There have been many advances in surgical residency education and similar interest exists in fellowship education. This study evaluated perceptions among spine surgeons about the specific competencies required for successful spine surgical fellowship training, and then compared these perceptions to clinical practice. Firstly, a questionnaire was administered to spine fellow trainees and academic spine surgeons across Canada in order to identify the cognitive and technical skills required for successful spine fellowship training. Fellowship trainees and supervisors had similar perceptions on the relative importance of specific cognitive and technical competencies. Differences in perceptions were found when comparing surgeons based on background residency specialty training (orthopaedic surgical or neurosurgical). Secondly, using administrative data, a retrospective study assessed volumes, surgeon characteristics, and outcomes for surgery of the degenerative lumbar spine in Ontario between 1995 and 2001. Neurosurgeons were found to perform more decompressions, and more total procedures, than orthopaedic surgeons with similar outcomes.

Buvo tirta išsigimstančių dalinių išvestinių diferencialinių lygčių sistema, sudaryta iš dviejų lygčių. Gauti formalūs tos sistemos sprendiniai, kurių struktūra yra tokia: kintamojo, pagal kurį išsigimsta sistemos eilė, laipsnis, padaugintas iš eksponentės, kurios rodiklyje yra to kintamojo polinomas neigiamais kintamojo laipsniais, ir ši sandauga padauginta iš laipsninės eilutės teigiamais kintamojo laipsniais. / A degenerative partial derivatives differential equations system consisting of two equations were analyzed. Formal solutions of a system were formed. The structure of solutions is as follows: variable, by which the system degenerates, degree is multiplied by the exponent, which subscript is the variable’s polynome with variable’s negative degrees, and this multiplication is multiplied by power series with positive variable degrees.

Degenerative suspensory ligament desmitis (DSLD) is a debilitating disease of connective tissues seen in many breeds but has become prevalent in the Peruvian Pasohorse. DSLD is believed to be a genetic disorder caused by one primary founder and most likely has a recessive mode of inheritance although a dominant or co-dominant mode of inheritance has not been ruled out. A genome scan using 259 microsatellite markers was used to test for linkage disequilibrium between one or more markers and DSLD. Two groups of Peruvian Pasohorses were selected from one population including the US and Canada. The only difference between the two groups of horses besides the size of the two groups was the presence of DSLD in the affected group and the absence of DSLD in the unaffected group. It was assumed that differences seen between the two groups in homozygosity and or common allele frequency could be an indication of linkage to DSLD. As a connective tissue disorder, there were a large number of candidate genes forDSLD to consider, yet no identical human or animal model exists. The genome scan identified five chromosomal regions where statistically significant differences were seen between affected and unaffected sample populations that could be indications of linkage to DSLD. Those chromosomes were: ECA 6, 7, 11, 14, and 26. Sequencing of a portion of the G domain in the Chondroitin Sulfate Proteoglycan2 (CSPG2) gene has mostly ruled out that segment of chromosome 14 as having linkage to DSLD. Further research needs to be conducted in the regions of ECA 6,7,11 and 26 where statistically significant differences were seen between the affected and unaffected groups, especially on ECA 6 and 11 since possible candidate genes are located in those regions based on the human comparative map.

With societies aging all around the world, the global burden of degenerative diseases is expected to increase exponentially. From the perspective drug development, degenerative diseases represent an especially challenging class. Clinical trials, in this context often termed disease progression studies, are long, costly, require many individuals, and have low success rates. Therefore, it is crucial to use informative study designs and to analyze efficiently the obtained trial data. The development of novel approaches intended towards facilitating both the design and the analysis of disease progression studies was the aim of this thesis. This aim was pursued in three stages (i) the characterization and extension of pharmacometric software, (ii) the development of new methodology around statistical power, and (iii) the demonstration of application benefits. The optimal design software PopED was extended to simplify the application of optimal design methodology when planning a disease progression study. The performance of non-linear mixed effect estimation algorithms for trial data analysis was evaluated in terms of bias, precision, robustness with respect to initial estimates, and runtime. A novel statistic allowing for explicit optimization of study design for statistical power was derived and found to perform superior to existing methods. Monte-Carlo power studies were accelerated through application of parametric power estimation, delivering full power versus sample size curves from a few hundred Monte-Carlo samples. Optimal design and an explicit optimization for statistical power were applied to the planning of a study in Alzheimer's disease, resulting in a 30% smaller study size when targeting 80% power. The analysis of ADAS-cog score data was improved through application of item response theory, yielding a more exact description of the assessment score, an increased statistical power and an enhanced insight in the assessment properties. In conclusion, this thesis presents novel pharmacometric methods that can help addressing the challenges of designing and planning disease progression studies.

