along the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with evoked activity composed of dynamics in the theta (around 4–8 Hz) and beta–gamma (around 15–40 Hz) ranges. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (6/40 Hz) activity prevailing in the left. This asymmetry is also present during syllables presentation, but the evoked responses in AAC are more heterogeneous, with the co-occurrence of alpha (around 10 Hz) and gamma (>25 Hz) activity bilaterally. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the 2 hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.
Editorial [2020, deutsch]
(2020)
Editorial [2020, english]
(2020)
Hintergrund: Patienten, die präoperativ an einer eisendefizitären Erythropoese (IDE) oder Anämie leiden, haben unabhängig von anderen Erkrankungen ein erhöhtes Risiko für postoperative Morbidität. Ein Eisenmangel ist der häufigste Grund für eine Anämie und kann, wenn er frühzeitig diagnostiziert wird, effizient mittels Eisensubstitution behandelt werden. Zink-Protoporphyrin (ZnPP) ist im Vergleich zu klassischen Parametern wie Ferritin ein vielversprechender Parameter, um eine IDE zu diagnostizieren. Bisher wurde der Parameter im Blut gemessen. Nun soll geprüft werden, ob eine nicht-invasive Messung valide Ergebnisse liefert.
Methoden: Von März 2017 bis April 2018 wurden am Universitätsklinikum Frankfurt Patienten, die für eine Operation mit einem erwarteten Blutverlust von >10% geplant waren, auf eine IDE untersucht. Die Messung von nicht-invasivem ZnPP (ZnPP-NI) wurde mit der ZnPP-Referenz-Messung des ZnPP/Häm-Verhältnisses mittels Hochleistungsflüssigchromatographie (ZnPP-HPLC) verglichen. Die analytische Performance beim Nachweis einer IDE wurde mit im Blut gemessenen klassischen Eisenstatusparameter (Ferritin, Transferrinsättigung [TSAT], löslicher Transferrinrezeptor [sTfR] und sTfR-Index [sTfR-F]) verglichen.
Ergebnis: In dieser prospektiven Studie konnten 285 chirurgische Patienten präoperativ untersucht werden. Die Limits of Agreement zwischen ZnPP-NI und ZnPP-HPLC betrugen 20,3 μmol/mol Häm (95% -Konfidenzintervall 18,0-21,3; Akzeptanzkriterien 24,4 μmol/mol Häm; absolute Bias -0,3 μmol/mol Häm). Die analytische Performance zum Nachweis einer IDE der im Blut gemessenen Parameter war: ZnPP-HPLC (0,95), sTfR (0,90), sTfR-F (0,89), ZnPP-NI (0,88), TSAT (0,87) und Ferritin (0,65).
Fazit: Beim Nachweis einer IDE ist ZnPP-NI besser geeignet als Ferritin und vergleichbar valide wie TSAT. Der Vergleich mit einem Multiparameter-Index-Test ergab, dass ZnPP-NI von ≤40 μmol/mol Häm den Ausschluss einer IDE ermöglicht und ein Wert von ≥65 μmol/mol Häm eine IDE wahrscheinlich macht. ZnPP-NI kann daher für eine schnelle Erstbewertung in der IDE-Diagnostik und im Anämie Management ohne Blutentnahme verwendet werden.
Super-resolution optical fluctuation imaging (SOFI) is a super-resolution microscopy technique that overcomes the diffraction limit by analyzing intensity fluctuations of statistically independent emitters in a time series of images. The final images are background-free and show confocality and enhanced spatial resolution (super-resolution). Fluorophore photobleaching, however, is a key limitation for recording long time series of images that will allow for the calculation of higher order SOFI results with correspondingly increased resolution. Here, we demonstrate that photobleaching can be circumvented by using fluorophore labels that reversibly and transiently bind to a target, and which are being replenished from a buffer which serves as a reservoir. Using fluorophore-labeled short DNA oligonucleotides, we labeled cellular structures with target-specific antibodies that contain complementary DNA sequences and record the fluctuation events caused by transient emitter binding. We show that this concept bypasses extensive photobleaching and facilitates two-color imaging of cellular structures with SOFI.
Ein wichtiges Teilgebiet der Organokatalyse stellt die Wasserstoffbrücken-vermittelte Katalyse dar. Als erfolgreiche katalytische Einheiten haben sich dabei diejenigen Systeme ausgezeichnet, die in der Lage sind mindestens zwei Wasserstoffbrücken zeitgleich auszubilden. Zu den bekanntesten Vertretern zählen hierbei sicher (Thio-) Harnstoffe sowie Guanidinium- und Amidinium-Ionen.
Im Rahmen der vorliegenden Doktorarbeit wurden drei Katalysatortypen mit Amidin- und Guanidingrundgerüst synthetisiert. Zum Einen wurde ein neues axial-chirale Amidin mit zusätzlicher Thioharnstoff-Funktion synthetisiert. Hierfür wurden drei aromatische Fragmente mittels zweier Suzuki-Kupplungen verknüpft und im Nachhinein mit einem chiralen Aminoalkohol über eine Williamson-Ethersynthese kondensiert. Die basenvermittelte, diastereoselektive Makrocyclisierung lieferte das axial chirale Amidin und stellte den Schlüsselschritt der Synthese dar. Schließich konnte durch Addition des erhaltenen Anilin-Derivats an ein Aryl-Isothiocyanat die Thioharnstoff-Funktionalität eingeführt werden.
