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Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Wissenschaftsvermittlung in der Wiege der Menschheit : das Cultural & Museum Centre Karonga, Malawi
(2006)
Karonga, der "Fossiliendistrikt" im Norden Malawis, ist reich an versteinerten Resten aus der Urzeit des Menschen. Doch wo einst die Wiege der Menschheit stand, leben Menschen heute an der Peripherie der kulturellen und wirtschaftlichen Entwicklung. Der Paläoanthropologe Friedemann Schrenk, der dort mit seinen amerikanischen Kollegen Timothy Bromage die raren Relikte unserer Vorfahren, Hominidenfossilien, entdeckte, hatte die Idee, das kulturelle und naturhistorische Erbe für die einheimische Bevölkerung in einem ungewöhnlichen Museumsprojekt erfahrbar zu machen. Das Cultural & Museum Centre Karonga präsentiert 240 Millionen Jahre Erdgeschichte "From Dinosaurs to Democracy" zum Anfassen, Erkunden und Hinterfragen.
Von einem, der auszog, das Alter zu erkunden : Ulrich Peter Ritters ganz persönliche "Alterspolitik"
(2007)
20 Bücher und mehr als 80 Aufsätze füllen Ulrich Peter Ritters Veröffentlichungsregister. Ab 1975 unterrichtete der gebürtige Essener am Fachbereich 02 der Johann Wolfgang Goethe-Universität als Professor für Hochschuldidaktik der Wirtschaftswissenschaften. Lehren für Studenten, die lehren lernen wollten, war damals en vogue. Und so gab Ritter im Wintersemester 1973/74 ein gut besuchtes Seminar für Tutoren sowie ein weniger frequentiertes Seminar zur Hochschuldidaktik für Hochschullehrer, wissenschaftliche Mitarbeiter und Studenten. Das war der Anfang seiner Karriere in Frankfurt. Eigentlich könnte der heute 72-Jährige nach 26 Jahren Lehre und Forschung eine Hände getrost in den Schoß legen. Mitnichten! Sein Ruhestand ist ein Unruhestand. Er, der zeit seines Lebens forschte und lehrte, lebt nun – gemeinsam mit seiner Frau Judy (71), einer Diplompädagogin und Organisationsberaterin – die Modelle seiner Forschung. ...
Global-scale assessments of freshwater fluxes and storages by hydrological models under historic climate conditions are subject to a variety of uncertainties. Using the global hydrological model WaterGAP 2.2, we investigated the sensitivity of simulated freshwater fluxes and water storage variations to five major sources of uncertainty: climate forcing, land cover input, model structure, consideration of human water use and calibration (or no calibration). In a modelling experiment, five variants of the standard version of WaterGAP 2.2 were generated that differed from the standard version only regarding the investigated source of uncertainty. Sensitivity was analyzed by comparing water fluxes and water storage variations computed by the variants to those of the standard version, considering both global averages and grid cell values for the time period 1971–2000. The basin-specific calibration approach for WaterGAP, which forces simulated mean annual river discharge to be equal to observed values at 1319 gauging stations (representing 54% of global land area except Antarctica and Greenland), has the highest effect on modelled water fluxes and leads to the best fit of modelled to observed monthly and seasonal river discharge. Alternative state-of-the-art climate forcings rank second regarding the impact on grid cell specific fluxes and water storage variations, and their impact is ubiquitous and stronger than that of alternative land cover inputs. The diverse model refinements during the last decade lead to an improved fit to observed discharge, and affect globally averaged fluxes and storage values (the latter mainly due to modelling of groundwater depletion) but only affect a relatively small number of grid cells. Considering human water use is important for the global water storage trend (in particular in the groundwater compartment) but impacts on water fluxes are rather local and only important where water use is high. The best fit to observed time series of monthly river discharge (Nash–Sutcliffe criterion) or discharge seasonality is obtained with the standard WaterGAP 2.2 model version which is calibrated and driven by a sequence of two time series of daily observation-based climate forcings, WFD/WFDEI. Discharge computed by a calibrated model version using monthly CRU 3.2 and GPCC v6 climate input reduced the fit to observed discharge for most stations. Taking into account the investigated uncertainties of climate and land cover data, we estimate that the global 1971–2000 discharge into oceans and inland sinks is between 40 000 and 42 000 km3 yr−1. The range is mainly due differences in precipitation data that affect discharge in uncalibrated river basins. Actual evapotranspiration, with approximately 70 000 km3 yr−1, is rather unaffected by climate and land cover in global sum but differs spatially. Human water use is calculated to reduce river discharge by approximately 1000 km3 yr−1. Thus, global renewable water resources are estimated to range between 41 000 and 43 000 km3 yr−1. The climate data sets WFD (available until 2001) and WFDEI (starting in 1979) were found to be inconsistent with respect to short wave radiation data, resulting in strongly different potential evapotranspiration. Global assessments of freshwater fluxes and storages would therefore benefit from the development of a global data set of consistent daily climate forcing from 1900 to current.
