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Die Literaturwissenschaft hat Thomas Braschs Lyrik bisher nicht als eigenständiges Phänomen behandelt, obwohl gerade sein Gedichtband „Der schöne 27. September“ von 1980 fulminant erfolgreich war. Die wenigen Seitenblicke, welche die Forschung diesem Zyklus bisher gewidmet hat, überzeugen im Großen und Ganzen recht wenig. Daher versucht die vorliegende Untersuchung, die bedauerliche Forschungslücke zu verringern. Im Mittelpunkt steht die Frage nach einer dem Band möglicherweise impliziten Ästhetik. Motivik, Sprache und Form der einzelnen Texte interessieren dabei ebenso wie das Arrangement des Ganzen. Ein Glücksumstand ist es, dass diese Arbeit auch das nachgelassene Material, welches sich im Thomas-Brasch-Archiv der Akademie der Künste, Berlin befindet, nutzen konnte, so dass sich hier eine umfassende Untersuchung der Genese der Gedichte und die Analyse des Zusammenspiels dieser Texte in „Der schöne 27. September“ ergänzen.
Background: Tuberous sclerosis complex (TSC) is a monogenetic, multisystem disorder characterized by benign growths due to TSC1 or TSC2 mutations. This German multicenter study estimated the costs and related cost drivers associated with organ manifestations in adults with TSC.
Methods: A validated, three-month, retrospective questionnaire assessed the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket (OOP), and nursing care-level costs among adult individuals with TSC throughout Germany from a societal perspective (costing year: 2019).
Results: We enrolled 192 adults with TSC (mean age: 33.4 ± 12.7 years; range: 18–78 years, 51.6% [n = 99] women). Reported TSC disease manifestations included skin (94.8%) and kidney and urinary tract (74%) disorders, epilepsy (72.9%), structural brain defects (67.2%), psychiatric disorders (50.5%), heart and circulatory system disorders (50.5%), and lymphangioleiomyomatosis (11.5%). TSC1 and TSC2 mutations were reported in 16.7% and 25% of respondents, respectively. Mean direct health care costs totaled EUR 6452 (median EUR 1920; 95% confidence interval [CI] EUR 5533–7422) per patient over three months. Medication costs represented the major direct cost category (77% of total direct costs; mean EUR 4953), and mechanistic target of rapamycin (mTOR) inhibitors represented the largest share (68%, EUR 4358). Mean antiseizure drug (ASD) costs were only EUR 415 (6%). Inpatient costs (8%, EUR 518) and outpatient treatment costs (7%; EUR 467) were important further direct cost components. The mean care grade allowance as an approximator of informal nursing care costs was EUR 929 (median EUR 0; 95% CI EUR 780–1083) over three months. Mean indirect costs totaled EUR 3174 (median EUR 0; 95% CI EUR 2503–3840) among working-age individuals (< 67 years in Germany). Multiple regression analyses revealed mTOR inhibitor use and persistent seizures as independent cost-driving factors for total direct costs. Older age and disability were independent cost-driving factors for total indirect costs, whereas epilepsy, psychiatric disease, and disability were independent cost-driving factors for nursing care costs.
Conclusions: This three-month study revealed substantial direct healthcare, indirect healthcare, and medication costs associated with TSC in Germany. This study highlights the spectrum of organ manifestations and their associated treatment needs in the German healthcare setting. Trial registration: DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
Animal experiments report contradictory findings on the presence of a behavioural and neuronal anisotropy exhibited in vertical and horizontal capabilities of spatial orientation and navigation. We performed a pointing experiment in humans on the imagined 3-D direction of the location of various invisible goals that were distributed horizontally and vertically in a familiar multilevel hospital building. The 21 participants were employees who had worked for years in this building. The hypothesis was that comparison of the experimentally determined directions and the true directions would reveal systematic inaccuracy or dimensional anisotropy of the localizations. The study provides first evidence that the internal representation of a familiar multilevel building was distorted compared to the dimensions of the true building: vertically 215% taller and horizontally 51% shorter. This was not only demonstrated in the mathematical reconstruction of the mental model based on the analysis of the pointing experiments but also by the participants’ drawings of the front view and the ground plan of the building. Thus, in the mental model both planes were altered in different directions: compressed for the horizontal floor plane and stretched for the vertical column plane. This could be related to human anisotropic behavioural performance of horizontal and vertical navigation in such buildings.
The structural diversity of terpenoids is limited by the isoprene rule which states that all primary terpene synthase products derive from methyl-branched building blocks with five carbon atoms. With this study we discover a broad spectrum of novel terpenoids with eleven carbon atoms as byproducts of bacterial 2-methylisoborneol or 2-methylenebornane synthases. Both enzymes use 2-methyl-GPP as substrate, which is synthesized from GPP by the action of a methyltransferase. We used E. coli strains that heterologously produce different C11-terpene synthases together with the GPP methyltransferase and the mevalonate pathway enzymes. With this de novo approach, 35 different C11-terpenes could be produced. In addition to eleven known compounds, it was possible to detect 24 novel C11-terpenes which have not yet been described as terpene synthase products. Four of them, 3,4-dimethylcumene, 2-methylborneol and the two diastereomers of 2-methylcitronellol could be identified. Furthermore, we showed that an E. coli strain expressing the GPP-methyltransferase can produce the C16-terpene 6-methylfarnesol which indicates the condensation of 2-methyl-GPP and IPP to 6-methyl-FPP by the E. coli FPP-synthase. Our study demonstrates the broad range of unusual terpenes accessible by expression of GPP-methyltransferases and C11-terpene synthases in E. coli and provides an extended mechanism for C11-terpene synthases.
