A5079013658- Mathematical Biology Tumor Growth
- Statistical Methods in Clinical Trials
- Cancer Cells and Metastasis
- Chemical Reactions and Isotopes
- Cancer Genomics and Diagnostics
- Antibiotics Pharmacokinetics and Efficacy
- Adrenal Hormones and Disorders
- Microfluidic and Capillary Electrophoresis Applications
- Medical Imaging Techniques and Applications
- Hormonal Regulation and Hypertension
- Lung Cancer Treatments and Mutations
- Statistical Methods and Inference
- Sexual Differentiation and Disorders
- Radiomics and Machine Learning in Medical Imaging
- Heavy Metal Exposure and Toxicity
- Pneumonia and Respiratory Infections
- Evolution and Genetic Dynamics
- Trace Elements in Health
- Gene Regulatory Network Analysis
- Radiopharmaceutical Chemistry and Applications
- Biosimilars and Bioanalytical Methods
- Wnt/β-catenin signaling in development and cancer
- Advanced Numerical Methods in Computational Mathematics
- Drug Solubulity and Delivery Systems
- Hemodynamic Monitoring and Therapy
University of Potsdam
2017-2025
Freie Universität Berlin
2017-2020
Roche (Switzerland)
2020
University of St. Gallen
2020
Institut de Mathématiques de Marseille
2014-2015
Centrale Marseille
2014
Aix-Marseille Université
2013-2014
Centre National de la Recherche Scientifique
2014
Institut Polytechnique de Bordeaux
2014
Délégation Provence et Corse
2013
Defining tumor stage at diagnosis is a pivotal point for clinical decisions about patient treatment strategies. In this respect, early detection of occult metastasis invisible to current imaging methods would have major impact on best care and long-term survival. Mathematical models that describe metastatic spreading might estimate the risk when no evidence available. study, we adapted top-down model make such estimates. The was constituted by transport equation describing growth endowed...
Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success critically ill patients. The objective this study was to investigate the target attainment standard meropenem dosing heterogeneous population, quantify impact full renal function spectrum on attainment, ultimately translate findings into tool for practical application.A prospective observational...
Model-informed precision dosing (MIPD) using therapeutic drug/biomarker monitoring offers the opportunity to significantly improve efficacy and safety of drug therapies. Current strategies comprise model-informed tables or are based on maximum a posteriori estimates. These approaches, however, lack quantification uncertainty and/or consider only part available patient-specific information. We propose three novel approaches for MIPD Bayesian data assimilation (DA) reinforcement learning (RL)...
Abstract Statistical modelling of covariate distributions allows to generate virtual populations or impute missing values in a dataset. Covariate typically have non-Gaussian margins and show nonlinear correlation structures, which simple descriptions like multivariate Gaussian fail represent. Prominent frameworks for distribution are copula-based models based on multiple imputation by chained equations (MICE). While both already found applications the life sciences, systematic investigation...
An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions therapy outcomes. Current Bayesian forecasting tools typically rely only on the most probable model parameters (maximum a posteriori (MAP) estimate). This MAP-based approach, however, does neither necessarily predict outcome nor it quantify risks treatment inefficacy or toxicity. assimilation (DA) methods overcome these limitations by providing...
Abstract Objectives Patients with congenital adrenal hyperplasia (CAH) require lifelong replacement therapy glucocorticoids. Optimizing hydrocortisone is challenging, since there are no established cortisol concentration targets other than the circadian rhythm profile. 17-hydroxyprogesterone (17-OHP) concentrations elevated in these patients and commonly used to monitor therapy. This study aimed characterize pharmacokinetics/pharmacodynamics (PK/PD) of using 17-OHP as a biomarker pediatric...
In oncology, longitudinal biomarkers reflecting the patient’s status and disease evolution can offer reliable predictions of response to treatment prognosis. By leveraging clinical data in patients with advanced non-small-cell lung cancer receiving first-line chemotherapy, we aimed develop a framework combining anticancer drug exposure, tumor dynamics (RECIST criteria), C-reactive protein (CRP) concentrations, using nonlinear mixed-effects models, evaluate quantify by means parametric...
