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Die Arbeit untersucht die Ad-hoc-Publizität unter der Geltung der MAR. In der Arbeit werden zuerst das Informationsmodell auf dem Kapitalmarkt und die Erforderlichkeit und Notwendigkeit der Regulierung des Kapitalmarkts durch gesetzliche Informationspflichten analysiert. Mithilfe eines Rückblicks auf die Entwicklung der Ad-hoc-Publizität in den Rechtsnormen wird ihr Sinn und Zweck untersucht. Die rechtlichen Anforderungen an Ad-hoc-Publizität unter der Geltung der MAR werden in einem weiteren Schritt untersucht. Der Schwerpunkt liegt dabei auf den Tatbestandsmerkmalen der Ad-hoc-Publizitätspflicht und dem Aufschub der Veröffentlichung. Darüber hinaus werden die Rechtsfolgen im Falle von Pflichtverstößen, insbesondere Anspruchsgrundlagen nach §§ 97, 98 WpHG analysiert. Im Hinblick auf die Ad-hoc-Publizität nach dem chinesischen Recht werden ihre historische Entwicklung in Rechtsnormen und ihr Sinn und Zweck untersucht. Eine dogmatische Analyse der Ad-hoc-Publizitätspflicht und der Rechtsfolgen beim Pflichtverstoß nach dem geltenden chinesischen Recht wird dann durchgeführt. Schließlich wird die Ad-hoc-Publizität nach der MAR und dem chinesischen Recht verglichen.
Im rechtsvergleichenden Teil der Untersuchung identifiziert der Verfasser bestimmte Besonderheiten und Defizite im chinesischen Recht. Den Regelungsansätzen der beiden Rechtssysteme liegen unterschiedliche rechtpolitische Zielsetzungen zugrunde. In der EU und in Deutschland steht der Konnex zum Insiderhandel im Vordergrund, denn diesem wird durch die Ad-Hoc Meldung der Boden entzogen. In China handelt es sich bei der Ad-hoc-Publizität konzeptionell eher um einen Annex zur Regelpublizität. Damit geht Hand in Hand, dass die Verfolgung zivilrechtlicher Ansprüche aufgrund falscher Ad-hoc-Meldungen in China der behördlichen Genehmigung bedarf. Der Verfasser macht auf dieser Grundlage Vorschläge zur (behutsamen) Rechtsfortbildung in China nach europäischem Vorbild.
This inventory intends to provide updated numbers of vascular plants occurring in Cyprus. Currently, 1649 indigenous taxa (species and subspecies) are known to occur in Cyprus. In addition 254 taxa belong to various categories of neophytes. The endemism rate of the indigenous flora amounts to 8.55 %, i. e. 141 taxa, while 33 species and subspecies belong to the category of near-endemic for which Cyprus bears significant responsibility for their conservation.
The recently described Phelipanche hedypnoidis from the Orobanche (Phelipanche) ramosa group has been found in Cyprus for the first time. So far, it is known only from one site at the south coast. Hedypnois rhagadioloides as host plant is confirmed. To meet the demands of a more traditional generic treatment the new combination Orobanche hedypnoidis is proposed.
Further noteworthy records of vascular plants in Cyprus (1997–2018) and some status clarifications
(2019)
This paper deals with specimen-based records of 74 taxa, most of them having a scattered occurrence or restricted distribution range in Cyprus. The following taxa are new to Cyprus or have been found in the wild for the first time: Aristida adscensionis subsp. adscensionis, Buglossoides incrassata subsp. splitgerberi, Cenchrus setaceus, Chenopodium rubrum, Gazania rigens, Malus domestica, Mespilus germanica, Mirabilis jalapa, Pyrus communis, Sambucus nigra and Spartium junceum. The new combination Urtica cypria (H. Lindb.) Hand for the endemic nettle species is proposed.
Tradescantia fluminensis is an invasive weed that has been recorded for the first time in Cyprus. The species occurs in river banks, mainly under shady conditions. It has been recorded in three sites, always at low density: Marathasa river (Lefkosia district), Kargotis river (Lefkosia district), Kryos river (Lemesos district).
The influence of temperature is regarded as particularly important for a structural health monitoring system based on ultrasonic guided waves. Since the temperature effect causes stronger signal changes than a typical defect, the former must be addressed and compensated for reliable damage assessment. Development of new temperature compensation techniques as well as the comparison of existing algorithms require high-quality benchmark measurements. This paper investigates a carbon fiber reinforced plastic (CFRP) plate that was fully characterized in previous research in terms of stiffness tensor and guided wave propagation. The same CFRP plate is used here for the analysis of the temperature effect for a wide range of ultrasound frequencies and temperatures. The measurement data are a contribution to the Open Guided Waves (OGW) platform: http://www.open-guided-waves.de. The technical validation includes initial results on the analysis of phase velocity variations with temperature and exemplary damage detection results using state-of-the-art signal processing methods that aim to suppress the temperature effect.
AMPA receptors and interacting proteins are importantly involved in mediating stress-dependent plasticity. Previously we reported that GluA1-containing AMPA receptors and their interaction with PDZ-proteins are required for the experience-dependent expression of behavioral despair in the forced swim test. However, it is unclear if the expression of GluA1-containing AMPA receptors is affected by this type of behavior. Here we investigated in wild type mice, whether hippocampal gene or protein levels of GluA1 or associated PDZ proteins is altered following forced swim stress. We show that expression of Dlg4 (the gene coding for PSD-95) was strongly reduced after two days of forced swimming. In contrast, levels of Dlg1, Gria1, and Gria2 (coding for SAP97, GluA1, and GluA2 respectively) were not affected after one or two days of forced swimming. The changes in gene expression largely did not translate to the protein level. These findings indicate a limited acute effect of forced swim stress on the expression of the investigated targets and suggest that the acute involvement of GluA1-containing AMPA receptors tor forced swim behavior is a result of non-genomic mechanisms.
Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2–3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period.
Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the “door-to-needle” time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire.
Interventions: We are applying a multi-level intervention in cooperation with three “STREAM multipliers” from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2–3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings.
Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and often has a poor prognosis. The present study investigated the role of the low affinity nerve growth factor receptor CD271 as a putative therapy target in HNSCC. Neurotrophins that bind to CD271 also have a high affinity for the tropomyosin receptor kinase family (Trk), consisting of TrkA, TrkB, and TrkC, which must also be considered in addition to CD271. A retrospective study and functional in vitro cell line tests (migration assay and cell sorting) were conducted in order to evaluate the relevance of CD271 expression alone and with regard to Trk expression. CD271 and Trks were heterogeneously expressed in human HNSCC. The vast majority of tumors exhibited CD271 and TrkA, whereas only half of the tumors expressed TrkB and TrkC. High expression of CD271-positive cells predicted a bad clinical outcome of patients with HNSCC and was associated with distant metastases. However, the human carcinomas that also expressed TrkC had a reduced correlation with distant metastases and better survival rates. In vitro, CD271 expression marked a subpopulation with higher proliferation rates, but proliferation was lower in tumor cells that co-expressed CD271 and TrkC. The CD271 inhibitor LM11A 31 suppressed cell motility in vitro. However, neither TrkA nor TrkB expression were linked to prognosis or cell proliferation. We conclude that CD271 is a promising candidate that provides prognostic information for HNSCC and could be a putative target for HNSCC treatment.