Zum Anderen wurde eine Reihe an C2-symmetrischer Bisamidine hergestellt. Sie wurden in einer N-Acetylcystein-katalysierten Reaktion zwischen Phthalonitril und den entsprechenden chiralen, vicinalen Diaminen hergestellt. Die erhaltenen Ausbeuten der Bisamidine wurden unmittelbar durch den sterischen Anspruch der Substituenten des jeweils eingesetzten Diamins bestimmt. Auf der einen Seite konnten bei Verwendung 1- und 2-Naphthyl-substituierter Diamine nur mäßige Ausbeuten erzielt werden. Auf der anderen Seite konnte man durch den Einsatz kleinerer Reste wie Phenyl nahezu quantitative Ausbeuten erzielen. Die Herstellung chiraler, vicinaler Diamine wurde über eine Diaza-Cope-Umlagerung realisiert.
Schließlich wurde ein C2-symmetrisches bicyclisches Guanidin hergestellt. Die Synthese begann mit einer Knoevenagel-artigen Kondensationsreaktion und anschließender Veresterung der erhaltenen Carbonsäure. Kinetische Racematspaltung des racemischen Esters unter Verwendung einer Lipase lieferte enantiomerenreines (S)-β-Phenylalanin, welches als Ausgangverbindung der überwiegend linearen Synthese diente. Das im Zuge der Synthese hergestellte chirale Triamin wurde schließlich mithilfe von Dimethyltrithiocarbonat zum Guanidin cyclisiert.
Alle drei Katalysatortypen wurden für die enantioselektive Steuerung diverser Reaktionen eingesetzt, u. A. der Diels-Alder-, Morita-Baylis-Hillman-, Friedel-Crafts-Reaktion und dem Schlüsselschritt der Quinkert-Dane-Estron-Synthese. Bei Letzterem handelt es sich um eine Diels-Alder-Reaktion, um den C-Ring eines Steroidgerüsts aufzubauen, welches durch wenige chemische Transformationen in das bedeutende weibliche Sexualhormon Estron überführt werden kann.
Goldenberg, Ido ; Erath, Julia W. ; Russo, Andrea M. ; Burch, Ashley E. ; Aßmus, Birgit ; Bonderman, Diana ; McNitt, Scott ; Kutyifa, Valentina
Background: Data on the arrhythmic burden of women at risk for sudden cardiac death are limited, especially in patients using the wearable cardioverter-defibrillator (WCD).
Objective: We aimed to characterize WCD compliance, atrial and ventricular arrhythmic burden, and WCD outcomes by sex in patients enrolled in the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II U.S. Registry).
Methods: In the WEARIT-II Registry, we stratified 2000 patients by sex into women (n = 598) and men (n = 1402). WCD wear time, ventricular and atrial arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates at the end of WCD use were evaluated.
Results: The mean WCD wear time was similar in women and men (94 days vs 90 days; P = .145), with longer daily use in women (21.4 h/d vs 20.7 h/d; P = .001). Burden of ventricular tachycardia or ventricular fibrillation was higher in women, with 30 events per 100 patient-years compared with 18 events per 100 patient-years in men (P = .017), with similar findings for treated and non-treated ventricular tachycardia/ventricular fibrillation. Recurrent atrial arrhythmias/sustained ventricular tachycardia was also more frequent in women than in men (167 events per 100 patient-years vs 73 events per 100 patient-years; P = .042). However, ICD implantation rate at the end of WCD use was similar in both women and men (41% vs 39%; P = .448).
Conclusion: In the WEARIT-II Registry, we have shown a higher burden of ventricular and atrial arrhythmic events in women than in men. ICD implantation rates at the end of WCD use were similar. Our findings warrant monitoring women at risk for sudden cardiac death who have a high burden of atrial and ventricular arrhythmias while using the WCD.
Christine Lagarde verband die Ankündigung ihres ersten, moderaten Rettungspakets mit der Aufforderung an die Mitgliedstaaten, fiskalische Hilfen bereitzustellen. Die Märkte scheinen sich das Vertrauen in die Fiskalpolitik indessen abgewöhnt zu haben. Da starke geldpolitische Signale zunächst ausblieben, ging die Talfahrt weiter, bis Lagarde im zweiten Versuch in die Fußstapfen ihres Vorgängers trat und die Schleusen öffnete.
When Christine Lagarde announced her first, moderate rescue package, she called upon member states to provide fiscal aid. But the markets showed to have lost confidence in fiscal policy. In the absence of strong monetary policy signals, the slide continued until Lagarde in her second attempt opened the floodgates.
Warum das Stichwort Corona Bonds so viele falsche Assoziationen weckt, und wie sie beschaffen sein müssten, damit auch Deutschland damit gut klarkommt: Vor der morgigen Sitzung der Eurogruppe spricht Max Steinbeis mit MATTHIAS GOLDMANN über seinen Vorschlag und die damit verknüpften Chancen und Risiken.
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.
González Palomares, Eugenia ; López Jury, Luciana ; García Rosales, Francisco ; Hechavarria-Cueria, Julio C.
