EFEITOS ESQUELÉTICOS DA TRAÇÃO REVERSA DA MAXILA UTILIZANDO TOMOGRAFIA COMPUTADORIZADA

Este estudo avaliou os efeitos esqueléticos da tração reversa da maxila utilizando imagens 2D (telerradiografia lateral) geradas a partir da tomografia de feixe cônico (imagens 3D). A amostra foi composta por 20 crianças (15 do gênero feminino, e 5 do masculino), com idade variando de 5,6 a 10,7 anos que apresentavam má-oclusão de Classe III de Angle. A tomografia foi realizada antes do tratamento (T1) e logo após o tratamento (T2). O tratamento foi realizado por meio da tração reversa da maxila utilizando-se o aparelho expansor Hyrax associado à máscara facial individualizada, com força de 600 a 800g de cada lado, durante 14 horas por dia. A correção da relação de caninos em Classe I ou com sua sobrecorreção em Classe II foi obtida após 4 a 8 meses de tratamento. Para verificar o erro sistemático e casual foi utilizado o teste t pareado e a fórmula de Dahlberg, respectivamente. O teste t pareado (p<0,05) mostrou diferença significante entre as medidas cefalométricas obtidas em T1 e T2. Na maxila houve aumento do SNA 2,2°, A-Nperp 1,47mm e em Co-A 2,58mm. Na mandíbula, SNB diminuiu -0,54° e P-Nperp, -1,45mm, enquanto Co-Gn aumentou 1,04mm. Houve melhora na relação maxilo-mandibular ANB 2,74° e Wits 4,23mm. As variáveis GoGn.SN, Gn.SN, FH.Md, Mx.Md, e AFAI aumentaram demonstrando que houve uma rotação da mandíbula no sentido horário. O plano palatino rotacionou no sentido anti-horário. Pode se concluir que o tratamento de tração reversa da maxila na idade precoce promoveu uma melhora na relação maxilo-mandibular devido a um avanço da maxila e um deslocamento da mandíbula para baixo e para trás.

OSTEOTOMIA SEGMENTAR DE MAXILA CASO CLÍNICO

A Osteotomia Segmentar de Maxila ou Osteotomia Le Fort I Segmentada é um procedimento que tem se tornado, cada vez mais comum, nas cirugias para as correções das deformidades dentofaciais, conhecidas como Cirurgias Ortognáticas. Este procedimento é muito bem indicado para a correção das discrepâncias maxilares, nos diferentes planos e num único tempo cirúrgico, otimizando assim, o tempo de tratamento a que o paciente é submetido. A estabilidade esquelética transversal e a oclusal dos pacientes, que são submetidos a este tipo de osteotomia, tem sido objeto de estudo na literatura , assim como também, os potenciais riscos e complicações inerentes a este procedimento como, a desvitalização dentária, fístula oro-nasal, perda dentária, necrose de algum segmento da maxila ou até mesmo, de toda a maxila. O objetivo deste trabalho é apresentar o caso clínico de um paciente submetido à osteotomia segmentar de maxila, e fazer uma revisão da literatura abrangendo os últimos 10 anos, com artigos que abordam a estabilidade deste tipo de procedimento, assim como também os potenciais riscos e complicações aos pacientes submetidos a este procedimento. Utilizando algumas palavras chave na base de dados eletrônica PUBMED, 12 artigos foram selecionados para este trabalho, no período de 2002 a 2012. A Osteotomia Segmentar de Maxila é um procedimento estável e seguro, com baixo índice de complicação, quando indicado corretamente e com os devidos cuidados no pré, trans e pós operatórios.

