Thèses sur le sujet « OSA treatment »

Continuous positive airway pressure (CPAP) is the primary therapy administered for those afflicted with obstructive sleep apnea (OSA). We examined the effects of CPAP therapy on physiological variables during a ramped exercise. The five male, OSA patients had mean values and standard deviations for RDI=60.7 +/- 19.1, BMI=29.9 +/- 2.9, and age=56 +/- 16.1 yr. Subjects were examined before and after 4 wk of CPAP therapy. After 4 wk of CPAP therapy, patient responses to exercise showed a 17.6%, (p<0.05) improvement in rating of perceived exertion (RPE) at identical power outputs (60% of the individual's apparent functional capacity). Statistical significance was not attained (p>0.05) upon analysis of the following parameters at 60% of the individuals maximum workload although there was a trend showing a decrease in these variables: heart rate (6% improvement), VO2 (11.7% improvement) systolic blood pressure (4% improvement), and rate pressure product (8.6% improvement). This data shows that the decrease in RPE during 60% of the individual's maximum predicted HR reserve corresponded with an increase in sleep quality (mean increase of 40%, 3.2 units) as measured by the Pittsburgh Sleep Quality Index before and after 4 wk of CPAP therapy. It was concluded that the improvement in exercise tolerance could be attributed to the subjective feelings of improved sleep quality after 4 wk of CPAP therapy. Key Words: Obstructive sleep apnea---CPAP--- exercise---physiological responses.
Master of Science

Un terzo della popolazione europea è affetta da apnee ostruttive del sonno (OSA), patologia che ha conseguenze negative su morbilità cardiovascolare e qualità della vita. L’OSA è caratterizzata da ripetuti episodi di collasso delle alte vie respiratorie che determinano ipossia intermittente, modifiche della pressione intratoracica e risvegli corticali. L’ipossia intermittente ha un ruolo chiave nel determinare le conseguenze cardiovascolari dei disturbi del respiro nel sonno e può sovrapporsi, peggiorandone la prognosi, a condizioni caratterizzate da ipossia tonica quali l’alta quota o le patologie respiratorie croniche o infettive, esacerbando lo stress ossidativo, l’angiogenesi e quindi l’attivazione del sistema nervoso simpatico con conseguenti incrementi della pressione arteriosa, della frequenza cardiaca e dell’infiammazione. Il trattamento gold standard per l’OSA è la terapia ventilatoria che risulta però non tollerata dalla metà dei pazienti che ne fanno uso. Nuove strategie terapeutiche sono pertanto auspicabili. Recentemente sono stati identificati specifici fattori fisiopatologici che contribuiscono allo sviluppo dell’OSA: un’elevata collassabilità delle vie aeree superiori, l’instabilità del sistema di controllo del respiro, una ridotta soglia di arousal ed una ridotta risposta compensatoria dei muscoli dilatatori della faringe. Quest’ultima è dovuta alla perdita di attività noradrenergica e aumento delle influenze muscariniche alle alte vie aeree. Il riconoscimento di questi tratti fisiopatologici ha permesso di ipotizzare e sviluppare nuove strategie terapeutiche per l’OSA. Obiettivo: Valutare l’efficacia della somministrazione per 1 settimana della combinazione di reboxetina (noradrenergico) ed ossibutinina (antimuscarinico) sul trattamento dell’OSA e dell’effetto dei farmaci sugli endotipi fisiopatologici. Metodi: E’ stato condotto uno studio randomizzato controllato cross-over in doppio cieco per comparare 4mg di reboxetina più 5mg di ossibutinina (reb-oxy) in pazienti con OSA. I pazienti sono stati sottoposti ad una polisonnografia basale (PSG), una dopo 7 notti di assunzione di reb-oxy ed una dopo 7 notti di assunzione di placebo per confrontare l’indice di apnea-ipopnea (AHI–outcome primario). Outcome secondari comprendevano il carico ipossico, modifiche degli endotipi, la variabilità della frequenza cardiaca, test di vigilanza. Risultati: Hanno completato lo studio 16 pazienti con età 57 [51-61] anni (mediana [range interquartilico]) ed indice di massa corporea 30 [26-36] kg/m2. Reb-oxy ha determinato una riduzione di AHI da 49 [35-57] eventi/h al basale a 18 [13-21] eventi/h (59% di riduzione mediana) e 39 [29-48] eventi/h (6% riduzione mediana) confrontato con il placebo (p<0·001). La frequenza cardiaca mediana durante la PSG è stata 65 [60-69] bpm al basale ed è aumentata fino a 69 [64-77] bpm dopo reb-oxy e 66 [59-70] bpm dopo placebo (p=0.02). La somministrazione di reb-oxy non ha comportato modifiche di variabilità della frequenza cardiaca, pressione arteriosa nelle 24 ore. Il test di vigilanza si è ridotto da 250 [239-312] ms al basale a 223 [172-244] ms dopo reb-oxy versus 264 [217-284] ms dopo placebo (p<0·001). Conclusioni: Il miglioramento delle conoscenze della fisiopatologia dell’OSA ha permesso di identificare la responsività muscolare delle alte vie come target principale di strategia terapeutica per l’OSA, predisponendo il percorso verso la medicina di precisione anche nel contesto dei disturbi del respiro nel sonno. Il nostro studio ha evidenziato il dato pionieristico dell’effetto positivo della somministrazione di reboxetina più ossibutinina sulla gravità dell’OSA e sull’ipossia associata agli eventi ostruttivi nel sonno. I risultati del nostro studio sottolineano la possibilità di una terapia personalizzata con farmaci per trattare l’OSA ed il carico ipossico ad essa relato.
