Orientador: Auteliano Antunes dos Santos Júnior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-16T08:34:31Z (GMT). No. of bitstreams: 1 Buenos_AlexandreAparecido_M.pdf: 7987843 bytes, checksum: e9789b79f50624aea527663a778fd255 (MD5) Previous issue date: 2010 / Resumo: O processo de usinagem de materiais metálicos causa tensões residuais que podem alcançar valores significativos e influenciar na vida em serviço de componentes mecânicos. Definir o processo adequado para cada aplicação requer a previsão de quão elevada será a tensão gerada em função das variáveis do processo utilizado. Para a usinagem de chapas planas por fresamento de topo, as tensões e deformações criadas se encontram próximas à superfície, que é onde se iniciam as principais falhas de componentes mecânicos. A fim de conhecer os valores das tensões resultantes é necessário medi-las, mas os métodos destrutivos usuais são trabalhosos, requerem a reconstrução do campo de tensões a partir do alívio das tensões e nem sempre podem ser utilizados. Os métodos não destrutivos mais comuns requerem equipamentos especializados, condições controladas e quase sempre são capazes de determinar as tensões apenas na superfície. Este trabalho propõe um método alternativo para a avaliação da intensidade das tensões geradas pelo processo de usinagem, utilizando ondas longitudinais criticamente refratadas (Lcr) e a teoria acustoelástica. O trabalho consiste em avaliar o efeito da variação dos principais parâmetros de usinagem: a velocidade de corte, o avanço e a profundidade de usinagem. Foram ensaiadas amostras de aço carbono de média resistência ASTM A36, utilizado em componentes estruturais. Tais amostras foram usinadas em diversas combinações de parâmetros, o que permitiu a criação de um conjunto de relações entre os parâmetros e a tensão resultante, e que pode ser usada para a definição do melhor ajuste dos parâmetros para cada aplicação / Abstract: The process of machining of metallic materials generates residual stresses that can reach significant values and influence the service life of mechanical components. The definition of process for every application requires a forecast of how high the stress will be generated according to the process variables used. For the machining of flat sheet using face milling, the stresses and strains are created near the surface, which is where the main failures of the mechanical components start. In order to know the magnitude of stresses it is necessary to measure them, but the usual destructive methods are complex, require the reconstruction of the stress field from the relief stress and can not always be used. The nondestructive methods frequently require specialized equipment, controlled conditions and almost always are be able to determine the stresses on the surface only. This dissertation proposes an alternative method for assessing the intensity of the residual stresses generated by the machining process, using critically refracted longitudinal waves (Lcr) and the acustoelastic theory. The work is to evaluate the effect of variation of the main machining parameters: cutting speed, feed per tooth and depth of cut in machining. We tested samples of carbon steel ASTM A36 of medium strength, used in structural components. These samples were machined in various combinations of parameters, which allowed the creation of a set of relationships between the parameters and the resulting stress. These can be used to define the best fit of the parameters for each application / Mestrado / Mecanica dos Sólidos e Projeto Mecanico / Mestre em Engenharia Mecânica

Desenvolveram-se métodos bioanalíticos para determinação de anfotericina B e fluconazol em apenas 200 L de plasma e líquor (LCR) através da cromatografia líquida de alta eficiência (CLAE UV-VIS). A anfotericina B foi determinada através de CLAE-VIS utilizando p-nitrofenol como padrão interno, após purificação das matrizes biológicas com acetonitrila, seguida da análise em coluna Nova Pak C18 (150 x 3,9mm, 4 micron) e fase móvel constituída por tampão acetato 0,1M pH 5,0 e acetonitrila (50:50,v/v) 0,5mL/min em 385nm; o tempo de corrida foi 15 min. Através da validação o método mostrou-se robusto com 0,2-25,0 µg/mL(linearidade, r2 0,9999), LD 0,1 µg/mL, precisão (5,4% e 6,9%), exatidão expressa através do erro sistemático (3,3% e 2,2%): intra e interdias). Os estudos de estabilidade evidenciaram 1,0% para o erro sistemático e 3% de