| 1. |
- Blaszczyk, Izabela, 1967-
(author)
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Upper limb assessment and treatment in cerebral palsy
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Cerebral palsy (CP) is a heterogeneous group of neurological disorders caused by fetal or infant brain damage that often involves deficits in upper limb (UL) posture and function. Knowledge about effective methods of assessment and treatment of UL in CP is not extensive. In this thesis, different aspects of these two are explored.In Paper I we retrospectively investigated the effect of a long-term treatment regime developed in Västerbotten county habilitation service. The treatment regime included intramuscular injections of botulinum toxin type A (BoNT-A) combined with occupational therapy (OT) and movement training. The results of passive extension of the wrist with fingers extended and the assessment of hand function in children with severe hand function impairment (initially House functional classification 0-1) were analyzed over time. Twenty-five children were divided into 3 groups depending on the treatment regime start age (before or after the age of 7) and treatment regime availability. We found significantly worse passive extension of the wrist with fingers extended in children who did not have a chance to benefit from therapy in early childhood. Additionally, an improvement in the passive movement of the wrists was noted in children who completed the treatment regime before the age of 7. Regarding hand function, a significant difference was found between children who received treatment in early childhood and those who received treatment as adolescents.The injections of BoNT-A in CP are common, however the monitoring of eventual side effects and adverse events (AEs) after this treatment is difficult to perform in clinical practice. To facilitate this process, we created a new, no previously validated questionnaire (Paper II). The questionnaire was given to patients or their caregivers to be completed after each BoNT-A treatment. 94% of participants returned the questionnaire. 80 % were filled in completely which proves the effectiveness of the applied form and the ease of its use in clinical practice. 61% of patients reported one or more different AEs or sides effects. In addition, we analyzed the risk for generalized and focal distal AEs reported by 38% of patients. Those may indicate the spread of BoNT-A toxin to the whole body, therefore requiring special attention. We found that females had a 1.899 relative risk with significant association (p=0.029) of reporting generalized and focal delayed AEs compared to males. The use of the questionnaire helped to make the decision to change or discontinue BoNT-A injections in 8 cases (11%).In some patients with dyskinetic type of CP (DCP) treated with BoNT-A to diminish the external rotation posture of the shoulders, a loss of treatment effect was observed, which contributed to the need to look for another method of treatment. In paper III, a surgical method to manage the external rotation posture of the shoulders is presented. The surgical procedure consists of weakening the strength of the externally rotating muscles by cutting the attachment of one of them (release of the posterior deltoid) and complete denervation of the other (denervation of the infraspinatus). The third shoulder external rotator (teres minor) remains intact. The results of this procedure performed in 7 shoulders in 6 patients (age 14-24) were analyzed using satisfaction questionnaire and pre-/postoperative video-recordings. Five of 6 patients were very satisfied with the treatment, one was neither satisfied nor dissatisfied. Four patients had an obvious improvement in their shoulder position confirmed on video recordings. In one, overcorrection in the form of internal shoulder rotation was observed.Assessment of the thumb in CP is important as the thumb impairment plays a crucial role in hand grip function. Paper IV presents a new tool called CP-thumb score, which addresses the occupational therapists to follow the changes in the thumb function and its posture. CP-thumb score has two parts: descriptive and score of the thumb’s CMC joint radial abduction. Thirty thumbs in 19 patients with all types of CP were assessed with CP-thumb score. All assessments were made based on available video recordings. Additionally, all thumbs were assessed using the House’s thumb-in-palm classification which has been shown to be unreliable. These two thumb assessments were compared with each other.
