Intresset för flervåningshus i trä ökar stadigt. Trä är ett lätt och mjukt material vilket är problematiskt med avseende på stomstabilisering och horisontella deformationer. Syftet har varit att undersöka förbandstyper för KL-trä och huvudfrågan var hur stommens horisontella deformationer påverkas av infästningstyperna och deras styvhet. En jämförande studie av självborrande skruvar och beräkning av deras förskjutningsmodul har utförts. En modell på 22 våningar med en stomme av KL-trä modellerades i RFEM. Analyser genomfördes för olika värden på förskjutningsmodul för att kunna jämföra de horisontella deformationerna. Resultatet visade på att deformationerna blev små och att skillnaden mellan olika förskjutningsmoduler gav en knappt märkbar skillnad i horisontell deformation, trots att variationen av värdet på förskjutningsmodulerna var stor. Detta kan förklaras av att modellen i sig är väldigt stabil, vilket främst skulle kunna bero på fasadelementens vertikala förskjutning och höjd. Andra bidragande orsaker var att modellen saknade urtag för dörrar och fönster, KL-elementens tjocklek samt att pågjutning av betong applicerades på varje våning. / The interest for multi storey buildings with timber is growing. Timber is a material that is light and ductile, characteristics that make timber a challenging material in terms of horizontal stabilization and horizontal displacements. The purpose was to examine connectors for CLT and the main question was how the horizontal displacement of the frame is affected by the connectors and their stiffness. A parametric study for self-tapping screws and calculation of their slip modulus was carried out. A model of a 22-storey building with a CLT frame was modelled in RFEM. Analyses were run for different values of the slip modulus for comparison of the horizontal displacements connected to each slip modulus. The results show that the deformations were small and that the differences in slip modulus only caused small differences in horizontal deformations even though the variation in slip modulus was wide. The reason for this could be due to the modelling; the model in itself is very stiff, possibly as a result of the façade panels’ vertical adjustment and height. Other factors contributing were the lack of openings for doors and windows in the model, the thickness of the CLT panels as well as the concrete decks on all floors.

This thesis consists of four research papers presenting a microdata analysis approach to assess and evaluate the Parkinson’s disease (PD) motor symptoms using smartphone-based systems. PD is a progressive neurological disorder that is characterized by motor symptoms. It is a complex disease that requires continuous monitoring and multidimensional symptom analysis. Both patients’ perception regarding common symptom and their motor function need to be related to the repeated and time-stamped assessment; with this, the full extent of patient’s condition could be revealed. The smartphone enables and facilitates the remote, long-term and repeated assessment of PD symptoms. Two types of collected data from smartphone were used, one during a three year, and another during one-day clinical study. The data were collected from series of tests consisting of tapping and spiral motor tests. During the second time scale data collection, along smartphone-based measurements patients were video recorded while performing standardized motor tasks according to Unified Parkinson’s disease rating scales (UPDRS). At first, the objective of this thesis was to elaborate the state of the art, sensor systems, and measures that were used to detect, assess and quantify the four cardinal and dyskinetic motor symptoms. This was done through a review study. The review showed that smartphones as the new generation of sensing devices are preferred since they are considered as part of patients’ daily accessories, they are available and they include high-resolution activity data. Smartphones can capture important measures such as forces, acceleration and radial displacements that are useful for assessing PD motor symptoms. Through the obtained insights from the review study, the second objective of this thesis was to investigate whether a combination of tapping and spiral drawing tests could be useful to quantify dexterity in PD. More specifically, the aim was to develop data-driven methods to quantify and characterize dexterity in PD. The results from this study showed that tapping and spiral drawing tests that were collected by smartphone can detect movements reasonably well related to under- and over-medication. The thesis continued by developing an Approximate Entropy (ApEn)-based method, which aimed to measure the amount of temporal irregularity during spiral drawing tests. One of the disabilities associated with PD is the impaired ability to accurately time movements. The increase in timing variability among patients when compared to healthy subjects, suggests that the Basal Ganglia (BG) has a role in interval timing. ApEn method was used to measure temporal irregularity score (TIS) which could significantly differentiate the healthy subjects and patients at different stages of the disease. This method was compared to two other methods which were used to measure the overall drawing impairment and shakiness. TIS had better reliability and responsiveness compared to the other methods. However, in contrast to other methods, the mean scores of the ApEn-based method improved significantly during a 3-year clinical study, indicating a possible impact of pathological BG oscillations in temporal control during spiral drawing tasks. In addition, due to the data collection scheme, the study was limited to have no gold standard for validating the TIS. However, the study continued to further investigate the findings using another screen resolution, new dataset, new patient groups, and for shorter term measurements. The new dataset included the clinical assessments of patients while they performed tests according to UPDRS. The results of this study confirmed the findings in the previous study. Further investigation when assessing the correlation of TIS to clinical ratings showed the amount of temporal irregularity present in the spiral drawing cannot be detected during clinical assessment since TIS is an upper limb high frequency-based measure.

