La crête neurale crâniale (CNC) est une structure transitoire et pluripotente de l’embryon des Vertébrés qui génère la totalité du squelette de la face et de la voûte crânienne et fournit les méninges et une vascularisation fonctionnelle au cerveau antérieur. Précocement, la CNC contrôle également la croissance du cerveau. Pour identifier les mécanismes par lesquels la CNC exerce son rôle trophique sur le cerveau, nous nous sommes intéressés à l’expression du gène Smad1, qui transduit divers voies de signalisation, et est massivement exprimé par les cellules de la CNC juste avant leur migration. L’inactivation de Smad1 par l'interférence ARN dans les CCN conduit à une microcéphalie sévère et une holoprosencéphalie partielle, qui résulte de la perte de l’expression de Fgf8 et Foxg1. Les expériences de sauvetage montrent que les cellules de la CNC régulent positivement Foxg1 indépendamment de Fgf8. De plus, nous montrons que la perte de fonction de Foxg1 dans le télencéphale affecte le développement du thalamus et du toit optique en dérégulant l’expression de Otx2 et de Foxa2 à leur niveau. Nous avons identifié les molécules médiatrices produites par les cellules de la CNC nécessaire au contrôle de l’expression de Foxg1. Nous montrons que les antagonsites de Bmp and Wnt, Noggin, Gremlin et Dkk1 sont indispensable pour initier la spécification du télencéphale. De plus, la régionalisation moléculaire des territoires télencephalique et di/mésencéphalique, requiert l’activité conjointe de Sfrp1 et Sfrp2, d’une part, et de Cerberus, d’autre part. L’ensemble des données acquises au cours de ces travaux documente les mécanismes moléculaires par lesquels la CNC participe de façon essentielle à la régionalisation moléculaire du cerveau des Vertébrés. / The cranial NC (CNC) is a transient structure of the vertebrate embryo, which is essential for brain ontogenesis and provides the developing brain with a skeletal and meningeal protection and functional vasculature. Early in development, CNC cells also control morphogenetic activities of brain organizers and stimulate the growth of prosencephalic alar plate. To understand how CNC conveys its trophic effect on the telencephalon, we have silenced the gene encoding for Smad1, a transcription factor expressed in the CNC cells, which transduces diverse morphogenetic pathways. Smad1 silencing results in microcephaly and partial holoprosencephaly, which early coincide with the loss of Fgf8 and Foxg1 in the telencephalon. Rescue experiments show that CNC cells can positively regulate Foxg1 expression independently of Fgf8 activity in the prosencephalic organizer. Furthermore, the depletion of Foxg1 activity in the telencephalon alters Otx2 and Foxa2 expression in the thalamus and tectum. We have identified the mediators produced by the CNC to control Foxg1 activity and showed that Bmp and Wnt antagonists, Noggin, Gremlin and Dkk1 initiate the specification of the telencephalon. Additionally, the molecular patterning of the telencephalic and di/mesencephalic compartments requires the activity of Sfrp1 and Sfrp2, and Cerberus, respectively. Altogether, we show that CNC cells controls brain patterning by regulating Foxg1 expression through a network of morphogen modulators controlled by Smad1 activity. / A crista neural cranial (CNC) é uma estrutura transiente em embriões de vertebrado, que possui um papel crucial no desenvolvimento da cabeça. A CNC é uma importante fonte de derivados mesenquimais. Recentes descobertas mostraram que as células da CNC possuem uma atividade trófica no desenvolvimento do tubo neural anterior, estimulando e organizando o desenvolvimento prosencefálico em oposição à sinalização Bmp presente nos tecidos adjacentes. Com o objetivo de entender como as células da CNC controlam a atividade de morfógenos durante o desenvolvimento do cérebro. Nós focamos nossos estudos no fator de transcrição Smad1, expresso pelas células da CNC, que controla a transcrição de Noggin. Noggin é um antagonista de Bmp que por sua vez controla a atividade de sua via de sinalização. Além disso, Smad1 interage com outras vias de sinalização com Fgf8 e Wnt. Para testar o papel de Smad1 nas células da CNC, nós eletroporamos o RNA dupla fita de Smad1 (dsSmad1) nas células da CNC em embriões de galinha no estágio de 4 somitos com a finalidade de bloquear sua tradução. Estes espécimes foram analisados em estágio mais avançados do desenvolvimento embrionário. A perda de função de Smad1 compromete o desenvolvimento das vesículas cefálicas, nos estágios de 26 somitos, E4, E6 e E8. Em cortes histológicos em E8, observou-se o aumento do volume ventral do cérebro destes embriões. Com o objetivo de entender como Smad1 controla o desenvolvimento das vesículas cefálicas, embriões no estágio de 26ss foram analisado por hibridização in situ. Nós observamos em embriões dsSmad1 a diminuição da expressão de Fgf8 na borda neural anterior e a completa ausência de expressão de Foxg1 no neuroectoderma prosencéfalico. A falta de Smad1, também gera a diminuição da expressão de Otx2 nos limites ventrais e laterais do telencéfalo, diencéfalo e mesencéfalo. Em contrapartida, nestes embriões observa-se o aumento da zona de expressão de Foxa2 na porção ventral do diencéfalo e mesencéfalo. O bloqueio de Smad1 também acarreta no aumento dos níveis de Dkk1, que é um importante inibidor da via de sinalização Wnt. Com o intuito de entender o mecanismo sobre o controle de Smad1, nós aumentamos os níveis de transcritos nas células da CNC de Dkk1. Como resultado deste aumento, observamos as mesmas modificações nos níveis dos transcritos de Fgf8, Foxg1, Otx2 e Foxa2. Interessantemente os efeitos do excesso de Dkk1 podem ser revertidos com a co-eletroporação do Smad1 constitutivamente fosforilada. Nós também analisamos a expressão de Foxg1 e Otx2 em embriões privados de Cubilin nas células da CNC. Estes embriões apresentam o mesmo padrão de expressão encontrados nos embriões dsSmad1. Interessantemente os nocautes para Cubilin apresentam diminuição da fosforilação de Smad1. Nossos resultados mostram que a presença de Smad1 nas células da CNC é extremamente importante para padronização e desenvolvimento do cérebro. Smad1 nas células da CNC funciona como um regulador da via de Bmp, através do controle transcricional de Noggin impedindo que o excesso de Bmp chegue até o tubo neural. Sendo assim, Smad1 controla o excesso de Bmp permitindo a indução e o desenvolvimento da região anterior por Fgf8.

