TY  - THES
A1  - Götz, Sebastian Reinhold
T1  - Nonlinear spectroscopy at the diffraction limit: probing ultrafast dynamics with shaped few-cycle laser pulses
T1  - Nichtlineare Spektroskopie am Beugungslimit: Untersuchung ultraschneller Dynamiken mit geformten Laserpulsen
N2  - 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-Pérot-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.
N2  - Ein experimenteller Aufbau zur Untersuchung von ultraschnellen Dynamiken am Beugungslimit wurde in dieser Arbeit entwickelt, charakterisiert und demonstriert. Sie hatte zum Ziel, im Rahmen von optischen Beobachtungen gleichzeitig an die physikalischen Grenzen von Längen- und Zeitskalen zu gehen
Es wurde ein Überblick über den verwendeten experimentellen Aufbau gegeben, zusammen mit den Überlegungen, die zur Auswahl der einzelnen Komponenten geführt haben. Für die Pulslänge der spektral breitbandigen Laserpulse wurde auf 9.3 fs gemessen, was nahe an der transformlimitierten Dauer von 7.6 fs liegt. Im beugungslimitierten Fokus eines Immersionsölobjektivs mit einer numerischen Apertur von 1.4 konnte das Licht räumlich auf eine Halbwertsbreite von unter 300 nm komprimiert werden.
Der Fokus des Mikroskopobjektivs wurde mit Hilfe der Streuung von nicht resonanten Nanopartikeln aus Gold ausgemessen, indem diese räumlich durch den Fokus gerastert wurden. Zur weiteren Untersuchung des Funktionsumfangs und der Grenzen des benutzten Pulsformers wurde dessen Eichprozedur geprüft. Die Abweichungen zwischen gewünschten und tatsächlich angelegten Pulsformen wurden auf Artefakte des Pulsformers zurückgeführt. Diese Artefakte beinhalten eine spannungsabhängige Beeinflussung der LCD-Pixel sowohl zwischen benachbarten Pixeln einer Schicht als auch zwischen Pixeln unterschiedlicher Schichten. Eine pixelabhängige Korrektur wurde implementiert, die eine Erweiterung der ursprünglichen Kalibrierung auf alle möglichen Spannungskombinationen der LCD-Pixel darstellt.
Die Möglichkeiten experimentellen Aufbaus wurden mit zwei Arten von Experimenten demonstriert: Messungen zur Bestimmung des nichtlinearen Brechungsindexes von Gold (Kapitel 3) sowie zweidimensionale Spektroskopie an mikrostrukturierten Oberflächen (Kapitel 4).
Für den nichtlinearen Brechungsindexes von Gold konnte an Dünnschichten eine obere Grenze von |n′′ 2 (Au)| < 0.6·10−16 m2/W für den Betrag des Imaginärteils und |n′ 2 (Au)| < 1.2·10−16 m2/W für den Betrag des Realteils festgesetzt werden. Simulationen mit der Finite-Differenzen-Methode an Y-förmige Nanostrukturen aus Gold zeigten, dass eine Phasenänderung von ∆Φ ≥ 0.07 rad zwischen zwei plasmonischen Moden ausreichend für eine experimentell sichtbare Kontraständerung der Fernfeldabstrahlung wäre. Da letztere nicht beobachtet werden konnte, wurde dieser Wert für ∆Φ als obere Grenze für die experimentell eingeführte Phasenänderung festgesetzt. Für die Zerstörschwelle wurde eine obere Grenze von 52 GW/cm2 gefunden.
In Kapitel 4, wurde eine neue Methode für nichtlineare Spektroskopie an Oberflächen vorgestellt. Sie trägt den Namen ”Kohärente zweidimensionale Fluoreszenz-Mikrospektroskopie“ und eignet sich zur Untersuchung ultraschneller Dynamiken in Nanostrukturen und molekularen Systemen am Beugungslimit.
Es wurden 2D-Spektren von räumlich isolierten Hotspots einer strukturierten Zink-Phthalocyanin (F16ZnPc) Dünnschicht mit 27-fachem Phasecycling aufgenommen. Als Grund für Artefakte in den 2D-Karten wurden Abweichungen zwischen den gewünschten und experimentellen Pulsformen identifiziert. Durch die in Kapitel 2 vorgestellten Optimierungen konnten die Abweichungen allerdings so stark reduziert werden, dass deren Trennung von der nichtlinearen Antwort der Probe möglich wurde.
