Introduction : Depuis 2007, la vaccination contre les infections à papillomavirus humains (HPV) est recommandée en complément du dépistage du cancer du col utérin (CCU). Cependant, au vu de la faible couverture vaccinale en France, l’impact épidémiologique de la vaccination est discuté, ainsi que le choix de la population cible et les moyens déployés pour son adhésion à la recommandation. Cette thèse propose des données et des outils originaux pour l’évaluation et l’optimisation de l’impact de la vaccination HPV en France. Pour les aspects quantitatifs, une modélisation de la transmission de l’infection à HPV appuyée sur des données détaillées décrivant les partenariats sexuels dans la population générale est nécessaire. L’exploration du lien potentiel entre la participation au dépistage du CCU des femmes précaires et leur choix d’administrer le vaccin HPV à leurs filles, l’appréciation de l’acceptabilité de la vaccination à partir des réseaux sociaux, et l’évaluation médico-économique de la pertinence de l’extension de la vaccination aux hommes, sont déterminants pour parfaire le ciblage des populations à atteindre.Méthodes : Nous avons développé une plateforme de modélisation destinée à l'étude des contacts sexuels et de la dynamique de transmission des infections par les HPV à partir des données de l’enquête Contexte de la Sexualité en France. Grâce à des modèles de mélange de lois, nous avons identifié des classes latentes d’activité sexuelle, permettant de définir des profils à risque d’infections sexuellement transmissibles. Ensuite, nous avons interrogé les femmes consultant au sein du Centre de Prévention et d’Éducation pour la Santé de Lille, ayant au moins une fille éligible à la vaccination HPV, sur leurs attitudes vis-à-vis du dépistage du CCU et de la vaccination. Puis, nous avons analysé les opinions exprimées par les internautes sur le forum en ligne d’un site d’information en santé, concernant la sécurité, l’efficacité et la perception du vaccin HPV. Enfin, nous avons réalisé une revue systématique des études médico-économiques relatives à l’extension de la vaccination HPV aux hommes.Résultats : Les simulations sur la plateforme de modélisation ont permis de reproduire les données de prévalence des infections à HPV mais les résultats restent sensibles aux hypothèses sur les comportements sexuels qui présentent des incohérences entre les hommes et les femmes. Cinq classes latentes d’activité sexuelle ont été identifiées pour les hommes ainsi que pour les femmes. Le cluster correspondant au niveau d’activité sexuelle le plus élevé représente 3,3% chez les femmes et 4,8% chez les hommes. Par ailleurs, le statut vaccinal des filles ne diffère pas selon le profil de dépistage de leur mère. L’argument majoritairement rapporté par les mères pour justifier la non-vaccination de leurs filles concerne le manque d’information, surtout parmi celles qui ne se dépistent pas. De plus, les opinions négatives, exprimées sur le forum de discussion en ligne, sont passées de 28,6 % des avis exprimés en 2006 à 42,2 % en 2013. Les arguments avancés par les « anti-vaccinaux » concernent la sécurité du vaccin et la perception de la vaccination. Enfin, les modèles médico-économiques montrent que l’extension de la vaccination aux hommes est très rarement une stratégie coût-efficace. Néanmoins, la vaccination ciblée des homosexuels masculins semble être la stratégie optimale du point de vue éthique et médico-économique.Discussion : La plateforme de modélisation des contacts sexuels constitue le socle de l’évaluation de l’impact de la vaccination HPV. La surveillance des forums de discussion en ligne permet le monitoring de l’acceptabilité de la vaccination et le ciblage des actions d’information. L’optimisation de couverture vaccinale nécessite la mise en place d’un programme organisé de vaccination des jeunes filles. À défaut d’une implémentation en milieu scolaire, les centres de prévention offrent une alternative intéressante. / Introduction: Since 2007, prophylactic vaccination against human papillomavirus (HPV) has been recommended in addition to cervical screening in French women. However, given the low vaccine coverage in France, the epidemiological impact of the vaccination is debated, as well as the choice of the target population and the means to ensure compliance with the recommendation. This doctoral thesis provides original data and tools for the evaluation and the improvement of the impact of HPV vaccination in France. For quantitative aspects, modelling HPV transmission based on the best data describing sexual partnerships in the general population is essential. The investigation of potential links between participation to cervical screening of deprived women and their choice of vaccinating their daughters, the appraisal of vaccine acceptability through social media and the cost-effectiveness evaluation of the relevance of extending the HPV vaccination program to include males are key elements to improve the focus on