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| 2. |
- Bourke, Grainne, 1970-
(author)
-
Magnetic resonance imaging and diffusion tensor imaging after brachial plexus injury and repair : Experimental and clinical study
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- Brachial plexus injuries (BPI) cause permanent upper limb paralysis and serious disability in adults and children. Timely identification of the severity of nerve injury and early appreciation of the inane potential for recovery would revolutionise management. Radiology supports clinical assessment but is not an independent marker of disease severity. Surgical evaluation in severe closed nerve injuries defines the reconstructive potential. This thesis explores aspects of BPI assessment and treatment that remain unsolved. Conventional magnetic resonance imaging (MRI) and novel diffusion tensor imaging (DTI) are evaluated in adults to gain a better understanding of their current diagnostic accuracy in BPI and future value in assessing nerve health. In neonates, this thesis evaluates the preganglionic effects related to timing of injury and repair and socioeconomic factors that influence the incidence and presentation of neonates to specialist centres. These currently controversial factors are important prerequisites to designing and evaluating the optimal objective imaging modality in this age group. Data from 29 high energy trauma BPI patients were analysed. The diagnostic accuracy of 1.5T MRI for BP root avulsion was 79% (Index test MRI, Reference standard Surgery). The negative predictive value was 81% meaning there was one occult avulsion in every 5 cases. DTI data sets from 12 patients with unilateral BPI and seven matched adult controls were acquired. The test was considered positive for root avulsion when there was a visible lack of continuity between tracts in the spinal cord and the brachial plexus. The mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated from a region of interest (ROI) - five 2.5mm2 pixels in the axial plane covering the lateral recess of the vertebral foramen. The overall diagnostic accuracy of DTI for determining root avulsion was 71% (95%CI 54, 85). The fractional anisotropy (FA) of avulsed roots was 10% lower than normal roots (95% [CI 7%,13%] p<0.001). The mean diffusivity (MD) of avulsed roots was 0.32x10-3mm2/s higher than normal intact roots (95%CI 0.11, 0.53; p><0.001). The T1 tracts were not clearly visualised in most BPI cases. The time course comparing survival of motoneurons in a neonatal rat BPI model, was evaluated at 2- 28 days after injury and repair. At day 10, the injury group survival of motoneurons was 22% and at 28 days only 9%of motoneurons remained. In the repair group the surviving neurons were 51% at 10 days and 20% at 28 days. The repair group had significantly reduced reactivity of macrophages and microglial cells in the C5/C6 ventral horn. In analysis (Index of Multiple Deprivation, IMD) of a 13 year, retrospective cohort series of 321 children with Obstetric Brachial Plexus injury (England), 109 (39%) were from the most deprived quintile. In Yorkshire and Humber 44% were from the most deprived quintile. No relationship was identified between severity of condition and IMD. These laboratory and clinical studies in adults, children and neonatal animals align with the real-time clinical conundrum in evaluating the injured nerve’s ability to recover to functional significance. ><0.001). The mean diffusivity (MD) of avulsed roots was 0.32x10-3mm2/s higher than normal intact roots (95%CI 0.11, 0.53;p<0.001). The T1 tracts were not clearly visualised in most BPI cases. The time course comparing survival ofmotoneurons in a neonatal rat BPI model, was evaluated at 2- 28 days after injury and repair. At day 10, the injury group survival of motoneurons was 22% and at 28 days only 9%of motoneurons remained. In the repair group the surviving neurons were 51% at 10 days and 20% at 28 days. The repair group had significantly reduced reactivity of macrophages and microglial cells in the C5/C6 ventral horn. In analysis (Index of Multiple Deprivation, IMD) of a 13 year, retrospective cohort series of 321 children with Obstetric Brachial Plexus injury (England), 109 (39%) were from the most deprived quintile. In Yorkshire and Humber 44% were from the most deprived quintile. No relationship was identified between severity of condition and IMD. These laboratory and clinical studies in adults, children and neonatal animals align with the real-time clinical conundrum in evaluating the injured nerve’s ability to recover to functional significance.
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| 3. |
- Eriksson, Lars, 1966-
(author)
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Att gestalta måltider – mise en place, dukning och servering : En metodstudie i servitörens hantverkskunnande
- 2021
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Doctoral thesis (other academic/artistic)abstract
- I restaurangbranschen har rationaliseringar tvingats fram och kunskap efterfrågas i mindre omfattning. Syftet med avhandlingen är därför att utveckla begrepp och pröva metoder för att återge och förmedla procedurer och göranden i hantverk för att därigenom visa vad som är servitörens yrkeskunskap. Avhandlingen undersöker metoder som fångar hantverkets sinnliga aspekter genom att synliggöra och vetenskapliggöra den dimensionen av ett hantverk. Den ledande frågan är hur servitörens hantverkskunnande för mise en place, dukning och servering kan visualiseras, kommuniceras och förstås?Olika metoder har prövats och forskningen har skett i och genom hantverk med egen restaurangerfarenhet som utgångspunkt. Film som metod har prövats för att vetenskapliggöra betydelsen av hantverkarens sinnliga bedömningar. Metoder från tidsgeografi, som förklarar det materiellas bundenhet till tid och rum, samt från taxonomi för tredimensionell visuell analys, som ger förståelse för gestaltning, har använts.Resultaten visar att hantverkaren oreflekterat tar stöd av sina egna sinnen för att bli effektivare och säkerställa sitt hantverksutförande. Resultaten visar även att de tidsgeografiska begreppen kapacitets-, kopplings- och auktoritetsrestriktioner möjliggör att identifiera och förklara de hinder som servitören tar hänsyn till vid planering och genomförande av en hantverksprocedur. När kunskap om förklaringar länkas samman med kunskap om förståelse, blir det möjligt att beskriva hur gästen i en måltidssituation kan styras och påverkas av estetiken. Genom ett flermetodologiskt tillvägagångssätt har hantverkskunnandet för procedurerna mise en place, dukning och servering artikulerats vetenskapligt i ord och bilder.
