<p>In the boreal forests of the Northern Hemisphere, time series of tree-ring width (TRW) and maximum density in the latewood (MXD) are highly correlated to local instrumental summer-temperature data and are thus widely used as proxies in high-resolution climate reconstructions. Hence, much of our present knowledge about climatic variability in the last millennium is based on tree-rings. However, many tree-ring records have a lack of data in the most recent decades, which severely hampers our ability to place the recent temperature increase in a longer-timescale perspective of natural variability.</p><p>The main objective of this thesis is to update and extend the Torneträsk TRW and MXD records in northern Sweden. Local instrumental climate-data is used to calibrate the new tree-ring records. The results show that TRW is mainly forced by temperature in the early growing season (June/July) while MXD has a wider response window (June – August) and has a higher correlation to temperature. Two reconstructions of summer temperature are made for (i) the last 7,400 years based on TRW, and (ii) the last 1,500 years based on a combination of TRW and MXD. The reconstructions show natural variability on timescales from years to several centuries. The 20th century does not stand out as a notably warm period in the long timescale perspective. A medieval period from AD 900 – 1100 is markedly warmer than the 20th century.</p><p>The environmental impact from a large explosive volcanic eruption in 1628/1627 BC is analysed in the tree rings of 14C-dated bog pines in south-central Sweden and in absolutely-dated subfossil pines from Torneträsk. The results show evidence of an impact in the southern site at approximately this time but no detectable impact in the North. </p><p>Subfossil trees of Fitzroya cupressoides in southern Chile were 14C-dated to approx. 50,000 years BP and amalgamated into a 1,229-year TRW chronology. This tree-ring record is the oldest in the world. The variability in this Last-glacial chronology is similar to the variability in present-day living trees of the same species. These results suggest that the growth–forcing mechanisms 50,000 years ago were similar to those at present.</p>

In the boreal forests of the Northern Hemisphere, time series of tree-ring width (TRW) and maximum density in the latewood (MXD) are highly correlated to local instrumental summer-temperature data and are thus widely used as proxies in high-resolution climate reconstructions. Hence, much of our present knowledge about climatic variability in the last millennium is based on tree-rings. However, many tree-ring records have a lack of data in the most recent decades, which severely hampers our ability to place the recent temperature increase in a longer-timescale perspective of natural variability. The main objective of this thesis is to update and extend the Torneträsk TRW and MXD records in northern Sweden. Local instrumental climate-data is used to calibrate the new tree-ring records. The results show that TRW is mainly forced by temperature in the early growing season (June/July) while MXD has a wider response window (June – August) and has a higher correlation to temperature. Two reconstructions of summer temperature are made for (i) the last 7,400 years based on TRW, and (ii) the last 1,500 years based on a combination of TRW and MXD. The reconstructions show natural variability on timescales from years to several centuries. The 20th century does not stand out as a notably warm period in the long timescale perspective. A medieval period from AD 900 – 1100 is markedly warmer than the 20th century. The environmental impact from a large explosive volcanic eruption in 1628/1627 BC is analysed in the tree rings of 14C-dated bog pines in south-central Sweden and in absolutely-dated subfossil pines from Torneträsk. The results show evidence of an impact in the southern site at approximately this time but no detectable impact in the North. Subfossil trees of Fitzroya cupressoides in southern Chile were 14C-dated to approx. 50,000 years BP and amalgamated into a 1,229-year TRW chronology. This tree-ring record is the oldest in the world. The variability in this Last-glacial chronology is similar to the variability in present-day living trees of the same species. These results suggest that the growth–forcing mechanisms 50,000 years ago were similar to those at present.

