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We present an overview of the current status of the European collaborative
project PAEON. The challenge of PAEON is to provide specialists in reproduc-
tive medicine with a computerised model of the menstrual cycle under normal
and various pathological conditions, which will allow them to get further in-
sight in fertility dynamics. This model also enables the simulation of treatment
protocols, which were used within in vitro fertilization. By the definition of
virtual patients through biologically admissible parametrizations our approach
allows not only the evaluation of a given treatment strategy in silico, but also
the design and optimization of such protocols. Once a protocol is formalized
in the virtual hospital, the success can be controlled by a treatment execution
monitor, which works then as a clinical decision support system. All these tools
will be combined in a virtual hospital environment, enabling the access to the
PAEON services through the web.
Our project aimed at building an in silico model based on our recently developed in vitro osteoarthritis (OA) model seeking for refinement of the model to enhance validity and translatability towards the more sophisticated simulation of OA. In detail, the previously 3D in vitro model is based on 3D chondrogenic constructs generated solely from human bone marrow derived mesenchymal stromal cells (hMSCs). Besides studying the normal state of the model over 3 weeks, the in vitro model was treated with interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) to mimic an OA-like environment.
In Silico Clinical Trials (ISCT), i.e., clinical experimental campaigns carried out by means of computer simulations, hold the promise to decrease time and cost for the safety and efficacy assessment of pharmacological treatments, reduce the need for animal and human testing, and enable precision medicine.
In this paper we present a case study aiming at quantifying, by means of a multi-arm ISCT supervised by intelligent search, the potential impact of precision medicine approaches on a real pharmacological treatment, namely the downregulation phase of a complex clinical protocol for assisted reproduction.
Effective marker placement for functional identification of the centre of rotation at the hip
(2012)
Exploration of different wave patterns in a model of the bovine estrous cycle by Fourier analysis
(2014)
Cows typically have different numbers of follicular waves during their hormonal cycle. Understanding the underlying regulations leads to insights into the reasons for declined fertility, a phenomenon that has been observed during the last decades. We present a systematic approach based on Fourier analysis to examine how parameter changes in a model of the bovine estrous cycle lead to different wave patterns. Even without any biological considerations, this allows to detect the responsible model parameters that control the type of periodicity of the solution, thus supporting experimental planning of animal scientists.
A seminar and interactive workshop on “In silico Methods –
Computational Alternatives to Animal Testing” was held in
Berlin, Germany, organized by Annemarie Lang, Frank Butt-
gereit and Andrea Volkamer at the Charité-Universitätsmedizin
Berlin, on August 17-18, 2017. During the half-day seminar, the
variety and applications of in silico methods as alternatives to
animal testing were presented with room for scientific discus-
sions with experts from academia, industry and the German fed-
eral ministry (Fig. 1). Talks on computational systems biology
were followed by detailed information on predictive toxicology
in order to display the diversity of in silico methods and the
potential to embrace them in current approaches (Hartung and
Hoffmann, 2009; Luechtefeld and Hartung, 2017). The follow-
ing interactive one-day Design Thinking Workshop was aimed
at experts, interested researchers and PhD-students interested in
the use of in silico as alternative methods to promote the 3Rs
(Fig. 2). Forty participants took part in the seminar while the
workshop was restricted to sixteen participants.