targeted populations.Methods: We developed a modelling platform to study the dynamics of HPV transmission, using data from Social Context of Sexuality, the latest national French sexual behavior study. Using finite mixture models, we identified latent classes of sexual activity to define profiles of partner acquisition with age, likely to have different risks of sexually transmitted infections. Then, we asked women attending the Centre for Preventive Medicine and Health Education of Lille, who had at least a daughter eligible for HPV vaccination, about their attitudes towards cervical screening and HPV vaccination. Next, we explored sentiments about HPV vaccine safety, efficacy and perceptions, spontaneously expressed by web users on the online discussion forum of a French-speaking health information website. Finally, we performed a systematic review of the cost-effectiveness studies about extending HPV vaccination to include males.Results: Simulations from the modelling platform reproduced HPV infection prevalence observed in France. Nevertheless, results were sensitive to assumptions about sexual behavior, with discrepancies between men and women. Five latent classes of sexual activity were identified in men and in women. The cluster describing the highest level of sexual behavior represents 3.3% in women and 4.8% in men. Besides, daughters’ vaccination profile did not differ with their mothers’ profile of participation to cervical screening. The main reason for not vaccinating their daughters reported by mothers was lack of information, especially for those non-compliant with cervical screening recommendations. Moreover, negative sentiments, reported by the health website forum, evolved from 28.6% of total opinions in 2006 to 42.2% in 2013. The arguments expressed by “anti-vaccine” postings involved most often vaccine safety and negative vaccine perceptions. Finally, cost-effectiveness analyses show that extending the HPV vaccination program to include males is rarely found to be a cost-effective strategy. Nevertheless, the targeted vaccination of men having sex with men seems to be the best strategy from ethical and cost-effectiveness points of view.Discussion: The modelling platform of sexual contacts represents the basis of the evaluation of HPV vaccination impact. The surveillance of online forums enables the monitoring of vaccine acceptability and hence the targeting of preventive messages. Improving the HPV vaccine coverage requires offering girls and young women an organized vaccination program. In the lack of a school-based vaccination program, Centres for Preventive Medicine and Health Education offer an interesting alternative.

In mammalian hearts, initiation of the heartbeat occurs in a region of specialised pacemaker cells known as the sinoatrial node (SAN). The SAN is a highly complex spatially distributed structure which displays considerable cellular heterogeneity and is subject to complex electrotonic interactions with the surrounding atrial tissue. In this study, biophysically detailed ionic models of central and peripheral SAN pacemaker cells are described. These models are able to accurately reproduce experimental recordings of the membrane potential from central and peripheral SAN tissue. These models are used to investigate frequency synchronisation of electrically coupled cardiac pacemaker cells. Based on simulation results presented, it is proposed that cellular heterogeneity in the SAN plays an important role in achieving rhythm coordination and possibly contributes to the efficient activation of the surrounding atrial myocardium. This represents an important, previously unexplored, mechanism underlying pacemaker synchronisation and cardiac activation in vivo. A spatial-gradient model of action potential heterogeneity within the SAN is then formulated using a large-scale least squares optimisation technique. This model accurately reproduces the smooth spatial variation in action potential characteristics observed in the SAN. One and two dimensional models of the intact SAN are then formulated and three proposed models of SAN heterogeneity are investigated: 1) the discrete-region model, in which the SAN consists of a compact central region surrounded by a region of transitional pacemaker cells, 2) the gradient model, in which cells of the SAN exhibit a smooth variation in properties from the centre to the periphery of the SAN, and 3) the mosaic model, in which SAN and atrial cells are scattered throughout the SAN region with the proportion of atrial cells increasing towards the periphery. Simulation results suggest that the gradient model achieves frequency entrainment more easily than the other models of SAN heterogeneity. The gradient model also reproduces action potential waveshapes and a site of earliest activation consistent with experimental observations in the intact SAN. It is therefore proposed that the gradient model of SAN heterogeneity represents the most plausible model of SAN organisation.