L'IRM de diffusion (IRMd) est une modalité d'imagerie médicale qui suscite un intérêt croissant dans la recherche en neuro-imagerie. Elle permet d'apporter in vivo des informations nouvelles sur les micro-structures locales des tissus. En chaque point d'une acquisition d'IRMd, la distribution des directions de diffusion des molécules d'eau est modélisée par un tenseur de diffusion. La nature multivariée de ces images requiert la conception de nouvelles méthodes de traitement adaptées. Le contexte de cette thèse est l'analyse automatique de changements longitudinaux intra-patient avec pour application le suivi de pathologies neuro-dégénératives. Notre recherche a ainsi porté sur le développement de nouveaux modèles et tests statistiques permettant la détection automatique de changements sur des séquences temporelles d'images de diffusion. Cette thèse a ainsi permis une meilleure prise en compte de la nature tensorielle des modèles d'ordre 2 (tests statistiques sur des matrices définies positives), une extension vers des modèles d'ordre supérieur et une gestion plus fine des voisinages sur lesquels les tests sont menés, avec en particulier la conception de tests statistiques sur des faisceaux de fibres. / Diffusion MRI is a new medical imaging modality of great interest in neuroimaging research. This modality enables the characterization in vivo of local micro-structures. Tensors have commonly been used to model the diffusivity profile at each voxel. This multivariate data set requires the design of new dedicated image processing techniques. The context of this thesis is the automatic analysis of intra-patient longitudinal changes with application to the follow-up of neuro-degenerative pathologies. Our research focused on the development of new models and statistical tests for the automatic detection of changes in temporal sequences of diffusion images. Thereby, this thesis led to a better modeling of second order tensors (statistical tests on positive definite matrices), to an extension to higher-order models, and to the definition of refined neighborhoods on which tests are conducted, in particular the design of statistical tests on fiber bundles.

abstract: Intervertebral Disc Degeneration (IVDD) is a complex phenomenon characterizing the desiccation and structural compromise of the primary joint in the human spine. The intervertebral disc (IVD) serves to connect vertebral bodies, cushion shock, and allow for flexion and extension of the vertebral column. Often presenting in the 4th or 5th decades of life as low back pain, this disease was originally believed to be the result of natural “wear and tear” coupled with repetitive mechanical insult, and as such most studies focus on patients between 40 and 50 years of age. Research over the past two decades, however, has demonstrated that environmental factors have only a modest effect on disc degeneration, with genetic influences playing a much more substantial role. Extensive research has focused on this process, though definitive risk factors and a clear pathophysiology have proven elusive. The aim of this study was to assemble a cohort of patients exhibiting definitive signs of degeneration who were well below the average age of presentation, with minimal or no exposure to suspected environmental risk factors and to conduct a targeted genome analysis in an attempt to elucidate a common genetic component. Through whole genome sequencing and analysis, the results corroborated findings in a previous study, as well as demonstrated a potential connection and influence between mutations found in IVD structural or functional genes, and the provocation of IVDD. Though the sample size was limited in scale and age, these findings suggest that further IVDD research into the association of variants in collagen, aggrecan and the insulin-like growth factor receptor genes of young patients with an early presentation of disc degeneration and minimal exposure to suspected risk factors is merited. / Dissertation/Thesis / Masters Thesis Biology 2016