Afin de mieux comprendre les bases physiopathologiques des tumeurs osseuses des mâchoires, nous avons étudié deux modèles de tumeurs associées à des mutations génétiques connues : la tumeur kératokystique odontogène (TKO), liée à la mutation de PTCH1, et le chérubinisme, lié à la mutation de SH3BP2. Au regard des travaux d’oncogénétique, nous formulons l’hypothèse que le développement des tumeurs ostéolytiques bénignes des mâchoires de l’enfant et leur agressivité repose sur un mécanisme génétique. Nous avons montré que la présence d’une mutation de PTCH1 (germinale avec syndrome de Gorlin) dans les TKO était un facteur de mauvais pronostic, stimulant un centre tumoral secondaire, responsable de lésions à distance, mais que cette agressivité pouvait aussi être liée à des mécanismes inflammatoires. Dans le chérubinisme, nous avons montré que la mutation était responsable du phénotype, mais que le type de mutation n’influençait pas le pronostic ni l’agressivité. L’agressivité tumorale est liée au phénotype des cellules géantes multinucléées (cellules myéloïdes à différenciation macrophagique ou ostéoclastique). Nous avons montré, que le modèle murin ne pouvait pas s’appliquer à la pathologie humaine, avec notamment un rôle très secondaire du TNF-α. Enfin nous avons démontré le rôle important de NFATc1 dans la physiopathologie du chérubinisme qui nous a permis de proposer, le tacrolimus, comme le premier agent thérapeutique efficace. Nos résultats suggèrent que les mutations induisent la pathologie et que les changements du microenvironnement (liés à la flore buccale ou à l’éruption dentaire) entretiennent la pathologie. / To determine pathophysiological bases of jawbone tumors, we studied two genetic models of jawbone tumors: keratocystic odontogenic tumors (KOT) associated to PTCH1 mutation and cherubism associated to SH3BP2 mutation. From oncogenetic theory, we postulate that genetic background controls the development of benign children jawbone tumors. From our work, we demonstrated that PTCH1 mutation (germline mutation in Gorlin syndrome) was an unfavorable prognosis factor for KOT, leading to distant and independent daughter tumors. Moreover, we showed, that chorionic inflammation was associated with a high recurrence rate. In cherubism, SH3BP2 mutation produced cherubism phenotype, but the type of mutation did not affect the aggressiveness of the disease. Cherubism aggressiveness was determined by the phenotype of giant multinucleated cells (whether osteoclasts or macrophages). Furthermore, we showed that murine model could not be transposed to human pathology; indeed it appeared that TNF- α did not play a critical role in human cherubism. On the other side, we showed that NFATc1 played a crucial role in cherubism pathophysiology; this observation allowed us to propose, the tacrolimus, as an effective treatment for this disease. Our results suggest that genetic background induced tumor development, and that microenvironment changes (due to flora of the oral cavity and to teeth eruptions) are responsible to the maintenance and the progression of the disease.

Afin de mieux comprendre les bases physiopathologiques des tumeurs osseuses des mâchoires, nous avons étudié deux modèles de tumeurs associées à des mutations génétiques connues : la tumeur kératokystique odontogène (TKO), liée à la mutation de PTCH1, et le chérubinisme, lié à la mutation de SH3BP2. Au regard des travaux d’oncogénétique, nous formulons l’hypothèse que le développement des tumeurs ostéolytiques bénignes des mâchoires de l’enfant et leur agressivité repose sur un mécanisme génétique. Nous avons montré que la présence d’une mutation de PTCH1 (germinale avec syndrome de Gorlin) dans les TKO était un facteur de mauvais pronostic, stimulant un centre tumoral secondaire, responsable de lésions à distance, mais que cette agressivité pouvait aussi être liée à des mécanismes inflammatoires. Dans le chérubinisme, nous avons montré que la mutation était responsable du phénotype, mais que le type de mutation n’influençait pas le pronostic ni l’agressivité. L’agressivité tumorale est liée au phénotype des cellules géantes multinucléées (cellules myéloïdes à différenciation macrophagique ou ostéoclastique). Nous avons montré, que le modèle murin ne pouvait pas s’appliquer à la pathologie humaine, avec notamment un rôle très secondaire du TNF-α. Enfin nous avons démontré le rôle important de NFATc1 dans la physiopathologie du chérubinisme qui nous a permis de proposer, le tacrolimus, comme le premier agent thérapeutique efficace. Nos résultats suggèrent que les mutations induisent la pathologie et que les changements du microenvironnement (liés à la flore buccale ou à l’éruption dentaire) entretiennent la pathologie. / To determine pathophysiological bases of jawbone tumors, we studied two genetic models of jawbone tumors: keratocystic odontogenic tumors (KOT) associated to PTCH1 mutation and cherubism associated to SH3BP2 mutation. From oncogenetic theory, we postulate that genetic background controls the development of benign children jawbone tumors. From our work, we demonstrated that PTCH1 mutation (germline mutation in Gorlin syndrome) was an unfavorable prognosis factor for KOT, leading to distant and independent daughter tumors. Moreover, we showed, that chorionic inflammation was associated with a high recurrence rate. In cherubism, SH3BP2 mutation produced cherubism phenotype, but the type of mutation did not affect the aggressiveness of the disease. Cherubism aggressiveness was determined by the phenotype of giant multinucleated cells (whether osteoclasts or macrophages). Furthermore, we showed that murine model could not be transposed to human pathology; indeed it appeared that TNF- α did not play a critical role in human cherubism. On the other side, we showed that NFATc1 played a crucial role in cherubism pathophysiology; this observation allowed us to propose, the tacrolimus, as an effective treatment for this disease. Our results suggest that genetic background induced tumor development, and that microenvironment changes (due to flora of the oral cavity and to teeth eruptions) are responsible to the maintenance and the progression of the disease.