Introduction: Obstructive sleep apnea (OSA) affects one third of the population in Europe and has major negative consequences for cardiovascular disease and quality of life. OSA is characterized by recurrent episodes of apneas and hypopneas associated with repetitive episodes of intermittent hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia, particularly with concomitant hypercapnia, activates the sympathetic nervous system and it is the major contributor to negative cardiovascular consequences. Intermittent hypoxia might also worsen concomitant tonic hypoxia due to high altitude or due to acute or chronic respiratory diseases by promoting oxidative stress and angiogenesis, thus increasing sympathetic activation with blood pressure elevation, inflammation and endothelial dysfunction. Although OSA and its hypoxic consequence are effectively alleviated with positive airways pressure, this treatment is yet unsatisfactory, being poorly tolerated by up to half of patients. Thus, new treatment strategies are strongly needed. With the aim of better understand OSA physiopathology, key contributors of its development have been identified and include upper airway collapsibility, ventilatory instability, low arousal threshold and reduced pharyngeal dilator muscle responsiveness during sleep, due to loss of noradrenergic drive and enhanced muscarinic influences to upper airway muscles. The recognition of these pathophysiological traits permitted to advance the research in the field of OSA new therapeutic perspectives. Aim: The aim of this study was to evaluate the effect of 1-week of reboxetine (a noradrenergic) plus oxybutynin (an antimuscarinic) on OSA severity (primary outcome) and their effect on endotypic traits and cardiovascular autonomic modulation. Methods: We performed a randomized, placebo-controlled, double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin (reb–oxy) to placebo in OSA subjects. After a baseline in-lab polysomnogram (PSG), patients performed PSGs after 7 nights of reb-oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI, primary outcome). Secondary outcomes included hypoxic burden, heart rate variability, blood pressure and heart rate changes and psychomotor vigilance test. Home oximetry evaluated overnight oxygen desaturation throughout treatment. Results: 16 subjects aged 57[51-61] years (median [interquartile range]) with body mass index 30[26-36] kg/m2 completed the study. Reb-oxy lowered AHI from 49[35-57] events/h at baseline to 18[13-21] events/h (59% median reduction) compared with 39[29-48] events/h (6% median reduction) on placebo (p<0·001). Response rate for reb-oxy was 81% versus 13% for placebo p<0·001). Median nocturnal heart rate during the PSG was 65 [60-69] bpm at baseline and increased to 69 [64-77] bpm on reb-oxy vs 66 [59-70] bpm on placebo (p=0.02). Reb-oxy administration was not associated with any modification in heart rate variability, 24-hour, day-time and night-time systolic and diastolic blood pressure. The psychomotor vigilance test decreased from 250[239-312] ms on baseline to 223[172-244] ms on reb-oxy versus 264[217-284] ms on placebo (p<0·001). Home oximetry illustrated acute and sustained improvement in oxygen desaturation index on reb-oxy versus placebo. Conclusions: The recent understanding of OSA pathophysiological mechanisms brought to hypothesize that, among the others, muscle responsiveness would be the main target to develop a precision medicine to treat OSA. We demonstrated that OSA severity and OSA-related hypoxic consequences are greatly decrease by the administration of reboxetine-plus-oxybutynin. These results highlight potential possibilities for personalized medicine with pharmacological therapy to treat OSA and its related hypoxic burden.

O objetivo principal do presente estudo foi avaliar o efeito do tratamento térmico das partículas strand (pré-tratamento) e dos painéis (pós-tratamento) sobre as propriedades físicomecânicas dos painéis, visando principalmente à melhoria de sua estabilidade dimensional. O delineamento experimental se constituiu de sete tratamentos, com a avaliação de: Duas temperaturas de tratamento das partículas (200 e 240°C) por um período de 60 minutos; do póstratamento térmico dos painéis produzidos com e sem a aplicação de parafina na temperatura de 220°C e por um período de 12 minutos; e do aumento do teor de adesivo e a aplicação de parafina em painéis sem tratamento térmico. Para cada tratamento foram produzidos três painéis com densidade nominal de 0,65 g/cm³, colados com adesivo à base de fenol-formaldeído. O ciclo de prensagem dos painéis foi o seguinte: pressão de 35 kgf/cm², temperatura de 160ºC e tempo de 8 minutos. A partir dos painéis produzidos, corpos-de-prova foram obtidos para a realização de ensaios físicos (Teor de umidade, densidade aparente, absorção de água e inchamento em espessura) e mecânicos (Módulo de ruptura, Módulo de elasticidade e Ligação interna), conduzidos conforme as normas ASTM D 1037 (2006) e DIN 52362 (1982). Mediante à análise dos resultados dos ensaios foi possível extrair as seguintes conclusões: Os painéis produzidos com as partículas tratadas termicamente a 240°C apresentaram-se superiores aos outros tratamentos em todas as propriedades físicas avaliadas, sendo portanto o tratamento com a melhor estabilidade dimensional. O pós-tratamento térmico promoveu melhora significativa das propriedades físicas dos painéis sem comprometer as propriedades mecânicas. O pré-tratamento térmico teve efeito mais pronunciado sobre as propriedades dos painéis do que o pós-tratamento térmico, proporcionando a melhoria das propriedades físicas e a diminuição das propriedades mecânicas. O aumento do teor de adesivo e a aplicação de parafina não se mostraram tão eficientes na estabilidade dimensional dos painéis OSB quanto o tratamento térmico aplicado nas partículas na temperatura de 240°C.
