Conselho Nacional de Desenvolvimento Científico e Tecnológico / There are approximate thirty years, started a debate among philosophers W. V. O. Quine and D. Davidson about where it should be located in the causal chain speaking- world, the element that determines the empirical meaning of observation sentences - henceforth will call this element of "stimulus." According to Quine, who supports what might be called the "proximal conception," such stimulus would be located on the sensory surface speaker, ie, in a position close to him in this causal chain - proximal stimulus -; Davidson, on the other hand, criticizes the proximal conception, because it would not be able to explain the public nature of language and he suggests Quine to abandon the proximal conception in favor of distal conception, sustained by himself, according to which such a stimulus would be located in own objects and events about which the sentences speak, ie, in a position farther from the speaker - distal stimulus. Despite the suggestion of Davidson, Quine insists until the end of his work in not officially sustain the distal conception, introducing, however, some modifications in its conception in order to escape the criticism proceeded by the author. Given this di-vergence between the two authors, this work aims to carry out the reconstruction and evaluation of this debate. It should be noted, first of all, that Quine is a philosopher very systematic and his theses are closely interconnected, so it is necessary a more general overview of his philosophy whenever one want to understand a particular problem that is inserted in it, otherwise prejudice the proper understanding of it. Therefore, this work will be divided into two main parts: the first one will be reserved for the attempt to situate the central problem that it will be examined in the wake of broader Quinean philosophy as a whole, while the second part will be devoted to the reconstruction of the debate. The conclusion reached is that the final formulation of the conception of Quine can be considered as satisfactory solution of many problems of the initial formulation of proximal conception since we follow the suggestion of Lars Bergström and understand that the meaning of a observation sentence must consist of a subject s dispositions to assent and dissent to sentence, instead of identifying the meaning with set of proximal stimuli that the speaker ties to sentence. Furthermore, though it may be possible to raise objections to the Quine s final solution, it may be considered more appropriate solution to the problems of proximal conception since compared to the suggestion made by Davidson, because the adoption of conception distal would not be satisfactory for Quine s philosophical purposes. / Há aproximados trinta anos, iniciou-se um debate entre os filósofos W. V. O. Quine e D. Davidson a respeito de onde deveria ser situado, na cadeia causal mundo-falante, o elemento que determina o significado empírico de frases de observação − doravante, chamar-se-á tal elemento de estímulo . De acordo com Quine, que sustenta o que se pode chamar de concepção proximal , tal estímulo estaria localizado na superfície sensorial do falante, ou seja, em posição próxima a este em referida cadeia causal − estímulo proximal −; Davidson, por outro lado, critica a concepção proximal, pelo fato de que a mesma não seria capaz de explicar a natureza pública da linguagem, e sugere a Quine seu abandono em prol da concepção distal, por ele próprio sustentada, conforme a qual tal estímulo estaria situado nos próprios objetos e eventos sobre os quais falam as frases, isto é, em posição maibs distante do falante − estímulo distal. A despeito da sugestão de Davidson, Quine insiste até o final de sua obra em não adotar oficialmente a concepção distal, introduzindo, contudo, algumas modificações em sua concepção a fim de escapar às críticas procedidas por aquele autor. Tendo em vista essa divergência entre os dois autores, a presente dissertação tem como objetivo proceder à reconstrução e avaliação desse debate. Há que se ressaltar, antes de tudo, que Quine é um filósofo muito sistemático e que suas teses estão intimamente conectadas entre si, de modo que se faz necessária uma visão mais geral de sua filosofia sempre que se deseja entender um problema específico que se encontra nela inserido, sob pena de prejudicar a adequada compreensão do mesmo. Por essa razão, este trabalho será dividido em duas partes principais: a primeira delas será reservada à tentativa de situar o problema central que será nele examinado no bojo mais amplo da filosofia quineana como um todo, enquanto a segunda parte será dedicada propriamente à reconstrução do debate. A conclusão a que se chega é que a formulação final da concepção de Quine pode ser considerada satisfatória como solução de muitos problemas da formulação inicial da concepção proximal desde se siga a sugestão de Lars Bergström e se entenda que o significado de uma frase de observação deve consistir nas disposições de um sujeito para assentir ou dissentir a ela, em vez de identificar o significado com o conjunto de estímulos proximais que o falante vincula a ela. Ademais, por mais que seja possível levantar objeções contra a solução final de Quine, ela pode ser considerada a saída mais adequada aos problemas da concepção proximal quando comparada à sugestão feita por Davidson, uma vez que a adoção da concepção distal não seria satisfatória para os propósitos filosóficos de Quine.