AIM: The aim of this investigation is to determine the prevalence of maxillary altered passive eruption in a dental school population. METHODS: 100 subjects were examined clinically and had models fabricated of their maxilla. Demographic, periodontal, cast measurements were recorded for each subject. Demographic variables recorded included age, gender, and ethnicity, history of orthodontic treatment, presence of incisal /occlusal wear, appearance of gingival excess, and presence of gingival asymmetry. Measurements made on cast included clinical crown length, clinical crown width, papillary height, and distance from the lateral gingival zenith to the gingival aesthetic line. Clinical crown width-to-length ratio was calculated. These measurements were compared to previously published standards. RESULTS: 83% of the subjects had central incisors with a clinical W:L ratio greater than .80. Logistical regression analysis determined that subjects with central incisors with an appearance of gingival excess were more likely to have a clinical W:L ratio greater than .80 (P<.0007; OR=79). ANOVA demonstrated that clinical crown length had a statistically significant relationship with gender (P<.0001), tooth type (P<.0001) and biotype (P<0.0026). Clinical crown width and clinical crown W:L ratio had a statistically significant relationship with gender (P<0.0007, P<.0001) and tooth type (P<0.0026, P<.0001). The average clinical crown length was 0.5-1.5 mm shorter than established ideal measurements. CONCLUSION: 83% of the subject population had central incisors that displayed altered passive eruption. Subjects who exceeded the clinical W:L ratio of .80 were more likely to have been classified as having the appearance of gingival excess or “gummy smile”. Esthetic crown lengthening should be considered to achieve desired esthetics in these subjects.

Le terme « cément » est utilisé pour désigner l’ensemble des tissus conjonctifs minéralisés retrouvés sur la surface externe de la racine d’une dent ainsi que sur certaines zones de l’émail ou au niveau du foramen apical. Il appartient à deux unités fonctionnelles : la dent et le parodonte et constitue avec l’os alvéolaire un point d’attache essentiel du ligament alvéolo-dentaire. Dans certaines conditions non encore élucidées la synthèse de l’une de ses variétés, le cément cellulaire mixte stratifié, est excessive, elle dépasse la « normalité » : il s’agit d’une hypercémentose. Une revue critique de la littérature nous a permis de mettre en évidence un certain nombre de problématiques concernant sa définition, sa classification, sa fréquence, ses étiologies et certaines de ses caractéristiques anatomiques. Afin d’y répondre nous avons élaboré un protocole d’étude dont le matériel comprenait trois séries d’Hommes sub-actuels (675 individus ; 8861 dents dont 419 hypercémentosées) et dont les méthodes ont fait appel à la photographie, la radiographie, la stéréomicroscopie, la microscopie électronique à balayage et l’histologie. Au terme de notre étude nous avons mis au point une définition et une classification de l’hypercémentose reposant sur des critères reproductibles, nous avons évalué sa fréquence au sein de grands échantillons et déterminé ses principales étiologies (éruption continue liée à la perte des dents antagonistes, parodontite apicale, atteintes parodontales, inclusion dentaire, pathologies générales, syndromes génétiques, hérédité, idiopathie). Nous avons également fourni certaines données inédites concernant les épaisseurs du cément hyperplasique et l’anatomie des foramens apicaux. Nos résultats ont enfin été appliqué à un certain nombre de dents néandertaliennes ce qui nous a permis de reconsidérer l’hypothèse selon laquelle l’importance des contraintes occlusales au sein de ce taxon est la cause principale des hypercémentoses. / The term "cement" is used to refer to all mineralised connective tissue found on the external surface of the root of a tooth and also on certain areas of the enamel or around the apical foramen. It pertains to two functional units, the tooth and the periodontium, and together with the alveolar bone forms an essential point of attachment for the periodontal ligament. In certain conditions that have still to be clarified, synthesis of one variety of cement, cellular mixed stratified cementum, is excessive, going beyond "normal" levels: this is hypercementosis. From a review of the literature, we identified a certain number of questions relating to the definition, classification, frequency, and etiologies of this term, and also to some of its anatomical characteristics. To find answers to these questions, we set up a study protocol on material consisting of three series of modern Humans (675 individuals; 8,861 teeth, 419 with hypercementosis), using photography, radiography, stereomicroscopy, scanning electron microscopy and histology techniques. From this we were able to produce a definition and a classification of hypercementosis based on reproducible criteria, we assessed frequency using a large set of samples and determined the main etiologies (continuous eruption associated with the loss of opposing teeth, apical periodontitis, periodontal injuries, dental inclusion, general pathologies, genetic syndromes, heredity, idiopathy). We were also able to provide new data on hyperplastic cement thicknesses and the anatomy of apical foramens. Finally, our results were applied to a number of Neanderthal teeth, which led us to reconsider the hypothesis according to which the importance of occlusal stress in this taxon is the main cause of hypercementosis.

This thesis examines Late Minoan Settlements in Crete that were destroyed or abandoned due to the consequences of the Santorini volcano eruption. A summary of geological history of Crete, Thera and the surrounding area is given in the first part. The next chapter sums up the research in the fields of relative and mainly absolute chronology, of which scientists have not yet been able to provide a convincing calendar date for the eruption of the volcano nor a possible fixed absolute chronology of the general Later Bronze Age not only in the Aegean. The development of the Santorini Volcano eruption in the Late Minoan IA period (LM IA) is described. According to the research, this eruption must have caused earthquakes and tsunamis. The possible impact on the near island of Crete, its inhabitants and settlements, mainly in the coastal area of north-northeast part of the island, is also discussed.

Esta pesquisa teve como objetivo verificar se existe relação entre o uso de terapia anti-retroviral por crianças portadoras do Vírus da Imunodeficiência Humana (HIV) contaminadas pela via vertical e a ocorrência de alterações de desenvolvimento da dentição permanente detectáveis radiograficamente. Foram avaliadas 76 crianças com idades entre 4 anos e um mês e 12 anos e 11 meses que foram distribuídas em 2 grupos: (1) 46 crianças portadoras do HIV em uso de terapia anti-retroviral; (2) 30 crianças sem a infecção. As crianças foram submetidas a radiografias panorâmicas para a avaliação dos estágios de calcificação dentária e através de exame clínico foi avaliada a freqüência de erupção dos dentes permanentes em ambos os grupos. Os resultados obtidos não mostraram diferença estatisticamente significativa nos estágios de calcificação (p=0,051) e na freqüência de erupção dos dentes permanentes (p=0,18), indicando que o uso de anti-retrovirais não interfere no desenvolvimento dentário de crianças portadoras do HIV adquirido pela via vertical / This survey was conducted to verify the correlation between the use of antiretroviral therapy and developmental disturbances in the permanent dentition of children vertically infected by the Human Immunodeficiency Virus (HIV). Seventy-six children aged from 4 years to 1 month and 12 years and 11 month were divided in two groups: 1) 46 children HIV-infected and under antiretroviral therapy; 2) 30 uninfected children. A panoramic radiograph for dental development evaluation was obtained from each child, in order to evaluate the dental calcification stages and the frequency of permanent teeth eruption in both groups. The results did not show any significant statistical difference on dental calcification stages (p=0,051) as well as the permanent teeth results of the frequency eruption (p=0,18) between the HIV-infected and the uninfected children, showing that the antiretroviral therapy does not interfere in the dental development of children infected by HIV acquired by vertical transmission

