Head and neck cancers account for 3% of all newly diagnosed cancers, of which 90% are squamous cell carcinomas (SCC). Improvements in surgery, radiotherapy and chemotherapy have done little to improve the mortality of this disease over the past 20 years while current clinicopathological predictors of disease outcome are sub-optimal. Identifying molecular targets of prognostic and therapeutic significance in head and neck squamous cell carcinomas (HNSCC) may help direct novel therapies to patients whom it is most likely to benefit. Accrued knowledge of the biology of HNSCC has highlighted specific aberrations in pRb and p53 pathways which warrant further study. An immunohistochemical analysis (IHC) in a cohort of 145 patients with SCC of the anterior tongue was performed. Protein expression of the pRb and p53 pathways and related molecules that directly or indirectly influence cell cycle progression at the G1/S phase checkpoint was assessed. We determined that over-expression of E2F-1 occurred in &gt35% of these cancers and associated with improved overall survival on univariate analysis. The strongest multivariate model included: regional lymph node status, tumour grade, p16INK4A, cyclin D1 and p14ARF. This is the first study to determine that p14ARF is an independent marker of both improved diseasefree survival and overall survival in a cohort of SCC of the anterior tongue. Unrecognized molecular heterogeneity is thought to account for the unpredictable clinical response to ZD1839, an EGFR tyrosine kinase inhibitor. We explored the anti-proliferative effects following ZD1839 treatment alone or in combination with radiotherapy in cyclin D1 and E2F-1 over-expressing SCC9 HNSCC cells. SCC9 cells over-expressing cyclin D1 or E2F-1 were highly resistant to ZD1839 treatment, while E2F-1 clones were also radioresistant. Combined therapy in SCC9 controls had a greater anti-proliferative effect than each individual treatment. These data showed that cyclin D1 and E2F-1 may have utility as markers of ZD1839 resistance. The data in this thesis contribute to our knowledge of the clinical behaviour and molecular pathology of HNSCC. Specifically the molecular data identifies novel markers of outcome in SCC of the anterior tongue such as p14ARF, and therapeutic response to ZD1839 such as cyclin D1 and E2F-1. This study addresses in part, the current issues and limitations of management in HNSCC and has the potential to contribute to strategies that may be developed to improve the outcome for patients who develop HNSCC in the future.

Commonly used craniofacial reference planes such as Frankfort Horizontal (FH) and sella nasion (SN) have shortcomings including their variable inter-individual orientation when related to true horizontal (HOR). Therefore, the aim of this study was to evaluate the potential usefulness of a range of craniofacial reference planes to HOR including those which have not been investigated before: Krogman-Walker line (KW line), neutral horizontal axis, foramen magnum line and posterior maxillary plane. A sample of 57 (38 female, 19 males) consecutive, pre-treatment orthodontic subjects aged 12 to 18 were photographically recorded in a standing mirror guided natural head position (NHP). Cephalograms taken at the same time were traced, oriented to a plumb line (true vertical) transferred from the photograph, and measured for statistical analysis. Thirty nine of these subjects were photographically recorded 2 months later to test the reproducibility of NHP. The results showed that the variability of the 11 selected craniofacial reference planes related to HOR was generally high. The planes illustrating lowest variability to HOR were FH and KW line with standard deviations of 4.6° and 4.7°, respectively. These, however, showed about double the variation in NHP reproducibility (Dahlberg 2.1°). The KW line and palatal plane were also oriented closest to HOR on average. Therefore, KW line and palatal plane are potential substitutes for the commonly used reference planes in the absence of a reliable NHP. However, NHP still represents a more valid craniofacial reference system than the investigated reference planes. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1297323 / Thesis (D.Clin.Dent.) - School of Dentistry, (Orthodonitics), 2007

