Indiana University-Purdue University Indianapolis (IUPUI) / Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease. Many researchers believe that an effective AD treatment will prevent the development of disease rather than treat the disease after a diagnosis. Therefore, the development of tools to detect AD-related pathology in early stages is an important goal. In this report, MRI-based markers of neurodegeneration are explored as biomarkers of AD. In the first chapter, the sensitivity of cross-sectional MRI biomarkers to neurodegenerative changes is evaluated in AD patients and in patients with a diagnosis of mild cognitive impairment (MCI), a prodromal stage of AD. The results in Chapter 1 suggest that cross-sectional MRI biomarkers effectively measure neurodegeneration in AD and MCI patients and are sensitive to atrophic changes in patients who convert from MCI to AD up to 1 year before clinical conversion. Chapter 2 investigates longitudinal MRI-based measures of neurodegeneration as biomarkers of AD. In Chapter 2a, measures of brain atrophy rate in a cohort of AD and MCI patients are evaluated; whereas in Chapter 2b, these measures are assessed in a pre-MCI stage, namely older adults with cognitive complaints (CC) but no significant deficits. The results from Chapter 2 suggest that dynamic MRI-based measures of neurodegeneration are sensitive biomarkers for measuring progressive atrophy associated with the development of AD. In the final chapter, a novel biomarker for AD, visual contrast sensitivity, was evaluated. The results demonstrated contrast sensitivity impairments in AD and MCI patients, as well as slightly in CC participants. Impaired contrast sensitivity was also shown to be significantly associated with known markers of AD, including cognitive impairments and temporal lobe atrophy on MRI-based measures. The results of Chapter 3 support contrast sensitivity as a potential novel biomarker for AD and suggest that future studies are warranted. Overall, the results of this report support MRI-based measures of neurodegeneration as effective biomarkers for AD, even in early clinical and preclinical disease stages. Future therapeutic trials may consider utilizing these measures to evaluate potential treatment efficacy and mechanism of action, as well as for sample enrichment with patients most likely to rapidly progress towards AD.

Alzheimer's disease (AD) is an increasing problem in modern society, both with regards to public health and cost of care. The causes of AD are not yet fully understood, and there is no cure or inhibiting drug. The aim of this thesis is to investigate the association between the bile acid profile as an indicator of dysbiosis and AD and mild cognitive impairment (MCI) using machine learning algorithms. The hypothesis that bile acid data can be used to predict AD or MCI at the time of diagnosis has been tested, and could not be confirmed. Somewhat better test results were obtained for the transition from normal cognitive function to MCI and from MCI to AD over time. Limitations relevant for this study included the possible uncertainties in the diagnostic patient data as well as in the relationship between bile acids and dysbiosis. The results from transitions in patient's diagnosis could warrant further research on the relationship between the bile acid profile or dysbiosis and changes in cognitive function. We suggest such research is conducted with more sophisticated models. / Alzheimers sjukdom (AD) är ett viktigt och ökande problem i dagens samhälle, både vad gäller folkhälsan och kostnaderna för samhället. Orsakerna bakom AD är än idag inte helt utredda och det finns inget botemedel eller bromsmedicin. Målet med den här studien är att undersöka sambandet mellan gallsyraprofilen som en indikator på dysbios och AD och mild kognitiv störning (MCI) med hjälp av maskininlärningsalgoritmer. Hypotesen att gallsyraprofilen kan användas för att förutsäga AD eller MCI vid diagnostillfället har studerats och kunde inte fastställas. Något bättre resultat erhölls vad gäller övergången från normal kognitiv funktion till MCI och från MCI till AD över tid. Begränsningar som är relavanta för studien inkluderar möjlig osäkerhet vad gäller diagnosen och även vad gäller sambandet mellan gallsyraprofilen och dysbios. Resultaten från förändringen i patienters diagnos kan vara en grund för fortsatt forskning om samband mellan gallsyraprofilen eller dysbios och förändringar i kognitiv funktion. Vi föreslår att mer sofistikerade modeller används för sådan forskning.