The main objective of this study was to evaluate the effect of thermal treatment of strand particles (pre treatment) and panels (post-treatment) on the physical and mechanical properties of the panels, aiming primarily to improve the dimensional stability. The experimental design was consisted of seven treatments, with the evaluation of: two temperatures of particle treatment (200 and 240 °C) during 60 minutes; thermal post-treatment of the panels produced with and without the application of paraffin at 220 ° C during 12 minutes; and the increase in adhesive content and application of paraffin on the panels without thermal treatment. Three panels were produced for each treatment with nominal density of 0.65 g/cm ³, bonded with phenol-formaldehyde adhesive. The pressing cycle of the panels was as follows: 8- minute press time, pressure of 35 kgf/cm ², and temperature of 160 °C. From the panels produced, specimens were obtained to conduct physical tests (moisture content, bulk density, water absorption and thickness swelling) and mechanical (Modulus of Rupture, Modulus of elasticity and internal bonding), tests according to ASTM D 1037 (2006) and DIN 52 362 (1982) standard. Through the analysis of test results it was possible to conclude: The panels produced with the particles thermally treated at 240°C were superior to the others for all physical properties evaluated, and therefore it was treatment with better dimensional stability. The post-thermal treatment caused a significant improvement of the physical properties of the panels without compromising the mechanical properties. The prethermal treatment had an effect on the properties of the panels that was more pronounced than the post-heat treatment, providing improved physical properties and lower mechanical properties. The increase in adhesive content and the application of paraffin were not as efficient in the dimensional stability of OSB as the thermal treatment applied on the particles at 240 ° C.

Pagrindinis darbo tikslas buvo nustatyti ir įvertinti šunų skrandžio ir dvylikapirštės žarnos opų susirgimų dažnumą, priežastis, klinikinių simptomų pasireiškimą, efektyviausius diagnozavimo bei gydymo metodus. Pasiekti šį tikslą, pirmiausiai mes išanalizavom virškinamojo trakto ligų bei skrandžio ir dvylikapirštės žarnos opų dažnumą. Antra, mes statistiškai isanalizavome labiausiai išreikštus klinikinius simptomus, budingus kraujo morfologinių ir biocheminių rodiklių pakitimus. Galiausiai, nustatėme efektyviausia diagnozavimo metodą bei taikomą gydymą. Nustatėme, kad 2012 metais, 16,66 proc. visų šunų ligų sudarė virškinamojo trakto ligos. Iš šių virškinamojo trakto ligų 3,04 % buvo skrandžio opaligė, tuo tarpu dvylikapirštės žarnos opų nebuvo nustatyta 2012 metais. Labiausiai išreikšti skrandžio ir dvylikapirštės žarnos opų klinikiniai simptomai buvo vėmimas (90,48 % pacientų) ir viduriavimas (57,14 % pacientų). Išanalizavus kraujo morgfologinius tyrimus buvo nustatyta neutrofilija (79,31 ± 0,9875 proc.), tuo tarpu kiti kraujo morfologiniai rodikliai buvo fiziologinėse normos ribose. Išanalizavus kraujo biocheminius tyrimus buvo nustatytas nežymus bilirubino kiekio padidėjimas kraujyje (8,59 ± 0,9549 µmol/l) ir sumažėjęs ALT (67,03 ± 9,7915 U/l). Endoskopinis tyrimas buvo nustatytas kaip efektyviausias diagnozavimo metodas. Naudojant šį metodą buvo diagnozuota 90,47 proc. pacientų. Gydymui dažniausiai buvo naudojama: gastroprotektoriai (90,48 proc.), gastroprokinetikai (80... [toliau žr. visą tekstą]
The main goal of this thesis was to determine and evaluate the frequency, ethiology, clinical symptoms, the most effective diagnostic and treatment methods for gastroduodenal ulcers in dogs. To achieve this goal at first we analized the frequency of gastrointestinal diseases and the frequency of gastroduodenal ulcers in dogs. Secondly, we statistically analized the most expressed clinical symptoms, the characteristic morphological and biochemical abnormalities of blood in dogs with gastroduodenal ulcers. Finally, we determined the most effective diagnostic and treatment methods. We determined that during 2012 years 16,66 % of all dogs diseases were gastrointestinal diseases (3,04% gastric ulcers, duodenal ulcers were not determined). The most expressed clinical symptoms for patients with gastroduodenal ulcers were vomiting (90,48%) and diarrhea (57,14%). Blood morphology showed high percentage of neutrophils (79,31 ± 0,9875 %), other morphological parameters were in physiologically normal range. Blood biochemistry showed little rise in bilirubin (8,59 ± 0,9549 µmol/l), and low ALT (67,03 ± 9,7915 U/l). We determined that the endoscopic method is the most effective method in diagnosing gastroduodenal ulcers. 90,47 % of gastroduodenal ulcers were diagnosed by using the endoscope. The most frequent treatment methods for gastroduodenal ulcers were gastro-protectors (90,48 % patients), gastroprokintetics (80,95 % patients), anti-acids (66,67 % patients), and diet (52,38 %... [to full text]