This study focuses on the career paths and career projections of teacher professionals who are at a stage in their professional roles where they have not embarked upon senior leadership positions in the schools in which they work. Often research has focused retrospectively on the career paths of those already in leadership posts rather than those who are expected to be aspiring to leadership, have discounted this option or are yet to make a decision. Increasing numbers of re-advertisements for headship posts indicates a lack of willing or suitable candidates applying. Changes to school staffing structures and the role of headteachers in recent years have resulted in greater responsibilities including financial matters and the maintenance of premises. Government policies in favour of schools becoming academies has removed local authority support and placed increased pressure on individual school leaders. These factors coupled with the external inspection system and the media focus on so called failing schools has led to the role of head becoming unattractive to many and this study aims to collect the views of a sample of teachers regarding this role. Six schools of similar type were selected from within one local authority and a survey was utilised in order to collect data. This was initially in the form of a questionnaire completed by seventy nine teachers from which twelve participants took part in two interviews each. Teachers were subsequently organised into one of four career categories; 'careerist', 'serendipity', 'active choice' and 'stuck'. Analysis of the data indicates that many teacher professionals do not plan to become senior leaders or heads. This is in agreement with many serving heads who in existing research claim not to have planned their routes to headship. However, the majority of the sample in this study have already ruled out the role of head, finding the pressures and perceived stress of the role unappealing and not wishing to lose their identity as classroom teachers. The underrepresentation of women in headteacher posts does not look likely to be addressed in the near future as females in the study are more likely to feel unable to pursue leadership roles often due to family commitments. A larger proportion of females have made the choice not to pursue leadership roles than males, even when those females did not necessarily have the pressures of home responsibilities. For many females future decisions regarding starting families and seeking promotions produced dilemmas that men did not appear to have to confront. These factors look likely to lead to continued headteacher shortages in the short term with no real incentives to encourage females to pursue such posts now or in the future.