High-Pressure Partial Oxidation (HP-POX) of natural gas is one of the techniques in the synthesis gas production by non-catalytic reforming. On the path to emissions reduction, all operating facilities must be optimized to satisfy environmental regulations. In a rapidly changing economic and political environment, technological development from lab-scale to demo-scale, and industrial-scale is no longer feasible. Therefore, new research and design methods must be applied. One of such methods commonly used in science and industry is numerical modeling, which utilizes Computational Fluid Dynamics (CFD), Reduce Order Models (ROMs), kinetic, and equilibrium models. The CFD models provide details about flow field, temperature distribution, and species conversion. However, the computational effort required to conduct such calculations is significant. The computationally expensive CFD models cannot be effectively used in the reactor optimization. Herewith, other modeling techniques utilizing kinetic and equilibrium models do not provide necessary details for process optimization and can only be used for adjustments of boundary conditions, investigation of specific processes occurring in the reactor, or development of sub-models for CFD. A numerical investigation was conducted to validate existing CFD models against benchmark experiments. The results reveled that the CFD model is sensitive to modeling parameters, when simulating complex flows where turbulence-chemistry interaction occurs. Moreover, it was shown that the results sensitivity increases along with the oxidizer/fuel inlet velocities ratio. Based on the conducted experiments, the CFD model validation resulted in definition of the modeling parameters suitable for modeling of HP-POX of natural gas. Based on the validated CFD model, a ROM for HP-POX of natural gas was developed. The model assumes that the reactor consists of several zones characterized by specific conversion processes. Moreover, the model considers inlet streams dissipation upon the injection, and includes several optimization stages that allows model adjustments for any reactor geometry and boundary conditions. It was shown that the developed ROM can reproduce global reactor characteristics at non-equilibrium conditions unlike other ROMs, kinetic, or equilibrium models. Moreover, the validation against CFD results showed that the ROM can correctly account for the \gls{rtd} in the reactors of different geometries and volumes without extensive additional optimization. Finally, new experiments were designed and conduced at semi-industrial HP-POX facility at TU Bergakademie Freiberg. The experiments aimed to study the influence of different oxidizer/fuel velocities ratios on the reactants mixing and process characteristics at high operating pressures. The high velocity difference between oxidizer and fuel was achieved by injection of High-Velocity Oxidizer (HVO). The experiments showed no significant influence of the HVO on the global reactor characteristics and overall species conversion process. However, the numerical analysis of the experimental results demonstrated that the oxidation zone is affected by the oxidizer inlet velocity, and becomes less efficient in the fuel conversion when the oxidizer/fuel inlet velocities ratio is increased. In summary, a sophisticated numerical model validation was conducted and sensitivity of the numerical results to the modeling parameters was carefully studied. The novel natural gas conversion technique was experimentally studied. Based on the conducted experiments and numerical evaluation a ROM was developed. The ROM is capable of producing high accuracy results and greatly decreases the computational effort and time needed for reactor development and optimization.

No description available.

This thesis focuses on service utilisation among children with mild ID and their families, their needs for support and their experiences of support. Aims The overall aim of the thesis was to explore and describe service utilisation patterns among families of children with mild ID from a systems perspective. Methods A cross-sectional, descriptive and comparative quantitative design was used to describe the extent of service utilisation among 84 children with mild ID and their families (paper I and II). The types and number of services utilised were investigated in relation to the child’s age, gender and school setting. Data concerning the services utilised were collected from the organisational records of social services and paediatric habilitation units. In paper III, a descriptive questionnaire design was used to describe the support needs of families of 38 children with mild ID. A confirmatory design was used to examine the relation between family needs for support and (a) parental self-efficacy and (b) parents’ control over services. A confirmatory design was also used to examine the relation between parents’ experiences of the helpfulness of the support and (a) parental self-efficacy and (b) parents’ control over services. In paper IV a longitudinal, comparative and confirmatory design was used to investigate whether social service utilisation patterns differ over time when children with mild ID in self-contained classes are compared with those integrated into mainstream classes (n=405). Results In total, 60% of the families utilised paediatric habilitation services, and 40% of the families used disability-related services provided by social services. The most commonly utilised services were services concerned support outside of the home, such as respite care and services to improve children’s participation in society. Approximately 25% of the families utilised social problems-related services provided by social services. The most commonly utilised services concerned those to support parents in their parenting roles and financial