Background: Outcomes of catheter ablation of atrial fibrillation (AF) are variable and the predictors of success require further elucidation since the identification of correctable risk factors could help to optimize therapy. We aimed to assess the impact of body mass index (BMI) in the overall safety and efficacy of catheter ablation of AF, with emphasis on the use of cryoballoon ablation and novel oral anticoagulants.
Methods and Results: There were 2497 consecutive patients undergoing catheter ablation of AF in 7 European high volume centers were stratified according to BMI (normal weight <25 kg/m2, pre‐obese 25–30 kg/m2, obesity 30–35 kg/m2, and morbid obesity ≥35 kg/m2) and comparisons of procedural outcomes evaluated. Pre‐obese and obese patients presented more comorbidities (hypertension, diabetes mellitus, and sleep apnea), and had higher rates of non‐paroxysmal AF ablation procedures. The rate of atrial 12‐month arrhythmia relapse increased alongside with BMI (35.2%, 35.7%, 43.6%, and 48.0% P<0.001). During a median follow‐up of 18.8 months (interquartile range 11–28), after adjusting for all baseline differences, BMI was an independent predictor of relapse (hazard ratio=1.01 per kg/m2; 95% CI 1.01–1.02; P=0.002), adding incremental predictive value to obstructive sleep apnea. BMI was not a predictor for any of the reported complications. Using novel oral anticoagulants and cryoballoon ablation was safe and efficacy was comparable with vitamin‐K antagonists and radiofrequency ablation.
Conclusions: Obese patients present with a more adverse comorbidity profile, more advanced forms of AF, and have lower chances of being free from AF relapse after ablation. Use of novel oral anticoagulants and cryoballoon ablation may be an option in this patient group.
In vivo functional diversity of midbrain dopamine neurons within identified axonal projections
(2019)
Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.
Intact-cell maldi-tof mass spectrometry for the authentication of drug-adapted cancer cell lines
(2019)
The use of cell lines in research can be affected by cell line misidentification. Short tandem repeat (STR) analysis is an effective method, and the gold standard, for the identification of the genetic origin of a cell line, but methods that allow the discrimination between cell lines of the same genetic origin are lacking. Here, we use intact cell MALDI-ToF mass spectrometry analysis, routinely used for the identification of bacteria in clinical diagnostic procedures, for the authentication of a set of cell lines consisting of three parental neuroblastoma cell lines (IMR-5, IMR-32 and UKF-NB-3) and eleven drug-adapted sublines. Principal component analysis (PCA) of intact-cell MALDI-ToF mass spectrometry data revealed clear differences between most, but not all, of the investigated cell lines. Mass spectrometry whole-cell fingerprints enabled the separation of IMR-32 and its clonal subline IMR-5. Sublines that had been adapted to closely related drugs, for example, the cisplatin- and oxaliplatin-resistant UKF-NB-3 sublines and the vincristine- and vinblastine-adapted IMR-5 sublines, also displayed clearly distinctive patterns. In conclusion, intact whole-cell MALDI-ToF mass spectrometry has the potential to be further developed into an authentication method for mammalian cells of a common genetic origin.
Anaplastic large cell lymphoma (ALCL) and classical Hodgkin lymphoma (cHL) are lymphomas that contain CD30-expressing tumor cells and have numerous pathological similarities. Whereas ALCL is usually diagnosed at an advanced stage, cHL more frequently presents with localized disease. The aim of the present study was to elucidate the mechanisms underlying the different clinical presentation of ALCL and cHL. Chemokine and chemokine receptor expression were similar in primary ALCL and cHL cases apart from the known overexpression of the chemokines CCL17 and CCL22 in the Hodgkin and Reed-Sternberg (HRS) cells of cHL. Consistent with the overexpression of these chemokines, primary cHL cases encountered a significantly denser T cell microenvironment than ALCL. Additionally to differences in the interaction with their microenvironment, cHL cell lines presented a lower and less efficient intrinsic cell motility than ALCL cell lines, as assessed by time-lapse microscopy in a collagen gel and transwell migration assays. We thus propose that the combination of impaired basal cell motility and differences in the interaction with the microenvironment hamper the dissemination of HRS cells in cHL when compared with the tumor cells of ALCL.
Inflammatory activation of astroglia adds to the pathology of various neurological diseases. Astrocytes respond to microglia-derived cytokines such as interleukin-1α (IL-1α) with enhanced inflammatory signaling. This provokes pro-inflammatory gene expression of, among others, the eicosanoid-generating enzyme prostaglandin endoperoxide synthase 2 (Ptgs2). Whereas metabolic regulation of innate immune cell inflammatory responses is intensely studied, pathways related to how metabolism modulates inflammatory signaling in astrocytes are underexplored. Here, we examined how mitochondrial oxidative phosphorylation affects inflammatory responses towards IL-1α and tumor necrosis factor α in neonatal rat astrocytes. Blocking respiratory complex I and III or adenosine triphosphate (ATP) synthase did not affect activation of inflammatory signaling by IL-1α, but did elicit differential effects on inflammatory gene mRNA expression. Remarkably, mRNA and protein expression of Ptgs2 by IL-1α was consistently up-regulated when oxidative phosphorylation was inhibited. The increase of Ptgs2 resulted from mRNA stabilization. Mitochondrial inhibitors also increased IL-1α-triggered secretion of eicosanoids, such as prostaglandin E2, prostaglandin F2α, and 6-keto-prostaglandin F1α, as assessed by liquid chromatography/mass spectrometry. Mechanistically, attenuating oxidative phosphorylation elevated adenosine monophosphate (AMP) and activated AMP-activated protein kinase (AMPK). AMPK silencing prevented Ptgs2 up-regulation by mitochondrial inhibitors, while AMPK activators recapitulated Ptgs2 mRNA stability regulation. Our data indicate modulation of astrocyte inflammatory responses by oxidative metabolism, with relevance towards eicosanoid production.
Background: Receiving a cancer diagnosis can be a major life event which causes distress even years after primary treatment.
Aim: To examine the prevalence of distress in older patients with cancer (OPCs) up until 5 years post-diagnosis, and identify predictors present at time of diagnosis. Results are compared with reference groups of middle-aged patients with cancer (MPCs) and older patients without a cancer diagnosis (OPs).
Design & setting: OPCs, MPCs, and OPs participated in a longitudinal cohort study in Belgium and the Netherlands by filling in questionnaires at designated time points from 2010–2019.
Method: Data from 541 patients were analysed using multivariable logistic regression analyses.
Results: At baseline, 40% of OPCs, 37% of MPCs, and 17% of OPs reported distress. After 5 years, 35% of OPCs, 23% of MPCs, and 25% of OPs reported distress. No significant predictors for long-term distress in OPCs and OPs were found. For MPCs, it was found that baseline distress (odds ratio [OR] 2.94; 95% confidence intervals [CI] = 1.40 to 6.19) and baseline fatigue (OR 4.71; 95% CI = 1.81 to 12.31) predicted long-term distress.
Conclusion: Distress is an important problem for people with cancer, with peaks at different moments after diagnosis. Feelings of distress are present shortly after diagnosis but they decrease quickly for the majority of patients. In the long term, however, OPCs in particular appear to be most at risk for distress. This warrants extra attention from primary healthcare professionals, such as GPs who are often patients’ first medical contact point. More research into risk factors occurring later in an illness trajectory might shed more light on predictors for development of long-term distress.
