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.

Visual analytics for behavioral and niche market segmentation

Companies require information in order to gain an improved understanding of their customers. Data concerning customers, their interests and behavior are collected through different loyalty programs. The amount of data stored in company data bases has increased exponentially over the years and become difficult to handle. This research area is the subject of much current interest, not only in academia but also in practice, as is shown by several magazines and blogs that are covering topics on how to get to know your customers, Big Data, information visualization, and data warehousing. In this Ph.D. thesis, the Self-Organizing Map and two extensions of it – the Weighted Self-Organizing Map (WSOM) and the Self-Organizing Time Map (SOTM) – are used as data mining methods for extracting information from large amounts of customer data. The thesis focuses on how data mining methods can be used to model and analyze customer data in order to gain an overview of the customer base, as well as, for analyzing niche-markets. The thesis uses real world customer data to create models for customer profiling. Evaluation of the built models is performed by CRM experts from the retailing industry. The experts considered the information gained with help of the models to be valuable and useful for decision making and for making strategic planning for the future.

Market Potential of Service Providers for Niche Vendor

Diplomityössä tarkastellaan palveluoperaattoreiden asemaa Länsi-Euroopan matkapuhelinpalvelumarkkinoilla. Tavoitteena on selvittää, ovatko palveluoperaattorit potentiaalisia asiakkaita tietylle matkapuhelinlisäpalvelujärjestelmien toimittajalle. Lisäksi tavoitteena on rakentaa liiketoimintalaskelmatyökalu, jolla tällaisen järjestelmäinvestoinnin kannattavuus voidaan osoittaa paitsi palveluoperaattorille, myös tämän loppuasiakkaille. Työ aloitetaan matkapuhelinpalvelumarkkinoilla toimivien osapuolten esittelyllä. Eri osapuolten asemaa ja merkitystä matkapuhelinpalvelumarkkinoilla käsitellään. Matkapuhelinpalvelumarkkinoiden kehitystä tarkastellaan uuden teknologian ja erityisesti tulevien palvelujen näkökulmasta. Tarkastelua jatketaan analysoimalla regulaation vaikutusta matkapuhelinpalvelumarkkinoihin. Erityisesti kiinnitetään huomiota regulaation motiiveihin sekä käytännön toteutukseen tietyissä Länsi-Euroopan maissa. Tutkimuksen toteuttamisessa merkittävässä osassa ovat asiantuntijahaastattelut sekä markkina-analyysiraportit.Markkina-analyysissa saatuja tuloksia hyödynnetään liiketoimintalaskelmatyökalun toteutuksessa. Työn tuloksena päädytään myös ratkaisuun palveluoperaattoreiden kiinnostavuudesta asiakassegmenttinä. Tämän lisäksi havaitaan muita potentiaalisia asiakassegmenttejä, joiden tämäntyyppiseen liiketoimintaan soveltuvuutta tutkitaan edelleen.

Behavioral Responses in Mice Selectively Bred for High and Low Levels of Open-Field Thigmotaxis

In animal psychology, the open-field (OF) test is a traditional method for studying different aspects of rodent behavior, with thigmotaxis (i.e., wallseeking behavior) being one of the best validated OF parameters employed to measure emotionality. The main purpose of the present study was to investigate the selection response in mice selectively bred for high and low levels of OF thigmotaxis (the HOFT and LOFT lines, respectively). The mice (N = 2048) were selected for 23 generations, resulting in bidirectional phenotypic divergence between the two lines; that is, the HOFT mice were more thigmotactic (i.e., more emotional) than the LOFT mice across the different generations. The origin of the line difference in thigmotaxis was further investigated by using the crossfostering paradigm, with the results suggesting that the divergence between the two lines was primarily innate in origin and not influenced by differing maternal behavior. The stability of the selection trait was examined by testing the animals at different ages as well as in varying conditions. The results indicated that the line difference in thigmotaxis was not affected by age at the time of testing, and it also persisted in the different OF testing situations as well as during pregnancy and lactation. The examination of a possible coselection of other characteristics revealed that the more thigmotactic HOFT mice lived longer than the less thigmotactic LOFT mice. In addition, the HOFT mice tended to rear and explore less than the LOFT mice, supporting the general assumption that emotionality and exploration are inversely related. The two lines did not generally differ in ambulation and defecation, that is, in the traditional OF indexes of emotionality, conforming to the suggestion that emotionality is a multidimensional construct. The effects of sex on different OF parameters were also assessed, with the results suggesting that among the HOFT and LOFT lines, the female mice were more emotional than the male mice. The examination of the temporal changes in the HOFT and LOFT lines’ OF behavior revealed some contradictory findings that also partially conflicted with general assumptions. Although this study did not show prominent differences in maternal responsiveness between the HOFT and LOFT mothers, the results suggested that the line divergence in emotionality was more pronounced in the presence of a pup after parturition than during pregnancy. The present study clearly demonstrates that OF thigmotaxis is a strong characteristic for producing two diverging lines of mice. The difference in thigmotaxis between the selectively bred HOFT and LOFT mice seemed to be a stable and robust feature of these animals, and it appeared to stem from a genetic background.