precisão na bandeja (tempo e condição de análise por 24 h), e os ciclos de congelamento evidenciaram boa estabilidade uma vez que todos os ensaios foram realizados em Laboratório de luz amarela. O fluconazol foi determinado através de CLAE-UV utilizando carbamazepina como padrão interno, após purificação das matrizes biológicas pela extração líquido-líquido com diclorometano em meio alcalino, seguido da análise em coluna Nova Pak C18 (150 x 3,9mm, 4 micron) e fase móvel constituída por água UP e acetonitrila (70:30,v/v) 0,5mL/min em 210nm; o tempo de corrida foi 15 min. O método mostrou-se robusto com 0,2-250 µg/mL(linearidade, r2 0,9998), LD 0,1µg/mL, com boa recuperação absoluta (98%) e relativa (100%), precisão 0,5%/1,3%, exatidão expressa através do erro sistemático (1,2%). Evidenciou-se ótima estabilidade para os extratos em bandeja (tempo e condição de análise por 24 h), na longa duração (20° C, 9 meses) e através dos ciclos de congelamento. Investigaram-se 21 pacientes adultos de ambos os sexos portadores de meningite criptocócica com AIDS após internação emergencial em terapia de alta dose com anfotericina B (1mg/Kg) e fluonazol (400 mg, 12/12 horas) durante 12 semanas. O monitoramento das concentrações de anfotericina B e fluconazol no plasma e no LCR forneceram as razões que permitiram estimar a penetração dos antifúngicos no SNC. Obtiveram-se concentrações de anfotericina B, médias (IC95%): 2,30 (0,02-5,08) µg/mL no plasma e 0,30 (0,19-0,36) µg/mL no LCR. As concentrações do fluconazol, médias (IC95%) foram: 31,7 (20,1-43,3) µg/mL no plasma e 19,4 (11,1-27,7) µg/mL no LCR. Com base nos resultados obtidos conclui-se que a penetração da anfotericina B foi insuficiente (10-27%), enquanto que a do fluconazol mostrou-se adequada com valores médios (IC95%) de 67 (47-87) %. / Analytical methods were developed to determine amphotericin B and fluconazole in only 200 L of plasma and in cerebrospinal fluid (CSF) by liquid chromatography (HPLC UVVIS). Amphotericin B was determined by HPLC - VIS using p-nitrophenol as internal standard, after the purification of biological matrices using acetonitrile, followed by chromatographic analysis in a Nova Pak C18 column (150 x 3.9mm, 4 micron) and mobile phase consisting of acetate buffer 0.1M pH 5.0 plus acetonitrile (50:50,v/v) 0.5mL/min at 385nm; the run time required was 15 min. Bioanalytical method validated showed robustness, 0.2-25,0µg/mL (linearity, r2 0.9999), DL 0.1µg/mL, precision (5.4%/6.0%), accuracy expressed as systematic error (3.3%/2.2%). The stability was investigated, error systematic was 1% for the vials on the rack (time and conditions of drug analysis, 24h). Thawing cycles showed good stability after three freezing-thawing cycles. All procedures were performed under yellow light at room temperature. Fluconazole was determined by HPLC - UV using carbamazepine as internal standard, after the purification of biological matrices using liquid-liquid extraction in alkaline medium, followed by chromatographic analysis in a Nova Pak C18 column (150 x 3.9mm, 4 micron) and mobile phase consisting of purified water plus acetonitrile (70:30,v/v) 0.5mL/min at 210nm; the run time required was 15 min. Bioanalytical method validated showed robustness, 0.2-250 µg/mL(linearity, r2 0.9998), DL 0.1µg/mL. Absolute recovery was 98% and relative recovery was 100%, intra/interday precision were 0,5/-1,3%; accuracy expressed as systematic error were 1.2%/1.2%.and relative recovery was 100%. Good stability for the vials on the rack (time and conditions of drug analysis, 24h) and long term stability (at 20o C for 9 months) were demonstrated. Also thawing cycles showed good stability after three freezing-thawing cycles. Twenty one adult patients of both sex were investigated. Inpatients with meningitis by Cryptococcus neoformans with AIDS were under high dose therapy with amphotericin B 1mg/Kg plus fluonazole 400 mg, every 12h during 12 weeks. Therapeutic monitoring of amphotericin B and fluconazole in plasma and in CSF showed ratios that indicate the penetration of antifungal drugs into CNS. Mean (CI95%) data were for amphotericin B 2.30 (0.02-5.08 ) µg/mL in plasma and 0.30 (0.19-0.36) µg/mL in CSF. Fluconazole showed 31.7 (20.1-43.3) µg/mL in plasma and 19.4 (11.1-27.7) µg/mL in CSF. Based on data obtained we conclude that the penetration of amphotericin B was poor (10-27%) while fluconazole was adequate 67% (47-87%), mean (CI95%).

