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Complex Adaptive Systems
Published in David A. Katerndahl, Directing Research in Primary Care, 2018
Complex systems live within a fitness landscape, a spatial description of a system’s possible states, in which the basic terrain is punctuated by peaks in fitness, varying in quantity, height of fitness, and size of its base (its basin of attraction). Fitness landscapes are dependent upon the system’s interconnectedness, but deformed by its environment and co-evolution. With no interconnections, the landscape consists of a single, high-fitness peak, but as interconnectedness increases, so does the number of local peaks while their individual fitness drops. Similarly, as the number of agents in a system increases, the expected fitness of local peaks decreases, and the number of steps needed to find a higher-fitness peak increases. Overall, system catastrophes can generally be avoided if the interconnectedness stays small, as the number of agents rises because the peaks with the highest fitness also have the largest basins of attraction (Kauffman, 1993). Thus, the fitness or effectiveness of a research team is dependent upon its size, its interconnections among team members, its environment within the department and institution, and its co-evolution over time.
Complexity, guidelines and ethics
Published in Deborah Bowman, John Spicer, Roger Higgs, Primary Care Ethics, 2018
In biological terms, coevolution means that adaptation by one organism alters the fitness and the fitness landscapes of other organisms. In human systems, coevolution emphasises the relationships between the coevolving entities. Through a complexity lens, it makes no sense to examine the evolution or performance of one individual in isolation – the GPR and patient coevolve.
Diversity, interconnectivity and sustainability
Published in Jan Bogg, Robert Geyer, Complexity, Science and Society, 2017
Peter M. Allen, Pierpaolo Andriani
According to the idea behind the concept of sweet spot, internal structures should be adjusted according to the external variety – the fitness landscape and its diversity. A fitness landscape is a representation of the diversity of the organisation group. If the organisations are clustered in the fitness landscape the diversity of the group is low. On the other hand, if the organisations are scattered on a wide area the diversity of the group is high. Clippinger argues that ‘the strategic challenge for management is to characterise accurately the degree of internal and external complexity of an organisation in order to select the appropriate strategy to achieve sustainable fitness’ [36: p.26]. Ashby [37] has conceptualised this balance between internal and external diversity with the concept of requisite variety. According to this law, there is no sense of creating complex internal processes if those are not needed, nor is it possible to survive with too simple processes in a complex environment.
Smoothing It Out: Military Health Care Supply Chain in Transition
Published in Hospital Topics, 2022
George Ramos, Eugene S. Schneller
The ongoing DHA transformation is not unlike efforts one observes in mergers across civilian hospital systems, where there are multiple enterprise, materials management, and procurement systems. The DoD aspires to be a fully integrated supply chain organization (FISCO) in which a series of practices, technologies, and processes approach industry best practices. One of the key features of an advanced FISCO organization is the reduction of complexity (Abdulsalam et al. 2015). A “complex system” is an enterprise with numerous components that interact with each other. The NK model, where N is the number of entities in the system and K is the number of interactions among the sub-units, can be conceptualized in an adaptable fitness landscape (Exhibit 3). From a management context, the peaks of the landscape can represent mix and numerousness of efforts associated with the organization’s goals. (Levinthal and Warglien 1999) Organizations move about this landscape, through organizational decisions, which may increase or decrease the peaks (Levinthal and Warglien 1999). The fitness landscape can be “smoothened” for easier management by reducing the entities in the system (“N”) or the interactions (“K”) among the entities.
Drug-based cancer therapy to overcome immune resistance by steering tumor evolution
Published in Expert Opinion on Drug Discovery, 2019
The proposed therapeutic strategy interferes with clonal evolution, perturbs the fitness landscape, and pushes the cell population down an immune-evasion pathway toward extinction, inviting clinical development. In a preliminary stage, therapeutic efficacy needs to be established on a humanized murine model with patient-derived tumor engraftment [8], validated vis-à-vis a cogent model of clonal dynamics of cancer cells exposed to a tuned selection pressure. The drug-based evolution-steering strategy outlined may well be combined mutatis mutandis with alternative ways of imposing immune surveillance, namely cancer vaccines or adoptive T-cell therapy. An assessment of such combinations is outside the scope of this work.
Ravaging SARS-CoV-2: rudimentary diagnosis and puzzling immunological responses
Published in Current Medical Research and Opinion, 2021
Tapan Kumar Mukherjee, Parth Malik, Radhashree Maitra, John R. Hoidal
It is further reported that the RdRp mutation, located at position 14,408, which is present in European viral genomes starting from February 20th, 2020, is associated with a higher number of point mutations compared to viral genomes from Asia. Given that RdRp works in complex machinery that includes critical proofreading activities, it is tempting to speculate that this mutation has contributed to impairing its proofreading capability. On average, the coronavirus accumulates about two mutations per month in its genome. Coronaviruses have genetic proofreading mechanisms21,22, and SARS-CoV-2 sequence diversity is very low23. Still, natural selection can act upon rare but favorable mutations resulting in antigenic drift and the gradual accumulation of mutations. The complex interplay between immunological resistance and the fitness landscape enables antibody resistance to develop across populations. The most widely studied mutation of SARC-CoV-2 is that of the spike gene. The mutation at position 23,403 has drawn a rigorous attention, in part because it changed the virus’ spike, the protein on its surface that attaches to human cells. The mutation changed the amino acid at position 614 of the spike from an aspartic acid (D) to a glycine (G), thus, G614. It has been reported that a SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. This mutation has substantially increased the COVID-19 infectivity24. Continuing surveillance of Spike mutations is, hence important for decoding the mechanistic understanding of the virus infection mechanism that could aid the developing vaccines and other relevant immunological interventions.