The auditory midbrain (inferior colliculus, IC) plays an important role in sound processing, acting as hub for acoustic information extraction and for the implementation of fast audio-motor behaviors. IC neurons are topographically organized according to their sound frequency preference: dorsal IC regions encode low frequencies while ventral areas respond best to high frequencies, a type of sensory map defined as tonotopy. Tonotopic maps have been studied extensively using artificial stimuli (pure tones) but our knowledge of how these maps represent information about sequences of natural, spectro-temporally rich sounds is sparse. We studied this question by conducting simultaneous extracellular recordings across IC depths in awake bats (Carollia perspicillata) that listened to sequences of natural communication and echolocation sounds. The hypothesis was that information about these two types of sound streams is represented at different IC depths since they exhibit large differences in spectral composition, i.e., echolocation covers the high-frequency portion of the bat soundscape (> 45 kHz), while communication sounds are broadband and carry most power at low frequencies (20–25 kHz). Our results showed that mutual information between neuronal responses and acoustic stimuli, as well as response redundancy in pairs of neurons recorded simultaneously, increase exponentially with IC depth. The latter occurs regardless of the sound type presented to the bats (echolocation or communication). Taken together, our results indicate the existence of mutual information and redundancy maps at the midbrain level whose response cannot be predicted based on the frequency composition of natural sounds and classic neuronal tuning curves.
González-González, Ana I. ; Schmucker, Christine ; Nothacker, Julia ; Nguyen, Truc Sophia ; Brückle, Maria-Sophie ; Blom, Jeanet ; Akker, J. M. van den ; Röttger, Kristian ; Wegwarth, Odette ; Hoffmann, Tammy ; Gerlach, Ferdinand M. ; Straus, Sharon E. ; Meerpohl, Jörg J. ; Muth, Christiane
Introduction End-of-life care is an essential task performed by most healthcare providers and often involves decision-making about how and where patients want to receive care. To provide decision support to healthcare professionals and patients in this difficult situation, we will systematically review a knowledge cluster of the end-of-life care preferences of older patients with multimorbidity that we previously identified using an evidence map.
Methods and analysis We will systematically search for studies reporting end-of-life care preferences of older patients (mean age ≥60) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception to September 2019. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date and language.
Two independent reviewers will assess eligibility, extract data and describe evidence in terms of study/population characteristics, preference assessment method and end-of-life care elements that matter to patients (eg, life-sustaining treatments). Risk of bias/applicability of results will be independently assessed by two reviewers using the Mixed-Methods Appraisal Tool. Using a convergent integrated approach on qualitative/quantitative studies, we will synthesise information narratively and, wherever possible, quantitatively.
Ethics and dissemination Due to the nature of the proposed systematic review, ethics approval is not required. Results from our research will be disseminated at relevant (inter-)national conferences and via publication in peer-reviewed journals. Synthesising evidence on end-of-life care preferences of older patients with multimorbidity will improve shared decision-making and satisfaction in this final period of life.
González-González, Ana I. ; Schmucker, Christine ; Nothacker, Julia ; Nury, Edris ; Dinh, Truc Sophia ; Brückle, Maria-Sophie ; Blom, Jeanet Wilhelmina ; Akker, Marjan van den ; Röttger, Kristian ; Wegwarth, Odette ; Hoffmann, Tammy ; Gerlach, Ferdinand M. ; Straus, Sharon E. ; Meerpohl, Jörg J. ; Muth, Christiane
Unpredictable disease trajectories make early clarification of end-of-life (EoL) care preferences in older patients with multimorbidity advisable. This mixed methods systematic review synthesizes studies and assesses such preferences. Two independent reviewers screened title/abstracts/full texts in seven databases, extracted data and used the Mixed Methods Appraisal Tool to assess risk of bias (RoB). We synthesized findings from 22 studies (3243 patients) narratively and, where possible, quantitatively. Nineteen studies assessed willingness to receive life-sustaining treatments (LSTs), six, the preferred place of care, and eight, preferences regarding shared decision-making processes. When unspecified, 21% of patients in four studies preferred any LST option. In three studies, fewer patients chose LST when faced with death and deteriorating health, and more when treatment promised life extension. In 13 studies, 67% and 48% of patients respectively were willing to receive cardiopulmonary resuscitation and mechanical ventilation, but willingness decreased with deteriorating health. Further, 52% of patients from three studies wished to die at home. Seven studies showed that unless incapacitated, most patients prefer to decide on their EoL care themselves. High non-response rates meant RoB was high in most studies. Knowledge of EoL care preferences of older patients with multimorbidity increases the chance such care will be provided.
Govoni, Mirco ; Bassi, Michele ; Vezzoli, Stefano ; Lucci, Germano ; Emirova, Aida ; Nandeuil, Marie Anna ; Petruzzelli, Stefano ; Jellema, Gera L. ; Afolabi, Ebenezer K. ; Colgan, Brendan ; Leaker, Brian ; Kornmann, Oliver ; Beeh, Kai Michael ; Watz, Henrik ; Singh, Dave
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.