Les encéphalites à anticorps (Ac) anti-récepteur NMDA (NMDAR) sont des pathologies auto-immunes nouvellement décrites ciblant un récepteur majeur du système nerveux central, le NMDAR. Les synapses glutamatergiques assurent la majeure partie de la transmission excitatrice du cerveau et les récepteurs ionotropiques au glutamate de type NMDA ont un rôle clé dans la plasticité synaptique, c'est-à-dire les modifications de la force de transmission synaptique constituant le corrélat cellulaire des processus d'apprentissage et de mémoire. Les études in vitro et in vivo de l'effet des Ac anti-NMDAR tendent à montrer une altération de la dynamique des NDMAR et une internalisation. Les Ac auraient un effet pathogénique pouvant expliquer des symptômes. Au cours de ma thèse, j'ai souhaité approfondir la compréhension de cette pathologie sur le plan clinique et mécanistique. Pour cela j'ai étudié les caractéristiques cliniques et histologiques des patients présentant une tumeur maligne associée, me permettant d'établir des recommandations de prise en charge au vu du taux de mortalité plus élevé chez ces patients et d'une fréquence plus importante de tératomes ovariens immatures que dans la population générale. En parallèle j'ai étudié l'effet des Ac anti-NMDAR sur la transmission et la plasticité synaptique dans un modèle murin d'administration chronique des anticorps. Ces études menées en électrophysiologie sur tranches aigües m'ont permis de mettre en évidence un effet des anticorps du LCR sur la plasticité synaptique significatif mais d'amplitude moindre que les études in vitro l'avaient suggéré. Nous avons également montré l'importance de la durée d'exposition aux anticorps / Anti-NMDAR autoimmune encephalitis is a newly described pathology, characterized by the presence of IgG antibodies (Abs) directed against NMDA receptor (NMDAR). Glutamatergic synapses are the main component of excitatory transmission in the adult brain and the ionotropic glutamate receptor NMDAR has a key role in synaptic plasticity. Synaptic plasticity is defined by the synapses property to modify their transmission strength and seems to be the cellular correlate of learning and memory. In vitro and in vivo studies on anti-NMDAR Abs effects showed an altered dynamic at the membrane followed by an internalization of NMDAR. Thus, Abs seem to have a pathogenic effect, able to explain clinical symptoms. During my thesis, I wanted to deepen the understanding of this pathology on the clinical and mechanistic level. To this end, I studied the clinical and histological features of patients with an associated tumor. Results obtained allow me to establish management recommendations considering the high mortality rate in these patients and a higher frequency of immature ovarian teratomas than in the general population. Simultaneously, I studied the effect of anti-NMDAR Abs on synaptic transmission and plasticity in a murine model allowing chronic Abs infusion. These results obtained by electrophysiology on acute slices allowed me to demonstrate an effect of CSF Abs on synaptic plasticity but of less amplitude that the in vitro studies had suggested. Results also highlighted the importance of the duration to antibodies exposure

Introducción: El conocimiento de los mecanismos neuroinflamatorios y neurodegenerativos que acontecen en la enfermedad de Alzheimer es aún limitado y la utilidad diagnóstica, pronóstica o de seguimiento del proceso, tanto en la fase DCL como en la EA establecida, de los diferentes marcadores moleculares es controvertida cuando no directamente contradictoria. La teoría patogénica más aceptada hoy en día es que las moléculas centrales de la vía amiloidea pondrían en marcha un proceso inflamatorio crónico, responsable del daño celular, en el que las citocinas tendría un papel preponderante a través de distintas vía de señalización. Objetivos: El objetivo primario comprende la evaluación de la síntesis de una amplia variedad de citocinas (CQs) dentro del SNC en pacientes con deterioro cognitivo leve (DCL) y Enfermedad de Alzheimer (EA), utilizando una técnica más sensible que la tradicional con el propósito de identificar si alguna o algunas CQs o ratio derivada de ellas tienen posibilidades de servir como marcadores diagnósticos de DCL y estudiar si estos mediadores solubles pueden utilizarse como elementos pronósticos/predictivos de evolución a EA desde el estado de DCL. Métodos: Se estudiaron los niveles de diferentes citocinas en LCR y suero mediante tecnología Luminex de 