@article{ReinersAsamFreyetal.2021, author = {Reiners, Philipp and Asam, Sarah and Frey, Corinne and Holzwarth, Stefanie and Bachmann, Martin and Sobrino, Jose and G{\"o}ttsche, Frank-M. and Bendix, J{\"o}rg and Kuenzer, Claudia}, title = {Validation of AVHRR Land Surface Temperature with MODIS and in situ LST — a TIMELINE thematic processor}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {17}, issn = {2072-4292}, doi = {10.3390/rs13173473}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246051}, year = {2021}, abstract = {Land Surface Temperature (LST) is an important parameter for tracing the impact of changing climatic conditions on our environment. Describing the interface between long- and shortwave radiation fluxes, as well as between turbulent heat fluxes and the ground heat flux, LST plays a crucial role in the global heat balance. Satellite-derived LST is an indispensable tool for monitoring these changes consistently over large areas and for long time periods. Data from the AVHRR (Advanced Very High-Resolution Radiometer) sensors have been available since the early 1980s. In the TIMELINE project, LST is derived for the entire operating period of AVHRR sensors over Europe at a 1 km spatial resolution. In this study, we present the validation results for the TIMELINE AVHRR daytime LST. The validation approach consists of an assessment of the temporal consistency of the AVHRR LST time series, an inter-comparison between AVHRR LST and in situ LST, and a comparison of the AVHRR LST product with concurrent MODIS (Moderate Resolution Imaging Spectroradiometer) LST. The results indicate the successful derivation of stable LST time series from multi-decadal AVHRR data. The validation results were investigated regarding different LST, TCWV and VA, as well as land cover classes. The comparisons between the TIMELINE LST product and the reference datasets show seasonal and land cover-related patterns. The LST level was found to be the most determinative factor of the error. On average, an absolute deviation of the AVHRR LST by 1.83 K from in situ LST, as well as a difference of 2.34 K from the MODIS product, was observed.}, language = {en} } @article{KuhnGrippFliederetal.2015, author = {Kuhn, Joachim and Gripp, Tatjana and Flieder, Tobias and Dittrich, Marcus and Hendig, Doris and Busse, Jessica and Knabbe, Cornelius and Birschmann, Ingvild}, title = {UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays}, series = {PLOS ONE}, volume = {10}, journal = {PLOS ONE}, number = {12}, doi = {10.1371/journal.pone.0145478}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136023}, pages = {e0145478}, year = {2015}, abstract = {Introduction The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery. Methods Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM) mode (UPLC-MRM MS). Internal standards (ISs) were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion. Results The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 mu g/L (r > 0.99). Limits of detection (LOD) in the plasma matrix were 0.21 mu g/L for dabigatran and 0.34 mu g/L for rivaroxaban, and lower limits of quantification (LLOQ) in the plasma matrix were 0.46 mu g/L for dabigatran and 0.54 mu g/L for rivaroxaban. The intraassay coefficients of variation (CVs) for dabigatran and rivaroxaban were < 4\% and 6\%; respectively, the interassay CVs were < 6\% for dabigatran and < 9\% for rivaroxaban. Inaccuracy was < 5\% for both substances. The mean recovery was 104.5\% (range 83.8-113.0\%) for dabigatran and 87.0\%(range 73.6-105.4\%) for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20 degrees C, 4 degrees C and even at RT for at least one week. A method comparison between our UPLC-MRM MS method, the commercially available automated Direct Thrombin Inhibitor assay (DTI assay) for dabigatran measurement from CoaChrom Diagnostica, as well as the automated anti-Xa assay for rivaroxaban measurement from Chromogenix both performed by ACL-TOP showed a high degree of correlation. However, UPLC-MRM MS measurement of dabigatran and rivaroxaban has a much better selectivity than classical functional assays measuring activities of various coagulation factors which are susceptible to interference by other coagulant drugs. Conclusions Overall, we developed and validated a sensitive and specific UPLC-MRM MS assay for the quick and specific measurement of dabigatran and rivaroxaban in human plasma.}, language = {en} } @article{ErmertFinkMorseetal.2012, author = {Ermert, Volker and Fink, Andreas H. and Morse, Andrew P. and Paeth, Heiko}, title = {The Impact of Regional Climate Change on Malaria Risk due to Greenhouse Forcing and Land-Use Changes in Tropical Africa}, series = {Environmental Health Perspectives}, volume = {120}, journal = {Environmental Health Perspectives}, number = {1}, doi = {10.1289/ehp.1103681}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135562}, pages = {77-84}, year = {2012}, abstract = {BACKGROUND: Climate change will probably alter the spread and transmission intensity of malaria in Africa. OBJECTIVES: In this study, we assessed potential changes in the malaria transmission via an integrated weather disease model. METHODS: We simulated mosquito biting rates using the Liverpool Malaria Model (LMM). The input data for the LMM were bias-corrected temperature and precipitation data from the regional model (REMO) on a 0.5 degrees latitude longitude grid. A Plasmodium falciparum infection model expands the LMM simulations to incorporate information on the infection rate among children. Malaria projections were carried out with this integrated weather disease model for 2001 to 2050 according to two climate scenarios that include the effect of anthropogenic land-use and land-cover changes on climate. RESULTS: Model-based estimates for the present climate (1960 to 2000) are consistent with observed data for the spread of malaria in Africa. In the model domain, the regions where malaria is epidemic are located in the Sahel as well as in various highland territories. A decreased spread of malaria over most parts of tropical Africa is projected because of simulated increased surface temperatures and a significant reduction in annual rainfall. However, the likelihood of malaria epidemics is projected to increase in the southern part of the Sahel. In most of East Africa, the intensity of malaria transmission is expected to increase. Projections indicate that highland areas that were formerly unsuitable for malaria will become epidemic, whereas in the lower-altitude regions of the East African highlands, epidemic risk will decrease. CONCLUSIONS: We project that climate changes driven by greenhouse-gas and land-use changes will significantly affect the spread of malaria in tropical Africa well before 2050. The geographic distribution of areas where malaria is epidemic might have to be significantly altered in the coming decades.}, language = {en} } @article{SamimiFinkPaeth2012, author = {Samimi, C. and Fink, A. H. and Paeth, H.