Abstract This study investigates the relationship between play and child development. This work is the continuation of a thesis on children’s verbal creativity stimulated by dialogical drama intervention which I defended in 2001 at the Vilnius Pedagogical University, Lithuania. The first doctoral thesis in educology resulted in the main intervention method (Dialogical Drama with Puppets) used in this project. The theoretical framework of the study is based on cultural-historical theories developed by Vygotsky and his followers. This approach has influenced on the methodological choices of the study and the concept of the zone of proximal development is a central concept in Vygotskian theory of human cultural development. The concept has been elaborated in an earlier publication (Hakkarainen & Bredikyte 2008) and is now used as an analytic tool. Other theoretical concepts of Vygotsky like the social situation of development, the unit, environment and mechanism of development are used. This study is a small sample from the whole research project, which integrated research studies, theoretical courses and practice of master’s degree students in early education. For families and children the project was a play club. From the theoretical point of view the project was a “genetic experiment”, a “playworld” and intervention study aiming at joint creative play of adults and children. In cultural-historical theory (cultural) environment is the source of qualitative developmental changes of individuals, but each child has to be motivated and self carry out developmental acts. These theoretical principles require special forms of social interaction “mutual interventions”. The methodological approach opens a new perspective to the study of play and development. Individual play development of some children is followed up several years. Cumulative effects and qualitative changes can be detected easier in this setting. Multi-age child groups change our understanding about play development. Empirical part of this study consists of a few cases, which demonstrate what kind of developmental trajectories are possible. It is impossible to tell exactly what the effect of our play environment is, but observations and interpretations can guide further research activity. The results of this study demonstrate in which conditions narrative intervention in joint playworld environment can lead to creative acts, what steps are necessary in the development of joint play, how mutuality in adult-child play supports child development, and what elements are essential in play producing pedagogy and professional growth. / Tiivistelmä Tämä tutkimus selvittää leikin ja lasten kehityksen välistä yhteyttä. Siinä työssä jatkuu tekijän edellisessä Vilnan pedagogisen yliopiston edukologian väitöskirjassa 2001 aloittama lasten luovuuden tutkimus dialogista draamaa käyttäen. Tämä tutkimus tuotti keskeisen intervention menetelmän (Dialoginen nukkedraama), jota nyt käytetään. Tämän tutkimuksen viitekehys perustuu Vygotskin ja hänen seuraajiensa kehittelemään kulttuuri-historialliseen teoriaan. Metodologiset ratkaisut ja Vygotskin kulttuurisen kehityksen teorian keskeinen käsite – lähikehityksen vyöhyke – ovat vaikuttaneet tutkimuksen toteutukseen. Tätä käsitettä on kehitelty aikaisemmassa julkaisussa (Hakkarainen & Bredikyte, 2008) ja sitä käytetään nyt analyyttisenä työvälineenä. Vygotskin muitakin teoreettisia käsitteitä kuten ”kehityksen sosiaalinen tilanne”, ”kehityksen analyysiyksikkö”, ”kehityksen ympäristö”, ja ”kehitysmekanismi” on otettu käyttöön. Tämä tutkimus on pieni siivu koko tutkimusprojektista, johon kytkeytyi varhaiskasvatuksen maisteriopiskelijoiden tutkimusopintoja, teoriakursseja ja harjoittelua. Perheiden ja osallistuvien lasten näkökulmasta projekti oli leikkikerho. Teoreettiselta näkökulmalta projektin ydin oli ”geneettinen eksperimentti”, ”leikkimaailma” ja ”interventiotutkimus”, joka pyrkii saamaan aikaan aikuisten ja lasten yhteistä luovaa leikkiä. Kulttuuri-historiallisessa teoriassa (psykologinen/ kulttuurinen) ymäristö on yksilön laadullisten kehityksen muutosten lähde, mutta jokaisen lapsen on oltava motivoitunut ja itse toteutettava kehittävät teot. Nämä teoreettiset periaatteet edellyttävät erityistä sosiaalisen vuorovaikutuksen muotoa ”vastavuoroista interventiota”. Käytetty metodologinen lähestymistapa avaa uuden mahdollisuuden tutkia leikkiä ja kehitystä. Joidenkin yksittäisten lasten leikin kehitystä on voitu seurata useita vuosia. Kasautuvat vaikutukset ja laadulliset muutokset voidaan todeta helpommin tällaisella tutkimusotteella. Eri-ikäisten lasten yhteiset leikkiryhmät auttavat ymmärtämään paremmin leikin olemusta ja kehitystä. Tutkimuksen empiirinen osa muodostuu yksitäistapauksista, jotka kertovat millaiset kehityskaaret ovat mahdollisia. Tarkkoja syitä ja seurauksia ei ole mahdollista leikkiympäristössä osoittaa, mutta havainnot ja tulkinnat ohjaavat jatkotutkimusta. Tutkimuksen tulokset kertovat millaisissa olosuhteissa narratiivinen interventio yhteisessä leikkiympäristössä voi johtaa luoviin tekoihin, miten yhteinen leikki voi kehittyä ja kehittää, millainen vastavuoroisuus aikuisen ja lasten leikissä tukee kehitystä sekä mitkä asiat ovat välttämättömiä leikin pedagogiikassa ja ammatillisessa kasvussa.

Diese retrospektive Studie untersucht 351 Patienten mit 358 proximalen Femurfrakturen, die zwischen 01/2008 und 12/2010 im Universitätsklinikum Göttingen behandelt wurden. Ziel war es, das Patientengut mit proximalen Femurfrakturen zu analysieren und Einflüsse der Versorgung sowie der Komorbiditäten auf die Komplikationen und das Outcome der Patienten herauszufinden. Alter und Geschlechterverteilung in diesem Patientengut entsprechen weitgehend den in der Literatur publizierten Angaben. Auffallend ist in dieser Untersuchung, dass Raucher und ehemalige Raucher zum Zeitpunkt der Fraktur signifikant jünger waren als Nichtraucher. Ebenso waren alkoholabhängige und ehemals alkoholabhängige Patienten signifikant jünger als Patienten, die keinen Alkoholabusus betrieben. Die Aussagekraft dieser Ergebnisse wird jedoch durch die geringen Fallzahlen der hier angesprochenen Teilgruppen gemindert. Dennoch ist ein Zusammenhang zwischen Rauchen/Alkoholkonsum und einer in jüngerem Lebensalter auftretenden Fraktur wahrscheinlich. Die höchste Krankenhausliegedauer wiesen Patienten nach H-TEP-Implantation sowie nach Schraubenosteosynthesen auf. Am kürzesten lagen Patienten nach DHS-Implantation. Bezogen auf das Alter zeigten im Gesamtpatientengut die 70-79-jährigen Patienten die längste Krankenhausaufenthaltsdauer. Hinsichtlich der Osteoporosetherapie muss nach den Ergebnissen dieser Studie von einer Minderversorgung in Diagnostik und Therapie ausgegangen werden. Postoperativ stieg der prozentuale Anteil entsprechend therapierter Patienten zwar leicht an, gemessen am Alter und dem Wissen über das Vorkommen von osteoporotischen Frakturen muss aber davon ausgegangen werden, dass bei deutlich mehr Patienten eine Antiosteoporosemedikation dringend notwendig wäre. Die häufigsten medizinischen Komplikationen waren Anämien, Elektrolytentgleisungen und Durchgangssyndrome. Die häufigsten chirurgischen Komplikationen waren Hämatome und Wundheilungsstörungen, gefolgt von mechanischen Komplikationen und Infektionen. Ein Zusammenhang zwischen Hämatomen, Wundheilungsstörungen und Infektionen mit einer präoperativen Antikoagulantientherapie konnte nicht festgestellt werden. Patienten mit Wundinfektionen waren multimorbider als das Gesamtpatientenkollektiv. Eine Zunahme der Komplikationsrate mit dem Alter konnte in dieser Untersuchung nicht nachgewiesen werden. Patienten mit chirurgischen Komplikationen waren geringfügig jünger als die Gesamtgruppe. Bei der Versorgung von