Drug combination: pharmaceutical technologies applied to the manufacturing of combined dosage forms for oral administration

Lo scopo di questa ricerca di dottorato è stato lo studio di una forma di dosaggio flessibile e personalizzabile, indirizzata alle necessità individuali di ogni paziente, per il trattamento dell’iperplasia prostatica benigna. La terapia proposta prevede l’utilizzo di due farmaci, un alfa bloccante (farmaco A) e un inibitore delle 5- fosfodiesterasi (farmaco B) e, somministrati in una singola forma di dosaggio contenenti differenti dosi e combinazioni dei due farmaci. Lo sviluppo di un sistema di rilascio per la somministrazione orale di farmaco A e farmaco B è stato realizzato grazie alla tecnologia Dome Matrix. La tecnologia si basa sull’assemblaggio di moduli utilizzati come elementi di controllo del rilascio. L’assemblaggio dei moduli può essere ottenuto attraverso diverse configurazioni. Sono stati quindi realizzati sistemi assemblati in grado di galleggiare sul contenuto gastrico; la prolungata permanenza della forma farmaceutica nello stomaco favorisce la solubilizzazione dei due principi attivi che quindi potrebbero raggiungere il sito di assorbimento nel primo tratto intestinale già in dispersione molecolare, condizione ideale per essere assorbiti. La prima parte della ricerca è stata focalizzata sulla realizzazione di un sistema assemblato a rilascio modificato di farmaco A. Moduli contenenti diversi dosaggi di farmaco sono stati assemblati in varie configurazioni e dosi differenti per ottenere una forma di dosaggio flessibile, adattabile alle esigenze terapeutiche del paziente. La seconda parte del lavoro di tesi ha riguardato la realizzazione di un sistema assemblato, contenente entrambi i farmaci in associazione. L’ultima parte della ricerca è stata svolta presso la “University of Texas at Austin” sotto la supervisione del Professor Nicholas Peppas. Il lavoro svolto è stato focalizzato sullo studio delle caratteristiche di rigonfiamento dei singoli moduli di farmaco e dei loro sistemi assemblati; il comportamento di tali sistemi è stato investigato anche grazie all’utilizzo della tecnica di tomografia computerizzata a raggi X.

Comparação das atividades musculares durante a mastigação nas maloclusões de classe I e II de Angle

O objetivo deste estudo foi comparar a atividade muscular dos músculos da face e pescoço nas maloclusões Classe I e II de Angle, segundo o sexo. A amostra constou de 36 indivíduos, sendo 22 indivíduos com maloclusão classe I com média de idade de 22,4 anos e 14 indivíduos com maloclusão Classe II com média de idade de 22,8 anos. Os registros foram realizados por um eletromiógrafo de superfície, sendo analisada a atividade dos músculos masseter, temporal feixe anterior, esternocleidomastoídeo e digástrico ventre anterior dos lados direito e esquerdo durante a mastigação dos alimentos uva passa, bolacha água e sal e goma de mascar-PLOC. Após análise estatística descritiva e análise de variância os resultados mostraram que houve diferença estatisticamente significante apenas para os músculos: masseter direito durante a mastigação de uva passa quando comparadas as maloclusões de Classe I e II no sexo masculino; para o músculo digástrico direito quando comparado sexo e as maloclusões Classe I e II durante a mastigação dos três alimentos. Por fim, para o músculo digástrico esquerdo durante a mastigação de uva passa também encontramos diferença estatisticamente significante entre os sexos para as maloclusões Classe I e II. Nossos resultados sugerem que dependendo da consistência do alimento o tipo de maloclusão e sexo podem influenciar na atividade muscular durante a função da mastigação.(AU)