}, title = {The 2007 flood in the Sahel: causes, characteristics and its presentation in the media and FEWS NET}, series = {Natural Hazards and Earth System Sciences}, volume = {12}, journal = {Natural Hazards and Earth System Sciences}, number = {2}, doi = {10.5194/nhess-12-313-2012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131790}, pages = {313 -- 325}, year = {2012}, abstract = {During the rainy season in 2007, reports about exceptional rains and floodings in the Sahel were published in the media, especially in August and September. Institutions and organizations like the World Food Programme (WFP) and FEWS NET put the events on the agenda and released alerts and requested help. The partly controversial picture was that most of the Sahel faced a crisis caused by widespread floodings. Our study shows that the rainy season in 2007 was exceptional with regard to rainfall amount and return periods. In many areas the event had a return period between 1 and 50 yr with high spatial heterogeneity, with the exception of the Upper Volta basin, which yielded return periods of up to 1200 yr. Despite the strong rainfall, the interpretation of satellite images show that the floods were mainly confined to lakes and river beds. However, the study also proves the difficulties in assessing the meteorological processes and the demarcation of flooded areas in satellite images without ground truthing. These facts and the somewhat vague and controversial reports in the media and FEWS NET demonstrate that it is crucial to thoroughly analyze such events at a regional and local scale involving the local population.}, language = {en} } @article{WertgenRichter2020, author = {Wertgen, Andreas G. and Richter, Tobias}, title = {Source credibility modulates the validation of implausible information}, series = {Memory \& Cognition}, volume = {48}, journal = {Memory \& Cognition}, issn = {0090-502X}, doi = {10.3758/s13421-020-01067-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234825}, pages = {1359-1375}, year = {2020}, abstract = {Validation of text information as a general mechanism for detecting inconsistent or false information is an integral part of text comprehension. This study examined how the credibility of the information source affects validation processes. Two experiments investigated combined effects of source credibility and plausibility of information during validation with explicit (ratings) and implicit (reading times) measurements. Participants read short stories with a high-credible versus low-credible person that stated a consistent or inconsistent assertion with general world knowledge. Ratings of plausibility and ratings of source credibility were lower when a credible source stated a world-knowledge inconsistent assertion compared with a low-credible source. Reading times on target sentences and on spillover sentences were slower when a credible source stated an assertion inconsistent with world knowledge compared with a low-credible source, suggesting that source information modulated the validation of implausible information. These results show that source credibility modulates validation and suggest a bidirectional relationship of perceived plausibility and source credibility in the reading process.}, language = {en} } @article{AppelSchulerVogeletal.2017, author = {Appel, Patricia and Schuler, Michael and Vogel, Heiner and Oezelsel, Amina and Faller, Hermann}, title = {Short Questionnaire for Workplace Analysis (KFZA): factorial validation in physicians and nurses working in hospital settings}, series = {Journal of Occupational Medicine and Toxicology}, volume = {12}, journal = {Journal of Occupational Medicine and Toxicology}, number = {11}, doi = {10.1186/s12995-017-0157-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157510}, year = {2017}, abstract = {Background: In recent years, there has been an increasing interest in psychosocial workplace risk assessments in Germany. One of the questionnaires commonly employed for this purpose is the Short Questionnaire for Workplace Analysis (KFZA). Originally, the KFZA was developed and validated for office workers. The aim of the present study was to examine the factorial validity of the KFZA when applied to hospital settings. Therefore, we examined the factorial structure of a questionnaire that contained all the original items plus an extension adding 11 questions specific to hospital workplaces and analyzed both, the original version and the extended version. Methods: We analyzed questionnaire data of a total of 1731 physicians and nurses obtained over a 10-year period. Listwise exclusion of data sets was applied to account for variations in questionnaire versions and yielded 1163 questionnaires (1095 for the extended version) remaining for factor analysis. To examine the factor structure, we conducted a principal component factor analysis. The number of factors was determined using the Kaiser criterion and scree-plot methods. Factor interpretation was based on orthogonal Varimax rotation as well as oblique rotation. Results: The Kaiser criterion revealed a 7-factor solution for the 26 items of the KFZA, accounting for 62.0\% of variance. The seven factors were named: "Social Relationships", "Job Control", "Opportunities for Participation and Professional Development", "Quantitative Work Demands", "Workplace Environment", "Variability" and "Qualitative Work Demands". The factor analysis of the 37 items of the extended version yielded a 9-factor solution. The two additional factors were named "Consequences of Strain" and "Emotional Demands". Cronbach's α ranged from 0.63 to 0.87 for these scales. Conclusions: Overall, the KFZA turned out to be applicable to hospital workers, and its content-related structure was replicated well with some limitations. However, instead of the 11 factors originally proposed for office workers, a 7-factor solution appeared to be more suitable when employed in hospitals. In particular, the items of the KFZA factor "Completeness of Task" might need adaptation for the use in hospitals. Our study contributes to the assessment of the validity of this popular instrument and should stimulate further psychometric testing.}, language = {en} } @article{EiseleBlozikStoerketal.2013, author = {Eisele, Marion and Blozik, Eva and St{\"o}rk, Stefan and Tr{\"a}der, Jens-Martin and Herrmann-Lingen, Christoph and Scherer, Martin}, title = {Recognition of depression and anxiety and their association with quality of life, hospitalization and mortality in primary care patients with heart failure - study protocol of a longitudinal observation study}, series = {BMC Family Practice}, volume = {14}, journal = {BMC Family Practice}, number = {180}, issn = {1471-2296}, doi = {10.1186/1471-2296-14-180}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121881}, year = {2013}, abstract = {Background: International disease management guidelines recommend the regular assessment of depression and anxiety in heart failure patients. Currently there is little data on the effect of screening for depression and anxiety on the quality of life and the prognosis of heart failure (HF). We will investigate the association between the recognition of current depression/anxiety by the general practitioner (GP) and the quality of life and the patients' prognosis. Methods/Design: In this multicenter, prospective, observational study 3,950 patients with HF are recruited by general practices in Germany. The patients fill out questionnaires at baseline and 12-month follow-up. At baseline the GPs are interviewed regarding the somatic and