Made available in DSpace on 2015-03-26T13:47:26Z (GMT). No. of bitstreams: 1 texto completo.pdf: 330178 bytes, checksum: 0d7d63bcceac97aa987ceb95abd2345a (MD5) Previous issue date: 2003-12-15 / The aim of this study was to evaluate the effects of gallium arsenite (Ga-As) diode laser application on rabbits knees with ostheoarthritis induced by intrarticular injection of carrageenan. Clinical evaluation in vivo showed that there was reduction in inflammatory signs and pain, with treated animals presenting a better performance and greater amplitude of movements, if compared with untreated animals. The degenerative processes resulting from the administration of carrageenan were evidenced in both groups by post-mortem macroscopic and microscopic assessment in both treated and control groups, which allowed inferring that laser diminished the presence of chemical mediators, reducing the inflammatory response and local lesions, including the degradation of glycosaminoglycans. Histological analysis of the synovial membrane revealed the presence of inflammatory cells distributed diffusely or in foci, the intensity of which was higher in control groups. It was concluded therefore that the rate of progression of ostheoarthritis was slowed down by lasertherapy. / O objetivo deste estudo foi avaliar os efeitos do laser a diodo de Arseneto de Gálio (As-Ga) aplicado no joelho de coelhos portadores de osteoartrite induzida pela aplicação intrarticular de carragenina. A avaliação clínica in vivo demonstrou diminuição dos sinais inflamatórios e da dor, permitindo melhor desempenho e maior amplitude de movimento do joelho dos coelhos tratados em comparação aos dos animais não tratados. A avaliação macroscópica e microscópica post-mortem evidenciaram os processos degenerativos decorrentes da administração de carragenina em ambos os grupos, tratado e controle. Os resultados permitiram inferir que o laser diminuiu a presença de mediadores químicos reduzindo, assim, a resposta inflamatória e as lesões locais, inclusive a degradação dos glicosaminoglicanos. A análise histológica da membrana sinovial demonstrou a presença de células inflamatórias, distribuídas difusamente ou em focos, em maior intensidade nos grupos controle. Concluiu-se, portanto, que o caráter progressivo da osteoartrite foi retardado pela laserterapia.

O RDW é um índice hematológico utilizado para avaliação quantitativa da anisocitose eritrocitária, sendo útil na diferenciação das causas de quadros anêmicos. Atualmente, na medicina humana, o RDW tem sido considerado como um importante fator prognóstico em quadros de ICC, mesmo na ausência de anemia. A CRP é considerada a principal proteína de fase aguda sendo amplamente utilizada como marcadora de inflamação. O objetivo deste estudo foi determinar se há diferença nos valores do RDW e da concentração da CRP em cães com DVDCM com e sem ICC, bem como nos diferentes estágios (A, B1, B2, C e D) da doença, segundo a classificação da ACVIM, comparados a cães de raças predispostas, mas sem a doença cardíaca, e associações entre as variáveis. Esta pesquisa constituiu um estudo clínico observacional prospectivo transversal de caráter exploratório, realizada em cães com DVDCM. Para tal, foram selecionados 141 cães, de até 20kg, machos e fêmeas. O grupo com ICC e sem ICC apresentaram menor número de hemácias, hemoglobina e hematócrito em relação ao grupo controle (P<0,001). O índice RDW não diferiu entre os grupos estudados quando foram alocados quanto ao estadiamento ACVIM (P= 0,25), quanto à presença de ICC (P= 0,146), ou de remodelamento cardíaco (P=0,078). Quanto à CRP, os grupos C e D (C: 2.251 ng/dL, 962,05-5.292,5 ng/dL e D: 3.628,4 