Graf, Christiana ; Welzel, Tania Mara ; Bogdanou, Dimitra ; Vermehren, Johannes ; Beckel, Anita ; Bojunga, Jörg ; Friedrich-Rust, Mireen ; Dietz, Julia ; Kubesch, Alica ; Mondorf, Antonia Maria ; Fischer, Sarah ; Lutz, Thomas ; Stoffers, Philipp Clemens ; Herrmann, Eva ; Poynard, Thierry ; Zeuzem, Stefan ; Dultz, Georg ; Mihm, Ulrike
Background: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters. Methods: 50 patients with chronic HCV who were treated with DAAs were screened, and 49 were enrolled in the study. Biochemical and virological data, as well as noninvasive liver fibrosis parameters, were prospectively collected at baseline, at the end of treatment (EOT) and 12 and 24 weeks post-treatment. Results: 45 of 46 patients achieved sustained virologic response (SVR). The prevalence of insulin resistance (HOMA-IR) after HCV clearance was significantly lower, compared to baseline (5.3 ± 6.1 to 2.5 ± 1.9, p < 0.001), which is primarily attributable to a significant decrease of fasting insulin levels (18.9 ± 17.3 to 11.7 ± 8.7; p = 0.002). In contrast to that, HCV eradication resulted in a significant increase in cholesterol levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL-C) levels) and Controlled Attenuated Score (CAP), although BMI did not significantly change over time (p = 0.95). Moreover, HOMA-IR correlated significantly with noninvasive liver fibrosis measurements at baseline und during follow-up (TE: r = 0.45; p = 0.003, pSWE: r = 0.35; p = 0.02, APRI: r = 0.44; p = 0.003, FIB-4: r = 0.41; p < 0.001). Conclusion: Viral eradication following DAA therapy may have beneficial effects on glucose homeostasis, whereas lipid profile seems to be worsened.
Imageability and emotionality ratings for 2592 German nouns (3–10 letters, one to three phonological syllables) were obtained from younger adults (21–31 years) and older adults (70–86 years). Valid ratings were obtained on average from 20 younger and 23 older adults per word for imageability, and from 18 younger and 19 older adults per word for emotionality. The internal consistency (Cronbach’s α) and retest rank-order stability of the ratings were high for both age groups (α and r ≥ .97). Also, the validity of our ratings was found to be high, as compared to previously published ratings (r ≥ .86). The ratings showed substantial rank-order stability across younger and older adults (imageability, r = .94; emotionality, r = .85). At the same time, systematic differences between age groups were found in the mean levels of ratings (imageability, d = 0.38; emotionality, d = 0.20) and in the extent to which the rating scales were used (imageability, SD = 24 vs. 19, scale of 0 to 100; emotionality, SD = 26 vs. 31, scale of −100 to 100). At the descriptive level, our data hint at systematically different evaluations of semantic categories regarding imageability and emotionality across younger and older adults. Given that imageability and emotionality have been reported, for instance, as important determinants for the recognition and recall of words, our findings highlight the importance of considering age-specific information in age-comparative cognitive (neuroscience) experimental studies using word materials. The age-specific imageability and emotionality ratings for the 2592 German nouns can be found in the electronic supplementary material...
An important question in banking is how strict supervision affects bank lending and in turn local business activity. Supervisors forcing banks to recognize losses could choke off lending and amplify local economic woes. But stricter supervision could also change how banks assess and manage loans. Estimating such effects is challenging. We exploit the extinction of the thrift regulator (OTS) to analyze economic links between strict supervision, bank lending and business activity. We first show that the OTS replacement indeed resulted in stricter supervision of former OTS banks. Next, we analyze the ensuing lending effects. We show that former OTS banks increase small business lending by roughly 10 percent. This increase is concentrated in well-capitalized banks, those more affected by the new regime, and cannot be fully explained by a reallocation from mortgage to small business lending after the crisis. These findings suggest that stricter supervision operates not only through capital but can also correct deficiencies in bank management and lending practices, leading to more lending and a reallocation of loans.
Die Frage der Frauenrechte in Afghanistan diente nach dem Sturz des Taliban-Regimes als Legitimation für das militärische und entwicklungspolitische Engagement der internationalen Gemeinschaft. Jedoch existieren bis heute nur wenige empirische Arbeiten, die Aufschluss über Lebenslagen afghanischer Frauen geben und Interventionen lokaler Akteur*innen untersuchen, die diese adressieren. Die vorliegende Dissertation, die in der feministischen Ethnologie und in der Ethnologie der Menschenrechte verortet ist, trägt dazu bei, diese Forschungslücken zu schließen.
Die Daten wurden in mehrmonatigen teilnehmenden Beobachtungen in zwei afghanischen Frauenrechts-NGOs und einem Frauenrechtsnetzwerk erhoben, ergänzt von 38 Interviews. Vier Interventionsformen gegen Gewalt an Frauen werden analysiert: Neben Frauenselbsthilfegruppen und Frauenhäusern sind dies Interaktionen mit religiösen und anderen Machtakteuren. Nach Merry (2006) werden die Interventionen als Aushandlungs- und Übersetzungsprozesse divergierender Vorstellungen über Geschlechternormen und soziale Praktiken innerhalb des afghanischen Normenpluralismus konzeptualisiert.