Schenkelhalsfrakturen erwiesen sich die Osteosynthesen anfälliger 71 gegenüber chirurgischen Komplikationen als Endoprothesen. Pertrochantäre Frakturen hatten eine erhöhte chirurgische Komplikationsrate bei der DHS im Vergleich zu intramedullären Nagelsystemen. Zeitnah nach der Aufnahme operierte Patienten waren jünger als spät operierte Patienten. Je später der Operationszeitpunkt, desto höher war die ASA-Einstufung. Entsprechend nahmen später als 24 Stunden und innerhalb von sechs bis 24 Stunden operierte Patienten mehr Medikamente ein als die innerhalb von sechs Stunden operierten Patienten. Die später als 24 Stunden Operierten lagen deutlich länger im Krankenhaus als die früher Operierten. Hinsichtlich des Auftretens von postoperativen Komplikationen konnte kein Zusammenhang mit dem Operationszeitpunkt festgestellt werden. Die im Krankenhaus verstorbenen Patienten wiesen eine im Vergleich zur Gesamtgruppe leicht erhöhte präoperative Verweildauer auf, aufgrund der geringen Fallzahlen ist die Aussagekraft aber gemindert. Die Verstorbenen waren nicht älter als das Gesamtpatientengut. Gemessen an der Anwendungshäufigkeit der Therapiemittel wiesen Patienten mit Endoprothesen eine höhere Letalität auf. Häufig waren Hochrasanz- oder Absturztraumen Unfallursache. Die verstorbenen Patienten, die durch einen banalen Sturz die Fraktur erlitten, waren multimorbider als die Gesamtgruppe.

Chloroperoxidase (CPO) from Caldariomyces fumago is a versatile heme enzyme with great potential for environmental and pharmaceutical applications. It catalyzes a plethora of reactions including halogenation, dismutation, epoxidation, and oxidation. The diverse catalytic capabilities of CPO have long been attributed to the protein’s distinct active site that combines structural features of peroxidases and cytochromes P450. Particularly, the role of the axial thiolate ligand in CPO catalysis has been much debated. Furthermore, no data are available on the role of hydrogen bonding between Arg 26-Asn 37 and Ala 27-Asn 33 of the proximal helix in defining the structural and catalytic properties of CPO. In order to investigate the influence of the proximal thiolate and the proximal hydrogen bond network on the structural and biochemical properties of CPO, several mutant CPOs were constructed and characterized using various spectroscopic techniques and enzymatic assays. Cysteine 29, which coordinates to the heme, was replaced with a His (C29H) to mimic the proximal ligation of classical peroxidases. The UV-Vis spectrum of the carbon monoxide complex of ferrous C29H mutant remained essentially identical to that of wild type (WT) CPO and P450 although the ferric state of the variant enzyme showed a spectral pattern reminiscent of a classical histidine ligated heme peroxidase. Histidine ligation was further confirmed by paramagnetic NMR spectroscopy. Contrary to a previous report, the specific chlorination activity of C29H was essentially abolished (less than 1% of that of WT CPO) but the epoxidation and peroxidation activities were enhanced 10-fold and 55-fold, respectively. These findings demonstrate for the first time that the heme ligand, Cys 29 in CPO, is not a prerequisite for CPO’s unique P450-like spectroscopic signatures but is constitutive for the protein’s versatile catalytic activities. Arginine 26 and Asparagine 33 in the proximal heme pocket were replaced with Ala (R26A, N33A, and R26A/N33A) to disrupt hydrogen bonding. Tertiary structures and heme environments of R26A, N33A, and R26A/N33A differed from those of WT CPO as determined by CD spectroscopy. The specific chlorination and dismutation activities of all mutants were almost abolished but the peroxidation and epoxidation rates were increased. These results show that the proximal hydrogen bond network plays an important role in maintaining the structure and catalytic diversity of CPO.

