Developing semantic pathway comparison methods for systems biology

Systems biology is an emerging multi-disciplinary field in which the behaviour of complex biological systems is studied by considering the interaction of many cellular and molecular constituents rather than using a “traditional” reductionist approach where constituents are studied individually. Systems are often studied over time with the ultimate goal of developing models which can be used to understand and predict complex biological processes, such as human diseases. To support systems biology, a large number of biological pathways are being derived for many different organisms, and these are stored in various databases. This pathway collection presents an opportunity to compare and contrast pathways, and to utilise the knowledge they represent. This thesis presents some of the first algorithms that are designed to explore this opportunity. It is argued that the methods will be useful to biologists in order to assess the biological plausibility of derived pathways, compare different biological pathways for semantic similarities, and to derive putative pathways that are semantically similar to documented biological pathways. The methods will therefore extend the systems biology toolbox that biologists can use to make new biological discoveries.Knowledge Foundation. Grant No. 2003/0215Information Fusion Research Program (University of Skovde, Sweden) Grant No 2003/010

Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks

The workshop titled “Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks” was co-organized by the Evidence-based Toxicology Collaboration and the European Food Safety Authority (EFSA) and hosted by EFSA at its headquarters in Parma, Italy on October 2 and 3, 2019. The goal was to explore integration of systematic review with mechanistic evidence evaluation. Participants were invited to work on concrete products to advance the exploration of how evidence-based approaches can support the development and application of adverse outcome pathways (AOP) in chemical risk assessment. The workshop discussions were centered around three related themes: 1) assessing certainty in AOPs, 2) literature-based AOP development, and 3) integrating certainty in AOPs and non-animal evidence into decision frameworks. Several challenges, mostly related to methodology, were identified and largely determined the workshop recommendations. The workshop recommendations included the comparison and potential alignment of processes used to develop AOP and systematic review methodology, including the translation of vocabulary of evidence-based methods to AOP and vice versa, the development and improvement of evidence mapping and text mining methods and tools, as well as a call for a fundamental change in chemical risk and uncertainty assessment methodology if to be conducted based on AOPs and new approach methodologies (NAM). The usefulness of evidence-based approaches for mechanism-based chemical risk assessments was stressed, particularly the potential contribution of the rigor and transparency inherent to such approaches in building stakeholders’ trust for implementation of NAM evidence and AOPs into chemical risk assessment

The precautionary principle. Between social norms and economic constructs

Cet article confronte les interprétations proposées pour le principe de précaution qui viennent de deux horizons différents : les théories économiques du risque qui s'inscrivent dans un cadre bayésien et les repères heuristiques de la doctrine validée par les institutions européennes et françaises. Les traits communs sont mis en évidence, mais aussi d'importantes différences quant aux concepts et aux contextes d'application. Malgré ces différences, l'analyse économique propose des éclairages utiles sur plusieurs questions controversées soulevées par la mise en œuvre du principe de précaution comme norme sociale. Cela concerne par exemple la réversibilité des mesures de précaution, la question de l'application directe du principe à toute personne ou aux seules autorités publiques et le problème de l'imputation de la charge de l'instruction scientifique des hypothèses de risque.

Critical comments on the WHO-UNEP State of the Science of Endocrine Disrupting Chemicals – 2012

AbstractEarly in 2013, the World Health Organization (WHO) released a 2012 update to the 2002 State of the Science of Endocrine Disrupting Chemicals. Several significant concerns have been identified that raise questions about conclusions reached in this report regarding endocrine disruption. First, the report is not a state-of-the-science review and does not follow the 2002 WHO recommended weight-of-evidence approach. Second, endocrine disruption is often presumed to occur based on exposure or a potential mechanism despite a lack of evidence to show that chemicals are causally established as endocrine disruptors. Additionally, causation is often inferred by the presentation of a series of unrelated facts, which collectively do not demonstrate causation. Third, trends in disease incidence or prevalence are discussed without regard to known causes or risk factors; endocrine disruption is implicated as the reason for such trends in the absence of evidence. Fourth, dose and potency are ignored for most chemicals discussed. Finally, controversial topics (i.e., low dose effects, non-monotonic dose response) are presented in a one-sided manner and these topics are important to understanding endocrine disruption. Overall, the 2012 report does not provide a balanced perspective, nor does it accurately reflect the state of the science on endocrine disruption

The feasibility and malleability of EBM+

The EBM+ programme is an attempt to improve the way in which present-day evidence-based medicine (EBM) assesses causal claims: according to EBM+, mechanistic studies should be scrutinised alongside association studies. This paper addresses two worries about EBM+: (i) that it is not feasible in practice, and (ii) that it is too malleable, i.e., its results depend on subjective choices that need to be made in order to implement the procedure. Several responses to these two worries are considered and evaluated. The paper also discusses the question of whether we should have confidence in medical interventions, in the light of Stegenga's arguments for medical nihilism