Chemical sensing is believed to be the oldest sensory ability. The chemical senses, olfaction and gustation, developed to detect and analyze information in the form of air- or waterborne chemicals, to find food and mates, and to avoid danger. The organization of the olfactory system follows the same principles in almost all living animals, insects as well as mammals. Likely, the similarities are due to parallel evolution – the same type of organisation seems to have arisen more than once. Therefore, the olfactory system is often assumed to be close to optimally designed for its tasks.Paradoxically, the workings of the olfactory system are not yet well known,although several milestone discoveries have been made during the last decades. The most well-known is probably the disovery of the olfactory receptor gene family,announced in 1991 by Linda Buck and Richard Axel. For this and subsequent work, they were awarded a Nobel Prize Award in 2004. This achievement has been of immense value for both experimentalists and theorists, and forms the basis of the current understanding of olfaction. The olfactory system has long been a focus for scientific interest within several fields, both experimental and theoretical, and it has often been used asa model system. And ever since the field of computational neuroscience was founded, the functions of the olfactory system have been investigated through computational modelling. In this thesis, I present several approaches to biologically realistic computational models of parts of the olfactory system, with an emphasis on the earlier stages of the vertebrate olfactory system – olfactory receptor neurons (ORNs) and the olfactory bulb (OB). I have investigated the behaviour of the enzyme CaMKII, which is known to be critical for olfactory adaptation (suppression of constant odour stimuli) in the ORN, using a biochemical model. By constructing several OB models of different size, I have shown that the size of the OB network has an impact on its ability to process noisy information. Taking into account the reported variability of geometrical, electrical and receptor-dependent neuronal characteristics, I have been able to model the frequency response of a population of ORNs. I have used this model to find the key properties that govern most of the ORN population’s response, and investigated some of the possible implications of these key properties in subsequent studies of the ORN population and the OB – what we call the fuzzy concentration coding hypothesis. / Detektion av kemiska ämnen anses allmänt vara den äldsta sensoriska förmågan. De kemiska sinnena, lukt och smak, utvecklades för att upptäcka och analysera kemisk information i form av luft- eller vattenburna ämnen, för att hitta mat och partners, och för att undvika fara. Luktsystemet är organiserat efter samma principer hos nästan alla djurarter, insekter såväl som däggdjur. Troligen beror likheterna på parallell evolution – samma organisation verkar ha uppstått mer än en gång. Därför antas det ofta att luktsystemet är nära optimalt anpassat för sina arbetsuppgifter.Paradoxalt nog är luktsystemets arbetsprinciper ännu inte väl kända, även om flera banbrytande framsteg gjorts de senaste decennierna. Det mest välkända är nog upptäckten av genfamiljen av luktreceptorer, som tillkännagavs 1991 av Linda Buck och Rikard Axel. För detta och efterföljande arbete belönades de med Nobelpriset år 2004. Upptäckten har varit mycket värdefull för både experimentalister och teoretiker, och är grunden för vår nuvarande förståelse av luktsystemet. Luktsystemet har länge varit ett fokus för vetenskapligt intresse inom flera fält, experimentella såväl som teoretiska, och har ofta använts som ett modellsystem. Och ända sedan fältet beräkningsneurobiologi grundades har luktsystemet undersökts genom datormodellering. I denna avhandling presenterar jag flera ansatser till biologiskt realistiskaberäkningsmodeller av luktsystemet, med tonvikt på de tidigare delarna av ryggradsdjurens luktsystem – luktreceptorceller och luktbulben. Jag har undersökt beteendet hos enzymet CaMKII, som anses vara kritiskt viktigt för adaptation (undertryckning av ständigt närvarande luktstimuli) i luktsystemet, i en biokemisk modell. Genom att konstruera flera olika stora modeller av luktbulben har jag visat att storleken på luktbulbens cellnätverk påverkar dess förmåga att behandla brusig information. Genom att ta hänsyn till nervcellernas rapporterade variationer i geometriska, elektriska och receptor-beroende karaktärsdrag har jag lyckats modellera svarsfrekvenserna från en population av luktreceptorceller. Jag har använt denna modell för att hitta de nyckelprinciper som styr huvuddelen av luktreceptorneuron-populationens svar, ochundersökt några av de tänkbara konsekvenserna av dessa nyckelprinciper i efterföljande studier av luktreceptorneuron-populationen och luktbulben – det vi kallar ”fuzzy concentration coding”-hypotesen. / QC20100723

