Abstract Healthy subjects show wide interindividual variation in their heart rate behavior, but the factors affecting heart rate dynamics are not well known. This research was undertaken to evaluate heart rate variability (HRV) and baroreflex sensitivity (BRS) in a large random sample of subjects without evidence of heart disease, and to estimate the relation of heart rate behavior to age, sex and cardiovascular risk factors. Short-term HRV was analyzed from 15-minute periods of standardized recording in supine and upright positions using time and frequency domain measures, and BRS was calculated using the Valsalva maneuver in an original randomly selected population of 600 hypertensive and 600 control middle-aged subjects. In addition, HRV was analyzed from the same segments using new measures based on fractals and complexity (chaos theory) of R - R interval dynamics in the same random population, and from 24-hour period in 114 healthy subjects aged from 1 to 82 years. Large interindividual variation was observed in the measures of HRV and BRS in middle-aged subjects; coefficient of variation (CV) of the standard deviation of R - R intervals (SDNN) 39% (54 ± 21 ms) and CV of BRS 49% (9.9 ± 4.9 ms/mmHg). In healthy middle-aged men, SDNN was weakly related to age (r = -0.19, p < 0.01), HDL cholesterol (0.19, p < 0.01), serum insulin (-0.23, p < 0.001) and triglyceride (-0.25, p < 0.001) levels. In women, SDNN was only related to insulin levels (r = -0.23, p < 0.001). BRS was related to systolic blood pressure (r = -0.31 and -0.30, in men and women respectively, p < 0.001 for both) and blood glucose (r = -0.25, p < 0.01) and serum insulin levels (r = -0.34, p < 0.001) in women. Lesser intersubject variation was observed in the non-linear measures of HRV; CV 14% of short-term scaling exponent (a1), a measure of fractal-like correlation properties of HRV, (1.21 ± 0.17) and CV 12% of approximate entropy, a measure of complexity, (1.13 ± 0.14). Neither a1 or ApEn was related to any risk factors. Women had lower overall short-term HRV (p < 0.01) and BRS (p < 0.001), but a higher spectral high-frequency component of HRV, higher ApEn and lower a1 (p < 0.001 for all) compared to men. The impairment in overall HRV was confined to the hypertensive subjects with metabolic features of the insulin resistance syndrome (IRS, n = 69), but the BRS and spectral high-frequency component were also impaired in hypertensive subjects without IRS compared to normotensive subjects. The 24-hour cardiac interbeat interval dynamics changed markedly from childhood to old age. Children showed similar complexity and fractal correlation properties of R - R intervals as young adults. Healthy aging resulted in R - R interval dynamics with higher regularity and predictability and altered fractal scaling. The traditional measures of HRV and BRS are weakly related to many cardiovascular risk factors in subjects without heart disease, but the interindividual variation of HRV and BRS is only partly explained by these factors, suggesting a genetic background of the intersubject variation in cardiovascular autonomic regulation. The new dynamical measures of HRV show less interindividual variation than the conventional measures of HRV in healthy subjects and are not related to cardiovascular risk variables, suggesting that these dynamical measures quantify the "intrinsic" capacity of a healthy cardiovascular control system without the significant influence of life-style, metabolic or demographic variables. However, there are sex and age-related differences also in the fractal and complexity measures of heart rate behavior.

