The purpose of the study was to provide training to peer tutors to teach students with mild and moderate disabilities sales tax computation using a simultaneous prompting procedure with fidelity. Non-target information presented during training sessions and generalization to natural environment settings was assessed. A multiple probe (days) across participants design was used to evaluate the effectiveness of the intervention on the dependent variables. The results showed peer tutors could use the simultaneous prompting procedure with fidelity to teach sales tax computation and students with disabilities could acquire sales tax computation. The students acquired the non-target information presented and generalization occurred in a natural setting.

The aim of the research presented in this thesis was to improve the characterisation of the changes in brain structure and function that occur at different stages of Alzheimer’s disease (AD) progression, from pre-symptomatic AD, to mild cognitive impairment (MCI), to clinically evident dementia, using magnetic resonance imaging (MRI) techniques. Baseline structural MRI data from a cohort of healthy older adults who were followed prospectively for ten years, during which time some developed MCI and some AD, were analysed. It was found that structural MRI could detect volume loss in medial-temporal lobes up to 7-10 years before clinical symptoms of AD appear. In addition, volumetric variability of medial-temporal regions detected by structural MRI across cognitively healthy older adults correlated with their performance on a task of visuospatial associative memory, and functional activation of the same regions occurred during successful performance of the same task on functional MRI (fMRI). Three groups of participants - cognitively healthy controls, people with MCI, and patients with probable AD - were then recruited and underwent a multimodal MRI protocol, which included functional sequences acquired at rest and during the execution of two different cognitive tasks (visuospatial associative memory and self-appraisal). Cross-sectional comparisons showed: (i) that successful visuospatial associative memory performance was associated with increased functional activity (measured with task fMRI) in lateral prefrontal regions in AD patients relative to controls and (ii) that increased functional activity overlapped with frontal brain networks showing increased functional connectivity (measured with resting fMRI) in the same AD patients. Further, by demonstrating group- and condition-specific decreased frontal activity in AD patients relative to controls during a self-appraisal fMRI task, it was shown the specific utility of fMRI to unravel cognitive mechanisms underlying specific neuropsychological symptoms such as unawareness of cognitive impairment (anosognosia) in MCI and AD. In conclusion, structural MRI can detect morphological changes in the preclinical stage of AD, possibly earlier than previously described, and these reliably match cognitive functioning in older adults. In the MCI and AD stages, once symptoms of cognitive impairment are clinically evident and measurable, task-related and resting functional MRI can inform on residual brain function detectable over and above the known changes in brain morphology and cognitive performance that have already occurred at these stages, emerging as a sensitive marker of residual ability that could potentially be used to measure the effect of new treatments.

Depressive symptoms are very common among people with neurocognitive disorder. The comorbidity of both diseases and the overlap of their symptoms complicates correct diagnosis and thus also the initiation of a correct treatment. The instruments of depression measuring in seniors with a severe cognitive deficit are also a discussed issue. The subject of the theoretical part is to describe the issue of depression and cognitive disorders in the old age with a focus on Alzheimer's disease, which is the most common mental disorder in the elderly together with depression. The goal of the empirical part of the thesis is to research based on the interviews with seniors if the most frequently used method of depression measuring in the elderly, Geriatric Depression Scale (GDS), is a suitable measuring instrument also in seniors with a cognitive deficit and further examine how these seniors actually experience the individual mood qualities which are the subjects of items in GDS. Forty seniors with a various degree of cognitive deficit participated in the research. The study results showed that the questionnaire is usable for seniors with a mild cognitive impairment and mild dementia. To detect the border of the cognitive deficit, below which it is not suitable to use the depression measuring method GDS, a...

National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structural- functional alterations of excitatory and inhibitory systems in the neocortex.