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| 4. |
- Moradi, Fatemeh, 1985-
(author)
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Working out work : from personal informatics to redesigning work
- 2016
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Doctoral thesis (other academic/artistic)abstract
- "Personal Informatics" (PI) and "Quantified Self" (QS) are two contemporary notions in the field of Human–Computer Interaction. Such hardware and software systems gather personalized quantified data and visualize them for the purpose of supporting self-reflection. Many of these systems focus on breaking the habit of prolonged sitting and increasing physical activity in our daily lives. The problems associated with the sedentary lifestyle and prolonged hours of sitting have been noted in many studies. In fact, stationary behavior is a risk factor for cardiovascular disease, diabetes and certain types of type of cancer. Nowadays we, as adults, spend more than 8 hours a day on work and work-related activities. As a consequence, the time spent sitting in office workspaces contributes to the majority of stationary behavior in our daily lives. Throughout history, designers and technocrats have constantly redesigned workspaces in attempts to increase work productivity and efficiency. Thus "modern" office work configuration includes desks and stationary computers and so office workers have become accustomed to prolonged sitting in their workplaces. In relation to this research problem, I have worked on my PhD thesis within the context of a four-year cross disciplinary research project in which we have been exploring ways of increasing physical activity and breaking the habit of prolonged sitting among office workers. This is a thesis in informatics and closely allied to medicine and it focuses on studying how contemporary office work affects the body and how to redesign this context. For this thesis, I conducted three empirical studies and designed and developed two prototypes - the "NEAT Lamp" and the "Talking Tree". The "Sport Co." study was the first quantitative study, and was followed by two qualitative observational ethnographic studies – the "Housing Co." study and the "Health Co." study. The research process adopted during the work can be described as an intertwined process consisting of three methodological approaches: observational ethnographic studies, concept development and prototyping. These three came together to form a coherent contextual design process for tackling the research question, "How can we approach the design of work in today's offices in order to make office workers more physically active in their workspaces?" This process resulted in five papers presenting various aspects and results of the research conducted. The results cover the role of bodies at work by considering the history of work design, knowledge about the local movement and mobility patterns of office workers in modern office spaces and eventually the design and evaluation of the two prototypes introduced in this thesis. Finally, I conclude this thesis by highlighting my overall contributions. The first contribution targets designers willing to design for increasing physical activity and breaking the habit of prolonged sitting in workspaces. In relation to this I introduce a design space as a tool for understanding the design of work in relation to worker’s bodies. The second contribution highlights how observational ethnographic studies, concept development, and prototyping can be combined when exploring the context of physical activity in office environments and it shows how contextual design might be a suitable approach for such studies. In addition, it emphasizes ways for how we can redesign work and expand our contextual knowledge. This, by examining and evaluating interactive prototypes in real office settings.