The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.
Die Wahrscheinlichkeit einer pathologischen Komplettremission (pCR) bei Brustkrebs nach neoadjuvanter Chemotherapie (NACT) nimmt zu; vor allem in den Subgruppen der tripel-negativen und HER-2-positiven Tumoren. Daher stellt sich die Frage, ob bei einer Komplettremission nach NACT eine operative Therapie der Brust notwendig ist, und ob es einen Vorteil für das onkologische Behandlungsergebnis hat, wenn kein Tumor mehr nachgewiesen werden kann. Ein Verzicht auf die Operation und gegebenenfalls auch auf die Radiotherapie ist jedoch nur auf der Basis einer verlässlichen pCR-Diagnose ohne Operation denkbar. Bildgebende Verfahren erreichen derzeit nicht die nötige Sensitivität und Spezifität, um die Diagnose einer pathologischen Komplettremission sicher zu stellen. Daher sind weitere Studien nötig, um herauszufinden, welche Methode die bestmögliche Evaluation des Tumoransprechens auf NACT erlaubt. Erste vielversprechende Ergebnisse zeigen sich in Studien zu bildgebungsgesteuerten, minimalinvasiven Biopsien nach NACT. Diese evaluieren die Möglichkeit einer pCR-Diagnose vor der Operation und könnten die Grundlage für weitere Studien zu einem möglichen Verzicht auf eine Operation in diesem ausgewählten Kollektiv sein.
"Wer trägt heute noch Trainingsanzüge in der Öffentlichkeit?", titelt die "Stilkritik" der Süddeutschen Zeitung im Mai 2010. Sportler jedenfalls nicht. Der aktuelle Bundestrainer der deutschen Fußballnationalmannschaft kleidet sich - "modisch top", "Stilikone" - selbst im Stadion in Designer-Anzüge. Dabei waren Sportler ursprünglich die einzige Zielgruppe des Ende der 1920er Jahre in den USA erfundenen 'tracksuit'. Die Kombination aus locker sitzender Hose mit Gummizug und Beinbündchen sowie Blouson mit Reißverschluss oder Sweatshirt sollte sie vor und nach ihren Aktivitäten wärmen. Ein Einsatz von Trainingsanzügen außerhalb des Sports war lange Zeit undenkbar. Die Modifizierung des Trainingsanzugs begann erst fünf Jahrzehnte nach seiner Erfindung.
Celan hat sowohl Werke zugeeignet – neben einzelnen Gedichten sind auch zwei seiner Gedichtbände als Akt der symbolischen Schenkung Personen gewidmet – als auch Einzelexemplare mit handschriftlichen Widmungen versehen. Hinzu kommt der Sonderfall der widmungslosen Festschriftzugaben. Über die historisch-kritische Bonner Celan-Ausgabe und den sorgsamen Kommentar in Barbara Wiedemanns Gesamtausgabe der Celan-Gedichte sind die Zueignungen auch in den Fällen zu ermitteln, wo Celan sie für den Erstdruck oder nachfolgende Veröffentlichungen wieder entfernte. Abseits meiner eigenen Beschäftigung mit Celans Widmungslyrik in Vergleich zu Widmungsgedichten Ilse Aichingers existiert bisher keine Forschungsarbeit zu Celans Widmungspraxis. Dabei belegen Briefe, dass Celan selbst beim Vorabdruck einzelner Gedichte auf die vorangestellte Widmung bestand: Die Widmung ist für ihn als
"eigenständige poetologisch-relevante Aussage ernstzunehmen". Einige seiner Dedikationen finden sich nur in der Textgenese und werden wieder getilgt, andere entstehen erst in der Fassung letzter Hand, und manche Widmungsgedichte finden nie in den Druck. Was auf den ersten Blick unübersichtlich und uneinheitlich wirkt, enthüllt bei genauerer Analyse Züge einer ästhetischen Praxis, die grundlegende Maximen in Celans Poetik berührt.
Microscopic transport approaches are the tool to describe the non-equilibrium evolution in low energy collisions as well as in the late dilute stages of high-energy collisions. Here, a newly developed hadronic transport approach, SMASH (Simulating Many Accelerated Strongly-interacting Hadrons) is introduced. The overall bulk dynamics in low energy heavy ion collisions is shown including the excitation function of elliptic flow employing several equations of state. The implications of this new approach for dilepton production are discussed and preliminary results for afterburner calculations at the highest RHIC energy are presented and compared to previous UrQMD results. A detailed understanding of a hadron gas with vacuum properties is required to establish the baseline for the exploration of the transition to the quark-gluon plasma in heavy ion collisions at high net baryon densities.
Background: The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder. Objective: The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective. Methods: A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC. Results: Of 365 participants, 36.7% (n = 134) reported the current or past intake of EVE, including 31.5% (n = 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m2 (median: 5.6 mg/m2, range 2.0–15.1 mg/m2) in children and adolescents and 4 ± 2.1 mg/m2 (median: 3.7 mg/m2, range 0.8–10.1 mg/m2) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE. Conclusions: From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.