The general topic of the thesis is the history of the Ordinary Language Philosophy. To be more precise, it deals with the critical arguments, which were raised against is. The thesis offers a short historical and sociological review of the Ordinary Language Philosophy. Critical analysis shows two things: 1) the main reason for the rejection was a different understanding of meaning (and consequences of such a understanding); 2) critics begged the question and already assumed the justification of these rejections in their arguments. The area of this criticism was: the paradigm case argument, the empirical nature of the statements of meaning produced by the Ordinary Language Philosophy, the structural elements of meaning and the political implications of the theory of meaning. The thesis criticizes the Ordinary Language Philosophy in those parts (and in such interpretations), where its understanding of meaning does not differ from the understanding of the critics and where they share common assumptions. On the other hand, the thesis argues for an interpretation, which avoids classical understanding of meaning in all its consequences. Finally, the thesis asks how the Ordinary Language Philosophy can be useful for contemporary debates.

The aim of this Master’s thesis is to achieve philosophical clarity on an interpretative problem I have been struggle with in Euripides’ Medea: That Medea murders her own children, while claimingto love them. Situated within the philosophical and literary tradition of ordinary language philosophy and ordinary language criticism, the thesis draws on ideas, theoretical discussions, and concepts from Ludwig Wittgenstein, Toril Moi, Stanley Cavell, Cora Diamond, and Niklas Forsberg – but also Søren Kierkegaard. The analysis is divided in two parts. The first is anarticulation of the grammar of my problem through Cora Diamond’s conception of the phenomenon “a difficulty of reality”, and an emulation of a hermeneutical strategy to deal with such problems, which I identify in Søren Kierkegaard’s Fear and Trembling. I reach the conclusion that the co-existence of Medea’s murder och love is a paradox, which cannot be thought. The second part of the analysis is an attempt to step out of this paradox. Here, I compare Medea to Stanley Cavell’s readings on the Shakespearean tragedies Othello and King Lear, and Cavell’s ideas on “lived scepticism”, “avoidance of love” and “best case of acknowledgment”. By doing this, I am able to form the hypothesis that Medea’s understanding of “love” has been severely damagedafter Jason’s betrayal, and that she actually fails to sensically mean that she loves her children. In its use of my own confusion as a starting point and in employing Toril Moi’s views on reading, this thesis continuously stresses the individual reader’s responsibility in literary interpretation, as well as the importance of daring to voice or personal struggles, questions, and interests – even (or especially) when reading great classics.

In vitro tissue engineering is a method for developing living and functional tissues external to the body, often within a device called a bioreactor to control the chemical and mechanical environment. However, the quality of bone tissue engineered products is currently inadequate for clinical use as the implant cannot bear weight. In an effort to improve the quality of the construct, hydrostatic pressure, the pressure in a fluid at equilibrium that is required to balance the force exerted by the weight of the fluid above, has been investigated as a mechanical stimulus for promoting extracellular matrix deposition and mineralisation within bone tissue. Thus far, little research has been performed into understanding the response of bone tissue cells to mechanical stimulation. In this thesis we investigate an in vitro bone tissue engineering experimental setup, whereby human mesenchymal stem cells are seeded within a collagen gel and cultured in a hydrostatic pressure bioreactor. In collaboration with experimentalists a suite of mathematical models of increasing complexity is developed and appropriate numerical methods are used to simulate these models. Each of the models investigates different aspects of the experimental setup, from focusing on global quantities of interest through to investigating their detailed local spatial distribution. The aim of this work is to increase understanding of the underlying physical processes which drive the growth and development of the construct, and identify which factors contribute to the highly heterogeneous spatial distribution of the mineralised extracellular matrix seen experimentally. The first model considered is a purely temporal model, where the evolution of cells, solid substrate, which accounts for the initial collagen scaffold and deposited extracellular matrix along with attendant mineralisation, and fluid in response to the applied pressure are examined. We demonstrate that including the history of the mechanical loading of cells is important in determining the quantity of deposited substrate. The second and third models extend this non-spatial model, and examine biochemically and biomechanically-induced spatial patterning separately. The first of these spatial models demonstrates that nutrient diffusion along with nutrient-dependent mass transfer terms qualitatively reproduces the heterogeneous spatial effects seen experimentally. The second multiphase model is used to investigate whether the magnitude of the shear stresses generated by fluid flow, can qualitatively explain the heterogeneous mineralisation seen in the experiments. Numerical simulations reveal that the spatial distribution of the fluid shear stress magnitude is highly heterogeneous, which could be related to the spatial heterogeneity in the mineralisation seen experimentally.