Avant leur mise sur le marché, l'évaluation clinique des médicaments repose sur des essais contrôlés randomisés. Bien qu'ils représentent la méthode de référence, leurs résultats sont nécessairement limités aux patients inclus dans ces essais. De plus, ils sont d’abord conçus pour mesurer l'efficacité des traitements, avant d’évaluer leurs effets indésirables. Concernant le syndrome d'apnées du sommeil (SAS), alors que de nombreux essais médicamenteux ont été menés, la plupart des résultats sont de faible niveau de preuve, voire contradictoires. Outre la durée et les effectifs limités de ces essais, une explication est que le SAS est une pathologie hétérogène en termes de symptômes et de physiopathologie, incluant divers "phénotypes" de patients. Des données de vie réelle sont donc nécessaires pour définir quels médicaments pourraient améliorer le SAS ou les comorbidités associées et quels patients pourraient en bénéficier. Au contraire, les cliniciens doivent être avertis que certains médicaments peuvent induire ou aggraver le SAS.La pharmacoépidémiologie fait désormais partie de toute enquête de pharmacovigilance, car elle permet une approche à la fois descriptive et comparative des notifications spontanées. Des associations entre l'exposition à un ou plusieurs médicaments et l'apparition d'effets indésirables peuvent ainsi être recherchées. Comme pour toutes les études observationnelles, la principale difficulté consiste à contrôler les facteurs de confusion. L'un des modèles couramment utilisés est l'analyse cas/non-cas, qui étudie la disproportionnalité entre le nombre d’effets indésirables rapportés avec le médicament d’intérêt, par rapport aux effets notifiés pour les autres médicaments. Nous avons ainsi montré des associations significatives entre l'utilisation de baclofène, des gabapentinoïdes ou de l'acide valproïque et la survenue de SAS dans la base de pharmacovigilance de l'OMS, suggérant le rôle du système GABAergique dans la pathogenèse des apnées centrales d’origine médicamenteuse. Un signal de disproportionnalité a également été observé pour le ticagrélor, reposant sur un mécanisme d'action différent.Les analyses pharmacoépidémiologiques permettent également d'étudier le bénéfice des médicaments en vie réelle. Le score de propension est utilisé pour minimiser les biais de sélection et recréer des conditions de comparabilité proches de celles des essais randomisés. À l'aide de ces méthodes statistiques, nous avons évalué l'intérêt potentiel de cibler le système rénine-angiotensine pour la prise en charge de l'hypertension artérielle chez les patients atteints d’apnées obstructives, en particulier avec l’utilisation des sartans. Chez ces mêmes patients apnéiques et hypertendus, nos travaux suggèrent que les diurétiques pourraient diminuer la sévérité des apnées, notamment en cas de surpoids ou d’obésité modérée. Des études prospectives sont désormais nécessaires afin de confirmer ces résultats, car les données de vie réelle ne peuvent se substituer aux essais cliniques contrôlés
The clinical evaluation of drugs before approval is based on randomized controlled trials. Although they are considered as the gold standard for testing drugs, their results are necessarily limited to patients included in the trials. Moreover, almost all clinical trials are primarily designed to assess the efficacy of a treatment, so safety is only a secondary concern. Regarding sleep apnea syndrome (SAS), while many drug trials have been conducted, most of the results are weak or even contradictory. In addition to limited trial duration and population size, one explanation is that the sleep apnea population is highly heterogeneous with respect to symptoms and physiological traits linked to disease pathogenesis, giving various patient “phenotypes”. Real-life data are therefore needed to define which drugs could improve SAS or associated comorbidities and who might benefit from them. On the contrary, clinicians need to be aware that some drugs may induce or worsen sleep apnea.Pharmacoepidemiology is now part of any pharmacovigilance survey, as it provides both descriptive and comparative approaches of spontaneous reports. Associations between the exposure to one or more drugs and the occurrence of adverse effects can thus be sought. As for all observational studies, the major difficulty is to control for confounding factors. One of the study designs commonly used, is the case/non-case analysis, which investigates disproportionality between the numbers of adverse drug reactions reported with the drug of interest compared to the number reported with all other drugs. In this way, we showed significant associations between the use of baclofen, gabapentinoids or valproic acid and the reporting of SAS in the WHO drug adverse event database, suggesting a role of the GABAergic system in the pathogenesis of drug-induced central sleep apnea. A disproportionality signal was also found for ticagrelor, based on a different mechanism of action.Pharmacoepidemiological analyses also make it possible to study the benefit of drugs in real-life. Propensity scores are used to minimize selection bias, leading to a comparability between the exposure groups close to that observed in randomized trials. Using these statistical methods, we have investigated the potential value of targeting the renin-angiotensin system for the management of hypertension in obstructive sleep apnea (OSA) patients, especially the use of sartans. For hypertensive apneic patients, our work suggests that diuretics could decrease the severity of OSA, particularly in the overweight or moderately obese. Prospective studies are now needed to confirm these findings, because real-life data cannot be a substitute for controlled clinical trials

Includes bibliographical references (leaves 68-75)
Objectives: To investigate whether or not OSAS patients from the South African population showed any cognitive impairment relative to healthy individuals from the same population, and to assess whether or not untreated OSAS patients and patients on CPAP treatment differed in their cognitive functioning.

