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Potential Neurophysiological Biomarkers for the Diagnosis of Age-related Neurodegenerative DiseasesMarková, Veronika January 2020 (has links)
The global population with dementia is rapidly increasing around the world.The major risk factor for dementia is aging. There is currently no treatmentavailable and the cost of symptomatic treatment is high. There is a growinginterest in possible clinical applications of non-invasive methods that are safeand easy-to-perform in diagnosis of dementia. The purpose of this paper is toinvestigate the usage of transcranial magnetic stimulation (TMS) withelectroencephalography (EEG) to diagnose dementia in early stages of thedisease. Early diagnosis is needed to reduce the costs of symptomatic care.When investigating the usage of TMS-EEG technology, we will look at how wecan distinguish dementia in different neurodegenerative diseases between eachother. More research is needed to suggest an accurate parameters fordiagnosis of dementia with this type of technology.
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Utility of High-Definition Fiber Tractography and Eye-Tracking for Measuring Outcome in Chronic Mild Traumatic Brain InjuryLindsey, Hannah M. 03 August 2020 (has links)
A complete understanding of the functional and structural impairments driving persistent post-concussive symptom (PCS) expression in approximately one-third of those who suffer from mild traumatic brain injury (mTBI) is essential for the development of effective treatment strategies and improving quality of life. While traditional outcome measures, such as neuropsychological testing and structural magnetic resonance imaging, are sensitive to the severe functional impairments and widespread tissue damage frequently seen after moderate-to-severe injuries, more advanced measures that are sensitive to the subtle changes in cognitive function and tissue microstructure that may underlie persistent PCS are necessary for the assessment of recovery from mTBI. Toward this end, the current study investigates the utility of eye-tracking analysis and high-definition fiber tractography (HDFT) as advanced measures of functional and microstructural outcome in 11 adults with chronic mTBI and varying levels of PCS (ages 20-60; mean time post-injury = 9.53 ± 6.74 years) in comparison to 10 healthy adults (ages 20-54). Performance on neuropsychological and eye-tracking tasks of processing speed, attention, and working memory, and HDFT-derived quantitative measures of the microstructural integrity of the forceps major, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, and superior longitudinal fasciculus were compared between groups, and the results were used to define discriminatory functions for mTBI classification. The relationships between neuropsychological and eye-tracking measures of cognitive function and HDFT-derived measures of tract integrity were explored, as was the utility of these functional and structural measures for predicting persistent PCS in chronic mTBI. The results suggest that eye-tracking analysis may be more specific to cognitive impairments resulting from mTBI than neuropsychological testing, and HDFT is highly sensitive and specific to the subtle microstructural changes that persist chronically in this population. Furthermore, white matter integrity assessed using HDFT is more strongly associated with impairments in processing speed, attention, and memory indicated through eye-tracking analysis relative to performance on neuropsychological tests. Finally, although the predictive utility of eye-tracking and HDFT for the experience of persistent PCS was not demonstrated in the present sample, the possibility that these data are confounded by symptom exaggeration, comorbid mental health impairment, or lack of self-awareness for functional deficits cannot be ruled out, and future research using large, homogenous sample of mTBI is necessary to validate the present findings.
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Mírná léčebná hypotermie a oxidativní stres po srdeční zástavě / Mild therapeutical hypothermia and oxidative stress after cardiac arrestKrüger, Andreas January 2016 (has links)
Successfull cardiopulmonary resuscitation is an essential life-saving tool; nevertheless, general ischemia during cardiac arrest may trigger different pathways that could turn even into a fatal damage; this condition is called post-cardiac arrest syndrome. It has been repeatedly shown that oxidative stress (OS) plays one of the key roles in the development of ischemia-reperfusion injury. However, current evidence on the possible participation of OS in the pathogenesis of post-cardiac arrest syndrome is insufficient. We tested following hypotheses: (i) ischaemia-reperfusion injury after cardiac arrest is accompanied by OS and (ii) mild therapeutical hypothermia decreases OS cardiac arrest. In the experimental part of our work we studied the effects of hypothermia and normothermia on hemodynamic parameters, markers of organ damage and on the OS burden in porcine model of cardiac arrest. Furthermore, we compared the effects of hypothermia with ischaemic postconditioning and nitric oxide administration in the porcine model of extracorporeal cardiopulmonary resuscitation. We found protective effects of hypothermia on all major endpoints including OS in comparison with normothermia; moreover, hypothermia improved also selected variables compared to ischemic postconditioning and nitric oxide. In the...