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| 5. |
- Pettersson, Jonas, 1979-
(author)
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Biosynthetic conduits and cell transplantation for neural repair
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Spinal cord injury results in complete failure of the central neurons to regenerate and is associated with cyst formation and enlargement of the trauma zone. In contrast to the spinal cord, axons in the injured peripheral nerve have the capacity to undergo some spontaneous regeneration. However, significant post-traumatic loss of nervous tissue causing long nerve gap is one of the main reasons for the poor restoration of function following microsurgical repair of injured nerves. The present thesis investigates the effects of biodegradable conduits prepared from fibrin glue and poly-beta-hydroxybutyrate (PHB) in combination with cultured Schwann cells, mesenchymal stem cells and extracellular matrix molecules on regeneration after spinal cord and peripheral nerve injury in adult rats. At 4-8 weeks after transplantation into the injured spinal cord, the PHB conduit was well integrated into the cavity but regenerating axons were found mainly outside the PHB. When suspension of BrdU-labeled Schwann cells was added to the PHB, regenerating axons filled the conduit and became associated with the implanted cells. Modification of the PHB surface with extracellular matrix molecules significantly increased Schwann cell attachment and proliferation but did not alter axonal regeneration. To improve the labeling technique of the transplanted cells, the efficacy of fluorescent cell tracers Fast Blue, PKH26, Vibrant DiO and Cell Tracker™ Green CMFDA was evaluated. All tested dyes produced very efficient initial labeling of olfactory ensheathing glial cells in culture. The number of Fast Blue-labeled cells remained largely unchanged during the first 4 weeks whereas the number of cells labeled with other tracers was significantly reduced after 2 weeks. After transplantation into the spinal cord, Fast Blue-labeled glial cells survived for 8 weeks but demonstrated very limited migration from the injection sites. Additional immunostaining with glial and neuronal markers demonstrated transfer of the dye from the transplanted cells to the host tissue. In a sciatic nerve injury model, the extent of axonal regeneration through a 10mm gap bridged with tubular PHB conduit was compared with a fibrin glue conduit. At 2 weeks after injury, the fibrin conduit supported similar axonal regeneration and migration of the host Schwann cells compared with the PHB conduit augmented with a diluted fibrin matrix and GFP-labeled Schwann cells or mesenchymal stem cells. The long-term regenerative response was evaluated using retrograde neuronal labeling. The fibrin glue conduit promoted regeneration of 60% of sensory neurons and 52% of motoneurons when compared with the autologous nerve graft. The total number of myelinated axons in the distal nerve stump in the fibrin conduit group reached 86% of the nerve graft control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89%, respectively. When a fibrin conduit was used to bridge a 20mm sciatic nerve gap, the weight of gastrocnemius muscle reached only 43% of the nerve graft control. The morphology of the muscle showed more chaotic appearance and the mean area and diameter of fast type fibers were significantly worse than those of the corresponding 10mm gap group. In contrast, both gap sizes treated with nerve graft showed similar fiber size. In summary, these results show that a PHB conduit promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal growth after transplantation into the injured spinal cord. The data suggest an advantage of the fibrin conduit for the important initial phase of peripheral nerve regeneration and demonstrate potential of the conduit to promote long-term neuronal regeneration and muscle recovery.
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| 6. |
- Schaakxs, Dominique, 1979-
(author)
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Stem cells for nerve repair and prevention of muscle atrophy
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Peripheral nerve injury (PNI) is common and despite modern microsurgical techniques of repair, functional restoration is always incomplete. This results in impaired sensation and reduced motor function alongside pain and cold intolerance. Traumatic PNI are often associated with loss of nerve tissue, creating a gap, and direct repair of the two damaged nerve stumps is not possible. These types of injuries are reconstructed using autologous nerve grafts but this is far from ideal since it necessitates the sacrifice of a functional nerve from elsewhere in the body. Chronic muscle atrophy because of the prolonged delay in nerve regeneration across gaps is a significant impediment to an optimal functional recovery. Tissue engineering and regenerative medicine approaches to nerve repair might one day replace the need for autologous nerve grafts. This thesis investigates the effects of adipose derived stem cells (ASC) on nerve regeneration and muscle recovery by using the stem cells for intramuscular injection and combined with a biomaterial, poly-3-hydroxybutyrate (PHB), to create a bioengineered artificial nerve repair construct. The mechanisms of interaction between the stem cells and neuromuscular system cells were investigated and with a view to translating this work into clinical practice, an optimal source of cells was investigated from human donors. It was hypothesized that injecting regenerative cells into muscle would reduce nerve injury induced muscle atrophy. A rat sciatic nerve lesion was performed and three different types of cells were injected into the denervated gastrocnemius muscle; either (1) undifferentiated ASC, (2) ASC induced to a ‘Schwann cell-like’ phenotype (dASC) or (3) primary Schwann cells. Nerves were either repaired by direct end-end suture or capped to prevent muscle reinnervation. One month later, functionality was measured using a walking track test, and muscle atrophy was assessed by examining muscle weight and histology. The Schwann cells and dASC groups showed significantly better scores on functional tests when compared with control injections of growth medium alone. Muscle weight and histology were also significantly improved in the cell groups in comparison with the control group. PHB strips seeded with either primary Schwann cells or dASC suspended in a fibrin glue matrix were used to bridge a 10mm rat sciatic nerve