All human beings experience emotion. However a number of individuals have difficulties recognizing, processing and regulating their emotions. This set of emotional "deficits' is classified as alexithymia, a multifaceted personality construct consisting of difficulties identifying feelings (DIF), difficulties describing feelings (DDF) and externally oriented thinking (EOT). The prevalence rate of alexithymia in alcohol use disorders is between 45 to 67%. A number of hypotheses related to the role of alexithymia in alcohol-dependence have been proposed, and it has been hypothesised that those with alexithymia use alcohol as a coping mechanism for stress, to become more assertive or improve interpersonal functioning. Yet, few research studies have comprehensively investigated alexithymia in alcohol­dependence. A lack of a theoretical framework examining alexithymia and alcohol is also apparent. Attachment theory and particularly parental bonding is considered a critical factor in the aetiology and development of alexithymia, but this hypothesis has not been thoroughly investigated. Thus, the purpose of Study 1 using meta-analysis was to explore, clarify and report the strength of the relationship between parenting style and alexithymia. The evidence indicated moderate to strong relationships of maternal care with overall alexithymia score, DDF and DIF. Moderate relationships were reported for maternal overprotection with DDF and overall alexithymia score. Moderate associations between paternal overprotection, DDF and total alexithymia score were also found. The findings of Study 1 confirmed an important association between maternal care and key elements of alexithymia, and highlighted the potential of attachment as a theoretical :framework for further research on alexithymia and alcohol-dependence. The objective of Study 2 was to explore the factorial validity of the Toronto Alexithymia Scale (TAS-20), the most commonly used assessment tool for alexithymia, in a sample of210 alcohol-dependent individuals. This group of participants had an alcohol use disorder diagnosis and were attending a Cognitive Behavioral Treatment (CBT) outpatient program. Data from this sample was used in Studies 2, 3, 4 and 5 with minor variations in the actual number of participants in each of these studies. Confirmatory factor analyses were conducted using Structural Equation Modelling to evaluate the factor structure of the TAS-20. Based on previously reported factor structures, both a two-factor and a three-factor model were examined, using maximum likelihood estimation. Four of the five fit indices and a chi-square difference test indicated a superior fit for the three-factor model compared to the two-factor model. Taken together these findings demonstrated that the original three-factor model of the TAS-20 was a more plausible fit to the data than the two­factor model. Given alexithymia's high prevalence in alcohol use disorders, valid assessment tools are critical. Study 2 confirmed the factorial validity of a self-report measure of alexithymia, the TAS-20. An objective assessment, the Observer Alexithymia Scale (OAS), has also been recommended to increase the validity of data collected. The objective of Study 3 was therefore to assess the validity and reliability of the Observer Alexithymia Scale (OAS) and the TAS-20. Data from the same 210 alcohol-dependent participants was used for Study 3. These participants were administered the TAS-20 at assessment and upon treatment completion at 12 weeks. Clinical psychologists provided observer assessment data for a subsample of 159 patients. The findings confirmed acceptable internal consistency, test-retest reliability and scale homogeneity for both the OAS and TAS-20. The TAS-20 was more strongly associated with alcohol-dependence than the OAS and also provided stronger predictive utility towards alcohol-dependence. Problems with the discriminant and convergent validity of the OAS were evident. These findings suggest that the T AS-20 was a more psychometrically robust instrument to measure alexithymia in alcohol use disorder outpatients compared to the OAS. A number of studies have examined alexithymia in relation to alcohol use disorders, yet there has been a lack of a theoretical framework to explore essential mechanisms in the link between alexithymia and alcohol-dependence. Study 4 introduced an integrative framework of attachment and expectancy theory, and examined theoretical relationships between attachment, alexithymia, alcohol expectancies and alcohol-dependence, in the same sample of 230 alcohol-dependent participants. Path analyses were conducted via Hierarchical Regression Analyses (for observed variables) and Structural Equation Modelling (for latent variables). Attachment was a significant predictor of alexithymia, but not for alcohol-dependence. There was also a significant prediction of DIF for the alcohol expectancy domain Assertion. The relationship between DIF and alcohol-dependence was partially mediated through the alcohol expectancy Affective Change, a key mechanism that contributes to our understanding of the link between DIF and alcohol-dependence. Taken together, these findings confirmed the importance of Affective Change in elucidating the highly rewarding effects of alcohol in those with combined alexithymia and alcohol-­dependence. Given that alexithymia may have an impact on the adherence and efficacy of psychological treatments, Study 5 examined potential differences on sociodemographic variables, alexithymia, attachment, alcohol expectancies, mood, craving and measures of alcohol-dependence between those who completed treatment and non-completers. The relationship between alexithymia and craving was also examined at baseline and at 12 week follow-up. Two hundred and eighty six consecutively treated participants diagnosed with an alcohol use disorder in an outpatient CBT program were included in the present study. There were significant differences between completers and non-completers on age, alcohol problem severity, dependent attachment, overall alexithymia score and DIF. This indicated more severe alcohol-dependence and attachment issues as well as higher levels of alexithymia in non-completers. Significant correlations between alexithymia, DIF and craving were evident as well as a significant relationship between DDF at baseline and craving at 12-week follow-up. To date, this is the first study to investigate alexithymia in relation to craving among those with alcohol-dependence, and suggests that a lack of emotional insight and confusion about feelings are associated with a stronger desire to drink alcohol. These findings highlight the potential importance of alexithymia in relation to treatment completion, and further research is needed to elucidate the role of alexithymia in relation to more standardised treatment outcome variables among those with alcohol use disorders. The developmental social-cognitive model presented partially integrates expectancy theory within attachment theory and for the first time provides a unified model to examine alexithymia in alcohol use disorders. The theoretical and clinical implications of this model are discussed in relation to a theoretical extension, molecular genetic factors, treatment approaches and future prevention of alcohol­dependence.

