@article{MicheletBindelliniMelinetal.2023,
  author    = {Michelet, Robin and Bindellini, Davide and Melin, Johanna and Neumann, Uta and Blankenstein, Oliver and Huisinga, Wilhelm and Johnson, Trevor N. and Whitaker, Martin J. and Ross, Richard and Kloft, Charlotte},
  title     = {Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach},
  series = {Frontiers in Pharmacology},
  volume    = {13},
  journal   = {Frontiers in Pharmacology},
  publisher = {Frontiers Media},
  address   = {Lausanne},
  issn      = {1663-9812},
  doi       = {10.3389/fphar.2022.1090554},
  pages     = {14},
  year      = {2023},
  abstract  = {Introduction: Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level. Methods: Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature. Results: Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBG(NLME) stable around 0.5 mu M vs. steady increase from 0.35 to 0.8 mu M for CBG (PBPK)). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (\& UDelta;OFV > -15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias. Discussion: Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK.},
  language  = {en}
}
@article{KortenkampKuzleReitzKoncebovski2023,
  author    = {Kortenkamp, Ulrich and Kuzle, Ana and Reitz-Koncebovski, Karen},
  title     = {Fachdidaktisches Wissen aus dem Fachwissen generieren},
  series = {PSI-Potsdam: Ergebnisbericht zu den Aktivit{\"a}ten im Rahmen der Qualit{\"a}tsoffensive Lehrerbildung (2019-2023) (Potsdamer Beitr{\"a}ge zur Lehrerbildung und Bildungsforschung ; 3)},
  journal   = {PSI-Potsdam: Ergebnisbericht zu den Aktivit{\"a}ten im Rahmen der Qualit{\"a}tsoffensive Lehrerbildung (2019-2023) (Potsdamer Beitr{\"a}ge zur Lehrerbildung und Bildungsforschung ; 3)},
  number    = {3},
  publisher = {Universit{\"a}tsverlag Potsdam},
  address   = {Potsdam},
  isbn      = {978-3-86956-568-2},
  issn      = {2626-3556},
  doi       = {10.25932/publishup-61760},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-617602},
  pages     = {171 -- 191},
  year      = {2023},
  abstract  = {Das Mathematik-Teilprojekt SPIES-M zielt auf eine st{\"a}rkere Professionsorientierung und die Verkn{\"u}pfung von Fachwissenschaft und Fachdidaktik in der universit{\"a}ren Lehrkr{\"a}ftebildung. Zu allen großen Inhaltsgebieten der Mathematik wurden neue Lehrveranstaltungen konzipiert und in den Studienordnungen s{\"a}mtlicher Lehr{\"a}mter Mathematik an der Universit{\"a}t Potsdam implementiert. F{\"u}r die Konzeption wurden theoriebasiert Gestaltungsprinzipien herausgearbeitet, die sowohl f{\"u}r das Design als auch f{\"u}r die Evaluation und Weiterentwicklung der Lehrveranstaltungen nach dem Design-Research-Ansatz genutzt werden k{\"o}nnen. Die Umsetzung der Gestaltungsprinzipien wird am Beispiel der Fundamentalen Idee der Proportionalit{\"a}t verdeutlicht und dabei aufgezeigt, wie Studierende dazu bef{\"a}higt werden k{\"o}nnen, fachdidaktisches Wissen aus fachmathematischen Inhalten zu generieren. Die Entwicklung des Professionswissens der Studierenden wird mithilfe unterschiedlicher Instrumente untersucht, um R{\"u}ckschl{\"u}sse auf die Wirksamkeit der neu konzipierten Lehrveranstaltungen zu ziehen. F{\"u}r die Untersuchungen im Mixed-Methods-Design werden neben Beobachtungen in Lehrveranstaltungen eigens konzipierte Wissenstests, Gruppeninterviews, Unterrichtsentw{\"u}rfe aus Praxisphasen und Lerntageb{\"u}cher genutzt. Die Studierendenperspektive wird durch Befragungen zur wahrgenommenen (Berufs-)Relevanz der Lehrveranstaltungen erhoben. Weiteres wesentliches Element der Begleitforschung ist die kollegiale Supervision durch sogenannte „Spies" (Spione), die die Veranstaltungen kriteriengeleitet beobachten und anschließend gemeinsam mit den Dozierenden reflektieren. Die bisherigen Ergebnisse werden hier pr{\"a}sentiert und hinsichtlich ihrer Implikationen diskutiert. Die im Projekt entwickelten Gestaltungsprinzipien als Werkzeug f{\"u}r Design und Evaluation sowie das Spies-Konzept der kollegialen Supervision werden f{\"u}r die Qualit{\"a}tsentwicklung von Lehrveranstaltungen zum Transfer vorgeschlagen.},
  language  = {de}
}
@article{HijaziFreitagLandwehr2023,
  author    = {Hijazi, Saddam and Freitag, Melina A. and Landwehr, Niels},
  title     = {POD-Galerkin reduced order models and physics-informed neural networks for solving inverse problems for the Navier-Stokes equations},
  series = {Advanced modeling and simulation in engineering sciences : AMSES},
  volume    = {10},
  journal   = {Advanced modeling and simulation in engineering sciences : AMSES},
  number    = {1},
  publisher = {SpringerOpen},
  address   = {Berlin},
  issn      = {2213-7467},
  doi       = {10.1186/s40323-023-00242-2},
  pages     = {38},
  year      = {2023},
  abstract  = {We present a Reduced Order Model (ROM) which exploits recent developments in Physics Informed Neural Networks (PINNs) for solving inverse problems for the Navier-Stokes equations (NSE). In the proposed approach, the presence of simulated data for the fluid dynamics fields is assumed. A POD-Galerkin ROM is then constructed by applying POD on the snapshots matrices of the fluid fields and performing a Galerkin projection of the NSE (or the modified equations in case of turbulence modeling) onto the POD reduced basis. A POD-Galerkin PINN ROM is then derived by introducing deep neural networks which approximate the reduced outputs with the input being time and/or parameters of the model. The neural networks incorporate the physical equations (the POD-Galerkin reduced equations) into their structure as part of the loss function. Using this approach, the reduced model is able to approximate unknown parameters such as physical constants or the boundary conditions. A demonstration of the applicability of the proposed ROM is illustrated by three cases which are the steady flow around a backward step, the flow around a circular cylinder and the unsteady turbulent flow around a surface mounted cubic obstacle.},
  language  = {en}
}