gap. After 12 weeks, functional and morphological analysis (walking track test, electromyography, muscle weight and muscle and nerve histology) was performed. The results showed significantly better functional results for the PHB strips seeded with cells versus the control group with fibrin matrix only. This correlated with less muscle atrophy and greater distal axon myelination in the cell groups. To further optimize the nerve regeneration and muscle recovery, the nerve gap lesion was repaired by treatment with the bioengineered constructs seeded with dASC or nerve autograft in combination with stem cell injection in the muscle. After 6 weeks, the best results were obtained in the nerve graft group combined with intramuscular dASC injection which showed significantly less atrophy than the other groups. The results also showed that using the stem cells in a matrix on a PHB strip in combination with intramuscular injections could significantly reduce muscle atrophy. In vitro experiments showed that dASC expressed a wide range of neurotrophic and myogenic factors including BDNF, VEGF-A, IGF-1 and HGF. Stem cell conditioned medium enhanced the proliferation of myoblast cell lines and primary Schwann cells. Various signaling pathways (PKA, MAP kinase) were involved in these effects dependent on the cell type investigated. Furthermore, in direct co-culture with myoblast cells, a small population of the cells fused together to form myotube-like structures and expressed myogenic markers. Human ASC were isolated from the deep and superficial layers of abdominal fat tissue obtained during abdominoplasty procedures. Cells from the superficial layer proliferated significantly faster than those from the deep layer. Superficial layer ASC induced significantly enhanced neurite outgrowth from neuronal cell lines when compared with the deep layer cells. However, RT-PCR and ELISA analysis showed that ASC isolated from both layers expressed similar levels of the neurotrophic factors NGF, BDNF and GDNF. In summary, these results show that stem cell therapy at both levels (the nerve lesion site and in the target denervated muscle) offers a promising approach for clinical application for treatment of peripheral nerve lesions. The bioengineered artificial nerve construct, combining PHB strip with cells, also provides a beneficial environment for nerve regeneration. Many of the benefits of the ASC are likely to be mediated through their secretome, a rich source of neurotrophic and myogenic factors. Thus adipose tissue contains a pool of regenerative stem cells which have significant potential application to tissue engineering and regenerative medicine for nerve repair.
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| 7. |
- Abdipour, Morteza, 1977-
(author)
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Arrangement Design Studies : the introduction of the digital wall in domestic environments
- 2021
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Licentiate thesis (other academic/artistic)abstract
- This research focuses on the emergence of 'digital walls' that can project images onto almost all or even the entirety of interior (and perhaps exterior) walls, and what implications this might have for how we arrange our rooms. It demonstrates the arrangement, i.e., the way that domestic products are arranged physically, of rooms changes in the domestic environment in a complex scenario when using large screens. Due to the fast-growing demand for large screens, this product could potentially be available to be used by people in their home environments; however, it does not yet exist in reality at this scale. Constructing large screens can be carried out using different production methods. Here, this concept is called the digital wall, a very thin wall-sized interactive screen. The characteristics of the digital wall will vary to be able to create different scenarios. One such scenario is a space in the home where the surface of the wall is covered with screens, which allows multiple possibilities to experience and interact with digital content. In this research, the social gathering space of homes, nowadays called the living room, is considered as a highly relevant space for installing the digital wall. In this space, the conceptual framework outlines the basic elements of the research and demonstrates the relationships between people’s interactions with the digital wall and domestic products in the domestic environment. I show two examples from design history to understand how arrangement changes impact the home environment: the transformation of the parlor to the living room, and entry of the television into the living room. These two examples are focused on the place in the home where people gather for socializing. The discussion of these examples led to the elaboration of the relationships between the elements in the conceptual framework.I explored relevant design research methodologies to bring this future scenario into the present to understand the relationships between people and the digital wall. I applied research through design and the constructive design research approaches to frame the design research methodology. In this thesis, I set up seven series of design studies in two cluster groups: Supportive studies and Main studies. All of the design studies were conducted in the Design Research Lab, the actual space for carrying out the design experiments, prototyping the digital wall, and the setting of the experiments for user participation. The Lab was fully equipped with relevant technology and allowed me to use multiple methods to collect data while people were experiencing the design study sessions. The Lab was useful as a platform to understand user experiences, barriers for interactions as well as people's experiences in a simulated space of a domestic environment. The main contribution of this research is to understand the forms of arrangement changes when people use the digital wall in homes. The research demonstrates two significant implications that are seen in two forms of arrangements: tangible arrangement and imperceptible arrangement. These findings are useful for both designers and users of the elements of domestic contexts and the relations that can be shaped by the presence of a digital wall in home environments. This understanding may provide design guidelines in future scenarios in which the digital wall is used in homes. The findings are also beneficial for designing the domestic environment, improving the arrangement of space, and raising the requirements for designing domestic products.