Hospital Acquired Infections (HAI) are a global patient safety challenge, costly to treat, and affect hundreds of millions of patients annually worldwide. It has been shown that the majority of HAI are transferred to patients by caregivers' hands and therefore, can be prevented by proper hand hygiene (HH). However, many factors including cognitive load, cause caregivers to forget to cleanse their hands. Hand hygiene compliance among caregivers remains low around the world. In this thesis I showed that it is possible to build a wearable accelerometer-based HH reminder system to identify ongoing nursing activities with the patient, indicate the high-risk activities, and prompt the caregivers to clean their hands. Eight subjects participated in this study, each wearing five wireless accelerometer sensors on the wrist, upper arms and the back. A pattern recognition approach was used to classify six nursing activities offline. Time-domain features that included mean, standard deviation, energy, and correlation among accelerometer axes were found to be suitable features. On average, 1-Nearest Neighbour classifier was able to classify the activities with 84% accuracy. A novel algorithm was developed to adaptively segment the accelerometer signals to identify the start and stop time of each nursing activity. The overall accuracy of the algorithm for a total of 96 events performed by 8 subjects was approximately 87%. The accuracy was higher than 91% for 5 out of 8 subjects. The sequence of nursing activities was modelled by an 18-state Markov Chain. The model was evaluated by recently published data. The simulation results showed that the high-risk of cross-contamination decreases exponentially by frequency of HH and this happens more rapidly up to 50%-60% hand hygiene rate. It was also found that if the caregiver enters the room with high-risk of transferring infection to the current patient, given the assumptions in this study, only 55% HH is capable of reducing the risk of infection transfer to the lowest level. This may help to prevent the next patient from acquiring infection, preventing an infection outbreak. The model is also capable of simulating the effects of the imperfect HH on the risk of cross-contamination.

Melt convection and solid phase movement play an important role in solidification processes, which significantly influence the formation of grain structures and solute segregations. In general, the melt convection and grain movement are a result of buoyancy forces. The densities within melt are different due to the variation of temperature and concentration, leading to thermally and solutally driven melt convection. Similarly, the density differences between the grains and the bulk melt cause the grain movement, leading to solid sedimentation or grain floating, as the case may be. Free, unattached solid grains are produced by partial remelting and fragmentation of dendrites, by mechanical disturbances such as stirring or vibration and by heterogeneous nucleation of grains in solidification of grain-refined alloys. In this way, movement of solid crystals during solidification can be ascertained in the following two cases. In the first case, during columnar solidification of non-grain-refined alloys, solid movement is possible in the form of dendrite fragments detached from the columnar stalks by the process of remelting and fragmentation. Movement of grains during columnar solidification gives rise to altogether different microstructure from columnar to equiaxed. In the second case, during equiaxed solidification of grain-refined alloys, the movement of solid crystals is possible in the form of equiaxed dendrite crystals nucleated due to presence of grain refiners. The rate and manner by which the free solids settle (or float) will influence macrosegregation in metal castings. Control of the solidification process is possible through an understanding of the solid movement and its effect on macrosegregation and microstructure. With this viewpoint, the overall objective of the present thesis is to study, experimentally and numerically, the phenomenon of solid phase movement during solidification. Through this study, deeper insights of the role of solid phase movement in solidification are developed which can be used for possible control of quality in castings. Both columnar and equiaxed solidification are considered. Models for transport phenomena associated with columnar solidification with solid phase movement are rarely found in the literature, because of inherent difficulty associated with consideration of microscopic features such as remelting and fragmentation. To tackle this problem, solidification modules for remelting and fragmentation are developed first, followed by integration of these molecules in a macroscopic solidification model. A Rayleigh number based fragmentation criterion is developed for detachment of dendrite fragments from the developing mushy zone, which determines the conditions favorable for fragmentation of dendrites. The criterion developed is a function of net concentration difference, liquid fraction, permeability, growth rate of mushy layer, and thermophysical properties of the material. The effect of various solidification parameters on fragmentation is highlighted. The integrated continuum model