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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.
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.
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. ...
Background: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active ‘probe’ molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors. Here we describe the use of a high-content cellular immunofluorescence assay as a method for demonstrating target engagement in cells.
Results: A panel of assays for the Jumonji C subfamily of KDMs was developed to encompass all major branches of the JmjC phylogenetic tree. These assays compare compound activity against wild-type KDM proteins to a catalytically inactive version of the KDM, in which residues involved in the active-site iron coordination are mutated to inactivate the enzyme activity. These mutants are critical for assessing the specific effect of KDM inhibitors and for revealing indirect effects on histone methylation status. The reported assays make use of ectopically expressed demethylases, and we demonstrate their use to profile several recently identified classes of KDM inhibitors and their structurally matched inactive controls. The generated data correlate well with assay results assessing endogenous KDM inhibition and confirm the selectivity observed in biochemical assays with isolated enzymes. We find that both cellular permeability and competition with 2-oxoglutarate affect the translation of biochemical activity to cellular inhibition.
Conclusions: High-content-based immunofluorescence assays have been established for eight KDM members of the 2-oxoglutarate-dependent oxygenases covering all major branches of the JmjC-KDM phylogenetic tree. The usage of both full-length, wild-type and catalytically inactive mutant ectopically expressed protein, as well as structure-matched inactive control compounds, allowed for detection of nonspecific effects causing changes in histone methylation as a result of compound toxicity. The developed assays offer a histone lysine demethylase family-wide tool for assessing KDM inhibitors for cell activity and on-target efficacy. In addition, the presented data may inform further studies to assess the cell-based activity of histone lysine methylation inhibitors.
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.
When assessing global water resources with hydrological models, it is essential to know about methodological uncertainties. The values of simulated water balance components may vary due to different spatial and temporal aggregations, reference periods, and applied climate forcings, as well as due to the consideration of human water use, or the lack thereof. We analyzed these variations over the period 1901–2010 by forcing the global hydrological model WaterGAP 2.2 (ISIMIP2a) with five state-of-the-art climate data sets, including a homogenized version of the concatenated WFD/WFDEI data set. Absolute values and temporal variations of global water balance components are strongly affected by the uncertainty in the climate forcing, and no temporal trends of the global water balance components are detected for the four homogeneous climate forcings considered (except for human water abstractions). The calibration of WaterGAP against observed long-term average river discharge Q significantly reduces the impact of climate forcing uncertainty on estimated Q and renewable water resources. For the homogeneous forcings, Q of the calibrated and non-calibrated regions of the globe varies by 1.6 and 18.5 %, respectively, for 1971–2000. On the continental scale, most differences for long-term average precipitation P and Q estimates occur in Africa and, due to snow undercatch of rain gauges, also in the data-rich continents Europe and North America. Variations of Q at the grid-cell scale are large, except in a few grid cells upstream and downstream of calibration stations, with an average variation of 37 and 74 % among the four homogeneous forcings in calibrated and non-calibrated regions, respectively. Considering only the forcings GSWP3 and WFDEI_hom, i.e., excluding the forcing without undercatch correction (PGFv2.1) and the one with a much lower shortwave downward radiation SWD than the others (WFD), Q variations are reduced to 16 and 31 % in calibrated and non-calibrated regions, respectively. These simulation results support the need for extended Q measurements and data sharing for better constraining global water balance assessments. Over the 20th century, the human footprint on natural water resources has become larger. For 11–18% of the global land area, the change of Q between 1941–1970 and 1971–2000 was driven more strongly by change of human water use including dam construction than by change in precipitation, while this was true for only 9–13 % of the land area from 1911–1940 to 1941–1970.
When assessing global water resources with hydrological models, it is essential to know the methodological uncertainties in the water resources estimates. The study presented here quantifies effects of the uncertainty in the spatial and temporal patterns of meteorological variables on water balance components at the global, continental and grid cell scale by forcing the global hydrological model WaterGAP 2.2 (ISI-MIP 2.1) with five state-of-the-art climate forcing input data-sets. While global precipitation over land during 1971–2000 varies between 103 500 and 111 000 km3 yr−1, global river discharge varies between 39 200 and 42 200 km3 yr−1. Temporal trends of global wa- ter balance components are strongly affected by the uncertainty in the climate forcing (except human water abstractions), and there is a need for temporal homogenization of climate forcings (in particular WFD/WFDEI). On about 10–20 % of the global land area, change of river discharge between two consecutive 30 year periods was driven more strongly by changes of human water use including dam construction than by changes in precipitation. This number increases towards the end of the 20th century due to intensified human water use and dam construction. The calibration approach of WaterGAP against observed long-term average river discharge reduces the impact of climate forcing uncertainty on estimated river discharge significantly. Different homgeneous climate forcings lead to a variation of Q of only 1.6 % for the 54 % of global land area that are constrained by discharge observations, while estimated renewable water resources in the remaining uncalibrated regions vary by 18.5 %. Uncertainties are especially high in Southeast Asia where Global Runoff Data Centre (GRDC) data availability is very sparse. By sharing already available discharge data, or installing new streamflow gauging stations in such regions, water balance uncertainties could be reduced which would lead to an improved assessment of the world’s water resources.
The assessment of water balance components using global hydrological models is subject to climate forcing uncertainty as well as to an increasing intensity of human water use within the 20th century. The uncertainty of five state-of-the-art climate forcings and the resulting range of cell runoff that is simulated by the global hydrological model WaterGAP is presented. On the global land surface, about 62 % of precipitation evapotranspires, whereas 38 % discharges into oceans and inland sinks. During 1971–2000, evapotranspiration due to human water use amounted to almost 1 % of precipitation, while this anthropogenic water flow increased by a factor of approximately 5 between 1901 and 2010. Deviation of estimated global discharge from the ensemble mean due to climate forcing uncertainty is approximately 4 %. Precipitation uncertainty is the most important reason for the uncertainty of discharge and evapotranspiration, followed by shortwave downward radiation. At continental levels, deviations of water balance components due to uncertain climate forcing are higher, with the highest discharge deviations occurring for river discharge in Africa (−6 to 11 % from the ensemble mean). Uncertain climate forcings also affect the estimation of irrigation water use and thus the estimated human impact of river discharge. The uncertainty range of global irrigation water consumption amounts to approximately 50 % of the global sum of water consumption in the other water use sector.
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.