<p>The development of the vertebrate head is a complex process involving interactions between a multitude of cell types and tissues. This thesis describes the development of the cranial neural crest and of the visceral arch muscles in the head of two species. One, the Mexican axolotl (<i>Ambystoma mexicanum</i>), is a basal tetrapod, whereas the other, the Australian lungfish (<i>Neoceratodus forsteri</i>), belongs to the Dipnoi, the extant sister group of the Tetrapoda. </p><p>The migration of neural crest cells, which form most of the bones and connective tissues in the head, and the morphogenesis of the jaw, was determined in the Mexican axolotl. It was shown that both the upper and lower jaws form from ventral condensations of neural crest cells in the mandibular arch. The dorsal condensation, earlier considered to give rise to the upper jaw, was shown to form the trabecula cranii.</p><p>The normal spatio-temporal development of visceral arch muscles was investigated in both the Mexican axolotl and the Australian lungfish. In axolotl, the muscles tended to start forming almost simultaneously in all visceral arches at their future origins and extend towards their future insertions at the onset of muscle fibre formation. In lungfish, fibres formed simultaneously throughout most of each muscle anlage in the first and second visceral arch, but were delayed in the branchial arches. The anlagen were first observed at their future insertion, from which they developed towards future origins. </p><p>To test the ability of neural crest cells to pattern the visceral arch muscles, migrating crest cells were extirpated from axolotl embryos, which resulted in a wide range of muscle malformations. In most cases, the muscles appeared in the right position but were small and extended in abnormal directions. This shows that neural crest cells are responsible not for the position of the muscles but for their correct anatomical pattern. Fate mapping showed that connective tissue surrounding myofibers is, at least partly, neural crest derived.</p><p>In conclusion, the work presented in this thesis shows that although early development may map out the patterns of later development, the differences between axolotl and lungfish head development are not seen until during morphogenesis. Further investigation of morphogenesis is needed to explain the great variation of head morphology seen in vertebrates today.</p>

Several recent studies have revealed that high caliber European professional soccer players often have diminished levels of neurological functioning, yet no study has been able to identify the specific aspect of soccer participation responsible for these decreases. In an effort to identify a source of mild traumatic brain injury present in everyday participation in soccer, this study investigated whether a single bout of heading a soccer ball would have acute detrimental, measurable effects on sensorimotor and neurocognitive functioning. We hypothesized that subjects would exhibit significant changes in postural stability, memory, and concentration immediately after an acute bout of repeated heading a soccer ball. Additionally, we evaluated the protective effect(s) associated with wearing a mouthguard while performing the acute bout of heading. Twenty-eight elite level soccer players (mean age, 20.9 �� 2.5 yrs) were randomly assigned to one of three experimental groups: Headers with mouthguard (n=10), Headers with no mouthguard (n=10), and Control (n=8). Subjects in the two treatment groups performed 12 headers of soccer balls projected at 40 km/hr from an electric soccer ball-launching machine. Postural stability was evaluated using a Biodex Stability System, while memory and concentration were assessed using Wechsler Digit Span (WDS) tests (digits forward and digits backward) in a 3 x 2 factorial ANOVA design (��=0.05). There were no significant main effects or interactions among the three measures of postural stability scores in the three groups (p>0.05). The WDS Forward group means ranged from 10.4 �� 1.8 to 13.5 �� 1.2 while the WDS Backward means ranged from 6.4 �� 1.1 to 7.7 �� 3.0, but were not different among the groups (p>0.05). We concluded that a single bout of 12 soccer headers approximating the number of headers performed during a typical NCAA Division I-A soccer practice did not produce significant deficits in postural stability, memory, or concentration. While our findings are similar to several recent studies, we suggest that more sensitive measurement tools such as ImPACT neurocognitive testing and functional magnetic resonance imaging be utilized to determine the effects of acute as well as chronic exposure to headers in soccer players. / Graduation date: 2003

