@phdthesis{Goetz2019, author = {G{\"o}tz, Sebastian Reinhold}, title = {Nonlinear spectroscopy at the diffraction limit: probing ultrafast dynamics with shaped few-cycle laser pulses}, doi = {10.25972/OPUS-19213}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192138}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {An experimental setup for probing ultrafast dynamics at the diffraction limit was developed, characterized and demonstrated in the scope of the thesis, aiming for optical investigations while simultaneously approaching the physical limits on the length and timescale. An overview of this experimental setup was given in Chapter 2, as well as the considerations that led to the selection of the individual components. Broadband laser pulses with a length of 9.3 fs, close to the transform limit of 7.6 fs, were focused in a NA = 1.4 immersion oil objective, to the diffraction limit of below 300 nm (FWHM). The spatial focus shape was characterized with off-resonance gold nanorod scatterers scanned through the focal volume. For further insights into the functionality and limitations of the pulse shaper, its calibration procedure was reviewed. The deviations between designed and experimental pulse shapes were attributed to pulse-shaper artifacts, including voltage-dependent inter-layer as well as intra-layer LCD-pixel crosstalk, Fabry-P{\´e}rot-type reflections in the LCD layers, and space-time coupling. A pixel-dependent correction was experimentally carried out, which can be seen as an extension of the initial calibration to all possible voltage combinations of the two LCD layers. The capabilities of the experimental setup were demonstrated in two types of experiments, targeting the nonlinearity of gold (Chapter 3) as well as two-dimensional spectroscopy at micro-structured surfaces (Chapter 4). Investigating thin films, an upper bound for the absolute value for the imaginary part of the nonlinear refractive index of gold could be set to |n′′ 2 (Au)| < 0.6·10-16 m2/W, together with |n′ 2 (Au)| < 1.2·10-16 m2/W as an upper bound for the absolute value of the real part. Finite-difference time-domain simulations on y-shaped gold nanostructures indicated that a phase change of ∆Φ ≥ 0.07 rad between two plasmonic modes would induce a sufficient change in the spatial contrast of emission to the far-field to be visible in the experiment. As the latter could not be observed, this value of ∆Φ was determined as the upper bound for the experimentally induced phase change. An upper bound of 52 GW/cm2 was found for the damage threshold. In Chapter 4, a novel method for nonlinear spectroscopy on surfaces was presented. Termed coherent two-dimensional fluorescence micro-spectroscopy, it is capable of exploring ultrafast dynamics in nanostructures and molecular systems at the diffraction limit. Two-dimensional spectra of spatially isolated hotspots in structured thin films of fluorinated zinc phthalocyanine (F16ZnPc) dye were taken with a 27-step phase-cycling scheme. Observed artifacts in the 2D maps were identified as a consequence from deviations between the desired and the experimental pulse shapes. The optimization procedures described in Chapter 2 successfully suppressed the deviations to a level where the separation from the nonlinear sample response was feasible. The experimental setup and methods developed and presented in the scope of this thesis demonstrate its flexibility and capability to study microscopic systems on surfaces. The systems exemplarily shown are consisting of metal-organic dyes and metallic nanostructures, represent samples currently under research in the growing fields of organic semiconductors and plasmonics.}, subject = {Ultrakurzzeitspektroskopie}, language = {en} } @article{KempertGoetzBlatteretal.2016, author = {Kempert, Sebastian and G{\"o}tz, Regina and Blatter, Kristine and Tibken, Catharina and Artelt, Cordula and Schneider, Wolfgang and Stanat, Petra}, title = {Training Early Literacy Related Skills: To Which Degree Does a Musical Training Contribute to Phonological Awareness Development?}, series = {Frontiers in Psychology}, volume = {7}, journal = {Frontiers in Psychology}, number = {1803}, doi = {10.3389/fpsyg.2016.01803}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165272}, year = {2016}, abstract = {Well-developed phonological awareness skills are a core prerequisite for early literacy development. Although effective phonological awareness training programs exist, children at risk often do not reach similar levels of phonological awareness after the intervention as children with normally developed skills. Based on theoretical considerations and first promising results the present study explores effects of an early musical training in combination with a conventional phonological training in children with weak phonological awareness skills. Using a quasi-experimental pretest-posttest control group design and measurements across a period of 2 years, we tested the effects of two interventions: a consecutive combination of a musical and a phonological training and a phonological training alone. The design made it possible to disentangle effects of the musical training alone as well the effects of its combination with the phonological training. The outcome measures of these groups were compared with the control group with multivariate analyses, controlling for a number of background variables. The sample included N = 424 German-speaking children aged 4-5 years at the beginning of the study. We found a positive relationship between musical abilities and phonological awareness. Yet, whereas the well-established phonological training produced the expected effects, adding a musical training did not contribute significantly to phonological awareness development. Training effects were partly dependent on the initial level of phonological awareness. Possible reasons for the lack of training effects in the musical part of the combination condition as well as practical implications for early literacy education are discussed.