Die Studie liefert Ergebnisse auf mehreren Ebenen. Erstens werden sowohl spezifische Bedingungen für die Wirksamkeit der untersuchten Interventionsformen herausgearbeitet als auch ihre jeweiligen Begrenzungen, welche in den vorherrschenden Machtdynamiken begründet sind. Deutlich wird zweitens der Nutzen der universalen Menschenrechte als Bezugs- und Legitimationsrahmen für die Aktivist*innen, wobei sich gleichermaßen zeigt, wo sich der Bezug auf Menschenrechte als problematisch erweist. Um Rückschlüsse für zukünftige Interventionen von Frauenrechts-NGOs auch über den afghanischen Kontext hinaus ziehen zu können, wird drittens eine Erweiterung des Theorie-Praxis-Modells nach Merry (2006) vorgeschlagen, welche die Kontextualisierung in Machtverhältnisse miteinbezieht, sowie Begrenzungen als Indikatoren für Aushandlungsspielräume postuliert.
Several studies suggested that transcription factor (TF) binding to DNA may be impaired or enhanced by DNA methylation. We present MeDeMo, a toolbox for TF motif analysis that combines information about DNA methylation with models capturing intra-motif dependencies. In a large-scale study using ChIP-seq data for 335 TFs, we identify novel TFs that are affected by DNA methylation. Overall, we find that CpG methylation decreases the likelihood of binding for the majority of TFs. For a considerable subset of TFs, we show that intra-motif dependencies are pivotal for accurately modelling the impact of DNA methylation on TF binding.
Recently, photochromic derivatives of nucleobases have drawn attention for regulating oligonucleotide hybridization with light for photopharmacological applications. The nucleobase moiety provides attractive interaction for hybridization, whereas the photochromic moiety can alter the interaction upon irradiation due to conformational changes. Herein we report the synthesis of 2‐phenyldiazenyl‐substituted 2’‐deoxyadenosine (dAAzo) and 2’‐deoxyguanosine (dGAzo) and investigate their influence in a DNA context by UV/Vis absorption, fluorescence and CD spectroscopies. For comparison, the literature‐known azobenzene C‐nucleoside DNAzo was used as a reference system. It could be shown that photochromic purines improve overall hybridization affinity compared to azobenzene C‐nucleosides. In particular, 2’‐deoxyadenosine analogue dAAzo increases melting temperatures by 7.5 °C in the favored trans state with 86 % of the switching efficiency of the reference system.
Density visualization pipeline: a tool for cellular and network density visualization and analysis
(2020)
Neuron classification is an important component in analyzing network structure and quantifying the effect of neuron topology on signal processing. Current quantification and classification approaches rely on morphology projection onto lower-dimensional spaces. In this paper a 3D visualization and quantification tool is presented. The Density Visualization Pipeline (DVP) computes, visualizes and quantifies the density distribution, i.e., the “mass” of interneurons. We use the DVP to characterize and classify a set of GABAergic interneurons. Classification of GABAergic interneurons is of crucial importance to understand on the one hand their various functions and on the other hand their ubiquitous appearance in the neocortex. 3D density map visualization and projection to the one-dimensional x, y, z subspaces show a clear distinction between the studied cells, based on these metrics. The DVP can be coupled to computational studies of the behavior of neurons and networks, in which network topology information is derived from DVP information. The DVP reads common neuromorphological file formats, e.g., Neurolucida XML files, NeuroMorpho.org SWC files and plain ASCII files. Full 3D visualization and projections of the density to 1D and 2D manifolds are supported by the DVP. All routines are embedded within the visual programming IDE VRL-Studio for Java which allows the definition and rapid modification of analysis workflows.
This article investigates the roles of psychological biases for deviations between subjective survival beliefs (SSBs) and objective survival probabilities. We model these deviations through age-dependent inverse S-shaped probability weighting functions. Our estimates suggest that implied measures for cognitive weakness increase and relative optimism decrease with age. Direct measures of cognitive weakness and optimism share these trends. Our regression analyses confirm that these factors play strong quantitative roles in the formation of SSBs. Our main finding is that cognitive weakness instead of optimism becomes with age an increasingly important contributor to the well-documented overestimation of survival chances in old age.
MicroRNA miR-181 - a rheostat for TCR signaling in thymic selection and peripheral T-Cell function
(2020)
The selection of T cells during intra-thymic d evelopment is crucial to obtain a functional and simultaneously not self-reactive peripheral T cell repertoire. However, selection is a complex process dependent on T cell receptor (TCR) thresholds that remain incompletely understood. In peripheral T cells, activation, clonal expansion, and contraction of the active T cell pool, as well as other processes depend on TCR signal strength. Members of the microRNA (miRNA) miR-181 family have been shown to be dynamically regulated during T cell development as well as dependent on the activation stage of T cells. Indeed, it has been shown that expression of miR-181a leads to the downregulation of multiple phosphatases, implicating miR-181a as ‘‘rheostat’’ of TCR signaling. Consistently, genetic models have revealed an essential role of miR-181a/b-1 for the generation of unconventional T cells as well as a function in tuning TCR sensitivity in peripheral T cells during aging. Here, we review these broad roles of miR-181 family members in T cell function via modulating TCR signal strength.
Griesinger, Frank ; Eberhardt, Wilfried E. E. ; Nusch, Arnd ; Reiser, Marcel ; Zahn, Mark-Oliver ; Maintz, Christoph ; Bernhardt, Christiane ; Losem, Christoph ; Stenzinger, Albrecht ; Heukamp, Lukas ; Büttner, Reinhard ; Marschner, Sebastian ; Jänicke, Martina ; Fleitz, Annette ; Spring, Lisa ; Sahlmann, Jörg ; Karatas, Aysun ; Hipper, Annette ; Weichert, Wilko ; Heilmann, Monika ; Sadjadian, Parvis ; Gleiber, Wolfgang ; Grah, Christian ; Waller, Cornelius ; Reck, Martin ; Rittmeyer, Achim ; Christopoulos, Petros ; Sebastian, Martin ; Thomas, Michael
Objectives: An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the “real-world” setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany.