Afin de mieux comprendre les bases physiopathologiques des tumeurs osseuses des mâchoires, nous avons étudié deux modèles de tumeurs associées à des mutations génétiques connues : la tumeur kératokystique odontogène (TKO), liée à la mutation de PTCH1, et le chérubinisme, lié à la mutation de SH3BP2. Au regard des travaux d’oncogénétique, nous formulons l’hypothèse que le développement des tumeurs ostéolytiques bénignes des mâchoires de l’enfant et leur agressivité repose sur un mécanisme génétique. Nous avons montré que la présence d’une mutation de PTCH1 (germinale avec syndrome de Gorlin) dans les TKO était un facteur de mauvais pronostic, stimulant un centre tumoral secondaire, responsable de lésions à distance, mais que cette agressivité pouvait aussi être liée à des mécanismes inflammatoires. Dans le chérubinisme, nous avons montré que la mutation était responsable du phénotype, mais que le type de mutation n’influençait pas le pronostic ni l’agressivité. L’agressivité tumorale est liée au phénotype des cellules géantes multinucléées (cellules myéloïdes à différenciation macrophagique ou ostéoclastique). Nous avons montré, que le modèle murin ne pouvait pas s’appliquer à la pathologie humaine, avec notamment un rôle très secondaire du TNF-α. Enfin nous avons démontré le rôle important de NFATc1 dans la physiopathologie du chérubinisme qui nous a permis de proposer, le tacrolimus, comme le premier agent thérapeutique efficace. Nos résultats suggèrent que les mutations induisent la pathologie et que les changements du microenvironnement (liés à la flore buccale ou à l’éruption dentaire) entretiennent la pathologie. / To determine pathophysiological bases of jawbone tumors, we studied two genetic models of jawbone tumors: keratocystic odontogenic tumors (KOT) associated to PTCH1 mutation and cherubism associated to SH3BP2 mutation. From oncogenetic theory, we postulate that genetic background controls the development of benign children jawbone tumors. From our work, we demonstrated that PTCH1 mutation (germline mutation in Gorlin syndrome) was an unfavorable prognosis factor for KOT, leading to distant and independent daughter tumors. Moreover, we showed, that chorionic inflammation was associated with a high recurrence rate. In cherubism, SH3BP2 mutation produced cherubism phenotype, but the type of mutation did not affect the aggressiveness of the disease. Cherubism aggressiveness was determined by the phenotype of giant multinucleated cells (whether osteoclasts or macrophages). Furthermore, we showed that murine model could not be transposed to human pathology; indeed it appeared that TNF- α did not play a critical role in human cherubism. On the other side, we showed that NFATc1 played a crucial role in cherubism pathophysiology; this observation allowed us to propose, the tacrolimus, as an effective treatment for this disease. Our results suggest that genetic background induced tumor development, and that microenvironment changes (due to flora of the oral cavity and to teeth eruptions) are responsible to the maintenance and the progression of the disease.

A estimativa de idade é um importante recurso em Odontologia Legal. Entre as diversas formas de se obter uma estimativa de idade, pesquisadores podem fazê-la por meio da análise do estágio de mineralização dos dentes permanentes. Este tipo de análise, torna possível que uma simples radiografia panorâmica possa fornecer dados relevantes para identificar um indivíduo falecido, por exemplo. Este estudo propõe a validação, análise da acurácia e a construção de fórmulas baseadas nos métodos de Liliequist e Lundberg com a adaptação de Hägg e Matsson (LLH), Haavikko (HKK) e Mornstad et al. (MSW) para a estimativa de idade pelo estágio de mineralização dos dentes permanentes em crianças e adolescentes brasileiros. Para alcançar este resultado, foram selecionadas radiografias panorâmicas de brasileiros em uma amostra contendo 1.009 radiografias (387 do sexo masculino e 622 do sexo feminino) com idade entre 8-15,99 anos. Destas radiografias, foram selecionadas apenas as que cumpriram com todos os requisitos dos critérios de inclusão e exclusão. Após a aplicação das metodologias, os resultados foram inseridos e trabalhados no Programa Excel, Pacote Estatístico STATA 13.0. (StataCorp LP, College Station, Texas, EUA) e MedCalc (Medcalc® Software, Mariakerke, Bélgica) de acordo com as necessidades do estudo. As amostras foram divididas sem distinção quanto ao sexo, com distinção quanto ao sexo, e com distinção quanto ao sexo