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Introduction: Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. This study estimated cost, cost-driving factors and quality of life (QoL) in patients with Dravet syndrome and their caregivers in a prospective, multicenter study in Germany.
Methods: A validated 3–12-month retrospective questionnaire and a prospective 3-month diary assessing clinical characteristics, QoL, and direct, indirect and out-of-pocket (OOP) costs were administered to caregivers of patients with DS throughout Germany.
Results: Caregivers of 93 patients (mean age 10.1 years, ±7.1, range 15 months–33.7 years) submitted questionnaires and 77 prospective diaries. The majority of patients (95%) experienced at least one seizure during the previous 12 months and 77% a status epilepticus (SE) at least once in their lives. Over 70% of patients had behavioural problems and delayed speech development and over 80% attention deficit symptoms and disturbance of motor skills and movement coordination. Patient QoL was lower than in the general population and 45% of caregivers had some form of depressive symptoms. Direct health care costs per three months were a mean of €6,043 ± €5,825 (median €4054, CI €4935-€7350) per patient. Inpatient costs formed the single most important cost category (28%, €1,702 ± €4,315), followed by care grade benefits (19%, €1,130 ± €805), anti-epileptic drug (AED) costs (15%, €892 ± €1,017) and ancillary treatments (9%, €559 ± €503). Total indirect costs were €4,399 ±€ 4,989 (median €0, CI €3466-€5551) in mothers and €391 ± €1,352 (median €0, CI €195-€841) in fathers. In univariate analysis seizure frequency, experience of SE, nursing care level and severe additional symptoms were found to be associated with total direct healthcare costs. Severe additional symptoms was the single independently significant explanatory factor in a multivariate analysis.
Conclusions: This study over a period up to 15 months revealed substantial direct and indirect healthcare costs of DS in Germany and highlights the relatively low patient and caregiver QoL compared with the general population.
Global Histories and Cultures of Statehood, libro editado por John L. Brooke, Julia Strauss y Greg Anderson, es una propuesta interesante de reflexión interdisciplinaria sobre las formaciones estatales en un marco temporal amplísimo: desde la Antigüedad hasta el siglo XX. Los capítulos que componen el libro fueron presentados en un programa de dos años en la Universidad Estatal de Ohio. La publicación es claramente el producto de un ejercicio de discusión colectiva de una red académica con sede en los Estados Unidos y, por tal motivo, la mayoría de sus miembros pertenecen a instituciones académicas en este país. ...
Circular RNAs (circRNAs), an important class of regulatory RNAs, have been shown to be the most prevalent in the brain compared with other tissues. However the processes governing their biogenesis in neurons are still elusive. Moreover, little is known about whether and how different biogenesis factors work in synchrony to generate neuronal circRNAs. To address this question, we pharmacologically inhibited the spliceosome and profiled rat neuronal circRNAs using RNA sequencing. We identified over 100 circRNAs that were up-regulated and a few circRNAs that were down-regulated upon spliceosome inhibition. Bioinformatic analysis revealed that up-regulated circRNAs possess significantly longer flanking introns compared with the un-changed circRNA population. Moreover, the flanking introns of up-regulated circRNAs harbor a higher number of distinct repeat sequences and more reverse complementary motifs compared with the unchanged circRNAs. Taken together, our data demonstrate that the biogenesis of circRNAs containing distinct intronic features becomes favored under conditions of limited spliceosome activity.
Every now and again, one is overcome by a sense of utter disbelief. How can it be that some conventional narratives are still so persistent and influential in this day and age? In fact, they are so pervasive that one feels compelled to put pen to paper in order to combat them. Among these narratives, we find the tale of cultural evolution, where law plays a fundamental role as an instrument for rationalizing archaic societies. Having rejected this kind of historiography in his last essay on the early history of law (ZRG RA 127, 1–13), the late Raymond Westbrook instead postulated new paradigms. Moving in the same direction, Philipp Ruch thwarts this story of civilizing progress in a twofold manner: In his eyes, honor and vengeance are not the anthropological factors that law has to contain in order to create civilization. According to Ruch, and the main thrust of his 2016 dissertation, it was in fact law in the context of honor and vengeance that produced emotionality. ...
