Welcome to the next module. This is again, Thomas Hartung from Johns Hopkins. In this module, we start with a lesson on risk of bias. So, what is risk of bias? Risk of bias means, what are the influential factors which could mean that my scientific evidence, which I'm receiving is not true? This is something which has been started to being formalized in the evidence-based medicine movement. Because we were facing the problem that very often, it made a difference who was paying for a study. There's a famous joke which says, studies that, water's running uphill are more expensive. Which means in the end, if you pay for it you can get whatever scientific result you want. So, in clinical medicine, people started to look into when is a clinical trial trustworthy, when it has been very objectively being set up, is the control over the interests of the sponsors versus the outcome of these studies? Very often, this does not come really as changing or manipulating the studies. Very often, it only comes as not reporting the bad outcomes, and this creates a bias in the literature, which is a very important aspect of bias. In Toxicology, we have additional problem, which is, we're not relying so much on clinical trials, we are relying on different data streams, we're relying on animal studies, sometimes epidemiology, we're relying increasingly on cell culture or computational models. For many of these, we don't have a framework for risk of bias and this is what we're going to discuss in this lesson. The next lesson, we'll address an example of a systematic review. It is one which is pioneered by the evidence-based toxicology collaboration and you will hear the director of the Evidence-Based Toxicology Collaboration, Katya Tsaioun, of our team talk about zebrafish. Zebrafish is a model which has become very popular in Toxicology. So, while there was a long time a trend to prefer moving away from mice to rats, dopes to go to dogs and mini-pigs, or even young human primates, there's also the parallel trend to go to lower organisms. Astonishingly, we don't lose a lot by moving through these organisms, but we lose a lot with respect to throughput and with respect to ethics. A very prominent model which was already [inaudible] accepted for testing of acute fish toxicity, is the zebrafish egg test. The zebrafish egg develops within 72 hours and you can visit or you can observe the development of a vertebrate. For this reason, people have thought this could also be an excellent test for developmental toxicity, because these transparent eggs are qualifying for testing thousands of chemicals at many concentrations with ease. You will hear how the Evidence-Based Toxicology Collaboration is trying to evaluate the existing evidence in comparison to the traditional studies in rats and rabbits, in order to find out how well does a zebrafish egg and its development reflect the development of an embryo in these mammals. So, listen to Katya about the status of this project as an example of how a systematic review of a toxicological method could look like and what challenges we are facing.