Proximal forearm fractures account for over 10% of all upper limb fractures. There is limited epidemiological data available and much of the literature focuses on the more complex fracture patterns, with the role of non-operative management for the isolated proximal forearm fracture still to be defined. Prospective short and long-term patient reported outcome data for simple isolated fractures of the radial head and olecranon would help define the indications for the non-operative management of these injuries. This thesis aims to test the hypothesis that non-operative management provides a comparable outcome to operative intervention for defined fractures of the proximal forearm. A large prospective database of 6872 fractures collected over a one-year period was used to define the epidemiology of proximal forearm fractures. A separate large prospective study carried out over an eighteen-month period using a pre-defined management protocol for all isolated radial head and neck fractures was analysed to determine the short and long-term outcome. Additional retrospective databases were collected and analysed to determine the short and long-term outcome for the non-operative and operative management of olecranon fractures, as well as the operative management of complex radial head fractures. Finally, two prospective randomised controlled trials (PRCTs) of isolated displaced fractures of the olecranon were carried out to compare 1) tension band wire (TBW) versus plate fixation in younger patients (< 75 years) and 2) operative versus non-operative management in elderly patients (≥75 years). The primary outcome measure for these studies was the upper limb specific patient reported Disabilities of the Arm, Shoulder and Hand (DASH) score. Secondary outcome measures included surgeon reported outcome scores, complication rates and cost. The incidence of proximal forearm fractures was 68 per 100,000. Radial head fractures fit a type D distribution curve (unimodal young man, bimodal woman) and radial neck type A (unimodal young man, unimodal older woman). Proximal ulna and olecranon fractures were both a type F (unimodal older man, unimodal older woman), with an increasing incidence after the 6th decade. Over 90% of proximal radial fractures were isolated stable fractures. Prospective analysis of 201 isolated proximal radius fractures found that the patient and surgeon reported outcome following primary non-operative management for Mason type 1 and type 2 (n=185) fractures was excellent in the short and long-term, with < 2% of patients undergoing secondary surgical intervention. At a mean of 10 years post injury (n=100), the mean DASH score was 5.8 and 92% of patients were satisfied. Factors associated with a poorer short and long-term patient reported outcome included increasing fracture displacement (≥5mm) and socio-economic deprivation. Retrospective analysis of 105 acute unstable complex radial head fractures found that the mean short-term functional outcome was good (mean Broberg and Morrey Score 80) following radial head replacement. In the long-term (mean 7 years), 28% of patients required removal or revision of the prosthesis, with younger patients and silastic implants independent risk factors (both p < 0.05). Retrospective analysis of 36 operatively managed isolated displaced olecranon fractures found satisfactory short and long-term outcomes, with the symptomatic metalwork removal rate 47% and the mean DASH 2.5 at a mean of seven years post injury. In the PRCT of plate (n=34) versus TBW (n=33) fixation, comparable functional and patient reported outcomes (DASH 8.5 vs 13.5; p=0.252) were found at one year following injury. Complication rates were significantly higher in the TBW group (63.3% vs 37.5%; p=0.042), predominantly due to a significantly higher rate of symptomatic metalwork removal (50.0% vs 21.9%; p=0.021), resulting in equivocal costs for both techniques (p=0.131). In older lower-demand patients, short and long-term retrospective analysis found very satisfactory outcomes following non-operative management of isolated displaced fractures of the olecranon, with patient satisfaction 91% and no patients requiring surgery for a symptomatic non-union. The preliminary results of the PRCT of non-operative (n=8) versus operative (n=11) management demonstrated comparable functional and patient reported outcomes at all points over the one-year following injury (all p≥0.05), with a higher rate of complications (81.8% vs 14.3%; p=0.013) and cost (p=0.01) following surgical intervention. The association found between fragility and the epidemiology of proximal forearm fractures highlighted the importance of considering non-operative management for these injuries. These findings support non-operative management for isolated stable radial head and neck fractures. For more complex injuries when radial head replacement is indicated, there is a high rate of removal or revision, with younger patients most at risk. In younger active patients with an isolated displaced fracture of the olecranon, TBW and plate fixation provide comparable short-term results, with TBW fixation as cost effective despite an increased rate of metalwork removal. In older lower demand patients, this data provides strong evidence for the non-operative management of isolated displaced olecranon fractures.