The synthesis of polynitrogen compounds is of fundamental importance due to their potential as environmentally-friendly high energy density materials. Attesting to the intrinsic difficulties related to their formation, only three polynitrogen ions, bulk stabilized as salts, are known. Here, magnesium and molecular nitrogen are compressed to about 50 GPa and laser-heated, producing two chemically simple salts of polynitrogen anions, MgN4 and Mg2N4. Single-crystal X-ray diffraction reveals infinite anionic polythiazyl-like 1D N-N chains in the crystal structure of MgN4 and cis-tetranitrogen N44− units in the two isosymmetric polymorphs of Mg2N4. The cis-tetranitrogen units are found to be recoverable at atmospheric pressure. Our results respond to the quest for polynitrogen entities stable at ambient conditions, reveal the potential of employing high pressures in their synthesis and enrich the nitrogen chemistry through the discovery of other nitrogen species, which provides further possibilities to design improved polynitrogen arrangements.
Kunstmekka und kitschig-schöne Serenissima : Teil 1/2: Rundgang über die 58. Biennale in Venedig
(2019)
Ein guter Grund alle zwei Jahre in die Serenissima zu reisen ist ihre Kunstbiennale. Seit über 100 Jahren, genauer seit 1895, öffnet von Mai bis November die größte Kunstschau der Welt in Venedig ihre Pforten.
Die Biennale verteilt sich auf mehrere Ausstellungsorte. Da sind die Giardini, ein für venezianische Verhältnisse großzügiger Park und zudem die einzige Grünanlage der Stadt. Sie beherbergen neben dem Zentralpavillon auch 28 nationale Länderpavillons, darunter einen deutschen Pavillon. 1999 kam aus Platzgründen das Arsenale, die Schiffswerft des ehemaligen Militärhafens, als Ausstellungsfläche hinzu. Zusätzlich verteilen sich weitere Länderpavillons und Ausstellungen über die Stadt, in angemieteten Etagen verschiedener Palazzi. Letztere zeigen sich zumeist als sehenswerte Architektur. Nicht selten lassen sich dort Kronleuchter aus Muranoglas, wertvolle Stofftapeten oder Wandmalereien sowie monumentale und reichverzierte Treppen bewundern.
May You Live in Interesting Times lautet der Titel, den der Amerikaner Ralph Rugoff, diesjähriger Kurator für die zentrale Ausstellung, der 58. Kunstbiennale gegeben hat. Die Besonderheit in diesem Jahr: Es stellen nur lebende Künstler aus und davon sind alle einmal sowohl in den Giardini als auch im Arsenale mit Werken vertreten. Die nationalen Länderpavillons haben jeweils eigene nationale Kuratoren und Künstler ausgewählt und bespielen ihre Häuser unabhängig vom Hauptmotto. Es kommen darüber hinaus auch noch viele sogenannte Kollateral-Ausstellungen in den berühmten Museen oder in bekannten Kirchen und Palazzi hinzu. Selbst ein einwöchiger Aufenthalt böte nicht genug Zeit, um alles zu sehen.
We investigate the default probability, recovery rates and loss distribution of a portfolio of securitised loans granted to Italian small and medium enterprises (SMEs). To this end, we use loan level data information provided by the European DataWarehouse platform and employ a logistic regression to estimate the company default probability. We include loan-level default probabilities and recovery rates to estimate the loss distribution of the underlying assets. We find that bank securitised loans are less risky, compared to the average bank lending to small and medium enterprises.
In this paper, we investigate the relation between buildings' energy efficiency and the probability of mortgage default. To this end, we construct a novel panel dataset by combining Dutch loan-level mortgage information with provisional building energy ratings that are calculated by the Netherlands Enterprise Agency. By employing the Logistic regression and the extended Cox model, we find that buildings' energy efficiency is associated with lower likelihood of mortgage default. The results hold for a battery of robustness checks. Additional findings indicate that credit risk varies with the degree of energy efficiency.
An album of 50 watercolour illustrations depicting Norfolk Island plants attributed to convict artist John Doody, in the early 1790s, and associated notes apparently written by William Paterson (1755-1810), one-time commander of the military detachment on Norfolk Island, Lieutenant Governor of New South Wales, and amateur botanist, are described and assessed. Illustrated are 48 plant species growing on Norfolk Island at the time, all but three of which are indigenous. The notes and the watercolours represent the only treatment of the island's flora in the 18th century and include descriptive and ecological material for the species at the time of first European occupation. Two of the species are now extinct. Paterson's notes also include an introductory description of the flora and fauna of the Island. The importance of this material to the modern study of the Norfolk Island flora is highlighted.
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.