Alzheimer's disease (AD) is neurodegenerative disorder that causes memory loss and cognitive dysfunction. It affects one in five people over the age of 80 and is distressing for both sufferers and their families. A transitional stage between normal ageing and dementia including AD is termed a mild cognitive impairment (MCI). Recent studies have shown that people with MCI may convert to AD over time although not all MCI cases progress to AD. Much research is now focussing on early detection of AD and diagnosing an MCI that will progress to AD to allow prompt treatment and disease management before the neurons degenerate to a stage beyond repair. Hence, the ability to obtain a method of identifying MCI is of great importance. Virtual reality plays an important role in healthcare and offers opportunities for detection of MCI. There are various studies that have focused on detection of early AD using virtual environments, although results remain limited. One significant drawback of these studies has been their limited capacity to incorporate levels of difficulty to challenge users' capability. Furthermore, at best, these studies have only been able to discriminate between early AD and healthy elderly with about 80% of overall accuracy. As a result, a novel virtual simulation called Virtual Reality for Early Detection of Alzheimer's Disease (VREAD) was developed. VREAD is a quick, easy and friendly tool that aims to investigate cognitive functioning in a group of healthy elderly participants and those with MCI. It focuses on the task of following a route, since Topographical Disorientation (TD) is common in AD. An investigation was set up with two cohorts: non-elderly and elderly participants. The findings with regard to the non-elderly are important as they represent a first step towards implementation with elderly people. The results with elderly participants indicate that this simulation based assessment could provide a method for the detection of MCI since significant correlations between the virtual simulation and existing neuropsychological tests were found. In addition, the results proved that VREAD is comparable with well-known neuropsychological tests, such as Cambridge Neuropsychological Automated Test Battery, Paired Associate Learning (CANTAB PAL) and Graded Naming Test (GNT). Furthermore, analysis through the use of machine learning techniques with regard to the prediction of MCI also obtained encouraging results. This novel simulation was able to predict with about 90% overall accuracy using weighting function proposed to discriminate between MCI and healthy elderly.

A mild gasification method has been developed to provide an innovative clean coal technology. The objectives of this study are to (a) incorporate a fixed rate devolatilization model into the existing 2D multiphase reaction model, (b) expand the 2D model to 3D and (c) utilize the improved model to investigate the mild-gasification process and guide modification of the mild-gasifier design. The Eulerain-Eulerian method is employed to calculate both the primary phase (air) and secondary phase (coal particles). The improved 3D simulation model, incorporated with a devolatilization model, has been successfully developed and employed to determine the appropriate draft tube dimensions, entrained flow residence time, The simulations also help determine the appropriate operating fluidization velocity range to sustain the fluidized bed depth without depleting the chars or blowing the char away. The results are informative, but require future experimental data for verification.

The incidence of mild blast traumatic brain injuryhas risen due tothe increased use of improvised explosive devices (IEDs) in militaryconflicts. Mild blast TBI (mbTBI) is especially relevant due to its lack of acutely observable symptoms, and to its association with long-term neurodegenerative and neuropsychiatric disorders. Predominantly, TBI patients often suffer from chronic stress, neuropathic pain and headaches, which greatly compromise the health and quality of life of these individuals. Treatments for neuropathic pain have been empirically found and produce little effect in lessening neuropathic pain, likely due to the lack of targeted therapies. This highlights the need for better understanding of the molecular mechanisms underlying neuropathicpain, TBI and chronic stress that could lead to mechanistic therapeutic targets. Oxidative stress is an important mechanism of the pathophysiology of neuropathic pain, TBI and chronic stress. We hypothesize that acrolein, an endogenously formed neurotoxin, is able to stay active in the body for up to 10 days, is involved in the pathophysiology of neuropathic pain in TBI and chronic stress. This study aims to correlate acrolein elevation in the body with neuropathic pain, deepen the understanding of underlying mechanisms of pain in TBI and chronic stress, and mitigate this pain with acrolein scavenging. The ultimate goal of this research is to provide therapies for TBI and chronic stress patients that can eliminate pain and significantly improve their healthand quality of life