AVALIAÇÃO DAS ALTERAÇÕES DO SORRISO EM INDIVÍDUOS SUBMETIDOS À EXPANSÃO RÁPIDA DA MAXILA

O objetivo deste estudo foi avaliar as possíveis alterações das características horizontais, verticais, de simetria e do arco do sorriso de pacientes com atresia maxilar submetidos à expansão rápida da maxila. A amostra consistiu de 81 fotografias extra-bucais do sorriso máximo de 27 pacientes com idade média de 10 anos e 3 meses. Foram realizadas fotografias do sorriso máximo nos períodos: inicial (antes da instalação do aparelho expansor); 3 meses após a fixação do parafuso expansor; 6 meses após a fixação do parafuso expansor. Para a calibragem e análise das fotografias foi utilizado o programa CEFX 2001 CDT. Os pontos fotométricos e as medidas a serem analisadas foram escolhidos após revisão da literatura do sorriso realizada. Para avaliar as alterações no sorriso durante as fases, foi utilizada a análise de variância ANOVA, com nível de significância de 5%. A expansão rápida da maxila promoveu aumento estatisticamente significante da dimensão transversal do sorriso; aumento da quantidade de exposição dos incisivos centrais e laterais superiores; manutenção da simetria entre os lados direito e esquerdo e da falta de paralelismo entre a curvatura das bordas dos incisivos superiores com a curvatura do lábio inferior (arco do sorriso).(AU)

Avaliação da influência dos formatos DICOM e JPEG na reprodutibilidade de pontos cefalométricos em Telerradiografia digital em Norma Frontal

A imagem digital no formato DICOM requer grande espaço para armazenamento, dificultando o arquivamento e transmissão da imagem via internet, sendo necessária, muitas vezes, a compressão das imagens por meio de formatos de arquivo como o JPEG. O objetivo neste estudo foi avaliar a influência dos formatos DICOM e JPEG, nos Fatores de Qualidade 100, 80 e 60, na reprodutibilidade intra e interexaminador na marcação de pontos cefalométricos em Telerradiografias digitais em Norma Frontal. A amostra consistiu de 120 imagens digitais de Telerradiografias em Norma Frontal, obtidas de 30 indivíduos. As 30 imagens originais, em formato DICOM, posteriormente, foram convertidas para o formato JPEG, nos Fatores de Qualidade 100, 80 e 60. Após cegar e randomizar a amostra, três ortodontistas calibrados marcaram os 18 pontos cefalométricos em cada imagem utilizando um programa de cefalometria computadorizada, que registra as medidas dos pontos cefalométricos em um sistema de coordenadas cartesianas X e Y. Nos resultados, os testes estatísticos de correlações intraclasses e análise de variância (ANOVA) apresentaram concordância de reprodutibilidade dos pontos cefalométricos em Telerradiografias digitais em Norma Frontal, tanto intra como interexaminador, com exceção dos pontos ZL, ZR, AZ, JR, NC, CN na coordenada Y e A6 na coordenada X, independentemente dos formatos de arquivo. Em conclusão, os formatos de arquivo DICOM e JPEG, nos Fatores de Qualidade 100, 80 e 60, não afetaram a reprodutibilidade intra e interexaminador na marcação dos pontos cefalométricos.(AU)

O gauche: poética da travessia entre Renato Russo e Carlos Drummond de Andrade

This dissertation, called “The gauche (O gauche): the poetry of crossing between Renato Russo and Carlos Drummond de Andrade”, discusses on the problematic subjection of the gauche which brings Drummond’s poetry into Renato Russo’s singularizing one, emphasizing such subjection and seeking to find the tension which dwells between both, pointing out at the poet and the songwriter the dislocations, the non-territorial process and the repetition of the difference. Thus, the act, the esthetics and the policy of writing do move from a textual, inter-textual character to a range of references, perceptions, dislocations, establishing within those spaces, elements residing in poetical cartographies which relate both writers on this rizomatic crossing for the writing of both is bound by desire and minorities. To do so, we chose, as research basis, authors such as Gilles Deleuze, Jacques Derrida, Félix Guattari, Jacques Ranciére, Michel Foucault, Maurice Blanchot, Julia Kristeva, Linda Hutcheon, among others who can wander through the established relations of this work.Thus, it constitutes the theoretical and discussion corpus responding to the qualitative implicit requirements of this dissertation. The literary body of this research has a selection of lyrics by Renato Russo and poems by Carlos Drummond presented as subjectivity corpus embracing ideas, affects, perceptions and images

Manifestações oculares em mulheres com síndrome dos ovários policísticos: prevalência e associação com fatores de risco metabólicos e inflamatórios