The purpose of this thesis is to identify the names of the students who died while attending the Brandon Indian Residential School (BIRS) and determine the location of the school’s burial grounds along with the number of unmarked graves on the school property. My research project uses mixed methods including; archival research, qualitative interviews, Ground-Penetrating Radar (GPR), Electromagnetic Ground Conductivity (EM38), control burns, and aerial photography to systematically survey the school’s burial grounds. My investigation into the deaths and burials of BIRS students aligns closely with a larger project being conducted by the Truth and Reconciliation Commission of Canada’s (TRC) Working Group on Missing Children and Unmarked Burials (n.d.). This Working Group attempts to locate the burial grounds for the Indian residential schools across Canada and identify the names of the students who died at the schools in the archives. This research was conducted in collaboration with Sioux Valley Dakota Nation, the University of Manitoba, Brandon University, the United Church of Canada, the Royal Canadian Mounted Police (RCMP), and in consultation with the TRC, Manitoba Historic Resources Branch, and Brandon Research Centre. By using an applied anthropological approach my thesis works to contribute to the ongoing TRC’s Missing Children’s Project. It is my hope that this research can assist the Sioux Valley Dakota Nation with future restoration, protection and commemoration plans. / May 2015

付記する学位プログラム名: 霊長類学・ワイルドライフサイエンス・リーディング大学院 / 京都大学 / 新制・課程博士 / 博士(理学) / 甲第24467号 / 理博第4966号 / 新制||理||1709(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)准教授 Huffman Michael Alan, 教授 古市 剛史, 教授 今井 啓雄 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM

Les méthodes non invasives d'évaluation des lésions tissulaires hépatiques les plus utilisées et les mieux validées sont l'élastométrie et le FibroTest. La stéatopathie non-alcoolique (NAFLD) est devenue la forme la plus fréquente de maladie hépatique. Différentes études suggèrent que la NAFLD est associée à un risque accru de mortalité, en particulier d'origine cardiovasculaire. Les objectifs de cette thèse étaient 1) de mieux définir certaines limites des méthodes non invasives d'évaluation de la fibrose hépatique; 2) d'évaluer la valeur pronostique du FibroTest et d'un biomarqueur de stéatose, le SteatoTest chez les patients ayant un diabète et/ou une dyslipidémie. Le travail réalisé a permis de montrer une variabilité interobservateur notable de l'élastométrie entre deux opérateurs expérimentés dans l'hépatite chronique virale C. La stéatose du foie, estimée par le SteatoTest, a été identifiée comme un facteur indépendant associé à la surestimation de la fibrose du foie par l'élastométrie chez les sujets ayant un diabète de type 2. Nous avons également mis en évidence une variabilité du test APRI et l'impact de l'activité nécrotico-inflammatoire sur ce test dont la formule comprend l'aspartate transaminase exprimée en multiple de la normale dans l'hépatite chronique virale C. Chez des patients à haut risque de NAFLD, nous avons pu démontrer la valeur pronostique à 10 ans du FibroTest et du SteatoTest, pour prédire la mortalité globale indépendamment des facteurs métaboliques. Le FibroTest était également prédictif de la mortalité d'origine hépatique et de l'incidence des complications cardiovasculaires et le SteatoTest de la mortalité d'origine cardiovasculaire / Several non-invasive methods have been proposed to replace liver biopsy. Transient elastography and FibroTest are the most widely used and best validated non-invasive methods to assess liver fibrosis. Subjects with metabolic disorders such as type-2 diabetes or dyslipidemia, have a high risk of non-alcoholic fatty liver disease (NAFLD). Evidence was previously provided to indicate that NAFLD is associated with an increased risk of cardiovascular disease and overall mortality. The aims of this thesis were. 1) to evaluate the main limitations of non-invasive methods to assess liver fibrosis. 2) to evaluate the prognostic value of liver biomarkers, such as FibroTest and SteatoTest, in patients with type-2 diabetes and/or dyslipidemia. We demonstrated a marked interobserver variability of transient elastography between two experienced operators in chronic hepatitis C. Hepatic steatosis, estimated by SteatoTest, was identified as an independent factor associated with an overestimation of liver fibrosis by transient elastography in patients with type-2 diabetes. We could also show the variability of the APRI test, based on the expression of aspartate aminotransferase relative to the upper limit of normal and the risk of overestimating fibrosis stage by this test due to necro-inflammatory activity in chronic hepatitis C. We reported that FibroTest and SteatoTest had a 10-year prognostic value for prediction of overall mortality independently of metabolic factors in patients at high risk of NAFLD. FibroTest was also predictive of liver-related death and incidence of cardiovascular events. In addition, SteatoTest had a prognostic value for cardiovascular-related death.