Wie man weiß, zählt der Sozialstaat der Industrieepoche zu den ganz großen Innovationen in der Institutionengeschichte. Es entsteht ausgehend vom europäischen Norden und Westen und schnell mit kontinentalen und globalen Dimensionen ein hochkomplexes Geflecht aus Organisationen, aus juridischen und nicht-juridischen Normen und aus sozialen Praktiken, das auf die große – für das Schicksal der kapitalistischen Ordnung mitentscheidende – Herausforderung der "sozialen Frage" antwortet. Dabei ist dieses Gefüge nicht strukturell einheitlich, sondern durch erhebliche nationale Variation geprägt. Darüber hinaus entstehen die Institutionen im Rahmen der Einzelstaaten in keiner Weise gleichzeitig, sondern auf einer langgestreckten Zeitachse. Dieser Befund der hochgradigen Varianz kennzeichnet den Sektor der industriellen Beziehungen, in dem kollektive Akteure wesentliche Aufgaben des Sozialstaats "übernehmen", in einer besonders intensiven Weise. Es ist dieser Bereich, auf den wir sogleich näher eingehen. Im Weiteren kommt es auf dem Kontinent mit dem Aufstieg nicht-demokratischer Regime und deren Versionen des Sozialstaats zu einer zusätzlichen Komplizierung. Und schließlich tritt die neue Makrostruktur – ihren genetischen Raum überschreitend – alsbald im globalen Rahmen in Erscheinung. Ihre weltweiten Wirkungen sind immens, wie das 100-jährige Jubiläum der ILO unterstreichen mag. Und die Rückwirkungen und Irritationen vor allem aus neuen dynamischen Zentren des demokratisch verfassten Kapitalismus, zunächst der USA und dann auch Japans, sind es nicht minder. ...
Introduction: An overview of the requirements for the head of a surgical department in Germany should be given.
Materials and methods: A retrospective literature research on surgical professional policy publications of the last 10 years in Germany was conducted.
Results: Surveys show that commercial influences on medical decisions in German hospitals have today become an everyday, predominantly negative, actuality. Nevertheless, in one survey, 82.9% of surgical chief physicians reported being very satisfied with their profession, compared with 61.5% of senior physicians and only 43.4% of hospital specialists. Here, the chief physician is challenged. Only 70% of those surveyed stated that they could rely on their direct superiors when difficulties arose at work, and only 34.1% regarded feedback on the quality of their work as sufficient. The high distress rate in surgery (58.2% for all respondents) has led to a lack in desirability and is reflected in a shortage of qualified applicants for resident positions. In various position papers, surgical residents (only 35% describe their working conditions as good) demand improved working conditions. Chief physicians are being asked to facilitate a suitable work-life balance with regular working hours and a corporate culture with participative management and collegial cooperation. Appreciation of employee performance must also be expressed. An essential factor contributing to dissatisfaction is that residents fill a large part of their daily working hours with non-physician tasks. In surveys, 70% of respondents stated that they spend up to ≥3 h a day on documentation and secretarial work.
Discussion: The chief physician is expected to relieve his medical staff by employing non-physician assistants to take care of non-physician tasks. Transparent and clearly structured training to achieve specialist status is essential. It has been shown that a balanced work-life balance can be achieved for surgeons. Family and career can be reconciled in appropriately organized departments by making use of part-time and shift models that exclude 24-h shifts and making working hours more flexible.
The artworks of the Peruvian artist Carlos Runcie Tanaka, who has his British and Japanese Roots combined in his surname, refer to pre-Columbian ceramics and traditional Peruvian, Japanese and European practices. He represented Peru in ARCOmadrid 2019, the 12th Havana Biennial, the XXVI Sao Paulo Biennial, the 49th Venice Biennale, and the I Bienal Iberoamericana de Lima. In August, we sat down to talk about music, the past, the present, and the future. We discussed how all references of time can be combined into one material.
By studying pre-Columbian ceramics, researchers have developed several interpretations about the lifestyle and cosmovision of the ancient Peruvian people. Many of the techniques and motifs included in these traditional practices are still being passed on to communities throughout the country today. This ancestral knowledge is a fundamental element of identity. Therefore, ceramic is a material that has made the generation of historical discourse and the preservation of cultural memory possible. At the same time, ceramics are connected to aspects of our daily life. As objects of daily use (such as mugs, plates and bowls) they contribute to the fulfillment of basic needs. They are also included in ritual and funerary practices. In conclusion, the use of ceramics can be understood not only in a practical sense, but in an artistic sense as well.
Therapy of acute myeloid leukemia (AML) is unsatisfactory. Histone deacetylase inhibitors (HDACi) are active against leukemic cells in vitro and in vivo. Clinical data suggest further testing of such epigenetic drugs and to identify mechanisms and markers for their efficacy. Primary and permanent AML cells were screened for viability, replication stress/DNA damage, and regrowth capacities after single exposures to the clinically used pan-HDACi panobinostat (LBH589), the class I HDACi entinostat/romidepsin (MS-275/FK228), the HDAC3 inhibitor RGFP966, the HDAC6 inhibitor marbostat-100, the non-steroidal anti-inflammatory drug (NSAID) indomethacin, and the replication stress inducer hydroxyurea (HU). Immunoblotting was used to test if HDACi modulate the leukemia-associated transcription factors β-catenin, Wilms tumor (WT1), and myelocytomatosis oncogene (MYC). RNAi was used to delineate how these factors interact. We show that LBH589, MS-275, FK228, RGFP966, and HU induce apoptosis, replication stress/DNA damage, and apoptotic fragmentation of β-catenin. Indomethacin destabilizes β-catenin and potentiates anti-proliferative effects of HDACi. HDACi attenuate WT1 and MYC caspase-dependently and -independently. Genetic experiments reveal a cross-regulation between MYC and WT1 and a regulation of β-catenin by WT1. In conclusion, reduced levels of β-catenin, MYC, and WT1 are molecular markers for the efficacy of HDACi. HDAC3 inhibition induces apoptosis and disrupts tumor-associated protein expression.
Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider’s dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of core methionines serve to mobilize the fold, which can thereby access various conformations and adapt the association interface for tight binding. Methionine in a hydrophobic core equips a protein with the capacity to dynamically change shape and thus to optimize its function.
Purpose: The aim of this study is to record material- and surface-dependent heat dissipation during the process of inserting implants into native animal bone. Materials and Methods: Implants made of titanium and zirconium that were identical in macrodesign were inserted under controlled conditions into a bovine rib tempered to 37 °C. The resulting surface temperature was measured on two bone windows by an infrared camera. The results of the six experimental groups, ceramic machined (1), sandblasted (2), and sandblasted and acid-etched surfaces (3) versus titanium implants with the corresponding surfaces (4, 5, and 6) were statistically tested. Results: The average temperature increase, 3 mm subcrestally at ceramic implants, differed with high statistical significance (p = 7.163 × 10−9, resulting from group-adjusted linear mixed-effects model) from titanium. The surface texture of ceramic implants shows a statistical difference between group 3 (15.44 ± 3.63 °C) and group 1 (19.94 ± 3.28 °C) or group 2 (19.39 ± 5.73 °C) surfaces. Within the titanium implants, the temperature changes were similar for all surfaces. Conclusion: Within the limits of an in vitro study, the high temperature rises at ceramic versus titanium implants should be limited by a very slow insertion velocity.