REABSORÇÃO CONDILAR INTERNA DA ARTICULAÇÃO TEMPOROMANDIBULAR NO PACIENTE ADOLESCENTE

A reabsorção condilar interna no adolescente (RCIA) é uma doença progressiva que afeta a articulação temporomandibular (ATM) e que pode resultar em maloclusão, deformidade facial, disfunção de ATM e dor. O aparecimento desta doença ocorre entre os 10 e os 15 anos, sendo mais freqüente em adolescentes do sexo feminino. Esses pacientes apresentam sinais clínicos característicos como: ângulo do plano oclusal e do plano mandibular aumentados, retrusão progressiva da mandíbula e maloclusão Classe II, com ou sem mordida aberta. Nos exames de imagem (tomografia computadorizada e ressonância magnética), observa-se reabsorção interna dos côndilos e deslocamento dos discos articulares da ATM. Tendo em vista a dificuldade em determinar a causa da RCIA e a importância em eliminar a dor e melhorar a função mastigatória, este estudo se propôs a avaliar as alterações promovidas no posicionamento mandibular, a sintomatologia dolorosa e a estabilidade do tratamento da RCIA, utilizando o protocolo de tratamento (Dr. Larry M. Wolford) em pacientes adolescentes submetidos a cirurgia de reposicionamento do disco articular e cirurgia ortognática, realizadas no mesmo ato cirúrgico. Neste estudo retrospectivo, foram avaliadas as telerradiografias laterais adquiridas na avaliação inicial (T1), pré-cirúrgica (T2), pós-cirúrgica imediata (T3) e de maior acompanhamento, com pelo menos um ano pós-cirurgia (T4) e questionários de dor e função mandibular de uma amostra de 24 pacientes com maloclusão de Classe II (20 do sexo feminino e 4 do sexo masculino) diagnosticados com RCIA, os quais foram submetidos ao protocolo de tratamento composto pela cirurgia de reposicionamento do disco articular da ATM concomitantemente à cirurgia ortognática. O protocolo de tratamento utilizado mostrou-se bastante positivo, uma vez que a estabilidade foi adquirida e uma melhora significativa nos níveis de dor e função mandibular foram atingidos. O tratamento dos pacientes diagnosticados com RCIA, através do protocolo de tratamento proposto, é um procedimento estável e atua diretamente em um ganho na redução da dor.

AVALIAÇÃO CEFALOMÉTRICA DA ESTABILIDADE DO TRATAMENTO COM O REGULADOR DE FUNÇÃO FRÄNKEL-2

O objetivo desta pesquisa consistiu em comparar as alterações dentárias, esqueléticas e tegumentares promovidas pelo aparelho de Fränkel-2 com um grupo controle, além de observar a estabilidade desses efeitos promovidos pelo tratamento, num período médio de 7,11 anos pós-tratamento. A amostra compreendeu um total de 90 telerradiografias em norma lateral, sendo 54 telerradiografias provenientes de 18 pacientes tratados com o RF-2 avaliados em três fases (T1:início de tratamento;T2: final de tratamento e T3: pós-tratamento) e 36 telerradiografias de 18 pacientes-controle, observados em dois tempos. Para comparação entre os grupos tratado e controle foi utilizado o teste t de Student não pareado. Já para a análise dos valores do grupo tratado nos três tempos (T1, T2 e T3) foi utilizada a Análise de Variância (ANOVA) a um critério e o teste de Tukey (p<0,05). As principais alterações proporcionadas pelo aparelho RF-2 observadas a partir da comparação do grupo tratado com o controle envolveram efeitos mandibulares, principalmente a protrusão e aumento do comprimento mandibular associado com uma rotação horária, que resultou em uma maior altura facial total (N-Me) e ântero-inferior (AFAI), além de suave rotação anti-horária do plano palatino (SN.PP). Os incisivos superiores retruíram e o inferior vestibularizou. Houve uma distalização relativa dos molares superiores juntamente com a diminuição do overjet , desta forma a convexidade do perfil facial tegumentar melhorou. No período pós-tratamento (T3) observou-se uma estabilidade sagital de maxila (SNA) e mandíbula (SNB), das variáveis do padrão facial, da inclinação do incisivo superior, do ângulo nasolabial e do overjet . A mandíbula e a maxila continuaram a crescer no sentido antero-posterior, juntamente com as alturas faciais Houve também a extrusão de incisivos e molares. Já o plano oclusal e o ângulo goníaco diminuíram na fase pós-tratamento.(AU)

