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In recent years there has been a growing use of expectancy theory to study motivation and performance in accounting environments. Such research efforts have resulted in reporting some inconsistent findings and low explanatory power for the expectancy model. In an attempt to increase the explanatory power of the model, several researchers have suggested the inclusion of nonexpectancy components in the model. This research was undertaken to develop an integrative expectancy model by incorporating some elements of goal setting theory and attribution theory into the expectancy formulation. The study was also designed to provide empirical evidence on the validity of a within-subject design of the proposed model through an empirical investigation of auditors* performance behaviors to meet budgeted time in public accounting firms. Alternative performance behaviors to meet budgeted time were modeled in three choice processes. The first deals with auditors choice to report unfiltered time (i.e. report actual time worked) as opposed to filtered time worked (i.e., underreporting and sign-off behaviors). The second process deals with auditors' choice to engage in underreporting as opposed to sign-off behaviors. The third process deals with auditors' choice to reduce or overrule some audit procedures based on professional judgment. Data were collected using an anonymous questionnaire from a sample of auditors at the staff, senior, and supervisory staff levels of fifty-three national, regional and local accounting firms in the Dallas- Fort Worth area. Data received from 671 participants were analyzed using th Automatic Interaction Detector (AID3) and multiple regression techniques. The findings of this research support the expectancy formulation and its relevancy to the accounting environments. However, five nonexpectancy variables were found to have significant relationships with auditors' choice processes to meet budgeted time. These five variables were supervision, budget feasibility, length of experience, organizational level and firm size classification.

Nesta dissertação, apresentam-se os fatores que permitem à Naturopatia/ Naturologia ser entendida como uma nova Racionalidade Médica. Para tanto, partiu-se do conceito de Racionalidades Médicas e suas dimensões: Cosmologia, Doutrina Médica, Morfologia e Dinâmica Vital, Diagnose e Terapêutica. Utilizou-se o método de investigação de abordagem qualitativa classificando-se, de acordo com Apolinário (2006), em descritiva, documental; conforme a fonte geradora das informações, sendo objetos da pesquisa programas de disciplinas, matrizes curriculares e informações fornecidas nos sites institucionais de ensino superior em Naturopatia, no mundo, e Naturologia, no Brasil. O objetivo desse trabalho foi demonstrar como se apresentam as dimensões constituintes de uma Racionalidade Médica para a Naturopatia/Naturologia. Conforme os critérios de inclusão e exclusão dezesseis instituições foram analisadas em sete países. Como resultado, a Naturopatia/Naturologia pode ser considerada uma nova Racionalidade Médica, sendo entendida nas seis dimensões: uma cosmologia sincrética, dada à posteriori pautada na esfera própria de cada sujeito; uma Doutrina Médica multidimensional, integral, holística e vitalista. De promoção, prevenção e controle das condições de saúde e adoecimento dos sujeitos; uma Morfologia e Dinâmica Vital associativas, uma composição sintética dos saberes ocidentais e orientais em ciências da saúde; um Sistema Diagnóstico, misto das ferramentas das Racionalidades Chinesa e Ayrvédica, das práticas da Racionalidade Biomédica (conforme legislação de cada país), das Práticas Integrativas e Complementares; um Sistema Terapêutico (não fechado) com diferentes práticas das Racionalidades Médicas, Terapêuticas Tradicionais, Fitoterapia, Florais e Aromas, Terapêuticas relacionadas à Nutrição e as Práticas Integrativas e Complementares. / This dissertation intends to know the factors that allow Naturopathy/Naturology to be understood as a new Medical Rationality. For such, we started from the concept of Medical Rationalities and their dimensions: Cosmology, Medical Doctrine, Morphology and Vital Dynamic, Diagnosis and Therapeutics. The method of qualitative research was used. Classifying, according to Apolinário (2006), in descriptive, documentary, according to the information generating source being object of research, the curriculum, discipline programs, information supplied in the sites of Naturopathy superior level institutions, worldwide, and Naturology, in Brazil. According to the inclusion and exclusion criteria, sixteen institutions were evaluated in seven countries. As a result, the Naturopathy/Naturology can be considered a new Medical Rationality, being understood in the six dimensions: a syncretic cosmology, given the posteriori ruled in the own sphere of each individual; a multidimensional, integral or holistic, vitalist Medical Doctrine. Of promotion, prevention and control of the health and illness conditions of the individuals; associative Morphology and Vital Dynamic, based on principles and evidences of several knowledge, the sum, therefore, of the western and eastern sciences; a mixed Diagnostic System of the tools of the Chinese and Ayurvedic rationalities, of the practices of the Biomedical rationality (according to the legislation of each country), of the Integrative and Complementary Practices; a Therapeutic System (not closed) with different practices of Medical Rationalities, Traditional Therapeutics, Phytotherapy, Florals and scents, Therapeutics related to Nutrition and to the Integrative and Complementary Practices.