developed is applied to stimulate the solidification of aqua-ammonia system in a side-cooled rectangular cavity. The numerical results are in good qualitative agreement with those of experiments reported in literature. A gentle ramp of the mushy zone due to settling of solid crystals, as also noticed in experimental literature, is observed towards the bottom of the cavity. The influence of various modeling parameters on solid phase movement and resulting macrosegregation is investigated through a parametric study. Movement of grains during columnar solidification gives rise to altogether different microstructure and sometimes may initiate a morphological transition of the microstructure from columnar to equiaxed if the number and size of equiaxed grains ahead of the columnar front become sufficient to arrest the columnar growth. The generalised model developed, considering solid phase movement during columnar solidification is used to predict columnar-to-equiaxed transition (CET) based on a prescribed cooling rate criterion. It is found that presence of convection significantly affects the solidification behaviour. Moreover, the movement of dendrite fragments and their accumulation at the columnar front further trigger the occurrence of CET. Cooling configuration, too significantly affects the nature of CET. In unidirectional solidification cases, the locations of CET are found to be in a plane parallel to the chill face. However, for the case of the non-unidirectional solidification (as in side-cooled cavity), the locations of CET need not be in a plane parallel to the chill face. In contrast to fixed columnar solidification, equiaxed solidification is poorly understood; in particular, the phenomena associated with solid crystal movement. Movement of unattached solid crystals, formed due to heterogeneous nucleation on grain-refiners, is induced by the convective currents as well as by buoyancy effects, causing the solid to sediment or to float, depending on density of solid compared to that of the bulk melt. While moving in the bulk melt these crystals can also remelt or grow. A series of casting experiments with AI-based alloys are performed to investigate the role and influence of movement of solid crystals on macrosegregation and microstructure evolution during equiaxed solidification. Controlled experiments are designed for studying, separately, settling and floatation of equiaxed crystals for different cooling conditions and configurations. Further, these experiments are carried out in convective and non-convective cases to understand the effect of convection on solid phase movement. Temperature measurements are performed at various locations in the mould during the experiments. After the cavity is solidified, microstructural and chemical analyses of the experimental samples are carried out, several notable features are observed in temperature histories, macrosegregation pattern, and microstructures due to settling/flotation phenomenon of solid crystals. It is found that the flow behavior of solid grains has a profound influence on the progress of solidification (in terms of grain size distribution and fraction eutectic) and macrosegregation distribution. In some cases, the induced flow due to solid phase movement can cause a flow reversal. The observations and quantitative data obtained from experiments, with the help of detailed solidification conditions provided, can be used for future validations of models for equiaxed solidification. Subsequently, numerical studies are carried out, using a modified version of the macroscopic model developed for columnar solidification with motion of solid crystals, to predict the transport phenomena during equiaxed solidification. The model is applied to simulate the solidification processes corresponding to each of the experimental cases performed in this study. For a better understanding of the phenomenon of movement of solid crystals, the following two special cases of solidification are also presented: 1) without movement of solid crystals and 2) movement of solid crystals without any relative velocity between solid and liquid phases. The numerical predictions showing nature of flow field and progress of solidification are substantiated by the experimental data for the thermal analysis, qualitative microstructural Images and quantitative microstructural analysis. It is concluded, with the help of various experiments and simulations, that movement of solid crystals influences the casting quality appreciably, in terms of macrosegregation and microstructures. It is expected that the improved understanding of the role and influence of solid phase movement during solidification processes (both columnar and equiaxed) obtained through this thesis will be useful for possible control of quality of as-cast products.