AVALIAÇÃO DA ESTABILIDADE DAS ALTERAÇÕES TRANSVERSAIS PROMOVIDAS PELO APARELHO REGULADOR DE FUNÇÃO FRANKEL 2, POR MEIO DE TELERRADIOGRAFIAS POSTEROANTERIORES

O objetivo desta pesquisa constituiu em avaliar, por meio das telerradiografias posteroanteriores, as alterações transversais promovidas pelo aparelho Frankel-2 em pacientes com maloclusão de Classe II, divisão 1, além de verificar a estabilidade das mesmas após um período médio de 7,11 anos pós-tratamento. A amostra compreendeu um total de 45 telerradiografias posteroanteriores provenientes de 15 pacientes tratados com o RF-2, realizadas em três fases: (T1) início do tratamento; (T2) final de tratamento; (T3) pós-tratamento. Foram avaliadas outras 36 telerradiografias posteroanteriores de 18 pacientes não tratados (grupo controle), acompanhados num período correspondente ao tratamento (T1-T2). As telerradiografias foram digitalizadas e foi utilizado o software Radiocef Studio 2 para realizar as mensurações das medidas cefalométricas. Para a comparação entre as alterações ocorridas no grupo tratado e no grupo controle, foi aplicado o teste t não pareado. Já para as modificações nas fases inicial, final e pós-tratamento no grupo tratado, foi empregada a Análise de Variância seguida do teste de comparações múltiplas de Tukey, com o valor crítico de 0,05. Os resultados mostraram que durante o período de tratamento as distâncias intercaninos inferiores e intermolares superiores aumentaram de forma estatisticamente significante. Já as distâncias que representam a largura da cavidade nasal, altura facial inferior, largura mandibular e distância intermolares inferiores não sofreram alterações estatisticamente significantes. No período pós-tratamento, observou-se uma suave redução nas distâncias intercaninos inferiores e intermolares superiores. Porém, considerando-se as alterações ocorridas devido ao crescimento e desenvolvimento transversal dos arcos dentários no período analisado, em que haveria uma redução destas distâncias, provavelmente houve uma estabilidade relativa das alterações dentárias transversais promovidas pelo RF-2. Portanto, pode-se concluir que o RF-2 não possui qualquer efeito esquelético transversal. Contudo, há um aumento das distâncias intermolares superiores e intercaninos inferiores durante o tratamento, que permanece relativamente estável, considerando-se as alterações ocorridas pelo crescimento e desenvolvimento normal dos arcos dentários.

The effect of mastery learning on a course in accounting information system (AIS): A comparison within public and private universities in Taiwan

The Accounting Information System (AIS) is an important course in the Department of Accounting (DoAc) of universities in Taiwan. This course is required for seniors not only because it meets the needs of the profession, but also because it provides continual study for the department's students.^ The scores of The National College and University Joint Entrance Examination (NUEE) show that students with high learning ability are admitted to public universities with high scores, while those with low learning ability are admitted only to private universities. The same situation has been found by the researcher while teaching an AIS course in DoAc of The Public Chun Shin University (CSU) and The Private Chinese Culture University (CCU).^ The purpose of this study was to determine whether low ability students enrolled in private universities in Taiwan in a mastery learning program could attain the same level as high ability students from public universities enrolled in a traditional program. An experimental design was used. The mastery learning method was used to teach three groups of seniors with low learning ability studying in the DoAc at CCU. The traditional method was used to teach the control group which consisted of senior students of DoAc of CSU with high learning ability. As a part of the mastery learning strategy, a formative test, quizzes, and homework were completed by the experimental group only, while the mid-term examination was completed by both groups as part of the course. The dependent variable was the summative test, the final examination. It was completed by both groups upon the course's completion.^ As predicted, there were significant differences between the two groups' results on the pretest. There were no significant differences between the two groups' results on the posttest. These findings support the hypothesis of the study and reveal the effectiveness of mastery learning strategies with low learning ability students. ^