BACKGROUND : Radiation oncology was these 20 last years revolutionized by the 3-dimensional conformal radiotherapy (3D-CRT) and its technical evolution, the intensity modulated radiotherapy (IMRT). Thanks to steep dose gradient dose distribution, these techniques allow to conform the prescribed dose to the Planning Target Volume (PTV) while significantly decreasing the dose delivered to the Organs at Risk (OAR). One critical step remains the accurate definition of the Gross Tumor Volume (GTV). If the GTV is underestimated, there is a risk of missing part of the target. If the GTV is overestimated, the risk is to overirradiate normal tissues. Today's gold standard for GTV definition is the Computed Tomography (CT) scanner. We though know that its poor soft tissues contrast is a factor of variability for target definition purpose. AIMS : It can be hypothesized that, for Head and Neck Squamous Cell Carcinomas located in the oropharynx or the laryngo-hypopharynx, the use of other anatomical (like Magnetic Resonance Imaging – MRI) or functional (like positron emission tomography with either 11C-methionine – MET-PET- or 18F-fluorol-deoxy-glucose – FDG-PET) imaging modalities could complement CT for GTV delineation, and have an impact on subsequent CTV and PTV delineation and dose distribution to the non target tissues outside the PTV. RESULTS : We could demonstrate that, providing an adequate and controlled methodology concerning image coregistration and tumor volume delineation on functional images, differences were observed for the delineation of primary tumor volume or GTV according to the modality used. Moreover, the trends were the same for both locations studied (oropharyngeal and laryngo-hypopharyngeal) : CT, MRI and MET-PET volumes were not significantly different in absolute volumes, but there was no total overlap, each imaging modality having the tendency to visualize different types and relatively specific pathways of tumor extension (e.g. : cartilages in MRI). What was very interesting was the significantly smaller FDG-PET volume which could have a real impact on radiation oncology practice by (1) allowing to reduce dose distribution and (2) providing fast and reproducible GTV delineation based on its functional characteristic. Furthermore, we could demonstrate on the subset of operated patients that these smaller FDG-PET volumes were not the fact of a volume underestimating delineation algorithm but well the reflection of true tumor extension. But one must keep in mind that because of spatial resolution limitations, there was still a significant overestimate of this true GTV. Also, none of the imaging modalities was able to visualize very small tumor extensions. This last fact put in the light the need for strict guidelines for CTV prediction based on GTV extension. This is what was done with the help of both anatomical and histo-pathological literature data. These guidelines were used to delineate CTVs on our images, allowing to perform comparative planning on primary tumor. It could be concluded that differences in GTV had not only an impact on CTV and subsequent PTV, but also on dose distribution, either on total irradiated volume or -perhaps more important- on mean dose to parotid glands. No significant effect could be observed on maximal dose to spinal cord. Compared to planning performed on macroscopy-based volumes, no significant difference could be found with what was done on PET-derived planning. CONCLUSION : This research paves the way for the use of FDG-PET for GTV delineation in planning the patients with oropharyngeal and laryngo-hypopharyngeal squamous cell carcinomas. / INTRODUCTION : La radiothérapie moderne a terriblement évolué ces 20 dernières années grâce au développement de la radiothérapie conformationnelle tridimensionnelle (3D-CRT) et de son évolution technique, la radiothérapie par modulation d'intensité (IMRT). Grâce à la création de gradients de dose très raides, ces techniques permettent de conformer au mieux la distribution de la dose au “Planning Target Volume” (PTV) tout en diminuant de manière significative la dose délivrée aux Organes à Risque (OAR). La précision de la définition du “Gross Tumor Volume” (GTV) ou volume tumoral macroscopique reste une étape cruciale dans le sens où une sous-estimation du volume augmente le risque de sous-doser la dose délivrée à la tumeur. Dans l'autre sens, la surestimation du volume tumoral conduit immanquablement à une surirradiation des tissus sains. La tomographie computée par scanner (CT) est l'imagerie de référence pour la définition du GTV. Cependant, le manque de constraste entre tissus mous – à fortiori entre la tumeur et les tissus environnants- constitue un facteur de variabilité reconnu quant à la précision de délimitation du GTV. BUTS : Pour les cancers de la sphère cervico-maxillo-faciale, en particulier pour les tumeurs épithéliales oropharyngées et laryngo-hypopharyngées, démontrer que l'usage complémentaire d'une autre imagerie anatomique comme la résonance magnétique (IRM) ou fonctionnelle comme la tomographie par émission de positrons utilisant soit la méthionine marquée au carbone 11 (MET-TEP), soit le fluoro-déoxy-glucose marqué au fluor 18 (FDG-TEP) peut améliorer la précision de la délimitation GTV. Dans ce cas, démontrer également que cela a un impact sur la délimitation des CTV et PTV sous-jacents et, in fine, sur la distribution de la dose aux tissus sains extérieurs au PTV. RESULTATS : Moyennant l'utilisation adéquate et contrôlée de méthodes de corégistration des images et de délimitation automatique des volumes en imagerie fonctionnelle, nous avons pu démontrer des différences en terme de GTV délimité selon les différentes modalités d'imagerie, avec une tendance identique que l'on se situe au niveau oropharyngé ou laryngo-hypopharyngé. Les GTV délimités sur CT, IRM et MET-TEP n'étaient pas significativement différents en valeurs absolues, mais chaque modalité avait tendance, au-delà d'une zone de congruence s'élevant en moyenne à 50% du volume total, à visualiser des extensions vers des zones anatomiques lui étant propre (ex. : les cartilages en IRM). Les volumes délimités en FDG-TEP étaient significativement plus petits que ceux délimités sur les autres modalités d'imagerie. Nous pûmes de plus démontrer sur un ensemble de patients opérés par laryngectomie totale que le FDG-TEP était aussi la plus précise des modalités d'imagerie. Cependant, par manque de résolution spatiale, aucune des modalités d'imagerie ne fut en mesure de couvrir totalement le GTV. Ce fait met en lumière le besoin de recommendations claires pour la prédiction du CTV sur base de l'extension du GTV. Ce travail fut réalisé sur base des données de la littérature anatomique (normale et pathologique). Ces recommendations furent utilisées pour délimiter les CTV sur les images CT, FDG-TEP et du spécimen chirurgical (les imageries IRM et MET-TEP ne furent pas analysées puisque n'apportant rien en regard du CT). Les PTV furent ensuite générés et une planification tridimensionnelle réalisée. Tant les CTV que les PTV délimités sur le FDG-TEP restaient significativement plus petits que leurs homologues délimités sur CT. Cette réduction permettait une réduction de la dose délivrée aux glandes parotides en particulier, aux tissus hors PTV de manière plus générale. CONCLUSION : Cette recherche ouvre la voie à l'utilisation du FDG-TEP pour la délimitation du GTV chez les patients atteints de tumeurs épithéliales des sphères oropharyngée et laryngo-hypopharyngée.

