Lost in translation: Toward a formal model of multilevel, multiscale medicine

For a broad spectrum of low level cognitive regulatory and other biological phenomena, isolation from signal crosstalk between them requires more metabolic free energy than permitting correlation. This allows an evolutionary exaptation leading to dynamic global broadcasts of interacting physiological processes at multiple scales. The argument is similar to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological subsystems. Not only is the living state characterized by cognition at every scale and level of organization, but by multiple, shifting, tunable, cooperative larger scale broadcasts that link selected subsets of functional modules to address problems. This multilevel dynamical viewpoint has implications for initiatives in translational medicine that have followed the implosive collapse of pharmaceutical industry 'magic bullet' research. In short, failure to respond to the inherently multilevel, multiscale nature of human pathophysiology will doom translational medicine to a similar implosion

Holistic, data-driven, service and supply chain optimisation: linked optimisation.

The intensity of competition and technological advancements in the business environment has made companies collaborate and cooperate together as a means of survival. This creates a chain of companies and business components with unified business objectives. However, managing the decision-making process (like scheduling, ordering, delivering and allocating) at the various business components and maintaining a holistic objective is a huge business challenge, as these operations are complex and dynamic. This is because the overall chain of business processes is widely distributed across all the supply chain participants; therefore, no individual collaborator has a complete overview of the processes. Increasingly, such decisions are automated and are strongly supported by optimisation algorithms - manufacturing optimisation, B2B ordering, financial trading, transportation scheduling and allocation. However, most of these algorithms do not incorporate the complexity associated with interacting decision-making systems like supply chains. It is well-known that decisions made at one point in supply chains can have significant consequences that ripple through linked production and transportation systems. Recently, global shocks to supply chains (COVID-19, climate change, blockage of the Suez Canal) have demonstrated the importance of these interdependencies, and the need to create supply chains that are more resilient and have significantly reduced impact on the environment. Such interacting decision-making systems need to be considered through an optimisation process. However, the interactions between such decision-making systems are not modelled. We therefore believe that modelling such interactions is an opportunity to provide computational extensions to current optimisation paradigms. This research study aims to develop a general framework for formulating and solving holistic, data-driven optimisation problems in service and supply chains. This research achieved this aim and contributes to scholarship by firstly considering the complexities of supply chain problems from a linked problem perspective. This leads to developing a formalism for characterising linked optimisation problems as a model for supply chains. Secondly, the research adopts a method for creating a linked optimisation problem benchmark by linking existing classical benchmark sets. This involves using a mix of classical optimisation problems, typically relating to supply chain decision problems, to describe different modes of linkages in linked optimisation problems. Thirdly, several techniques for linking supply chain fragmented data have been proposed in the literature to identify data relationships. Therefore, this thesis explores some of these techniques and combines them in specific ways to improve the data discovery process. Lastly, many state-of-the-art algorithms have been explored in the literature and these algorithms have been used to tackle problems relating to supply chain problems. This research therefore investigates the resilient state-of-the-art optimisation algorithms presented in the literature, and then designs suitable algorithmic approaches inspired by the existing algorithms and the nature of problem linkages to address different problem linkages in supply chains. Considering research findings and future perspectives, the study demonstrates the suitability of algorithms to different linked structures involving two sub-problems, which suggests further investigations on issues like the suitability of algorithms on more complex structures, benchmark methodologies, holistic goals and evaluation, processmining, game theory and dependency analysis