Patients and methods: This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1.
Results: In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4–10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9–9.2) with druggable ALK alterations.
Conclusion: Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation.
Das Versprechen der Demokratie ist nicht, dass dem Willen des Volkes Geltung verschafft wird. Denn den Willen des Volkes gibt es nicht. Es gibt vielmehr nur unzählige Kombinationen von Meinungen und Interessen, aus denen jeweils von neuem ein dem Volk zurechenbarer Wille gebildet werden muss. In dem so gebildeten Willen werden sich nie alle wieder finden. Das Versprechen der Demokratie ist aber, dass alle bei der Bildung des Willens mitwirken und also Einfluss auf das Ergebnis nehmen können und dass der jeweiligen Mehrheit nicht alles erlaubt ist, insbesondere nicht, die Minderheit um ihre Chancen zu bringen, selbst Mehrheit zu werden, samt den Voraussetzungen, die dafür nötig sind.
Purpose of Review: Attention deficit hyperactivity disorder (ADHD) shows high heritability in formal genetic studies. In our review article, we provide an overview on common and rare genetic risk variants for ADHD and their link to clinical practice.
Recent findings: The formal heritability of ADHD is about 80% and therefore higher than most other psychiatric diseases. However, recent studies estimate the proportion of heritability based on singlenucleotide variants (SNPs) at 22%. It is a matter of debate which genetic mechanisms explain this huge difference. While frequent variants in first mega-analyses of genome-wideassociation study data containing several thousand patients give the first genome-wide results, explaining only little variance, the methodologically more difficult analyses of rare variants are still in their infancy. Some rare genetic syndromes show higher prevalence for ADHD indicating a potential role for a small number of patients. In contrast, polygenic risk scores (PRS) could potentially be applied to every patient. We give an overview how PRS explain different behavioral phenotypes in ADHD and how they could be used for diagnosis and therapy prediction.
Summary: Knowledge about a patient’s genetic makeup is not yet mandatory for ADHD therapy or diagnosis. PRS however have been introduced successfully in other areas of clinical medicine, and their application in psychiatry will begin within the next years. In order to ensure competent advice for patients, knowledge of the current state of research is useful forpsychiatrists.
Grimm, Oliver ; Nägele, Magdalena Maria ; Küpper-Tetzel, Lea ; Greck, Moritz de ; Plichta, Michael M. ; Reif, Andreas
Rationale: Dysregulation of dopaminergic neurotransmission, specifically altered reward processing assessed via the reward anticipation in the MID task, plays a central role in the etiopathogenesis of neuropsychiatric disorders. Objectives: We hypothesized to find a difference in the activity level of the reward system (measured by the proxy reward anticipation) under drug administration versus placebo, in that amisulpride reduces, and L-DOPA enhances, its activity. Methods: We studied the influence of dopamine agonist L-DOPA and the antagonist amisulpride on the reward system using functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task in n = 45 healthy volunteers in a randomized, blinded, cross-over study. Results: The MID paradigm elicits strong activation in reward-dependent structures (such as ventral striatum, putamen, caudate, anterior insula) during reward anticipation. The placebo effect demonstrated the expected significant blood oxygen level–dependent activity in reward-dependent brain regions. Neither amisulpride nor L-DOPA led to significant changes in comparison with the placebo condition. This was true for whole-brain analysis as well as analysis of a pre-defined nucleus accumbens region-of-interest mask. Conclusion: The present results cast doubt on the sensitivity of reward anticipation contrast in the MID task for assessing dopamine-specific changes in healthy volunteers by pharmaco-fMRI. While our task was not well-suited for detailed analysis of the outcome phase, we provide reasonable arguments that the lack of effect in the anticipation phase is not due to an inefficient task but points to unexpected behavior of the reward system during pharmacological challenge. Group differences of reward anticipation should therefore not be seen as simple representatives of dopaminergic states.
Grimm, Oliver ; Weber, Heike ; Kittel-Schneider, Sarah ; Kranz, Thorsten Manfred ; Jacob, Christian P. ; Lesch, Klaus-Peter J. ; Reif, Andreas
While impulsivity is a basic feature of attention-deficit / hyperactivity disorder (ADHD), no study explored the effect of different components of the Impulsiveness (Imp) and Venturesomeness (Vent) scale (IV7) on psychiatric comorbidities and an ADHD polygenic risk score (PRS). We used the IV7 self-report scale in an adult ADHD sample of 903 patients, 70% suffering from additional comorbid disorders, and in a subsample of 435 genotyped patients. Venturesomeness, unlike immediate Impulsivity, is not specific to ADHD. We consequently analyzed the influence of Imp and Vent also in the context of a PRS on psychiatric comorbidities of ADHD. Vent shows a distinctly different distribution of comorbidities, e.g., less anxiety and depression. PRS showed no effect on different ADHD comorbidities, but correlated with childhood hyperactivity. In a complementary analysis using principal component analysis with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD criteria, revised NEO Personality Inventory, Imp, Vent, and PRS, we identified three ADHD subtypes. These are an impulsive–neurotic type, an adventurous–hyperactive type with a stronger genetic component, and an anxious–inattentive type. Our study thus suggests the importance of adventurousness and the differential consideration of impulsivity in ADHD. The genetic risk is distributed differently between these subtypes, which underlines the importance of clinically motivated subtyping. Impulsivity subtyping might give insights into the organization of comorbid disorders in ADHD and different genetic background.