Older age is a primary risk factor for the development of cardiovascular disease in part through the stiffening of the large cardiothoracic elastic arteries (e.g., aorta, carotid arteries). Aging is also associated with reduced cognitive function, cerebrovascular reactivity and brain white matter integrity, but whether these changes in brain structure and function are associated with age-related large artery stiffness remains unclear. In contrast, older adults who have high aerobic fitness demonstrate attenuated large artery stiffness and better cognitive performance compared to their sedentary counterparts, but the effects of aerobic fitness on white matter integrity and cerebrovascular reactivity with aging are conflicting and limited. Moreover, whether high aerobic fitness-associated lower large artery stiffness in older adults is associated with, and perhaps mediates, the beneficial changes in cognitive function and white matter structure remains unknown. The purpose of this study was to investigate the extent to which high aerobic fitness is associated with preserved white matter structure, cerebrovascular reactivity, and cognitive performance in aged individuals, and if these changes in brain structure and function are associated with attenuated large artery stiffness. In young (n=19, 23.6 ± 2.5 years) and old (n=22, 64.4 ± 4.2 years) healthy adults, large elastic artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV, aortic stiffness) via non-invasive applanation tonometry of carotid and femoral pulse waveforms and carotid artery beta-stiffness index (β-stiffness index) and compliance using high-resolution ultrasound and carotid blood pressure via applanation tonometry. Aerobic fitness was measured as maximal exercise oxygen uptake (VO2max) using respiratory gas analysis on an upright cycle ergometer. Older subjects were stratified as high or low fit based on gender and age VO2max classification. Letter, pattern and N-Back cognitive tests were used to assess processing speed and working memory respectively. Fractional anisotropy (FA) from diffusion tensor images and Blood Oxygenation Level Dependent (BOLD) imaging was used to assess cerebrovascular reactivity (CVR) response to a breath hold and brain activation during a working memory task. The association between large artery stiffness and FA was then assessed using a voxel-wise general linear model approach and a region-of-interest analysis. Our results confirmed age-related increases in cfPWV, carotid β-stiffness index and central (carotid) but not brachial systolic blood pressure, and expected reductions in carotid compliance, VO2max, working memory and processing speed, and in white matter integrity in select brain regions (bilateral cingulate, frontal, occipital, temporal). In contrast, we found no age-associated differences in CVR to breath hold stimulus or change in BOLD response to the N-Back. In our cohort of health adults, we found that the age-related changes in large artery stiffness were not attenuated by high compared with low VO2max. Among older adults, large elastic artery stiffness was not associated with regional white matter integrity or cerebrovascular reactivity in any regions-of-interest. Greater carotid artery compliance and lower β-stiffness index was associated with higher processing speed, while compliance was related to higher d'Prime scores and lower reaction time on the 2-Back task among the older adults. CVR to a breath hold stimulus was not related to any measure of cognitive performance. VO2max was not associated with any measures of vascular function, brain structure, function or cognition, indicating relations between large artery stiffness and cognition were independent of aerobic fitness capacity. Taken together, these data suggest that select measures of cognitive performance, but not white matter structure or CVR, may be susceptible to age-related changes in carotid stiffness/compliance and that are unaffected by aerobic fitness. More work is needed to understand the mechanisms by which age-related declines in carotid artery compliance and increased carotid stiffness are associated with reductions in cognitive function in older adults.