The group of neurodegenerative diseases, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) all exhibit inclusions containing amyloid-type α-synuclein (α-syn) aggregates within degenerating brain cells. α-syn also exists as soluble oligomeric species that are hypothesized to represent intermediates between its native and aggregated states. These oligomers are present in brain extracts from patients suffering from synucleinopathies and hold great potential as biomarkers. Although easily prepared in vitro, oligomers are metastable and dissociate over time, thereby complicating α-syn oligomer research. Using the small amine-reactive cross-linker, formaldehyde (FA), we successfully stabilized α-syn oligomers without affecting their size, overall structure or antigenicity towards aggregate-conformation specific α-syn antibodies FILA and MJFR-14-6-4-2. Further, cross-linked α-syn oligomers show resistance towards denaturant like urea and SDS treatment and remain fully functional as internal standard in an aggregation-specific enzyme-linked immunosorbent assay (ELISA) despite prior incubation with urea. We propose that FA cross-linked α-syn oligomers could serve as important calibrators to facilitate comparative and standardized α-syn biomarker studies going forward.
Narratives 2.0 : a multi-dimensional approach to semi-public storytelling in WhatsApp voice messages
(2019)
Based on a corpus of voice message narratives in German WhatsApp group chats, the present study contributes to research on social media storytelling in that it focusses on stories of personal experience which are embedded in a communication platform which favours a continuous dialogic exchange, narrated to well-defined non-anonymous publics and multimodal (comprised of visual and audible posting types). To capture the characteristics of this type of social media storytelling, the paper argues that Ochs and Capps’ (2001) dimensional model originally developed for conversational narratives (including the dimensions of tellability, tellership, embeddedness, linearity, moral stance) should be expanded by the dimensions of publicness, multimodality and sequencing. The prototype of storytelling in WhatsApp group chats is based on recent personal experiences; it is related by a single teller as an initial, sequentially non-embedded and linearly organised “big package” story (in a single voice message sometimes introduced by a text message containing an abstract); other group members routinely document their evaluative stances in rather conventionalised text message responses in the semi-public group space.
This contribution aims to describe privacy, publicness and anonymity as essential analytic dimensions for media linguistic research. The dimensions are not inherent in and predetermined by the technical features and forms of communication provided by mobile devices, but are used by the participants as an orientation grid for shaping their online and offline practices in and with mobile media. Considering both mobile device use in the public realm and the dissemination of increasingly private content in social media (which is said to lead to ‘blurred boundaries’ between the private and the public), the paper provides a brief overview of the main developments in mobile media research: Studies adopting various approaches – e. g. sociological-ethnographic, linguistic and media studies – illustrate how publicness, privacy and anonymity are actively shaped and brought about by mobile media users in face-to-face and remote social encounters. As this shows that publicness, privacy and anonymity are still relevant concepts for users, future media linguistics studies should focus on the dynamic multimodal practices by which they are contextualized and accomplished.
Die peripartale Depression tritt während der Schwangerschaft und in den 12 Monaten nach der Geburt auf. Zusätzlich zu Symptomen einer depressiven Episode ist die peripartale Depression durch schwangerschafts- oder kindbezogene Symptome wie infantizidale Vorstellungen, Gefühlslosigkeit gegenüber dem Kind, Versagensängste oder Insuffizienzgefühle als Mutter gekennzeichnet. Die Prävalenz liegt bei 7 bis 10 % präpartal und 7 bis 20 % postpartal. Folge ist ein erhöhtes Risiko für frühzeitige Wehentätigkeit, geringes Geburtsgewicht, intrauterine Wachstumsstörungen, Verhaltensstörungen und gestörte kognitive Entwicklung des Kindes. Außerdem steigt die Wahrscheinlichkeit für Mutter und Kind, im weiteren Leben erneut an einer Depression zu erkranken. Therapieoptionen stehen insbesondere psychotherapeutische Verfahren wie Interpersonelle Psychotherapie und Kognitive Verhaltenstherapie und eine antidepressive Therapie zur Verfügung.
Ziel der Arbeit war es, die Publikationen zu Depression und Schwangerschaft nach szientometrischen Kriterien zu analysieren und Charakteristika und Tendenzen der Forschung zu erkennen und zu interpretieren.
Nach Definition des Suchbegriffes wurden mithilfe der Datenbank Web of Science bzw. Web of Science Core Collection alle Publikationen zu Depression im Rahmen der Schwangerschaft von 1900 bis 2012 inklusive aller bibliometrischer Daten analysiert. Die Daten wurden nach Bereinigung hinsichtlich qualitativer Gesichtspunkte und szientometrischer Parameter wie Zitierungen, Zitationsrate und modifiziertem h-Index der Publikationen, Autoren, Institutionen und Nationen untersucht. Dabei wurden zusätzlich Genderaspekte und sozioökonomische Faktoren berücksichtigt.
Insgesamt wurden 7.330 Veröffentlichungen zu Pregnancy and Depression analysiert. 95,9 % davon waren in englischer Sprache veröffentlicht. Seit 1982 konnte eine kontinuierliche Zunahme der jährlichen Publikationen verzeichnet werden. Die Zahl der Zitierungen stieg seit 1979 ebenso jährlich an. Dabei sank die Zitationsrate seit 1990. Besonders viele Arbeiten wurden im Journal of Affective Disorders und im Archives of Womens Mental Health veröffentlicht. Unter den Forschungseinrichtungen fielen die Harvard University und St. George’s, University of London durch besonders viele Publikationen auf.
Wichtigste Wissenschaftsstandorte waren die USA, Großbritannien, Australien und Kanada, was sich in den meisten Publikationen, Zitierungen und den höchsten modifizierten h Indizes äußerte, gefolgt von meist europäischen Staaten. Unter Berücksichtigung sozioökonomischer Faktoren ergaben sich mehrere Besonderheiten: Die skandinavischen Staaten Norwegen, Schweden und Finnland finden sich unter den produktivsten Ländern nach Bereinigung um die Bevölkerungszahl. Nationen mit mittlerem und niedrigem Einkommen (Low- and middle income countries = LAMICs) wie Pakistan, Südafrika und Äthiopien leisten einen relevanten Beitrag zur Forschung, berücksichtigt man das Bruttoinlandsprodukt oder die Zahl der Wissenschaftler. Internationale Kooperation dieser Nationen entstanden insbesondere mit Großbritan-nien. Durch diese Zusammenarbeit wurde einerseits auf die höhere Prävalenz von Perinataler Depression in Entwicklungs und Schwellenländern hingewiesen. Andererseits wurde die schwangerschaftsassoziierte Depression als wichtiges Element von Global Mental Health anerkannt.
Seit 1992 veröffentlichen pro Jahr mehr Frauen als Männer zu Peripartaler Depression. Die weibliche Autorenschaft liegt bei 63 %. Unter den produktivsten Wissenschaftlern sind 8 Autorinnen und 6 Autoren. Die produktivsten Autoren sind die US Amerikanerin K.L. Wisner und die Britin L. Murray. Letztere wurde am häufigsten zitiert und führt die Liste der modifizierten h Indizes mit einem Wert von 68 an. Für den britischen Autor und Begründer des Screening-Instruments Edinburgh Postnatal Depression Scale (EPDS) J.L. Cox wurde die höchste Zitationsrate berechnet.