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Pour rendre compte du traitement de l’information visuo-spatiale, l’hypothèse dominante est celle du calepin visuo-spatial (Baddeley, 1986). Cependant l’approche multi-systèmes est actuellement remise en question et les théories fonctionnelles défendent l’idée d’un système mnésique unique. C’est dans cette perspective que se situe notre recherche qui s’organise autour de trois questions. La première consiste à définir les traitements visuo-spatiaux mis en œuvre lors de la manipulation d’informations visuo-spatiales. La seconde tente d’établir des profils comportementaux des traitements visuo-spatiaux caractéristiques du vieillissement normal et pathologique (Alzheimer). La troisième porte sur l’expression de la flexibilité cognitive chez des sujets âgés lors de la résolution des blocs de Corsi.Deux expériences ont été réalisées dans lesquelles les participants (sujets Alzheimer et contrôles) devaient résoudre la tâche de Corsi, dans sa version ordre direct (expérience 1) et dans ces versions ordre direct et indirect (expérience 2). Les données ont été exploitées en recourant à une méthodologie d’analyse de protocoles individuels. Dans la première expérience, nous nous sommes intéressée aux erreurs rencontrées. Dans la seconde étude, nous avons étendu nos analyses aux traitements visuo-spatiaux inhérents à ces erreurs. Les résultats obtenus ont permis de définir cinq traitements visuo-spatiaux (vectoriel, vectoriel partiel, identité stricte, approximatif et mixte), de mettre en évidence des profils comportementaux concernant le traitement vectoriel partiel et identité stricte pour les sujets âgés sains lors de la condition indirecte et de montrer l’expression de flexibilité cognitive spontanée lors des traitements visuo-spatiaux séquentiels. Nos analyses ont ainsi permis de proposer une approche différente du traitement de l’information visuo-spatiale en substituant le concept de traitement visuo-spatial à celui de calepin visuo-spatial. / Currently, to account visuospatial information processing, the dominant hypothesis is that of the visuospatial sketchpad (Baddeley, 1896). However, such models postulating the existence of several independent modules are being questioned and recent functional theories defend a single memory system. Our research therefore is organized in this perspective around three questions.The first one aim to define the different visuospatial processing when visuospatial information is needed. The second one is to attempt to establish behavioral profiles of the visuospatial processing by normal ageing people and pathological one (Alzheimer). The third question is to express the cognitive flexibility of elderly patients when solving the Corsi block-tapping task.Two experiments were conducted where participants (seniors affected by Alzheimer’s disease ‘AD’ and a control group of elderly) had to solve the Corsi block-tapping task, in the direct condition (experiment 1) and in the direct and indirect conditions (experiment 2). The data were analyzed using the methodology of individual protocols analysis. In the first experiment, we examined different errors encountered during the resolution of the task. In the second research we extended our analysis to visuospatial processing associated with these errors.We identified five major visuospatial processing: “the vector processing”, “partially vectorial”, “strict identity”, “approximate identity” and “mixed”, to highlight behavioral profiles on the ‘partially vectorial’ processing and ‘strict identity’ to the healthy elderly subjects in the indirect condition and show the expression of spontaneous flexibility in AD patients and normal subjects. Our analysis allowed us to propose a different approach that improve knowledge about both normal and pathological (here Alzheimer’s disease) ageing. Analyzing the subjects in action, conducts to speak in terms of visuospatial processing rather than visuospatial sketchpad.

