O presente estudo teve como objetivo avaliar a Punção Aspirativa por Agulha Fina (PAAF) em diferentes técnicas de coloração, em lesões nodulares de cavidade oral e região de cabeça e pescoço, quanto a sua sensibilidade, especificidade e acurácia, nas colorações de Panótico, Papanicolau e Hematoxilina-Eosina . Foram selecionados 46 pacientes consecutivamente que procuraram a Clínica da Disciplina de Estomatologia Clínica da FOUSP, portadores de lesões nodulares em cavidade oral e região de cabeça e pescoço. Como critérios de inclusão foram selecionados pacientes de ambos os sexos, todas as etnias, acima dos 5 anos de idade, sem restrição de comorbidades e que foram realizadas PAAF com confirmação diagnóstica pela biópsia. Como critérios de exclusão da pesquisa estão os pacientes abaixo dos 5 anos de idade e pacientes que foram somente submetidos a PAAF sem confirmação diagnóstica pela biópsia. O material obtido pela PAAF foi enviado em 6 lâminas diferentes, corados pelo método de Panótico, Papanicolau e Hematoxilina-Eosina a um mesmo patologista apenas com o diagnóstico clínico. Após a emissão do laudo da PAAF, o laudo do anátomo patológico era emitido, servindo como padrão ouro. Após os cálculos, o resultado da sensibilidade, especificidade e acurácia para o método de coloração com o Panótico foram de 28,6%, 76%, 15,4, respectivamente, para o método de coloração com o Papanicolau foram de 71,4%, 76,7%, 23,3%, respectivamente e para o método de coloração com a Hematoxilina-Eosina foram de 82,1%, 23,3%, 28,6%, respectivamente. Houve diferença estatisticamente significativa na proporção de sensibilidade, especificidade e acurácia entre as diferentes técnicas de coloração (X2 13,27, p=0,01). Podemos concluir que, na metodologia do presente estudo, as colorações de Hematoxilina-Eosina e Papanicolau demonstraram a mesma sensibilidade, para diagnosticar neoplasias malignas. A coloração de Hematoxilina-Eosina demonstrou uma melhor especificidade para diagnosticar neoplasias benignas, quando comparadas com a colorações de Papanicolau e Panótico. A coloração de Hematoxilina-Eosina demonstrou uma melhor acurácia, para dar diagnóstico definitivo, seguida das colorações de Papanicolau e Panótico. / The present study aimed to evaluate the Fine Needle Aspiration Biopsy in different staining techniques in nodular lesions of the oral cavity and head and neck region, as their sensitivity, specificity and accuracy, staining with Panoptic, Papanicolaou and Hematoxylin-Eosin. 46 patients who sought the Clinic of the Discipline of Clinical Stomatology at FOUSP were selected consecutively, with nodular lesions in the oral cavity and head and neck region. Inclusion criteria were patients of both sexes, all ethnicities, above 5 years-old, with no restriction of comorbidities and FNAB performed with confirmation by biopsy. Exclusion criteria were patients under 5 years-old and patients who only underwent FNAB without confirmation by biopsy. The material obtained by FNAB was sent on 6 different slides, stained by the method of Panoptic, Papanicolaou and Hematoxylin-Eosin, to the same pathologist only with the clinical diagnosis. After the final report of FNAB, the biopsy report was issued, serving as gold standard. After the calculations, the results of sensitivity, specificity and accuracy for Panoptic staining were 28.6%, 76% and 15.4%, respectively. The result of sensitivity, specificity and accuracy for Papanicolaou staining were 71,4%, 76.7% and 23.3%, respectively. The result of sensitivity, specificity and accuracy for Hematoxylin-Eosin staining were 82.1%, 23.3%, 28.6%, respectively. There was a statistically significant difference in the proportion of sensitivity, specificity and accuracy between the different staining techniques (X2 13.27, p = 0.01). We can conclude, in the methodology of this study that, Hematoxylin-Eosin and Papanicolaou stains showed the same sensitivity of diagnosing malignant neoplasms. The Hematoxylin-Eosin stain showed a better specificity for diagnosing benign neoplasms, compared with Papanicolaou and Panoptic stains. Hematoxylin-eosin stain showed better accuracy, to give definitive diagnosis, followed by Papanicolaou and Panoptic stains.

