Detektion okkulter medullärer Schilddrüsenkarzinome bei Patienten eineruniversitären Schilddrüsen-Ambulanz: Diagnostischer Wert von Calcitonin-Screening, Pentagastrintest und Gastrinrezeptorszintigraphie

Ziel der vorliegenden Arbeit war es an einer großen Zahl von Patienten den Wert des Calcitonin Screenings zur Frühdiagnostik des medullären Schilddrüsenkarzinoms zu untersuchen. Insbesondere wurde untersucht, ab welchem Grenzwert des basalen Calcitoninwertes im Serum mit einem medullären Schilddrüsenkarzinom oder der mutmaßlichen Präkanzerose des hereditären medullären Schilddrüsenkarzinoms, der neoplastischen C-Zell Hyperplasie, gerechnet werden muss. Ergänzend wurde der diagnostische Wert der Pentagastrin-stimulierten Calcitoninkonzentration im Serum untersucht, ebenso der zu wählenden Grenzwert. Als nuklearmedizinisches bildgebendes Verfahren wurde präoperativ neben der Sonographie, eine CCK-2-Rezeptor Szintigraphie mit 111Indium-D-Glu1-sulfatiertem Minigastrin durchgeführt und verglichen, ob eine pathologische Anreicherung mit der Calcitoninkonzentration im Serum und dem histologischen Befund korreliert. Abschließend wurde bewertet, ob die aktuell durchgeführte diagnostische Kaskade sinnvoll ist. Die untersuchte Patientengruppe stammt aus einer universitären Schilddrüsenambulanz. Es wurden alle Patienten mit vorhandener Schilddrüse, die sich zur Schilddrüsenuntersuchung vorstellten, in die Studie einbezogen. In 47 Monaten wurde bei 4858 Patienten die basale Calcitoninkonzentration im Serum gemessen. 300 Patienten zeigten eine erhöhte Calcitoninkonzentration im Serum, das heißt bei Frauen mehr als 4,6 pg/ml und bei Männern mehr als 11,5 pg/ml. Bei 259 Patienten erfolgte ein Pentagastrin-Stimulationstest. Bei 1,1 % dieser Patienten stieg der Calcitoninwert im Serum nach Stimulation mit Pentagastrin auf Werte über 100 pg/ml an. Den Patienten, bei denen der Calcitoninwert im Serum nach Stimulation mit Pentagastrin weniger als 100 pg/ml betrug, wurde eine jährliche Kontrolle der basalen Calcitoninkonzentration empfohlen. 34 von 55 Patienten ließen vor Thyreoidektomie eine CCK-2-Rezeptor- Szintigraphie mit 111Indium-D-Glu1-sulfatiertem Minigastrin durchführen. Letztendlich wurden 32 Patienten operiert und bei zwei Patienten histologisch 102 ein medulläres Schilddrüsenkarzinoms diagnostiziert. Die Prävalenz an einem medullären Schilddrüsenkarzinom zu erkranken betrug 0,04 %. Sowohl die basalen Calcitoninwerte, als auch die Calcitoninwerte nach Pentagastrinstimulation lagen bei den Patienten mit einem medullären Schilddrüsenkarzinom deutlich über den Calcitoninwerten die bei Patienten gemessen wurden, bei denen eine C-Zell Hyperplasie oder histologisch normales Schilddrüsengewebe vorlag. Die Calcitoninwerte bei beiden Patienten mit medullärem Schilddrüsenkarzinom überschritten die gewählten Grenzwerte um ein Vielfaches. Zur Unterscheidung zwischen einer neoplastischen, einer nodulären oder diffusen C-Zell Hyperplasie oder unauffälligem Schilddrüsengewebe, ist die Bestimmung des basalen und stimulierten Calcitoninwertes dagegen nicht hilfreich. Wie die Ergebnisse zeigen, ist es umso wichtiger die diagnostische Reihenfolge einzuhalten. Es sollte routinemäßig der Calcitoninwert im Serum bestimmt werden und bei pathologischem Ergebnis (Grenzwert abhängig vom Assay)zunächst ein Stimulationstest mit Pentagastrin durchgeführt werden, da erst ab einem Stimulationswert von 100 pg/ml mit einem medullärem Schilddrüsenkarzinom oder einer neoplastischen C-Zell Hyperplasie zu rechnen ist. Der in der vorliegenden Arbeit verwendete Grenzwert von 100,0 pg/ml ist korrekt gewählt, da dadurch mehr Schilddrüsen mit bereits pathologischen Gewebsveränderungen, als gesunde Schilddrüsen operativ entfernt wurden. Deshalb sollte die Thyreoidektomie erst bei pathologisch ausfallendem Pentagastrintest erfolgen. Die Gastrinszintigraphie mit 111Indium-D-Glu1-sulfatiertem Minigastrin ist zur Primärdiagnose eines medullären Schilddrüsenkarzinoms ungeeignet, sie spielt jedoch eine wichtige Rolle zur postoperativen Verlaufskontrolle und zur Rezidivbzw. Metastasensuche bei persistierend erhöhtem oder ansteigendem Calcitoninwert im Serum