Weltweit ist eine rasante Zunahme des Artensterbens auch bei der Klasse Aves zu verzeichnen. Durch Umweltveränderungen und unzählige andere menschliche Einflüsse (z.B. illegaler Handel) ist fast ein Drittel der Papageienpopulation (Psittaciformes) vom Aussterben bedroht. Eine Möglichkeit, diesen Trend aufzuhalten, besteht in der gezielten und effektiven Nachzucht bedrohter Arten in der Obhut von Menschen mit dem Ziel der späteren Wiederauswilderung. Leider waren bisher solche Bemühungen oft erfolglos. Dies ist der Tatsache geschuldet, dass fundierte wissenschaftliche Untersuchungen zum Reproduktionsstatus nahezu fehlen und ein Transfer der hormonanalytischen Methoden vom Säugetier zum Vogel nicht so einfach möglich ist. Ziel der vorliegenden Arbeit war die Etablierung von Methoden zur Hormonbestimmung in verschiedenen Medien beim männlichen Papagei, mit deren Hilfe eine Einordnung des Reproduktionsstatus möglich ist. Im Vordergrund standen dabei vor allem nicht-invasive Techniken, die mit deutlich geringerem Stress für die Tiere verbunden sind. Als Vertreter für die Gruppe der Papageienartigen wurden Wellensittiche (Melopsittacus undulatus, n=11), Nymphensittiche (Nymphicus hollandicus, n=9) und Halsbandsittiche (Psittacula krameri, n=7) ausgewählt und endokrinologisch untersucht. Diese Vögel wurden vom Bundesverband für fachgerechten Natur- und Artenschutz e.V. (BNA) zur Verfügung gestellt. Die Hormonanalyse erfolgte in den regelmäßig gesammelten Blut-, Speichel- und Kotproben der männlichen Psittaziden. Neben dem Sexualhormon Testosteron wurden die Blutspiegel des Stresshormons Corticosteron bestimmt, da eine mögliche Beziehung zwischen Stress und Testosteronsekretion besteht. In den Vorversuchen wurden zunächst geeignete Methoden für die Hormonanalyse in den verschiedenen Medien beim Papagei entwickelt. Zur Extraktion von Testosteron aus den Blut- und Kotproben erwies sich Diethylether als gut geeignet, während Speichel direkt ohne Extraktion im Testosteron-Enzymimmunoassay eingesetzt wurde. Da Papageien hauptsächlich primär konjugierte Testosteronmetabolite (85%) ausscheiden, wurden die Kotproben nach dem Trocknen und Einwiegen mit Hilfe der β-Glucuronidase/Arylsulfatase hydrolysiert und dann mit Diethyether extrahiert. Die Corticosteronanalyse im Plasma der Papageien erfolgte durch Fällung der Proteine mittels absolutem Alkohol und Einsatz der Plasmaextrakte in den Radioimmunoassay. Bei den verschiedenen Papageienspezies traten während der Untersuchungsperiode vergleichbare Plasma-Testosteronkonzentrationen auf. Die höchsten Plasmaspiegel (0,36 ng/ml) wiesen die Wellensittiche im März 2007 auf, ähnliche Konzentrationen (0,34 ng/ml) erreichten die Nymphensittiche im Februar 2007. Demgegenüber zeigten die Halsbandsittiche geringere maximale Konzentrationen (0,26 ng/ml) im November 2007. Im Kot der Papageien wurden erwartungsgemäß deutlich höhere Testosteronwerte gemessen, weil die Steroidausscheidung im Kot kumulativ eine zurückliegende Zeitperiode und Blut den aktuellen Hormonstatus zum Zeitpunkt der Probennahme widerspiegelt. Bezüglich der Haltungs- und Umweltbedingungen zeigten die Papageien maximale Testosteronspiegel während der kalten Jahreszeit, bei kurzer (Halsbandsittich) bzw. zunehmender Tageslichtlänge (Wellen- und Nymphensittich) und Haltung in der Innenvoliere. Dabei spielte die Niederschlagsmenge in der gemäßigten Klimazone offenbar weniger eine Rolle in der aviären Reproduktion. Die Verlaufsuntersuchungen des Stresshormons Corticosteron im Blut der Papageien ergaben speziesspezifische Unterschiede hinsichtlich der Konzentrationen, zeitlichen Verläufe und in Bezug zum Testosteronspiegel. Auffällig hohe Corticosteronkonzentrationen zeigten die nicht domestizierten Halsbandsittiche (15,9 – 35,6 ng/ml) im Vergleich zu den Wellensittichen (1,76 – 17,1 ng/ml) und Nymphensittichen (4,06 – 12,1 ng/ml), bei denen sich vermutlich im Laufe der Domestikation eine verminderte Sensibilität der HPA-Achse ausgebildet hat. In Bezug zum Plasma-Testosteronspiegel war bei den Wellen- und Halsbandsittichen ein gegenläufiger Zusammenhang erkennbar, wobei beim Nymphensittich eine positive Korrelation zwischen der Testosteron- und Corticosteronkonzentrationim Plasma bestand. Zusammenfassend lässt sich sagen, dass durch die Testosteronanalyse in Kot und Plasma eine Einordnung des Reproduktionsstatus beim Wellen-, Nymphen- und Halsbandsittich möglich ist. Es ist jedoch sinnvoll, Proben zu verschiedenen Zeitpunkten vergleichend zu betrachten, um die tierindividuellen Unterschiede zu berücksichtigen. Offensichtlich stehen die Steroidhormone der Gonaden und der Nebenniere zueinander in Beziehung, sodass auch Corticosteron in der Reproduktionsdiagnostik von männlichen Psittaziden Anwendung finden sollte.