Duplicação rápida de prótese total: passo-a-passo

This study presents a simple, fast and low cost technique for fabrication new conventional dentures from the duplication of old prosthesis in use by the patient. Colorless acrylic resin was poured into the moulds obtained by duplication of prosthesis. With the replicas obtained a functional impressions using polyether should be performed and they are stabilized with occlusal registration in acrylic resin. The molds need to be castings and mounted on an semi-adjustable articulator. The artificial teeth are positioned with the assistance of a guide made condensation silicone to reproduce the positioning of the teeth of the old prosthesis and fixed with wax 7. After approval of the teeth on the trial in wax, without adjustment of the planes, the prosthesis may be processed in the laboratory. After occlusal adjustment in the articulator the same can be installed.

Morfometria dos forames mandibular, mentual e infraorbital de Lobo-guará Chrysocyon brachyurus, Illiger, 1815 aplicada a bloqueios anestésicos

CHAPTER II - The Chrysocyon brachyurus is the biggest South American canid which has a high frequency of dental injuries, both in wild and captivity. Thus, veterinary procedures are necessary to preserve the feeding capacity of hundreds of captive specimens worldwide. The aim of this study was to study the mandibular morphometry of maned wolf with emphasis on the establishment of anatomic references to the anesthetic blockage of the inferior alveolar and mental nerves. Therefore, 15 measurements in 22 hemimandibles of C. brachyurus adults were taken. For extra-oral technique of blockage of the inferior alveolar nerve at the level of the mandibular foramen, it is stated that the needle should be advanced, close to the medial surface of the mandibular ramus, by 11.4 mm perpendiculary from the palpable concavity. Alternatively, the needle can be introduced for 30.4 mm from the angular process at 20-25 degrees angle with the ventral margin. For blocking only the mentual nerve, it is recommended the introduction of needle for 10 mm, close to the lateral aspect of the mandibular body, at the level of the lower first premolar. The mandibular foramen showed similars position, size and symmetry in the maned wolfs specimens examined. The comparison of the data with those available for other carnivores reflects the necessity for determining these anatomical references specifically for each species.

Advanced Techniques for Image Quality Assessment of Modern X-ray Computed Tomography Systems

X-ray computed tomography (CT) imaging constitutes one of the most widely used diagnostic tools in radiology today with nearly 85 million CT examinations performed in the U.S in 2011. CT imparts a relatively high amount of radiation dose to the patient compared to other x-ray imaging modalities and as a result of this fact, coupled with its popularity, CT is currently the single largest source of medical radiation exposure to the U.S. population. For this reason, there is a critical need to optimize CT examinations such that the dose is minimized while the quality of the CT images is not degraded. This optimization can be difficult to achieve due to the relationship between dose and image quality. All things being held equal, reducing the dose degrades image quality and can impact the diagnostic value of the CT examination.

A recent push from the medical and scientific community towards using lower doses has spawned new dose reduction technologies such as automatic exposure control (i.e., tube current modulation) and iterative reconstruction algorithms. In theory, these technologies could allow for scanning at reduced doses while maintaining the image quality of the exam at an acceptable level. Therefore, there is a scientific need to establish the dose reduction potential of these new technologies in an objective and rigorous manner. Establishing these dose reduction potentials requires precise and clinically relevant metrics of CT image quality, as well as practical and efficient methodologies to measure such metrics on real CT systems. The currently established methodologies for assessing CT image quality are not appropriate to assess modern CT scanners that have implemented those aforementioned dose reduction technologies.