Performance Comparison of Behavioral Finance -based Investment Strategies in the Finnish Stock Market 1996-2010

In this thesis traditional investment strategies (value and growth) are compared to modern investment strategies (momentum, contrarian and GARP) in terms of risk, performance and cumulative returns. Strategies are compared during time period reaching from 1996 to 2010 in the Finnish stock market. Used data includes all listed main list stocks, dividends and is adjusted in case of splits, and mergers and acquisitions. Strategies are tested using different holding periods (6, 12 and 36 months) and data is divided into tercile portfolios based on different ranking criteria. Contrarian and growth strategies are the only strategies with improved cumulative returns when longer holding periods are used. Momentum (52-week high price1) and GARP strategies based on short holding period have the best performance and contrarian and growth strategies the worst. Momentum strategies (52-week high price) along with short holding period contrarian strategies (52-week low price2) have the lowest risk. Strategies with the highest risk are both growth strategies and two momentum strategies (52-week low price). The empirical results support the efficiency of momentum, GARP and value strategies. The least efficient strategies are contrarian and growth strategies in terms of risk, performance and cumulative returns. Most strategies outperform the market portfolio in all three measures. 1 Stock ranking criterion (current price/52-week highest price) 2 Stock ranking criterion (current price/52-week lowest price)

The Effects of Service Quality, Customer Satisfaction and Customer Perceived Value on Behavioral Intentions

The intent of this research was to develop a model that describes the extent to which customer behavioral intentions are influenced by service quality, customer satisfaction and customer perceived value in the business-to-business service context. Research on customer behavioral intentions is quite fragmented and no generalized model has been presented. Thus, there was need for empirical testing. This study builds on the services marketing theory and assesses the relationships between the identified constructs. The data for the empirical analysis was collected via a quantitative online survey and a total of 226 usable responses were obtained for further analysis. The model was tested in an employment agency service setting. The measures used in this survey were first assessed by using confirmatory factor analysis (CFA) after which the hypothesized relationships were further verified using structural equation modeling (SEM) in LISREL 8.80. The analysis identified that customer satisfaction played a pivotal role in the model as it was the only direct antecedent of customer behavioral intentions, however, customer perceived value showed a strong indirect impact on buying intentions via customer satisfaction. In contrast to what was hypothesized, service quality and customer perceived value did not have a direct positive effect on behavioral intentions. Also, a contradicting finding with current literature was that sacrifice was argued to have a direct but positive impact on customer perceived value. Based on the findings in this study, managers should carefully think of their service strategies that lead to their customers’ favorable behavioral intentions.