Of the 22.5 million individuals infected with the human immunodeficiency virus (HIV) in sub-Saharan Africa, 62% of patients requiring treatment had access to highly active antiretroviral therapy (HAART) in 2011. The delivery of HAART and the appropriate laboratory monitoring of HIV positive individuals in sub-Saharan African countries has become a public health priority, an intervention which has and will continue to dramatically reduce HIV-related morbidity and mortality. Routine laboratory monitoring of HIV infected individuals should ideally include CD4+ T cell testing to assess when to start ART, viral load monitoring to assess virological failure on ART and when indicated, HIVDR genotyping.However, this is often not implemented in resource limited settings due to challenges such as inadequate infrastructure and laboratory capacity, amongst others. Thus the Affordable Resistance Testing for Africa (ART-A) initiative was established to develop an affordable HIV drug resistance testing (HIVDR) algorithm applicable to Africa. The objective of this study was to evaluate the role of in vitro HIVDR phenotyping in the context of HIV-1 subtype C (the most prevalent circulating subtype in sub-Saharan Africa), genotyping and genotypic interpretation tools using existing algorithms, as well as novel virological failure detection tools for clinical patient management. Current gold standard HIVDR phenotyping technologies use an HIV-1 subtype B backbone to create recombinant viruses with patient-derived polymerase (protease and partial reverse transcriptase). This backbone could impact on the in vitro phenotyping results of non-B subtypes, and therefore it was deemed necessary to establish the applicability of HIVDR phenotypic testing of subtype C polymerase when a commercially available subtype B backbone is used. One hundred and fourteen HIV-1 subtype C samples were HIVDR phenotyped against 17 antiretroviral drugs using both subtype B and C backbones and showed a high level of concordance between the two backbone phenotypic resistance profiles (95.8%; 1590 of 1660 fold change comparisons). Natural assay variability was largely responsible for discordant results. Results confirmed that HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is independent of the virus backbone subtype. No conclusions could be made for protease inhibitor resistance since limited samples from 2nd line failure were available. Subsequently, the HIVDR genotypic and phenotypic results of the 114 patient samples were compared to determine whether genotyping is a viable alternative to phenotyping. Results showed a 92.3% concordance between genotyping and phenotyping of individual drug comparisons for a number of HIVDR profiles. Discrepancies were attributed to phenotypic assay variability in addition to the role of mutation mixtures, which impacted genotypic interpretations. Overall, HIVDR genotyping is a reliable tool to detect and interpret antiretroviral drug resistance in HIV-1 subtype C infected patients, and can thus be used for clinical patient management. Once the accuracy of HIVDR genotyping was established, the development, validation and evaluation of a potential virological failure assay (ARTA-VFA) and a simplified HIVDR (ARTA-HIVDRultralight) assay was undertaken. A simplified and conceptually novel approach using a qualitative viral load assay with a pre-determined cut-off that gives a threshold above which virological failure (VF) could be confirmed and below which treatment success was likely, was tested. A real-time PCR (ARTA-VFA) assay was developed which involved the amplification of a short sequence of the HIV-1 LTR region from RNA extracted either from plasma and/or dried blood spots (DBS). The ARTA-VFA was tested on 409 patient samples,and successfully amplified samples from all major HIV-1 group M subtypes with equal specificity. The VF was qualitatively classified as a viral load >1000 RNA copies/ml in plasma samples, and >5000 RNA copies/ml in DBS samples. Comparative testing yielded accurate VF determination for therapy-switching in approximately 93% of clinical cases tested, compared to current gold standard quantitative viral load assays. A simplified HIVDR genotyping assay (ARTA-HIVDRultralight) targeting the region of RT harboring all major RT inhibitor resistance mutation positions, thus providing all relevant susceptibility data for first-line regimen failures was developed and assessed. The ARTAHIVDRultralight assay was designed to be practical, faster, and more affordable, show flexibility with respect to equipment (open platform), use DBS or plasma as starting material and amplify and sequence a smaller amplicon (RT). The assay performed well when compared to the in-house assay used in the laboratory at the time for both 212 plasma and 25 DBS samples, yielding identical mutations and subsequent resistant profiles. Furthermore, a theoretical in silico exercise to investigate the consequences of using 125,329 shortened RT genotype (ARTA-HIVDRultralight) as compared to full-length RT sequences showed >95% and >90% concordance when using the Stanford HIVdb algorithm and the virco®TYPE tool, respectively. Differences noted were minor and unlikely to have any impact on clinical decision-making. Overall, this study illustrated that the short RT sequences can be reliably used to generate HIVDR genotypes using the Stanford HIVdb and virco®TYPE algorithms and reduce sequencing costs substantially. A field evaluation using the ARTA-VFA and ARTA-HIVDRultralight on 288 clinical samples was conducted, showing that the accuracy and precision of both assays (using 248 plasma or 40 DBS sampling methods) compared well to the reference methodology, thereby extending access of testing to more remote settings.These assays were designed to either be used as a testing strategy of initially assessing VF,and once confirmed performing an HIVDR assay, or alternatively to be used separately as stand-alone, or within different laboratory tiers in resource limited settings. It is envisaged that the ARTA-VFA could be used in the middle laboratory tier, and if confirmatory, patient samples can be referred to a reference laboratory with the available infrastructure for HIVDR testing using the ARTA-HIVDRultralight. Lastly, an automated sequence analysis and editing software for use in correct base calling of nucleotide/mutation mixtures in HIVDR genotyping was validated on 1624 sequences. Compared to reference software, where interpretation is often operator dependent, this software performed extremely well, with minor discrepancies noted. The automated software can be used to reduce subjectivity, time taken for analysis which is often the rate-limiting step and thus improving the turn-around time and clinical relevance of HIVDR genotyping. Overall, the results obtained describe the validation of using HIVDR genotyping as an alternative tool to phenotyping, and the subsequent development and validation of simple, affordable, "open-platform" alternatives to currently used methods for virological failure monitoring, and accommodate a centralized approach to HIVDR with DBS testing in resource limited settings.