Las aminas biógenas se localizan en alimentos relacionados con procesos de fermentación, maduración o degradación (cerveza, queso, pescado, vino,...). Desempeñan un importante papel en su calidad organoléptica, siendo también claros exponentes de las características tecnológicas e higiénico-sanitarias de los procesos a los que han sido sometidos en su elaboración.
El objetivo fundamental de esta Tesis Doctoral ha sido investigar cuál es el rol que la cromatografía líquida de alta resolución y la extracción en fase sólida pueden desempeñar en el establecimiento de métodos de control analítico de aminas biógenas en vinos.
La estructura general de la memoria está dividida en dos partes, correspondiendo la primera de ellas a la introducción teórica de los apartados relacionados con el desarrollo de los métodos optimizados y aplicados en la parte experimental de la tesis, y que constituyen la segunda parte de ella.
Todos los métodos descritos están publicados en revistas de reconocido prestigio internacional, dando lugar a un total de siete artículos de interés científico.

碩士
輔仁大學
資訊工程學系
100
Obstructive sleep apnea is the common diseases of modern people. Most of the obstructive sleep apnea patients can accept the medical treatment by carrying the continuous positive airway pressure device to sleep. However, some of the patients complain to improvement the condition of sleep quality. They need complicate polysomnography examination and clinical diagnosis to judge the improvement. It is an important issue about how to design a sleep quality index to help the clinicians to diagnose the improvement of obstructive sleep apnea patients after continuous positive airway pressure treatment. This work proposes a sleep quality evaluation system for sleep quality improvement according to the signal features of electroencephalogram and electrocardiogram and fuzzy theory. The experimental results show that the sleep quality evaluation is positive correlated to the apnea-hypopnea index. The sleep quality evaluation can find the clear sleep improvement of the patients after continuous positive airway pressure treatment.

博士
國立陽明大學
生物醫學影像暨放射科學系
104
Obstructive sleep apnea (OSA) is accompanied by neurocognitive impairments and autonomic nervous system changes that suggest central nervous system hypoxic injuries and oxidative stress alterations in various brain regions mediating sleep-related behaviors. Retention of cognitive and mood problems after treatment, sustained elevated sympathetic outflow, and impaired autonomic responses to transient challenges indicate disturbances of neural functions. The functional alterations of the brain in OSA likely result from injuries to neural structures, but the natures of such injuries are not fully understood. Some past literatures have focused on the brain structural deficits caused by OSA. Voxel-based morphometry (VBM) analysis has been used, for example, to evaluate the differences in gray matter volume between patients with OSA and normal controls. The bilateral hippocampus and lateral temporal areas revealed decreased gray matter volume in patients with OSA, with these decreased volumes being associated with significant cognitive impairment. Using diffusion tensor imaging (DTI), past studies have also indicated that white matter is extensively affected in OSA patients compared to normal controls; the alterations include changes to axons linking major structures within the limbic system; the pons; the frontal, temporal, and parietal cortices; and projections to and from the cerebellum. Functional magnetic resonance imaging (fMRI) has also been used to evaluate sleep apnea patients, but fMRI studies have yet to provide any definite conclusions explaining the relationship between brain area functions and structural deficits. Recently, resting-state fMRI has been applied to construct these complicated intrinsic brain functional networks under conditions in which patients are not asked to perform specific tasks. In the first part of the investigations detailed in this dissertation, we used DTI to evaluate the cerebral white matter changes in OSA patients. The DTI results showed that OSA impairs white matter integrity in vulnerable regions and that these impairments are associated with increased disease severity. The white matter changes were also positively correlated with systemic inflammation. In the second part of our investigations, we further established the link between white matter damage and autonomic dysfunction. These findings will help us in ongoing research regarding brain function changes in OSA, as well as its pathophysiology. The treatments for OSA include the administration of continuous positive airways pressure (CPAP), the use of an oral appliance (OA), surgery, and observation. The severity of the disease determines which of these different treatment options is utilized, but there is no evidence thus far regarding the recovery of brain functions, if any, after the various treatments. In the third part of our investigations, we investigated the associations among clinical disease severity, systemic inflammation, cognitive deficits, and corresponding gray matter volume (GMV) changes of OSA, as well as any changes in these associations after surgery. We found that increased disease severity and systemic inflammation can alter GMV in vulnerable regions. In addition, we found that surgical treatment may improve the disease severity and level of systemic inflammation, with subsequent recovery in brain structures and their functions. The key aim of the study described in this dissertation was to evaluate the recovery of brain structures and brain functions after treatment using advanced MRI processing technologies in order to improve the prognosis of patients with OSA and to improve related clinical applications going forward.

PURPOSE: The aim of our randomized clinical trial is to produce stronger evidence supporting barbed repositioning pharyngoplasty (BRP) as a therapeutic option for the treatment of obstructive sleep apnea (OSA). METHODS: The trial was a single-centre prospective controlled trial with two parallel arms (group A: BRP; group B: observation) and randomization. Baseline and 6 months polygraphy evaluating the apnea hypopnea index (AHI), oxygen desaturation index (ODI) and lowest oxygen saturation (LOS) were performed. To test the differences among groups the Student’s t-test. The role of each factor (univariate analysis) and their independent effect (multivariate analysis) was explored using logistic regression model as appropriate. Linear regression was also conducted. RESULTS: A significant reduction of AHI, ODI, LOS and Epworth Sleepiness Scale (ESS) values were recorded in the BRP group. BRP showed to be more effective than observation. Logistic regression showed that preoperative AHI is related significantly to postoperative AHI within the BRP group. A linear regression showed that higher baseline AHI predicts more significant postoperative absolute AHI reduction. CONCLUSIONS: BRP appears to be a promising technique and might be included within the surgical armamentarium of a sleep surgeon. Patients affected by severe OSA may benefit from this surgery with more significant reduction of AHI values.