Objetivos: Estimar a prevalência de alterações do filme lacrimal e da doença do olho seco (DOS), comparar as mudanças na pressão intraocular (PIO) e comparar as espessuras macular e da camada de fibras nervosas da retina (CFNR), entre mulheres com síndrome dos ovários policísticos (SOP) e mulheres saudáveis, estratificando-as em condições clínicas, metabólicas e inflamatórias. Metodologia: O estudo incluiu 45 mulheres com SOP e 47 mulheres saudáveis ovulatórias submetidas a avaliações clínico-ginecológicas e oftalmológicas, incluindo propedêuticas para a avaliação do filme lacrimal e medida da PIO, e medição da espessura macular, da CFNR e parâmetros do disco óptico usando tomografia de coerência óptica. Resultados: Tempo de ruptura do filme lacrimal (TRFL; p=0.001) e impregnação por fluoresceína (p=0.006) apresentaram diferenças estatisticamente significantes entre os grupos estudados. A prevalência de DOS foi de 44,4% nas portadoras de SOP. Houve redução estatisticamente significativa do TRFL na presença de SOP (p=0.001). Além disso, houve efeito estatisticamente significativo de intolerância à glicose e síndrome metabólica/inflamação na impregnação por fluoresceina (p=0.004; p=0.015, respectivamente). A PIO encontrou-se estatisticamente mais elevada no grupo SOP que no grupo controle (p=0.011). Houve um aumento na média do IPC (índice pressão-córnea) com a associação entre SOP e da síndrome metabólica (p = 0.005); A média da espessura da CNFR superior ao redor do nervo óptico foi estatisticamente mais espessa nas voluntárias com SOP que nas voluntárias saudáveis (p=0.036); Após estratificação pela presença de resistência insulínica, as médias dos subcampos das espessuras maculares “macular interno temporal, macular interno inferior, macular interno nasal e macular externo nasal, foram mais espessas no grupo SOP que no grupo controle (p<0.05); Houve associação significativa entre obesidade e resistência insulínica (p=0.037), e intolerância à glicose (p=0.001), com aumento médio do componente principal 1 (CP1), e, na presença de síndrome metabólica (p<0.0001), com aumento médio do componente principal 2 (CP2), respectivamente, em relação à espessura macular total. Na presença de obesidade e inflamação, houve redução no escore médio da CP2 (p=0.034), em relação à espessura da CFNR na mácula. xviii Conclusões: Há uma associação da SOP, suas alterações metabólicas e inflamatórias com alterações do filme lacrimal e com mudanças na PIO. A diminuição na espessura da CFNR macular e aumento da espessura total macular estão possivelmente associadas às alterações metabólicas, e, o aumento na espessura da CFNR ao redor do nervo óptico estão provavelmente associadas às alterações hormonais, inerentes à SOP.

Um retrato do marginal brasileiro mediante o trabalho do ator com as personagens de Plínio Marcos em “Navalha na carne"

This thesis presented is to research the actor's work in the construction of physical actions, according to the methodology developed by Constantin Stanislavski in his analysis of dramatic action, called "method of physical action", applied to questions of scenic representation of the Brazilian marginal, according to the look "cruel" and realistic / naturalistic Plinio Marcos playwright. Based on the circumstances given by Pliniano universe, the intention is to contribute to the reflection on the actor's work on the scene with the marginal characters in "Razor in the Flesh", highlighting some important aspects, to assist in the construction of this fictional world. You want to create conditions for the formation of an actor that leverages the scene the contradictions and conflicts of this work. The research aims from the theoretical and practical study as a methodological hypothesis, producing critical reflection from the creative process of the agent with the realization of a scenic experiment focused on psychophysical technique of this Russian pedagogue. Thus, we intend to have a look at the method of physical actions focusing on his last great contribution to the work, especially the procedure of active analysis by doing a reading from "Razor in the Flesh" through this creative scenic exercise, extending the studies concerning the actor's art. This research is a general explanation about the trajectory of Stanislavski to his encounter with the physical action, while, highlights the inconsistencies of understanding of his work around the world. Stanislavski initially developed the "method" having as a backdrop, the realist aesthetic - a dialogue relationship between reality and the scene - through a style which creates a theatrical reality, and consequently, artistic, not literally naturalistic way through an integral mimicry. That is, the representation of work in realistic theater aesthetics should be developed in order to create a theatrical reality. Stanislavski believes that theater is convention, since the actor's work on himself should encourage this second nature, scenic.