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| 8. |
- Brohlin, Maria
(author)
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Mesenchymal stem cells for repair of the peripheral and central nervous system
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Bone marrow-derived mesenchymal stem cells (MSC) have been shown to provide neuroprotection after transplantation into the injured nervous system. The present thesis investigates whether adult human and rat MSC differentiated along a Schwann cell lineage could increase their expression of neurotrophic factors and promote regeneration after transplantation into the injured peripheral nerve and spinal cord. Human and rat mesenchymal stem cells (hMSC and rMSC) expressed characteristic stem cell surface markers, mRNA transcripts for different neurotrophic factors and demonstrated multi-lineage differentiation potential. Following treatment with a cocktail of growth factors, the hMSC and rMSC expressed typical Schwann cells markers at both the transcriptional and translational level and significantly increased production of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Age and time in culture are of relevance for clinical settings and growth-promoting effects of hMSC from young donors (16-18 years) and old donors (67-75 years) were compared. Undifferentiated hMSC from both young and old donors increased total neurite length of cultured dorsal root ganglion (DRG) neurons. Differentiation of hMSC from the young donors, but not the eldery donors, further enhanced the neurite outgrowth. Undifferentiated hMSC were cultured for eleven weeks in order to examine the effect of in vitro expansion time on neurite outgrowth. hMSC from the young donors maintained their proliferation rate and their ability to enhance neurite outgrowth from DRG neurons. Using a sciatic nerve injury model, a 10mm gap was bridged with either an empty tubular fibrin glue conduit, or conduits containing hMSC, with and without cyclosporine treatment. Cells were labeled with PKH26 prior to transplantation. At 3 weeks after injury the conduits with cells and immunosuppression increased regeneration compared with an empty conduit. PKH26 labeled human cells survived in the rat model and the inflammatory reaction could be suppressed by cyclosporine. After cervical C4 hemisection, BrdU/GFP-labeled rMSC were injected into the lateral funiculus rostral and caudal to the spinal cord lesion site. Spinal cords were analyzed 2-8 weeks after transplantation. Transplanted MSC remained at the injection sites and in the trauma zone for several weeks and were often associated with numerous neurofilament-positive axons. Transplanted rMSC induced up-regulation of vascular endothelial growth factor in spinal cord tissue rostral to the injury site, but did not affect expression of brain-derived neurotrophic factor. Although rMSC provided neuroprotection for rubrospinal neurons and significantly attenuated astroglial and microglial reaction, cell transplantation caused aberrant sprouting of calcitonin gene-related peptide immunostained sensory axons in the dorsal horn. In summary these results demonstrate that both rat and human MSC can be differentiated towards the glial cell lineage, and show functional characteristics similar to Schwann cells. hMSC from the young donors represent a more favorable source for neurotransplantation since they maintain proliferation rate and preserve their growth-promoting effects in long-term cultures. The data also suggest that differentiated MSC increase expression of neurotrophic factors and support regeneration after peripheral nerve and spinal cord injury.