Thus the purpose of this doctoral project was to develop, assess, and implement new phantoms, image quality metrics, analysis techniques, and modeling tools that are appropriate for image quality assessment of modern clinical CT systems. The project developed image quality assessment methods in the context of three distinct paradigms, (a) uniform phantoms, (b) textured phantoms, and (c) clinical images.

The work in this dissertation used the “task-based” definition of image quality. That is, image quality was broadly defined as the effectiveness by which an image can be used for its intended task. Under this definition, any assessment of image quality requires three components: (1) A well defined imaging task (e.g., detection of subtle lesions), (2) an “observer” to perform the task (e.g., a radiologists or a detection algorithm), and (3) a way to measure the observer’s performance in completing the task at hand (e.g., detection sensitivity/specificity).

First, this task-based image quality paradigm was implemented using a novel multi-sized phantom platform (with uniform background) developed specifically to assess modern CT systems (Mercury Phantom, v3.0, Duke University). A comprehensive evaluation was performed on a state-of-the-art CT system (SOMATOM Definition Force, Siemens Healthcare) in terms of noise, resolution, and detectability as a function of patient size, dose, tube energy (i.e., kVp), automatic exposure control, and reconstruction algorithm (i.e., Filtered Back-Projection– FPB vs Advanced Modeled Iterative Reconstruction– ADMIRE). A mathematical observer model (i.e., computer detection algorithm) was implemented and used as the basis of image quality comparisons. It was found that image quality increased with increasing dose and decreasing phantom size. The CT system exhibited nonlinear noise and resolution properties, especially at very low-doses, large phantom sizes, and for low-contrast objects. Objective image quality metrics generally increased with increasing dose and ADMIRE strength, and with decreasing phantom size. The ADMIRE algorithm could offer comparable image quality at reduced doses or improved image quality at the same dose (increase in detectability index by up to 163% depending on iterative strength). The use of automatic exposure control resulted in more consistent image quality with changing phantom size.

Based on those results, the dose reduction potential of ADMIRE was further assessed specifically for the task of detecting small (<=6 mm) low-contrast (<=20 HU) lesions. A new low-contrast detectability phantom (with uniform background) was designed and fabricated using a multi-material 3D printer. The phantom was imaged at multiple dose levels and images were reconstructed with FBP and ADMIRE. Human perception experiments were performed to measure the detection accuracy from FBP and ADMIRE images. It was found that ADMIRE had equivalent performance to FBP at 56% less dose.

Using the same image data as the previous study, a number of different mathematical observer models were implemented to assess which models would result in image quality metrics that best correlated with human detection performance. The models included naïve simple metrics of image quality such as contrast-to-noise ratio (CNR) and more sophisticated observer models such as the non-prewhitening matched filter observer model family and the channelized Hotelling observer model family. It was found that non-prewhitening matched filter observers and the channelized Hotelling observers both correlated strongly with human performance. Conversely, CNR was found to not correlate strongly with human performance, especially when comparing different reconstruction algorithms.

The uniform background phantoms used in the previous studies provided a good first-order approximation of image quality. However, due to their simplicity and due to the complexity of iterative reconstruction algorithms, it is possible that such phantoms are not fully adequate to assess the clinical impact of iterative algorithms because patient images obviously do not have smooth uniform backgrounds. To test this hypothesis, two textured phantoms (classified as gross texture and fine texture) and a uniform phantom of similar size were built and imaged on a SOMATOM Flash scanner (Siemens Healthcare). Images were reconstructed using FBP and a Sinogram Affirmed Iterative Reconstruction (SAFIRE). Using an image subtraction technique, quantum noise was measured in all images of each phantom. It was found that in FBP, the noise was independent of the background (textured vs uniform). However, for SAFIRE, noise increased by up to 44% in the textured phantoms compared to the uniform phantom. As a result, the noise reduction from SAFIRE was found to be up to 66% in the uniform phantom but as low as 29% in the textured phantoms. Based on this result, it clear that further investigation was needed into to understand the impact that background texture has on image quality when iterative reconstruction algorithms are used.