Estudo da estrutura subsuperficial da província Borborema com correlação de ruído sísmico

Ambient seismic noise has traditionally been considered as an unwanted perturbation in seismic data acquisition that "contaminates" the clean recording of earthquakes. Over the last decade, however, it has been demonstrated that consistent information about the subsurface structure can be extracted from cross-correlation of ambient seismic noise. In this context, the rules are reversed: the ambient seismic noise becomes the desired seismic signal, while earthquakes become the unwanted perturbation that needs to be removed. At periods lower than 30 s, the spectrum of ambient seismic noise is dominated by microseism, which originates from distant atmospheric perturbations over the oceans. The microsseism is the most continuous seismic signal and can be classified as primary – when observed in the range 10-20 s – and secondary – when observed in the range 5-10 s. The Green‘s function of the propagating medium between two receivers (seismic stations) can be reconstructed by cross-correlating seismic noise simultaneously recorded at the receivers. The reconstruction of the Green‘s function is generally proportional to the surface-wave portion of the seismic wavefield, as microsseismic energy travels mostly as surface-waves. In this work, 194 Green‘s functions obtained from stacking of one month of daily cross-correlations of ambient seismic noise recorded in the vertical component of several pairs of broadband seismic stations in Northeast Brazil are presented. The daily cross-correlations were stacked using a timefrequency, phase-weighted scheme that enhances weak coherent signals by reducing incoherent noise. The cross-correlations show that, as expected, the emerged signal is dominated by Rayleigh waves, with dispersion velocities being reliably measured for periods ranging between 5 and 20 s. Both permanent stations from a monitoring seismic network and temporary stations from past passive experiments in the region are considered, resulting in a combined network of 33 stations separated by distances between 60 and 1311 km, approximately. The Rayleigh-wave, dispersion velocity measurements are then used to develop tomographic images of group velocity variation for the Borborema Province of Northeast Brazil. The tomographic maps allow to satisfactorily map buried structural features in the region. At short periods (~5 s) the images reflect shallow crustal structure, clearly delineating intra-continental and marginal sedimentary basins, as well as portions of important shear zones traversing the Borborema Province. At longer periods (10 – 20 s) the images are sensitive to deeper structure in the upper crust, and most of the shallower anomalies fade away. Interestingly, some of them do persist. The deep anomalies do not correlate with either the location of Cenozoic volcanism and uplift - which marked the evolution of the Borborema Province in the Cenozoic - or available maps of surface heat-flow, and the origin of the deep anomalies remains enigmatic.

Processos criativos com alunos-atores idosos: caminhos de uma dramaturgia de pertencimento

The present work is to present an experience artistic and pedagogical means of a laboratory-developed with senescent students from their memory files. Unlike other works developed with students of the third age, we make use of the archives of memory, where the drama takes from improvisations developed memories, in other words, the text is built not just recollected by students. Our work, however, is built by a look from the outside. The affective memories narrated by students serve as an engine for text construction and spectacle titled Vamos Falar de Amor. In this experiment the teacher-director also becomes an dramaturgista, and uses her imagination, that also comes filled with her own memories, in order to complete the gaps of the narrative, in a hybrid process in which the collective memory interlace the individual memory, transforming epic into dramatic. Here the route designed to get to the construction of the text and left the text for the second scripture, the spectacle. We want to show that old age is comprised of various hues, and that this phase of human development brings aspects that differ from old to old, and that education and theater can be a resumption of the social role of the elderly in contemporary surroundings. Therefore, the dramaturgy of memory creates the dramaturgy of belonging, facilitating in many aspects the Scenic Play with the elderly ones.