The thesis is focused on a research and the evaluation of the nurse role during the invasive methods in chronic pain treatment and on a research the patient satisfaction and expectation with the nurses approach during the invasive methods in chronic pain treatment. The basis for the thesis processing is qualitative ? quantitative research carried out in the departments of pain treatment in four hospitals, in University Hospital Motol, University Hospital Brno, Hospital České Budějovice a.s., University Hospital PlzeňAlejSvobody. Qualitative research focuses on nurses working in the department of pain treatment using a method of questioning with the technique of non-standardized interview. Within qualitative research, we was looking for the answer to the research question: What is the nurse role during the invasive technique in chronic pain treatment? It was found, from the results of the interviews and their analysis, that nurses have within the invasive performance wide field of action and their role is changing in various stages of the entire performance. In all phases of the invasive performance, it´s essential the communication between the nurse and the patient. In the phase before the invasive performance and afterwards is the most dominated the educational role, except for the nursing role. Quantitative research using the questionnaire was intended for patients in the departments of pain treatment. The following predetermined hypothesis were verified using quantitative research: H1: Patients are satisfied with the nurses approach during the invasive techniques in pain treatment. H2: Patients with chronic pain during the invasive methods are expecting especially the empathetic approach from nurses. Evaluation of the questionnaires, which were voluntarily completed by patients, can be ended that both given hypothesis H1 and H2 have been confirmed and that the targets of qualitative researches have been met. The space for improvement can be found in the patient education before the invasive performance. Therefore We created educational material for patients. This educational material is not intended to replace the education conducted by nurses, it rather serves as a basis for the questions preparation that the patient will want to clarify before the invasive performance.

Weltweit ist eine rasante Zunahme des Artensterbens auch bei der Klasse Aves zu verzeichnen. Durch Umweltveränderungen und unzählige andere menschliche Einflüsse (z.B. illegaler Handel) ist fast ein Drittel der Papageienpopulation (Psittaciformes) vom Aussterben bedroht. Eine Möglichkeit, diesen Trend aufzuhalten, besteht in der gezielten und effektiven Nachzucht bedrohter Arten in der Obhut von Menschen mit dem Ziel der späteren Wiederauswilderung. Leider waren bisher solche Bemühungen oft erfolglos. Dies ist der Tatsache geschuldet, dass fundierte wissenschaftliche Untersuchungen zum Reproduktionsstatus nahezu fehlen und ein Transfer der hormonanalytischen Methoden vom Säugetier zum Vogel nicht so einfach möglich ist. Ziel der vorliegenden Arbeit war die Etablierung von Methoden zur Hormonbestimmung in verschiedenen Medien beim männlichen Papagei, mit deren Hilfe eine Einordnung des Reproduktionsstatus möglich ist. Im Vordergrund standen dabei vor allem nicht-invasive Techniken, die mit deutlich geringerem Stress für die Tiere verbunden sind. Als Vertreter für die Gruppe der Papageienartigen wurden Wellensittiche (Melopsittacus undulatus, n=11), Nymphensittiche (Nymphicus hollandicus, n=9) und Halsbandsittiche (Psittacula krameri, n=7) ausgewählt und endokrinologisch untersucht. Diese Vögel wurden vom Bundesverband für fachgerechten Natur- und Artenschutz e.V. (BNA) zur Verfügung gestellt. Die Hormonanalyse erfolgte in den regelmäßig gesammelten Blut-, Speichel- und Kotproben der männlichen Psittaziden. Neben dem Sexualhormon Testosteron wurden die Blutspiegel des Stresshormons Corticosteron bestimmt, da eine mögliche Beziehung zwischen Stress und Testosteronsekretion besteht. In den Vorversuchen wurden zunächst geeignete Methoden für die Hormonanalyse in den verschiedenen Medien beim Papagei entwickelt. Zur Extraktion von Testosteron aus den Blut- und Kotproben erwies sich Diethylether als gut geeignet, während Speichel direkt ohne Extraktion im Testosteron-Enzymimmunoassay eingesetzt wurde. Da Papageien hauptsächlich primär konjugierte Testosteronmetabolite (85%) ausscheiden, wurden die Kotproben nach dem Trocknen und Einwiegen mit Hilfe der β-Glucuronidase/Arylsulfatase hydrolysiert und dann mit Diethyether extrahiert. Die Corticosteronanalyse im Plasma der Papageien erfolgte durch Fällung der Proteine mittels absolutem Alkohol und Einsatz der Plasmaextrakte in den Radioimmunoassay. Bei den verschiedenen Papageienspezies traten während der Untersuchungsperiode vergleichbare Plasma-Testosteronkonzentrationen auf. Die höchsten Plasmaspiegel (0,36 ng/ml) wiesen die Wellensittiche im März 2007 auf, ähnliche Konzentrationen (0,34 ng/ml) erreichten die Nymphensittiche im Februar 2007. Demgegenüber zeigten die Halsbandsittiche geringere maximale Konzentrationen (0,26 ng/ml) im November 2007. Im Kot der Papageien wurden erwartungsgemäß deutlich höhere Testosteronwerte gemessen, weil die Steroidausscheidung im Kot kumulativ eine zurückliegende Zeitperiode und Blut den aktuellen Hormonstatus zum Zeitpunkt der Probennahme widerspiegelt. Bezüglich der Haltungs- und Umweltbedingungen zeigten die Papageien maximale Testosteronspiegel während der kalten Jahreszeit, bei kurzer (Halsbandsittich) bzw. zunehmender Tageslichtlänge (Wellen- und Nymphensittich) und Haltung in der Innenvoliere. Dabei spielte die Niederschlagsmenge in der gemäßigten Klimazone offenbar weniger eine Rolle in der aviären Reproduktion. Die Verlaufsuntersuchungen des Stresshormons Corticosteron im Blut der Papageien ergaben speziesspezifische Unterschiede hinsichtlich der Konzentrationen, zeitlichen Verläufe und in Bezug zum Testosteronspiegel. Auffällig hohe Corticosteronkonzentrationen zeigten die nicht domestizierten Halsbandsittiche (15,9 – 35,6 ng/ml) im Vergleich zu den Wellensittichen (1,76 – 17,1 ng/ml) und Nymphensittichen (4,06 – 12,1 ng/ml), bei denen sich vermutlich im Laufe der Domestikation eine verminderte Sensibilität der HPA-Achse ausgebildet hat. In Bezug zum Plasma-Testosteronspiegel war bei den Wellen- und Halsbandsittichen ein gegenläufiger Zusammenhang erkennbar, wobei beim Nymphensittich eine positive Korrelation zwischen der Testosteron- und Corticosteronkonzentrationim Plasma bestand. Zusammenfassend lässt sich sagen, dass durch die Testosteronanalyse in Kot und Plasma eine Einordnung des Reproduktionsstatus beim Wellen-, Nymphen- und Halsbandsittich möglich ist. Es ist jedoch sinnvoll, Proben zu verschiedenen Zeitpunkten vergleichend zu betrachten, um die tierindividuellen Unterschiede zu berücksichtigen. Offensichtlich stehen die Steroidhormone der Gonaden und der Nebenniere zueinander in Beziehung, sodass auch Corticosteron in der Reproduktionsdiagnostik von männlichen Psittaziden Anwendung finden sollte.

