This thesis develops biophysically-based data-driven mathematical models of intracellular calciumdynamics in ventricularmyocytes for both normal and genetically modified mouse hearts, based on species- and temperature-consistent experimental data. The models were subsequently applied to quantitatively examine the changes in calcium dynamics in mice with cardiomyocyte-specific knockout (KO) of the cardiac sarco/endoplasmic reticulum ATPase (SERCA2) gene, to determine the contributing mechanisms which underlie the ultimate development of heart failure in these animals. In Chapter 1, with emphasis on calcium dynamics and calcium regulation in heart failure, an overview of cardiac electrophysiology, excitation-contraction coupling and mathematical models of cardiac electrophysiology is provided. In Chapter 2, models of calcium dynamics in the ventricular myocytes from the C57BL/6 mouse heart at a physiological temperature is developed and validated based on species- and temperature-consistent measurements. In Chapter 3, the C57BL/6 model framework is re-parameterised to experimental data from the control and SERCA2 KO mice at 4 weeks after gene deletion. The models are then used to quantitatively characterise changes in calcium dynamics in the KO animals and the role of the compensatory mechanisms. In Chapter 4, the model framework is extended to include differential distributions of ion channels in the sarcolemma and the calcium dynamics in the sub-sarcolemmal space, with parameters in these sub-components fitted to experimentally measured calcium dynamics from the control and KO cardiomyocytes at 7-week after gene deletion. Finally in Chapter 5, conclusions are drawn, the limitations of this study are discussed, and the future extensions to this study are described.

This thesis presents a comprehensive work on computerised analysis of fetal heart rate (FHR) features, including feature extraction, feature selection, analysis of influencing factors and setting up/validation of a computerised decision support system. Firstly, a novel feature – pattern readjustment – was extracted and tested. Clinical data were used to train a Support Vector Machine (SVM) to detect pattern readjustment. Then, the association of pattern readjustment and adverse labour outcome was investigated. The validation results with clinical experts show that the pattern readjustment can be accurately detected, while the study on labour outcome shows that the feature is related to fetal acidemia at birth. Secondly, Genetic Algorithms were employed as a feature selection method to select a best subset of FHR features and to use them to predict fetal acidemia with linear and nonlinear SVM. The diagnostic power of the classifier output using selected features was tested on the total set of 7,568 cases. As the classifier output increases, there is a consistent increase of the risk of fetal acidemia. Thirdly, an important influencing factor on FHR features - signal loss – was investigated. A bivariate model was built to estimate error based on signal loss. Validation results show that the bivariate model can accurately predict the error generated by signal loss. The influence of signal loss on labour outcome classification was also investigated. Finally, a computerised decision support system to estimate the risk of fetal acidemia was set up based on the above studies. The system was validated using new retrospective data. Validation results show that the system is capable of predicting adverse labour outcome and providing timely decision support. It is the first time an intrapartum computerised FHR decision support system has been built and validated on this size of dataset. With further improvements, such a system could be implemented clinically in the long term.

This thesis describes the development of a framework for computational modelling of electromechanics in the mouse, with the purpose of being able to integrate cellular and tissue scale observations in the mouse and investigate physiological hypotheses. Specifically, the framework is applied to interpret electromechanical coupling mechanisms and the progression of heart failure in genetically modified mice. Chapter 1 introduces the field of computational biology and provides context for the topics to be investigated. Chapter 2 reviews the biological background and mathematical bases for electromechanical models, as well as their limitations. In Chapter 3, a set of efficient computational methods for coupled cardiac electromechanics was developed. Among these are a modified Newton method combined with a solution predictor which achieves a 98% reduction in computational time for mechanics problems. In Chapter 4, this computational framework is extended to a multiscale electromechanical model of the mouse. This electromechanical model includes our novel cardiac cellular contraction model for mice, which is able to reproduce murine contraction dynamics at body temperature and high pacing frequencies, and provides a novel explanation for the biphasic force-calcium relation seen in cardiac myocytes. Furthermore, our electromechanical model of the left ventricle of the mouse makes novel predictions on the importance of strong velocity-dependent coupling mechanisms in generating a plateau phase of ventricular pressure transients during ejection. In Chapter 5, the framework was applied to investigate the progression of heart failure in genetically modified 'Serca2 knockout' mice, which have a major disruption in mechanisms governing calcium regulation in cardiac myocytes. Our modelling framework was instrumental in showing for the first time the incompatibility between previously measured cellular calcium transients and ventricular ejection. We were then able to integrate new experimental data collected in response to these observations to show the importance of beta-adrenergic stimulation in the progression of heart failure in these knockout mice. Chapter 6 presents the conclusions and discusses possibilities for future work.