Análise cefalométrica: ortodontistas x radiologistas

Cephalometric analysis is the mensuration of linear and angular measures through demarcation points as distances and lines on teleradiography, and is considered of fundamental importance for diagnosis and orthodontic planning. In this manner, the objective of this research was to compare cephalometric measurements obtained by dentists and radiologists from the analysis of the same radiograph, in a computerized cephalometric analysis program. All research participants marked 18 cephalometric points on a 14-inch notebook computer, as directed by the program itself (Radiocef 2®). From there, they generated 14 cephalometric parameters including skeletal, dental-skeletal, dental and soft tissue. In order to verify the intra-examiner agreement, 10 professionals from each group repeated the marking of the points with a minimum interval of eight days between the two markings. The intra-group variability was calculated based on the coefficients of variation (CV). The comparison between groups was performed using the Student t-test for normally distributed variables, and using the Mann-Whitney test for those with non-normal distribution. In the group of orthodontists, the measurements of Pog and 1-NB, SL, S-Ls Line, S-Li Line and 1.NB showed high internal variability. In the group of radiologists, the same occurred with the values of Pog and 1-NB, S-Ls Line, S-Li Line and 1.NA. In the comparison between groups, all the analyzed linear values and two angular values showed statistically significant differences between radiologists and dentists (p <0.05). According to the results, the interexaminer error in cephalometric analysis requires more attention, but does not come from a specific class of specialists, being either dentists or radiologists.

Explorando a execução de técnicas estendidas no oboé encontradas em quatro peças contemporâneas

This dissertation presents an investigation of the evolutionary process of extended oboe techniques, through literary analysis and practical research. The objective of this work is to provide assistance to oboists interested in learning these techniques. Additionally, this work encourages the student, through the process of experimentation, to explore the questions that may arise around the aesthetics of sound, the concept of gesture as an additional visual and aural element in music, and the collaboration and “real-time” creation processes. Discussed within the work, are the relationship between the instrument (the oboe) and extended techniques, and two possible definitions of extended techniques, provided by Luk Vaes (2009) and Gardner Read (1993). Also explored are the how and why some composers have utilized extended techniques in their compositions, including brief discussions relating to extended techniques in real-time composition (improvisation), extended techniques and technological resources, theatrical gesture as an extended technique, and suggestions of how musicians might approach theatrical gestures in performance. Four works were visited: “I Know This Room So Well” – Lisa Bielawa (2007-9); “Four Pieces for Oboe and Piano” – Ernst Krenek (1966); “In Freundschaft” – Karlheinz Stockhausen (1978); “Atem” – Mauricio Kagel (1969-70); and an exploration of the difficulties and solutions associated with each extended technique found within these pieces, was carried out. The following founding works on extended oboe techniques were used, as a basis for research: books - Heinz Holliger’s Pro Musica Nova (1972); Gardner Read’s Compendium of Modern Instrumental Techniques (1993); Peter Veale & Claus-Steffen Mahnkopf’s The Techniques of Oboe Playing (1994); and Libby Van Cleve’s Oboe Unbound: Contemporary Techniques (2004); and articles - Nora Post’s “Monophonic sound resources for the oboe: Part I – Timbre” (1984), “Part II- Pitch and other techniques” (1984), and “Multiphonics for the oboe” (1982).

Estrutura crustal e mantélica da província Borborema através de funções do receptor e dispersão de ondas superficiais