Die Flexibilität und der Funktionsumfang zur Analyse mikroskopischer Systeme der im Rahmen dieser Arbeit entwickelten experimentellen Aufbauten und Methoden wurde demonstriert. Repräsentativ für die wachsenden Forschungsfelder der organischen Halbleiter und der Plasmonik wurden exemplarisch Systeme bestehend aus metall-organischen Farbstoffen und metallischen Nanostrukturen untersucht.
KW  - Ultrakurzzeitspektroskopie
KW  - Fluoreszenzspektroskopie
KW  - Fourier-Spektroskopie
KW  - Nanostruktur
KW  - Konfokale Mikroskopie
KW  - Coherent Multidimensional Spectroscopy
KW  - Laser Pulse Shaping
KW  - LCD Pulse Shaper
KW  - Surface Plasmon
KW  - Kohärente Multidimensionale Spektroskopie
KW  - Laserpulsformung
KW  - LCD Pulsformer
KW  - Oberflächenplasmon
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-192138
ER  - 
TY  - JOUR
A1  - Kempert, Sebastian
A1  - Götz, Regina
A1  - Blatter, Kristine
A1  - Tibken, Catharina
A1  - Artelt, Cordula
A1  - Schneider, Wolfgang
A1  - Stanat, Petra
T1  - Training Early Literacy Related Skills: To Which Degree Does a Musical Training Contribute to Phonological Awareness Development?
JF  - Frontiers in Psychology
N2  - 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.
KW  - phonological awareness
KW  - musical training
KW  - phonological training
KW  - preschool children
KW  - early literacy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165272
VL  - 7
IS  - 1803
ER  - 
TY  - JOUR
A1  - Helaß, Madeleine
A1  - Greinacher, Anja
A1  - Götz, Sebastian
A1  - Müller, Andreas
A1  - Gündel, Harald
A1  - Junne, Florian
A1  - Nikendei, Christoph
A1  - Maatouk, Imad
T1  - Age stereotypes towards younger and older colleagues in registered nurses and supervisors in a university hospital: A generic qualitative study
JF  - Journal of Advanced Nursing
N2  - 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.
KW  - age stereotypes
KW  - nurses
KW  - older employees
KW  - qualitative approaches
KW  - supervisors
KW  - younger employees
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262751
VL  - 78
IS  - 2
SP  - 471
EP  - 485
ER  - 
TY  - JOUR
A1  - Isberner, Nora
A1  - Kraus, Sabrina
A1  - Grigoleit, Götz Ulrich
A1  - Aghai, Fatemeh
A1  - Kurlbaum, Max
A1  - Zimmermann, Sebastian
A1  - Klinker, Hartwig
A1  - Scherf-Clavel, Oliver
T1  - Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice-a prospective single-center trial
JF  - Cancer Chemotherapy and Pharmacology
N2  - 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.
KW  - toxicity
KW  - Ruxolitinib
KW  - graft versus host disease
KW  - therapeutic drug monitoring
KW  - CYP3A4
KW  - CYP2C9
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266476
SN  - 1432-0843
VL  - 88
IS  - 6
ER  - 
TY  - JOUR
A1  - Gerner, Bettina
A1  - Aghai-Trommeschlaeger, Fatemeh
A1  - Kraus, Sabrina
A1  - Grigoleit, Götz Ulrich
A1  - Zimmermann, Sebastian
A1  - Kurlbaum, Max
A1  - Klinker, Hartwig
A1  - Isberner, Nora
A1  - Scherf-Clavel, Oliver
T1  - A physiologically-based pharmacokinetic model of ruxolitinib and posaconazole to predict CYP3A4-mediated drug–drug interaction frequently observed in graft versus host disease patients
JF  - Pharmaceutics
N2  - 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.
KW  - physiologically based pharmacokinetic (PBPK) modeling
KW  - ruxolitinib
KW  - posaconazole
KW  - drug–drug interactions (DDIs)
KW  - graft versus host disease
KW  - cytochrome P450 3A4 (CYP3A4)
KW  - pharmacokinetics
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297261
SN  - 1999-4923
VL  - 14
IS  - 12
ER  -