Stärkung des literarischen Kompetenzerwerbs durch induktive und deduktive Erarbeitung literarischer Grundlagen - zwei Methoden im Vergleich

Within literary studies, students are confronted with an enormous reading workload and are expected not only to be able to name and explain the basic concepts and working methods within a very short time, but also to apply their knowledge to concrete examples. Especially in the seminars, it is therefore important to optimally support the students in this learning process. Although there are many successful teaching concepts, there is often a lack of specific analyses of the effects on the student's learning process. This practice-oriented contribution introduces a Scholarship of Teaching and Learning project, which focuses on the apparently simple but very complex question of whether the inductive (i. e. from the example to the rule) or deductive (i. e. starting from the general) method is more effective for teaching literary competences. The conclusion will be based on the student's subjective perceptions of how supportive these two methods were for their learning process.Studierende der Literaturwissenschaft sind mit einem enormen Lesepensum konfrontiert und sollen innerhalb kürzester Zeit nicht nur die grundlegenden Konzepte und Arbeitsweisen der Wissenschaft benennen und erklären können, sondern ihr Wissen auch auf konkrete Beispiele anwenden. Vor allem in den Seminaren ist es deshalb wichtig, die Studierenden bei diesem Lernprozess optimal zu unterstützen. Obgleich es vielzählige erfolgreiche Lehrkonzepte gibt, fehlt oft eine gezielte Analyse der Auswirkungen auf den Lernprozess der Studierenden. Dieser praxisorientierte Beitrag stellt ein Scholarship of Teaching and Learning-Projekt vor, in dessen Mittelpunkt die anscheinend einfache, aber doch sehr komplexe Frage steht, ob die induktive (d. h. vom Beispiel zur Regel) oder deduktive Methode (d. h. vom Allgemeinen ausgehend) bei der Vermittlung literarischer Kompetenzen in der subjektiven Wahrnehmung der Studierenden effektiver bei der Unterstützung des Lernprozesses ist

Seroprevalence of Schmallenberg virus infection in sheep and goats flocks in Germany, 2012-2013

Schmallenberg virus (SBV) is a member of the family Bunyaviridae and mainly affects ruminants. It is transmitted by biting midges, first and foremost Culicoides spp., and causes congenital malformations reflected in arthrogryposis-hydranencephaly (AH) syndrome. The aim of this study was to collect data on the emergence of SBV as a new arthropod-borne disease introduced into Europe in 2011. Germany was located in the core region of the 2011/2012 epidemic. Following two seroprevalence studies in the north-west of Germany in 2012, this study focused on the epidemiology and distribution of SBV throughout 130 small ruminant flocks in the whole country. Blood samples were obtained of 30 animals per flock and a SBV-specific questionnaire was used to collect operating data of the farms. The median within-herd seroprevalence for all 130 flocks tested was 53.3% with a total range from 0% to 100%. The median within-herd seroprevalence for goats was 30% [interquartile range (IQR): 40.3%] and 57% for sheep (IQR: 43.3%). Small ruminant flocks kept permanently indoors or housed overnight had a significantly lower seroprevalence than flocks kept permanently outdoors. In addition, this study revealed a significantly lower seroprevalence in the north-east of Germany. These results show that small ruminants in Germany are still at risk of contracting new SBV infections following incomplete seroconversion of flocks especially in the north-east of Germany. This might contribute to SBV becoming enzootic in central and northern Europe. Furthermore, the survey revealed that housing animals at least during mating and early pregnancy may reduce the risk of new SBV infections and may thus be an option to reduce losses as long as there is no licensed vaccine available on the German market