}, language = {en} } @article{HelassGreinacherGoetzetal.2022, author = {Helaß, Madeleine and Greinacher, Anja and G{\"o}tz, Sebastian and M{\"u}ller, Andreas and G{\"u}ndel, Harald and Junne, Florian and Nikendei, Christoph and Maatouk, Imad}, title = {Age stereotypes towards younger and older colleagues in registered nurses and supervisors in a university hospital: A generic qualitative study}, series = {Journal of Advanced Nursing}, volume = {78}, journal = {Journal of Advanced Nursing}, number = {2}, doi = {10.1111/jan.15021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262751}, pages = {471 -- 485}, year = {2022}, abstract = {Aim This study aimed to identify and compare age stereotypes of registered nurses and supervisors in clinical inpatient settings. Design Generic qualitative study using half-standardized interviews. Method Nineteen face-to-face interviews and five focus groups (N = 50) were conducted with nurses of varying levels at a hospital of maximum medical care in Germany between August and November 2018 and were subjected to structured qualitative content analysis. Results Reflecting the ageing process and cooperation in mixed-age teams, nursing staff and supervisors defined similar age stereotypes towards older and younger nurses reminiscent of common generational labels 'Baby Boomers' and Generations X. Their evaluation created an inconsistent and contradictory pattern differing to the respective work context and goals. Age stereotypes were described as both potentially beneficial and detrimental for the individual and the cooperation in the team. If a successfully implemented diversity management focuses age stereotypes, negative assumptions can be reduced and cooperation in mixed-age teams can be considered beneficial. Conclusion Diversity management as measures against age stereotypes and for mutual acceptance and understanding should include staff from various hierarchical levels of the inpatient setting.}, language = {en} } @article{IsbernerKrausGrigoleitetal.2021, author = {Isberner, Nora and Kraus, Sabrina and Grigoleit, G{\"o}tz Ulrich and Aghai, Fatemeh and Kurlbaum, Max and Zimmermann, Sebastian and Klinker, Hartwig and Scherf-Clavel, Oliver}, title = {Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial}, series = {Cancer Chemotherapy and Pharmacology}, volume = {88}, journal = {Cancer Chemotherapy and Pharmacology}, number = {6}, issn = {1432-0843}, doi = {10.1007/s00280-021-04351-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266476}, pages = {973-983}, year = {2021}, abstract = {Purpose Knowledge on Ruxolitinib exposure in patients with graft versus host disease (GvHD) is scarce. The purpose of this prospective study was to analyze Ruxolitinib concentrations of GvHD patients and to investigate effects of CYP3A4 and CYP2C9 inhibitors and other covariates as well as concentration-dependent effects. Methods 262 blood samples of 29 patients with acute or chronic GvHD who were administered Ruxolitinib during clinical routine were analyzed. A population pharmacokinetic model obtained from myelofibrosis patients was adapted to our population and was used to identify relevant pharmacokinetic properties and covariates on drug exposure. Relationships between Ruxolitinib exposure and adverse events were assessed. Results Median of individual mean trough serum concentrations was 39.9 ng/mL at 10 mg twice daily (IQR 27.1 ng/mL, range 5.6-99.8 ng/mL). Applying a population pharmacokinetic model revealed that concentrations in our cohort were significantly higher compared to myelofibrosis patients receiving the same daily dose (p < 0.001). Increased Ruxolitinib exposure was caused by a significant reduction in Ruxolitinib clearance by approximately 50\%. Additional comedication with at least one strong CYP3A4 or CYP2C9 inhibitor led to a further reduction by 15\% (p < 0.05). No other covariate affected pharmacokinetics significantly. Mean trough concentrations of patients requiring dose reduction related to adverse events were significantly elevated (p < 0.05). Conclusion Ruxolitinib exposure is increased in GvHD patients in comparison to myelofibrosis patients due to reduced clearance and comedication with CYP3A4 or CYP2C9 inhibitors. Elevated Ruxolitinib trough concentrations might be a surrogate for toxicity.}, language = {en} } @article{GernerAghaiTrommeschlaegerKrausetal.2022, author = {Gerner, Bettina and Aghai-Trommeschlaeger, Fatemeh and Kraus, Sabrina and Grigoleit, G{\"o}tz Ulrich and Zimmermann, Sebastian and Kurlbaum, Max and Klinker, Hartwig and Isberner, Nora and Scherf-Clavel, Oliver}, title = {A physiologically-based pharmacokinetic model of ruxolitinib and posaconazole to predict CYP3A4-mediated drug-drug interaction frequently observed in graft versus host disease patients}, series = {Pharmaceutics}, volume = {14}, journal = {Pharmaceutics}, number = {12}, issn = {1999-4923}, doi = {10.3390/pharmaceutics14122556}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297261}, year = {2022}, abstract = {Ruxolitinib (RUX) is approved for the treatment of steroid-refractory acute and chronic graft versus host disease (GvHD). It is predominantly metabolized via cytochrome P450 (CYP) 3A4. As patients with GvHD have an increased risk of invasive fungal infections, RUX is frequently combined with posaconazole (POS), a strong CYP3A4 inhibitor. Knowledge of RUX exposure under concomitant POS treatment is scarce and recommendations on dose modifications are inconsistent. A physiologically based pharmacokinetic (PBPK) model was developed to investigate the drug-drug interaction (DDI) between POS and RUX. The predicted RUX exposure was compared to observed concentrations in patients with GvHD in the clinical routine. PBPK models for RUX and POS were independently set up using PK-Sim\(^®\) Version 11. Plasma concentration-time profiles were described successfully and all predicted area under the curve (AUC) values were within 2-fold of the observed values. The increase in RUX exposure was predicted with a DDI ratio of 1.21 (C\(_{max}\)) and 1.59 (AUC). Standard dosing in patients with GvHD led to higher RUX exposure than expected, suggesting further dose reduction if combined with POS. The developed model can serve as a starting point for further simulations of the implemented DDI and can be extended to further perpetrators of CYP-mediated PK-DDIs or disease-specific physiological changes.}, language = {en} }