In this dissertation, I provide a left-to-right incremental parsing approach for Headdriven Phrase Structure Grammar (HPSG; Pollard and Sag (1987, 1994)). HPSG is a lexicalized, constraint-based theory of grammar, which has also been widely exploited in computational linguistics in recent years. Head-final languages are known to pose problems for the incrementality of head-driven parsing models, proposed for parsing with constraint-based grammar formalisms, in both psycholinguistics and computational linguistics. Therefore, here I further focusmy attention on processing a head-final language, specifically Turkish, to highlight any challenges that may arise in the case of such a language. The dissertation makes two principal contributions, the first part mainly providing the theoretical treatment required for the computational approach presented in the second part. The first part of the dissertation is concerned with the analysis of certain phenomena in Turkish grammar within the framework of HPSG. The phenomena explored in this part include word order variation and relativization in Turkish. Turkish is a head-final language that exhibits a considerable degree of word order freedom, with both local and long-distance scrambling. I focus on the syntactic aspects of this freedomin simple and complex Turkish sentences, detailing the assumptions Imake both to dealwith the variation in the word order, and also to capture certain restrictions on that variation, within the HPSG framework. The second phenomenon, relativization in Turkish, has drawn considerable attention in the literature, all accounts so far being within the tradition of transformational grammar. Here I propose a purely lexical account of the phenomenon within the framework of HPSG, which I claim is empirically more adequate than previous accounts, as well as being computationally more attractive. The motivation behind the work presented in the second part of the dissertation mainly stems from psycholinguistic considerations. Experimental evidence (e.g. Marslen- Wilson (1973)) has shown that human language processing is highly incremental, meaning that humans construct aword-by-word partial representation of an utterance as they hear each word. Here I explore the computational effectiveness of an incremental processing mechanism for HPSG grammars. I argue that any such processing mechanism has to employ some sort of nonmonotonicity in order to guarantee both completeness and termination, and propose a way of doing that without violating the soundness of the overall approach. I present a parsing approach for HPSG grammars that parses a string of words fromleft to right, attaching every word of the input to a global structure as soon as it is encountered, thereby dynamically changing the structure as the parse progresses. I further focus on certain issues that arise in incremental processing of a “free”word order, head-final language like Turkish. First, I investigate howthe parser can benefit from the case values in Turkish in foreseeing the existence of an embedded phrase/clause before encountering its head, thereby improving the incrementality of structuring. Second, I propose a strategy for the incremental recovery of filler-gap relations in certain kinds of unbounded dependency constructions in Turkish, which further enables one to capture a number of (strong) preferences that humans exhibit in processing certain examples with potentially ambiguous long-distance dependency relations.