assistance. In contrast to older children, younger children were more likely to utilise paediatric habilitation services. Older children utilised a higher number of disability-related service types provided by social services. Few differences were found between males and females. The majority of families did not utilise such services that are provided by social services. It was rare for families to use both disability-related services and those that address social problems during the same year. Commonly reported family needs concerned information about what services are available for their child, their child's impairment, how to respond to their child's behaviour and how to teach their child skills. Other common needs included access to parent support networks, to find suitable leisure activities for the child, and more alone time for parents. In contrast to families with mothers who did not participate in paid work, families with mothers who were employed expressed a lower requirement for support such as counselling, contact with other parents of children with impairments, more friends and more alone time for parents. Similar results werefound for families with mothers with higher levels of education. Parents with higher levels of perceived self-efficacy reported a lower need for information, as did also parents with higher levels of control over services. Parents with higher levels of control over services experienced the support as being more helpful. Children with mild ID who attended self-contained classes were more likely to utilise paediatric habilitation services than children integrated in mainstream classes. The same pattern was found for utilisation of disability-related services provided by social services. Integrated children who changed school setting to attend self-contained classes were more likely to begin to utilise disability-related services in comparison with those children who continued to be integrated. The former also had a higher likelihood of increasing the number of disability-related service types utilised. Conclusions In addition to disability-related problems, families of children with mild ID may also be at a higher risk of experiencing social problems when compared with the general population. Furthermore, very few families utilised both disability-related services and services addressing social problems. This implies that collaboration flaws exist between those professionals concerned with child welfare services and those concerned with disability-related services. A strong predictor of service utilisation was the type of school setting: children attending self-contained classes had a higher rate of service utilisation than those attending mainstream classes. This indicates that service systems outside of school are designed to collaborate with groups of pupils in special classes rather than individual children in mainstream classes. The strong need for information by families indicates that an ecological framework should be used to identify those factors that affect information availability and effectiveness. To increase parents’ perceived level of control over services, HSO professionals need to work in a capacity building manner with the explicit goal to enhance parental self-efficacy.

The population of China is ageing. Accompanying this aging population, dementia and frailty have a growing importance. However there is little consensus on the association between dementia and frailty, in terms of how the criteria that are part of this two syndromes overlap, as both disorders are age-related and increase the risk for falls, further leading to loss of independence. To meet the above needs, the thesis describes research into different frailty diagnostic criteria, as well as its association with dementia symptoms. We examined cognitive measures that can be used for assessment of Mild Cognitive Impairment (MCI) and dementia screening (the Hopkins Verbal Learning Test, HVLT) and compared its discriminant ability with the commonly used cognitive screening tool, the Mini-Mental State Examination (MMSE) in distinguishing Cognitive Impairment (including MCI and dementia) from No Cognitive Impairment (NCI, normal controls) in two community-dwelling elderly Chinese populations and in one institutionalised elderly population in Shanghai, China. Subsequently we investigated whether physical and cognitive symptoms clustered together to form frailty phenotypes. We employed indicators that have been widely used to diagnose frailty, including physical measures (grip strength, Time-Up and Go test, 15 feet gait speed test and Berg balance test), and psychological measures (the HVLT and the MMSE) to predict cognitive impairment (CI) and frailty. Additionally, we described demographics (age, gender, education) and other potential modifiers when detecting cognitive impairment and functional disability. We then built up a model for possible frailty phenotype using various indicators. Lastly, we examined whether demographic (age, gender, education and profession), and lifestyle (smoking/alcohol history, exercise frequency, and dietary habit) could be used to predict future cognitive impairment. It was found that advanced age, lower education (no or primary level), and being vegetarian were significant risk factors for cognitive impairment. Furthermore, whereas high consumption of green vegetables is a protector against cognitive impairment, high intake of tofu was negatively related to cognitive performance among community-dwelling elderly in China. To meet the above needs, the thesis describes research into different frailty diagnostic criteria, as well as its association with dementia symptoms. We examined cognitive measures that can be used for assessment of Mild Cognitive Impairment (MCI) and dementia screening (the Hopkins Verbal Learning Test, HVLT) and