Mathematical modeling and optimal control of malaria

Malaria continues to infect millions and kill hundreds of thousands of people worldwide each year, despite over a century of research and attempts to control and eliminate this infectious disease. Challenges such as the development and spread of drug resistant malaria parasites, insecticide resistance to mosquitoes, climate change, the presence of individuals with subpatent malaria infections which normally are asymptomatic and behavioral plasticity in the mosquito hinder the prospects of malaria control and elimination. In this thesis, mathematical models of malaria transmission and control that address the role of drug resistance, immunity, iron supplementation and anemia, immigration and visitation, and the presence of asymptomatic carriers in malaria transmission are developed. A within-host mathematical model of severe Plasmodium falciparum malaria is also developed. First, a deterministic mathematical model for transmission of antimalarial drug resistance parasites with superinfection is developed and analyzed. The possibility of increase in the risk of superinfection due to iron supplementation and fortification in malaria endemic areas is discussed. The model results calls upon stakeholders to weigh the pros and cons of iron supplementation to individuals living in malaria endemic regions. Second, a deterministic model of transmission of drug resistant malaria parasites, including the inflow of infective immigrants, is presented and analyzed. The optimal control theory is applied to this model to study the impact of various malaria and vector control strategies, such as screening of immigrants, treatment of drug-sensitive infections, treatment of drug-resistant infections, and the use of insecticide-treated bed nets and indoor spraying of mosquitoes. The results of the model emphasize the importance of using a combination of all four controls tools for effective malaria intervention. Next, a two-age-class mathematical model for malaria transmission with asymptomatic carriers is developed and analyzed. In development of this model, four possible control measures are analyzed: the use of long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic, and screening and treatment of asymptomatic individuals. The numerical results show that a disease-free equilibrium can be attained if all four control measures are used. A common pitfall for most epidemiological models is the absence of real data; model-based conclusions have to be drawn based on uncertain parameter values. In this thesis, an approach to study the robustness of optimal control solutions under such parameter uncertainty is presented. Numerical analysis of the optimal control problem in the presence of parameter uncertainty demonstrate the robustness of the optimal control approach that: when a comprehensive control strategy is used the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the design of cost-effective strategies for disease control with multiple interventions, even under considerable uncertainty of model parameters. Finally, a separate work modeling the within-host Plasmodium falciparum infection in humans is presented. The developed model allows re-infection of already-infected red blood cells. The model hypothesizes that in severe malaria due to parasite quest for survival and rapid multiplication, the Plasmodium falciparum can be absorbed in the already-infected red blood cells which accelerates the rupture rate and consequently cause anemia. Analysis of the model and parameter identifiability using Markov chain Monte Carlo methods is presented.

Competitive policy and pricing in business-to-business relationships within the EC market.

Tutkielman tarkoituksena oli tarkastella hinnoittelun ja hinnanalennusten merkitystä toimittaja-asiakassuhteissa yritysmarkkinoilla, sekä sitä kuinka kilpailuoikeus säätelee hinnoittelua. Tutkielman ensisijaisena tavoitteena oli selvittää kuinka alennuspolitiikka tulisi laatia jotta se olisi EY:n kilpailuoikeuden mukaan sallittu. Aluksi hinnoittelupolitiikkaan ja strategiaan vaikuttavia seikkoja tarkasteltiin teoreettisesti ja tämän pohjalta laadittua viitekehystä sovellettiin empiiristä tutkimusta suoritettaessa. Empiirinen tutkimus oli normatiivinen case-tutkimus, jossa tarkasteltiin kahdessa toimittaja-asiakassuhteessa noudatettuja hinnoittelu- ja alennuskäytäntöjä. Aineisto kerättiin haastattelemalla toimittajan myyntihenkilöitä, ja lisänä käytettiin yrityksen sisäistä materiaalia. Analyysin tulokset osoittivat nykyisissä käytännöissä joitakin kilpailuoikeudellisia ristiriitaisuuksia, ja näihin annettiin parannusehdotuksia.