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science, 2017 / Aim: The aim of this study was to quantify random and systematic setup errors in a population of head and neck cancer patients for the purposes of evaluating departmental positioning and immobilization techniques, verification and treatment protocols, as well as validating the treatment margins used. Methods and Materials: All patients had more than one phase of radiation, each consisting of different megavoltage photon field arrangements. Some phases were also treated with electron fields in addition to the photon fields. Random and systematic setup errors in all three principal directions were calculated for two groups of patients, using record and verify system couch position data. For one group (20 patients) the positioning and immobilization device system was mechanically localized to the treatment couch, and for the other group (38 patients), it was visually centered on the treatment couch. Within both groups of patients, the patient position was either verified online with portal imaging or verified offline on a conventional radiotherapy simulator. Results: For the patient group treated with the base plate visually centered on the treatment table the population random and systematic setup errors calculated for the photon fields were only indicative of setup uncertainties in the anterior-posterior direction. For the patient group treated with the base plate localized to the treatment couch, the population random and systematic setup errors were found to be within the 5 mm clinical to planning target volume expansion margin used at Livingstone Hospital. Due to treatment couch position differences from fraction to fraction, setup errors made during this study could not reliably be determined for electron field treatments Conclusions: Results indicate that the base plate should be localized to the treatment couch when calculating random and systematic setup errors for photon fields using the couch position as a surrogate for patient position. For this method to be used to calculate setup errors for electron fields, shielding should always be fastened to the same position at the endface of the applicator. Offline and online verification did not significantly influence systematic setup errors. / XL2018

Hydro power can be defined as converting the energy of flowing water into useful mechanical power by a turbine or water wheel. A micro hydro system typically has an electrical generation capacity of less than 100 kilo watts. These systems are usually constructed to supply power to individuals or groups of individuals who are independent of the power supply grid. The scope of this project is to outline the principles of micro hydro and to document the design process of a micro hydro site. This will include the measurements, calculations, and methods performed in a feasibility study for a potential site. The desired outcome of the project is to develop a viable solution to gain energy independence at a remote site owned by the author.

Low-head dams are capable of creating dangerous counter-currents just downstream from the structure. These dangerous counter-currents are known as submerged hydraulic jumps and are responsible for hundreds of fatalities at numerous low-head dams across the United States. The counter-current creates high upstream-directed surface velocities across the width of the channel, making it nearly impossible for an individual to escape. This submerged jump can occur during a range of upstream and downstream conditions. Effective, safe and low-cost remediation options must be explored in order to prevent further fatalities at these structures. This document explores such a remediation option: the Multiple Staggered Deflector Design. This remediation option will disrupt uniform upstream-directed surface velocities across the channel within a submerged jump for nearly all downstream conditions that create a submerged jump for a range of upstream conditions. The dam modification is designed such that an individual will escape the submerged jump without severe injury or harm, while being relatively inexpensive and simple to install.

Head Start, the largest early childhood organization in the United States, was federally mandated to employ bachelor degreed operational employees, with no additional funds. The purpose of this multiple case study was to explore effective strategies that successful leaders of Head Start Nonprofit Organizations use to retain operational employees. The population of this study included 5 Head Start CEOs/Program Directors in 5 Head Start nonprofit organizations in Alabama who successfully retained operational employees in their organization. Kouzes and Posner's transformational leadership theory provided a conceptual framework for this study. Data were collected via telephone interviews and employee records from the human resources department. Reviewed human resource documents included the highest level of credentials for the leader, the policy for degree requirement for operational employees, and the number of operational employees, and the participants' highest level of education. The data were analyzed using inductive analysis which consisted of a line-by-line approach to review data identifying words, phrases, ideas, and actions consistent among participants and organizations to identify patterns and themes. Results indicated that Head Start leaders used incentives, continuous training, educational support, and job benefits to retain their operational employees. The implications for social change include the potential for young children to receive optimal teaching and caregiving from retained qualified operational employees.

For radiation treatment of cancer and image-based quantitative assessment of treatment response, target structures like tumors and lymph nodes need to be segmented. In current clinical practice, this is done manually, which is time consuming and error-prone. To address this issue, a semi-automated graph-based segmentation approach was developed. It was validated with 60 real datasets, segmented by two users manually and with this new algorithm, and 44 scans of a phantom dataset. The results showed a statistically significant improvement in intra- and interoperator consistency of segmentations, a statistically significant improvement in speed of segmentation, and reasonable accuracy against consensus images and phantoms. As such, the algorithm can be applied in cases that otherwise would use manual segmentation.

No description available.