compared its discriminant ability with the commonly used cognitive screening tool, the Mini-Mental State Examination (MMSE) in distinguishing Cognitive Impairment (including MCI and dementia) from No Cognitive Impairment (NCI, normal controls) in two community-dwelling elderly Chinese populations and in one institutionalised elderly population in Shanghai, China. Subsequently we employed these two cognitive measures to investigate whether they were part of the frailty syndrome among elderly from the community-based studies. We investigated whether physical and cognitive symptoms clustered together to form frailty phenotypes. We employed indicators that have been widely used to diagnose frailty, including physical measures (grip strength, Time-Up and Go test, 15 feet gait speed test and Berg balance test), and psychological measures (the HVLT and the MMSE) to predict cognitive impairment (CI). We found four distinct subtypes of elderly characterised by increasing care needs: 1. Persona elderly as defined by age >78, year of education<6 years, grip strength <11.8 KG, and a MMSE total score <25; 2. Persona Physical frailty (fitness), defined by a total score on the Timed-Up and Go (TUG) test >12.7 seconds and 15 feet gait speed >4.4 seconds; 3. Persona Cognitive impairment, defined by a MMSE total score <25, a HVLT Immediate Recall (IR) score <15, and a HVLT Delayed Recall (DR) <5; 4. Persona Physical frailty (balance,) defined by a Berg Balance test score of <53. Additionally, we described demographics (age, gender, education) and other potential modifiers when detecting cognitive impairment and functional disability. We then built up a model for possible frailty phenotype using various indicators, Frailty here was defined as: 1. Low BMI as measured by this algorithm: BMI= Weight (kg)/Height (m)2 2. Weakness (upper and lower body): grip strength in the lowest quintile, adjusted for gender; and TUG get up with assistance or unable to get up 3. Slowness (lower body): TUG score in the lowest quintile, adjusted for gender; and 15 feet gait speed in the lowest quintile, adjusted for gender; 4. Poor balance: Berg Balance test score in the lowest quintile, adjusted for gender; 5. Low physical activity: engaging in exercise less than once per week. An individual with 4 or more present frailty components out of a total of 7 was considered to be frail , whereas equal or less than 3 characteristics were hypothesized to be pre-frail . Those with no present frailty components were considered as robust. Lastly, we examined whether demographic (age, gender, education and profession), and lifestyle (smoking/alcohol history, exercise frequency, and dietary habit) could be used to predict future cognitive impairment (as defined by a HVLT IR score of ≤19). The results of our studies show that compared to the MMSE, the HVLT is superior in differentiating MCI and dementia from NCI, and is also less affected by demographic factors in detecting frailty. Furthermore, in the current study, physical, psychological, demographic and other modifiable risk factors cluster together into different phenotypes of cognitive impairment and functional disability in these cohorts. A phenotype of frailty is built up using BMI, grip strength, TUG, 15 feet gait speed, balance and exercise frequency as indicators. The most common was the elderly phenotype followed by the cognitively impaired. A novel finding of the current study is that only 4.8% (8 out 168) of the whole sample fulfilled all three categories in the current study (cognitive impairment, functional disability and frailty). Finally, advanced age, lower education (no or primary level), and being vegetarian were significant risk factors for cognitive impairment. Furthermore, whereas high consumption of green vegetables is a protector against cognitive impairment, high intake of tofu was negatively related to cognitive performance among community-dwelling elderly in China.

Tidigare studier har visat att individer med lindrig intellektuell funktionsnedsättning uppvisar en generellt lägre läsförmåga än individer med typisk utveckling. Vad detta bottnar i är oklart men mycket forskning tyder på att språkliga förmågor har en inverkan på läsförmågan. Föreliggande studie syftar till att undersöka eventuella samband mellan läsförmåga och språkliga förmågor hos barn och unga vuxna med lindrig intellektuell funktionsnedsättning i åldrarna 12 till 25 år.  De språkliga förmågor som undersöktes var fonologisk medvetenhet, snabb benämning (RAN), ordförråd, grammatisk förståelse samt språkförståelse. Testningarna genomfördes på deltagarnas respektive skolor utspridda i mellersta och södra Sverige. Råpoängen från respektive test användes i korrelations- och regressionsanalys för att kartlägga eventuella samband. I studien medverkade totalt 27 barn och unga vuxna i åldrarna 13;06–25;09 år. Resultaten visar att RAN och fonologisk medvetenhet har starka signifikanta samband med avkodning som helhet vilka tillsammans förklarar 72,3 % av variansen. Läsförståelse har starka signifikanta samband med fonologisk medvetenhet, grammatisk förståelse, avkodning som helhet och språkförståelse, där avkodning som helhet, språkförståelse och ordförråd förklarar 62,4 % av variansen. Ortografisk avkodning uppvisar ett starkare samband med läsförståelse än fonologisk avkodning. Resultaten i studien överensstämmer med tidigare forskning som menar att fonologisk medvetenhet och RAN är av vikt för alla typer av avkodning och att avkodning i sig påverkar läsförståelsen hos individer med såväl typisk utveckling som med lindrig intellektuell funktionsnedsättning. Däremot går resultaten i föreliggande studie emot tidigare forskning som inte kunnat visa att ordförrådet har signifikant påverkan på läsförståelsen hos individer med lindrig intellektuell funktionsnedsättning. Sammanfattningsvis visar resultaten