Chloroperoxidase (CPO) is a heme-thiolate protein with exceptional versatility and great potential as a biocatalyst. The CPO reactive species, Compound I ( Cpd I) is of particular interest, as well as the Cytochrome P450 (P450) -type monoxygenase catalytic activity, which has significant biotechnological potential. Proximal hydrogen bonding of the axial sulfur with the backbone amides (NH•••S) is a conserved feature of heme-thiolate enzymes. In CPO, the effect of NH•••S bonds is amplified by the dipole moment of the proximal helix. The role of the proximal region has been disputed as to whether it simply protects the axial sulfur, or whether it additionally influences catalysis via modulation of the push effect. The objective of the research presented herein is two-fold. First, the influence of the NH•••S bonds on Cpd I formation is determined by obtaining the reaction coordinate, starting from a peroxide bound heme, for two model systems (one with proximal residues providing NH•••S bonds and one without) and comparing the results. Secondly, the influence of the proximal region on the epoxidation of Cis-β-methylsterene is obtained. This is performed similarly to the first objective however, the reaction coordinate begins with a Cpd I-CBMS complex and the proximal contribution is extended to include the influence of the proximal helix dipole. Our findings show that the proximal region stabilizes Cpd 0 relative to all other minima and reduces the barrier for Cpd 0’s formation. The stability of protonated Compound 0 is reduced, favoring a hybrid homo-heterolytic relative to a classic heterolytic mechanism for O-O bond scission. Additionally, the proximal region significantly enhances CPO’s reactivity; the Cβ-O bond barrier is stabilized, while Cα-O-Cβ ring closure becomes barrierless. The stabilization of the reaction barrier correlates with increased electron density transfer to residues of the proximal pocket and involves a change in the electron transfer mechanism. These results can be traced to a reduction in the pKa of the heme-bound substrate and an increase in oxidation potential, a result of the proximal region reducing the “push effect”.

This study investigates the lithological characteristics, and lateral and vertical facies trends of poorly understood, deep-marine matrix-rich sedimentary rocks. Two laterally extensive, well-exposed outcrops of slope and proximal basin floor deposits were investigated from the Neoproterozoic Windermere Supergroup. Significantly, matrix-rich beds have been found to undergo the same lateral trends (over ~200-650 m) in both outcrops. Initially, thicker, clayey sandstone transitions laterally to a bipartite bed with the development of an upper, planar-based, more matrix-rich unit. Further laterally, the basal unit progressively thins until it pinches out, and all that remains is the upper, more matrix-rich unit – a sandy claystone. It too thins and then pinches out. Draping the entire transect is a thin, matrix-poor structured unit overlain by a mudstone or claystone cap. These trends are interpreted to reflect a progressive but rapid lateral evolution of flow structure controlled primarily by particle settling, namely sand, from mud-rich avulsion-related flows.