碩士
國立成功大學
電機工程學系
89
In this thesis, an interactive tele-clinic system is developed using the Object-Oriented Analysis and Design (OOA&D) technique to analyze the objects and then the Unified Modeling Language (UML) to build the object models. The traditional designing methodology, Processing Modeling, focuses mainly on the description of the system flow, and lacks the description of system objects and between-object relationship. Due to this reason, a system developed on Process Modeling does not posses the flexibility of system modification. However, a clinic system involves clinic work flow and management policies. It is not unusual to see that management policies and outpatient services change, resulting that system work flow changes and therefore, system object interaction relationship changes. This is particular serious in Taiwan with the frequent change of National Health Insurance policies. In view of all these system issues, this thesis proposes using the technique of object-based Analysis and Design in developing the tele-clinic system. In contrast to the Process Modeling emphasizing only on process relationship, Object-Based Analysis and Design provides the techniques for describing data, process and network modeling at the same time. In Object-Based Analysis and Design not only the data but also their relationships with other data objects are described and their constructed system functions are modularized. The designed system will therefore present more modularized system function architecture, facilitating the system in maintenance and updating due to future functionality expansion and upgrading. Thus future system work flow change can be more easily adapted into the so-designed tele-clinic system. A clinic system involves various necessary functions including the patient doctor interaction, registration flow, doctor schedule arrangement, patient record storage and retrieval, payment and system management. In order to approach these functions so as to provide as much function of a hospital, this system integrated with real-time video and audio transmission and electronic patient data delivering. Furthermore, to solve the problems possibly arisen when running a clinic system in network, this system is also embedded with XML database for recording patient records, real-time mutual identification mechanism for doctor and patient on-line identifying each other, and coupon mechanism for maintaining patient and doctor relationship. So designed, the system will be superior in both its designing technology and embedded functions in achieving customer relationship management.

Pierwotniaki (Protozoa) są nieodłącznym elementem sieci troficznej półnaturalnego ekosystemu wodnego jakim jest osad czynny. Rola pierwotniaków w konwencjonalnych oczyszczalniach ścieków był przedmiotem wielu badań na przestrzeni dziesiątków lat i jest dość dobrze poznana. Obecnie wśród oczyszczalni ścieków dominują obiekty o podwyższonej skuteczności usuwania biogenów, przystosowane do wysokiej/wydajnej redukcji stężenia związków azotu i fosforu. Osady pracujące w oczyszczalniach zaprojektowanych do usuwania biogenów różnią się od osadów z konwencjonalnych oczyszczalni składem gatunkowym bakterii jak i pierwotniaków. Fakt ten sugeruje, że wyniki z wcześniejszych badań nie powinny być automatycznie przenoszone na zespoły mikroorganizmów zasiedlające osady w oczyszczalniach nowego typu. W niniejszej rozprawie badano, ekologiczną rolę pierwotniaków w osadzie czynnym z podwyższonym usuwaniem biogenów. Sprawdzono również na ile pierwotniaki mogą zostać wykorzystane jako bioindykatory ˗ wskaźniki biologiczne w ocenie efektywności procesu oczyszczania ścieków z zastosowaniem osadu czynnego z podwyższonym usuwaniem biogenów. W tym celu przeprowadzono trzy eksperymenty w skali laboratoryjnej oraz roczny monitoring czterech komunalnych oczyszczalni ścieków. W badaniach laboratoryjnych przeprowadzonych w bioreaktorach wykazano, że zwiększone zagęszczenie orzęsków pełzających z gatunku Aspidisca cicada nie wpływa na liczebność oraz efektywność działania/pracy bakterii pierwszego etapu nitryfikacji, a co za tym idzie na efektywność redukowania stężenia amoniaku w ściekach. Wpływ pierwotniaków na formowanie osadu czynnego oraz na stopień mineralizacji związków azotu i fosforu w fazie „rozruchu”, nie był jednoznaczny, a wyniki zależały od układu eksperymentalnego i jego skali. W niewielkiej skali i w prostym układzie eksperymentalnym zespół bakterii w obecności pierwotniaków wydajniej mineralizował związki węgla, azotu i fosforu. W bioreaktorach symulujących proces SBR nie wykazano istotnych różnic pomiędzy różnymi zespołami bakterii, pierwotniaków i wrotków w mineralizacji związków węgla, azotu i fosforu. Zaobserwowano różnice w średniej wielkości kłaczków osadu pomiędzy różnymi zespołami bakterii, pierwotniaków i wrotków. Najmniejsze powierzchniowo kłaczki znajdowały się w zespołach bakterii w obecności zespołu składającego się z wiciowców, ameb nagich, orzęsków i wrotków. Fakt ten można wytłumaczyć zwiększoną presją konsumentów głównie wrotków. W eksperymencie symulującym dwudziestoczterogodzinny deficyt tlenu w bioreaktorach, zaobserwowano niższy stopień redukcji związków azotu i fosforu w bioreaktorach poddanych deficytowi niż w bioreaktorach kontrolnych. Nie odnotowano natomiast wyraźnych zmian w strukturze zbiorowiska bakterii nitryfikacyjnych, akumulujących polifosforany, pierwotniaków i metazoa pomiędzy grupami zabiegowymi. W warunkach laboratoryjnych nie udało się wskazać w zbiorowisku pierwotniaków i metazoa gatunków wskaźnikowych dla deficytu tlenowego. W trakcie badań w bioreaktorach zaobserwowano dużą zmienność w zagęszczeniach i składzie gatunkowym mikroorganizmów wewnątrz grup eksperymentalnych. Wysoka zmienność wewnątrz grup eksperymentalnych wraz z małą liczbą powtórzeń prawdopodobnie uniemożliwiła wykrycie istotnych różnic pomiędzy zabiegami. Roczny monitoring zespołu pierwotniaków i metazoa w czterech oczyszczalniach ścieków wykazał, że zespół mikroorganizmów osadu czynnego zależy od indywidualnych cech danego bioreaktora oraz pory roku. Z badanych parametrów procesowych, temperatura najlepiej tłumaczyła zmienność wśród zespołów pierwotniaków i metazoa w osadach czynnych. Na podstawie zebranych danych dotyczących zespołu mikroorganizmów, parametrów procesowych oraz stopnia redukcji zanieczyszczeń nie udało się jednoznacznie wskazać gatunków przydatnych do oceny jakości pracy oczyszczalni z podwyższonym usuwaniem biogenów.