As intervenções cognitivas voltadas a idosos saudáveis ainda encontram-se pouco estudadas na literatura nacional, apesar de terem sido investigadas em outros países. O treino de memória oferecido a idosos com Comprometimento Cognitivo Leve (CCL) tem recebido cada vez mais atenção de pesquisadores e parece também beneficiar esta população. Não se sabe se o treino tem efeito a longo prazo e nem se os benefícios são os mesmos para idosos saudáveis e com CCL. Esta pesquisa teve como intuito avaliar o impacto do treino de memória de oito sessões oferecido a idosos controles normais (CN) e com CCL com alta escolaridade em parâmetros cognitivos. Para isso, contamos com a participação de 61 idosos acompanhados pela equipe multidisciplinar do Laboratório de Neurociências LIM 27 do Instituto de Psiquiatria da FMUSP aleatoriamente divididos em grupo experimental - GE (sendo 17 CN e 18 com CCL) e grupo controle - GC (sendo 12 CN e 14 com CCL). Estes grupos foram avaliados em quatro momentos diferentes, a saber, antes da intervenção (T0), uma semana após o término da intervenção (T1), um mês após a última avaliação (T2) e seis meses após T1 (T3). O GE recebeu treino de memória com ênfase na categorização e grifos entre T0 e T1. O GC realizou todas as avaliações no mesmo tempo de GE, mas o treino foi lhes oferecido depois de T3. Observou-se melhora em ambos os grupos GE de T0 para T1 quando comparados ao grupo GC em testes de atenção, velocidade de processamento, estratégias mnemônicas, e em testes de memória. Estes efeitos parecem se manter a curto e a longo prazo, mostrando, de maneiras diferentes, os benefícios do treino e a existência de plasticidade cognitiva em ambas as populações estudadas / The cognitive interventions aimed at elderly healthy are little studied in the national literature, despite having been investigated in other countries. The memory training offered to seniors with mild cognitive impairment (MCI) has received increasing attention from researchers and also seems to benefit this population. It is not known whether the training has long-term effect, nor whether the benefits are the same for healthy elderly and MCI. This study was aimed to evaluate the impact of eight memory training sessions offered to elderly normal controls (NC) and seniors with MCI in cognitive parameters. For this, we had the participation of 61 older people accompanied by a multidisciplinary team of the Laboratory of Neurosciences LIM 27, Institute of Psychiatry, FMUSP randomly divided into experimental group - EG (including 17 NC and 18 with MCI) and control group - CG (being 12 NC and 14 with MCI). These groups were evaluated at four different times, namely before the intervention (T0), one week after the intervention (T1), one month after the last assessment (T2) and six months after T1 (T3). EG received memory training with emphasis on categorization and underline words between T0 and T1. The CG performed all the assessments at the same time EG, but the training was offered to them after T3. Improvement was observed in both groups EG from T0 to T1 when compared to the CG on tests of attention, processing speed, mnemonic strategies, and memory tests. These effects seem to keep the short and long term, showing, in different ways, the benefits of training and the existence of cognitive plasticity in both populations studied

