A multiscale model for collagen alignment in wound healing

It is thought that collagen alignment plays a significant part in scar tissue formation during dermal wound healing. We present a multiscale model for collagen deposition and alignment during this process. We consider fibroblasts as discrete units moving within an extracellular matrix of collagen and fibrin modelled as continua. Our model includes flux induced alignment of collagen by fibroblasts, and contact guidance of fibroblasts by collagen fibres. We can use the model to predict the effects of certain manipulations, such as varying fibroblast speed, or placing an aligned piece of tissue in the wound. We also simulate experiments which alter the TGF-β concentrations in a healing dermal wound and use the model to offer an explanation of the observed influence of this growth factor on scarring

Cancer modelling: Getting to the heart of the problem

Paradoxically, improvements in healthcare that have enhanced the life expectancy of humans in the Western world have, indirectly, increased the prevalence of certain types of cancer such as prostate and breast. It remains unclear whether this phenomenon should be attributed to the ageing process itself or the cumulative effect of prolonged exposure to harmful environmental stimuli such as ultraviolet light, radiation and carcinogens (Franks and Teich, 1988). Equally, there is also compelling evidence that certain genetic abnormalities can predispose individuals to specific cancers (Ilyas et al., 1999). The variety of factors that have been implicated in the development of solid tumours stems, to a large extent, from the fact that ‘cancer’ is a generic term, often used to characterize a series of disorders that share common features. At this generic level of description, cancer may be viewed as a cellular disease in which controls that usually regulate growth and maintain homeostasis are disrupted. Cancer is typically initiated by genetic mutations that lead to enhanced mitosis of a cell lineage and the formation of an avascular tumour. Since it receives nutrients by diffusion from the surrounding tissue, the size of an avascular tumour is limited to several millimeters in diameter. Further growth relies on the tumour acquiring the ability to stimulate the ingrowth of a new, circulating blood supply from the host vasculature via a process termed angiogenesis (Folkman, 1974). Once vascularised, the tumour has access to a vast nutrient source and rapid growth ensues. Further, tumour fragments that break away from the primary tumour, on entering the vasculature, may be transported to other organs in which they may establish secondary tumours or metastases that further compromise the host. Invasion is another key feature of solid tumours whereby contact with the tissue stimulates the production of enzymes that digest the tissue, liberating space into which the tumour cells migrate. Thus, cancer is a complex, multiscale process. The spatial scales of interest range from the subcellular level, to the cellular and macroscopic (or tissue) levels while the timescales may vary from seconds (or less) for signal transduction pathways to months for tumour doubling times The variety of phenomena involved, the range of spatial and temporal scales over which they act and the complex way in which they are inter-related mean that the development of realistic theoretical models of solid tumour growth is extremely challenging. While there is now a large literature focused on modelling solid tumour growth (for a review, see, for example, Preziosi, 2003), existing models typically focus on a single spatial scale and, as a result, are unable to address the fundamental problem of how phenomena at different scales are coupled or to combine, in a systematic manner, data from the various scales. In this article, a theoretical framework will be presented that is capable of integrating a hierarchy of processes occurring at different scales into a detailed model of solid tumour growth (Alarcon et al., 2004). The model is formulated as a hybrid cellular automaton and contains interlinked elements that describe processes at each spatial scale: progress through the cell cycle and the production of proteins that stimulate angiogenesis are accounted for at the subcellular level; cell-cell interactions are treated at the cellular level; and, at the tissue scale, attention focuses on the vascular network whose structure adapts in response to blood flow and angiogenic factors produced at the subcellular level. Further coupling between the different spatial scales arises from the transport of blood-borne oxygen into the tissue and its uptake at the cellular level. Model simulations will be presented to illustrate the effect that spatial heterogeneity induced by blood flow through the vascular network has on the tumour’s growth dynamics and explain how the model may be used to compare the efficacy of different anti-cancer treatment protocols

A learning laboratory approach for business improvement : the case of discontinuous innovation

This paper considers the current situation within Australian manufacturing SMEs and their approaches to innovation and international competitive advantage. Using the viewpoint and language of complexity theory, we consider the variety of possibilities available to SMEs in this area. We then consider a particular international project on Discontinuous Innovation, how this has been deployed in Europe and Australia and the knowledge gained from our interactions with Australian SMEs to date around this project. Finally we consider the general development of a &ldquo;Learning Laboratory&rdquo; approach to working with SMEs and the differences required to make such approach successful in Europe and in different settings in Australia.<br /

A toolkit of designs for mixing discrete event simulation and system dynamics

In recent years there has been significant interest in multimethodology and the mixing of OR/MS methods, including Discrete Event Simulation (DES) with System Dynamics (SD). Several examples of mixing DES and SD are described in the literature but there is no overarching framework which characterises the spectrum of options available to modellers. This paper draws on a sample of published case studies, in conjunction with the theoretical literature on mixing methods, to propose a toolkit of designs for mixing DES and SD which can be implemented as a set of questions which a modeller should ask in order to guide the choice of design and inform the associated project methodology. The impetus for this work was the perceived need to transfer insight from reported practice in order to formalise how the two methods can be and have been mixed

Realizing value from project implementation under uncertainty : an exploratory study using system dynamics