psychological comorbidities of their patients. During the follow-up assessment, data on hospitalization and mortality are provided by the general practice. Based on baseline data, the patients are allocated into three observation groups: HF patients with depression and/or anxiety recognized by their GP (P+/+), those with depression and/or anxiety not recognized (P+/-) and patients without depression and/or anxiety (P-/-). We will perform multivariate regression models to investigate the influence of the recognition of depression and/or anxiety on quality of life at 12 month follow-up, as well as its influences on the prognosis (hospital admission, mortality). Discussion: We will display the frequency of GP-acknowledged depression and anxiety and the frequency of installed therapeutic strategies. We will also describe the frequency of depression and anxiety missed by the GP and the resulting treatment gap. Effects of correctly acknowledged and missed depression/anxiety on outcome, also in comparison to the outcome of subjects without depression/anxiety will be addressed. In case results suggest a treatment gap of depression/anxiety in patients with HF, the results of this study will provide methodological advice for the efficient planning of further interventional research.}, language = {en} } @phdthesis{Freitag2011, author = {Freitag, Claudia}, title = {Quantifizierung von Aminos{\"a}uren in Infusionsl{\"o}sungen mittels Hochleistungsfl{\"u}ssigkeitschromatographie-(Tandem) - Massenspektrometrie(HPLC-[MS/]MS) Methodenentwicklung und Validierung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65198}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Das Ziel vorliegender Arbeit war die Entwicklung einer HPLC-MS(/MS)-Methode, die im Rahmen der pharmazeutischen Qualit{\"a}tskontrolle zur direkten Quantifizierung von Aminos{\"a}uren (AS) in Infusionsl{\"o}sungen angewendet werden kann. Die Zielset-zung schloss eine Validierung innerhalb der f{\"u}r die Zweckbestimmung vorgesehenen Grenzen ein. Im Rahmen der Methodenentwicklung wurde das ESI-MS/MS-Fragmentierungs-muster von 21 Aminos{\"a}uren, von 20 stabil-isotopenmarkierten Aminos{\"a}uren, die als interne Standards verwendet wurden, sowie von einigen weiteren Substanzen bestimmt. Nach Kenntnis von Precursor- und Produktionen erstellte man eine SRM-Methode zur spezifischen MS/MS-Analyse. Dabei wurden durch das jeweilige Frag-mentierungsmuster bedingte Interferenzen bei den zu untersuchenden Aminos{\"a}uren bestimmt, die bei der zu erarbeitenden HPLC-MS-Methode beachtet werden mussten. Die Methodenentwicklung zur HPLC-MS-Analytik von underivatisierten AS umfasste mit der RP-HPLC unter Verwendung eines Ionenpaarreagenzes (IP) und der hydrophilen Interaktionschromatographie (HILIC) zwei verschiedene chromatographi-sche Ans{\"a}tze. Bei der Anwendung der RP-HPLC ergaben sich Probleme. Die Verwendung eines IP, im vorliegenden Fall TDFHA (Tridecafluorheptans{\"a}ure), f{\"u}hrte zu langen Equilibrierungs-, Re-Equilibrierungs- und Sp{\"u}lzeiten und damit bei zwar relativ kurzer HPLC-Laufzeit zu einem aber insgesamt hohen Zeitaufwand. Gleich-zeitig war die LC-MS-Anlage auf diese Anwendung fixiert, da das Ionenpaarreagenz das Ger{\"a}t stark verschmutzte und dadurch andere Analysen erheblich st{\"o}rte. Zudem waren die Retentionszeiten der Analyten trotz langer Equilibrierungszeiten schlecht reproduzierbar, so dass eine solche Methode im Rahmen der pharmazeutischen Qualit{\"a}tskontrolle schwer validierbar w{\"a}re. Weiterf{\"u}hrende Untersuchungen erfolgten daher nicht. In nachfolgenden Studien mit der HILIC wurden verschiedene Einflussparameter (Anteil organischer Phase im Fließmittel, pH-Wert des Fließmittels, Temperatur der S{\"a}ule, Pufferkonzentration im Fließmittel, Gradientenelution) auf die Trennung der AS an einer ZIC®-HILIC-S{\"a}ule untersucht. Durch Optimierung der Parameter wurde so eine HILIC-HPLC-Methode entwickelt, bei der 21 AS und 20 ihrer isotopen-markierten Referenz-AS innerhalb von 20 min eluierten. Diejenigen AS, bei denen im Rahmen der Fragmentierungsstudien Interferenzen aufgrund gleicher bzw. {\"a}hnlicher Massen der Precursor- bzw. Produktionen aufgetreten waren, wurden chroma-tographisch getrennt. Gleichzeitig hat sich die SIM-Analyse als anwendbar erwiesen. Die Anwendung des spezifischeren SRM-Modus und damit der Tandem-Massenspektrometrie war nicht erforderlich. Im Rahmen der nachfolgenden Studien zur Validierung ergab sich, dass die entwickelte Methode {\"u}ber einen weiten Bereich eine lineare Abh{\"a}ngigkeit zwischen Konzentrations- und Messwerten zeigte. F{\"u}r drei der 21 AS (NAcCys, NAcTyr, Pro) wurde die quadratische Regression mit dem Anpassungstest nach Mandel als geeig-neteres Regressionsmodell ermittelt. Bei Untersuchungen zur Wiederfindung wurde ein Einfluss der Matrix-L{\"o}sung der Infusionsl{\"o}sung festgestellt, der zu Abweichungen hinsichtlich des Quotienten AreaAS / AreaIS f{\"u}hrte, so dass eine Quantifizierung innerhalb der geforderten Grenzen bei Kalibrierung {\"u}ber reine Standardl{\"o}sungen nicht m{\"o}glich war. Die Validierung wurde daher nachfolgend in der Matrixl{\"o}sung durchgef{\"u}hrt. Dabei wurde gezeigt, dass mit der entwickelten HILIC-HPLC-MS-Methode Aminos{\"a}uren in Infusionsl{\"o}sungen mit hoher Pr{\"a}zision und Richtigkeit bestimmt werden k{\"o}nnen. Neun der 21 untersuchten AS konnten im Bereich von 30\% - 350\%, zehn weitere im Bereich von 50\% - 350\% innerhalb der zur Gehaltsbestimmung von pharmazeutischen Formulierungen vorgeschriebenen Grenzen (Wiederfindung Einzelbestimmung: 98\% -102.0\%, Mittelwert einer Dreifachbestimmung: 98.5\% - 101.5\%) quantifiziert werden. F{\"u}r His und Phe gelang allerdings keine Quantifizierung innerhalb der Akzeptanzkriterien, wobei der Grund hierf{\"u}r in weiteren Studien gekl{\"a}rt werden m{\"u}sste. Mit der entwickelten Methode ist damit eine gleichzeitige Quantifizierung verschiedener AS-Infusionsl{\"o}sungsformulierungen m{\"o}glich, die sich bei gleicher Matrix in der Konzentration an AS unterscheiden. Beispielsweise seien hier die Formulierungen „Aminoplasmal® E 5\% / 10\% /15\%" genannt, die mit der validierten Methode erfassbar sind. Die Probenvorbereitung beschr{\"a}nkt sich dabei auf den Zusatz der IS-Formulierung zur Infusionsl{\"o}sung und einen Verd{\"u}nnungsschritt. Die Quanti-fizierung erfolgt {\"u}ber eine 5-Punkt-Kalibriergerade, die aus einer AS- und IS-Standardmischung, nach Zusatz der einfach herzustellenden Elektrolyt-Matrix, erstellt wird. Die Analysenzeit der HPLC-MS-Methode betr{\"a}gt einschließlich Equilibrie-rungszeit 35 min und ist damit deutlich k{\"u}rzer als die 120 min, die bei der nach wie vor zur AS-Analytik allgemein gebr{\"a}uchlichen Ionenaustauschchromatographie mit Ninhydrin-Nachs{\"a}ulenderivatisierung anzusetzen sind.