e idade. A comparação dos métodos foi realizada pela diferença de médias da idade dentária com a idade cronológica (ID-IC). A acurácia foi analisada pela Diferença Absoluta (DA). O teste normalidade de Skewness e Kurtosis foi empregado e, dependendo do resultado, os dados foram submetidos ao Test t de Student, ou ao teste de Wilcoxon, para amostras pareadas. Como resultado das comparações sem qualquer distinção quanto ao sexo, a melhor acurácia foi obtida por LLH (DA = 0,97 e ID-IC = 0,58), HKK (DA = 1,42 e ID-IC = -1,35) e MSW (DA = 2,48 e ID-IC = 3,08). Com distinção quanto ao sexo, os valores para o masculino foram: LLH (DA = 0,91 e ID-IC = -0,45), HKK (DA = 1,80 e ID-IC = -1,75) e MSW (DA = 2,74 e ID-IC = 1,17); e para o feminino LLH (DA = 1,01 e ID-IC = -0,67), HKK (DA = 1,17 e ID-IC = -1,09) e MSW (DA = 2,31 e ID-IC = 0,53). Na comparação com distinção entre sexo e idade houve um predomínio respectivamente da técnica de LLH, seguida de HKK e MSW. As equações de regressão aplicadas na mesma amostra apresentaram em média DA = 0,72 e ID-IC = -0,01. Também, algumas fórmulas de regressão múltipla foram construídas a partir dos dados apresentados para as metodologias de LLH e HKK, exceto para MSW que não forneceu dados suficientes para o software criar equações. Ao final, foi possível concluir que é possível a validação das metodologias apresentadas para a população brasileira e que a metodologia que mais se aproximou da população brasileira foi o método de Liliequist e Lundberg com a adaptação de Hägg e Matsson. / Age estimation is an important resource in Forensic Dentistry. Among several ways to obtain the age estimation, researchers may do it by analyzing the mineralization stage of permanent teeth. This type of analysis allows that a simple panoramic radiograph to provide relevant data to identify a deceased individual, for example. This study proposes the validation, accuracy analysis and construction of formulas based on the methods Liliequist and Lundberg with the adaptation of Hägg and Matsson (LLH), Haavikko (HKK) and Mornstad et al. (MSW) for the estimation of age by the stage of mineralization of permanent teeth in Brazilian children and adolescents. To achieve the results, panoramic radiographs of Brazilians were selected in a sample containing 1009 radiographs (387 males and 622 females) aged 8-15.99 years. Of these radiographs, it was selected only those that fulfilled all the requirements of the inclusion and exclusion criteria. After applying the methodologies, the results were inserted and worked in the Excel Program, Statistical Package STATA 13.0. (StataCorp LP, College Station, Texas, USA) and MedCalc (Medcalc® Software, Mariakerke, Belgium) according to the needs of the study. The samples were divided without splitting sex, with splitting sex and with splitting sex and age. The comparison of methods was performed by the mean differences between dental age and chronological age (DA-CA). Accuracy was analyzed by Absolute Difference (AD). The Skewness e Kurtosis normality test was employed and the Student t test, or the Wilcoxon test, for paired samples was submitted depending on the results. The results of comparisons informed, without any distinction as to sex, the best accuracy was obtained by LLH (AD = 0.97 and DA-CA = 0.58), HKK (AD = 1.42 and DA-CA = -1.35) and MSW (AD = 2.48 and DA-CA = 3.08). With distinction to sex the values for male were: LLH (AD = 0.91 and DA-CA = -0.45), HKK (AD = 1.80 and DA-CA = -1.75) and MSW (AD = 2.74 and DA-CA = 1.17); and for female: LLH (AD = 1.01 and DA-CA = -0.67), HKK (AD = 1.17 and DA-CA = -1.09) and MSW (AD = 2.31 and DA-CA = 0.53). In the comparison with distinction between sex and age, there was a predominance of the LLH technique, followed by HKK and MSW, respectively. The regression equations applied in the same sample presented mean AD = 0.72 and DA-CA = -0.01. In addition, some multiple regression formulae were constructed from the data presented for LLH and HKK methodologies, except for MSW, which did not provide enough data for the software to create equations. At the end, it was possible to conclude that it is possible to validate the methodologies presented in the Brazilian population and the methodology that most approached the Brazilian population was the Liliequist and Lundberg method with the adaptation of Hägg and Matsson.