Die Gallia Narbonensis gilt als eine der am stärksten romanisierten Provinzen des Imperium Romanum. Gefördert wurde dieser Umstand sicherlich durch die Nähe zu Italien und die recht frühe Provinzialisierung des Gebietes seit dem 2. Jhdt. v. Chr.1 Dabei wurde in der Forschung oft die Frage gestellt, ob ebenso die Agrarstrukturen Italiens, sprich eine auf Sklavenarbeit beruhende Großvillenwirtschaft, in der Narbonensis etabliert wurden. Trotz des eigentlich spärlichen Quellenmaterials ist die Antwort überraschenderweise meistens positiv. Das Ziel dieses Artikels besteht nun darin, diese Aussagen einer kritischen Prüfung zu unterziehen. Hierzu werden insbesondere Inschriften zur Klärung des Sozialstatus der landwirtschaftlichen Arbeitskräfte herangezogen. Ein kurzer Vergleich mit einigen epigraphischen Belegen aus den benachbarten Provinzen und eine Prüfung der Aussagefähigkeit weiterer Quellen, darunter archäologischer und ikonographischer Zeugnisse, soll die Analyse abrunden.
Needlestick injuries: a density-equalizing mapping and socioeconomic analysis of the global research
(2020)
Groneberg, Jan David Alexander ; Braumann, Hannah ; Rolle, Stefan ; Quarcoo, David ; Klingelhöfer, Doris ; Fischer, Axel ; Nienhaus, Albert ; Brüggmann, Dörthe
Background: Needlestick injuries have caused a deleterious effect on the physical and mental health of millions of health-care workers over the past decades, being responsible for occupational infections with viruses such as HIV or hepatis C. Despite this heavy burden of disease, no concise studies have been published on the global research landscape so far.
Methods: We used the New Quality and Quantity Indices in Science platform to analyze global NSI research (n = 2987 articles) over the past 115 years using the Web of Science and parameters such as global versus country-specific research activities, semi-qualitative issues, and socioeconomic figures.
Results: Density-equalizing mapping showed that although a total of n = 106 countries participated in NSI research, large parts of Africa and South America were almost invisible regarding global participation in NSI research. Average citation rate (cr) analysis indicated a high rate for Switzerland (cr = 25.1), Italy (cr = 23.5), and Japan (cr = 19.2). Socioeconomic analysis revealed that the UK had the highest quotient QGDP of 0.13 NSI-specific publications per bill. US-$ gross domestic product (GDP), followed by South Africa (QGDP = 0.12). Temporal analysis of HIV versus hepatitis research indicated that NSI-HIV research culminated in the early 1990s, whereas NSI-hepatitis research increased over the observed period from the 1980s until the last decade.
Conclusion: Albeit NSI research activity is generally increasing, the growth is asymmetrical from a global viewpoint. International strategies should be followed that put a focus on NSI in non-industrialized areas of the world.
Gronenborn, Detlef ; Thiemeyer, Heinrich ; Cramer, Anja ; Antunes, Nicolas ; Neubauer, Dieter ; Pétrequin, Pierre
In the nineteenth century, two Neolithic axe-heads were reported from the Michelsberg enclosure system at Kapellenberg. The recent identification of an unusually large tumulus, from which the axe-heads were almost certainly once recovered, reveals that socio-political hierarchisation, linked to the emergence of high-ranking elites in Brittany and the Paris Basin during the fifth millennium cal BC, may have extended into Central Europe.
Supranational rules, national discretion: increasing versus inflating regulatory bank capital?
(2020)
We study how higher capital requirements introduced at the supranational level affect the regulatory capital of banks across countries. Using the 2011 EBA capital exercise as a quasi-natural experiment, we find that treated banks exploit discretion in the calculation of regulatory capital to inflate their capital ratios without a commensurate increase in their book equity and without a reduction in bank risk. Regulatory capital inflation is more pronounced in countries where credit supply is expected to tighten, suggesting that national authorities forbear their domestic banks to meet supranational requirements, with a focus on short-term economic considerations.
Envy, the inclination to compare rewards, can be expected to unfold when inequalities in terms of pay-off differences are generated in competitive societies. It is shown that increasing levels of envy lead inevitably to a self-induced separation into a lower and an upper class. Class stratification is Nash stable and strict, with members of the same class receiving identical rewards. Upper-class agents play exclusively pure strategies, all lower-class agents the same mixed strategy. The fraction of upper-class agents decreases progressively with larger levels of envy, until a single upper-class agent is left. Numerical simulations and a complete analytic treatment of a basic reference model, the shopping trouble model, are presented. The properties of the class-stratified society are universal and only indirectly controllable through the underlying utility function, which implies that class-stratified societies are intrinsically resistant to political control. Implications for human societies are discussed. It is pointed out that the repercussions of envy are amplified when societies become increasingly competitive.