To further investigate this phenomenon with more realistic textures, two anthropomorphic textured phantoms were designed to mimic lung vasculature and fatty soft tissue texture. The phantoms (along with a corresponding uniform phantom) were fabricated with a multi-material 3D printer and imaged on the SOMATOM Flash scanner. Scans were repeated a total of 50 times in order to get ensemble statistics of the noise. A novel method of estimating the noise power spectrum (NPS) from irregularly shaped ROIs was developed. It was found that SAFIRE images had highly locally non-stationary noise patterns with pixels near edges having higher noise than pixels in more uniform regions. Compared to FBP, SAFIRE images had 60% less noise on average in uniform regions for edge pixels, noise was between 20% higher and 40% lower. The noise texture (i.e., NPS) was also highly dependent on the background texture for SAFIRE. Therefore, it was concluded that quantum noise properties in the uniform phantoms are not representative of those in patients for iterative reconstruction algorithms and texture should be considered when assessing image quality of iterative algorithms.

The move beyond just assessing noise properties in textured phantoms towards assessing detectability, a series of new phantoms were designed specifically to measure low-contrast detectability in the presence of background texture. The textures used were optimized to match the texture in the liver regions actual patient CT images using a genetic algorithm. The so called “Clustured Lumpy Background” texture synthesis framework was used to generate the modeled texture. Three textured phantoms and a corresponding uniform phantom were fabricated with a multi-material 3D printer and imaged on the SOMATOM Flash scanner. Images were reconstructed with FBP and SAFIRE and analyzed using a multi-slice channelized Hotelling observer to measure detectability and the dose reduction potential of SAFIRE based on the uniform and textured phantoms. It was found that at the same dose, the improvement in detectability from SAFIRE (compared to FBP) was higher when measured in a uniform phantom compared to textured phantoms.

The final trajectory of this project aimed at developing methods to mathematically model lesions, as a means to help assess image quality directly from patient images. The mathematical modeling framework is first presented. The models describe a lesion’s morphology in terms of size, shape, contrast, and edge profile as an analytical equation. The models can be voxelized and inserted into patient images to create so-called “hybrid” images. These hybrid images can then be used to assess detectability or estimability with the advantage that the ground truth of the lesion morphology and location is known exactly. Based on this framework, a series of liver lesions, lung nodules, and kidney stones were modeled based on images of real lesions. The lesion models were virtually inserted into patient images to create a database of hybrid images to go along with the original database of real lesion images. ROI images from each database were assessed by radiologists in a blinded fashion to determine the realism of the hybrid images. It was found that the radiologists could not readily distinguish between real and virtual lesion images (area under the ROC curve was 0.55). This study provided evidence that the proposed mathematical lesion modeling framework could produce reasonably realistic lesion images.

Based on that result, two studies were conducted which demonstrated the utility of the lesion models. The first study used the modeling framework as a measurement tool to determine how dose and reconstruction algorithm affected the quantitative analysis of liver lesions, lung nodules, and renal stones in terms of their size, shape, attenuation, edge profile, and texture features. The same database of real lesion images used in the previous study was used for this study. That database contained images of the same patient at 2 dose levels (50% and 100%) along with 3 reconstruction algorithms from a GE 750HD CT system (GE Healthcare). The algorithms in question were FBP, Adaptive Statistical Iterative Reconstruction (ASiR), and Model-Based Iterative Reconstruction (MBIR). A total of 23 quantitative features were extracted from the lesions under each condition. It was found that both dose and reconstruction algorithm had a statistically significant effect on the feature measurements. In particular, radiation dose affected five, three, and four of the 23 features (related to lesion size, conspicuity, and pixel-value distribution) for liver lesions, lung nodules, and renal stones, respectively. MBIR significantly affected 9, 11, and 15 of the 23 features (including size, attenuation, and texture features) for liver lesions, lung nodules, and renal stones, respectively. Lesion texture was not significantly affected by radiation dose.