Im Gegensatz zu Veröffentlichungen in gynäkologischen Fachzeitschriften oder szientometrischen Arbeiten zu psychiatrischen Erkrankungen wie Schizophrenie ist der Frauenanteil in allen untersuchten Teilbereichen dem Männeranteil überlegen. Einzige Ausnahme ist die Letztautorenschaft. Diese Ergebnisse stellen eine Besonderheit dar, da eine weibliche Dominanz der Wissenschaft im Schnittbereich zwischen Psychiatrie, Psychosomatik, Psychologie und Frauenheilkunde bisher nicht beschrieben ist.
Comprehensive landscape of active deubiquitinating enzymes profiled by advanced chemoproteomics
(2019)
Enzymes that bind and process ubiquitin, a small 76-amino-acid protein, have been recognized as pharmacological targets in oncology, immunological disorders, and neurodegeneration. Mass spectrometry technology has now reached the capacity to cover the proteome with enough depth to interrogate entire biochemical pathways including those that contain DUBs and E3 ligase substrates. We have recently characterized the breast cancer cell (MCF7) deep proteome by detecting and quantifying ~10,000 proteins, and within this data set, we can detect endogenous expression of 65 deubiquitylating enzymes (DUBs), whereas matching transcriptomics detected 78 DUB mRNAs. Since enzyme activity provides another meaningful layer of information in addition to the expression levels, we have combined advanced mass spectrometry technology, pre-fractionation, and more potent/selective ubiquitin active-site probes with propargylic-based electrophiles to profile 74 DUBs including distinguishable isoforms for 5 DUBs in MCF7 crude extract material. Competition experiments with cysteine alkylating agents and pan-DUB inhibitors combined with probe labeling revealed the proportion of active cellular DUBs directly engaged with probes by label-free quantitative (LFQ) mass spectrometry. This demonstrated that USP13, 39, and 40 are non-reactive to probe, indicating restricted enzymatic activity under these cellular conditions. Our extended chemoproteomics workflow increases depth of covering the active DUBome, including isoform-specific resolution, and provides the framework for more comprehensive cell-based small-molecule DUB selectivity profiling.
Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.
Critique, and especially radical critique of reason, is under pressure from two opponents. Whereas the proponents of "post-critical" or "acritical" thinking denounce critique as an empty and self-righteous repetition of debunking, the decriers of "post-truth" accuse critique of having helped to bring about our current "post-truth" politics. Both advocate realism as a limit critique must respect, but Vogelmann defends the claim that we urgently need radical critiques of reason because they offer a more precise diagnosis of the untruths in politics the two opponents of critique are rightfully worried about. Radical critiques of reason are possible, he argues, if we turn our attention to the practices of criticizing, if we refrain from a sovereign epistemology, and if we pluralize reason without trivializing it. In order to demonstrate the diagnostic advantage of radical critiques of reason, he briefly analyzes the political and epistemic strategy at work in two exemplary untruths in politics.
Critique, and especially radical critique of reason, is under pressure from two opponents. Whereas the proponents of "post-critical" or "acritical" thinking denounce critique as an empty and self-righteous repetition of debunking, the decriers of "post-truth" accuse critique of having helped to bring about our current "post-truth" politics. Both advocate realism as a limit critique must respect, but I will defend the claim that we urgently need radical critiques of reason because they offer a more precise diagnosis of the untruths in politics the two opponents of critique are rightfully worried about. Radical critiques of reason are possible, I argue, if we turn our attention to the practices of criticizing, if we refrain from a sovereign epistemology, and if we pluralize reason without trivializing it. In order to demonstrate the diagnostic advantage of radical critiques of reason, I briefly analyze the political and epistemic strategy at work in two exemplary untruths in politics.
Background and Aims: Vitamin D has an inhibitory role in the inflammatory signaling pathways and supports the integrity of the intestinal barrier. Due to its immunomodulatory effect, vitamin D plays a role in chronic inflammatory bowel disease (IBD) and a deficiency is associated with an increased risk for a flare. We aimed to investigate to what extent the 25-hydroxyvitamin D (25(OH)D3) level correlates with disease activity and whether a cut-off value can be defined that discriminates between active disease and remission. Methods: Patients with IBD, treated at the University Hospital Frankfurt were analyzed retrospectively. The 25(OH)D3 levels were correlated with clinical activity indices and laboratory chemical activity parameters. A deficiency was defined as 25(OH)D3 levels <30 ng/mL. Results: A total of 470 (257 female) patients with IBD were included, 272 (57.9%) with Crohn’s disease (CD), 198 (42.1%) with ulcerative colitis (UC). The median age of the patients was 41 (18–84). In 283 patients (60.2%), a vitamin D deficiency was detected. 245 (53.6%) patients received oral vitamin D supplementation, and supplemented patients had significantly higher vitamin D levels (p < 0.0001). Remission, vitamin D substitution, and male gender were independently associated with the 25(OH)D3 serum concentration in our cohort in regression analysis. A 25(OH)D3 serum concentration of 27.5 ng/mL was the optimal cut-off value. Conclusion: Vitamin D deficiency is common in IBD patients and appears to be associated with increased disease activity. In our study, vitamin D levels were inversely associated with disease activity. Thus, close monitoring should be established, and optimized supplementation should take place.
The multifaceted p21 (Cip1/Waf1/CDKN1A) in cell differentiation, migration and cancer therapy
(2019)
Loss of cell cycle control is characteristic of tumorigenesis. The protein p21 is the founding member of cyclin-dependent kinase inhibitors and an important versatile cell cycle protein. p21 is transcriptionally controlled by p53 and p53-independent pathways. Its expression is increased in response to various intra- and extracellular stimuli to arrest the cell cycle ensuring genomic stability. Apart from its roles in cell cycle regulation including mitosis, p21 is involved in differentiation, cell migration, cytoskeletal dynamics, apoptosis, transcription, DNA repair, reprogramming of induced pluripotent stem cells, autophagy and the onset of senescence. p21 acts either as a tumor suppressor or as an oncogene depending largely on the cellular context, its subcellular localization and posttranslational modifications. In the present review, we briefly mention the general functions of p21 and summarize its roles in differentiation, migration and invasion in detail. Finally, regarding its dual role as tumor suppressor and oncogene, we highlight the potential, difficulties and risks of using p21 as a biomarker as well as a therapeutic target.
Introduction: Definitive chemoradiation (CRT) followed by high-dose-rate (HDR) brachytherapy (BT) represents state-of-the-art treatment for locally-advanced cervical cancer. Despite use of this treatment paradigm, disease-related outcomes have stagnated in recent years, indicating the need for biomarker development and improved patient stratification. Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT.
Methods: We identified 74 patients with FIGO Stage Ib to IVb cervix squamous cell carcinoma. Baseline immunohistochemical scoring of PLK3 and pT273 Caspase 8 levels was performed on pre-treatment samples. Correlation was then assessed between marker expression and clinical endpoints, including cumulative incidences of local and distant failure, cancer-specific survival (CSS) and overall survival (OS). Data were then validated using The Cancer Genome Atlas (TCGA) dataset.