The volume defined by the rigid cranium is shared by the brain, blood and cerebrospinal fluid (CSF). With every heartbeat the arterial blood volume briefly increases and venous blood and CSF are forced out of the cranium, leading to pulsatility in CSF flow and intracranial pressure (ICP). Altered CSF pulsatility has been linked to idiopathic normal pressure hydrocephalus (INPH), which involves enlarged cerebral ventricles and symptoms of gait/balance disturbance, cognitive decline and urinary incontinence that may be improved by implantation of a shunt. The overall aim of this thesis was to investigate the fluid dynamics of the CSF system, with a focus on pulsatility, and how they relate to INPH pathophysiology and treatment. Mathematical modelling was applied to data from infusion tests, where the ICP response to CSF volume manipulation is measured, to analyse the relationship between mean ICP and ICP pulse amplitude (AMP) before and after shunt surgery in INPH (paper I-II). The observed relationship, designated the pulsatility curve, was found to be constant at low ICP and linear at high ICP, corresponding to a shift from constant to ICP dependent compliance (paper I). Shunt surgery did not affect the pulsatility curve, but shifted baseline ICP and AMP along the curve towards lower values. Patients who improved in gait after surgery had significantly larger AMP reduction than those who did not, while ICP reduction was similar, suggesting that improving patients had baseline ICP in the linear zone of the curve before surgery. Use of this phenomenon for outcome prediction was promising (paper II). The fluid dynamics of an empirically derived pulsatility-based predictive infusion test for INPH was also investigated, with results showing strong influence from compliance (paper III). Clinical ICP data at different body postures was used to evaluate three models describing postural effects on ICP. ICP decreased in upright positions, whereas AMP increased. The model describing the postural effects based on hydrostatic changes in the venous system, including effects of collapse of the jugular veins in the upright position, accurately predicted the measured ICP (paper IV). Cerebral blood flow and CSF flow in the aqueduct and at the cervical level was measured with phase contrast magnetic resonance imaging, and compared between healthy elderly and INPH (paper V). Cerebral blood flow and CSF flow at the cervical level were similar in INPH patients and healthy elderly, whereas aqueductal CSF flow differed significantly. The pulsatility in the aqueduct flow was increased, and there was more variation in the net flow in INPH, but the mean net flow was normal, i.e. directed from the ventricles to the subarachnoid space (paper V). In conclusion, this thesis introduced the concept of pulsatility curve analysis, and provided evidence that pulsatility and compliance are important aspects for successful shunt treatment and outcome prediction in INPH. It was further confirmed that enhanced pulsatility of aqueduct CSF flow was the most distinct effect of INPH pathophysiology on cerebral blood flow and CSF flow. A new model describing postural and hydrostatic effects on ICP was presented, and the feasibility and potential importance of measuring ICP in the upright position in INPH was demonstrated. / <p>Forskningsfinansiär: </p><p>European Union, ERDF: Objective 2, Northern Sweden (grant no. 158715-CMTF). </p>

Type 2 diabetes is a global disease which affects an increasing number of peopleevery year. At the heart of the disease lies insulin resistance in the target tissues,primarily fat and muscle. The insulin resistance is caused by the failure of a complexsignalling network, and several mechanistic hypotheses for this failure havebeen proposed. Herein, we evaluate a hypothesis that revolves around the proteinmammalian target of rapamycin (mTOR) and its feedback signals to insulin receptorsubstrate-1 (IRS1). In particular, we have re-examined this hypothesis andrelevant biological data using a mathematical modelling approach. During the course of modelling we gained several important insights. For instance,the model was unable to reproduce the relation between the EC50-valuesin the dose-response curves for IRS1 and its serine residue 312 (Ser-312). Thisimplies that the presented hypothesis, where the phosphorylation of Ser-312 liesdownstream of the tyrosine phosphorylation of IRS1, is inconsistent with the provideddata, and that the hypothesis or the data might be incorrect. Similarly, wealso realized that in order to fully account for the information in the dose-responsedata, time curves needed to be incorporated into the model. A preliminary model is presented, which explains most of the data-sets, butstill is unable to describe all the details in the data. The originally proposed hypothesisas an explanation to the given data has been revised, and our analysisserves to exemplify that an evaluation of a mechanistic hypothesis by mere biochemicalreasoning often misses out on important details, and/or leads to incorrectconclusions. A model-based approach, on the other hand, can efficiently pin-pointsuch weaknesses, and if combined with a comprehensive understanding of biologicalvariation and generation of experimental data, mathematical modelling canprove to be a method of great potential in the search for mechanistic explanationsto the cause of insulin resistance in type 2 diabetics.