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THE USE OF ALTERNATIVE NORMALIZATION APPROACHES TO UNDERSTAND CHANGES IN SARS-CoV-2 CONCENTRATIONS IN WASTEWATERIsaksson, Frida January 2022 (has links)
Following the detection of SARS-CoV-2 RNA fragments in wastewater in March 2020, the use of wastewater-based epidemiology is rapidly emerging as a non-invasive approach to assessing community wide COVID-19 prevalence. Wastewater-based epidemiology is promoted as a complement to clinical testing in terms of improving public health authorities’ preparedness and supporting them in taking required interventions to protect the public health. To utilize the occurrence of SARS-CoV-2 in wastewater in a public health context and evaluate trends in viral prevalence on a community level, robust data interpretation is required. This master's thesis work examines what is currently known about the factors that influence the concentrations of SARS-CoV-2 in wastewater, as well as the impact of alternative normalization approaches on the relationship between viral wastewater data and clinical case numbers. The work is divided into two parts where this report provides a state-of-the-art review as well as an overview of key findings in the accompanied scientific paper. The study involved collection of wastewater samples from two different sized wastewater treatment plants (WWTPs) in Luleå municipality, between January and March 2021. Concentrations of SARS-CoV-2 RNA were quantified in each sample as well as concentrations of total nitrogen (TN), total phosphorus (TP) and pepper mild mottle virus (PMMoV). Average daily WWTP flow and environmental data (precipitation and temperature) were continuously measured over the sampling period. The population size was estimated based on mass loads of TN and TP and literature values of the domestic contribution of these parameters to the sewer system. The viral wastewater data was normalized using the estimations of population size, census data, WWTP flow and PMMoV. The impact of the alternative normalization approaches was evaluated using statistical analyses to explore the relationship to clinical case numbers. The result showed that the strength of the correlation between the different normalization approaches and clinical case data differed between the WWTPs. However, within each WWTP the differences in correlation between the different normalization approaches and clinical cases were not significant. Moreover, normalization using WWTP flow (i.e., viral loads) showed a stronger correlation to clinical cases compared to population and PMMoV normalized viral loads. However, when comparing wastewater data between the two catchment areas, the normalization approaches utilizing population (either census or TN and TP estimated population) or PMMoV better reflect the number of clinical cases. Additionally, according to time-shifted analysis, wastewater data of SARS-CoV-2 RNA predated an increase in clinical cases by 0-2 and 5-8 days, respectively, for the larger and smaller WWTPs.
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Experimental and numerical investigation of fuel flexibility and pollutant emissions in novel combustion technologies using renewable synthetic fuelsFerrarotti, Marco 07 September 2020 (has links) (PDF)
By 2050, Europe needs to have drastically decoupled its economic growth from its emissions of CO2. This is a direct response to the compelling evidence from the increasing risks of climate change brought about by the anthropogenic Greenhouse Gas (GHG) emissions and pollutant emissions (NOx). A replacement of significant percent of fossil fuels with renewable energy sources will be needed. However, energy production from most renewable energy sources, is typically intermittent and unpredictable. This requires a reliable mid-long term energy storage to synchronize production and demand. The Power-to-Fuel option or chemical storage can be the key for a sustainable energy system. Indeed, converting the excess of renewable energy into second generation fuels will unlock a long-term and high-density energy storage, ensuring also a reduction of the carbon footprint. These ”green” non-conventional fuels are blends of CH4, H2, CO and NH3. However, to achieve Power-to fuel, the development of an efficient combustion technology, coupled with virtually zero pollutant emissions, stable working conditions with different load and fuel and significant energy saving is required. In the last years, a so-called MILD or flameless combustion has drawn attention for its ability of meeting the mentioned targets. However, the studies available in literature are conducted on Jet in hot co-flow-like systems or they face conventional fuels, such as natural gas or methane. The examples using non-conventional fuels are scarce and limited to few operating conditions. In this framework, this PhD thesis focuses on a threefold aspect. Experimental campaigns investigated fuel flexibility of flameless combustion in the ULB furnace. A progressive addition of hydrogen in methane enhanced combustion features, reducing