Introduction: Antimalarial resistance, particularly artemisinin resistance, is a major threat to P. falciparum malaria elimination efforts worldwide. Urgent intervention is required to tackle artemisinin resistance but field data on which to base planning of strategies are limited. The aims were to collect available field data and develop population level mathematical models of P. falciparum malaria treatment and artemisinin resistance in order to determine the optimal strategies for elimination of artemisinin resistant malaria in Cambodia and treatment of pre-hospital and severe malaria in Cambodia and Bangladesh. Methods: Malaria incidence and parasite clearance data from Cambodia and Bangladesh were collected and analysed and modelling parameters derived. Population dynamic mathematical models of P. falciparum malaria were produced. Results: The modelling demonstrated that elimination of artemisinin resistant P. falciparum malaria would be achievable in Cambodia in the context of artemisinin resistance using high coverages with ACT treatment, ideally combined with LLITNs and adjunctive single dose primaquine. Sustained efforts would be necessary to achieve elimination and effective surveillance is essential, both to identify the baseline malaria burden and to monitor parasite prevalence as interventions are implemented. A modelled policy change to rectal and intravenous artesunate in the context of pre-existing artemisinin resistance would not compromise the efficacy of ACT for malaria elimination. Conclusions: By being developed rapidly in response to specific questions the models presented here are helping to inform planning efforts to combat artemisinin resistance. As further field data become available, their planned on-going development will produce increasingly realistic and informative models which can be expected to play a central role in planning efforts for years to come.

The heart is one the most important organs in the human body and many other live creatures. The electrical activity in the heart controls the heart function, and many heart diseases are linked to the abnormalities in the electrical activity in the heart. Mathematical equations and computer simulation can be used to model the electrical activity in the heart. The heart models are challenging to solve because of the complexity of the models and the huge size of the problems. Several cell models have been proposed to model the electrical activity in a single heart cell. These models must be coupled with a heart model to model the electrical activity in the entire heart. The bidomain model is a popular model to simulate the propagation of electricity in myocardial tissue. It is a continuum-based model consisting of non-linear ordinary differential equations (ODEs) describing the electrical activity at the cellular scale and a system of partial differential equations (PDEs) describing propagation of electricity at the tissue scale. Because of this multi-scale, ODE/PDE structure of the model, splitting methods that treat the ODEs and PDEs in separate steps are natural candidates as numerical methods. First, we need to solve the problem at the cellular scale using ODE solvers. One of the most popular methods to solve the ODEs is known as the Rush-Larsen (RL) method. Its popularity stems from its improved stability over integrators such as the forward Euler (FE) method along with its easy implementation. The RL method partitions the ODEs into two sets: one for the gating variables, which are treated by an exponential integrator, and another for the remaining equations, which are treated by the FE method. The success of the RL method can be understood in terms of its relatively good stability when treating the gating variables. However, this feature would not be expected to be of benefit on cell models for which the stiffness is not captured by the gating equations. We demonstrate that this is indeed the case on a number of stiff cell models. We further propose a new partitioned method based on the combination of a first-order generalization of the RL method with the FE method. This new method leads to simulations of stiff cell models that are often one or two orders of magnitude faster than the original RL method. After solving the ODEs, we need to use bidomain solvers to solve the bidomain model. Two well-known, first-order time-integration methods for solving the bidomain model are the semi-implicit method and the Godunov operator-splitting method. Both methods decouple the numerical procedure at the cellular scale from that at the tissue scale but in slightly different ways. The methods are analyzed in terms of their accuracy, and their relative performance is compared on one-, two-, and three-dimensional test cases. As suggested by the analysis, the test cases show that the Godunov method is significantly faster than the semi-implicit method for the same level of accuracy, specifically, between 5 and 15 times in the cases presented. Second-order bidomain solvers can generally be expected to be more effective than first-order bidomain solvers under normal accuracy requirements. However, the simplest and the most commonly applied second-order method for the PDE step, the Crank-Nicolson (CN) method, may generate unphysical oscillations. We investigate the performance of a two-stage, L-stable singly diagonally implicit Runge-Kutta method for solving the PDEs of the bidomain model and present a stability analysis. Numerical experiments show that the enhanced stability property of this method leads to more physically realistic numerical simulations compared to both the CN and Backward Euler (BE) methods.