}, subject = {Aminos{\"a}uren}, language = {de} } @article{SteinmannPaeleckeHabermannGeinitzetal.2012, author = {Steinmann, Diana and Paelecke-Habermann, Yvonne and Geinitz, Hans and Aschoff, Raimund and Bayerl, Anja and B{\"o}lling, Tobias and Bosch, Elisabeth and Bruns, Frank and Eichenseder-Seiss, Ute and Gerstein, Johanna and Gharbi, Nadine and Hagg, Juliane and Hipp, Matthias and Kleff, Irmgard and M{\"u}ller, Axel and Sch{\"a}fer, Christof and Schleicher, Ursula and Sehlen, Susanne and Theodorou, Marilena and Wypior, Hans-Joachim and Zehentmayr, Franz and van Oorschot, Birgitt and Vordermark, Dirk}, title = {Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases}, series = {BMC Cancer}, volume = {12}, journal = {BMC Cancer}, number = {283}, doi = {10.1186/1471-2407-12-283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135254}, year = {2012}, abstract = {Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 \%) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 \%) survived. Nine patients were not able to be followed up. 62 patients (70.5 \% of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 \% vs. 37 \%), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.}, language = {en} } @article{RodriguesUlrichMusseletal.2017, author = {Rodrigues, Johannes and Ulrich, Natalie and Mussel, Patrick and Carlo, Gustavo and Hewig, Johannes}, title = {Measuring prosocial tendencies in Germany: sources of validity and reliablity of the revised prosocial tendency measure}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, doi = {10.3389/fpsyg.2017.02119}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159351}, pages = {2119}, year = {2017}, abstract = {The prosocial tendencies measure (PTM; Carlo and Randall, 2002) is a widely used measurement for prosocial tendencies in English speaking participants. This instrument distinguishes between six different types of prosocial tendencies that partly share some common basis, but also can be opposed to each other. To examine these constructs in Germany, a study with 1067 participants was conducted. The study investigated the structure of this German version of the PTM-R via exploratory factor analysis, confirmatory factor analysis, correlations with similar constructs in subsamples as well as via measurement invariance test concerning the original English version. The German translation showed a similar factor structure to the English version in exploratory factor analysis and in confirmatory factor analysis. Measurement invariance was found between the English and German language versions of the PTM and support for the proposed six-factor structure (altruistic, anonymous, compliant, dire, emotional and public prosocial behavior) was also found in confirmatory factor analysis. Furthermore, the expected interrelations of these factors of prosocial behavior tendencies were obtained. Finally, correlations of the prosocial behavior tendencies with validating constructs and behaviors were found. Thus, the findings stress the importance of seeing prosocial behavior not as a single dimension construct, but as a factored construct which now can also be assessed in German speaking participants.}, language = {en} } @article{UrlaubKaiserScherf‐Claveletal.2021, author = {Urlaub, Jonas and Kaiser, Reinhard P. and Scherf-Clavel, Oliver and Bolm, Carsten and Holzgrabe, Ulrike}, title = {Investigation of isomerization of dexibuprofen in a ball mill using chiral capillary electrophoresis}, series = {Electrophoresis}, volume = {42}, journal = {Electrophoresis}, number = {17-18}, doi = {10.1002/elps.202000307}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225852}, pages = {1790 -- 1799}, year = {2021}, abstract = {Besides the racemate, the S-enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S-Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg\(^{2+}\), Ca\(^{2+}\), or Zn\(^{2+}\) ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 μm fused-silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) as chiral selector. The quantification of R-Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68-5.49\% R-Ibu (R\(^{2}\) = 0.999), recovery was found to range between 97 and 103\%, the RSD of intra- and interday precision below 2.5\%, and the limit of quantification for R- in S-Ibu was calculated to be 0.21\% (extrapolated) and 0.15\% (dilution of racemic ibuprofen), respectively. Isomerization of S-Ibu was observed under basic conditions by applying long milling times and high milling frequencies.}, language = {en} } @article{SzymskiAschenbachKrutschetal.2021, author = {Szymski, Dominik and Aschenbach, Leonard and Krutsch, Volker and Alt, Volker and Meffert, Rainer and Krutsch, Werner and Fehske, Kai}, title = {Injury epidemiology in men's professional team sports: is media analysis helpful?}, series = {Archives of Orthopaedic and Trauma Surgery}, volume = {141}, journal = {Archives of Orthopaedic and Trauma Surgery}, number = {4}, issn = {1434-3916}, doi = {10.1007/s00402-020-03743-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266690}, pages = {655-661}, year = {2021}, abstract = {Introduction Epidemiological injury surveillance in professional sports is often based on online media analysis in order to collect necessary data. However, the validation of this study protocol is lacking. Therefore, this study aimed to identify the validity of injury surveillance in men's professional team sports based on media reports. Methods In a retrospective cohort study, the validity of media-data-relating injuries was investigated in participating teams of the highest two German divisions in men's professional basketball (BB) and handball (HB) in the season 2018/2019. Injury protocols completed by the team physicians were compared to those of sports media injury reports. Results The study population was composed of 133 athletes (54 BB and 79 HB). Of 343 injuries reported by the team physicians, 151 (44\%) could be identified by means of sports media reports. Severe injuries (n = 75, 72\%) were reported more likely in sports media compared to less severe injuries (n = 76, 32\%, p < 0.00001). Odds ratio (OR) was 5.33 (95\% CI 3.22-8.82). No differences regarding injury reporting could be seen between the two team sports. Conclusion For severe injuries, media analysis may be a sufficient method for data collection in popular men's professional ball sports. An underestimation of true injury prevalence lies within the range of previous reported investigations concerning the validation of injury surveillance methods. Non-severe injuries could not be verified via media analysis in professional handball and basketball.}, language = {en} } @article{DietzConradKuenzeretal.2014, author = {Dietz, Andreas J. and Conrad, Christopher and Kuenzer, Claudia and Gesell, Gerhard and Dech, Stefan}, title = {Identifying Changing Snow Cover Characteristics in Central Asia between 1986 and 2014 from Remote Sensing Data}, series = {Remote Sensing}, volume = {6}, journal = {Remote Sensing}, number = {12}, issn = {2072-4292}, doi = {10.3390/rs61212752}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114470}, pages = {12752-12775}, year = {2014}, abstract = {Central Asia consists of the five former Soviet States Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan, therefore comprising an area of similar to 4 Mio km(2). The continental climate is characterized by hot and dry summer months and cold winter seasons with most precipitation occurring as snowfall. Accordingly, freshwater supply is strongly depending on the amount of accumulated snow as well as the moment of its release after snowmelt. The aim of the presented study is to identify possible changes in snow cover characteristics, consisting of snow cover duration, onset and offset of snow cover season within the last 28 years. Relying on remotely sensed data originating from medium resolution imagers, these snow cover characteristics are extracted on a daily basis. The resolution of 500-1000 m allows for a subsequent analysis of changes on the scale of hydrological sub-catchments. Long-term changes are identified from this unique dataset, revealing an ongoing shift towards earlier snowmelt within the Central Asian Mountains. This shift can be observed in most upstream hydro catchments within Pamir and Tian Shan Mountains and it leads to a potential change of freshwater availability in the downstream regions, exerting additional pressure on the already tensed situation.