Cette thèse présente quelques approches expérimentales destinées à mesurer les propriétés mécaniques de films de polymères ultraminces, d'épaisseurs comprise entre 20 et quelques centaines de nanomètre. Nous présentons principalement la conception et l'exploitation d'une expérience de démouillage de films ultraminces sur substrat liquide. Nous montrons dans un premier temps que cette technique permet une mesure simple des propriétés viscoélastiques des films de polymères au dessus de Tg. Les résultats obtenus sur des films ultraminces mettent en évidence que le module au plateau caoutchoutique du polystyrene n'est pas affecté par le confinement, alors même que la viscosité est fortement réduite lorsque l'épaisseur des films est comparable au rayon de gyration des polymères. Divers phénomènes liés au mouillage ou au démouillage de films sont également abordés. Dans une seconde partie, nous présentons une autre expérience fondée sur une instabilité mécanique sur des films vitreux. Une simple observation des motifs induits permet de suivre l'évolution du module élastique dans le domaine vitreux. Enfin, une étude portant sur les possibilités d'investigations des effets de surface et d'interface par AFM sur des élastomères chargés est présentée dans une troisième partie.

The overall aim of this thesis was to develop, deploy and evaluate new IT-based methods for supporting treatment and assessment of treatment of advanced Parkinson’s disease. In this condition a number of different motor and non-motor symptoms occur in episodes of varying frequency, duration and severity. In order to determine outcome of treatment changes, repeated assessments are necessary. Hospitalization for observation is expensive and may not be representative for the situation at home. Paper home diaries have questionable reliability and storage and retrieval of results are problematic. Approaches for monitoring using wearable sensors are unable to address important non-motor symptoms. A test battery system consisting of both self-assessments of symptoms and motor function tests was constructed for a touch screen mobile phone. Tests are performed on several occasions per day during test periods of one week. Data is transmitted over the mobile net to a central server where summaries in different symptom dimensions and an overall test score per patient and test period are calculated. There is a web application that graphically presents the results to treating clinical staff. As part of this work, a novel method for assessment of spiral drawing impairment useful during event-driven sampling was developed. To date, the system has been used by over 100 patients in 10 clinics in Sweden and Italy. Evidence is growing that the test battery is useful, reliable and valid for assessment of symptoms during advanced Parkinson’s disease. Infusion of a levodopa/carbidopa gel into the small intestine has been shown to reduce variation in plasma drug levels and improve clinical response in this patient category. A pharmacokinetic-pharmacodynamic model of this intestinal gel infusion was constructed. Possibly this model can assist the process of individualization of dosage for this treatment through in numero simulations. Results from an exploratory data analysis indicate that severity measures during oral levodopa treatment may be factors to consider when deciding candidates for infusion treatment.

A challenge for the clinical management of Parkinson's disease (PD) is the large within- and between-patient variability in symptom profiles as well as the emergence of motor complications which represent a significant source of disability in patients. This thesis deals with the development and evaluation of methods and systems for supporting the management of PD by using repeated measures, consisting of subjective assessments of symptoms and objective assessments of motor function through fine motor tests (spirography and tapping), collected by means of a telemetry touch screen device. One aim of the thesis was to develop methods for objective quantification and analysis of the severity of motor impairments being represented in spiral drawings and tapping results. This was accomplished by first quantifying the digitized movement data with time series analysis and then using them in data-driven modelling for automating the process of assessment of symptom severity. The objective measures were then analysed with respect to subjective assessments of motor conditions. Another aim was to develop a method for providing comparable information content as clinical rating scales by combining subjective and objective measures into composite scores, using time series analysis and data-driven methods. The scores represent six symptom dimensions and an overall test score for reflecting the global health condition of the patient. In addition, the thesis presents the development of a web-based system for providing a visual representation of symptoms over time allowing clinicians to remotely monitor the symptom profiles of their patients. The quality of the methods was assessed by reporting different metrics of validity, reliability and sensitivity to treatment interventions and natural PD progression over time. Results from two studies demonstrated that the methods developed for the fine motor tests had good metrics indicating that they are appropriate to quantitatively and objectively assess the severity of motor impairments of PD patients. The fine motor tests captured different symptoms; spiral drawing impairment and tapping accuracy related to dyskinesias (involuntary movements) whereas tapping speed related to bradykinesia (slowness of movements). A longitudinal data analysis indicated that the six symptom dimensions and the overall test score contained important elements of information of the clinical scales and can be used to measure effects of PD treatment interventions and disease progression. A usability evaluation of the web-based system showed that the information presented in the system was comparable to qualitative clinical observations and the system was recognized as a tool that will assist in the management of patients.