Results: PLK3 expression levels were associated with pT273 Caspase 8 levels (p = 0.009), as well as N stage (p = 0.046), M stage (p = 0.026), and FIGO stage (p = 0.001). By the same token, pT273 Caspase 8 levels were associated with T stage (p = 0.031). Increased PLK3 levels corresponded to a lower risk of distant relapse (p = 0.009), improved CSS (p = 0.001), and OS (p = 0.003). Phospho T273 Caspase 8 similarly corresponded to decreased risk of distant failure (p = 0.021), and increased CSS (p < 0.001) and OS (p < 0.001) and remained a significant predictor for OS on multivariate analysis. TCGA data confirmed the association of low PLK3 expression with resistance to radiotherapy and BT (p < 0.05), as well as increased propensity for metastasis (p = 0.019). Finally, a combined PLK3 and pT273 Caspase 8 score predicted for decreased distant relapse (p = 0.005), and both improved CSS (p < 0.001) and OS (p < 0.001); this combined score independently predicted distant failure (p = 0.041) and CSS (p = 0.003) on multivariate analyses.
Conclusion: Increased pre-treatment tumor levels of PLK3 and pT273 Caspase 8 correspond to improved disease-related outcomes among cervical cancer patients treated with CRT plus BT, representing a potential biomarker in this context.
Introduction: Our aim was to highlight the characteristics of pediatric Meckel's diverticulum with a special focus on its complications.
Methods: We report a group of seven patients with Meckel's diverticulum and its resection from the Department of Pediatric Surgery between 2012 and 2017. We reviewed all patient records, clinical presentation, and intraoperative findings. The diagnosis was confirmed by surgery and pathology. For a systematic literature review, we used PubMed, Medline and Google Scholar search engines to locate articles containing terms such as Meckel's diverticulum, children, pediatric, complications and symptomatic. We included article reporting on case series in English and German on pediatric patients only.
Results: All included patients (n = 7) were symptomatic. Some patients showed isolated symptoms, and others presented with a combination of symptoms that consisted of abdominal pain, bloody stool or vomiting. The median age of our seven cases was 3.5 years, including 4 male and 3 female patients. Intestinal obstruction was the most common complication; it was seen in 5 out of 7 patients (intussusception in 4 cases, volvulus in 1 case). Ectopic gastric tissue was identified in 3 cases, and inclusion of pancreatic tissue was observed in 1 case. The literature review identified 8 articles for a total of 641 patients aged between 1 day and 17 years and a male:female ratio of 2.6:1. From this group, 528 patients showed clinical symptoms related to Meckel's diverticulum. The most common symptom was abdominal pain and bloody stool. The most common surgical finding in symptomatic patients was intestinal obstruction (41%), followed by intestinal hemorrhage (34%). Complications such as perforation (10%) and diverticulitis (13%) were less frequently reported. Heterotopic tissue was confirmed on histopathology in 53% of all patients enclosing gastric, pancreatic, and both gastric and pancreatic mucosae. In one case, large intestine tissue could be found. Overall, one death was reported.
Conclusion: The presented case series and literature review found similar clinical presentations and complications of Meckel's diverticulum in children. Intestinal obstruction and bleeding are more frequent than inflammation in pediatric Meckel's diverticulum. Bowel obstruction is the leading cause for complicated Meckel's diverticulum in patients younger than 12 years.
About 200 years ago, legal concepts based on the idea of formal equality prevailed. Over the last 150 years, however, the law has tried on a large scale to establish substantive equality, or at least to alleviate social and economic imbalances. To this day, the law which has undertaken this task has grown in scope and become increasingly differentiated. It has become one of the most important components of modern legal systems and has a history with its own distinctive contours. The terms used to summarise the corresponding legal materials are manifold: law of the welfare state, law of the provident state (état providence) (François Ewald), social law, social welfare law, etc. ...
The use of contractual engineering to create channels of credit intermediation outside of the realm of banking regulation has been a recurring activity in Western financial systems over the last 50 years. After the financial crisis of 2007 and 2008, this phenomenon, at that time commonly referred to as ‘shadow banking’, evoked a large-scale regulatory backlash, including several specific regulatory constraints being placed on non-bank financial institutions (NBFI). This paper proposes a different avenue for regulators to keep regulatory arbitrage under control and preserve sufficient space for efficient financial innovation. Rather than engaging in the proverbial race between hare and hedgehog that is emerging with increasingly specific regulation of particular contractual arrangements, this paper argues for a normative approach to supervision. We outline this approach in detail by showing that regulators should primarily analyse the allocation of tail risk inherent in the respective contractual arrangements. Our paper proposes to assign regulatory burdens equivalent to prudential banking regulation, in case these arrangements become only viable through indirect or direct access to an (ad hoc) public backstop. In order to make the pivotal assessment, regulators will need information about recent contractual innovations and their risk-allocating characteristics. According to the scholarship on regulatory networks serving as communities of interpretation, we suggest in particular how regulators should structure their relationships with semi-public gatekeepers such as lawyers, auditors and consultants to keep abreast of the real-world implications of evolving transactional structures. This paper then uses the rise of credit funds as a non-bank entities economically engaged in credit intermediation to apply this normative framework, pointing to recent contractual innovations that call for more regulatory scrutiny in a multipolar regulatory dialogue.
The article analyses how the decrees of the Council of Trent regarding marriage were used by the Church of Rome as a tool to contrast mixed marriages in Early Modern Europe. It investigates how these decrees were evaded by local churches in order to administer a practice of confessional coexistence impossible to eradicate, and how they were manipulated by actors – even Protestants – to put an end to undesirable unions. It also presents the interpretation that the Church of Rome made of the Tametsi to resolve the age-old issue of mixed marriages in the Low Countries, issuing the Benedictine Declaration, later applied to other contexts with a strong Protestant presence – above all out-side Europe. Although the Council of Trent claimed to have fixed a homogeneous and flawless nuptial ritual, the various local practices did not always adapt to it. Indeed, they bypassed it; sometimes refused it. This led parish priests and missionaries to turn to Rome for the resolution of concrete cases. The decisions taken for individual cases became a normative reference point. It was produced by the continuous interaction and negotiation with local churches and went on in fact to profoundly influence the sacramental rituality of marriages, which Tametsi had claimed were fixed and immutable.
Worldwide, academics and practitioners are developing ‘planning-oriented’ approaches to reduce the negative impacts of car traffic for more sustainable urban and transport development. One such example is the design of car-reduced neighborhoods, although these are controversial issues in the hegemonic ‘system’ of automobility. Despite the reduction of emissions and frequent recognition as ‘best practice examples’, ‘planning-critical’ research questions the underlying objectives and narratives of such sustainable developments. Our study contributes to this research perspective by improving the understanding of narratives that emerge along with car-reduced housing developments. For this purpose, we analyze two car-reduced neighborhoods in the City of Darmstadt (Germany) by conducting interviews with different actors involved in the planning and implementation processes. Our investigation reveals that the development of car-reduced neighborhoods (i) is consciously embedded in the context of sustainability, (ii) is characterized by power relations, (iii) follows normative indicators, and (iv) does not always correspond to lived realities. Altogether, the traced narratives of car-reduced neighborhoods are embedded in the overarching debate on sustainability, while at the same time revealing the dependence of society on the automobile. Thus, the hegemonic ‘system’ of automobility—although it is beginning to crack—continues to exist.