In the Everest valley of Nepal, because of the rugged mountain terrain, the ‘roads' are nothing more than dirt mountain footpaths. Most of the material is conveyed over long distances by professional porters who carry impressive burdens in a wicker basket supported by a strap looped over their head. We measured the body weight and loads carried by the Himalayan porters passing along the busy footpath to Namche Bazaar, the main market place of the Everest region. On average, the porters were carrying loads equivalent to 90% of their body weight on the last day of a 7-9 day trip covering a horizontal distance of ~100 km with >8000 m of total ascents and >6300 m of total descents. Interestingly, these porters adopt a specific rhythm of walking: they generally walk slowly and make very frequent rest stops using a T-stick or stone-platforms built along the trail to support the load during the pause. It has been shown that African women could carry head-supported loads more economically than Western subjects because they have developed a mechanical energy-saving strategy. Similarly, Nepalese porters could also have developed a mechanism to carry economically their very heavy loads. To test this hypothesis, we measured the energy consumption and the mechanical work done during level walking under different loading and speed conditions in the Nepali porters and in Western subjects. We compared these results to those of the African women. Nepalese porters carry loads at a lower cost than either the control subjects or the African women. For example, for a load equivalent to 60% of body weight, western Caucasian subjects increases their metabolic rate by 60%, the African women by 40% and the Nepalese porters by only 30%. Contrary to the African women who are taking advantage of the load to reduce the work performed, Nepalese porters do not modify their gait while carrying a load. Consequently, the mechanical work performed is not reduced as compared to control subjects walking at same speed-load combinations. Yet the Nepalese porters are the most economical load-carriers measured to date, particularly while carrying heavy loads at walking speeds slower than 1.4 m/s, but the exact mechanisms by which they save energy are still unknown. G. J. Bastien et al. Eur J Appl Physiol 94, 76 (2005); G. J. Bastien et al. Science 308, 1755 (2005); G. J. Bastien et al. J Exp Biol submitted.

The current study examined the influence of classroom age composition (the variability in ages of children in the classroom) on low-income preschool children's rates of change in multiple domains of school readiness. The sample consisted of 4,417 preschool children enrolled in 207 classrooms in a large, diverse Head Start program. Children were assessed throughout the year on four school readiness domains: emergent literacy, emergent numeracy, social and emotional skills, and approaches to learning. Multilevel modeling was employed to examine the main effect of classroom age composition as well as the interaction between classroom age composition and child's age as predictors of children's rates of change in these school readiness domains. Results showed that classroom age composition did not uniformly influence rates of change in school readiness for all children. Instead, a significant interaction between child's age and classroom age composition indicated that younger children developed skills in the domain of approaches to learning at an increased rate when placed in classrooms with a large age composition (i.e., in classrooms with a greater degree of age-mixing). This study extends literature focused on identifying classroom structures that promote positive development of school readiness skills, particularly for at-risk children.