The second study demonstrating the utility of the lesion modeling framework focused on assessing detectability of very low-contrast liver lesions in abdominal imaging. Specifically, detectability was assessed as a function of dose and reconstruction algorithm. As part of a parallel clinical trial, images from 21 patients were collected at 6 dose levels per patient on a SOMATOM Flash scanner. Subtle liver lesion models (contrast = -15 HU) were inserted into the raw projection data from the patient scans. The projections were then reconstructed with FBP and SAFIRE (strength 5). Also, lesion-less images were reconstructed. Noise, contrast, CNR, and detectability index of an observer model (non-prewhitening matched filter) were assessed. It was found that SAFIRE reduced noise by 52%, reduced contrast by 12%, increased CNR by 87%. and increased detectability index by 65% compared to FBP. Further, a 2AFC human perception experiment was performed to assess the dose reduction potential of SAFIRE, which was found to be 22% compared to the standard of care dose.

In conclusion, this dissertation provides to the scientific community a series of new methodologies, phantoms, analysis techniques, and modeling tools that can be used to rigorously assess image quality from modern CT systems. Specifically, methods to properly evaluate iterative reconstruction have been developed and are expected to aid in the safe clinical implementation of dose reduction technologies.

Essays in Macroeconomics

My dissertation consists of three self-contained essays on macroeconomics. Chapter 2 "Churning, firm inter-connectivity, and labor market fluctuations'' studies the implications of firm inter-connectivity and irreversibility of inter-firm cooperation relationships on the business cycle. Chapter 3 "Inter-sector matching efficiency and sectoral comovement'' examines the comovement of sectoral labor markets when there is search friction in the inter-firm matching market. Chapter 4 "Lumpy investment and endogenous investment price'' (Joint work with Linxi Chen) studies the endogenous fluctuation of investment price induced by search friction in the investment goods market and partial irreversibility of capital adjustment. Each of the essays investigates the implication of market frictions, such as search friction and partial irreversibility, to the business cycle from a different perspective.

Premotor Mechanisms for Orofacial Coordination

The mouth, throat, and face contain numerous muscles that participate in a large variety of orofacial behaviors. The jaw and tongue can move independently, and thus require a high degree of coordination among the muscles that move them to prevent self-injury. However, different orofacial behaviors require distinct patterns of coordination between these muscles. The method through which motor control circuitry might coordinate this activity has yet to be determined. Electrophysiological, immunohistochemical, and retrograde tracing studies have attempted to identify populations of premotor neurons which directly send information to orofacial motoneurons in an effort to identify sources of coordination. Yet these studies have not provided a complete picture of the population of neurons which monosynaptically connect to jaw and tongue motoneurons. Additionally, while many of these studies have suggested that premotor neurons projecting to multiple motor pools may play a role in coordination of orofacial muscles, no clear functional roles for these neurons in the coordination of natural orofacial movements has been identified.

In this dissertation, I took advantage of the recently developed monosynaptic rabies virus to trace the premotor circuits for the jaw-closing masseter muscle and tongue-protruding genioglossus muscle in the neonatal mouse, uncovering novel premotor inputs in the brainstem. Furthermore, these studies identified a set of neurons which form boutons onto motor neurons in multiple motor pools, providing a premotor substrate for orofacial coordination. I then combined a retrogradely traveling lentivirus with a split-intein mediated split-Cre recombinase system to isolate and manipulate a population of neurons which project to both left and right jaw-closing motor nuclei. I found that these bilaterally projecting neurons also innervate multiple other orofacial motor nuclei, premotor regions, and midbrain regions implicated in motor control. I anatomically and physiologically characterized these neurons and used optogenetic and chemicogenetic approaches to assess their role in natural jaw-closing behavior, specifically with reference to bilateral masseter muscle electromyogram (EMG) activity. These studies identified a population of bilaterally projecting neurons in the supratrigeminal nucleus as essential for maintenance of an appropriate level of masseter activation during natural chewing behavior in the freely moving mouse. Moreover, these studies uncovered two distinct roles of supratrigeminal bilaterally projecting neurons in bilaterally synchronized activation of masseter muscles, and active balancing of bilateral masseter muscle tone against an excitatory input. Together, these studies identify neurons which project to multiple motor nuclei as a mechanism by which the brain coordinates orofacial muscles during natural behavior.