An existing mathematical model of ordinary differential equations was studied to better understand the interactions between hepatitis C virus (HCV) and the immune system cells in the human body. Three possible qualitative scenarios were explored: dominant CTL response, dominant antibody response, and coexistence. Additionally, a sensitivity analysis was carried out to rank model parameters for each of these scenarios. Therapy was addressed as an optimal control problem. Numerical solutions of optimal controls were computed using a forward-backward sweep scheme for each scenario. Model parameters were estimated using ordinary least squares fitting from longitudinal data (serum HCV RNA measurements) given in reported literature.

In this thesis we modify an existing model for the spread of resistant bacteria in a hospital. The existing model does not account for some of the trends seen in the data found in literature. The new model takes some of these trends into account. For the new model, we examine issues relating to identifiability, sensitivity analysis, parameter estimation, uncertainty analysis, and equilibrium stability.

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Purpose: Drug interactions are a concern in oncology with the shift toward oral antineoplastics (OAs). Using electronic databases to screen for drug interactions with OAs is a common practice. There is little literature to guide clinicians on the reliability of these systems with OAs. The primary objective of this study was to explore the sensitivity of commonly available drug interaction databases in detecting drug interactions with OAs. Methods: A list of 20 drug interactions with OAs was developed by two Board-certified oncology pharmacists. The list included multiple types of drug interactions. The sensitivity in detecting these interactions by MicroMedex, Facts & Comparisons, Lexi-Interact, and Epocrates were evaluated. These databases were chosen based on their local availability and widespread use in practice. Drugs.com was evaluated as a surrogate for a patient-accessible drug interaction database. The Cochran Q test was used to assess the sensitivity distribution across the five groups. Results: Lexi-Interact and Drugs.com had a sensitivity of 95% for the 20 tested drug interaction pairs. Epocrates had a sensitivity of 90%, and both Micromedex and Facts & Comparisons had a sensitivity of 70%. There was a statistically significant difference (P = .016) in the distribution across the databases in detecting clinically significant drug interactions. Conclusion: Commonly used databases for identifying drug interactions with oral antineoplastics vary significantly in their sensitivity. Clinicians should not rely on a single database and should consider using multiple resources as well as sound clinical judgment. Further work is needed in this area.

The Motion Sensitivity Test (MST) is a clinical protocol designed to measure motion-provoked dizziness during a series of 16 quick changes to head or body positions. The MST has been used as a guide for developing an exercise program for patients with motion-provoked dizziness and as a treatment outcome measure to monitor the effectiveness of vestibular rehabilitation therapy. This study determined validity, test-retest reliability, and interrater reliability of the MST. Fifteen individuals with motion-provoked dizziness and ten control individuals were tested during sessions occurring 90 min and/or 24 hr after baseline testing. The MST was found to be reliable across raters (intraclass correlation coefficient [ICC] = 0.99) and test sessions (ICC = 0.98 and 0.96). Test validity was good. The results indicated that the MST can be used reliably in clinical practice to develop exercise programs for patients with motion-provoked dizziness and to provide evidence of intervention efficacy

abstract: This study investigated the relation between Sensory Processing Sensitivity (SPS) temperament and depression, and whether such a relation might be further influenced by the indirect effects of parenting environment and empathic personal distress. A moderated mediation model was proposed to explain the underlying relations among SPS, depression, parenting environment and empathic personal distress. That is, greater levels of SPS temperament might predict higher levels of empathic personal distress, which then leads to increasing likelihood of experiencing depression. Moreover, it was predicted that this mediation relation might be significantly stronger under a less positive parenting context. The present study recruited 661 participants from a U.S. university and implemented questionnaires in an online survey. There was a significant main effect of SPS temperament in predicting empathic personal distress and depression, such that the more sensitive individuals reported higher empathic personal distress and depression. There also was a significant main effect of parenting environment on depression, where more positive parenting was associated with less depression. Empathic personal distress was found to partially mediate the relation between SPS and depression. That is, the association between SPS and depression could be partially explained by empathic personal distress. However, parenting environment did not moderate the main effect of SPS temperament on depression, the main effect of SPS on empathic personal distress, or the mediation model. / Dissertation/Thesis / Masters Thesis Psychology 2019

The high cost of experimentation and product development in the field of microelectromechanical systems (MEMS) has led to a greater emphasis on simulation-based design for increasing first-pass design success and reliability. The use of compliant or flexible mechanisms can help eliminate friction, wear, and backlash, but compliant MEMS are sensitive to variations in material properties and geometry. This dissertation proposes approaches for design stage uncertainty analysis, model validation, and robust optimization of nonlinear compliant MEMS to account for critical process uncertainties including residual stress, layer thicknesses, edge bias, and material stiffness. Methods for simulating and mitigating the effects of non-idealities such joint clearances, semi-rigid supports, non-ideal loading, and asymmetry are also presented. Approaches are demonstrated and experimentally validated using bistable micromechanisms and thermal microactuators as examples.