High anxiety is associated with an increased risk of developing cardiovascular disease (CVD), in particular, atherosclerotic coronary artery disease. However, the mechanisms by which anxiety contributes to the development of CVD are unclear. Unlike other common psychiatric disorders such as depression, anxiety and its effects on CVD risk has not been studied extensively. Moreover, whether elevated anxiety is associated with arterial stiffness and vascular endothelial dysfunction, biomarkers of CVD risk, in healthy adults and whether a psychological intervention designed to lower anxiety levels in healthy adults with moderate to high baseline anxiety levels ameliorates vascular dysfunction remains unclear. The purpose of this study was twofold; first to determine the extent to which moderate to high anxiety levels are associated with vascular dysfunction including aortic stiffness as measured by carotid-femoral pulse wave velocity (cf-PWV), carotid artery stiffness via ultrasound-based β-stiffness index, and forearm resistance artery function measured as peak forearm blood flow using venous occlusion plethysmograph (VOP). Secondly, to determine whether the empirically validated Acceptance and Commitment Training (ACT) anxiety intervention improved vascular function after 12 weeks and if this was associated with reductions in anxiety in adults with moderate to high baseline anxiety levels. Our results indicated that there was no association between increased anxiety levels and any of the three vascular outcomes of interest. Conversely, there was an association between the ACT intervention participation and improvement in forearm resistance artery function independent of age, sex, education, race/ethnicity, BMI and STAI Trait anxiety. Taken together, these data suggest that although higher State and Trait anxiety was not associated with aortic stiffness, carotid stiffness or forearm resistance artery function, and the ACT intervention was associated with improved peripheral resistance artery function. Additional studies are needed to determine whether this effect occurs earlier than 12 weeks and sustained longer that 12 weeks, and whether it occurs in adults with CVD risk factors (i.e. atherosclerosis), non-white racial/ethnic backgrounds and in resistance vessel function in response to intra-arterial vasoactive agonists such as acetylcholine.

Dans le monde d’aujourd’hui de multiples acteurs de la technologie numérique produisent des quantités infinies de données. Capteurs, réseaux sociaux ou e-commerce, ils génèrent tous de l’information qui s’incrémente en temps-réel selon les 3 V de Gartner : en Volume, en Vitesse et en Variabilité. Afin d’exploiter efficacement et durablement ces données, il est important de respecter la dynamicité de leur évolution chronologique au moyen de deux approches : le polymorphisme d’une part, au moyen d’un modèle dynamique capable de supporter le changement de type à chaque instant sans failles de traitement ; d’autre part le support de la volatilité par un modèle intelligent prenant en compte des données clé seulement interprétables à un instant « t », au lieu de traiter toute la volumétrie des données actuelle et historique.L’objectif premier de cette étude est de pouvoir établir au moyen de ces approches une vision intégratrice du cycle de vie des données qui s’établit selon 3 étapes, (1) la synthèse des données via la sélection des valeurs-clés des micro-données acquises par les différents opérateurs au niveau de la source, (2) la fusion en faisant le tri des valeurs-clés sélectionnées et les dupliquant suivant un aspect de dé-normalisation afin d’obtenir un traitement plus rapide des données et (3) la transformation en un format particulier de carte de cartes de cartes, via Hadoop dans le processus classique de MapReduce afin d’obtenir un graphe défini dans la couche applicative.Cette réflexion est en outre soutenue par un prototype logiciel mettant en oeuvre les opérateurs de modélisation sus-décrits et aboutissant à une boîte à outils de modélisation comparable