Systematic review of Late Jurassic sauropods from the Museu Geológico collections (Lisboa, Portugal)

The Museu Geológico collections house some of the first sauropod references of the Lusitanian Basin Upper Jurassic record, including the Lourinhasaurus alenquerensis and Lusotitan atalaiensis lectotypes, previously considered as new species of the Apatosaurus and Brachiosaurus genera, respectively. Several fragmentary specimens have been classical referred to those taxa, but the most part of these systematic attributions are not supported herein, excluding a caudal vertebra from Maceira (MG 8804) considered as cf. Lusotitan atalaiensis. From the material housed in the Museu Geológico were identified basal eusauropods (indeterminate eusauropods and turiasaurs) and neosauropods (indeterminate neosauropods, diplodods and camarasaurids and basal titanosauriforms). Middle caudal vertebrae with lateral fossae, ventral hollow border by pronounced ventrolateral crests and quadrangular cross-section suggest for the presence of diplodocine diplodocids in north area of the Lusitanian Basin Central Sector during the Late Jurassic. A humerus collected from Praia dos Frades (MG 4976) is attributed to cf. Duriatitan humerocristatus suggesting the presence of shared sauropod forms between the Portugal and United Kingdom during the Late Jurassic. Duriatitan is an indeterminate member of Eusauropoda and the discovery of new material in both territories is necessary to confirm this systematic approach. The studied material is in according with the previous recorded paleobiodiversity for the sauropod clade during the Portuguese Late Jurassic, which includes basal eusauropods (including turiasaurs), diplodocids and macronarians (including camarasaurids and basal titanosauriforms).

Adesp. fr. 700 K.-Sn. y "Andrómeda" de Eurípides

adesp. fr. 700 Kn.-Sn. podría proceder de Andrómeda de Eurípides y no de una Níobe. Los siguientes elementos de los frs. (a) y (b) pueden responder a lo que se conoce de la tragedia de Eurípides: (a) la semejanza con una estatua; (b) la novia de Hades; (c) el silencio del personaje; (d) la colaboración con las Moiras; (e) el contraste entre la fortuna regia y la desgracia y el sufrimiento de los padres. No es, por tanto, necesario modificar el texto recibido para eliminar μάγους πάγας y la referencia a las trampas mágicas en el v. 5, que cuadra bien con Medusa y Perseo.

Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA

Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs possess anticancer potential, but exploitation of these antiproliferative properties is limited by their toxicities. We previously reported the utility of a cationic amphipathic fusogenic peptide, RALA, to traffic anionic nucleic acids into various cell types in the form of cationic nanoparticles. We hypothesized that complexation with RALA could similarly be used to conceal a BP's hydroxyapatite affinity, and to enhance bioavailability, thereby improving anticancer efficacy. Incubation of RALA with alendronate, etidronate, risedronate, or zoledronate provoked spontaneous electrostatic formation of cationic nanoparticles that did not exceed 100 nm in diameter and that were stable over a range of temperatures and for up to 6 h. The nanoparticles demonstrated a pH responsiveness, possibly indicative of a conformational change, that could facilitate release of the BP cargo in the endosomal environment. RALA/BP nanoparticles were more potent anticancer agents than their free BP counterparts in assays investigating the viability of PC3 prostate cancer and MDA-MB-231 breast cancer cells. Moreover, RALA complexation potentiated the tumor growth delay activity of alendronate in a PC3 xenograft model of prostate cancer. Taken together, these findings further validate the use of BPs as repurposed anticancer agents.