Cardiac motion is a highly complex and integrated process of vital importance as it sustains the primary function of the heart, that is pumping blood. Cardiac tissue microstructure, in particular the alignment of myocytes (also referred to as fibre direction) and their lateral organisation into laminae (or sheets), has been shown by both experimental and computational research to play an important role in the determination of cardiac motion patterns. However, current models of cardiac electromechanics, although already embedding structural information in the models equations, are not yet able to fully reproduce the connection between structural dynamics and cardiac deformation. The aim of this thesis was to develop an electromechanical modelling framework to investigate the impact of tissue structure on cardiac motion, focussing on left ventricular contraction in rat. The computational studies carried out were complemented with a preliminary validation study based on experimental data of tissue structure rearrangement during contraction from diffusion tensor MRI.

Detta arbete handlar om utomhuspedagogik, mer specifikt om hur lärare arbetar med utomhusmiljö i NO-undervisningen, hur deras förutsättningar ser ut och vilka för och nackdelar de anser finns med utomhuspedagogik. Jag har gjort en enkätundersökning som har skickats ut till alla kommunala F-3 skolor i en mellanstor stad i mellersta Sverige. Resultatet i min studie är baserat på 23 enkätsvar. Resultatet visade att de allra flesta lärare hade en positiv bild av utomhuspedagogik och ansåg att det gynnade elevernas kunskapsutveckling. Framförallt eftersom det eleverna lärde sig konkretiserades när de kunde vara utomhus och fick möjlighet att använda flera olika sinnen. Resultatet visade även att det fanns en del begränsningar när man skulle ha undervisningen utomhus, det som flest lärare ansåg vara en begränsning var tillgången till den personal som behövdes för att undervisningen skulle fungera. Slutligen kunde man också se att lärarna upplevde att eleverna var positiva till undervisning utomhus.

This article explores who the people in the mountain world are and what makes them choose the activities they do through a questionnaire survey with information about gender, age, place of birth, education level, mountain habit and the sense of accessibility, self-esteem and factors that influence the choice of mountain activities. The results from the study show that most people who visit the mountains come from southern Sweden and from outside the Nordic countries. Many of these visit the mountains several times a year. A majority of respondents also feel included in the target groups that they think nature tourism is focusing on, which are those with good economics, high level of education, associated middle or upper classes, and already introduced in the mountain environment. Non-white persons were some who, according to the interviewees, were not prioritized by nature tourism, and among the interviewees were also non-white in extreme minority. Factors that affect the interviewees' choices about what they choose to do for activities in the mountains are above all the tour company, but also the economy and old habit. As to what makes the respondents choose not to do certain activities in the mountains, there is also a society that is the biggest factor, followed by ignorance, economy and uncertainty.

No description available.

This essay is about how the concepts of resilience and vulnerability are expressed in local vulnerability analyses. The essay also highlights underlying structures and driving forces to risk and vulnerability in the selected risk- and vulnerability analyses. The purpose is to examine and analyze how resilience and vulnerability in society is reflected in local risk- and crisis management with a selection of municipal risk- and vulnerability assesments as an exempel. The chosen method in this work is qualitative text analysis. The result indicates that the general focus in the analyzed material is on municipal activties and events of chock or crisis. The perspectives on risk and vulnerability that is being used equates risks with events and vulnerability as the effect of those events. In regards of resilience and the 3D Resilience framework from Bené et al.(2012) the risk- and vulnerability analyses are therefore at most related to the first two dimensions: absorption and adaption. Above all the municipalities wants to attain stability and robustness while resisting the effects of chock or crisis events to be able to revert to pre-chock state. Vulnerability is being reflected as a contrast to the abilities the municipalities aim for with their crisis response. That sort of understanding and assessment of risk and vulnerability pays barely no attention at all to underlying driving forces to risk and crisis. Even if in some cases there seems to be a will to try and include issuess like social vulnerability and social inequalities.