Cette thèse s'inscrit dans le contexte de l'optimisation convexe. Elle apporte à ce domaine deux contributions principales. La première porte sur les méthodes d'optimisation convexe non lisse appliquées à la vision par ordinateur. Quant à la seconde, elle fournit de nouveaux résultats théoriques concernant la manipulation de mesures de divergences, telles que celles utilisées en théorie de l'information et dans divers problèmes d'optimisation. Le principe de la stéréovision consiste à exploiter deux images d'une même scène prises sous deux points de vue, afin de retrouver les pixels homologues et de se ramener ainsi à un problème d'estimation d'un champ de disparité. Dans ce travail, le problème de l'estimation de la disparité est considéré en présence de variations d'illumination. Ceci se traduit par l'ajout, dans la fonction objective globale à minimiser, d'un facteur multiplicatif variant spatialement, estimé conjointement avec la disparité. Nous avons mis l'accent sur l'avantage de considérer plusieurs critères convexes et non-nécessairement différentiables, et d'exploiter des images multicomposantes (par exemple, des images couleurs) pour améliorer les performances de notre méthode. Le problème d'estimation posé est résolu en utilisant un algorithme parallèle proximal basé sur des développements récents en analyse convexe. Dans une seconde partie, nous avons étendu notre approche au cas multi-vues qui est un sujet de recherche relativement nouveau. Cette extension s'avère particulièrement utile dans le cadre d'applications où les zones d'occultation sont très larges et posent de nombreuses difficultés. Pour résoudre le problème d'optimisation associé, nous avons utilisé des algorithmes proximaux en suivant des approches multi-étiquettes relaxés de manière convexe. Les algorithmes employés présentent l'avantage de pouvoir gérer simultanément un grand nombre d'images et de contraintes, ainsi que des critères convexes et non convexes. Des résultats sur des images synthétiques ont permis de valider l'efficacité de ces méthodes, pour différentes mesures d'erreur. La dernière partie de cette thèse porte sur les problèmes d'optimisation convexe impliquant des mesures d'information (Phi-divergences), qui sont largement utilisés dans le codage source et le codage canal. Ces mesures peuvent être également employées avec succès dans des problèmes inverses rencontrés dans le traitement du signal et de l'image. Les problèmes d'optimisation associés sont souvent difficiles à résoudre en raison de leur grande taille. Dans ce travail, nous avons établi les expressions des opérateurs proximaux de ces divergences. En s'appuyant sur ces résultats, nous avons développé une approche proximale reposant sur l'usage de méthodes primales-duales. Ceci nous a permis de répondre à une large gamme de problèmes d'optimisation convexe dont la fonction objective comprend un terme qui s'exprime sous la forme de l'une de ces divergences / Convex optimization aims at searching for the minimum of a convex function over a convex set. While the theory of convex optimization has been largely explored for about a century, several related developments have stimulated a new interest in the topic. The first one is the emergence of efficient optimization algorithms, such as proximal methods, which allow one to easily solve large-size nonsmooth convex problems in a parallel manner. The second development is the discovery of the fact that convex optimization problems are more ubiquitous in practice than was thought previously. In this thesis, we address two different problems within the framework of convex optimization. The first one is an application to computer stereo vision, where the goal is to recover the depth information of a scene from a pair of images taken from the left and right positions. The second one is the proposition of new mathematical tools to deal with convex optimization problems involving information measures, where the objective is to minimize the divergence between two statistical objects such as random variables or probability distributions. We propose a convex approach to address the problem of dense disparity estimation under varying illumination conditions. A convex energy function is derived for jointly estimating the disparity and the illumination variation. The resulting problem is tackled in a set theoretic framework and solved using proximal tools. It is worth emphasizing the ability of this method to process multicomponent images under illumination variation. The conducted experiments indicate that this approach can effectively deal with the local illumination changes and yields better results compared with existing methods. We then extend the previous approach to the problem of multi-view disparity estimation. Rather than estimating a single depth map, we estimate a sequence of disparity maps, one for each input image. We address this problem by adopting a discrete reformulation that can be efficiently solved through a convex relaxation. This approach offers the advantage of handling both convex and nonconvex similarity measures within the same framework. We have shown that the additional complexity required by the application of our method to the multi-view case is small with respect to the stereo case. Finally, we have proposed a novel approach to handle a broad class of statistical distances, called $varphi$-divergences, within the framework of proximal algorithms. In particular, we have developed the expression of the proximity operators of several $varphi$-divergences, such as Kulback-Leibler, Jeffrey-Kulback, Hellinger, Chi-Square, I$_{alpha}$, and Renyi divergences. This allows proximal algorithms to deal with problems involving such divergences, thus overcoming the limitations of current state-of-the-art approaches for similar problems. The proposed approach is validated in two different contexts. The first is an application to image restoration that illustrates how to employ divergences as a regularization term, while the second is an application to image registration that employs divergences as a data fidelity term

The aim of the present study is to investigate how three Swedish teachers view literary discussion as a tool for teaching and learning. A socio-cultural perspective with Vygotsky’s zone of proximal development and Dysthe’s dialogic/monologic classroom serves as the theoretical point of departure. The study is based on qualitative semistructured interviews with three Swedish teachers, all working in upper secondary school. An interview guide was established on the basis of previous research in the field of literary discussion. The interviews showed that the teachers had a positive view of conversations and discussions as a tool for teaching and learning, since they see good progression in the pupils’ reading comprehension, their conception of literature, and analytical ability. Literary discussions are chiefly appreciated as a tool that comes into its own as a method in teaching an aspect of a subject and as preparation for a written examination. Another finding is that the teachers’ positive outlook on literary discussion includes a view of teachers as being active and present when help and support should be close at hand for the pupils.

