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For newly authorised medicinal products with new active substances, a benefit assessment is carried out at the time of their market access in Germany. The subject of this assessment is the question of the additional benefit of the new active substance compared to the current standard therapy (the "appropriate comparator") with regard to patient-relevant outcomes. Orphan drugs (medicinal products for rare diseases) are treated separately. For these, the additional benefit is considered proven with market access, regardless of the actual data. Only with annual sales of at least 30 million euros a regular assessment will be conducted. In this case, data for comparison with an appropriate comparator has to be submitted. An analysis shows that in such regular benefit assessments, an additional benefit cannot be proven for orphan drugs in more than half of the cases. In 2019, in recognition of the often insufficient evidence base for orphan drugs, the "Anwendungsbegleitende Datenerhebung" (AbD: collection of routine practice data) was established as a further component of the benefit assessment. Accordingly, the Federal Joint Committee (G-BA) can demand an AbD for orphan drugs as well as for medicinal products with a conditional marketing authorisation or marketing authorisation under exceptional circumstances. The pharmaceutical company is responsible for conducting the AbD. The AbD has to generate data on the new active substance as well as meaningful data for comparison with the appropriate comparator. The AbD is to be conducted as a study without randomisation, and the G-BA has to determine concrete specifications on the methodology and patient-relevant endpoints.The first step of the AbD is the preparation of a study protocol (SP) and a statistical analysis plan (SAP) under the responsibility of the company. These documents are checked with regard to their content-related and methodological suitability for conducting the AbD including the associated evaluation of the, Für neu zugelassene Arzneimittel mit neuen Wirkstoffen wird zum Zeitpunkt ihres Marktzugangs in Deutschland eine Nutzenbewertung durchgeführt. Gegenstand dieser Nutzenbewertung ist die Frage nach dem Zusatznutzen des neuen Wirkstoffs gegenüber der aktuellen Standardtherapie (der "zweckmäßigen Vergleichstherapie") bezüglich patientenrelevanter Endpunkte. Für Orphan Drugs (Arzneimittel für seltene Erkrankungen) gibt es eine Sonderregel. Für diese gilt der Zusatznutzen mit Marktzugang als belegt, unabhängig von der tatsächlichen Datenlage. Erst bei einem Jahresumsatz von mindestens 30 Mio. Euro wird ein Orphan Drug regulär bewertet, so dass in diesem Fall auch Daten gegenüber der zweckmäßigen Vergleichstherapie vorgelegt werden müssen. Eine Analyse zeigt, dass sich bei solchen regulären Nutzenbewertungen in mehr als der Hälfte der Fälle für Orphan Drugs kein Zusatznutzen nachweisen lässt. Im Jahr 2019 wurde in Kenntnis der oftmals unzureichenden Datenlage die Anwendungsbegleitende Datenerhebung (AbD) als weiterer Baustein der Nutzenbewertung etabliert. Der Gemeinsame Bundesausschuss (G-BA) kann demnach für Orphan Drugs sowie für Arzneimittel mit bedingter Zulassung oder Zulassung unter außergewöhnlichen Umständen eine AbD fordern, für deren Durchführung dann der pharmazeutische Unternehmer zuständig ist. Mit der AbD müssen nicht nur Daten zum neuen Wirkstoff, sondern aussagekräftige Daten zum Vergleich mit der zweckmäßigen Vergleichstherapie generiert werden. Die AbD ist als Studie ohne Randomisierung durchzuführen, und der G-BA hat konkrete Vorgaben zur Methodik und zu patientenrelevanten Endpunkten zu bestimmen.Erster Schritt der AbD ist die Erstellung eines Studienprotokolls (SP) und eines statistischen Analyseplans (SAP) in Verantwortung des pharmazeutischen Unternehmers. Diese Dokumente werden hinsichtlich ihrer inhaltlichen und methodischen Eignung für die Durchführung der AbD einschließlich der zugehörigen Auswertung geprüft. Die Adjustierung für Confounder stel

The expansion of the synthetic aperture radar (SAR) to the emerging THz spectrum has enabled a new era of applications in the areas of automobile, security, non-destructive testing, and material characterization. Thanks to the sub-mm wavelength, extraction of material surface properties is possible and of significant interest for the THz SAR applications. The properties define the surface scattering behavior, which is relational to the applied frequency. This study focuses on surface classification. We evaluate the scattering behavior of a rough surface and a smooth surface at 1.5 THz based on a SAR processing sequence that is introduced in this paper. First, we form the 3D SAR images of the metallic objects and then evaluate the surface properties based on the variation in the energy reflected by the object's surface.