ng/dL, 4.1592,3-6.254,5 ng/dL) apresentaram concentração maior que o grupo controle (1.685,5 ng/dL, 1.045,45-3.795,5 ng/dL). Quanto ao estadiamento da DVDCM os grupos diferiram entre si (P=0,014) porém, não foi possível identificar quais grupos apresentaram diferença. O grupo com ICC (2.939,7-1.304,25-5.908,8 ng/dL) apresentou maior concentração de CRP em relação ao grupo controle (1.685 ng/dL, 1.1015,45-3.795,5 ng/dL) (P=0,03). O grupo com remodelamento (4.916,66±6.102,14) apresentou maior concentração de CRP em relação ao grupo sem remodelamento (2.510,67±3,26) (P=0,009). Houve correlação positiva fraca entre CRP e número total de leucócitos (r=0,197; P=0,019). Conclui-se que apesar de não ter sido detectada diferença significativa para o RDW houve tendência a valores maiores nos cães com remodelamento comparados aos sem remodelamento. A concentração de CRP foi maior nos cães com remodelamento cardíaco em relação àqueles sem remodelamento e nos cães com ICC em relação aos cães sem ICC e àqueles de raças predispostas, mas sem alterações cardíacas. A dosagem sérica de CRP juntamente com outros marcadores e exames complementares já utilizados rotineiramente, poderá ser útil na avaliação e acompanhamento de pacientes portadores de DVDCM / RDW is a hematological index used for anisocytosis quantitative assesment, and useful to diferenciate anemic states. In human medicine, it has been considered an important prognostic factor in heart failure (HF), even in the absence of anemia. CRP is considered the main acute phase protein, and it is widely used as a marker of inflammation. An exploratory prospective cross sectional study was conducted aiming to determine whether there is a difference in RDW and CRP concentration in dogs with chronic degenerative mitral valve disease (CDMVD) with and without HF, presence of remodeling, as well as between the different disease stages (A, B1, B2, C e D - ACVIM), compared to dogs of predisposed breeds, but without heart disease. For this study, 141 dogs, up to 20kg, males and females were distributed in groups in order to achieve the main golas. Dogs with and without HF presented smaller number of red blood cells, hemoglobin and hematocrit compared to control group (P<0.001). RDW was not diferente between groups for CDMVD stages (P= 0.25), regarding HF presence (P= 0.146), or cardiac remodeling (P=0.078). Groups C and D (C: 2,251 ng/dL, 962.05-5,292.5 ng/dL e D: 3,628.4 ng/dL, 4,1592.3-6,254.5 ng/dL) presented higher CRP concentration compared to control (1,685.5 ng/dL, 1,045.45-3,795.5 ng/dL). There was a difference in CRP concentration between groups, however, it was not possible to identify the differing groups (P=0.014). CRP concentration was higher in HF group (2,939.7-1,304.25-5,908.8 ng/dL) compared to control (1,685 ng/dL, 1,1015.45-3,795.5 ng/dL) (P=0.03). CRP concentration was higher in cardiac remodeling group (4,916.66±6,102.14) in relation to the group without remodeling (2,510.67±3.26) (P=0.009). There was a weak positive correlation between CRP and total leucocyte count (r=0.197; P=0.019). We conclude that although we could not identify a significative difference for RDW, there was a tendency to increased values in dogs with cardiac remodeling. CRP concentration was higher in cardiac remodeling group and in HF group compared to control. CRP serum together with other markers and auxiliary exames already routinely used may provide useful information for assessment and follow up of dogs with CDMVD