37 pacientes diagnosticados de DCL en la consulta de deterioro cognitivo del Hospital General Universitario de Alicante. Por otro lado, se estudió una cohorte de 24 controles sin quejas subjetivas u objetivas de alteraciones de su capacidad cognitiva. A los 12 meses y tras una nueva punción lumbar, los pacientes se clasificaron como DCL-E (estable, no evolucionados a EA) y DCL-EA (que habían desarrollado EA), volviendo a medir las concentraciones de citocinas en LCR y suero. Se realizó estudio estadístico de estos marcadores y sus ratios en ambos grupos. Resultados: Los dos resultados mayores de este proyecto ha sido la detección de un índice IL6/IL10 en LCR, para los pacientes DCL, con un VPN del 80% a la hora de descartar la presencia de deterioro cognitivo y, en segundo lugar el hallazgo de otro índice IL10S/L, al comparar los valores de esa citocina en suero y LCR de pacientes evolucionados a EA con los del grupo control, con una sensibilidad del 80% para seleccionar pacientes sin riesgo de desarrollar EA. La significación estadística de este segundo índice es independiente de la representada por ßA lo que apunta a mecanismos de acción distintos o bien a momentos de actuación diferentes. Conclusiones: Nuestros resultados apoyan la participación de las citocinas en el proceso inflamatorio de la EA y su valor como marcadores secundarios, con valor diagnóstico/pronóstico, en esto pacientes. Su aplicación puede tener sentido en aquellos casos en los que la clasificación de un paciente es dudosa mediante los métodos diagnósticos habituales.

A dynamic decision making framework implementing multi criteria routing of multimedia services at private-public network border with access technology convergence is presented. The ingredients of the framework include information model, semantics capturing via ontology, information sharing and dissemination mechanisms and rule/policy specifications methodology. The control and management over the infrastructure is carried out by revamping the sole signaling protocols (SIP, diameter and SNMP). DEN-ng is enhanced and tagged in accordance with the requirements over the underlying framework. A dedicated language for the platform is proposed that has its deep roots inside the framework to avoid conflicts and overlapping. A dynamic decision engine is developed for routing the requests/sessions at private-public network border over the underlying multi-homed environment. Multi Criteria Decision Making (MCDM) theory is used for decision computation/calculation and the adapted methods are exploited according to the scenario and decision computation mode while keeping in view the corresponding enforcement mode. A test bed is developed to validate the proposed framework. The proposed system offers higher throughput and lowers call-dropping probability with an add-on susceptible delay.

Gene transfer techniques such as retroviral transduction have many applications such as cell marking, cell reprogramming, and therapeutics. Transgene expression, however, is often variable and maintaining long-term expression is problematic in progenitor cell types. To better control transgene expression, research has focused on the optimized use of cis-regulatory elements, such as promoters, enhancers and insulators. In addition to controlling gene expression, these regulatory elements modulate the nuclear organization of the transgene. The integration site also exerts significant effects on steady state and temporal transgene expression via the neighbouring chromatin environment. The first part of this thesis describes the co-operation of modified β-globin intronic elements in providing high-level expression and favorable nuclear localization. I demonstrate that these elements are compatible with efficient lentivirus transduction for globin gene therapy purposes. In the second chapter, I examine high-expressing EGFP retroviral transgenes and show that such steady state expression may exhibit rapid transcriptional fluctuations, which is modulated by different transcriptional dynamics at different integration sites. Finally, in the last chapter, I evaluate the use of a 3’D4Z4 insulator element in maintaining long-term EGFP transgene expression in ES cells, and discover integration-site specific temporal dynamics in retroviral vector expression. Overall, my results demonstrate that using multiple regulatory elements and insulating these elements from different types of genomic loci optimize transgene expression and dynamics in progenitor cells.