This thesis is concerned with methodologies for the accurate quantitative modelling of molecular biological systems. The first part is devoted to the chemical Langevin equation (CLE), a stochastic differential equation driven by a multidimensional Wiener process. The CLE is an approximation to the standard discrete Markov jump process model of chemical reaction kinetics. It is valid in the regime where molecular populations are abundant enough to assume their concentrations change continuously, but stochastic fluctuations still play a major role. We observe that the CLE is not a single equation, but a family of equations with shared finite-dimensional distributions. On the theoretical side, we prove that as many Wiener processes are sufficient to formulate the CLE as there are independent variables in the equation, which is just the rank of the stoichiometric matrix. On the practical side, we show that in the case where there are m_1 pairs of reversible reactions and m_2 irreversible reactions, there is another, simple formulation of the CLE with only m_1+m_2 Wiener processes, whereas the standard approach uses 2m_1+m_2. Considerable computational savings are achieved with this latter formulation. A flaw of the CLE model is identified: trajectories may leave the nonnegative orthant with positive probability. The second part addresses the challenge when alternative, structurally different ordinary differential equation models of similar complexity fit the available experimental data equally well. We review optimal experiment design methods for choosing the initial state and structural changes on the biological system to maximally discriminate between the outputs of rival models in terms of L_2-distance. We determine the optimal stimulus (input) profile for externally excitable systems. The numerical implementation relies on sum of squares decompositions and is demonstrated on two rival models of signal processing in starving Dictyostelium amoebae. Such experiments accelerate the perfection of our understanding of biochemical mechanisms.

Traditionally, differential-equation models for population dynamics have considered organisms as "fixed" entities in terms of their behaviour and characteristics. However, there have been many observations of adaptivity in organisms, both at the level of behaviour and as an evolutionary change of traits, in response to the environmental conditions. Taking such adaptiveness into account alters the qualitative dynamics of traditional models and is an important factor to be included, for example, when developing reliable model predictions under changing environmental conditions. In this thesis, we consider piecewise-smooth and smooth dynamical systems to represent adaptive change in a 1 predator-2 prey system. First, we derive a novel piecewise-smooth dynamical system for a predator switching between its preferred and alternative prey type in response to prey abundance. We consider a linear ecological trade-off and discover a novel bifurcation as we change the slope of the trade-off. Second, we reformulate the piecewise-smooth system as two novel 1 predator-2 prey smooth dynamical systems. As opposed to the piecewise-smooth system that includes a discontinuity in the vector fields and assumes that a predator switches its feeding strategy instantaneously, we relax this assumption in these systems and consider continuous change in a predator trait. We use plankton as our reference organism because they serve as an important model system. We compare the model simulations with data from Lake Constance on the German-Swiss-Austrian border and suggest possible mechanistic explanations for cycles in plankton concentrations in spring.

The retina is the ocular tissue responsible for the detection of light. Its extensive demand for oxygen, coupled with a concomitant elevated supply, renders this tissue prone to both hypoxia and hyperoxia. In this thesis, we construct mathematical models of the retina, formulated as systems of reaction-diffusion equations, investigating its oxygen-related dynamics in healthy and diseased states. In the healthy state, we model the oxygen distribution across the human retina, examining the efficacy of the protein neuroglobin in the prevention of hypoxia. It has been suggested that neuroglobin could prevent hypoxia, either by transporting oxygen from regions where it is rich to those where it is poor, or by storing oxygen during periods of diminished supply or increased uptake. Numerical solutions demonstrate that neuroglobin may be effective in preventing or alleviating hypoxia via oxygen transport, but that its capacity for oxygen storage is essentially negligible, whilst asymptotic analysis reveals that, contrary to the prevailing assumption, neuroglobin's oxygen affinity is near optimal for oxygen transport. A further asymptotic analysis justifies the common approximation of a piecewise constant oxygen uptake across the retina, placing existing models upon a stronger theoretical foundation. In the diseased state, we explore the effect of hyperoxia upon the progression of the inherited retinal diseases, known collectively as retinitis pigmentosa. Both numerical solutions and asymptotic analyses show that this mechanism may replicate many of the patterns of retinal degeneration seen in vivo, but that others are inaccessible to it, demonstrating both the strengths and weaknesses of the oxygen toxicity hypothesis. It is shown that the wave speed of hyperoxic degeneration is negatively correlated with the local photoreceptor density, high density regions acting as a barrier to the spread of photoreceptor loss. The effects of capillary degeneration and treatment with antioxidants or trophic factors are also investigated, demonstrating that each has the potential to delay, halt or partially reverse photoreceptor loss. In addition to answering questions that are not accessible to experimental investigation, these models generate a number of experimentally testable predictions, forming the first loop in what has the potential to be a fruitful experimental/modelling cycle.