Co-opetition: Coexistence of cooperation and competition in public sector – A case study in one city’s public companies

Business actions do not take place in isolation. Complementary competencies and capabilities are the most important resources in the exponential knowledge growth. These resources are partially accessed via business partners. A company needs partners and the capability to cooperate, but also the awareness of the competitive tension, when operating in the market with multiple actors. The co-opetition research studies the occurrence and the forms of simultaneous cooperation and competition between companies or their units. Public sector’s governmental and municipal organs have been transformed into companies over the past years. Despite of their non-profit nature, public sector and public companies are adopting business doctrines from private sector towards efficient business operations. This case study aims to show, how co-opetition concept can be observed within public sector companies and in their operations with others, how public companies cooperate but also compete with others and why this happens. This thesis also explicates advantages and disadvantages of the co-opetition phenomenon.

Evolutionary Ecology of Mountain Birch in Subarctic Stress Gradients: Interplay of Biotic and Abiotic Factors in Plant-Plant Interactions and Evolutionary Processes

In nature, variation for example in herbivory, wind exposure, moisture and pollution impact often creates variation in physiological stress and plant productivity. This variation is seldom clear-cut, but rather results in clines of decreasing growth and productivity towards the high-stress end. These clines of unidirectionally changing stress are generally known as ‘stress gradients’. Through its effect on plant performance, stress has the capacity to fundamentally alter the ecological relationships between individuals, and through variation in survival and reproduction it also causes evolutionary change, i.e. local adaptations to stress and eventually speciation. In certain conditions local adaptations to environmental stress have been documented in a matter of just a few generations. In plant-plant interactions, intensities of both negative interactions (competition) and positive ones (facilitation) are expected to vary along stress gradients. The stress-gradient hypothesis (SGH) suggests that net facilitation will be strongest in conditions of high biotic and abiotic stress, while a more recent ‘humpback’ model predicts strongest net facilitation at intermediate levels of stress. Plant interactions on stress gradients, however, are affected by a multitude of confounding factors, making studies of facilitation-related theories challenging. Among these factors are plant ontogeny, spatial scale, and local adaptation to stress. The last of these has very rarely been included in facilitation studies, despite the potential co-occurrence of local adaptations and changes in net facilitation in stress gradients. Current theory would predict both competitive effects and facilitative responses to be weakest in populations locally adapted to withstand high abiotic stress. This thesis is based on six experiments, conducted both in greenhouses and in the field in Russia, Norway and Finland, with mountain birch (Betula pubescens subsp. czerepanovii) as the model species. The aims were to study potential local adaptations in multiple stress gradients (both natural and anthropogenic), changes in plant-plant interactions under conditions of varying stress (as predicted by SGH), potential mechanisms behind intraspecific facilitation, and factors confounding plant-plant facilitation, such as spatiotemporal, ontogenetic, and genetic differences. I found rapid evolutionary adaptations (occurring within a time-span of 60 to 70 years) towards heavy-metal resistance around two copper-nickel smelters, a phenomenon that has resulted in a trade-off of decreased performance in pristine conditions. Heavy-metal-adapted individuals had lowered nickel uptake, indicating a possible mechanism behind the detected resistance. Seedlings adapted to heavy-metal toxicity were not co-resistant to others forms of abiotic stress, but showed co-resistance to biotic stress by being consumed to a lesser extent by insect herbivores. Conversely, populations from conditions of high natural stress (wind, drought etc.) showed no local adaptations, despite much longer evolutionary time scales. Due to decreasing emissions, I was unable to test SGH in the pollution gradients. In natural stress gradients, however, plant performance was in accordance with SGH, with the strongest host-seedling facilitation found at the high-stress sites in two different stress gradients. Factors confounding this pattern included (1) plant size / ontogenetic status, with seedling-seedling interactions being competition dominated and host-seedling interactions potentially switching towards competition with seedling growth, and (2) spatial distance, with competition dominating at very short planting distances, and facilitation being strongest at a distance of circa ¼ benefactor height. I found no evidence for changes in facilitation with respect to the evolutionary histories of plant populations. Despite the support for SGH, it may be that the ‘humpback’ model is more relevant when the main stressor is resource-related, while what I studied were the effects of ‘non-resource’ stressors (i.e. heavy-metal pollution and wind). The results have potential practical applications: the utilisation of locally adapted seedlings and plant facilitation may increase the success of future restoration efforts in industrial barrens as well as in other wind-exposed sites. The findings also have implications with regard to the effects of global change in subarctic environments: the documented potential by mountain birch for rapid evolutionary change, together with the general lack of evolutionary ‘dead ends’, due to not (over)specialising to current natural conditions, increase the chances of this crucial forest-forming tree persisting even under the anticipated climate change.