Training executive functions in the laboratory and in real life : cognitive consequences of computer-based exercises and bilingualism

The question of the trainability of executive functions and the impact of such training on related cognitive skills has stirred considerable research interest. Despite a number of studies investigating this, the question has not yet been solved. The general aim of this thesis was to investigate two very different types of training of executive functions: laboratory-based computerized training (Studies I-III) and realworld training through bilingualism (Studies IV-V). Bilingualism as a kind of training of executive functions is based on the idea that managing two languages requires executive resources, and previous studies have suggested a bilingual advantage in executive functions. Three executive functions were studied in the present thesis: updating of working memory (WM) contents, inhibition of irrelevant information, and shifting between tasks and mental sets. Studies I-III investigated the effects of computer-based training of WM updating (Study I), inhibition (Study II), and set shifting (Study III) in healthy young adults. All studies showed increased performance on the trained task. More importantly, improvement on an untrained task tapping the trained executive function (near transfer) was seen in Study I and II. None of the three studies showed improvement on untrained tasks tapping some other cognitive function (far transfer) as a result of training. Study I also used PET to investigate the effects of WM updating training on a neurotransmitter closely linked to WM, namely dopamine. The PET results revealed increased striatal dopamine release during WM updating performance as a result of training. Study IV investigated the ability to inhibit task-irrelevant stimuli in bilinguals and monolinguals by using a dichotic listening task. The results showed that the bilinguals exceeded the monolinguals in inhibiting task-irrelevant information. Study V introduced a new, complementary research approach to study the bilingual executive advantage and its underlying mechanisms. To circumvent the methodological problems related to natural groups design, this approach focuses only on bilinguals and examines whether individual differences in bilingual behavior correlate with executive task performances. Using measures that tap the three above-entioned executive functions, the results suggested that more frequent language switching was associated with better set shifting skills, and earlier acquisition of the second language was related to better inhibition skills. In conclusion, the present behavioral results showed that computer-based training of executive functions can improve performance on the trained task and on closely related tasks, but does not yield a more general improvement of cognitive skills. Moreover, the functional neuroimaging results reveal that WM training modulates striatal dopaminergic function, speaking for training-induced neural plasticity in this important neurotransmitter system. With regard to bilingualism, the results provide further support to the idea that bilingualism can enhance executive functions. In addition, the new complementary research approach proposed here provides some clues as to which aspects of everyday bilingual behavior may be related to the advantage in executive functions in bilingual individuals.

Brand attitudes influence on city brand image, and their impact on behavioral intention

The main objective of this Master’s Thesis was to examine the perceived city brand image of tourists and residents. It was aimed to accomplish by examining first the contribution of city attributes and marketing communications on forming brand attitudes, and then discover how the brand attitudes influence on city brand image. The impact of brand attitudes and city brand image on behavioral intention was also reviewed. The empirical part of the thesis was conducted with a quantitative method through online-based survey. The sample (n = 492) consisted of tourists and residents of the case city. The data was analyzed with statistical analyses by SPSS program. Brand attitudes, based on the main attributes, were calculated through multi-attribute attitude model. The results confirmed exposure to marketing communications has direct and positive influence on brand attitudes, especially the offline marketing communications. The findings revealed brand attitudes impact directly on city brand image perception. Brand attitudes and brand image dimensions had direct impact on tourists and residents’ behavioral intention. The findings provide important information for the city marketers. They increase marketers understanding on how target population perceives the city brand image and how it impacts on their future behavior. This thesis reveals the perception of current city brand image and gives guidance on what to emphasize in city branding to increase city’s attractiveness in conjunction with its economic development. Furthermore, the created framework can be utilized also in the future researches.

Gamification as a means for employee motivation, personal engagement and behavioral outcomes: a gamification system developers’ perspective

A major challenge faced by companies today is the engagement gap at the workplace and how to motivate employees to engage in less intrinsically motivating work activities that are valuable for the organization. The objective of this study is to investigate gamification as a means for employee motivation and personal engagement that result in behavioral outcomes from the gamification developers’ perspective. Theories of work motivation and engagement are viewed in relation to gamification. The empirical part conducts a qualitative multiple-case study. The data is analyzed with the CAQDAS NVivo. The empirical findings suggest that gamification can enhance employee motivation, but careful consideration of extrinsic motivators is necessary to avoid their detrimental effect on intrinsic motivation. Employee self-determination is built through internalization of gamified system’s goals reaching autonomous motivation to engage in the target behavior. Employee engagement is built by fulfilling the psychological conditions of meaningfulness, safety and availability. The results suggest that gamification can build employee motivation and engagement leading to behavior change if designed with the business objectives in mind. Moreover, the gamified system needs to be renewed to address the changes in the business environment and reflect them in the employee behavior.