Osteoarthritis (OA) is the most common form of human joint disease causing significant pain and disability. Current treatment for hip OA is limited to pain management and joint replacement for end-stage disease. The development of methods for early diagnosis and new treatment options are urgently needed to minimise the impact of the disease. Studies of hip OA have shown that hip joint morphology correlates with susceptibility to hip OA and disease progression. Bone shape analyses play an important role in disease diagnosis, pre-operative planning, and treatment analysis as well as in epidemiological studies aimed at identifying risk factors for hip OA. Statistical Shape Models (SSMs) are being increasingly applied to imaging-based bone shape analyses as they provide a means of quantitatively describing the global shape of the bone. This is in contrast to conventional clinical and research practice where the analysis of bone shape is reduced to a series of measurements of lengths and angles. This thesis describes the development of a novel fully automatic software system that segments the proximal femur from anteroposterior (AP) pelvic radiographs by densely placing 65 points along its contour. These annotations can then be used for the detailed morphometric analysis of proximal femur shape. The performance of the system was evaluated on a large dataset of 839 radiographs of mixed quality. Achieving a mean point-to-curve error of less than 0.9mm for 99% of all 839 AP pelvic radiographs, this is the most accurate and robust automatic method for segmenting the proximal femur in two-dimensional radiographs yet published. The system was also applied to a number of morphometric analyses of the proximal femur, showing that SSM-based radiographic proximal femur shape significantly differs between males and females, and is highly symmetric between the left and right hip joint of an individual. In addition, the research described in this thesis demonstrates how the point annotations resulting from the system can be used for univariate and multivariate genetic association analyses, identifying three novel genetic variants that contribute to radiographic proximal femur shape while also showing an association with hip OA.The developed system will facilitate complex morphometric and genetic analyses of shape variation of the proximal femur across large datasets, paving the way for the development of new options to diagnose, treat and prevent hip OA.

The current study empirically tested four models of type II diabetic patient adherence, including wellness, screening, medication, and treatment adherence. Four mediators were proposed patient understanding, agreement, trust, and motivation were tested for each model. The current study is grounded in patient-centered communication, responding to Street’s (2013) call to model pathways between communication and patient health outcomes. Moreover, the study argues that adherence, for type II diabetic patients should be conceptualized as four distinct clusters of behavior (wellness, screening, medication, and treatment). A sample of (n=817) type II diabetes patients from the U.S. under the care of a medical provider and taking medication for their type II diabetes were surveyed. Findings from the present study indicate that the relationship between patient-centered communication and patient-health outcomes is mediated by proximal outcomes. The results contribute to our understanding or patient-centered communication, patient understanding, agreement, trust, and motivation, and adherence behaviors. Resulted indicated that while three of the four proposed hypotheses were supported, the most commonly studied type of adherence (medication), the relationship between patient-centered communication and medication adherence was not mediated. The current study ends with a discussion and implication of the findings as well as directions for future research