Intensive land use is a driving force for biodiversity decline in many ecosystems. In semi-natural grasslands, land-use activities such as mowing, grazing and fertilization affect the diversity of plants and arthropods, but the combined effects of different drivers and the chain of effects are largely unknown. In this study we used structural equation modelling to analyse how the arthropod communities in managed grasslands respond to land use and whether these responses are mediated through changes in resource diversity or resource quantity (biomass). Plants were considered resources for herbivores which themselves were considered resources for predators. Plant and arthropod (herbivores and predators) communities were sampled on 141 meadows, pastures and mown pastures within three regions in Germany in 2008 and 2009. Increasing land-use intensity generally increased plant biomass and decreased plant diversity, mainly through increasing fertilization. Herbivore diversity decreased together with plant diversity but showed no response to changes in plant biomass. Hence, land-use effects on herbivore diversity were mediated through resource diversity rather than quantity. Land-use effects on predator diversity were mediated by both herbivore diversity (resource diversity) and herbivore quantity (herbivore biomass), but indirect effects through resource quantity were stronger. Our findings highlight the importance of assessing both direct and indirect effects of land-use intensity and mode on different trophic levels. In addition to the overall effects, there were subtle differences between the different regions, pointing to the importance of regional land-use specificities. Our study underlines the commonly observed strong effect of grassland land use on biodiversity. It also highlights that mechanistic approaches help us to understand how different land-use modes affect biodiversity.
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
In südlichen Gefilden wächst so manches, was in Maßen genossen dem Wohlbefinden dient. Dies gilt nicht nur für Heilkräuter und Rotwein, sondern vermutlich auch für andere für den Mittelmeerraum typische Getränke und Speisen. Auf der Suche nach diesen "natürlichen Apotheken" erfassen Wissenschaftler aus Deutschland und sechs weiteren europäischen Ländern derzeit seltene Unterarten bewährter Nutzpflanzen wie Thymian, Olive, Wein und Orange. Sie erforschen, ob die seit Jahrhunderten überlieferten Schutzund Heilungskräfte der Gewächse einer wissenschaftlichen Prüfung standhalten und worauf sie beruhen. Die Frankfurter Gruppe um Prof. Dr. Walter Müller hat dabei insbesondere Stoffe im Blick, die das Nervensystem beeinflussen. Macht mediterrane Kost wirklich geistig fit?
Glioblastoma is one of the most aggressive malignant brain tumors, with a survival time less than 15 months and characterized by a high radioresistance and the property of infiltrating the brain. Recent data indicate that the malignancy of glioblastomas depends on glutamatergic signaling via ionotropic glutamate receptors. In this study we revealed functional expression of Ca2+-permeable NMDARs in three glioblastoma cell lines. Therefore, we investigated the impact of this receptor on cell survival, migration and DNA double-strand break (DSB) repair in the presence of both, glutamate and NMDAR antagonists, and after clinically relevant doses of ionizing radiation. Our results indicate that treatment with NMDAR antagonists slowed the growth and migration of glutamate-releasing LN229 cells, suggesting that activation of NMDARs facilitate tumor expansion. Furthermore, we found that DSB-repair upon radiation was more effective in the presence of glutamate. In contrast, antagonizing the NMDAR or the Ca2+-dependent transcription factor CREB impaired DSB-repair similarly and resulted in a radiosensitizing effect in LN229 and U-87MG cells, indicating a common link between NMDAR signaling and CREB activity in glioblastoma. Since the FDA-approved NMDAR antagonists memantine and ifenprodil showed differential radiosensitizing effects, these compounds may constitute novel optimizations for therapeutic interventions in glioblastoma.
(1) Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are biologically at high risk for the development of loco–regional recurrences after postoperative radiotherapy (PORT) but at intermediate risk according to clinical risk factors may benefit from additional concurrent chemotherapy. In this matched-pair study, we aimed to identify a corresponding predictive gene signature. (2) Methods: Gene expression analysis was performed on a multicenter retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients who were treated with PORT alone. Propensity score analysis was used to identify matched patient pairs from both cohorts. From differential gene expression analysis and Cox regression, a predictive gene signature was identified. (3) Results: 108 matched patient pairs were selected. We identified a 2-metagene signature that stratified patients into risk groups in both cohorts. The comparison of the high-risk patients between the two types of treatment showed higher loco–regional control (LRC) after treatment with PORT-C (p < 0.001), which was confirmed by a significant interaction term in Cox regression (p = 0.027), i.e., the 2-metagene signature was indicative for the type of treatment. (4) Conclusion: We have identified a novel gene signature that may be helpful to identify patients with high-risk HNSCC amongst those at intermediate clinical risk treated with PORT, who may benefit from additional concurrent chemotherapy.