The 100th anniversary of the Weimar Constitution’s promulgation has brought a number of new stimuli to a historiography that has for a long time focused largely on the Weimar Republic’s failure. Two prominent recent publications – Udo Di Fabio’s study and a collective volume edited by Horst Dreier und Christian Waldhoff – are reviewed in this issue by the Brazilian constitutional historian Marcelo Neves. His review and the last months’ public debate on the merits and flaws of the Weimar Constitution in Germany, which was framed by current concerns about the state of Western democracies, show to what extent constitutional history is always also a conversation about the present. ...
Background: We aimed to investigate the potential effects of a 4-week motor–cognitive dual-task training on cognitive and motor function as well as exercise motivation in young, healthy, and active adults.
Methods: A total of 26 participants (age 25 ± 2 years; 10 women) were randomly allocated to either the intervention group or a control group. The intervention group performed a motor–cognitive training (3×/week), while the participants of the control group received no intervention. Before and after the intervention period of 4 weeks, all participants underwent cognitive (d2-test, Trail Making Test) and motor (lower-body choice reaction test and time to stabilization test) assessments. Following each of the 12 workouts, self-reported assessments (rating of perceived exertion, enjoyment and pleasant anticipation of the next training session) were done. Analyses of covariances and 95% confidence intervals plotting for between group and time effects were performed.
Results: Data from 24 participants were analysed. No pre- to post-intervention improvement nor a between-group difference regarding motor outcomes (choice-reaction: F = 0.5; time to stabilization test: F = 0.7; p > 0.05) occurred. No significant training-induced changes were found in the cognitive tests (D2: F = 0.02; Trail Making Test A: F = 0.24; Trail Making Test B: F = 0.002; p > 0.05). Both enjoyment and anticipation of the next workout were rated as high.
Discussion: The neuro-motor training appears to have no significant effects on motor and cognitive function in healthy, young and physically active adults. This might be explained in part by the participants’ very high motor and cognitive abilities, the comparably low training intensity or the programme duration. The high degree of exercise enjoyment, however, may qualify the training as a facilitator to initiate and maintain regular physical activity. The moderate to vigorous intensity levels further point towards potential health-enhancing cardiorespiratory effects.
During the drafting process from the 1920s to 1940s, the Weimar Constitution (WRV) played a decisive role in shaping Chinese social(-ist) con- stitutions, especially the part related to the social- economic issue. Through the lens of cultural trans- lation, this paper seeks to explain how the WRV was adapted, reinterpreted, and recontextualized throughout several rounds of constitution making in China. By focusing on the roles played by the translators, legislators, and interpreters, this paper discusses how the social rights created by the WRV were translated into the fundamental policy of the 1947 Constitution of the Republic of China. More- over, regarding »policy« as the legal instrument for regulating the social-economic life, and even broader fields, it triggers the modern transforma- tion of Chinese meritocracy and reinforces the national legal tradition depicted in its modern form. To some extent, this case study on cultural translation of constitutional law discloses the mechanism, both temporarily and spatially, for the intercultural communication of the normative information.
Background: Although anterior cruciate ligament (ACL) tear-prevention programs may be effective in the (secondary) prevention of a subsequent ACL injury, little is known, yet, on their effectiveness and feasibility. This study assesses the effects and implementation capacity of a secondary preventive motor-control training (the Stop-X program) after ACL reconstruction.
Methods and design: A multicenter, single-blind, randomized controlled, prospective, superiority, two-arm design is adopted. Subsequent patients (18–35 years) with primary arthroscopic unilateral ACL reconstruction with autologous hamstring graft are enrolled. Postoperative guideline rehabilitation plus Classic follow-up treatment and guideline rehabilitation plus the Stop-X intervention will be compared. The onset of the Stop-X program as part of the postoperative follow-up treatment is individualized and function based. The participants must be released for the training components. The endpoint is the unrestricted return to sport (RTS) decision. Before (where applicable) reconstruction and after the clearance for the intervention (aimed at 4–8 months post surgery) until the unrestricted RTS decision (but at least until 12 months post surgery), all outcomes will be assessed once a month. Each participant is consequently measured at least five times to a maximum of 12 times. Twelve, 18 and 24 months after the surgery, follow-up-measurements and recurrence monitoring will follow. The primary outcome assessement (normalized knee-separation distance at the Drop Jump Screening Test (DJST)) is followed by the functional secondary outcomes assessements. The latter consist of quality assessments during simple (combined) balance side, balance front and single-leg hops for distance. All hop/jump tests are self-administered and filmed from the frontal view (3-m distance). All videos are transferred using safe big content transfer and subsequently (and blinded) expertly video-rated. Secondary outcomes are questionnaires on patient-reported knee function, kinesiophobia, RTS after ACL injury and training/therapy volume (frequency – intensity – type and time). All questionnaires are completed online using the participants’ pseudonym only.
Group allocation is executed randomly. The training intervention (Stop-X arm) consists of self-administered home-based exercises. The exercises are step-wise graduated and follow wound healing and functional restoration criteria. The training frequency for both arms is scheduled to be three times per week, each time for a 30 min duration. The program follows current (secondary) prevention guidelines.
Repeated measurements gain-score analyses using analyses of (co-)variance are performed for all outcomes.
Trial registration: German Clinical Trials Register, identification number DRKS00015313. Registered on 1 October 2018.
You wait ages for a bus, the saying goes, and then two (or three) come along at once. A similar feeling set in when Oxford University Press published two volumes on legal history in its Oxford Handbooks series within the space of four weeks last year. They are a welcome addition to the prestigious and well-established series that now boasts hundreds of volumes, including around 50 on history and over three dozen on law. The latter do not only cover established sub-disciplines of legal studies, such as jurisprudence and philosophy of law (2002), comparative law (2006, 2nd ed. 2019), international trade law (2009), the law of the sea (2015), European Union law (2015), criminal law (2014) and intellectual property (2018), but also more recent and emerging fields, including international environmental law (2007), empirical legal research (2010), behavioural economics and law (2014), international adjudication (2013), international climate change law (2016) and law and economics (3 vols., 2017). The Handbooks have become increasingly specialised with titles focusing on narrow topics such as individual national constitutions (USA, 2015; India, 2016; Canada, 2017) and important, but nevertheless discrete legal issues, for example, US health law (2017) and the sources of international law (2017). The obvious question was why, nearly two decades after the launch of the series, there was such a thing as an Oxford Handbook of American Sports Law (2018) but still no volume on the history of law. The absence of such a title was all the more striking in light of the publication of books in the series dealing with individual fields of legal history, such as the Oxford Handbook of the History of International Law (2012), the Oxford Handbook of Roman Law and Society (2016), the Oxford Handbook of Carl Schmitt (2017) and the Oxford Handbook of English Law and Literature, 1500–1700 (2017). ...
Den Auftakt zum Oxford Handbook of European Legal History machen fünf Beiträge, die unter der Überschrift "Approaches to European Legal History: Historiography and Methods" versammelt sind. Um sie in Beziehung zu setzen, habe ich im Folgenden drei Fragenkomplexe formuliert, die die gemeinsamen Aspekte dieses Quintetts abbilden. Die Beiträge werden in der Reihenfolge ihres Auftretens im Handbuch referiert. Zur Vermeidung von Redundanzen haben die Nachgeordneten im Wiederholungsfalle der Argumente das Nachsehen und werden "nur" als Verweis genannt.