Project Implementation is not a trivial task even after careful planning and scheduling. One of the reasons is the existence of unexpected events at strategic and operational levels during the project execution process. This paper presents a system dynamics model of a project monitoring and control system. Embedded with both strategic and tactical uncertainties, the model experiments with typical remedial actions to disturbances during the implementation of a project under a behavioral paradigm. Simple proportional adjustment seems to work well under low levels of unexpected disturbances but prospect theory-based behavior works better under extreme situations. Our findings indicate over-reacting behavior, which is influenced by biases and reporting errors, can generate project escalation. Thus, thresholds for remedial actions should be implemented in project control and monitoring systems to avoid over-reacting behavior leading to escalation and waste of resources

Factors Affecting Successful Implementation of Government Funded Projects in Technical Institutions in Garissa County

Several government funded projects in tertiary institutions have stalled; others have been completed but not in line with the intended specifications while others exceed the stipulated completion periods. A project which is unsuccessful exceeds its schedule and budget whether it is eventually completed or not. Public institutions are generally afraid of project failure because they make big investments to the project in terms of money, time and manpower. This study sought to determine the factors affecting implementation of public projects funded by the National Government in Technical Training Institutions in Garissa County, Kenya. The objectives of the study were; to determine the influence of government funding on project implementation; to establish the influence of security on project implementation; to find out the influence of monitoring and evaluation in Government funded projects, and to determine the influence of stakeholder

Sedimentary evolution of the Le Danois contourite drift systems (southern Bay of Biscay, NE Atlantic):A reconstruction of the Atlantic Mediterranean Water circulation since the Pliocene

The evolution of the Le Danois contourite depositional systems (CDS) during the Pliocene and Quaternary was investigated based on high-resolution seismic reflection data. From old to young, six seismic units (U1-U6) bounded by major discontinuities (H1-H6) were identified. Regarding variations of the bottom-current circulation, four evolution stages of the Le Danois CDS were identified, including onset (similar to 5.3 to 3.5-3.0 Ma), initial (3.5-3.0 to 2.5-2.1 Ma), intermediate (2.5-2.1 to 0.9-0.7 Ma) and drift-growth (0.9-0.7 Ma to present day) stages. The CDS associated with the Atlantic Mediterranean Water (AMW) along the middle continental slope initiated at similar to 3.5-3 Ma and was widely built after the Mid-Pleistocene Transition (MPT; 0.9-07 Ma). At a shallower water depth, a second CDS associated with the Eastern North Atlantic Central Water (ENACW) started to develop from the late Quaternary (similar to 0.47 Ma) onwards. In the AMW-related drift system, the Le Danois Drift was generated both under glacial and interglacial climatic oscilations. Repeated internal structures in unit 5 that consist of acoustically transparent lower parts, moderate amplitude upper parts and high amplitude erosional surfaces at the top, are compared with interglacial/glacial cycles since the middle Pleistocene to the present day. These cyclic features suggest coarsening-upward sequences of the Le Danois Drift and processes related to enhanced AMW during glacial stages. The estimated sedimentation rate of the Le Danois CDS reached a maximum during the MPT (at least similar to 27 cm/ky) and then decreased until present-day (similar to 5 cm/ky). Variations of sedimentary stacking patterns and processes of the Le Danois CDS imply full domination of the intermediate water mass along the central Atlantic and southwest European continental slopes from the late Pliocene (similar to 3.5-3.0 Ma) onwards

Impact of epidemic outbreaks (COVID-19) on global supply chains: A case of trade between Turkey and China

COVID-19 has negative impacts on supply chain operations between countries. The novelty of the study is to evaluate the sectoral effects of COVID-19 on global supply chains in the example of Turkey and China, considering detailed parameters, thanks to the developed System Dynamics (SD) model. During COVID-19 spread, most of the countries decided long period of lockdowns which impacted the production and supply chains. This had also caused decrease in capacity utilizations and industrial productions in many countries which resulted with imbalance of maritime trade between countries that increased the freight costs. In this study, cause and effect relations of trade parameters, supply chain parameters, demographic data and logistics data on disruptions of global supply chains have been depicted for specifically Turkey and China since China is the biggest importer of Turkey. Due to this disruption, mainly exports from Turkey to China has been impacted in food, chemical and mining sectors. This study is helpful to plan in which sectors; the actions should be taken by the government bodies or managers. Based on findings of this study, new policies such as onshore activities should consider to overcome the logistics and supply chain disruptions in global supply chains. This study has been presented beneficial implications for the government, policymakers and academia

Theorizing Reactive Reflexivity: Lifestyle Displacement and Discordant Performances of Taste

Culturally oriented consumer research has predominantly been framed by two ideal types of reflexivity, which we characterize as existential and critical reflexivity. Drawing from our research on divorced women who have been displaced from their domestically oriented, middle-class lifestyles, we develop an alternative conceptualization—reactive reflexivity—that highlights a different relationship among consumer agency, social structures, and identity goals and practices. Rather than embracing their post-divorce lifestyles as a revitalizing challenge (per existential reflexivity) or liberation from a constraining gender role (per critical reflexivity), our participants felt estranged from their current lifestyle and reflexively viewed their pre-divorce lifestyle as a structure of relative empowerment that had afforded emotional, aesthetic, and status-oriented benefits. In reflexive response to these perceived lifestyle discontinuities, they engaged in discordant practices of taste that sought to insulate their aesthetic predispositions from structurally imposed socioeconomic constraints and, ultimately, to accomplish a reactive identity goal of regaining their displaced status as middle-class homemakers. We discuss the implications of our analysis for theorizations of consumer taste and the relationships between gender ideologies and reflexive consumption practices