What do Sports Sponsors Really Want? The effects of service quality, service value and customer satisfaction on behavioral intentions in sports sponsorship context

The aim of this Master’s thesis was to study the antecedents of customer satisfaction and behavioral intentions and their relative relationships in the sports sponsorship context. The possible antecedents under investigation in the current research are service value and service quality. As the academic background in the sports sponsorship literature is still rather modest there was a need for further empirical testing. The theoretical part of the research builds on the existing services marketing literature with sports sponsorship and business-to-business contexts in mind. The empirical study focused on the case company Liiga-SaiPa Oy. The data for the empirical analysis was collected via quantitative online survey. The total sample consisted of 357 the case company’s business customers and a total of 80 usable responses were collected. The data was analyzed by using statistical analysis software, SPSS. According to the results of the empirical analysis the most important antecedent of behavioral intentions in the underlying context is customer satisfaction. Also service value was found to have a direct and positive relationship with behavioral intentions. Moreover no indirect relationships through satisfaction were found between service quality and service value and behavioral intentions. However both constructs of service value and service quality were diagnosed to have a direct and positive effect on customer satisfaction. Service quality was also found to be a direct antecedent of service value with other service value benefits. However a contradicting finding with the current literature was, that service value sacrifices were not found to have a significant relationship with overall service value perceptions.

Promoting Healthy Lifestyles with Personalized, APOE Genotype Based Health Information: The Effects on Psychological-, Health Behavioral and Clinical Factors

There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.

Macroalgal Defenses Against Herbivory: Causes and Consequences of Intraspecific Variation

In marine benthic communities, herbivores consume a considerable proportion of primary producer biomass and, thus, generate selection for the evolution of resistance traits. According to the theory of plant defenses, resistance traits are costly to produce and, consequently, inducible resistance traits are adaptive in conditions of variable herbivory, while in conditions of constant/strong herbivory constitutive resistance traits are selected for. The evolution of resistance plasticity may be constrained by the costs of resistance or lack of genetic variation in resistance. Furthermore, resource allocation to induced resistance may be affected by higher trophic levels preying on herbivores. I studied the resistance to herbivory of a foundation species, the brown alga Fucus vesiculosus. By using factorial field experiments, I explored the effects of herbivores and fish predators on growth and resistance of the alga in two seasons. I explored genetic variation in and allocation costs of resistance traits as well as their chemical basis and their effects on herbivore performance. Using a field experiment I tested if induced resistance spreads via water-borne cues from one individual to another in relevant ecological conditions. I found that in the northern Baltic Sea F. vesiculosus communities, strength of three trophic interactions strongly vary among seasons. The highly synchronized summer reproduction of herbivores promoted their escape from the top-down control of fish predators in autumn. This resulted into large grazing losses in algal stands. In spring, herbivore densities were low and regulated by fish, which, thus,enhanced algal growth. The resistance of algae to herbivory increased with an increase in constitutive phlorotannin content. Furthermore, individuals adopted induced resistance when grazed and when exposed to water-borne cues originating from grazing of conspecific algae both in the laboratory and in field conditions. Induced resistance was adopted to a lesser extent in the presence of fish predators. The results in this thesis indicate that inducible resistance in F. vesiculosus is an adaptation to varying herbivory in the northern Baltic Sea. The costs of resistance and strong seasonality of herbivory have likely contributed to the evolution of this defense strategy. My findings also show that fish predators have positive cascading effects on F. vesiculosus which arise via reduced herbivory but possibly also through reduced resource allocation to resistance. I further found evidence that the spread of resistance via water-borne cues also occurs in ecologically realistic conditions in natural marine sublittoral. Thus, water-borne induction may enable macroalgae to cope with the strong grazing pressure characteristic of marine benthic communities. The results presented here show that seasonality can have pronounced effects on the biotic interactions in marine benthic communities and thereafter influence the evolution of resistance traits in primary producers.