Introdução: Déficits de memória episódica constituem o marcador cognitivo mais frequente em pacientes com Comprometimento Cognitivo Leve (CCL).Estudos prévios mostram que déficits de memória episódica podem ser minimizados nestes pacientes por intervenções comportamentais. Entretanto, os mecanismos cerebrais envolvidos nos efeitos do treino cognitivo ainda são pouco explorados. O objetivo deste estudo foi avaliar o correlato neural por ressonância magnética funcional de um treino breve de memória em pacientes com CCL e compará-los com os achados em idosos saudáveis. Foram avaliados 18 pacientes com CCL e 19 idosos controles com a utilização de ressonância magnética funcional (RMf) em uma tarefa de codificação de listas de palavras com diferentes graus de relação semântica antes e após uma sessão de treino de estratégias de memória. Na sessão pré-treino, os participantes foram instruídos a memorizar as palavras durante a sessão de RMf sem qualquer orientação sobre o uso de estratégias de codificação. Após um treino breve no qual estratégias específicas de organização e agrupamento semântico foram exercitadas, os sujeitos foram reconduzidos ao aparelho de ressonância magnética e realizaram a sessão pós-treino, na qual foram instruídos a utilizar a estratégia treinada durante o paradigma de codificação de palavras. Os resultados dos exames de ressonância magnética funcional foram processados e analisados com o programa FSL versão 4.1. Ambos os grupos apresentaram aumento no número de palavras evocadas associado ao uso da estratégia treinada. Em ambos os grupos foi observado um aumento do sinal BOLD após o treino em regiões do córtex pré-frontal dorsolateral esquerdo e do córtex parietal bilateral. No grupo de idosos controles, entretanto, foi observada também uma redução da ativação em regiões do córtex parietal posterior esquerdo e cíngulo posterior bilateral, do córtex pré-frontal medial e cíngulo anterior direitos, do lóbulo parietal inferior e do córtex temporal superior direitos, do córtex pré-frontal dorsolateral direiro e do córtex óribito-frontal bilateral. A interação grupo x tempo foi significativa em áreas do córtex pré-frontal dorsolateral e ventromedial direitos. Estes resultado indicam que existem diferenças no recrutamento de regiões pré-frontais em resposta ao uso de estratégias de codificação em paradigmas de codificação de palavras entre pacientes com CCL e idosos cognitivamente saudáveis / The present studyinvestigated the effects of different applicationsof verbal learning strategies duringepisodicmemory encoding in patients with Mild Cognitive Impairment (MCI) (n=18) and normal controls (n=17) using functional magnetic resonance imaging (fMRI).The main goal of this study was to verify whether externally guided increases in verbal learning strategy application during episodic memory encoding modulate brain activity in memory-related networks in the same level in MCI as in controls. Participantswerescanned twice, using a word-list encoding fMRI paradigm.In the first session, self-initiated encoding strategies were used to intentionally memorize words during encoding. In the second session, participants received an explicit instruction to apply a semantic organization strategy (i.e. semantic clustering)to perform the task. The fMRI word list learning paradigm consisted of alternating blocks of encoding and resting baseline conditions. To perform the spontaneous fMRI session, participants were not instructed about the semantic organization of the words in the lists beforehand or given any practice with related lists. Therefore, any grouping by category observed in the subsequent free recall at the end of this fMRI acquisition was presumed to be self-initiated by the subject. At the end of the spontaneous session, each subject received a brief period of guidance or instructions to apply semantic strategies and organize words in terms of semantic categories during encoding, using a new set of word lists. Immediately after practicing the application of the strategy, participants were scanned again using the same type of paradigm as in the first session, except for the use of new set of word lists and the explicit instruction to apply semantic clustering.Free recall and strategic index scores were assessedafter each session. fMRI brain activation and deactivation during encoding of word lists in memory-related networks were examined across sessions. Results from the fMRI analysis revealed that after the explicit orientation to apply the verbal learning strategy, greater recruitment of frontoparietal network regions were observed in both MCI and control groups in relation to the unconstrained encoding condition. Group-differences in functional deactivations, however, were observed in the medial prefrontal (mPFC) cortex and in the right superior frontal gyrus, two critical nodes of the default mode network, related to the absence of modulation in the activity of the mPFC, along with a lack of suppression of the right superior frontal gyrus in MCI, in response to the increased use of the encoding strategy. A different association between improvement in strategy use and session-related changes in activation of the medial orbitalfrontal cortex between groups was also confirmed. That is, improvements in strategy use in controls contribute to a great extent in the amount of deactivation in OFC, whereas in patients, only a small portion of the increase in activation in this region was predicted by increases in strategy application