}, language = {en} } @phdthesis{Steinhauer2002, author = {Steinhauer, Sven}, title = {Erhebung pharmakokinetischer Daten von Cisaprid, SC-72393, Haloperidol, Linezolid, Methotrexat und Ketoprofen nach Methodenentwicklung und Validierung durch LC-MS/MS-Detektion}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5803}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2002}, abstract = {Zur Bestimmung von geringen Wirkstoffkonzentrationen in biologischen, speziell human-biologischen Matrizes wie Blut, Urin oder Mikrodialysat bedarf es einer Analysentechnik, die den Wirkstoff mit einem H{\"o}chstmaß an Selektivit{\"a}t, Spezifit{\"a}t und Pr{\"a}zision bestimmen kann. Daneben muß die verwendetete Methode eine hohe Geschwindigkeit aufweisen und sehr robust sein, da bei der heutigen marktwirtschaftlichen Lage Analysensysteme eine optimale Auslastung erfahren m{\"u}ssen. Aus diesem Grund ist der Umbau oder die Umstellung der Methode von einem zum anderen Wirkstoff ohne nennenswerten Zeitverlust ein maßgeblicher Faktor. Als Technik, die diese Anforderungen optimal erf{\"u}llt, hat sich in den letzten Jahren die LC-MS/MS-Technik etabliert. Sie ist den bislang {\"u}berwiegenden Methoden, wie GC-MS-Techniken oder HPLC-UV-Detektion bzw. Fluoreszenztechniken in Bezug auf die oben genannten Parameter deutlich {\"u}berlegen. In der vorliegenden Arbeit wurden f{\"u}r die Wirkstoffe Cisaprid, SC-72393, Haloperidol, Linezolid, Methotrexat und Ketoprofen LC-MS/MS-Methoden entwickelt oder via unabh{\"a}ngiger Laborvalidierung auf die lokalen Gegebenheiten transferiert und zur Bestimmung pharmakokinetischer Parameter zur Anwendung gebracht. Ziel der Methodenentwicklung war es die hohe Selektivit{\"a}t und Empfindlichkeit des Detektors zu nutzten, um bei geringen Probenvolumina eine Bestimmungsgrenze zu erreichen, die es erm{\"o}glichte ausreichend viele Meßwerte zu bestimmen, um die pharmakokinetischen Parameter der Wirkstoffe zu berechnen. Zus{\"a}tzlich wurde eine Maximierung des Probendurchsatzes und eine Minimierung des personellen und materiellen Aufwandes angestrebt ohne dabei einen Qualit{\"a}tsverlust der Methode zu erleiden. Eine gelungene Methoden-entwicklung bedurfte daher der Optimierung der Probenaufarbeitung, die sich neben den chemisch-physikalischen Eigenschaften des Wirkstoffes haupts{\"a}chlich an der Menge der zur Verf{\"u}gung stehenden Probe orientierte. Das chromato-graphische System hingegen hing weitestgehend von den chemischen Eigenschaften des Analyten und von den massenspektroskopischen Bedingungen ab, die verdampfbare Puffer im Fließmittel erforderten. Diese drei zu optimierenden Teilbereiche, die miteinander interagieren, wurden jeweils sorgsam aufeinander abgestimmt, um eine Methode zu entwickeln, die die zu erwartenden Wirkstoffkonzentrationen in der jeweiligen Matrix sicher und robust bis hin zum Quantifizierungslimit bestimmen konnte.}, subject = {Wirkstoff}, language = {de} } @phdthesis{Stiefl2004, author = {Stiefl, Nikolaus Johannes}, title = {Entwicklung, Validierung und Anwendung einer neuen translations- und rotationsinvarianten 3D-QSAR-Methodik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8230}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2004}, abstract = {Die vorliegende Arbeit beschreibt die Entwicklung und Validierung der neuartigen 3D-QSAR Technik Mapping Property Distributions of Molecular Surfaces (MaP). Die Methode ist gegen{\"u}ber Translation und Rotation invariant, d. h. eine {\"U}berlagerung der Molek{\"u}le, wie sie zum Beispiel f{\"u}r CoMFA n{\"o}tig ist, entf{\"a}llt. MaP basiert auf der Charakterisierung der Molek{\"u}le nach ihrer F{\"a}higkeit Wasserstoffbr{\"u}cken auszubilden, sowie ihrer Hydrophobie / Hydrophilie. Dabei werden jedoch nicht nur die atombasierten Eigenschaften, sondern auch die Oberfl{\"a}cheneigenschaften der Molek{\"u}le zur Charakterisierung genutzt. Diese Losl{\"o}sung von der chemischen Struktur der Verbindungen erlaubt es, die f{\"u}r die Ligand-Rezeptor-Interaktion (bzw. Substrat-Enzym-Interaktion) wichtigen Grenzfl{\"a}chen zu charakterisieren. Die wichtigsten methodischen Elemente der MaP-Technik, sowie die erhaltenen Ergebnisse der untersuchten Datens{\"a}tze sollen hier noch einmal in kurzer Form dargestellt werden: Die theoretische Basis des MaP-Deskriptors bilden so genannte Radialverteilungsfunktionen. Mittels dieser selektiven Distanz-Z{\"a}hlstatistiken (SDZS) k{\"o}nnen sowohl die Form der Molek{\"u}le, als auch die Verteilung der einzelnen Oberfl{\"a}cheneigenschaften zueinander, in einem einzelnen Vektor beschrieben werden. Die MaP-Variablen kodieren dabei die Gr{\"o}ße (absolute Anzahl an Eintr{\"a}gen), sowie die Orientierung (Distanz) verschiedener Oberfl{\"a}cheneigenschaften zueinander. Die Grundlage der Oberfl{\"a}cheneigenschaften stellen atomare Charakteristika wie das Wasserstoffbr{\"u}ckenbindungspotential sowie die atomare Hydrophobie / Hydrophilie dar. Diese Eigenschaften werden den Atomen mittels einfacher Regeln (Wasserstoffbr{\"u}cken) bzw. einer Substruktursuche (Hydrophobie / Hydrophilie) zugewiesen und dann auf die Oberfl{\"a}che projiziert. Um die mathematische Transformation der Rohdaten in die SDZS zu erm{\"o}glichen, muss die Molek{\"u}loberfl{\"a}che durch gleichverteilte Oberfl{\"a}chenpunkte diskretisiert werden. Da diese Anforderung von gebr{\"a}uchlichen analytischen Oberfl{\"a}chenberechnungsmethoden, wie zum Beispiel dem GEPOL-Algorithmus, nicht erf{\"u}llt wird, wurde der GEPOL-Algorithmus so modifiziert, dass ein Zusammenhang zwischen der Oberfl{\"a}chengr{\"o}ße und der Anzahl an Oberfl{\"a}chenpunkten gegeben ist. Da es aufgrund dieser Diskretisierung jedoch zum Verlust der Invarianz gegen{\"u}ber Translation und Rotation kommen kann, wurde der Bestimmung der Molek{\"u}loberfl{\"a}chen eine spezielle Technik zur Ausrichtung der Molek{\"u}le im Koordinatensystem (Kanonisierung) vorgeschaltet. Dadurch wird ein identischer MaP-Deskriptor unabh{\"a}ngig von der Position der Molek{\"u}le im Raum garantiert. Um den Diskretisierungsfehler der Oberfl{\"a}chenbestimmung weiter zu reduzieren, wurde eine unscharfe Z{\"a}hlweise bei der Berechnung des MaP-Deskriptors adaptiert. Diese erlaubt es, Eintr{\"a}ge die an den Kategoriengrenzen des MaP-Vektors liegen, auf die beiden n{\"a}chsten Zentren zu verteilen. Dadurch werden kleine Schwankungen in den Distanzwerten kompensiert. Zur Modellbildung werden die infomativsten Variablen (MIV) mit Hilfe der ‚Reverse-Elimination-Method'-Tabu-Suche (REM-TS) identifiziert. Die so erhaltenen MIV's k{\"o}nnen auf die Molek{\"u}le zur{\"u}ckprojiziert werden, was