INTRODUÇÃO: A hipertensão arterial pulmonar (HAP) é uma doença grave da circulação pulmonar, cuja adequada caracterização ainda depende do cateterismo cardíaco direito. A tomografia de impedância elétrica (TIE) é uma ferramenta de imagem não-invasiva que permite a estimativa a beira-leito da perfusão pulmonar através da medida da variação de impedância durante a sístole (deltaZQ). Embora a busca por métodos não-invasivos que possam descrever a HAP venha crescendo, dados a respeito da aplicação da TIE em pacientes com HAP permanecem escassos. OBJETIVOS: Avaliar a relação entre deltaZQ e perfil hemodinâmico, gravidade e prognóstico de pacientes com HAP. MÉTODOS: Pacientes acompanhados na Unidade de Circulação Pulmonar (InCor-HCFMUSP) e submetidos ao cateterismo cardíaco (por suspeita de HAP ou piora clínica) foram simultaneamente avaliados com a TIE. Foi possível medir deltaZQ por meio de acoplamento eletrocardiográfico. A variação de impedância relativa à ventilação (deltaZV) e a relação deltaZV/deltaZQ também foram analisadas. Com base nos resultados do cateterismo, os pacientes foram divididos em 2 grupos: HAP e aqueles com hemodinâmica normal, nomeados normopressóricos (NP). deltaZQ, deltaZV/deltaZQ e deltaZQ corrigido pelo parâmetro antropométrico peso (deltaZQ*p) foram comparados entre os grupos, correlacionados com parâmetros hemodinâmicos invasivos e analisados como preditores de mortalidade. RESULTADOS: Após o cateterismo, 35 pacientes compuseram o grupo HAP e 8 pacientes, o NP. Os pacientes com HAP apresentaram redução significativa de deltaZQ em comparação aos NP, bem como aumento na relação deltaZV/deltaZQ. Observou-se correlação entre deltaZQ e parâmetros hemodinâmicos, particularmente volume sistólico (VS) (r = 0,66, r2 = 0,43; p < 0,001). O parâmetro peso aumentou a correlação entre deltaZQ e VS (r = 0,77, r2 = 0,59; p < 0,001). Durante o período de estudo, 7 pacientes morreram; eles apresentavam perfil hemodinâmico pior, redução de deltaZQ comparados aos sobreviventes e uma desproporção ainda maior da relação deltaZV/deltaZQ. A sobrevida global em 36 meses foi de 65%. A sobrevida foi menor no grupo de pacientes com deltaZQ*p < 154,6% ou deltaZV/deltaZQ > 12. CONCLUSÕES: A medida de deltaZQ, particularmente corrigida pelo peso, está associada ao perfil hemodinâmico de pacientes com HAP, e sua redução, associada com gravidade de doença e pior prognóstico / BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe disease of the pulmonary circulation, which still relies on the right heart catheterization (RHC) for its accurate characterization. Electrical impedance tomography (EIT) is a non-invasive image tool that allows the bedside estimation of lung perfusion through the measurement of impedance variation during systole (deltaZQ). Although the search for non-invasive methods for evaluation of PAH is developing, data concerning application of EIT in PAH patients remain scant. OBJECTIVES: To evaluate the relationship between deltaZQ and the hemodynamic profile, severity, and prognosis of PAH patients. METHODS: Patients followed at the Pulmonary Circulation Unit (InCor-HCFMUSP) and submitted to RHC (due to the suspicion of PAH or clinical worsening) were simultaneously evaluated by means of EIT. It was possible to measure deltaZQ by producing ECG-gated EIT images. The impedance variation related to ventilation (deltaZV) and the deltaZV/deltaZQ ratio were also analyzed. Based on the results of RHC, patients were discriminated into 2 groups: PAH and those with normal hemodynamics, referred as normo-pressoric (NP) group. deltaZQ, deltaZVdeltaZQ, and deltaZQ corrected by the anthropometric parameter weight (deltaZQ*w) were compared between groups, correlated to hemodynamic parameters, and analyzed as predictors of mortality. RESULTS: After RHC, 35 patients composed the PAH group, and 8 patients, the NP one. PAH patients showed a significant reduction of deltaZQ as compared to NP, as well as an increase of deltaZV/deltaZQ. A significant correlation between deltaZQ and hemodynamic parameters was found, particularly with stroke volume (SV) (r = 0.66, R2 = 0.43; p < 0.001). Weight correction increased the correlation between deltaZQ and SV (r = 0.77, R2 = 0.59; p < 0.001). During the study period, 7 patients died; they presented a worse hemodynamic profile, reduction of deltaZQ compared to PAH survivors, and an even higher deltaZV/deltaZQ ratio. The overall survival at 36 months was 65%. Patients with deltaZQ*w < 154.6 Kg.% or deltaZV/deltaZQ >12 presented worse survival. CONCLUSIONS: deltaZQ, particularly corrected by weight, is associated with hemodynamic status of PAH patients and its reduction is associated with disease severity and worse prognosis