Angesichts der in Deutschland und anderswo präzedenzlosen Eingrenzung des rechtlich Erlaubten stehen die begrenzenden Rechtsverordnungen, Allgemeinverfügungen und vollziehenden Maßnahmen des Staates im Zentrum grundrechtlicher Aufmerksamkeit. Freiheitsschonendere Alternativen werden in erster Linie durch das Prisma der Erforderlichkeit in den Blick genommen. Sich in einer Pandemielage gegen Beschränkungen zu entscheiden, erscheint grundrechtlich unverdächtig. Doch wäre es das tatsächlich? Im Folgenden werden zwei unterschiedliche Szenarien einer solchen Entscheidung vorgestellt und es wird ein näherer Blick auf die Folgen für den individuellen Grundrechtsgebrauch geworfen. Es zeigen sich Grundrechtsfragen, die im Ergebnis auch für die Beurteilung des beschränkenden Staates aufgeworfen sind.
Gross, Eva M. ; Lahkar, Bibhuti P. ; Subedi, Naresh ; Nyirenda, Vincent R. ; Klebelsberg, Eva ; Jakoby, Oliver
In recent years, reports of elephants causing damage in rural villages by destroying houses and foraging on stored food have been increasing, but little is known about the determinants and magnitude of this damage. In this study, we have examined the extent of property damage by elephants (Loxodonta africana and Elephas maximus), in one African and two Asian study areas over a six‐year period. A total of 1,172 damaged constructions were observed on site, involving detailed damage assessment by trained enumerators and standardized interviews with witnesses. Depending on the study area, between 67.1 and 86.4% of damage events were attributed to single, individual elephants or pairs of males. The majority of properties were damaged in search for food (62.5–76.7% respectively). Property damage caused higher mean losses than crop damage on farmland in all study areas. Results suggest that property damage by elephants has been largely underestimated and needs to form a focus in future human–elephant conflict research. We suggest a need to reduce the attractiveness of villages by storing food in locked and safe places, away from sleeping areas and to foster the development of elephant safe stores, appropriate to the particular cultural background of the target area.
This article has two aims: it discusses the use and function of a very specific contract clause in Hellenistic time and explores the possibilities and limits to use databases and their automated searches and visualisations as heuristic tools. It is argued, that praxis … kata to diagramma is mainly a regional variety of an executionclause and not connected to the Greek type lawcourts as supposed by Mitteis and Wolff. Graph-databases can help to see different possible decisive features at the same time and show, which connections are more intensive than others, but automated analysis is slowed down and blurred by the lack of categorizing specific to the questions of legal history
This article has two aims: it discusses the use and function of a very specific contract clause in Hellenistic time and explores the possibilities and limits to use databases and their automated searches and visualisations as heuristic tools. It is argued, that praxis … kata to diagramma is mainly a regional variety of an executionclause and not connected to the Greek type lawcourts as supposed by Mitteis and Wolff. Graph-databases can help to see different possible decisive features at the same time and show, which connections are more intensive than others, but automated analysis is slowed down and blurred by the lack of categorizing specific to the questions of legal history
The insertion of membrane proteins requires proteinaceous complexes in the cytoplasm, the membrane, and the lumen of organelles. Most of the required complexes have been described, while the components for insertion of β‐barrel‐type proteins into the outer membrane of chloroplasts remain unknown. The same holds true for the signals required for the insertion of β‐barrel‐type proteins. At present, only the processing of Toc75‐III, the β‐barrel‐type protein of the central chloroplast translocon with an atypical signal, has been explored in detail. However, it has been debated whether Toc75‐V/ outer envelope protein 80 (OEP80), a second protein of the same family, contains a signal and undergoes processing. To substantiate the hypothesis that Toc75‐V/OEP80 is processed as well, we reinvestigated the processing in a protoplast‐based assay as well as in native membranes. Our results confirm the existence of a cleavable segment. By protease protection and pegylation, we observed intermembrane space localization of the soluble N‐terminal domain. Thus, Toc75‐V contains a cleavable N‐terminal signal and exposes its polypeptide transport‐associated domains to the intermembrane space of plastids, where it likely interacts with its substrates.
Groß, Tilman ; Wack, Gesine ; Syhr, Katharina Martina Janice ; Tolmachova, Tanya ; Seabra, Miguel C. ; Geisslinger, Gerd ; Niederberger, Ellen ; Schmidtko, Achim ; Kallenborn-Gerhardt, Wiebke
Tissue injury and inflammation may result in chronic pain, a severe debilitating disease that is associated with great impairment of quality of life. An increasing body of evidence indicates that members of the Rab family of small GTPases contribute to pain processing; however, their specific functions remain poorly understood. Here, we found using immunofluorescence staining and in situ hybridization that the small GTPase Rab27a is highly expressed in sensory neurons and in the superficial dorsal horn of the spinal cord of mice. Rab27a mutant mice, which carry a single-nucleotide missense mutation of Rab27a leading to the expression of a nonfunctional protein, show reduced mechanical hyperalgesia and spontaneous pain behavior in inflammatory pain models, while their responses to acute noxious mechanical and thermal stimuli is not affected. Our study uncovers a previously unrecognized function of Rab27a in the processing of persistent inflammatory pain in mice.