die Interpretation der berechneten Modelle stark vereinfacht. Zur Visualisierung der Ergebnisse k{\"o}nnen die Variablen unter Zuhilfenahme der unscharfen Z{\"a}hlweise nochmals gefiltert werden, um die Interpretation hoch besetzter Variablen zu vereinfachen. Da es aufgrund der Variablenselektion zu einer Zufallskorrelation in der Modellbildung kommen kann, werden die erhaltenen Modelle einer strengen Validierung unterzogen. Dabei werden neben der sehr anspruchsvollen ‚Lass-mehrere-Objekte-heraus'-Kreuzvalidierung als G{\"u}tefunktion der Variablenselektion auch ein Permutationstest der Modelle sowie eine Testdatenvorhersage angewandt. Durchl{\"a}uft ein Modell all diese Validierungsschritte erfolgreich, so ist die Wahrscheinlichkeit einer Zufallskorrelation sehr gering. Um die Anwendbarkeit und die G{\"u}te des MaP-Deskriptors zu {\"u}berpr{\"u}fen, wurden verschiedene Datens{\"a}tze untersucht. Diese k{\"o}nnen entsprechend ihrer Zielsetzung in unterschiedliche Gebiete aufgeteilt werden. Der erste Datensatz (Steroide) wird in der QSAR h{\"a}ufig als Vergleichsdatensatz eingesetzt. Ein weiterer Datensatz umfasst strukturell sehr heterogene Substanzen, die ein augenirritierendes Potential aufweisen (ECETOC). Inhibitoren des EndothelinA-Rezeptors (ETA) bildeten einen weiteren Datensatz. Die enthaltenen Molek{\"u}le sind im Datenraum stark in Untergruppen geklustert. Weiterhin wurden konformell sehr flexible, allostere Modulatoren des muskarinischen M2-Rezeptors (M2-Modulatoren) untersucht. Dieser Datensatz diente aufgrund der hohen Flexibilit{\"a}t der Molek{\"u}le auch zur {\"U}berpr{\"u}fung der konformellen Abh{\"a}ngigkeit der Methode. Die Erweiterung des Standardparametersatzes wurde mit Hilfe von Naphthylisochinolin-Derivaten (NIQ) untersucht, die eine Aktivit{\"a}t gegen Plasmodium falciparum aufweisen. Ein weiterer Datensatz, deren Molek{\"u}le die {\"O}ffnungswahrscheinlickeit ATP-abh{\"a}ngiger Kalium-Kan{\"a}le erh{\"o}ht (KCO), wurde herangezogen, um den Vorteil der mathematischen Transformation der MaP-Technik gegen{\"u}ber der von GRIND benutzten MACC-2-Transformation herauszustellen. Inhibitoren des nicotinischen Acetylcholin-Rezeptors (CAR) bildeten einen weiteren Datensatz f{\"u}r den bisher keine QSAR-Studie vorlag. Zur strukturbasierten Validierung der Methode wurden Inhibitoren der Acetylcholinesterase (APZ-Datensatz) untersucht. Hierbei wurde gepr{\"u}ft, ob die aus der Kristallstruktur der Acetylcholinesterase wichtigen Ligand-Enzym-Wechselwirkungen durch MaP beschrieben werden. Die Ergebnisse dieser Untersuchungen lassen folgenden R{\"u}ckschl{\"u}sse zu: Im Vergleich mit bereits etablierten 3D-QSAR-Techniken wie CoMFA, CoMSIA oder GRID/PLS f{\"u}hrt die MaP-Technik zu vergleichbar guten Modellen (Steroide, ETA, M2-Modulatoren). Durch die Losl{\"o}sung vom strukturellen Grundger{\"u}st der Substanzen k{\"o}nnen auch strukturell diverse Datens{\"a}tze gut modelliert und die relevante Information extrahiert werden (ECETOC). Dies ist mit Deskriptoren, die eine gemeinsame Ausrichtung der Molek{\"u}le ben{\"o}tigen (z.B. CoMFA), oft nicht m{\"o}glich. Auch Datens{\"a}tze, deren Objekte geklustert vorliegen, k{\"o}nnen mittels MaP gut modelliert werden. MaP ist dabei in der Lage die relevante Information sowohl zwischen, als auch innerhalb der einzelnen Gruppen zu extrahieren (ETA). Auch f{\"u}r Datens{\"a}tze, deren Molek{\"u}le eine sehr hohe Flexibilit{\"a}t aufweisen, ist es m{\"o}glich mit MaP gute Modelle zu erhalten (M2-Modulatoren, APZ). Hierbei ist es jedoch wichtig, zu beachten, dass MaP als 3D-QSAR-Technik gegen{\"u}ber der Konformation der Molek{\"u}le nicht invariant ist. Bei der Anwendung der Methode zeigte sich jedoch, dass kleine konformelle {\"A}nderungen der Verbindungen oft einen sehr geringen Einfluss auf die Ergebnisse der Methode haben (M2-Modulatoren, APZ). Bei der Untersuchung der NIQ-Daten zeigte sich, dass unter Verwendung der MaP-Standardparameter bereits die relevanten Eigenschaften der Molek{\"u}le charakterisiert werden k{\"o}nnen. Allerdings f{\"u}hrte eine Erweiterung dieser Parameter zu einer Vereinfachung der Interpretation der Ergebnisse. Hierbei ist jedoch darauf zu achten, dass die Modellvalidierung strikt eingehalten werden muss. Der Vorteil der mathematischen Transformation der Rohdaten (SDZS) gegen{\"u}ber der von GRIND verwendeten MACC-2 Transformation konnte mittels der KCO-Daten aufgezeigt werden. Das erhaltene Modell spiegelte sehr sch{\"o}n die bereits bekannten Struktur-Wirkungs-Beziehungen wider. Leider ist die publizierte Datenlage in diesem Falle noch nicht ausreichend, um einen abschließenden Vergleich der beiden konkurrierenden Techniken zu erm{\"o}glichen. Beim CAR-Datensatz war MaP in der Lage, neben der bekannten, relevanten strukturellen Allylalkoholgruppe ein weiteres strukturelles Merkmal zu identifizieren. Abschließend konnte gezeigt werden, dass MaP in der Lage ist, die f{\"u}r die Wechselwirkung zwischen Acetylcholinesterase und Ligand wichtigen Interaktionsstellen und Charakteristika eindeutig zu identifizieren (APZ-Datensatz). Diese Eigenschaften wurden zur besseren Interpretation der Ergebnisse in die Bindetasche projiziert. Die Ergebnisse dieser Untersuchungen zeigen, dass die entwickelte Technik ein weites Anwendungsspektrum besitzt, leicht zu interpretieren ist und sich dabei durch ihre Robustheit auszeichnet. Vor allem aber liefert MaP aussagekr{\"a}ftige 3D-QSAR-Modelle. Bei der MaP-Methode handelt es sich jedoch nicht nur um einen neuen Molek{\"u}ldeskriptor, sondern um eine Kombination aus Deskriptor, mathematischer Modellierung, Modellvalidierung und Modellvisualisierung. Obwohl MaP in Hinsicht auf Modellqualit{\"a}t und Modellinterpretierbarkeit Techniken wie zum Beispiel CoMFA in nichts nachsteht, sind aufgrund der einfachen und trotzdem hocheffizienten mathematischen Grundlagen folgende Erweiterungen denkbar: (1) als dreidimensionale Technik ist MaP von den Ausgangskonformationen der Molek{\"u}le abh{\"a}ngig. Findet sich im untersuchten Datensatz ein starres Molek{\"u}l (M2-Modulatoren) oder aber sind Informationen {\"u}ber einen m{\"o}glichen Bindungsmodus vorhanden, so k{\"o}nnen diese Konformationen relativ leicht erhalten werden. Da dies jedoch nicht immer der Fall ist, ist eine Erweiterung der Technik in die vierte Dimension (konformelle Flexibilit{\"a}t) wichtig. Dass dies prinzipiell m{\"o}glich ist, konnte Hopfinger bereits zeigen. Da die mathematische Grundlage der MaP-Technik sehr einfach ist, sollte diese Art der Erweiterung in die vierte Dimension auch f{\"u}r MaP m{\"o}glich sein. (2) Momentan ist der MaP-Deskriptor auf Verkn{\"u}pfungen zwischen zwei Oberfl{\"a}chenpunkten beschr{\"a}nkt. Diese Einschr{\"a}nkung k{\"o}nnte dazu f{\"u}hren, dass Inkremente ein und derselben Variablen aus verschiedenen Teilen des Molek{\"u}ls stammen. Wenn nur ein Teil davon Eigenschaften kodieren, die relevant f{\"u}r die Ligand-Rezeptor-Interaktion sind, k{\"o}nnte dies theoretisch zu Inkonsistenzen in dem resultierenden Modell f{\"u}hren. Bei den bislang untersuchten Datens{\"a}tzen konnte dies noch nicht beobachtet werden. Eine m{\"o}gliche Erkl{\"a}rung hierf{\"u}r ist, dass die MaP-Variablen zu einem gewissen Grad redundant sind, d.h. das selbe Ph{\"a}nomen kann durch verschiedene Variablen beschrieben werden. Von diesen redundanten Variablen werden durch die strenge Validierung diejenigen vom Suchalgorithmus der Variablenselektion identifiziert, die am wenigsten mit anderen Eigenschaften vermengt sind. Prinzipiell ist eine solche Problematik jedoch denkbar. Um die Wahrscheinlichkeit eines derartigen Ph{\"a}nomens weiter zu reduzieren, sollten die bisher genutzten Zweipunktverkn{\"u}pfungen auf drei Punkte erweitert werden.