Na presente tese foi investigado o desempenho de camadas de organo-silanos sobre chapas de aço-carbono, similares às utilizadas na fabricação de veículos da indústria automobilística. As técnicas utilizadas neste estudo compreenderam a Espectroscopia de Impedância Eletroquímica (EIE) e a Resistência de Polarização Linear, por meio das quais foram determinadas respectivamente, as propriedades resistivas dos filmes e a redução das velocidades de corrosão do substrato. O estudo compreendeu a avaliação de diversos organo-silanos funcionais e não-funcionais, submetidos a diferentes condições experimentais. Os ensaios preliminares tiveram por finalidade selecionar aqueles com melhor desempenho como sistemas de proteção em monocamadas. A partir desta seleção e,, informações da literatura, novos ensaios foram conduzidos por meio de um Projeto Fatorial de Experimentos, combinando os silanos funcionais com melhor desempenho com outro silano não-funcional, designado como 1,2-bis(trietoxilsilil)etano (BTSE). Esta combinação teve por finalidade produzir camadas duplas de silanos para proteger o aço-carbono. As variáveis independentes estudadas foram a combinação entre as camadas de BTSE e do silano funcional, além das condições de hidrólise, temperatura e tempo de cura destes filmes. As variáveis dependentes ou resposta utilizadas foram: a impedância real a 0,03 Hz, obtida no ensaio de EIE, e a densidade de corrente de corrosão, originada das medidas de Resistência de Polarização Linear. Dentre as várias alternativas testadas, os melhores resultados foram apresentados pela combinação de camadas de BTSE com bis-(g-trimetoxisililpropil)amina (BTSPA) e BTSE com VS (viniltrietoxisilano) onde a primeira combinação determinou uma redução da ordem de 95% na velocidade de corrosão em relação a uma chapa sem tratamento e uma perda de espessura da ordem de 70% menor que um corpo-deprova revestido apenas com uma camada convencional de fosfatização. O BTSPA já na seleção inicial havia demonstrado excelentes resultados de proteção apenas como película monocamada, tendo seu desempenho melhorado consideravelmente em conjunto como o BTSE. Na segunda combinação, a velocidade de corrosão foi 90% menor do que num corpo-de-prova desprotegido e até 40% menor do que num corpo-de-prova revestido com uma camada de fosfato. / The aim of this thesis was the investigation performance of organo-silane layers on mild steel, similar to that used in car bodies in automotive assembly plants. The electrochemical impedance spectroscopy (EIS) and the polarization resistance (Rp) were used as tools to evaluate the resistive layers properties and the substrate corrosion rate, respectively. Several non-functional and functional silanes were evaluated under different experimental conditions. Preliminary testing was conducted in order to select the silane with best performance as monolayer protection. Based on this preliminary performance results and supplementary information from papers, new tests were conducted using a design of experiments (DOE), combining the best functional monolayers silanes with the non-functional silane 1,2- bis(triethoxylsilyl)ethane (BTSE). This combination had the intention to produce double-layers silane films to protect the mild steel. The independent variables tested in DOE were: combination between the BTSE and the functional silane layers, hydrolysis parameters, temperature and the time film curing. The real impedance values at 0,03 Hz, obtained in the EIE tests, and the polarization resistance were taken as response (dependent) variables to evaluate the design. Among the different alternatives, the best results were presented by combining the BTSE layer with the BTSPA (bis-(g trimetoxysilylpropyl)amine layer and BTSE layer with VS (vinyl triethoxy silane) layer. The first silanes combination had shown a 95% decrease in corrosion rate when compared to a non-treated sheet and a thickness loss 70% lower than on a specimen coated with ordinary phosphate layer. Already in the initial selection the BTSPA did show excellent protection results just as monolayer film, and its performance increased significantly when applied together with BTSE. The second silanes combination, had presented a 90% decrease in corrosion rate when compared to a non-treated sheet and a thickness loss 40% lower than a specimen coated with ordinary phosphate layer.