京都大学 / 新制・課程博士 / 博士(薬科学) / 甲第23831号 / 薬科博第146号 / 新制||薬科||16(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 山下 富義, 教授 髙倉 喜信, 准教授 伊藤 美千穂 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Yes / There is limited information regarding the views of patients, as healthcare consumers, on visual field testing, and no information regarding their preferences for future test developments. This study aimed to increase knowledge of patients' subjective experience of visual field assessment and to explore their opinions and priorities regarding current active areas of research and development. Online questionnaire with purposive sampling design. Adults who regularly perform visual field tests in Australia who report having glaucoma or being at risk of glaucoma. An anonymous survey, implemented using the Qualtrics webtool, with both closed and open ended questions designed to explore opinions regarding visual field testing, visit attendance for perimetry, as well as priorities for developments. The survey assessed three domains: 1) opinions regarding visual field test duration and visit frequency; 2) subjective experience; and 3) perspectives on future developments for perimetry. 152 complete survey responses were obtained. The median (IQR) age of participants was 66 (60-72) years. Most participants (70%) had experience of performing more than 11 visual field tests. Participants recalled that they completed visual field tests in median of 6 minutes (IQR: 5-8 minutes) and were willing to accept additional time (median: 5, IQR: 3-6 minutes) to obtain more information. Participants were prepared to increase both the number of visual field tests per eye and the frequency of visual field tests (median: 3, IQR: 2-4 visits per year), in order to gain more information about their visual status. Regarding future developments, the most preferred option was "similar test times but an increase in the level of information about my visual field", which ranked significantly higher than all other options including "shorter test times that maintain the currently available level of information about my visual field." Our study confirms, in a different population and healthcare system, previous research reporting patient perspectives on visual field assessment. We further reveal that healthcare consumers show a strong preference for accurate information about their vision and report being prepared to undergo longer visual field tests or more visual field tests to achieve that outcome.

Genes and environment interact to determine an individual’s vulnerability or resilience to several psychiatric disorders, including alcohol use disorder (AUD). Alcohol use is often initiated during adolescence and early onset drinking is associated with increased risk for later AUD. Childhood and adolescence are periods of extensive brain maturation, which makes young individuals more susceptible to environmental influence. However, little is known about early environmental influence on reward pathways and behaviors involved in the development of AUD. Changes in the endogenous opioid and dopamine systems, as well as individual differences in risk behaviors are all believed to play important roles in the increased vulnerability seen after adverse early life events and early onset drinking. The overall aim of the thesis was therefore to investigate the influence of early environmental factors on adolescent alcohol intake, endogenous opioids, dopamine dynamics and alcohol-induced effects in rats to increase our knowledge of neurobiological factors underlying vulnerability to AUD. Furthermore, individual behavioral differences and their correlation to basal and drug-induced neurobiological responses in rats were also investigated. Animal models of different early environments, e.g. maternal separation and social vs. single housing, and adolescent alcohol consumption have been used to study effects on behavior, endogenous opioid peptides and dopamine dynamics. The results identified the amygdala and dorsal striatum as interesting brain regions in which endogenous opioids and dopamine, respectively, are impacted by early environmental factors. The amygdala and the dorsal striatum are both hypothesized to be involved in the shift from initial drug use to compulsive use and changes in these areas may be underlying environmentally increased vulnerability to AUD. Furthermore, behavioral phenotypes in relation to individual neurobiological responses were identified. High risk-taking behavior was associated with a more pronounced response to amphetamine, but the inherent dopamine response was instead associated with risk-assessment behavior. In conclusion, several brain regions of interest for future research were identified. Furthermore, the results contribute to increased understanding of factors involved in the development of vulnerability for AUD in adolescents and young adults.