Providing Information by Resource- Constrained Data Analysis

The Collaborative Research Center SFB 876 (Providing Information by Resource-Constrained Data Analysis) brings together the research fields of data analysis (Data Mining, Knowledge Discovery in Data Bases, Machine Learning, Statistics) and embedded systems and enhances their methods such that information from distributed, dynamic masses of data becomes available anytime and anywhere. The research center approaches these problems with new algorithms respecting the resource constraints in the different scenarios. This Technical Report presents the work of the members of the integrated graduate school

Using stable isotopes to inform water resource management in forested and agricultural ecosystems

Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques

Preventing and Reducing Coercive Measures—An Evaluation of the Implementation of the Safewards Model in Two Locked Wards in Germany

IntroductionAggression and violence are highly complex problems in acute psychiatry that often lead to the coercive interventions. The Safewards Model is an evidence-informed conflict-reduction strategy to prevent and reduce such incidents. The aim of this study was to evaluate the implementation of this model with regard to coercive interventions in inpatient care.Materials and MethodsWe evaluated outcomes of the implementation of the Safewards Model in two locked psychiatric wards in Germany. Frequency and duration of coercive interventions applied during a period of 11 weeks before and 11 weeks after the implementation period were assessed through routine data. Fidelity to the Safewards Model was assessed by the Organization Fidelity Checklist.ResultsFidelity to the Safewards Model was high in both wards. The overall use of coercive measures differed significantly between wards [case-wise: χ2 (1, n = 250) = 35.34, p ≤ 0.001; patient-wise: χ2 (1, n = 103) = 21.45, p ≤ 0.001] and decreased post-implementation. In one ward, the number of patients exposed to coercive interventions in relation to the overall number of Patients decreased significantly [χ2 (1, 281) = 6.40, p = 0.01]. Furthermore, the mean duration of coercive interventions overall declined significantly [U(55,21) = −2.142, p = 0.032] with an effect size of Cohen’s d = −0.282 (95% CI: −0.787, 0.222) in that ward. Both aspects declined as well in the other ward, but not significantly.DiscussionResults indicate that the implementation of the Safewards interventions according to the model in acute psychiatric care can reduce coercive measures. They also show the role of enabling factors as well as of obstacles for the implementation process

The Mitochondrial Chaperone Protein TRAP1 Mitigates α-Synuclein Toxicity

Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]α-Synuclein–induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]α-Synuclein expression. In addition, decreased TRAP1 expression in [A53T]α-Synuclein–expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T]α-Synuclein–induced sensitivity to rotenone treatment. In human (non)neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T]α-Synuclein–induced sensitivity to oxidative stress treatment. [A53T]α-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T]α-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T]α-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to α-Synuclein

