Milena Cukic Radenkovic
Although we have been familiar with Euclidean geometry concepts since childhood, we may notice that clouds are not spheres (nor are coastal lines), mountains are not cones, tree branches are not straight lines, and lighting (nor a dog bark) does not travel in a straight line either (to paraphrase genial Benoit Mandelbrot). What was once the subject of weird and fanciful mathematics of 18th and 19th-century mathematics was kept under the scientific carpet for long as a `Gallery of mathematical monsters` and considered anomalous to the conventional view. All that is also connected to the Theory of complex systems dynamics (and Information theory) and has lots of overlaps with statistical physics.
The focus of my research is on bridging several scientific fields I am active in, specifically human physiology (its applications in clinical medicine & Health), biomedical engineering, instrumentation and measurement, and complex systems dynamics stemming from statistical physics. In my quest for practical applications that can improve the current state of the healthcare system, I exposed myself to various research fields and scientific questions. Although seemingly very different, all those physical processes can be treated with a nonlinear approach that can increase our understanding of ever-unpredictable, irregular, nonlinear, and noisy signals that are wildly different from standard perception. Scientific projects from developing functional electrical stimulators for patients with spinal cord injury to applying fractal analysis to electroencephalogram recorded during and after the transcranial magnetic stimulation of the brain, to nonlinear analysis of meteorological data to early detection of parkinsonism before the onset of clinical symptoms to early detection of depression and monitoring by utilizing IoT & Telehealth, to improving the transdermal transfer of fentanyl so we can minimize the suffering of cancer patients with acute chronic pain. Every time we want to describe natural structures, forms, and processes we should remember that instead of oversimplified linear description, we should strive to apply the fractal and nonlinear approach to build closer-to-reality models.
Improvement of a Digital Twin model for transdermal fentanyl application
Transdermal drug delivery systems are important technology to administrate drugs in a noninvasive and controlled manner. Empa developed Digital Twin for transdermal fentanyl delivery striving to minimize the number of cancer patients who are suffering from chronic, acute pain and are transferred from morphine to fentanyl, in the most optimal manner avoiding unwanted side effects and over (or under) dosing. It was shown earlier that one-size-fits-all in pain management is causing problems in the majority of cases and that individual tailoring of transdermal fentanyl therapy is an improved approach to personalized care. Skin is the largest human organ and possibly the best route for optimally controlled transport of drugs that are lipophilic and of smaller molecular size (under 500Da). Contrary to the standard way of calculating the initial dose for the patient who is rotated from morphine to fentanyl use, based on the potency of the drug, Digital twin takes into account a number of other factors that can affect pharmacokinetics and pharmacodynamics and consequentially individual perception of pain. Calibrating a mathematical model by comparing its predicted response (drug uptake) with experimental observations is effectively inverse modeling. Together with our partner from Cantonal Hospital in St. Gallen (KSSG), we are working on the improvement of a Digital Twin model for transdermal fentanyl application, and our collaboration is granted from several granting sources (Novartis, OPO, Margit Weisheit Foundation, Parrotia Foundation, KSSG).