Gene transfer techniques such as retroviral transduction have many applications such as cell marking, cell reprogramming, and therapeutics. Transgene expression, however, is often variable and maintaining long-term expression is problematic in progenitor cell types. To better control transgene expression, research has focused on the optimized use of cis-regulatory elements, such as promoters, enhancers and insulators. In addition to controlling gene expression, these regulatory elements modulate the nuclear organization of the transgene. The integration site also exerts significant effects on steady state and temporal transgene expression via the neighbouring chromatin environment. The first part of this thesis describes the co-operation of modified β-globin intronic elements in providing high-level expression and favorable nuclear localization. I demonstrate that these elements are compatible with efficient lentivirus transduction for globin gene therapy purposes. In the second chapter, I examine high-expressing EGFP retroviral transgenes and show that such steady state expression may exhibit rapid transcriptional fluctuations, which is modulated by different transcriptional dynamics at different integration sites. Finally, in the last chapter, I evaluate the use of a 3’D4Z4 insulator element in maintaining long-term EGFP transgene expression in ES cells, and discover integration-site specific temporal dynamics in retroviral vector expression. Overall, my results demonstrate that using multiple regulatory elements and insulating these elements from different types of genomic loci optimize transgene expression and dynamics in progenitor cells.

The theme of this diploma thesis is the capital adequacy of Czech banks in the context of macro-prudential policy. The aim of this diploma thesis is quantitative and qualitative analysis of the capital ratios of the Czech banking sector in the context of Basel III and CRD IV capital regulation. The work for the selected period analyzes the development of the capital structure of the Czech banking sector as a whole and for individual segments of banks. The work also focuses on the determinants that influenced the capital changes in addition to the change in the volume of capital itself. The resistance of the banking sector to the unfavorable development of the financial system is analyzed through the stress tests of the Czech National Bank.

Au niveau du canal central (CC) du tronc cérébral et de la moelle épinière, on trouve des neurones au contact avec le liquide céphalorachidien (Nc-LCR). Les Nc-LCR sont GABAergiques et projettent une seule dendrite dans le CC qui se termine par une large protrusion. Ils expriment sélectivement le canal PKD2L1 pour lequel des fonctions de chimio- et mécanorécepteur ont été démontrées. Compte tenu de leur localisation, de leur morphologie et de l’expression sélective de PKD2L1, les Nc-LCR représenteraient une nouvelle population de neurones sensoriels dans le SNC. Au cours de ma thèse, je me suis concentrée sur la caractérisation des canaux Ca2+ et les mécanismes de signalisation Ca2+ dans les Nc-LCR bulbo-spinaux de souris. Je rapporte que les Nc-LCR expriment des canaux Ca2+ qui sont modulés par les récepteurs métabotropiques GABAB et muscarinique. Je montre aussi l'implication des stocks intracellulaires dans la régulation du Ca2+ intracellulaire. Ensuite, je démontre pour la première fois la relation fonctionnelle entre la protrusion et le soma et indique que la protrusion serait dépourvu de conductance ionique active. Enfin, pour aborder le rôle des Nc-LCR, j'ai développé des modèles chimiogénétiques (DREADDs) et optogénétiques (channelrhodopsin) chez la souris afin de manipuler sélectivement l'activité Nc-LCR. Dans l'ensemble, les résultats de mon étude de doctorat contribuent à mieux comprendre les Nc-LCR bulbo-spinaux des mammifères en en contribuant à la caractérisation de leur physiologie et modulation. Ils ouvrent également la voie à de futures études qui permettront de démontrer le rôle de cette population neuronale dans la régulation de l'activité du SNC. / Cerebrospinal fluid-contacting neurons (CSF-cNs) located in the ependymal region around the central canal (CC) in the brainstem and the spinal cord are GABAergic neurons that project a single dendrite to the CSF and ends with a large protrusion. They selectively express PKD2L1 channel suggested to act as chemo- and mechanoreceptor. Considering their localization, morphology and selective expression of PKD2L1 channel, CSF-cNs would represent a novel population of sensory neurons within the CNS. To better understand the role of CSF-cNs in mammals, it is necessary to describe the physiological properties and modulation of CFS-cNs. In the present study, I focused on Ca2+ channels and Ca2+ signaling mechanisms in mouse medullo-spinal CSF-cNs. I report that Ca2+ channels in CSF-cNs undergo modulation by metabotropic GABAB and muscarinic acetylcholine receptors. I further show the involvement of intracellular Ca2+ stores in the regulation of intracellular Ca2+. Next, I demonstrate for the first time functional relationship between bud and soma and indicate that the bud would be devoid of active ionic conductance. Finally, to address the role of CSF-cNs, I developed chemogenetic (DREADDs) and optogenetic (channelrhodopsin) mice models to be able to selectively manipulate CSF-cN activity. Altogether, the results of my PhD study contribute to better understanding mammalian medullo-spinal CSF-cNs by providing valuable information on their physiology and modulation. They also set ground for further studies carried out in ex-vivo preparation or in vivo models to demonstrate their role in the regulation of CNS activity.