The objective of the thesis is to improve plant yield through optimization and optimal control based on the GreenLab plant growth model. Therefore, the thesis proposed a methodology for investigation of plant yield improvement，whose characteristics are that (1) investigations are all based on the functional-structural plant growth model GreenLab and (2) heuristic optimization algorithm and optimal control techniques are applied to the plant growth model in order to improve plant yield. By applying optimization techniques on different species of plants (crops or trees) and for different kinds of optimization problems, common characteristics that a plant with high yield should possess were obtained. The optimal results in the thesis revealed the source-sink dynamics during the plant growth. The optimization results can be considered as references to guide breeding for ideotype and to improve cultivation modes. The optimization application of GreenLab could thus be possibly used to the agricultural decision support system.To achieve the aims of the thesis, the thesis investigated the effects of endogenous factors and exogenous environmental factors of plant growth on plant yield separately. First, given environmental conditions, the thesis investigated endogenous factors, and then the thesis did optimal control on exogenous environmental factors given plant genotype. Therefore, the problems investigated in the thesis consist of general optimization problems and optimal control problems.The main contributions of the thesis include following issues: According to the species of plants, single optimization problems, multi-objective optimization problems and optimization problems with constraints with respect to plant endogenous factors were formulated and investigated, in order to find the ideotype of plants with high plant yield. A population based algorithm is more suitable for the optimization problems in this thesis. Due to its better performance compared with other heuristic optimization algorithms, all optimization problems were solved by a population-based, heuristic optimization algorithm, namely Particle Swarm Optimization (PSO). Optimal control on the pruning strategy was formulated and investigated in the thesis. As GreenLab can be considered as discrete dynamic system and the objective function of the optimal control problem is analytical, the gradient based method, which is based on the variational approach and Lagrange theory, was used to solve the optimal control problem. Moreover, the optimal solutions were compared with the ones found by PSO, in order to validate the PSO method. The insect population dynamics was modeled mathematically, which was compatible with the plant model GreenLab in terms of spatial and temporal scales, to study the effect of biotic factors on plant growth. The interaction among plants, pests and auxiliaries was implemented, and the ecosystem model, which involves the three tri-trophic components, was thus developed in the thesis. The tri-trophic ecosystem model can simulate the insect population dynamics and the plant growth with consideration of the interaction of insects. Moreover, the tri-trophic ecosystem model considered the partition of individuals in the insect population among plant organs, which is not taken into account in the previous works. A global sensitivity analysis method Morris method was used to analyze the most important parameters and the least influential parameters to model outputs of interest. Through optimization on pest management techniques, the optimal strategies of the application of the pest management techniques were obtained. Estimation of GreenLab parameters with about 400 sets of observation data of 44 tomato genotypes was done in the thesis, by using a generalized non-linear least square algorithm. Taking the estimated parameter values as parameter space, the GreenLab model parameters were optimized, in order to maximize the fruit yield. Through the analysis of the correlation of estimated and optimal parameters with the fruit yield by statistical analysis methods, the most important parameters that result in the difference of fruit yield were found. According to the correlation and optimization results, the phenotypic differences among genotypes were explained from the physiological point of view.

Hospital Acquired Infections (HAI) are a global patient safety challenge, costly to treat, and affect hundreds of millions of patients annually worldwide. It has been shown that the majority of HAI are transferred to patients by caregivers' hands and therefore, can be prevented by proper hand hygiene (HH). However, many factors including cognitive load, cause caregivers to forget to cleanse their hands. Hand hygiene compliance among caregivers remains low around the world. In this thesis I showed that it is possible to build a wearable accelerometer-based HH reminder system to identify ongoing nursing activities with the patient, indicate the high-risk activities, and prompt the caregivers to clean their hands. Eight subjects participated in this study, each wearing five wireless accelerometer sensors on the wrist, upper arms and the back. A pattern recognition approach was used to classify six nursing activities offline. Time-domain features that included mean, standard deviation, energy, and correlation among accelerometer axes were found to be suitable features. On average, 1-Nearest Neighbour classifier was able to classify the activities with 84% accuracy. A novel algorithm was developed to adaptively segment the accelerometer signals to identify the start and stop time of each nursing activity. The overall accuracy of the algorithm for a total of 96 events performed by 8 subjects was approximately 87%. The accuracy was higher than 91% for 5 out of 8 subjects. The sequence of nursing activities was modelled by an 18-state Markov Chain. The model was evaluated by recently published data. The simulation results showed that the high-risk of cross-contamination decreases exponentially by frequency of HH and this happens more rapidly up to 50%-60% hand hygiene rate. It was also found that if the caregiver enters the room with high-risk of transferring infection to the current patient, given the assumptions in this study, only 55% HH is capable of reducing the risk of infection transfer to the lowest level. This may help to prevent the next patient from acquiring infection, preventing an infection outbreak. The model is also capable of simulating the effects of the imperfect HH on the risk of cross-contamination.

Didactic proposals on modelling in mathematics education mostly give priority to models which describe, explain as well as partially forecast and provide mathematical solutions to real situations. A view of the modelling concept of informatics, which also initiates rapidly generalised deliberations of models, can also make a contribution to the spectrum of models, which are treated in a meaningful sense in mathematics lessons so as to expand some interesting aspects. In this paper, this is illustrated by means of conceptual design models – and, here, especially of process models – using the example of elevator organisation in a multi-storey construction.