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This thesis involves the study of compressive and infectious neurological diseases in dogs, including the evaluation of functional recovery with intervertebral disc disease (IVD) thoracolumbar paraplegics and without deep pain perception (DPP) underwent surgical treatment, dogs with neurological signs associated to distemper (NSAD) and neoplasms of the central nervous system (CNS). Retrospective studies were conducted by reviewing the records of Veterinary neurology department (Veterinarian Hospital), of Federal University of Santa Maria. 208 cases were analyzed between March 2003 and June 2014. The satisfactory functional recovery of paraplegic dogs without DPP was observed in 73.3% (11/15) of the dogs. Recovery time after surgery occurred in one day [9% (01)], between 15 and 30 days [63.7% (07)] and over than 30 days [27.3% (03)]. 134 dogs with NSSD were studied, 39 definitive diagnosis (Group A) and 95 presumptive diagnosis (Group B). Adults were affected in 60.4%, followed by 31.3% of young and 8.2% old dogs. Neurological signs were varied according to the site of lesions in the CNS. According to the owners, the vaccine was applied only by veterinarians in 68% of dogs and clinical examination was performed in 56%, increasing the risk of vaccine failure. The CNS neoplasms occurred mainly in Boxers (35%), and the predominantly affected age-group was 5-year-old or older (92.3%). The course of clinical signs was higher for spinal cord (7-420 days) than for intracranial neoplasms (7-115 days). The most frequently neurological signs observed in dogs with brain and spinal cord neoplasms were, respectively, changes in the conscience level (58%) and hyperesthesia (57%) in neoplasms of the spinal cord. The cortico-thalamic region and T3-L3 spinal cord segment were the most frequently anatomical sites involved (58% and 43% respectively). Meningioma was the most frequently primary neoplasms affecting the brain and the spinal cord of dogs, consisting respectively of 40% and 75% of the cases. / Esta tese envolveu o estudo de doenças neurológicas compressivas e infecciosa em cães, incluindo a avaliação da recuperação funcional com doença do disco intervertebral (DDIV) toracolombar, paraplégicos e sem percepção à dor profunda (PDP) submetidos ao tratamento cirúrgico, cães com sinais neurológicos associados à cinomose (SNAC) e com neoplasmas do sistema nervoso central. Os estudos retrospectivos foram realizados por meio de revisão dos registros neurológicos de cães atendidos pelo Setor de Neurologia Veterinária, do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria. Foram analisados 208 casos, entre março de 2003 e junho de 2014. De acordo com nossos resultados, a recuperação funcional de cães paraplégicos sem PDP em decorrência da DDIV toracolombar ocorreu em 73.3% (11/15). O tempo de recuperação funcional após a cirurgia foi de um dia [9% (01)], entre 15 e 30 dias [63.7% (07)] e maior do que 30 dias [27.3% (03)]. Foram incluídos 134 cães com SNAC, sendo 39 com diagnóstico definitivo (Grupo A) e 95 com diagnóstico presuntivo (Grupo B). Os cães adultos foram acometidos em 60.4% das vezes, seguido de 31.3% dos filhotes e 8.2% dos idosos. Os SNAC variaram de acordo com a fase de infecção e distribuição das lesões no sistema nervoso central (SNC). Os resultados normais do líquido cerebroespinhal e hemograma não excluíram o diagnóstico definitivo. A vacina foi aplicada por médicos veterinários em 68% dos cães e a avaliação clínica prévia à vacinação foi realizada em 56% dos pacientes. Os neoplasmas do SNC foram observados principalmente em cães Boxer (35%), com idade entre cinco e 10 anos (92.3%). A evolução dos sinais clínicos foi maior para medula espinhal (ME) (7-420 dias) do que para os intracranianos (7- 115 dias). O sinal neurológico predominante foi a alteração do nível de consciência (58%) em cães com neoplasma encefálico e a hiperestesia espinhal (57%) naqueles com neoplasmas da ME. As regiões tálamo-cortical e segmento medular entre T3-L3 foram as mais acometidas por neoplasias do SNC (58% e 43% respectivamente). O meningioma foi o neoplasma primário mais frequente no encéfalo (40%) e na ME (75%) dos cães avaliados.