Made available in DSpace on 2016-04-18T21:39:44Z (GMT). No. of bitstreams: 8 Valderez de Almeida Donzelli1.pdf: 2513417 bytes, checksum: 39732bb9cc22ff6c7d8b226a01c7fbb3 (MD5) Valderez de Almeida Donzelli2.pdf: 3170782 bytes, checksum: 5bec891551d4e67354a5cb930c33b44a (MD5) Valderez de Almeida Donzelli3.pdf: 3092150 bytes, checksum: d7f43803b4c7e0a2393cc4faa9f5db7f (MD5) Valderez de Almeida Donzelli4.pdf: 3808963 bytes, checksum: 80f16c085a45c26b9ee5aa087fecb887 (MD5) Valderez de Almeida Donzelli5.pdf: 2761540 bytes, checksum: 6b89bedf4c70eb288d052ad64721157d (MD5) Valderez de Almeida Donzelli6.pdf: 3455846 bytes, checksum: 29fde75066aafda6127105ade4238eca (MD5) Valderez de Almeida Donzelli7.pdf: 3390797 bytes, checksum: bea566456cc4e0ff6ddf3fffb614b78a (MD5) Valderez de Almeida Donzelli8.pdf: 2402725 bytes, checksum: 1447647552515388643c1d9896a3803b (MD5) Previous issue date: 2011-08-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The technology environment in the broadcast area using analog technology was defined and did not offer a great research interest, in specific topics related to development of the transmitting antenna for broadcast television. With the implementation of the transmission system employing digital technology, which adds as main news the possibility of mobility and portability of the receiving system, the interest in studies and researches returned, showing one of the main themes to be developed using circular polarization or elliptical compared with horizontal polarization, that was most used by broadcasters. Given this new scenario and the need for evaluation by a scientific methodology of the radiating system in the transmission station performance, goals were established that define the scope for this research: to analyze the influence of the radiating system depending on the desired coverage area and the reception possibilities internal fixed , external fixed, portable and mobile, considering the diversity specific propagation environment of the region studied due to topographical and environmental condition. The criteria to be used will be the theoretical propagation prediction and field survey of the signals received which will provide data for the analysis of variables that influence the behavior of the transmission system, considering the location and technical characteristics of the main transmission station installation and different polarization of the radiating system configurations in horizontal, vertical and elliptical. / O cenário tecnológico na área de transmissão empregando tecnologia analógica estava bem segmentado e não oferecia um ambiente de grande interesse em pesquisas específicas para desenvolvimentos de temas relacionados a antena de transmissão para televisão aberta. Com a implantação do sistema de transmissão empregando a tecnologia digital, que agrega como principal novidade a possibilidade de mobilidade e portabilidade do sistema de recepção , o interesse nos estudos e pesquisas retomou, apresentando como um dos principais temas a serem desenvolvidos a utilização de polarização circular ou elíptica comparada com a polarização horizontal, que era a mais utilizada pela emissoras. Tendo em vista este novo cenário e a necessidade de avaliação por meio de uma metodologia científica do comportamento do sistema irradiante de transmissão no resultado no desempenho da estação transmissora, foram estabelecidas as metas que definem o escopo para este trabalho: analisar a influência do tipo de sistema irradiante em função da área de cobertura desejada e das possibilidades de recepção fixa interna, fixa externa, portátil e móvel, frente às diversidades específicas do ambiente de propagação da região estudada devido às condições topográficas e ambientais. Os critérios a serem empregados serão os teóricos de predição de propagação e prático de levantamento de campo dos sinais recebidos os quais irão fornecer dados para a análise das variáveis que influenciam no comportamento do sistema de transmissão, considerando o local e as características técnicas de instalação da estação de transmissão principal e variando a polarização do sistema irradiante nas configurações horizontal, vertical e elíptica.

Ökad kunskap om djurs beteendesyndrom kan möjliggöra förbättrade bevarandeåtgärder för hotade arter. I den här studien genomgick 108 blankålar (Anguilla anguilla) två beteendetester; “open-field test” och “novel-object test”. Ålars morfologi och val av föda, habitat och dygnsaktivitet har i tidigare studier visats hänga ihop. I den här studien undersökte jag om det fanns något samband mellan ålarnas morfologi, aktivitet samt respons på främmande föremål. De ålar som var mest aktiva under open-field-testet var också de ålar som visade störst intresse för det främmande föremålet i novel-object-testet. Det fanns dock inte något samband mellan morfologi och aktivitet eller mellan morfologi och respons på främmande föremål. Detta innebär att ett utforskande och djärvt beteendesyndrom har upptäckts hos vissa av ålarna, medan den bakomliggande faktorn fortsätter vara okänd. / Increased knowledge of behavioural syndromes may contribute to enhancing our conservation methods for endangered species. In this study, the behavior of 108 silver eels (Anguilla anguilla) was assessed in two assays: an open-field test and a novel-object test. Eel morphology and diel activity as well as diet and habitat use have previously been shown to correlate with each other. In this study, I investigated the potential relationship between the morphology, activity and response to a novel object. The most active eels during the open-field test were also the ones that expressed the most interest for the novel object. There was, however, no correlation between morphology and activity or morphology and response to the novel object. This means an exploring and bold behaviour syndrome was discovered amongst some of the eels, whilst the underlying cause remains unknown.