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Purpose: Ailanthus altissima is one of the world’s most invasive species with a globally problematic spread. Pollen is dispersed locally and partially airborne. We aimed at investigating if (i) A. altissima pollen can be detected in relevant quantity in the air and if (ii) sensitization to A. altissima can be detected in patients with seasonal exacerbation of atopic diseases. Patients and Methods: We recorded distribution of A. altissima in Leipzig, Germany. In 2019 and 2020, pollen was collected with a Hirst-type pollen trap placed on the roof of the University Hospital. Specific IgE investigations were performed in children and adults with history of atopic diseases with deterioration between May and July. We analysed specific IgE for A. altissima, Alternaria sp., birch, grasses, profilins, polcalcins and crossreacting carbohydrates. Results: We found abundant growth of A. altissima and pollen was detected from early June to mid-July with a maximum pollen concentration of 31 pollen/m3. Out of 138 patients (63 female, 69 children/adolescents), 95 (69%) had seasonal allergic rhinitis, 84 (61%) asthma, and 43 (31%) atopic dermatitis. Sensitization to A. altissima was shown in 59 (42%). There were no significant differences between age groups. In 59% of patients sensitized (35/59), there was no sensitization to possibly cross-reacting structures. Conclusion: Sensitization to A. altissima pollen could be detected in 42% of our patients with atopic diseases, suggesting allergenic potential of this neophyte. In the context of further spread with climate change, eradication strategies and population-based sensitization studies are needed.

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Zum 50-jährigen Jubiläum des Ethnologischen Seminars der Universität Zürich wird dem ersten Lehrstuhlinhaber Lorenz Löffler eine Ausstellung mit Publikation gewidmet. Seine ehemaligen Studierenden und Mitarbeitenden sind dem engagierten Professor bis heute verbunden. Doch wie sollte er als Ethnologe erinnert werden? Wir meinen: vor allem durch seine Forschungen bei den Schwendbau-Gesellschaften der Chittagong Hill Tracts im äussersten Osten Bangladeschs. Diesen bäuerlichen Gesellschaften blieb er ein Leben lang tief verbunden. On the occasion of the 50th anniversary of the Ethnological Seminar of the University of Zurich, an exhibition and publication will be devoted to the first chair holder, Lorenz Löffler. His former students and staff are still connected to the dedicated professor today. But how should he be remembered as an ethnologist? We think: first and foremost through his research among the swidden cultivation societies of the Chittagong Hill Tracts in the far east of Bangladesh. Throughout his life he remained deeply attached to these farming societies.

Contains fulltext : 229376.pdf (publisher's version ) (Open Access), Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45(-/-) mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.

AIMS Cardiovascular magnetic resonance (CMR) imaging is an important tool in the assessment of paediatric cardiac disease. Reported reference values of ventricular volumes and masses in the paediatric population are based on small cohorts and several methodologic differences between studies exist. We sought to create steady-state free precession (SSFP) CMR reference values for biventricular volumes and mass by combining data of previously published studies and re-analysing these data in a standardized manner. METHODS AND RESULTS A total of 141 healthy children (68 boys) from three European centres underwent cine-SSFP CMR imaging. Cardiac structures were manually contoured for end-diastolic and end-systolic phases in the short-axis orientation according to current standardized CMR post-processing guidelines. Volumes and masses were derived from these contours. Age-related reference curves were constructed using the lambda mu sigma method. Median age was 12.7 years (range 0.6-18.5). We report biventricular volumes and masses, unindexed and indexed for body surface area, stratified by age groups. In general, boys had approximately 15% higher biventricular volumes and masses compared with girls. Only in children aged <6 years old no gender differences could be observed. Left ventricle ejection fraction was slightly higher in boys in this study population (median 67% vs. 65%, P = 0.016). Age-related reference curves showed non-linear relations between age and cardiac parameters. CONCLUSION We report volumetric SSFP CMR imaging reference values for children aged 0-18 years old in a relatively large multi-centre cohort. These references can be used in the follow-up of paediatric cardiac disease and for research purposes.