De nombreuses méthodes ont été développées pour estimer l’âge au décès de l’adulte mature. De plus, l’observation de certaines lésions dégénératives amène parfois l’anthropologue à classer un sujet chez les individus âgés, plus spécifiquement lorsqu’elles atteignent la colonne vertébrale. Or si l’ostéoarthrose rachidienne a fait l’objet de nombreux articles en paléopathologie, l’exploitation de l’ensemble des articulations vertébrales au sein d’une méthodologie est quasi inexistante. Ainsi, afin de déterminer le rôle d’une étude paléopathologique dans le vieillissement osseux, nous avons mis au point une méthode originale d’enregistrement des données.Cette méthode, basée sur un découpage topographique du rachis et un système de cotation des lésions arthrosiques, permet d’étudier l’atteinte dégénérative grâce à l’obtention d’un score de sévérité pondéré à l’état de conservation de la vertèbre. Le matériel d’étude est constitué de 750 individus répartis équitablement sur 3 périodes historiques (médiévale, moderne et contemporaine) permettant ainsi d’effectuer une comparaison diachronique des résultats. Les 250 individus constituant l’échantillon contemporain proviennent de collections documentées (Schoten, Belgique ; Bologne, Italie ; Sassari, Sardaigne). L’âge des sujets ostéoarchéologiques a été estimé grâce aux méthodes utilisant la surface auriculaire de l’os coxal (Lovejoy, 1985 et Schmitt, 2005). La même estimation a été faite sur les collections âge/sexe connus afin de déterminer le pourcentage d’erreur commis sur nos échantillons médiéval et moderne. Pour chaque articulation rachidienne nous avons testé statistiquement la relation entre l’âge au décès et les scores de sévérité, ainsi que les dissemblances d’atteinte en fonction du sexe et de la latéralité. Des études qualitatives ont également été entreprises, permettant ainsi d’observer l’expansion des modifications dégénératives en fonction des différentes classes d’âge.Au terme de ce travail de recherche, nous avons constaté l’existence d’une relation entre l’âge et la sévérité des atteintes dégénératives vertébrales. Cependant ce lien est modéré par divers facteurs variant en fonction des articulations et des segments vertébraux. Parmi ces facteurs, nous avons relevé le sexe et la latéralité. Des informations concernant le mode de développement des lésions dégénératives rachidiennes ont également été acquises. Ainsi, nous avons observé que l’OA se développait dans un premier temps de manière progressive le long du rachis, puis, avec l’âge et selon le type d’articulation, les lésions se concentrent sur les mêmes vertèbres (celles étant le plus soumises aux forces biomécaniques). C’est également sur ces mêmes vertèbres que se manifestent les lésions les plus sévères. Ainsi, il semble indispensable, lors d’une étude paléoépidémiologique, d’avoir un nombre minimum de vertèbres et parmi celles-ci les vertèbres les plus sollicitées en pré requis. De plus, nous préconisons lors d’un examen paléopathologique, de considérer plus que la sévérité même de la lésion, le nombre de zone atteintes comme estimateur de l’âge au décès. / Various methods have been developed to estimate age at death of adults and anthropologists sometimes use degenerative vertebral lesions. In paleopathology contrary to vertebral degenerative disease (VDD) that has been extensively studied, the whole vertebral joints have almost never been investigated by standardized methodology that allows approximating the epidemiological performance of various vertebral joints in relation to articular degeneration. In order to better define the paleoepidemiological aspects of bone ageing we have developed a research program based on the recording of degenerative lesions in the vertebral joints.This approach is based on a topographic division of spine and a grading system of degenerative lesions, permits the study VDD using “a severity score” according to the state of vertebral preservation. We studied 750 spines provided equally from three samples (medieval, modern and contemporary) to compare periods. The 250 contemporary spines are from documented collections of Schoten (Belgium), Bologna (Italy) and Sassari (Sardinia). Age estimation was made for each archaeological sample using methods based on the observation of the sacro-iliac joint surface (Lovejoy, 1985 and Schmitt, 2005). The same estimation of age has been made with known sex and age collections in order to calculate error estimates. For each joint of the spine, statistical tests have been made to study relationship between the age at death and “the severity score” and to compare variability between sex and spine laterality. Quantitative studies have also been made to observe degenerative change resulting from advancing age.At the end of this work, we observed the relation between age and the severity of VDD. That link can vary according to joint type, spinal segment and various factors such as sex or laterality. Information concerning the evolution of degenerative lesions has been acquired. VDD appears initially to progressively affect the entire spine and then with aging, degenerative lesions focus on the same vertebrae (those that are the most used biomechanically). Those vertebrae always show the most severe lesions. Thus it is essential for paleoepidemiologic studies to include a minimal number of vertebrae and among them those that are the most used. We also suggest considering the number of affected zones to estimate age at death instead of the lesion severity.