One of the most meaningful technical innovations in cycling over the past two decades was the development of mobile power meters. With the ability to measure the physical strain under “real world” outdoor conditions, the knowledge of the demand during cycling has improved enormously. Power output has been described as the most direct measure of intensity during cycling and consequently power meters becomes a popular tool to monitor the training and racing of cyclists. However, only limited research data are available on the utilisation of power meters for performance assessment in the field or the analysis of training data. Therefore, the aims of the thesis were to evaluate the ecological validity of a field test, to provide an extensive insight into the longitudinal training strategies of world-class cyclists and to investigate the effects of interval training in the field at difference cadences. The first study aimed to assess the reproducibility of power output during a 4-min (TT4) and a 20-min (TT20) time-trial and the relationship with performance markers obtained during a laboratory graded exercise test (GXT). Ventilatory and lactate thresholds during a GXT were measured in competitive male cyclists (n = 15; VO2max 67 ± 5 mL . min−1 . kg−1; Pmax 440 ± 38 W ). Two 4- min and 20-min time-trials were performed on flat roads. Strong intraclass-correlations for TT4 (r = 0.98; 95 % CL: 0.92-0.99) and TT20 (r = 0.98; 95 % CL: 0.95-0.99) were observed. TT4 showed a bias ± random error of −0.8 ± 23W or −0.2 ± 5.5%. During TT20 the bias ± random error was −1.8 ± 14 W or 0.6 ± 4.4 %. Both time-trials were strongly correlated with performance measures from the GXT (p < 0.001). Significant differences were observed between power output during TT4 and GXT measures (p < 0.001). No significant differences were found between TT20 and power output at the second lactate-turn-point (LTP 2) (p = 0.98) and respiratory compensation point (RCP) (p = 0.97). In conclusion, TT4 and TT20 mean power outputs are reliable predictors of endurance performance. TT20 was in agreement with power output at RCP and LTP 2. Study two aimed to quantify power output (PO) and heart rate (HR) distributions across a whole season in elite cyclists. Power output and heart rate were monitored for 11 months in ten male (age: 29.1 ± 6.7 y; VO2max: 66.5 ± 7.1 mL . min−1 . kg−1) and one female (age: 23.1y; VO2max: 71.5 mL . min−1 . kg−1) cyclist. In total, 1802 data sets were sampled and divided into workout categories according to training goals. The PO at the RCP was used to determine seven intensity zones (Z1-Z7). PO and HR distributions into Z1-Z7 were calculated for all data and workout categories. The ratio of mean PO to RCP (intensity factor, IF) was assessed for each training session and for each interval during the training sessions (IFINT). Variability of PO was calculated as coefficient of variation (CV ). There was no significant difference in the distribution of PO and HR for the total season (p = 0.15), although significant differences between workout categories were observed (p < 0.001). Compared with PO, HR distributions showed a shift from low to high intensities. IF was significantly different between categories (p < 0.001). The IFINT was related to performance (p < 0.01), although the overall IF for the session was not. Also, total training time was related to performance (p < 0.05). The variability in PO was inversely associated with performance (p < 0.01). In conclusion, HR accurately reflects exercise intensity over a total season or low intensity workouts but is limited when applied to high intensity workouts. Better performance by cyclists was characterised by lower variability in PO, greater training volume and the production of higher exercise intensities during intervals. The third study tested the effects of low-cadence (60 rev . min−1) uphill (Int60) or high-cadence (100 rev . min−1) flat (Int100) interval training on PO during 20 min uphill (TTup) and flat (TTflat) time-trials. Eighteen male cyclists (VO2max: 58.6 ± 5.4 mL . min−1 . kg−1) were randomly assigned to Int60, Int100 or a control group (Con). The interval training comprised of two training sessions per week over four weeks, which consisted of 6 bouts of 5 min at the PO at RCP. For the control group, no interval training was conducted. A two-factor ANOVA revealed significant increases on performance measures obtained from GXT (Pmax: 2.8 ± 3.0 %; p < 0.01; PO and VO2 at RCP: 3.6 ± 6.3 % and 4.7 ± 8.2 %, respectively; p < 0.05; and VO2 at ventilatory threshold: 4.9 ± 5.6 %; p < 0.01), with no significant group effects. Significant interactions between group and the uphill and flat time-trials, pre vs. post-training on time-trial PO were observed (p < 0.05). Int60 increased PO during both, TTup (4.4 ± 5.3 %) and TTflat (1.5 ± 4.5 %), whereas the changes were − 1.3 ± 3.6 %; 2.6 ± 6.0 % for Int100 and 4.0 ± 4.6 %; − 3.5 ± 5.4 % for Con, during TTup and TTflat, respectively. PO was significantly higher during TTup than TTflat (4.4 ± 6.0 %; 6.3 ± 5.6 %; pre and post-training, respectively; p < 0.001). These findings suggest that higher forces during the low-cadence intervals are potentially beneficial to improve performance. In contrast to the GXT, the time-trials are ecologically valid to detect specific performance adaptations.