O mercado cinematográfico pode ser caracterizado como uma indústria de entretenimento com a produção de bens de informação que são também bens de experiência, cuja qualidade só é conhecida após o consumo. Deste modo, a revisão crítica se torna importante para induzir seu consumo, fornecendo previamente algum grau de informação sobre a qualidade do bem. Segue-se o trabalho de Reinstein e Snyder (2005) para determinar se as revisões críticas conduzidas por consumidores e por críticos profissionais online afetam o tempo de exibição de filmes no mercado americano de cinema, medido em quantidades de semanas, conforme modelos de duração/sobrevivência na literatura. Para esta finalidade foi gerado, a partir de sites de cinemas americanos (Box Office Mojo e Rotten Tomatoes), um banco de dados extremamente rico com informações semanais de todos os filmes disponíveis no cinema americano de 2004 a 2015. Especificamente, investigou-se os efeitos das revisões críticas de críticos profissionais de primeira linha (Tops) e de consumidores, conforme a média das notas atribuídas na semana de lançamento de cada filme. No que se refere à avaliação dos consumidores foi aplicada a computação afetiva, que reconhece o sentimento e a emoção em suas resenhas online para captar o efeito boca a boca potencializado pelas mídias sociais e fornecendo, portanto, uma análise mais profunda do boca a boca online. O estudo controla por possíveis problemas de endogeneidade decorrente de simultaneidade, usando as críticas somente antes e durante a semana de lançamento dos filmes. Os resultados sugerem que os críticos profissionais exercem grande influência no tempo de duração dos filmes em cartaz, bem como a positividade dos consumidores em relação ao filme. No entanto, o efeito dos críticos profissionais é em média 3 vezes maior do que dos consumidores. Adicionalmente, pode-se observar que algumas emoções afetam a expectativa de vida dos filmes a depender do gênero do mesmo / The movie market may be considered as entertainment industry, which produces experience goods that is also information goods, whose quality is only known only after consumption. Thus, critical reviews becomes important to induce consumption, since it provides some level of information about product quality. We follow Reinstein and Snyder (2005) works in order to determine if experts and consumers online critical reviews affect the survival time of movies at the American movie market, measured by number of weeks, according to survival analysis models in the literature. For this purpose, an extremely rich database with weekly information on all the films available in American cinema from 2004 to 2015 was generated from American movie sites (Box Office Mojo and Rotten Tomatoes). Specifically, we investigate the effects of critical reviews from top professionals and from consumers, according to the average ratings assigned in each movie\'s release week. As far as consumer assessment was concerned, affective computing was applied, which recognizes the sentiment (sentiment analysis) and emotion (emotion mining) in their online reviews to capture the word-of-mouth effect boosted by social media. The study controls for possible problems of endogeneity due to simultaneity, using the criticisms before and during the week of release of the films. The results suggest that the professional critics exert a great influence on the duration of the films in exhibition, as well as the positivity of the consumers in relation to the film. Thus, the effect of professionals are 5 times greater, generally, than the effect of the consumer critics. Additionally, it can be observed that some emotions affect movie life expectancy depending on the its genre

O anticorpo anti-proteína P ribossomal é um dos marcadores sorológicos do lúpus eritematoso sistêmico, previamente associado a glomerulonefrite lúpica classe V (ISN-RPS). Neste trabalho foi avaliado o prognóstico renal em pacientes que possuem positividade para este anticorpo. Sessenta pacientes foram avaliados para parâmetros de sobrevida renal. Onze pacientes (18%) apresentaram positividade sorológica exclusiva para anticorpo anti-P ribossomal e vinte e oito pacientes (47%) para anti-dsDNA. Ao final do período de seguimento, foi observado que os pacientes anti-P positivos apresentaram uma maior sobrevida renal (11,0 ± 4,5 vs. 9,2 ± 4,5 anos, p=0,03) quando comparados aqueles anti-P negativos, assim como menor frequência de necessidade de terapia substitutiva renal (0 vs. 35% p = 0,025). Pacientes anti-P positivos apresentaram também maior frequência de classe V (91% vs. 31%, p < 0.001) e menor incidência de alterações proliferativas (45% vs. 82%, p = 0,021) na avaliação da biópsia renal quando comparados aos pacientes sem a positividade para este anticorpo. Os dados reforçam a hipótese de que o anticorpo