à un AGL et, permettant une mise en place assistée d'un ou plusieurs traitements sur BigData / Nowadays, multiple actors of Internet technology are producing very large amounts of data. Sensors, social media or e-commerce, all generate real-time extending information based on the 3 Vs of Gartner: Volume, Velocity and Variety. In order to efficiently exploit this data, it is important to keep track of the dynamic aspect of their chronological evolution by means of two main approaches: the polymorphism, a dynamic model able to support type changes every second with a successful processing and second, the support of data volatility by means of an intelligent model taking in consideration key-data, salient and valuable at a specific moment without processing all volumes of history and up to date data.The primary goal of this study is to establish, based on these approaches, an integrative vision of data life cycle set on 3 steps, (1) data synthesis by selecting key-values of micro-data acquired by different data source operators, (2) data fusion by sorting and duplicating the selected key-values based on a de-normalization aspect in order to get a faster processing of data and (3) the data transformation into a specific format of map of maps of maps, via Hadoop in the standard MapReduce process, in order to define the related graph in applicative layer.In addition, this study is supported by a software prototype using the already described modeling tools, as a toolbox compared to an automatic programming software and allowing to create a customized processing chain of BigData

Cancers often resurrect embryonic molecular programs to promote disease progression. In melanomas, which are tumors of the neural crest (NC) lineage, a molecular signature of the embryonic NC is often reactivated. These NC factors have been implicated in promoting pro-tumorigenic features like proliferation, migration and therapy resistance. However, the molecular mechanisms that establish and maintain NC identities in melanomas are largely unknown. Additionally, whether the presence of a NC identity has any clinical relevance for patient melanomas is also unclear. Here, using comparative genomic approaches, I have a) identified a novel role for GDF6-activated BMP signaling in reawakening a NC identity in melanomas, and b) identified a NC signature as a clinical predictor of melanoma progression. Like the genomes of many solid cancers, melanoma genomes have widespread copy number variations (CNV) harboring thousands of genes. To identify disease-promoting drivers amongst such huge numbers of genes, I used a comparative oncogenomics approach with zebrafish and human melanomas. This approach led to the identification of a recurrently amplified oncogene, GDF6, that acts via BMP signaling to invoke NC identities in melanomas. In maintaining this identity, GDF6 represses the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, allowing melanoma cells to remain undifferentiated and survive. Functional analysis in zebrafish embryos indicated a role of GDF6 in blocking melanocyte differentiation, suggesting that the developmental function of GDF6 is reiterated in melanomas. In clinical assessments, a major fraction of patient melanomas expressed high GDF6, and its expression correlated with poor patient survival. These studies provide novel insights into regulation of NC identities in melanomas and offer GDF6 and components of BMP pathway as targets for therapeutic intervention. In additional studies, I wanted to test whether a broader NC identity in melanomas had any clinical relevance. In these studies, I performed transcriptome analysis of zebrafish melanomas and derived a 15-gene NC signature. This NC gene signature positively correlated with the expression of SOX10, a known NC marker in human melanomas. Patients whose melanomas expressed this signature showed poor overall survival. These findings identify an important predictive signature in human melanomas and also illuminate the clinical importance of NC identity in this disease.