The term "personality" nowadays occurs more often not only in psychological studies of humans but also in animal studies. Studying of personality help us to define the behavioural characteristics which can vary within the age, sexes, species or enviroments. Behavioral experiments are used to detect these behavioral patterns and they can divide the animals into the different groups. The subject of our research became three populations of house mouse (Mus musculus sensu lato) which we tested in a series of experiments involving free exploration, forced exploration, hole- board test, test of vertical activity and Elevated plus-maze. These experiments should reveal wheter the mice differ in their behaviour through the context of sex, comensalism or subspecies. We found (with in excepcion of one test) that intrapopulation variability differences are very small but interpopulation differences purely increase in the cas of comensalism and effects of subspecies. Keywords: Mus musculus, comensalism, open fieldtest, Elevated plus-maze, Principal Component Analysis (PCA)

Esta tese apresenta, o projeto de uma perfuratriz que permite a execução de cinco tipos de fundação profunda, e o desenvolvimento de um ensaio de campo que possibilita avaliar as resistências por atrito lateral desenvolvidas entre o instrumento envolvido pelo solo escavado e o terreno natural. A perfuratriz foi projetada para executar estacas dos tipos hélice contínua monitorada, escavadas com trado mecânico, hélice segmentada monitorada, raiz e hollow-auger. As estacas dos tipos hélice contínua monitorada e as escavadas com trado mecânico são muito utilizadas no Brasil; as estacas raiz e hollow-auger são utilizadas em situações especiais e a estaca hélice segmentada monitorada é mais recente, mas sua aplicação tem tido um crescimento importante nos últimos dez anos. Para a perfuratriz multifuncional são apresentados cálculos e desenhos básicos dos principais conjuntos. Para a nova investigação de campo, denominada FDT - Full Displacement Test, é apresentado um desenvolvimento teórico com base no princípio universal da conservação de energia que, em termos práticos, resulta na obtenção da parcela de atrito lateral, denominado atrito lateral unitário equivalente (fse). Os resultados obtidos a partir dos dados aquisitados pelo sistema de monitoramento eletrônico da perfuratriz apresentaram-se concordantes entre si, indicando a possibilidade de praticamente se conseguir a repetibilidade do ensaio. Entre os diversos ensaios realizados, foi dada ênfase aos ensaios realizados no campo experimental de Fundações e Geotecnia da Faculdade de Engenharia Agrícola FEAGRI, da Universidade de Campinas - UNICAMP e foram feitas correlações com as resistências obtidas nas provas de carga estáticas realizadas no local por Albuquerque (2001), a partir dos ajustes feitos para o nível instrumentado na profundidade de 11,70 m para o qual foi determinado um fator (G2), para cada tipo de estaca ensaiada (escavada, hélice contínua e ômega). A partir dos ajustes feitos para o nível 11,70 m foram feitas previsões de capacidade de carga por atrito lateral para os outros níveis instrumentados (5,00 m; 11,10 m e 12,00 m), sendo que os resultados apresentaram-se concordantes. / This thesis presents the design of a drilling rig that allows the execution of five types of deep foundation, and the development of a field test that allows measuring the skin friction resistance developed between the instrument involved by the excavated ground and the natural soil. The drilling rig was designed to make continuous flight auger, bored pile, continuous flight auger with segmented auger, root pile and hollow-auger pile. The continuous flight auger and bored piles are widely used in Brazil; the root pile and hollow-auger pile are used for in special conditions, and the continuous flight auger with segmented auger, is although more recent, but its application has had increased application grown in over the last ten years. For the multifunctional drilling rig, calculations and basic designs of the main sets are presented. For the new field test denominated FDT - Full Displacement Test, a theoretical development based on the universal principle of energy conservation was made carried out resulting and the result, in practical terms, was to obtain in the attainment of the skin friction defined in this thesis as equivalent unit skin friction (fse). The results obtained from the data acquired by the electronic monitoring system of drilling rigs were consistent among themselves, indicating the possibility of practically achieve the repeatability of the test. Among the various tests performed, emphasis was given to tests in the experimental field of foundations and geotechnics, of the College of Agricultural Engineering FEAGRI, Campinas University UNICAMP, and were correlated to the skin friction resistance obtained from the static load tests performed on site by Albuquerque (2001), based on the adjustments done to the instrumented level depth of 11.70 m, for which a factor (G2) was given in each type tested (bored, C.F.A and omega). From the adjustments made to the 11,70 m level, load-bearing capacity of skin friction predictions were made for other instrumented levels (5.00 m; 11.10 m and 12.00 m) presenting consistent results.