Triloger har utvecklats till att idag utgöra en viktig del av Europeiska unionens ordinarie lagstiftningsförfarande. Dessa informella förhandlingsmöten mellan unionslagstiftarna, med deltagande av kommissionen, har förändrat den praktiska tillämpningen av fördragens bestämmelser om lagstiftningsförfarandet fastän de inte omnämns i fördragen. Samtidigt som trilogerna har gjort processen mer effektiv har de haft en negativ påverkan på insynen i förfarandet. I denna uppsats studeras hur fenomenet triloger genom åren har uttryckts juridisk i den institutionella unionsrätten. Kritiken mot trilogerna och andra aktuella händelser som möjligen kan förändra trilogernas rättsliga ställning utvärderas. / Trilogues have evolved to become an important part of the European Union’s ordinary legislative procedure. These informal negotiating meetings between the Union legislators, with the participation of the Commission, have changed the practical application of the Treaty rules on the legislative procedure without being mentioned in primary law. While the trilogue system has made the process more efficient, it has had a negative impact on the transparency of the process. This paper aims to study how the trilogue phenomenon has been legally expressed in the institutional Union law. The criticism against trilogues and other recent events are also examined in order to assess how these possibly can change the legal status of trilogues. / Les trilogues ont connu une évolution en devenant une partie intégrante et importante de la procédure législative ordinaire de l’Union Européenne. Ces réunions de négociations informelles entre les législateurs européens, avec la participation de la Commission, ont modifiées l’application pratique des règles des traités sur la procédure législative sans être mentionnées dans le droit primaire. Bien que les trilogues aient rendu le processus plus efficace, ils ont indéniablement eu un impact négatif sur la transparence de la procédure. Cette thèse vise à reconstruire comment le phénomène des trilogues a été exprimé en termes légaux dans le droit institutionnel de l’Union. Les critiques à l’encontre des trilogues et d’autres actualités sont aussi étudiées afin d’évaluer la façon dont ceux-ci éventuellement peuvent modifier le statut juridique des trilogues.

Bakgrund: Bedömning av näringstillstånd och näringstillförsel är komplicerad vid svår sepsis och septisk chock beroende på sjukdomenskomplexitet. Patienternas upplevelser om mat, dryck och ätande under och efter intensivvård utgör en viktig parameter för bedömning avnäringstillförsel men är sparsamt undersökt. Syftet var att kartlägga dokumenterad bedömning av näringstillstånd och näringstillförsel samt undersöka patientens upplevelse om mat, dryck och ätande vid svår sepsis och septisk chock. Metod: Studien genomfördes med case study design där mixade metoder användes. En kvantitativ journalgranskning av näringstillförsel och näringstillstånd kombinerades med en kvalitativ innehållsanalys av fem patienters upplevelser och minnen. Resultat: Skiftande bedömning av näringstillstånd och näringstillförsel framkom, alltifrån detaljerad dokumentation till sparsam och fragmenterad. Fastlagda rutiner för näringsbedömning följdes inte. Etablerade metoder fångade inte risk för näringsproblem. Dokumentation om näringstillförsel var detaljerad under intensivvårdstiden och mer knapphändig under vårdtid på vårdavdelningarna. Patienterna hade unika minnen och upplevelser, av törst, förlorad hungerkänsla och förvåning över hur fort orken försvann, men sedan kom tillbaka.Slutsats: En systematisk och regelbunden uppföljning av näringstillförsel och en individuell, personinriktad vård behövs för förståelse för patientens unika tillstånd vid kritisk sjukdom. Ytterligare studier behövs för utveckling av instrument för detektering av näringsproblem under och efter intensivvård. / Background: Assessment of nutritional status and support are complicated in the care of patients with severe sepsis and septic chock due to complexity of disease. Patient opinions on food and food intake may serve as important parameters when deciding the amount and kind of nutritional support but are sparsely investigated. The purpose was to describe assessment of nutritional status and nutritional support in patients with severe sepsis and septic chock and to investigate patient experiences of food, drinking and eating during and after intensive care. Method: A case study design was conducted using mixed methods. Assessment of nutritional status and support in medical record were investigated quantitatively in five patients. Experiences and memories were analysed qualitatively using content analysis. Result: Diverse results emerged from detailed to sparse and fragmented judgements, planning and measures taken. Established assessment tools didn´t capture nutritional problems. ICU documentation was detailed while documentation during ordinary ward care was scanty. The patients had unique experiences and memories of thirst, weight, loss of hunger and astonishment of quick loss and return of energy. Conclusion: A systematic and regular control of nutritional support and individual care is required to understand the uniqueness of patient status incritical disease. Further investigation is needed concerning tools for detection of nutritional problems during and after intensive care.