the ignition delay time and increasing the reactivity of the system, possibly losing its flameless behavior. Indeed, a threshold of 25% H2 was defined for reaching flameless/MILD conditions, characterized by still low pollutant emissions and temperature peak. This is in line with the goal of introducing “green” hydrogen into the natural gas pipeline (up to 20%) to reduce CO2 emissions. Further experimental campaigns tested the role of the injection geometry (varying the air injector ID) and fuel lance length to reduce NO emissions and retrieve flameless/MILD conditions for high hydrogen content. Finally, ammonia/hydrogen blends were tested. Results suggests that stoichiometry has a major impact on NO emissions. An optimal window, minimizing both NO and NH3-slip emissions was defined using an equivalence ratio of 0.9. To qualitatively describe the observed trends, a simplified reactors network was considered. The analysis highlighted the most important reactions correlated to NO formation and the reason of the NO reduction at stoichiometry condition. On the other side an affordable and reliable numerical model was optimized and tested in the Adelaide Jet in Hot Co-flow burner. The latter is a simplified burner capable of mimicking MILD combustion conditions. A set of RANS simulations were run using the Partially Stirred Reactor (PaSR) approach, investigating different mixing model formulations: a static, a fractal-based and a dynamic formulation, based on the resolution of transport equations for scalar variance and dissipation rate. A study about the role of combustion models and kinetic mechanisms on the prediction of NO formation was also conducted. Finally, an analysis of the choice of a Heat Release Rate (HRR) marker for MILD (HM1 flame) and not MILD (HM3 flame) conditions was carried out. Once having awareness of the capability of the proposed numerical model, simulations were conducted to define the key aspects in simulating a flameless furnace, varying the composition of the fuel, considering methane/hydrogen and ammonia/hydrogen blends. In particular, for the latter case, existing kinetic schemes showed a major over-estimation of NO emissions, reason why an optimization study was conducted in a simplified reactor (well stirred reactor) using a Latin Hypercube Sampling. Finally, the first-of-its-kind digital twin based on CFD simulations for a furnace operating in flameless combustion conditions was created. A reduced- order model (ROM) based on the combination of Proper Orthogonal Decomposition (POD) and Kriging was developed for the prediction of spatial fields (i.e. temperature) as well as pollutant in the exhausts. / D’ici 2050, l’Europe devra découpler sa croissance économique de ses émissions de CO2. Il s’agit d’une réponse nécessaire au changement climatique et à la pollution de l’air induits par les émissions atmosphérique de gaz à effet de serre (GES) et de polluants (NOx). Un remplacement d’un pourcentage significatif des combustibles fossiles par des sources d’énergie renouvelables sera nécessaire. Cependant, la production d’énergie à partir des sources renouvelables est généralement intermittente et imprévisible. Cela nécessite un stockage d’énergie fiable à moyen et long terme, pour synchroniser la production et la demande d’énergie. L’option Power-to-Fuel, ou stockage chimique, peut être la clé d’un système énergétique durable. En effet, la conversion de l’excès d’énergie renouvelable en carburants de deuxième génération permettra de débloquer un stockage d’énergie à long terme et à haute densité, en assurant également une réduction de l’empreinte carbone. Ces carburants non conventionnels « verts » sont des mélanges de CH4, H2, CO et NH3. Cependant, pour exploiter le potentiel du Power-to-Fuel, il est nécessaire de développer une technologie de combustion efficace, avec des émissions de polluants pratiquement nulles, assurant des conditions de travail stables avec une charge et des carburants différents et des économies d’énergie significatives. Au cours des dernières années, une combustion dite « MILD », ou sans flamme, a attiré l’attention pour sa capacité à atteindre les objectifs mentionnés. Cependant, les études disponibles dans la littérature sont menées sur des systèmes de laboratoire (jet in hot co-flow) et avec des carburants conventionnels comme le gaz naturel ou le méthane. Les exemples utilisant des carburants non conventionnels sont rares et limités à quelques conditions de fonctionnement.Dans ce cadre, cette thèse de doctorat se concentre sur un triple aspect.Des campagnes expérimentales ont étudié la flexibilité du combustible dans un four sans flamme installé à l'ULB. L’ajout progressif d’hydrogène dans le méthane permet d’améliorer les caractéristiques de combustion, en réduisant le délai d’allumage et augmentant la réactivité du système, ce qui, par contre, cause un éloignement du système des conditions sans flamme. En effet, un seuil supérieur de 25% H2 a été identifié pour les mélanges méthane/hydrogène, pour travailler dans des conditions sans flammes (MILD), caractérisées par