Introdução: No mundo especula-se que 15 a 20 milhões tenham infecção crônica pelo HDV. No Brasil, a área endêmica de hepatite Delta corresponde aos estados da Amazônia Ocidental, incluindo Rondônia. Hepatite Delta é a mais grave e com mais rápida evolução para cirrose dentre as hepatites virais. Poucos estudos avaliaram os aspectos epidemiológicos, clínicos e laboratoriais de uma coorte de pacientes em nosso país e no mundo. Objetivos: Em uma coorte de pacientes acompanhados em um serviço de referência: 1. Avaliar as características demográficas, epidemiológicas e clínicas; 2. Avaliar a frequência de doença hepática avançada; 3. Avaliar as características da população atendida com idade <=18 anos; 4. Avaliar a acurácia de escores não invasivos (razão AST/ALT, APRI e FIB-4) na determinação dos diferentes graus de fibrose. Métodos: Trata-se de um estudo transversal, descritivo, de uma coorte de pacientes retrospectivamente identificadas no ambulatório especializado em hepatites virais, pertencente ao Centro de Pesquisa em Medicina Tropical do Estado de Rondônia (CEPEM), situado na cidade de Porto Velho, com diagnóstico de infecção pelo HDV. Foram incluídos todos os pacientes com diagnóstico dessa infecção por sorologia (ELISA) ou por biologia molecular (HDV-RNA reagente), matriculados e atendidos neste serviço entre novembro de 1996 a março de 2015. Resultados: Dentre 4.101 pacientes diagnosticado com HBV, 224 (5,5%) apresentavam coinfecção com o HDV, e 205 foram incluídos nas análises. Dentre eles, 132 (64,4%) eram do sexo masculino, com idade média de 35,1 anos. O contato familiar foi o fator de exposição para infecção pelo VHB/VHD mais frequente. A determinação do genótipo do HDV foi obtida em 78 pacientes, destes 74 (94,9%) eram genótipo III e 4 (5,1%) genótipo I. Noventa e dois (44,9%) pacientes apresentavam evidência de doença hepática avançada. Dentre os pacientes incluídos 22 (10,7%) tinham idade <= 18 anos, sendo que 6 (27,3%) apresentavam sinais e sintomas de doença hepática avançada ou fulminante à primeira consulta. Métodos não invasivos foram calculados e comparados à biópsia hepática em 50 pacientes. A razão AST/ALT não teve valor significativo para avaliar fibrose em nenhum dos estágios. APRI e FIB-4 tiveram melhor desempenho para avaliar fibrose significativa (>=F2), com acurácia de 86 e 80, respectivamente. Conclusões: 1. O HDV representa importante agravo de saúde pública em Rondônia com frequência expressiva entre pessoas do sexo masculino e população indígena; 2. A presença da infecção pelo HDV esteve associada a expressivo número de complicações hepáticas e foi frequente causa de óbito na população analisada, particularmente entre adultos jovens; 3. Entre pacientes com idade <= 18 anos a hepatite delta esteve associada a significante morbidade e mortalidade e a falta de adesão dessa população pareceu contribuir para esse tipo de desfecho; 4. A utilização dos métodos não invasivos (APRI e FIB-4) foi capaz de identificar pacientes com fibrose significativa entre indivíduos infectados com HDV na Amazônia brasileira, podendo, apesar de todas as limitações destes métodos servir como alternativa para avaliação de fibrose hepática significativa, na ausência de outros métodos mais efetivos / Introduction: In the world, it is speculated that 15 to 20 million people have chronic HDV infection. In Brazil, the endemic area of hepatitis Delta corresponds to the states of the Western Amazon, including Rondônia. Hepatitis Delta is the most serious and most rapidly evolving cirrhosis among viral hepatitis. Few studies have evaluated the epidemiological, clinical, and laboratory aspects of a cohort of patients in our country and around the world. Objectives: In a cohort of patients followed at a referral service: 1. Evaluate demographic, epidemiological and clinical characteristics; 2. Assess the frequency of advanced liver disease; 3. Evaluate the characteristics of the population served with age <=18 years; 4. To evaluate the accuracy of non-invasive scores (AST/ALT ratio, APRI and FIB-4) in determining the different degrees of fibrosis. Methods: This is a cross-sectional, descriptive study of a cohort of patients retrospectively identified in the ambulatory specialized in viral hepatitis, belonging to the Research Center of Tropical Medicine of Rondônia State (CEPEM), located in the city of Porto Velho. All patients diagnosed with this serological method (ELISA) or molecular biology (HDV-RNA), enrolled in this service between November 1996 and March 