av föreliggande studie att flertalet språkliga förmågor kan förklara variansen av såväl de olika typerna av avkodning som läsförståelse. Resultatet kan bidra till ökad kunskap kring bakomliggande faktorer till den nedsatta läsförmåga som observeras hos individer med lindrig intellektuell funktionsnedsättning. Resultaten tyder dock på att vidare forskning behövs för att fastställa vilka övriga faktorer som kan förklara resterande varians samt att stärka fynden i föreliggande studie. / Previous studies have shown that individuals exhibiting mild intellectual disability show a lower reading ability than individuals with typical development. The reasons behind these differences are unclear. However, research shows that specific language abilities affect reading ability. The present study aims to investigate any possible correlations between language ability and reading ability in young people with mild intellectual disability, aged 12 to 25 years. The examined linguistic abilities were phonological awareness, rapid automatized naming (RAN), vocabulary, grammatical comprehension and language comprehension. Testing was held at the participants’ schools in various parts of central and southern Sweden. The raw scores were used in correlation and regression analyses to map out any correlations. A total of 27 participants with ages ranging between 13;06 years and 25;09 years were included in the study. The results showed that RAN and phonological awareness had strong significant correlations to decoding and that they together can account for 72.3 % of its variance. Reading comprehension showed strong significant correlations to phonological awareness, grammatical comprehension, decoding, and language comprehension. Language comprehension and vocabulary explained 62.4 % of the variance in reading comprehension. Word decoding showed a stronger correlation to reading comprehension than phonological decoding. The results of the present study are in large parts compatible with previous research, which supports the findings that phonological awareness and RAN are of importance to decoding ability, and that decoding in turn has an impact on reading comprehension in individuals with both typical development and intellectual disability. However, the results in the present study are at odds with previous research, which has not found significant correlations between vocabulary and reading comprehension in individuals with mild intellectual disability. In summation, results of the present study show that a number of linguistic abilities can explain the variance of both decoding and reading comprehension. Hopes are that the results from the present study can contribute to furthering knowledge of the underlying factors which explain why individuals with mild intellectual disabilities generally are poor readers. More research is needed to confirm which other factors can explain the remaining variance and to strengthen the results of the present study.

Tidigare forskning har funnit samband mellan gång och kognitiv funktion, men sambandet mellan lindrig kognitiv svikt (MCI) och gång är inte helt klarlagt. Syftet med den föreliggande examensuppsatsen var således att undersöka hur gångvariabler och gångvariabilitet är påverkat hos personer med MCI i relation till kognitivt friska individer. Studien genomfördes i det pågående projektet the Healthy Ageing Initiative vid Umeå Universitet. Totalt 1937 personer inkluderades i studien. Samtliga var 70 år gamla och bosatta i Umeå kommun. Totalt 112 personer bedömdes ha MCI utifrån instrumentet Mini-Mental State Examination (MMSE). Gånganalys genomfördes med den elektroniska gångmattan GAITRite® system och deltagarna utförde fyra gångförsök: egenvald hastighet, snabb hastighet, kognitiv dual task och motorisk dual task. Resultatet visade att det finns skillnader mellan grupper vad gäller både spatiala och temporala aspekter, främst i de tre första försöken. Exempelvis uppvisade gruppen MCI lägre gånghastighet, kortare steg och kliv samt längre double support och kortare swing. Gruppen MCI uppvisade högre variabilitet under kognitiv dual task. Ett flertal gång- och variabilitets-variabler under kognitiv dual task kunde, enligt logistisk regression, predicera sannolikheten att ha MCI. Resultaten indikerar att gången hos de med MCI kan ge ökad fallrisk. / Previous research has found a connection between gait and cognitive function. However, the relationship between mild cognitive impairment (MCI) and gait has not been fully explored. Thus, the aim of this study was to examine how spatiotemporal gait parameters, and gait variability, are affected in people with MCI compared to cognitively healthy individuals (CHI). The study was carried out in cooperation with the Healthy Ageing Initiative research project, Umeå University, Sweden. A total of 1937 participants were included in the study. All participants were 70-years old and residents of the municipality Umeå. A total of 112 participants were classified as having MCI, as measured with the Mini-Mental State Examination (MMSE). Gait analysis was performed with the GAITRite® system, and participants performed four trials: preferred pace, fast pace, cognitive dual task and motor dual task. Results showed group differences in both spatial and temporal aspects of gait, especially during the first three trials. For example, participants with MCI walked more slowly, had shorter steps and strides, as well as a longer duration of the double support phase and lower duration of the swing phase. Participants with MCI revealed higher gait variability during cognitive dual task. Several of these variability variables, as well as spatiotemporal variables, could predict probability of having MCI, as seen through logistic regression. Results indicate that the gait observed in MCI could be related to a higher risk of falling.