Contexte & objectifs: L’avènement de biomarqueurs in vivo pour la maladie d’Alzheimer a révolutionné la recherche clinique dans ce domaine. Nous avons comparé le taux de positivité pour le biomarqueur tau (statut-T) dérivé de l’interprétation visuelle des études TEP au [18F]flortaucipir (FTP), de l’analyse quantitative du FTP et de la mesure de la protéine Tau phosphorylée en position 281 (PTau181) dans le liquide céphalorachidien (LCR). Méthodologie: Nous avons inclus 351 participants avec divers diagnostics cliniques provenant de trois cohortes ayant subi une étude TEP au FTP ainsi qu’une mesure du PTau181 dans un délai de 18 mois. Le statut-T a été dérivé de : (1) l’interprétation visuelle à l’aveugle du FTP par deux observateurs; (2) la quantification SUVR (standardized uptake value ratio) du FTP d’une région d’intérêt composite temporale (seuil : SUVR ≥ 1.27) ; (3) la concentration dans le LCR de Elecsys® Phospho-Tau (181P) (Roche Diagnostics) (seuil : PTau181 ≥ 24.5 pg/ml). Résultats: L’interprétation visuelle du FTP a entraîné le plus haut taux de T+, alors que les T+ par quantification SUVR augmentaient progressivement des sujets cognitivement normaux (CN) vers les sujets avec troubles cognitifs légers (TCL) et ceux avec démence de type Alzheimer (DA). Le taux de T+ par PTau181 était intermédiaire à ceux de l’analyse visuelle et quantitative du FTP pour les CN, similaire à la quantification SUVR pour les TCL et plus faible chez les DA. La concordance entre le statut-T par paire de modalité fluctuait de 68% à 76% et variait selon le diagnostic, étant plus élevé chez les DA. L’interprétation visuelle du FTP offrait la plus haute sensibilité (0.96) pour discriminer entre les sujets avec TCL ou DA amyloïde-positifs des sujets CN et non-Alzheimer, mais une spécificité plus faible (0.60). La spécificité était la plus élevée avec la quantification SUVR (0.91) avec une sensibilité de 0.89, alors que la sensibilité (0.73) et la spécificité (0.72) étaient de même niveau pour le PTau181 dans le LCR. Conclusion: Le choix d’un biomarqueur tau pourrait varier selon le stade de la maladie et les objectifs de recherche visant à maximiser la sensibilité ou la spécificité. L’interprétation visuelle des TEP tau augmente la sensibilité en comparaison avec la quantification seule, en particulier dans les stades précoces de la maladie. / Background & purpose: The advent of in vivo biomarkers for Alzheimer’s disease (AD) pathology has transformed clinical research in this field. The purpose of this study is to compare rates of tau biomarker positivity (T-status) per the 2018 AD Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181) concentration. Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from: (1) FTP blinded visual assessment by two raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥ 1.27); (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/ml). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and to AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T- status between modality pairs ranged from 68% to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ+ MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was the most sensitive (0.96) but the least specific (0.60) approach. Specificity was highest with FTP SUVR (0.91) with a sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of a tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.