A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment Al exposure. Baseline exposure and the contamination severely limit feasibility TK studies administering naturally occurring isotope
Model-informed precision dosing (MIPD) is a quantitative framework that combines prior knowledge on the drug-disease-patient system with patient data from therapeutic drug/ biomarker monitoring (TDM) to support individualized in ongoing treatment. Structural models and parameter distributions used MIPD approaches typically build clinical trials involve only limited number of patients selected according some exclusion/inclusion criteria. Compared trial population, population practice can be...
The McKendrick/Von Foerster equation is a transport with non-local boundary condition that appearsfrequently in structured population models. A variant of this size structure has beenproposed as metastatic growth model by Iwata et al.  Here we will show how family models 1D or 2D structuring variables, based on the model, can bereformulated into an integral counterpart, Volterra convolution type, for which rich numerical andanalytical theory exists. Furthermore, point out potential...
Paclitaxel/platinum chemotherapy, the backbone of standard first-line treatment advanced non-small cell lung cancer (NSCLC), exhibits high interpatient variability in response and toxicity burden. Baseline blood biomarker concentrations tumor size (sum diameters) at week 8 relative to baseline (RS8) are widely investigated prognostic factors. However, joint analysis data on demographic/clinical characteristics, levels, chemotherapy exposure-driven early for improved prediction overall...
Recent work on Model Informed Drug Discovery and Development (MID3) has noted the need for clarity in model description used quantitative disciplines such as pharmacology statistics.1-3 Currently, models are encoded a variety of computer languages shared through publications that rarely include original code generally lack reproducibility. The DDMoRe Description Language (MDL) been developed primarily language standard to facilitate sharing knowledge understanding models. Models now not just...
Summary Context Optimization of hydrocortisone replacement therapy is important to prevent under‐ and over dosing. Hydrocortisone pharmacokinetics complex as circulating cortisol protein bound mainly corticosteroid‐binding globulin (CBG) that has a circadian rhythm. Objective A detailed analysis the CBG rhythm its impact on exposure after administration. Design Methods was measured 24 hours in 14 healthy individuals and, employing modelling simulation approach using semi‐mechanistic...
Evolution of metastatic melanoma (MM) under B-RAF inhibitors (BRAFi) is unpredictable, but anticipation crucial for therapeutic decision. Kinetics changes in growth are driven by molecular and immune events, thus we hypothesized that they convey relevant information decision making.We used a retrospective cohort 37 MM patients treated BRAFi only with at least 2 close CT-scans available before BRAFi, as model to study kinetics before, after BRAFi. All metastases (mets) were individually...
Cells are able to communicate and coordinate their function within tissues via secreted factors. Aberrant secretion by cancer cells can modulate this intercellular communication, in particular highly organised such as the liver. Hepatocytes, major cell type of liver, secrete Dickkopf (Dkk), which inhibits Wnt/ β-catenin signalling an autocrine paracrine manner. Consequently, Dkk modulates expression target genes. We present a mathematical model that describes regulation hepatic gene under...
The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic (PK) processes such as particle deposition, drug dissolution, and mucociliary clearance. Although each single process has been systematically investigated, a quantitative understanding on their interaction remains limited hence identifying optimal formulation characteristics for still challenging. To investigate this complex interplay, the can be integrated into mathematical models. However, existing modeling...
Paclitaxel-associated peripheral neuropathy (PN), a major dose-limiting toxicity, significantly impacts patients' quality of life/treatment outcome. Evaluation risk factors often ignores time PN onset, precluding the impact time-dependent factors, e.g., drug exposure, needed to comprehensively characterize PN. We employed parametric time-to-event (TTE) analysis describe course first occurrence clinically relevant grades ≥2 (PN2+, <i>n</i> = 105, common terminology criteria v4.0) and...
Statistical modelling of covariate distributions allows to generate virtual populations or impute missing values in a dataset. Covariate typically have non-Gaussian margins and show nonlinear correlation structures, which simple multivariate Gaussian fail represent. Prominent frameworks for distribution are copula-based models based on multiple imputation by chained equations (MICE). While both already found applications the life sciences, systematic investigation their goodness-of-fit...