[pt] O estudo de fluxo saturado - não saturado em solos exige o conhecimento das funções de relação, como a curva característica (q x h) e a curva de condutividade hidráulica (K x h). Para determinar estas relações o presente trabalho utiliza o modelo de van Genuchten- Mualem, o qual está implementado numa ferramenta numérica que permite a utilização da retroanálise como método para determinação dos parâmetros do modelo. O principal objetivo deste trabalho é a avaliação de um método que permita a estimativa dos parâmetros do modelo de van Genuchten-Mualem, a partir de dados coletados em campo ou laboratório para, então, realizar-se a análise de fluxo saturado - não saturado e a estimativa dos parametros de van Genuchtem-Mualem. Finalmente, a as condições de fluxo saturado - não saturado em duas encostas foram simuladas, em duas e três dimensões, a fim de verificar a variação de fluxo nestes casos. / [en] The study of saturated and non saturated flow in soils requires the knowledge of relation functions, as water retention curve (q vs. h) and hydraulic conductivity curve (K vs. h).In order to determine these relations, this research uses van Genuchten-Mualem`s model, which is implemented on a numerical based method. This tool allows the inverse solution as a method to determine the parameters of the model. The main objective of this research is the evaluation of a method which allows the estimative of the required parameters by the chosen model, determined based on field or laboratory data, so then, based on these parameters, saturated and non- saturated flow analysis were carried out and the estimative of parameters of van Genuchten-Mualem`s model. Finally, saturated and non-saturated simulations were made on two slopes. These simulations were followed by 2D and 3D models, in order to verify the flow variation on these cases.

Traumatic brain injury (TBI) is a severe condition and a major cause of death and disability. There is no pharmacological treatment available in clinical practice today and knowledge of brain injury mechanisms is of importance for development of neuroprotective drugs. The aims of the thesis were to get a better understanding of astrocyte reactions and immune responses, as well as behavioral changes after focal unilateral cortical contusion injury and diffuse bilateral central fluid percussion injury in rats and mice. In the focal injury models, the astrocyte reactions were generally restricted to the ipsilateral hemisphere. After diffuse TBI, vimentin and glial fibrillary acidic protein (GFAP) positive reactive astrocytes were bilaterally expressed in brain regions even distant from the injury site, including regions where axonal injury was seen. Early after diffuse TBI, there was a robust immune response, including activation of macrophages/microglia (Mac-2+) and infiltration of neutrophils (GR-1+) and T-cells (CD3+). In order to measure functional outcome, the recently established Multivariate Concentric Square Field™ (MCSF) test for complex behaviors, including risk taking and explorative strategies was used. The Morris water maze (MWM) was applied for testing learning and memory. The MCSF test revealed alterations in risk taking, risk assessment and exploratory behavior, in the mice subjected to focal injury whereas mice subjected to the diffuse injury showed a deviant stereotyped behavior. After focal injury mice showed a decreased ability to adapt to the arena in the second trial, when tested repeatedly in the MCSF test. Mice subjected to diffuse injury had an impaired memory but not learning, in the MWM test. Post-injury treatment with the anti-inflammatory anti-interleukin-1β (IgG2 a/k) antibody showed a positive effect on functional outcome in the diffuse injury model. Altogether, the results demonstrate that focal and diffuse TBI models produce differences in cellular reactions and behavioral outcome and that the immune response plays a key role in the pathology after brain injury.