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| 9. |
- Jegers, Kalle, 1978-
(author)
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Pervasive GameFlow : Identifying and Exploring the Mechanisms of Player Enjoyment in Pervasive Games
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Pervasive games are computer games that build, to various extents, on social interaction as a driving force in the game play, on integration between physical and virtual worlds and on constant access to constantly ongoing games from virtually every existing context (anytime, anywhere gaming). This new genre of computer games presents many challenges for both researchers and industry; one of the most important is how to understand enjoyable player experiences in this new kind of computer gaming. The purpose of this thesis is to identify and explore the mechanisms in pervasive game designs that are of most importance for creating enjoyable Pervasive gaming experiences, and further to translate the findings of the exploration into a playability model for pervasive games. My empirical work focuses on the most important aspects for creating enjoyable player experiences when playing pervasive games. Evaluation methods from the usability and playability area have been deployed in order to identify what factors and aspects the players consider of most importance for their experience when they play pervasive games. Three specific pervasive games have been studied; SupaFly, Pervasive Treasure Hunt and Furiae. Theoretically, the thesis departs from existing knowledge about Playability, and the most prominent and accepted frameworks for understanding player experiences in computer gaming have been considered. Of the existing models and frameworks, the GameFlow model was selected as a theoretical point of departure. The main contribution of the thesis consists of a model for understanding player enjoyment in pervasive games - the Pervasive GameFlow model. Pervasive GameFlow elaborates the GameFlow model by adding 14 new criteria identified in the empirical evaluations of three pervasive games, criteria of great importance for enjoyable Player experiences in pervasive games. Further, the thesis answers questions concerning how the players are putting the anytime, anywhere and mobility aspects of pervasive games into practice - how they perceive and handle games that offer constantly ongoing game play. The results also provide insights into the reach or impact of the novel Pervasive aspects of pervasive games and their importance for the players and player experiences. Finally, the thesis provides notes on how evaluation of pervasive games should be performed.
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| 10. |
- Karalija, Amar, 1984-
(author)
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Diagnostic and therapeutic strategies following spinal cord and brachial plexus injuries
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Traumatic injuries to the spinal cord and brachial plexus induce a significant inflammatory response in the nervous tissue with progressive degeneration of neurons and glial cells, and cause considerable physical and mental suffering in affected patients. This thesis investigates the effects of the antioxidants N-acetyl-cysteine (NAC) and acetyl-L- carnitine (ALC) on the survival of motoneurons in the brainstem and spinal cord, the expression of pro-apoptotic and pro-inflammatory cell markers, axonal sprouting and glial cell reactions after spinal hemisection in adult rats. In addition, a novel MRI protocol has been developed to analyse the extent of neuronal degeneration in the spinal cord. Rubrospinal neurons and tibial motoneurons were pre-labelled with the fluorescent tracer Fast Blue one week before cervical C3 or lumbar L5 spinal cord hemisection. The intrathecal treatment with the antioxidants NAC (2.4mg/day) or ALC (0.9 mg/day) was initiated immediately after injury using Alzet2002 osmotic mini pumps. Spinal cord injury increased the expression of apoptotic cell markers BAX and caspase 3, induced significant degeneration of rubrospinal neurons and spinal motoneurons with associated decrease in immunoreactivity for microtubule-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker glial fibrillary acidic protein and microglial markers OX42 and ED1 was markedly increased. Treatment with NAC and ALC attenuated levels of BAX, caspase 3, OX42 and ED1 expression after 2 weeks postoperatively. After 4-8 weeks of continuous intratheca ltreatment, NAC and ALC rescued approximately half of the rubrospinal neurons and spinal motoneurons destined to die, promoted axonal sprouting, restored the density of MAP2 and synaptophysin immunoreactivity and reduced the microglial reaction. However, antioxidant therapy did not affect the reactive astrocytes in the trauma zone. The inflammation modulating properties of ALC were also studied using cultures of human microglial cells. ALC increased the microglial production of interleukin IL-6 and BDNF, thereby possibly mediating the anti-inflammatory and pro-regenerative effects shown in vivo. To study degeneration in the spinal cord following pre-ganglionic and post-ganglionic brachial plexus injuries, adult rat models of ventral root avulsion and peripheral nerve injury were used. A novel MRI protocol was employed and the images were compared to morphological changes found in histological preparations. Ventral root avulsion caused degeneration of dendritic branches and axonal terminals in the spinal cord, followed by significant shrinkage of the ventral horn. Extensive astroglial and microglial reactions were detected in the histological preparations. Peripheral nerve injury reduced the density of dendritic branches but did not cause shrinkage of the ventral horn. Quantitative analysis of MRI images demonstrated changes in the ventral horn following ventral root avulsion only, thus validating the developed MRI technique as a possible tool for the differentiation of pre-ganglionic and post-ganglionic nerve injuries.
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