}, language = {de} } @phdthesis{Bleuel2021, author = {Bleuel, Gabriel}, title = {Entwicklung und Validierung eines quantitativen Verfahrens zur Beurteilung der Viabilit{\"a}t von entsprechend der GMP-Richtlinien hergestellter Knorpelimplantate f{\"u}r das Knie}, doi = {10.25972/OPUS-24248}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242481}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Due to the reversing age pyramid in Germany, more and more people are already suffering from joint cartilage damage. But not only age, but also accidents and sports injuries and being overweight can lead to irreversible cartilage defects. Although there are various treatment options, the previous methods cannot be considered a permanent cure. As part of the international research project BIO-CHIP, a promising treatment method with novel drugs was to be investigated. The patient's own cartilage cells from the nose serve as the starting material for the drug, a manufactured cartilage implant. These are isolated, multiplied and ultimately cultivated on a matrix to form a cartilage implant. In addition to toxicological and biological safety tests, an essential prerequisite for the approval of the implant is the assessment of the viability. This was previously carried out on the basis of histology from the pathology department. The aim of the present work was the development and validation of a standardized and objective viability test for the chondrocytes within the cartilage matrix. For this, the LDH was used as a marker for irreversibly damaged cells. The LDH concentration could be measured with the CyQuant LDH assay by measuring the absorption. It could be proven that LDH has the required stability and detectability in the medium. With the help of the lysis, of cultivated mini-cartilage implants, the maximum achievable LDH concentrations could be determined. A calibration curve was generated using these concentrations. This serves to assess the viability of future measured absorptions of the supernatant medium. The developed method does not require any invasive interventions on the implant and is characterized by its simple implementation, since only the protrusion has to be measured. The validation of the method certified a high level of robustness, linearity, accuracy and precision.}, subject = {Hyaliner Knorpel}, language = {de} } @article{MayrKleinRutzingeretal.2021, author = {Mayr, Stefan and Klein, Igor and Rutzinger, Martin and Kuenzer, Claudia}, title = {Determining temporal uncertainty of a global inland surface water time series}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {17}, issn = {2072-4292}, doi = {10.3390/rs13173454}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245234}, year = {2021}, abstract = {Earth observation time series are well suited to monitor global surface dynamics. However, data products that are aimed at assessing large-area dynamics with a high temporal resolution often face various error sources (e.g., retrieval errors, sampling errors) in their acquisition chain. Addressing uncertainties in a spatiotemporal consistent manner is challenging, as extensive high-quality validation data is typically scarce. Here we propose a new method that utilizes time series inherent information to assess the temporal interpolation uncertainty of time series datasets. For this, we utilized data from the DLR-DFD Global WaterPack (GWP), which provides daily information on global inland surface water. As the time series is primarily based on optical MODIS (Moderate Resolution Imaging Spectroradiometer) images, the requirement of data gap interpolation due to clouds constitutes the main uncertainty source of the product. With a focus on different temporal and spatial characteristics of surface water dynamics, seven auxiliary layers were derived. Each layer provides probability and reliability estimates regarding water observations at pixel-level. This enables the quantification of uncertainty corresponding to the full spatiotemporal range of the product. Furthermore, the ability of temporal layers to approximate unknown pixel states was evaluated for stratified artificial gaps, which were introduced into the original time series of four climatologic diverse test regions. Results show that uncertainty is quantified accurately (>90\%), consequently enhancing the product's quality with respect to its use for modeling and the geoscientific community.}, language = {en} } @article{ScharbatkeBehrensSchmalzingetal.2016, author = {Scharbatke, Eva C. and Behrens, Frank and Schmalzing, Marc and Koehm, Michaela and Greger, Gerd and Gnann, Holger and Burkhardt, Harald and Tony, Hans-Peter}, title = {Association of improvement in pain with therapeutic response as determined by individual improvement criteria in patients with rheumatoid arthritis}, series = {Arthritis Care \& Research}, volume = {68}, journal = {Arthritis Care \& Research}, number = {11}, doi = {10.1002/acr.22884}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186817}, pages = {1607-1615}, year = {2016}, abstract = {Objective To use statistical methods to establish a threshold for individual response in patient-reported outcomes (PROs) in patients with rheumatoid arthritis. Methods We used an analysis of variance model in patients on stable therapy (discovery cohort) to establish critical differences (d(crit)) for the minimum change associated with a significant individual patient response (beyond normal variation) in the PRO measures of pain (0-10), fatigue (0-10), and function (Funktionsfragebogen Hannover questionnaire; 0-100). We then evaluated PRO responses in patients initiating adalimumab in a noninterventional study (treatment cohort). Results In the discovery cohort (n=700), PROs showed excellent long-term retest reliability. The minimum change that exceeded random fluctuation was conservatively determined to be 3 points for pain, 4 points for fatigue, and 16 points for function. In the treatment cohort (n=2,788), 1,483 patients (53.2\%) achieved a significant individual therapeutic response as assessed by Disease Activity Score in 28 joints (DAS28)-d(crit) (1.8 points) after 12 months of adalimumab treatment; 68.5\% of patients with a DAS28-d(crit) response achieved a significant improvement in pain, whereas approximately 40\% achieved significant improvements in fatigue or function. Significant improvements in all 3 PROs occurred in 22.7\% of patients; 22.8\% did not have any significant PRO responses. In contrast, significant improvements in all 3 PROs occurred in only 4.4\% of 1,305 patients who did not achieve a DAS28-d(crit) response at month 12, and 59.1\% did not achieve any significant PRO responses. Conclusion The establishment of critical differences in PROs distinguishes true responses from random variation and provides insights into appropriate patient management.