La prévalence des troubles du sommeil et de douleur chronique est élevée chez le patient ayant subi un traumatisme crânien cérébral léger (TCCL). L’interaction entre ces plaintes est suggérée chez les patients avec un TCCL mais son étiologie reste encore peu connue. Les résultats de recherche présentés dans le premier article de cette thèse suggèrent que les patients avec un TCCL qui souffrent de douleur ont une modification des ondes cérébrales durant leur sommeil, ce qui pourrait expliquer en partie comment les deux symptômes interagissent. De plus, la douleur, surtout si associée à des troubles de l’humeur, semble jouer un rôle majeur dans la persistance des symptômes post-commotionnels. Le deuxième article de cette thèse décrit une exacerbation des symptômes post-commotionnels chez le patient ayant eu un TCCL et souffrant de douleur. La persistance ou l’apparition de la douleur chronique à long terme serait prédite par le polymorphisme val66met du gène brain-derived neurotrophic factor (BDNF). Une étude subséquente, présentée dans le troisième article, nous a permis d’approfondir les bases génétiques et cellulaires du rôle du BDNF dans la persistance des symptômes post-commotionnels. Des polymorphismes fréquents dans le gène BDNF ont révélé des variantes liées au mauvais pronostic suite à un TCCL. De plus, l’analyse de cellules extraites de patients ayant subi un TCCL démontrent que l’expression de la protéine BDNF peut être modifiée chez le patient de génotype met66 et ayant subi un TCCL, lui conférant ainsi un rôle neuroprotecteur potentiel. En résumé, nous avons tenté de démontrer dans cette thèse que la douleur suite à un TCCL joue un rôle important dans les perturbations du sommeil et dans la persistance des symptômes post-commotionnels. Une prédisposition génétique pourrait contribuer à expliquer le mauvais pronostic et la chronicité des symptômes post-commotionnels suite à un TCCL. / Mild traumatic brain injury (MTBI) is a major public health concern as patients are left, amongst other symptoms, with sleep complaints and chronic pain. An interaction between these symptoms is suggested. For instance, a night of poor sleep is usually followed by hypersensitivity to pain and chronic pain always leads to sleep complaints. This interaction is suggested following an MTBI, however, data sustaining that hypothesis are still lacking. Data from the first article suggest that pain and other post-concussion symptoms are correlated with sleep-wake disturbances post-MTBI. MTBI patients with pain have more rapid electroencephalographic (EEG) waves during sleep than those without pain. This may suggest that there is an intrinsic physiological relationship between the two complaints. Moreover, pain seems to play an important role in the persistence of post-concussive symptoms. The second article of this thesis describes and details the exacerbation of post-concussive symptoms in the presence of pain following MTBI. The val66met polymorphism in the Brain-derived neurotrophic factor (BDNF) gene is an important predisposing factor for chronic pain. Lastly, a subsequent study, presented in the third article details the genetic and cellular basis of the role of BDNF in the persistence of post-concussive symptoms. Common polymorphisms in the BDNF genes were genotyped and revealed variants related to post-concussive symptoms following MTBI. Moreover, protein expression studies in lymphoblast cells of MTBI patients showed a modified expression of BDNF with the met genotype that might be neuroprotective. In summary, this thesis first shows that pain contributes to sleep-wake disturbances following MTBI and that the chronicity of post-concussive symptoms, including chronic pain, may be dependent on polymorphisms in the BDNF gene.

A mild gasification method has been developed to provide an innovative clean coal technology. The objective of this study is to developed a numerical model to investigate the thermal-flow and gasification process inside a specially designed fluidized-bed mild gasifier using the commercial CFD solver ANSYS/FLUENT. Eulerain-Eulerian method is employed to calculate both the primary phase (air) and secondary phase (coal particles). The Navier-Stokes equations and seven species transport equations are solved with three heterogeneous (gas-solid), two homogeneous (gas-gas) global gasification reactions. Development of the model starts from simulating single-phase turbulent flow and heat transfer to understand the thermal-flow behavior followed by five global gasification reactions, progressively with adding one equation at a time. Finally, the particles are introduced with heterogeneous reactions. The simulation model has been successfully developed. The results are reasonable but require future experimental data for verification.