une faible augmentation de température et des émissions de polluants amoindries .Cela est conforme à l’objectif d’introduire de l’hydrogène « vert » dans le gazoduc (jusqu’à 20%) afin de réduire les émissions de CO2. D’autres campagnes expérimentales se sont focalisées sur le rôle de la géométrie d’injection (variation du diamètre de l’injecteur d’air) et de la longueur de la lance du carburant pour réduire les émissions des oxydes d’azote et récupérer les conditions sans flamme/MILD pour une teneur élevée en hydrogène. Enfin, des mélanges ammoniac/hydrogène ont été testés. Les résultats suggèrent que la stœchiométrie a un impact majeur sur les émissions d’oxydes d’azote. Une fenêtre optimale minimisant les émissions de NO et d’ammoniac imbrulées a été définie en utilisant un rapport d'équivalence de 0,9. Pour tracer qualitativement les tendances observées, un réseau de réacteurs simplifié a été construit. L’analyse a mis en évidence les réactions les plus importantes pour la formation des NOx et elle a permis de justifier la réduction des oxydes d’azote à l’état stœchiométrique.De l’autre côté, un modèle numérique robuste et fiable a été optimisé et testé pour le brûleur Jet in Hot Co-flow de l’Université d’Adelaide. Ce dernier est un brûleur simplifié capable de simuler les conditions de combustion MILD/sans flamme. Un ensemble de simulations RANS ont été effectuées à l’aide de l’approche du réacteur partiellement agité (Partially Stirred Reactor – PaSR - en anglais), en examinant les différentes formulations de modèles de mélange :une formulation statique, fractale et dynamique, basée sur la résolution des équations de transfert pour la variance scalaire et le taux de dissipation. Une étude sur le rôle des modèles de combustion et des mécanismes cinétiques dans la prédiction de la formation des oxydes d’azote a également été réalisée. Enfin, une analyse sur le choix d’un marqueur de taux de dégagement de chaleur (Heat Release Rate – HRR – en anglais) pour les conditions MILD et non MILD a été réalisée. Après validation, les modèles développés ont été utilisés pour définir les aspects clés de la simulation d’un four sans flamme, en variant la composition du combustible, pour des mélanges méthane/hydrogène et ammoniac/hydrogène. En particulier, pour ce dernier cas, les schémas cinétiques existants ont montré une surestimation importante des émissions d’oxydes d’azote, raison pour laquelle une étude d’optimisation a été menée dans un réacteur simplifié.Enfin, le premier jumeau numérique en son genre, basé sur des Simulations numériques de Dynamique de Fluides (CFD – Computational Fluid Dynamics en anglais) pour un four fonctionnant dans des conditions de combustion sans flamme, a été créé. Un modèle à ordre réduit (ROM – Reduced Order Model en anglais) basé sur la combinaison de la Décomposition Orthogonale aux valeurs Propres (POD) et du Kriging a été développé pour la prédiction des variables d’intérêt (température et espèces chimiques majeures) ainsi que des polluants dans les fumées. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished
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The Effect of Explicit Timing on Math Performance Using Interspersal Assignments with Students with Mild/Moderate DisabilitiesHou, Fangjuan 01 May 2010 (has links)
Explicit timing and interspersal assignments have been validated as effective methods to facilitate students' math practice. However, no researchers have explored the combinative effect of these two methods. In Study 1, we extended the literature by comparing the effect of explicit timing with interspersal assignments, and interspersal assignments without timing. Generally, participants' rate of digits correct on easy and hard addition problems was higher during the explicit timing condition than during the untimed condition. However, the participants' rate of digits correct decreased after initial implementation of the explicit timing condition.
Motivation plays a crucial role in maintaining performance levels and helping students make continuous progress. Preferred reinforcers and setting academic targets have been widely utilized as active motivational components to increase the likelihood of a successful strategy in school settings. In Study 2, we employed a brief MSWO reinforcer assessment to identify individual student's low- and high-preference reinforcers and examined the effects of explicit timing on interspersed assignments combined with high preference or low preference reinforcers, and setting academic targets. In general, explicit timing combined with preferred reinforcers and academic targets produced a more sustainable effect on participants' rate of digits correct than explicit timing alone. In addition, high-preference reinforcers were more effective than low-preference reinforcers for three of five participants. For two participants, an increasing trend was observed when low preference reinforcers were contingent on meeting academic targets. These results are discussed relative to using preference assessments with students with mild/moderate disabilities.