An increased share of construction with timber is one possible way of achieving more sustainable and energy-efficient life cycles of buildings. The main reason is that wood is a renewable material and buildings require a large amount of resources. Timber buildings taller than two storeys were prohibited in Europe until the 1990s due to fire regulations. In 1994, this prohibition was removed in Sweden.     Some of the early multi-storey timber buildings were associated with more complaints due to impact sound than concrete buildings with the same measured impact sound class rating. Research in later years has shown that the frequency range used for rating has not been sufficiently low in order to include all the sound characteristics that are important for subjective perception of impact sound in light weight timber buildings. The AkuLite project showed that the frequency range has to be extended down to 20 Hz in order to give a good quality of the rating. This low frequency range of interest requires a need for knowledge of the sound field distribution, how to best measure the sound, how to predict the sound transmission levels and how to correlate numerical predictions with measurements.     Here, the goal is to improve the knowledge and methodology concerning measurements and predictions of low frequency impact sound in light weight timber buildings. Impact sound fields are determined by grid measurements in rooms within timber buildings with different designs of their joist floors. The measurements are used to increase the understanding of impact sound and to benchmark different field measurement methods. By estimating transfer functions, from impact forces to vibrations and then sound pressures in receiving rooms, from vibrational test data, improved possibilities to correlate the experimental results to numerical simulations are achieved. A number of excitation devices are compared experimentally to evaluate different characteristics of the test data achieved. Further, comparisons between a timber based hybrid joist floor and a modern concrete floor are made using FE-models to evaluate how stiffness and surface mass parameters affect the impact sound transfer and the radiation.     The measurements of sound fields show that light weight timber floors in small rooms tend to have their highest sound levels in the low frequency region, where the modes are well separated, and that the highest levels even can occur below the frequency of the first room mode of the air. In rooms with excitation from the floor above, the highest levels tend to occur at the floor levels and in the floor corners, if the excitation is made in the middle of the room above. Due to nonlinearities, the excitation levels may affect the transfer function in low frequencies which was shown in an experimental study. Surface mass and bending stiffness of floor systems are shown, by simulations, to be important for the amount of sound radiated.     By applying a transfer function methodology, measuring the excitation forces as well as the responses, improvements of correlation analyses between measurements and simulations can be achieved / ProWood / Silent Timber Build / Urban Tranquility / BioInnovation FBBB

Pore forming toxins are known for their ability to efficiently form transmembrane pores which eventually leads to cell lysis. PFTs have potential applications in devel-oping novel drug and gene delivery strategies. Although structural aspects of many pore forming toxins have been studied, very little is known about the dynamics and subsequent rupture mechanisms. In the first part of the thesis, a combined experimental and modeling study to understand the lytic action of Cytolysin A (ClyA) toxins on red blood cells (RBCs) has been presented. Lysis experiments are carried out on a 1% suspension of RBCs for different initial toxin concentrations ranging from 100 – 500 ng/ml and the extent of lysis is monitored spectrophotometrically. Using a mean field approach, we propose a non – equilibrium adsorption-reaction model to quantify the rate of pore formation on the cell surface. By analysing the model in a pre-lysis regime, the number of pores per RBC to initiate rupture was found to lie between 400 and 800. The time constants for pore formation are estimated to lie between 1-25 s and monomer conformation time scales were found to be 2-4 times greater than the oligomerization times. Using this model, we are able to predict the extent of cell lysis as a function of the initial toxin concentration. Various kinetic models for oligomerization mechanism have been explored. Irreversible sequential kinetic model has the best agreement with the available experimental data. Subsequent to the mean field approach, a population balance model was also formulated. The mechanics of cell rupture due to pore formation is poorly understood. Efforts to address this issue are concerned with understanding the changes in the membrane mechanical properties such as the modulus and tension in the presence of pores. The second part of the thesis is concerned with using atomic force microscopy to measure the mechanical properties of cells. We explore the possibility of employing tapping mode AFM (TM-AFM) to obtain the elastic modulus of soft samples. The dynamics of TM-AFM is modelled to predict the elastic modulus of soft samples, and predict optimal cantilever stiffness for soft biological samples. From experiments using TM-AFM on Nylon-6,6 the elastic modulus is predicted to lie between 2 and 5 GPa. For materials having elastic moduli in the range of 1– 20 GPa, the cantilever stiffness from simulations is found to lie in the range of 1 – 50 N/m. For soft biological samples, whose elastic moduli are in the range of 10-1000 kPa, a narrower range of cantilever stiffness (0.1 – 0.6 N/m), should be used.