PERNA, NICHOLAS (D.M.A., Vocal Pedagogy and Performance) Effects of Nasalance on the Acoustical Properties of the (May 2008) Tenor Passaggio and Head Voice Abstract of a doctoral essay at the University of Miami. Doctoral essay supervised by Professor David Alt and Professor Rachel L. Lebon. No. of pages in text. (73) This study aims to measure the effect that nasality has on the acoustical properties of the tenor passaggio and head voice. Not to be confused with forward resonance, nasality here will be defined as nasalance, the reading of a Nasometer, or the percentage of nasal and oral airflow during phonation. A previous study by Peer Birch et. al. has shown that professional tenors used higher percentages of nasalance through their passaggio. They hypothesized that tenors used nasalance to make slight timbral adjustments as they ascended through passaggio. Other well respected authors including Richard Miller and William McIver have claimed that teaching registration issues is the most important component of training young tenors. It seemed logical to measure the acoustic effects of nasalance on the tenor passaggio and head voice. Eight professional operatic tenors participated as subjects performing numerous vocal exercises that demonstrated various registration events. These examples were recorded and analyzed using a Nasometer and Voce Vista Pro Software. Tenors did generally show an increase of nasalance during an ascending B-flat major scale on the vowels [i] and [u]. Perhaps the most revealing result was that six of seven tenors showed at least a 5-10% increase in nasalance on the note after their primary register transition on the vowel of [a]. It is suggested that this phenomenon receive further empirical scrutiny, because, if true, pedagogues could use nasalance as a tool for helping a young tenor ascend through his passaggio.

The current study investigated the relationship between peer interactions and school readiness children enrolled in Head Start. The constructs of displayed and received physical aggression, relational aggression, and prosocial behavior within children's peer interactions were examined through direct observation. School readiness was measured through direct assessment. It was hypothesized that aggression within peer interactions would predict lower school readiness, while prosocial behaviors within peer interactions would predict better school readiness. Sex was also hypothesized to moderate the relationship between relational aggression, relational victimization, physical aggression, physical victimization and school readiness. It was hypothesized that relational aggression and victimization would more severely impact the school readiness of girls and physical aggression and victimization would more severely impact the school readiness of boys. Structural equation modeling (SEM) analyses revealed that physical aggression and victimization as well as displayed and received prosocial behavior did not significantly predict school readiness. Relational aggression predicted better school readiness. Also, sex moderated the relationship between relational victimization and school readiness such that relational victimization predicted better school readiness for girls, but did not predict school readiness for young boys. Knowledge gained from this study can inform preschool classroom practices on the role that peer aggression and prosocial behavior play in individual differences in children's school readiness.

Previous research indicates that joint storybook reading between caregivers (parents or teachers) and children can have positive effects on the oral language development of young children (Whitehurst et al., 1988; Dickinson & Smith, 1994). This study aimed to add to this body of research by providing information on the relationship between teachers’ language complexity and vocabulary strategies used during storybook reading and vocabulary outcomes for monolingual and dual language learners in linguistically diverse Head Start classrooms. Videotapes of 23 Head Start teachers were coded and analyzed for vocabulary instruction strategies and language complexity during storybook reading using hierarchical regression techniques to determine how these factors related to gains in student vocabulary over the course of a year. Students’ oral language was assessed using the Peabody Picture Vocabulary Test (PPVT) and the Learning Express vocabulary sub-test (LE). Teacher’s language complexity was calculated with respect to both quantity (mean length of utterance) and quality (type/token ratio and use of uncommon words). Teacher’s use of vocabulary strategies was examined with respect to the words chosen for instruction and the strategies used to instruct those words. Overall, teachers in this study tended to choose high utility words to instruct, but the strategies used to teach those words, and the number of words chosen for instruction, were often not optimally aligned with best practices in vocabulary instruction (Beck et al., 2002). For the PPVT outcome measure, teachers’ use of higher numbers of vocabulary instruction strategies per word was differentially related to students’ vocabulary outcomes based on the student’s prior vocabulary knowledge, such that the use of more vocabulary instruction strategies per word was negatively related to vocabulary outcomes for students who began the year with the smallest vocabularies. There was also a significant interaction between teachers’ use of uncommon words and students’ prior vocabulary knowledge, though this relationship was only statistically significant for the PPVT outcome. Teachers’ use of more complex language was differentially related to students’ outcomes. Students who began the year with the lowest vocabulary levels exhibited a positive relationship between the teacher’s use of uncommon words and vocabulary outcomes, while average or higher vocabulary students showed a negative relationship between increased exposure to these uncommon words and their vocabulary outcomes. The implications for teachers’ professional development are discussed.