Accounting for competition, governance and accountability during institutional change in not-for-profit and public sector organisations

Purpose The aim of this thesis1 is to analyse theoretically how institutionalisation of competitive tendering2, governance and budgetary policies cannot be taken for granted to lead to accountability among institutional actors3. The nature of an institutionalised management accounting policy, its relevance as a source of power in organisational decision making, and in negotiating inter-organisational relationships, are also analysed. Practical motivation The practical motivation of the thesis is to show how practitioners and policy makers can institutionalise changes which improve the power of management accounting and control systems4 as a mechanism of accountability among institutional actors and in negotiating relationships with other organisations. Theoretical motivation and conceptual approach The theoretical motivation of the thesis is to extend the institutional framework of management accounting change proposed by Burns and Scapens (2000) by using the theories of critical realism, communicative action, negotiated order and the framework of circuits of power. The Burns and Scapens framework needs further theorisation to analyse the relationship between the institutionalisation of management accounting and accountability; and the relevance of management accounting information in negotiating in inter-organisational relationships. Methodology and field studies Field research took place in public and not-for-profit health care organisations and a municipality in Finland from 2008 to 2013. Data were gathered by document analysis, interviews, participation in meetings and observations. Findings The findings are explained in four different essays that show that institutionalisation of competitive tendering, governance and budgetary policies cannot be taken for granted to lead to accountability among institutional actors. The ways by which institutional actors think and act can be influenced by other institutional mechanisms, such as inter-organisational circuits of power and intraorganisational governance policies, independent of the institutional change process. The relevance of institutionalised management accounting policies in negotiating relationships between two or more organisations depends on processes and contexts through which institutional actors use management accounting information as a tool of communication, mutual understanding and power. Research limitations / implications The theoretical framework used can be applied validly in other studies. The empirical findings cannot be generalised directly to other organisations than the organisations analysed. Practical implications Competitive tendering and budgetary policies can be institutionalised to shape actions of institutional actors within an organisation. To lead to accountability, practitioners and policy makers should implement governance policies that increase the use of management accounting information in institutional actors’ thinking, actions and responsibility for their actions. To reach a negotiated order between organisations, institutionalised management accounting policies should be used as one of the tools of communication aiming to reach mutual agreement among institutional actors.

THE MARKETING OF SOCIAL ENTERPRISES: Understanding the concepts of marketing and market orientation of social enterprises within the context of Pakistani market

The concepts of social entrepreneurship and social enterprises have been extensively discussed in the previous two decades, yet the topic is still not matured yet. Most of the available literature is focused on defining these terms. Similarly, limited number of authors has discussed the marketing function of these enterprises or how marketing is interpreted in social entrepreneurship models. However, there is a plethora of literature on marketing entailing many different theories, amongst which the newest one is the “market orientation concept”. Market orientation is a mix of customer orientation, competitor orientation and inter-functional coordination suggesting marketing to be a part of the business philosophy. This study focuses on the marketing and market orientation of social enterprises while giving an overview of the literature of marketing and market orientation in social enterprises. This study aims to provide two basic questions, 1) what is the literature on marketing and market orientation of social enterprises while explaining the literature of social enterprises in Pakistan and 2) how these concepts are interpreted in social enterprises in Pakistani market. Key features of research methodology include case study approach while conducting thematic analysis using thematic networks. The results indicate that only a limited number of authors have discussed market orientation concept in social enterprises. The results from the interview data indicate the usage of marketing by a firm unconsciously without a specific marketing department. In addition to that, it has been found that in social enterprise world competition is tackled through a win-win approach with a view that many enterprises working for society improve the society which is the basic mission of any social enterprise. The data also showed that in Pakistani market, social enterprise concept is not legally used yet, which allows for more room for innovation. This study intends to give a new perspective to the theorists to use market orientation concept in social enterprises and also to managers to use marketing as their business philosophy in order to satisfy the stakeholders for better delivery of their businesses and as well for social good.