Hace ya varios años Gamarra dejó de ser ese lugar comercial que producía tantas ventas a lo largo del año. Debido a la fuerte competencia del mercado y la falta de valor agregado en sus productos, el Cluster Textil se encuentra en una grave crisis. El centro de enseñanza y difusión de la Moda propone espacios para estas nuevas necesidades de la zona. No solo se quiere capacitar a sus empleados para que puedan competir en la industria, si no también se busca dotar a Gamarra de espacios que les permitan difundir sus productos y sobretodo sus marcas. El partido arquitectónico nació por el análisis del entorno, sus aspectos climáticos, accesibilidad y condiciones ambientales. Se buscó en este que se creen espacios integradores los cuales sirvan de conexión entre Gamarra y el Centro, repotenciando a ambos. El centro de enseñanza y difusión de la moda busca convertir a Gamarra en el Nuevo centro de la Moda metropolitano mediante la capacitación de sus integrantes y la difusión de sus marcas en espacios adecuados y de calidad. / For many years now, Gamarra has ceased to be the go-to commercial destination, with substantial sales and margins throughout the year. Due to strong market competition and lack of added value in its products, the Textile Cluster is currently in a serious crisis. The Fashion Diffusion and Education Center proposes spaces for the new needs in the area. Not only does it want to train its entrepreneurs, so that they can compete in the industry, but also to provide Gamarra with spaces that allow them to diffuse their products and all their brands. The architectural concept was born from an analysis of the area, its climatic aspects, accessibility and environmental conditions. The concept aims for the creation of integrated spaces between Gamarra and the Center that serve as a connection and empower both. The Fashion Promulgation and Education Center seeks to transform Gamarra into the new Metropolitan Fashion Center, by training its entrepreneurs and spreading its brands through quality. / Trabajo de suficiencia profesional

The advent of scRNA-seq has rapidly advanced our understanding of complex systems by enabling the researcher to look at the full transcriptional profile within each cell, with the potential to reveal intercellular communications within a tissue. To map these communications, I created SignallingSingleCell, an R package that provides an end-to-end approach for the analysis of scRNA-seq data, with a particular focus on building ligand and receptor signaling networks. Using these powerful techniques, we sought to dissect the heterogenous population of cells recently reported within the BMDC culture system. From this data we were able to determine the cell type composition, identify the different myeloid responses to similar stimuli, and unify recent conflicting studies about the populations within this system. We then applied these tools to study vitiligo, an autoimmune disease of the skin, to answer fundamental questions about the initiation and progression of disease. We found signatures of increased antigen presentation through MHC-I, loss of immunotolerance cytokines such as TGFB1 and IL-10, and changes in the complex chemokine circuits that influence T cell localization, including an essential role for CCR5 in Treg function. In order to identify and characterize the autoreactive T cells that are responsible for the targeted destruction of melanocytes, we then paired scRNA-seq with TCR-seq and MHC-II complexes loaded with melanocyte antigen. From this data we contrast the transcriptional state of melanocyte specific T cells to bystanders found within the skin and circulation.

Current assessments for evaluating the progression of Parkinson’s Disease are largely qualitative and based on small sets of data obtained from occasional doctor-patient interactions. There is a clinical need to improve the techniques used for mitigating common Parkinson’s Disease symptoms. Available data sets for researching the disease are minimal, hindering advancement toward understanding the underlying causes and effectiveness of treatment and therapies. Mobile devices present an opportunity to continuously monitor Parkinson’s Disease patients and collect important information regarding the severity of symptoms. The evolution of digital technology has opened doors for clinical research to extend beyond the clinic by incorporating complex sensors in commonly used devices. Leveraging these sensors to quantify characteristic Parkinson’s Disease symptoms may drastically improve patient care and the reliability of symptom assessment. The goal of this project is to design and develop a system for measuring and analyzing the cardinal symptoms of Parkinson’s using mobile devices. An application for the iPhone and Apple Watch is developed, utilizing the sensors on the devices to collect data during the performance of motor tasks. Assessments for tremor, bradykinesia, and postural instability are implemented to mimic UPDRS evaluations normally performed by a neurologist. The application connects to a cloud-based server to transfer the collected data for remote access and analysis. Example MatLab analysis demonstrates potential approaches for extracting meaningful data to be used for monitoring the progression of Parkinson’s Disease and the effectiveness of treatment and therapies. High-level verification testing is performed to show general efficacy of the assessment tasks. The system design successfully lays the groundwork for a mobile device-based assessment tool to objectively measure Parkinson’s Disease symptoms