Detta är en studie som undersöker hur lek kan fungera som metod under den naturvetenskapligaundervisningen för elever i årskurs 1-2. Studien är kvalitativ ochutgår från en fenomenologisk ansats där den enskilda individens syn på lek undersöks.Data har insamlats med hjälp av intervjuer och observationer som genomförs itvå klasser, en årskurs 1 och en årskurs 2. Intervjuerna görs med klasslärarna i respektiveklass och samtliga elever intervjuas i fokusgrupper, totalt antal elever sommedverkar i studien är 32 stycken. Tidigare forskning visar att det tycks sakna tidigareforskning på hur lek påverkar elevers lärande. Den visar också att lärares kunskapom den naturvetenskapliga undervisningen påverkar elevernas intresse. Läraresointresse och okunskap i ämnet genererar i att elevens naturliga lust inte tastillvara på utan ger i det långa loppet elever som ser naturvetenskap som någontingtråkigt och oviktigt. Resultatet av denna studie visar att lek kan fungera som metodi den naturvetenskapliga undervisningen men att det är viktigt med både introduktion,genomförande och återkoppling efteråt för att hjälpa eleverna att kopplaleken till lärandet. Resultatet visar också att begreppet lek är svårdefinierat och attde lärare som deltagit i studien har olika uppfattningar om vad lek som undervisningsmetodär. Intervjuer med elever visar att en del har svårt att förstå att de lärsig när undervisningsmetoden är lek medan en del elever uppskattar det och menaratt de lär sig mer när de får gestalta och använda kroppen.

Syftet med denna studie är att få en djupare förståelse för hur turismens utveckling på en destination i Stockholms skärgård påverkar destinationens hållbarhet. För att undersöka detta har studien avgränsats till Sandhamn då det är en av de populäraste destinationerna i Stockholms skärgård. I studien har både kvantitativ- och kvalitativ metod i form av en triangulering tillämpats. Den kvantitativa delen består av statistik från olika aktörer för att påvisa turismens utveckling i skärgården. Den kvalitativa delen utgörs av intervjuer och en observation som använts för att undersöka vad utvecklingen beror på, samt vad den lett till. Statistiken påvisar en stagnering av besökare i skärgården medan respondenterna motsäger sig detta och istället menar att det kommer mer besökare, dock under en kortare period. Utvecklingen är således inte hållbar då mängden turister som kommer under denna korta period tär på öns infrastruktur och överskrider öns bärkraft. Under den långa lågsäsongen, när turisterna inte kommer, uppstår istället lönsamhetsproblem för destinationens aktörer. Avslutningsvis kan det konstateras att det bristande samarbetet är en bidragande orsak till den förkortade säsongen och skulle behöva förbättras för att fördela besökarna jämnare över året. / This study is intended to gain a comprehensive understanding of how the advancement of tourism in Stockholm’s archipelago affects the destination’s sustainability. To examine the multitude of variables that affect sustainability, the paper is centered on Sandhamn, as it is one of the most popular destinations within Stockholm’s archipelago. Throughout the study, both the quantitative and qualitative methods were implemented in the form of a triangulation. In order to demonstrate the development of tourism within the archipelago, the study utilized statistics from various actors as the quantitative portion of this paper. The qualitative part consists of interviews as well as an observation that has been applied to investigate the integral components of development and its outcomes. The statistics show a stagnation of tourists in the archipelago; however, the respondents disagree and conversely argue that there has been an influx of tourists, but that they are staying for a shorter period of time. Thus, proving that the development is not sustainable; as the number of tourists who come during this shorter period have a significant impact on the island's infrastructure and exacerbates the island's sustainability. During the extended low season, when tourists are at their minimum, profitability problems arise; thereby, leading to an entirely new issue for the destination's actors. In conclusion, it can be inferred that the lack of cooperation is a contributing factor to the shortened season and would need to be improved to redistribute the visitors more evenly throughout the year.