2015, were included. Results: Out of 4,101 patients diagnosed with infection by HBV, 224 (5.5%) had coinfection with the hepatitis delta virus, and 205 were included in the analyzes. Among them, 132 (64.4%) were males, with a mean age at the time of enrollment of 35.1 years. Family contact was the most frequent exposure factor for HBV/HDV infection. It was identified seventy-eight patients (94.9%) of genotype III and four (5.1%) of genotype I. Ninety-two (44.9%) patients had evidence of advanced liver disease. Among the patients included, 22 (10.7%) were aged <= 18 years, and 6 (27.3%) had signs and symptoms of advanced or fulminant liver disease at the first visit. Noninvasive methods were calculated and compared to liver biopsy in 50 patients. The AST/ALT ratio had no significant value for evaluating fibrosis in any of the stages. APRI and FIB-4 had better performance to evaluate significant fibrosis (>=F2), with the accuracy of 86 and 80 respectively. Conclusions: 1. The hepatitis delta virus represents an important public health problem in the State of Rondônia, affecting both adults and children, with significant frequency among males and the indigenous population; 2. The presence of HDV infection was associated with a significant number of hepatic complications and was a frequent cause of death in the analyzed population, particularly among young adults; 3. Among patients aged <= 18 years, delta hepatitis was associated with significant morbidity and mortality and the lack of adherence of this population to follow-up seemed to contribute to this type of outcome; 4. The use of the non-invasive APRI and FIB-4 methods were able to identify patients with significant fibrosis among individuals infected with HDV in the Brazilian Amazon, although all limitations of these methods may serve as an alternative for the evaluation of significant hepatic fibrosis in the absence of other more effective methods

The diploma thesis deals with the education of children with disorders of autistic spectrum in Kindergartens. The theoretical part describes autism from the historical point of view and also the classification of disorders of the autistic spektrum and diagnostics. Educating of children with special educational needs, preschool education, appropriate support for children with disorders of autistic spectrum in preschool age, games with children with disorders of autistic spectrum, examples of used interventions in preschool age, services for children and their parents are also described in the theoretical part. The analytical part deals with forms of support of children with autistic disorders in normal Kindergarten and which methods are used in their education. The aim of this part was to find out in what form did the pedagogues got the knowledge about methods of supporting education of children with autism disorders. We did an interviews with three pedagogues to complete the survey. From our survey we found out that the padagogues mostly use the structured learning method. This method is considered as the most appropirate in domestic literature. KEY WORDS Pre-shool child, disorder of autistic spectrum, Kindergarten, invasive methods, special educational needs

Hormones influence life of all animals. Not only they affect physiological changes in organisms, but also impact their behaviour. This work focuses at two main groups of steroid hormones: glucocorticoids and androgens. Glucocortiods are activated in response to stress. Their levels can be measured using non-invasive methods, which have a range of advantages. The main advantage is the feedback-free sample collection for enzyme immunoassay. As the measurement involves metabolites of the hormones rather than the hormones themselves, prior validation of the method is, however, necessary. This work reports on a study aiming to validate non-invasive measurement on the Madagascar Ground Gecko (Paroedura Picta). The validation was based on ACTH challenge test: Synacthen Depot was injected, which should lead to increased blood level of glucocorticoids. The validation, however, was not successful. The measurement did not discover significant increase in the levels of the metabolites of glucocorticoids. In addition, the work focuses on behavioural effects of testosterone, the primary androgen. Hormonal manipulations have been carried out on several male and female specimens. The results have discovered differences in sexual behaviour between control groups. On the other hand, the hormonal manipulations had no...