}, language = {en} } @article{TimmermansvanderTolTimmermansetal.2015, author = {Timmermans, Wim J. and van der Tol, Christiaan and Timmermans, Joris and Ucer, Murat and Chen, Xuelong and Alonso, Luis and Moreno, Jose and Carrara, Arnaud and Lopez, Ramon and Fernando de la Cruz, Tercero and Corcoles, Horacio L. and de Miguel, Eduardo and Sanchez, Jose A. G. and Perez, Irene and Belen, Perez and Munoz, Juan-Carlos J. and Skokovic, Drazen and Sobrino, Jose and Soria, Guillem and MacArthur, Alasdair and Vescovo, Loris and Reusen, Ils and Andreu, Ana and Burkart, Andreas and Cilia, Chiara and Contreras, Sergio and Corbari, Chiara and Calleja, Javier F. and Guzinski, Radoslaw and Hellmann, Christine and Herrmann, Ittai and Kerr, Gregoire and Lazar, Adina-Laura and Leutner, Benjamin and Mendiguren, Gorka and Nasilowska, Sylwia and Nieto, Hector and Pachego-Labrador, Javier and Pulanekar, Survana and Raj, Rahul and Schikling, Anke and Siegmann, Bastian and von Bueren, Stefanie and Su, Zhongbo (Bob)}, title = {An Overview of the Regional Experiments for Land-atmosphere Exchanges 2012 (REFLEX 2012) Campaign}, series = {Acta Geophysica}, volume = {63}, journal = {Acta Geophysica}, number = {6}, doi = {10.2478/s11600-014-0254-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136491}, pages = {1465-1484}, year = {2015}, abstract = {The REFLEX 2012 campaign was initiated as part of a training course on the organization of an airborne campaign to support advancement of the understanding of land-atmosphere interaction processes. This article describes the campaign, its objectives and observations, remote as well as in situ. The observations took place at the experimental Las Tiesas farm in an agricultural area in the south of Spain. During the period of ten days, measurements were made to capture the main processes controlling the local and regional land-atmosphere exchanges. Apart from multi-temporal, multi-directional and multi-spatial space-borne and airborne observations, measurements of the local meteorology, energy fluxes, soil temperature profiles, soil moisture profiles, surface temperature, canopy structure as well as leaf-level measurements were carried out. Additional thermo-dynamical monitoring took place at selected sites. After presenting the different types of measurements, some examples are given to illustrate the potential of the observations made.}, language = {en} } @phdthesis{Baumeister2004, author = {Baumeister, Joachim}, title = {Agile development of diagnostic knowledge systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-9698}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2004}, abstract = {The success of diagnostic knowledge systems has been proved over the last decades. Nowadays, intelligent systems are embedded in machines within various domains or are used in interaction with a user for solving problems. However, although such systems have been applied very successfully the development of a knowledge system is still a critical issue. Similarly to projects dealing with customized software at a highly innovative level a precise specification often cannot be given in advance. Moreover, necessary requirements of the knowledge system can be defined not until the project has been started or are changing during the development phase. Many success factors depend on the feedback given by users, which can be provided if preliminary demonstrations of the system can be delivered as soon as possible, e.g., for interactive systems validation the duration of the system dialog. This thesis motivates that classical, document-centered approaches cannot be applied in such a setting. We cope with this problem by introducing an agile process model for developing diagnostic knowledge systems, mainly inspired by the ideas of the eXtreme Programming methodology known in software engineering. The main aim of the presented work is to simplify the engineering process for domain specialists formalizing the knowledge themselves. The engineering process is supported at a primary level by the introduction of knowledge containers, that define an organized view of knowledge contained in the system. Consequently, we provide structured procedures as a recommendation for filling these containers. The actual knowledge is acquired and formalized right from start, and the integration to runnable knowledge systems is done continuously in order to allow for an early and concrete feedback. In contrast to related prototyping approaches the validity and maintainability of the collected knowledge is ensured by appropriate test methods and restructuring techniques, respectively. Additionally, we propose learning methods to support the knowledge acquisition process sufficiently. The practical significance of the process model strongly depends on the available tools supporting the application of the process model. We present the system family d3web and especially the system d3web.KnowME as a highly integrated development environment for diagnostic knowledge systems. The process model and its activities, respectively, are evaluated in two real life applications: in a medical and in an environmental project the benefits of the agile development are clearly demonstrated.}, language = {en} } @article{BischoffRingstedPetersenetal.2014, author = {Bischoff, Joakim M. and Ringsted, Thomas K. and Petersen, Marian and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan and Werner, Mads U.}, title = {A Capsaicin (8\%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {10}, issn = {1932-6203}, doi = {10.1371/journal.pone.0109144}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115198}, pages = {e109144}, year = {2014}, abstract = {Background: Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8\% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods: Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8\% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0-10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results: The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95\% CI]: 5.0 [0.09 to 9.9]; P=0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [-0.1 to 3.9] and 0.6 [-1.2 to 2.5] fibers/mm, respectively (P=0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions: The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application.}, language = {en} } @article{GuederBrennerAngermannetal.2012, author = {G{\"u}der, G{\"u}lmisal and Brenner, Susanne and Angermann, Christiane E. and Ertl, Georg and Held, Matthias and Sachs, Alfred P. and Lammers, Jan Willem and Zanen, Peter and Hoes, Arno W. and St{\"o}rk, Stefan and Rutten, Frans H.}, title = {"GOLD or lower limit of normal definition? a comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75193}, year = {2012}, abstract = {Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed postbronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Agedependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. Results: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28\%) patients, and the three LLNs misclassified 114 (46\%), 96 (39\%), and 98 (40\%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 \% predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50\% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.}, subject = {Medizin}, language = {en} }