Protozoa are inherent elements of the food web of the semi-natural aquatic ecosystem, which is the active sludge. Over decades the role of protozoa in conventional wastewater treatment plants was well known and the subject of many studies. Nowadays, among the wastewater treatment plants (WWTPs) dominate facilities with biological nutrient removal (BNR). These WWTPs are adapted to efficient reduction of nitrogen and phosphorus compounds concentration. The conventional WWTPs differed in biological characteristics of activated sludge in comparison to activated sludge in new technologies such as advanced treatments for nutrient removal. This fact suggests that the results from previous studies should not be automatically transferred to microbial communities that purify sewage in a new type of treatment. In this PhD thesis, the ecological role of protozoa in WWTP with BNR was investigated. It was also checked whether protozoa can be used as bio indicators in assessing the effectiveness of the BNR process. For this purpose, three experiments were carried out on a laboratory scale and annual monitoring of four full-scale treatment plants. In laboratory experiments conducted in bioreactors, the increased density of crawling ciliates species Aspidisca cicada did not affect the number and efficiency of ammonia oxidizing bacteria (AOB), and in consequence efficiency of reduction rate of ammonia in sewage. The influence of protozoa on the formation of activated sludge and on the degree of mineralization of nitrogen and phosphorus compounds in the "start-up" phase was not unambiguous, and the results depended on the experimental setup and scale. On a small scale and in a simple experimental setup, the bacterial community with presence of protozoa efficiently mineralized the compounds of carbon, nitrogen and phosphorus. In bioreactors simulating the sequencing batch reactor (SBR) process, differences in the mineralization of carbon, nitrogen and phosphorus compounds were not found between experimental groups of bacteria, protozoa and rotifers. Differences were observed in the mean sludge flocs size between different community of bacteria, protozoa and rotifers. The smallest flocs were found in bioreactors with the presence of microbial community consisted of flagellates, amoebas, ciliates and rotifers. This fact can be explained by the increased consumers pressure, mainly rotifers. In the experiment simulating the twenty-four-hour oxygen shortage in bioreactors, a lower rate of reduction of nitrogen and phosphorus compounds was observed in bioreactors treated oxygen shortage. On the other hand, no significant changes were noticed in the structure of the nitrifying bacteria, polyphosphate accumulating organisms, protozoa and metazoa community between experimental groups. In laboratory conditions, none of the protozoa and metazoa species could be treated as bio indicator for oxygen shortage condition. During the research in bioreactors a high variability in the densities and species community composition of microorganisms was observed within experimental groups. High variability within experimental groups, along with a small number of repetitions, probably limited the detection of significant differences between treatments. The annual monitoring of protozoa and metazoa community in four full scale wastewater treatment plants showed that the microorganisms community composition in activated sludge depends on the individual characteristics of a given bioreactor and the year seasons. From the studied process parameters, the temperature best explained the variability among protozoan and metazoa community. Based on the collected data on the microorganism group, process parameters and pollution reduction rate, it was not possible to clearly identify potential species useful for assessing the quality of treatment plants with biological nutrient removal.

This thesis examines how military members and veterans with Operational Stress Injuries are treated by Canadian justice systems. It suggests a correlation between mental injuries sustained on operations by military personnel and propensities for military and societal misconduct. By comparing civilian and military processes with American justice counterparts, a plan to improve the existing Canadian legal landscape is proposed. Using an analysis of the underlying philosophy and purpose of military justice, a problem solving diversionary court is recommended, along with legislative and policy amendments. The use of a consent-based “Treatment Standing Court Martial” would place military justice officials parallel to civilian justice alternative measures programs, and in a better position to break the cycle of recidivism among veterans by addressing root causes. Education to reduce stigma along with military-civilian partnerships are also advocated to enhance the detection of mental illness and to foster early treatment for military personnel and veterans. The overall goals of the work include: reducing recidivism, improving operational efficiency and taking care of military members, veterans and their families.