Light-matter interaction in the strong coupling regime is of profound interest for fundamental quantum optics, information processing and the realization of ultrahigh-resolution sensors. Here, we report a new way to realize strong light-matter interaction, by coupling metamaterial plasmonic "quasi-particles" with photons in a photonic cavity, in the terahertz frequency range. The resultant cavity polaritons exhibit a splitting which can reach the ultra-strong coupling regime, even with the comparatively low density of quasi-particles, and inherit the high Q-factor of the cavity despite the relatively broad resonances of the Swiss-cross and split-ring-resonator metamaterials used. We also demonstrate nonlocal collective interaction of spatially separated metamaterial layers mediated by the cavity photons. By applying the quantum electrodynamic formalism to the density dependence of the polariton splitting, we can deduce the intrinsic transition dipole moment for single-quantum excitation of the metamaterial quasi-particles, which is orders of magnitude larger than those of natural atoms. These findings are of interest for the investigation of fundamental strong-coupling phenomena, but also for applications such as ultra-low-threshold terahertz polariton lasing, voltage-controlled modulators and frequency filters, and ultra-sensitive chemical and biological sensing.
For reasons of curiosity, we perused the two recent Oxford handbooks on legal history looking for discussions of digital methods in legal history. One of the fundamental decisions to be made when organizing such a handbook is defining which methodological approaches deserve an article of their own and which ones are to be understood rather as cross-cutting themes to be discussed in the context of many articles dedicated to other things. In the case of digital methods in legal history, this decision seems to have been a tough one – at one point, you can find a curious reference to a "chapter on 'Legal History and Digital Humanities'" (OHBLH 354), but in the final publication there is no such text.
However, discussing digital methods in the context of other subjects has, in our opinion, the disadvantage that more systematic, methodological arguments cannot really be developed. Put more concretely, the most "substantial" contributions regarding digital methods are, for whatever reason, those on "The Intellectual History of Law" by Assaf Likhovski, on "Taking the Long View" by Paul D. Halliday, on "Quantitative Legal History" by Daniel Klerman, and on "Indian Law" by Mitra Sharafi, all of which are in the Oxford Handbook on Legal History. (Equally surprising, there is no mention of digital methods at all in Angela Fernandez’s "Legal History as The History of Legal Texts".) However, even these articles do not really "discuss" digital methods, rather they merely refer to them (and to some projects) as contributions of sorts to their respective fields of interest.
Thus, if you are looking for digital methods in those handbooks, you can hardly find more than some namedropping passages where things like "digital mapping […], network analysis […], text analysis" (OHBLH 845f.) are mentioned, together with references to example projects where they have been employed but without any explanation as to:
–why these methods are mentioned and not others,
–what they are doing, to which end and under what circumstances,
–what, possibly transformative, impact these methods have on the (respective sub-) field of legal history, and
–what a scholar considering to apply these methods should be aware of.
While the space for this is limited, the present Forum contribution tries to mitigate the scarcity of such discussions by presenting and discussing a few textual analyses that make use – for demonstration purposes – of digital methods. Some other methods of analysis, network analysis, and geo-mapping (among others), cannot be covered here, but we provide a link to an online bibliography where you can find them applied to legal history or a related domain, and discussed critically. A general discussion of digital perspectives beyond concrete methods of analysis concludes this contribution.
State-of-the-art climate models contain, to a significant degree, empirical components. In particular, subgrid-scale (SGS) parameterizations are usually highly tuned against observations or high-resolution model data. While this enables the models to minimize the error during hindcasts, it is not guaranteed that it yields a benefit for climate projections because of climate change. In this thesis the Fluctuation-Dissipation theorem (FDT) is used to update the statistics of the system in the presence of an external forcing. If the empirical parameters are tuned objectively to the data (i.e., they depend on the statistics of the data), then they might be updated with the FDT. This ansatz is tested within a framework of a semi-empirical model (SEM) based on the leading variance patterns of a quasigeostrophic three-layer model (QG3LM) and supplemented by a purely data-driven parameterization. We show that the FDT is able to successfully update the tuning parameters of the data-driven SGS closure, resulting in a systematic improvement in model performance in comparison to an untreated SEM. Ideally, SGS parameterizations should contain little to no tuning parameters. Thus, complementary to the FDT approach we investigate a stochastic SGS closure constrained by first principles that is calculated using the stochastic mode reduction (SMR). The SMR allows for an analytic derivation of the SGS closure from the model equations while requiring only minimal tuning. We successfully apply the SMR to the QG3LM and construct the reduced stochastic model (RSM). Furthermore, we show that the RSM is more robust against an external forcing than the SEM. Additionally, we find that, under appropriate conditions, the FDT is able to update the empirical parts of the RSM. Yet, only for the response in mean streamfunction the RSM provides useful results, while the response in covariance of the streamfunction is incorrect for most cases. Nevertheless, we obtain a remarkably accurate response in both moments for the RSM in an idealized setting. In combination with the results of the FDT study this indicates that the considered RSM is too low dimensional and encourages us to investigate the response of larger RSMs in the future.
Five decades of US, UK, German and Dutch music charts show that cultural processes are accelerating
(2019)
Analysing the timeline of US, UK, German and Dutch music charts, we find that the evolution of album lifetimes and of the size of weekly rank changes provide evidence for an acceleration of cultural processes. For most of the past five decades, number one albums needed more than a month to climb to the top, nowadays an album is in contrast top ranked either from the start, or not at all. Over the last three decades, the number of top-listed albums increased as a consequence from roughly a dozen per year, to about 40. The distribution of album lifetimes evolved during the last decades from a log-normal distribution to a power law, a profound change. Presenting an information–theoretical approach to human activities, we suggest that the fading relevance of personal time horizons may be causing this phenomenon. Furthermore, we find that sales and airplay- based charts differ statistically and that the inclusion of streaming affects chart diversity adversely. We point out in addition that opinion dynamics may accelerate not only in cultural domains, as found here, but also in other settings, in particular in politics, where it could have far reaching consequences.
The presence of moral theology and scholasticism in the recently published Oxford Handbook of Legal History and Oxford Handbook of European Legal History is very limited. The first volume aims to be iconoclastic. It explicitly does not seek to provide a kind of global historical account but instead presents some of the innovative methodological perspectives guiding current legal historical research. Thomas Duve, writing about the contribution of the School of Salamanca to the theorization of a certain framework of "indigenous rights" during the period of colonial domination, is thus the only contributor to this volume who mentions moral theology. In the Handbook of European Legal History, there are two articles on important scholastic contributions to legal history that also deal with the influence of Salamanca and related scholastic authors to equally wide fields of legal thinking. Wim Decock discusses authors of the second scholasticism in the context of the law of property and obligations (611–632), and David Ibbetson writes on natural law (566–582). In the following, I will focus on Ibbetson’s chapter, which only partially matches the ambitious intended aims of the volume editors (Pihlajamäki, Dubber, Godfrey): to "chart the landscape of contemporary research" and to show the global impact that European legal systems had "from the fifteenth century onwards". ...