The Borborema Province, located in northeastern Brazil, has a basement of Precambrian age and a tectonic framework structured at the Neoproterozoic (740-560 Ma). After separation between South America and Africa during the Mesozoic, a rift system was formed, giving rise to a number of marginal and inland basins in the Province. After continental breakup, episodes of volcanism and uplift characterized the evolution of the Province. Plateau uplift was initially related to magmatic underplating of mafic material at the base of the crust, perhaps related to the generation of young continental plugs (45-7 Ma) along the Macau-Queimadas Alignment (MQA), due to a small-scale convection at the continental edge. The goal of this study is to investigate the causes of intra-plate uplift and its relationship to MQA volcanism, by using broadband seismology and integrating our results with independent geophysical and geological studies in the Borborema Province. The investigation of the deep structure of the Province with broadband seismic data includes receiver functions and surface-wave dispersion tomography. Both the receiver functions and surface-wave dispersion tomography are methods that use teleseismic events and allow to develop estimates of crustal parameters such as crustal thickness, Vp/Vs ratio, and S-velocity structure. The seismograms used for the receiver function work were obtained from 52 stations in Northeast Brazil: 16 broadband stations from the RSISNE network (Rede Sismográfica do Nordeste do Brasil), and 21 short-period and 6 broadband stations from the INCT-ET network (Instituto Nacional de Ciência e Tecnologia – Estudos Tectônicos). These results add signifi- cantly to previous datasets collected at individual stations in the Province, which include station RCBR (GSN - Global Seismic Network), stations CAUB and AGBL (Brazilian Lithosphere Seismic Project IAG/USP), and 6 other broadband stations that were part of the Projeto Milênio - Estudos geofísicos e tectônicos na Província Borborema/CNPq. For the surface-wave vii tomography, seismograms recorde at 22 broadband stations were utilized: 16 broadband stations from the RSISNE network and 6 broadband stations from the Milênio project. The new constraints developed in this work include: (i) estimates of crustal thickness and bulk Vp/Vs ratio for each station using receiver functions; (ii) new measurements of surfassewave group velocity, which were integrated to existing measurementes from a continental-scale tomography for South America, and (iii) S-wave velocity models (1D) at various locations in the Borborema Province, developed through the simultaneous inversion of receiver functions and surface-wave dispersion velocities. The results display S-wave velocity structure down to the base of the crust that are consistent with the presence of a 5-7.5 km thick mafic layer. The mafic layer was observed only in the southern portion of the Plateau and absent in its northern portion. Another important observation is that our models divide the plateau into a region of thin crust (northern Plateau) and a region of thick crust (southern Plateau), confirming results from independent refraction surveys and receiver function analyses. Existing models of plateau uplift, nonetheless, cannot explain all the new observations. It is proposed that during the Brazilian orogeny a layer of preexisting mafic material was delaminated, as a whole or in part, from the original Brasiliano crust. Partial delamination would have happened in the southern portion of the plateau, where independent studies found evidence of a more resistant rheology. During Mesozoic rifting, thinning of the crust around the southern Plateau would have formed the marginal basins and the Sertaneja depression, which would have included the northern part of the Plateau. In the Cenozoic, uplift of the northern Plateau would have occurred, resulting in a northern Plateau without mafic material at the base of the crust and a southern Plateau with partially delaminated mafic layer.

Atuações e papéis femininos: o corpo a corpo da atriz no teatro pernambucano durante a ditadura militar

This research investigated the female performance in Pernambuco theater during the Brazilian military dictator ship in the 1970s, analyzing the works of four actresses of theater groups Hermilo Borba Filho, Experiential and Expression, who acted in the period. Launches a look at the female body in the theater from a body scenic transgression: the conscience of a body insubordination in response to a given context. However, before delineated an overview of the artistic and socio - cultural position of women in the theater, in the periods prior to the dictatorship in Brazil and Pernambuco, covering theatrical and historical references, in order to reflect on how these settings interfered in the picture Social actr ess under the dictatorship. The groups are revisited by the looks of interpreters, which was perceived that female targeted search relationships, and in this context, relations with other theater groups of the time, with other artists of the groups that we re inserted with the dictatorial context with censorship, with the offender engaged and theater, with the body. In parallel, it develops a reflection on the scenic body that opposed the dictatorship, a body that violates the established norms, the Transgre ssor Body. The research also discusses an analogy between the work of the actresses who opposed the military regime and militant women. Starting from analyzes with interviews with the actresses from the methodologies of Oral History and Discourse Analysis, the study is developed by building up connections between the testimonies of the artists and the philosophical assumptions of Henri Bergson, on the body and memory. It is also designed to reflect on the changes of the female body in the theater in history , also in line with the philosophical concept of Becoming Woman Felix Guattari. It was found, therefore, that the actresses from the nineteenth century, were a group of female social actors who changed the position of women in history; the stigmatization o f the actress by profession, considered indecent in previous centuries, left traces in some areas today and the idea of the liberation of the female body propagated by feminism in the 1970s, was configured at the time as the best way to protest and will influence, in some contexts, the representation of women in their theatrical make.