Ambient-noise tomography of the wider Vienna Basin region

We present a new 3-D shear-velocity model for the top 30 km of the crust in the wider Vienna Basin region based on surface waves extracted from ambient-noise cross-correlations. We use continuous seismic records of 63 broad-band stations of the AlpArray project to retrieve interstation Green’s functions from ambient-noise cross-correlations in the period range from 5 to 25 s. From these Green’s functions, we measure Rayleigh group traveltimes, utilizing all four components of the cross-correlation tensor, which are associated with Rayleigh waves (ZZ, RR, RZ and ZR), to exploit multiple measurements per station pair. A set of selection criteria is applied to ensure that we use high-quality recordings of fundamental Rayleigh modes. We regionalize the interstation group velocities in a 5 km × 5 km grid with an average path density of ∼20 paths per cell. From the resulting group-velocity maps, we extract local 1-D dispersion curves for each cell and invert all cells independently to retrieve the crustal shear-velocity structure of the study area. The resulting model provides a previously unachieved lateral resolution of seismic velocities in the region of ∼15 km. As major features, we image the Vienna Basin and Little Hungarian Plain as low-velocity anomalies, and the Bohemian Massif with high velocities. The edges of these features are marked with prominent velocity contrasts correlated with faults, such as the Alpine Front and Vienna Basin transfer fault system. The observed structures correlate well with surface geology, gravitational anomalies and the few known crystalline basement depths from boreholes. For depths larger than those reached by boreholes, the new model allows new insight into the complex structure of the Vienna Basin and surrounding areas, including deep low-velocity zones, which we image with previously unachieved detail. This model may be used in the future to interpret the deeper structures and tectonic evolution of the wider Vienna Basin region, evaluate natural resources, model wave propagation and improve earthquake locations, among others

Arrival angles of teleseismic fundamental mode Rayleigh waves across the AlpArray

The dense AlpArray network allows studying seismic wave propagation with high spatial resolution. Here we introduce an array approach to measure arrival angles of teleseismic Rayleigh waves. The approach combines the advantages of phase correlation as in the two-station method with array beamforming to obtain the phase-velocity vector. 20 earthquakes from the first two years of the AlpArray project are selected, and spatial patterns of arrival-angle deviations across the AlpArray are shown in maps, depending on period and earthquake location. The cause of these intriguing spatial patterns is discussed. A simple wave-propagation modelling example using an isolated anomaly and a Gaussian beam solution suggests that much of the complexity can be explained as a result of wave interference after passing a structural anomaly along the wave paths. This indicates that arrival-angle information constitutes useful additional information on the Earth structure, beyond what is currently used in inversions

Shear-wave velocity structure beneath the Dinarides from the inversion of Rayleigh-wave dispersion

Highlights • Rayleigh-wave phase velocity in the wider Dinarides region using the two-station method. • Uppermost mantle shear-wave velocity model of the Dinarides-Adriatic Sea region. • Velocity model reveals a robust high-velocity anomaly present under the whole Dinarides. • High-velocity anomaly reaches depth of 160 km in the northern Dinarides to more than 200 km under southern Dinarides. • New structural model incorporating delamination as one of the processes controlling the continental collision in the Dinarides. The interaction between the Adriatic microplate (Adria) and Eurasia is the main driving factor in the central Mediterranean tectonics. Their interplay has shaped the geodynamics of the whole region and formed several mountain belts including Alps, Dinarides and Apennines. Among these, Dinarides are the least investigated and little is known about the underlying geodynamic processes. There are numerous open questions about the current state of interaction between Adria and Eurasia under the Dinaric domain. One of the most interesting is the nature of lithospheric underthrusting of Adriatic plate, e.g. length of the slab or varying slab disposition along the orogen. Previous investigations have found a low-velocity zone in the uppermost mantle under the northern-central Dinarides which was interpreted as a slab gap. Conversely, several newer studies have indicated the presence of the continuous slab under the Dinarides with no trace of the low velocity zone. Thus, to investigate the Dinaric mantle structure further, we use regional-to-teleseismic surface-wave records from 98 seismic stations in the wider Dinarides region to create a 3D shear-wave velocity model. More precisely, a two-station method is used to extract Rayleigh-wave phase velocity while tomography and 1D inversion of the phase velocity are employed to map the depth dependent shear-wave velocity. Resulting velocity model reveals a robust high-velocity anomaly present under the whole Dinarides, reaching the depths of 160 km in the north to more than 200 km under southern Dinarides. These results do not agree with most of the previous investigations and show continuous underthrusting of the Adriatic lithosphere under Europe along the whole Dinaric region. The geometry of the down-going slab varies from the deeper slab in the north and south to the shallower underthrusting in the center. On-top of both north and south slabs there is a low-velocity wedge indicating lithospheric delamination which could explain the 200 km deep high-velocity body existing under the southern Dinarides