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The COMT p.Val158Met Polymorphism and Cognitive Performance in Adult Development, Healthy Aging and Mild Cognitive ImpairmentDegen, Christina, Zschocke, Johannes, Toro, Pablo, Sattler, Christine, Wahl, Hans-Werner, Schönknecht, Peter, Schröder, Johannes 10 August 2022 (has links)
Background: The impact of genetic polymorphisms on cognition is assumed to increase with
age as losses of brain resources have to be compensated for. We investigate the relation of
catechol-O-methyltransferase (COMT) p.Val158Met polymorphism and cognitive capacity in
the course of adult development, healthy aging and the development of mild cognitive impairment
(MCI) in two birth cohorts of subjects born between 1930 and 1932 or between 1950
and 1952. Methods: Thorough neuropsychological assessment was conducted in a total of
587 participants across three examination waves between 1993 and 2008. The COMT genotype
was determined as a restriction fragment length polymorphism after PCR amplification
and digestion with Nla III. Results: Significant effects of the COMT p.Val158Met polymorphism
were identified for attention and cognitive flexibility in the younger but not the older cohort.
Conclusion: These results confirm the importance of the COMT p.Val158Met genotype on
tasks assessing attention and cognitive flexibility in midlife but not in healthy aging and the
development of MCI. Our findings suggest that the influence of COMT changes as a function
of age, decreasing from midlife to aging.
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Body mass index and polygenic risk predict conversion to Alzheimer’s diseaseMoody, Jena N. 04 October 2021 (has links)
No description available.
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Jugular venous reflux and brain parenchyma volumes in elderly patients with mild cognitive impairment and Alzheimer's diseaseBeggs, Clive B., Chung, C.P., Bergsland, N., Wang, P.N., Shepherd, Simon J., Cheng, C.Y., Dwyer, Michael G., Hu, H.H., Zivadinov, R. January 2013 (has links)
Yes / To determine whether or not jugular venous reflux (JVR) is associated with structural brain parenchyma changes in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). 16 AD patients (mean (SD): 81.9 (5.8) years), 33 MCI patients (mean (SD): 81.4 (6.1) years) and 18 healthy elderly controls (mean (SD): 81.5 (3.4) years) underwent duplex ultrasonography and magnetic resonance imaging scans to quantify structural brain parenchyma changes. Normalized whole brain (WB), gray matter (GM) and white matter (WM) volumes were collected, together with CSF volume. JVR was strongly associated with increased normalized WB (p = 0.014) and GM (p = 0.002) volumes across all three subject groups. There was a trend towards increased WB and GM volumes, which was accompanied by decreased CSF volume, in the JVR-positive subjects in both the MCI and AD groups. When the MCI and AD subjects were aggregated together significant increases were observed in both normalized WB (p = 0.009) and GM (p = 0.003) volumes for the JVR-positive group. No corresponding increases were observed for the JVR-positive subjects in the control group. Through receiver operating characteristic analysis of the brain volumetric data it was possible to discriminate between the JVR-positive and negative AD subjects with reasonable accuracy (sensitivity = 71.4%; specificity = 88.9%; p = 0.007). JVR is associated with intracranial structural changes in MCI and AD patients, which result in increased WB and GM volumes. The neuropathology of this unexpected and counterintuitive finding requires further investigation, but may suggest that JVR retrogradely transmits venous hypertension into the brain and leads to brain tissues swelling due to vasogenic edema.
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Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL TrialCheng, Wenke, Fuernau, Georg, Desch, Steffen, Freund, Anne, Feistritzer, Hans-Josef, Pöss, Janine, Buettner, Petra, Thiele, Holger 05 December 2023 (has links)
Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels
reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating
acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little
is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in
patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the
effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized
mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating
AMI were enrolled and assigned to MTH (33 ◦C) for 24 h or normothermia at a 1:1 ratio. Blood
samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3.
Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed.
Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was
analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results:
There were differences in MCP-1 levels over time between patients in MTH and normothermia groups
(P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group
(day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL;
p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range,
87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of
therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of
all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling
phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI
compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming.
Trial registration: NCT01890317.
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