anti-P é um marcador útil de um melhor prognóstico renal em pacientes portadores de lúpus eritematoso sistêmico / Antibodies to ribossomal P proteins are one of the serologic markers of systemic lupus erythematosus, previously described as associated to class V lupus glomerulonephritis (ISN-RPS). Our study assessed renal prognosis in patients with anti-P antibodies. Sixty consecutive SLE patients with biopsyproven nephritis (2004 ISN/RPS) were evaluated for renal survival parameters. Eleven patients (18%) had exclusive anti-P positivity and 28 (47%) patients anti-dsDNA. The post-biopsy follow-up analysis demonstrated that anti-P positive patients disclosed better renal survival (11.0 ± 4.5 vs. 9.2 ± 4.5 years, p = 0.03) as well as lower frequency of patients requiring dialysis (0 vs. 35% p = 0.025). The frequency of class V nephritis was higher in anti-P positive patients (91% vs. 31%, p < 0.001) and the occurrence of proliferative lesions at biopsy was lower in these patients (45% vs. 82%, p=0.021). Our data supports the notion that anti-P antibody is a valuable marker to predict a better long-term renal outcome in lupus patients

在此篇論文中，我們提出一個慢性Ｂ型肝炎病毒感染病程之數學模型。因為在病症間的轉移機率(Transition probability)是隨著患者的年齡變動，所以在過去的文獻中，已經有學者提出，在疾病轉移機率模型中，應加入國民生命表(Life table)，藉此讓機率模型更符合Ｂ型肝炎病患的生命歷程。但是過去的文獻中，學者並沒有利用加入國民生命表之後疾病模型做進一步的病程分析。在這篇論文當中，我們假設原始的疾病轉移模型是符合馬可夫鏈的性質，並且提出一種加入國民生命表的方法，賦予疾病有年齡相關特性之模型。根據文獻數據和類馬可夫機率性質，我們使用著名的Chapman-Kolmogorov公式計算Ｂ型肝炎的自然病程機率，並畫出病人的生存機率曲線(Survival curve)。文章最後將會藉由兩個例子來介紹此篇論文提出的模型。實驗數據結果證實，此模型不僅提供了一個更精確的方法去分析在病症與死亡間的轉移機率、平均餘命(Life expectancy)、以及在不同年齡的存活機率(Survival probability)，並且可以更進一步的分析且瞭解病情狀態之間的轉移狀況。 / In this thesis, we propose a new mathematical model extending the natural history of hepatitis B virus (HBV) prognosis progression on chronic HBV infection. Since the actual transition probabilities between symptoms are dependent of ages, it has been proposed that the life table should be accommodated to the HBV prognosis progression model so that it can more properly explain the disease progression of the HBV patients. But in the literature, no further disease analysis and applications of it with the life table are discussed. In this thesis, we assume that the original disease progression is described by a Markov model, and propose a new method to combine the HBV progression with the life table so that the proposed model integrates data from the life table and allows the accommodation of age-dependent properties of the target disease. With clinical data based on annual incidence rates, the entire model is Semi-Markov based in nature. Computation methods similar to the celebrated Chapman-Kolmogorov equation can be applied to study the associated probability of each likely trajectory with desired initial ages and health states under the scenarios of natural history and various treatment policies. This method provides a more accurate way to analyze the transitions between symptoms, such as the mean life expectancy or the survival probabilities at different ages. We will give examples to demonstrate the proposed method in this thesis. Numerical results show the proposed model not only provides a more accurate method to analyze the mean life expectancy, the survival probabilities at different ages, and the transition probabilities from symptoms to death but also helps us to understand the transitions between symptoms.

可轉換公司債為複合式證券，除了具有債券性質外，並給予持有者於債券流通期間內行使轉換為股票之權利。以存活分析方法探討可轉債之研究尚屬少見，本論文乃以台灣上市櫃公司發行之5年期可轉債為研究資料，先整理出與公司經營有關的變數，再分別以Cox模式與再發事件之兩種邊際模型(marginal model)：A-G (Anderson-Gill) 模式、PWP-TT (Prentice-Williams-Petersen)模式為研究分析方法，探討可轉債之流通時間及大量交易時間的問題。本論文並將可轉債分類為債券類型、混合類型和權益類型，且由於不同類型可轉債之流通時間有所差異，因此以其為分層條件加入模式中進行分析。研究結果發現，資產總額、總負債率、TCRI評等及董監持股率等變數，具有顯著解釋可轉債流通時間的能力，可見公司財務負債狀況與穩定性與流通期間有關；而最高差價(當月最高股價與轉換價之相對差價)、長期負債率、總負債率及股價報酬率等變數，則可顯著解釋大量交易的發生時間，表示公司財務負債狀況與股價利潤差與大量交易發生之快慢有關，其中資產總額、最高差價、TCRI評等及股價報酬率之係數均顯著為正，長期負債率、總負債率及董監持股率之係數則顯著為負。由於平均表現之存活曲線與經驗存活曲線相當接近，以Kolmogorov-Smirnov檢定多無顯著差異，顯示這些模式有不錯的配適能力；至於對個別公司估計出之存活曲線，則或有與經驗存活曲線相差較多的現象，顯示所建立的模式可對個別公司提供可轉債即將結束流通或發生大量交易之預警。 / Convertible bonds are hybrid securities that possess the properties of bonds and the right to convert bonds into shocks. Few articles employed survival analysis to analyze the characteristics of convertible bonds. To investigate the effects of the issuer’s financial information to the duration of circulation and the timing of the massive trading about convertible bonds, Taiwan’s 5-year convertible bonds were collected, and three methods of survival analysis were employed：Cox model、A-G (Anderson-Gill) model and PWP-TT(Prentice-Williams-Petersen) model. We classified convertible bonds as debt-like, equity-like, and hedge-like, and then make the classification as a stratification condition later. In summary, total Assets, total debt ratio, TCRI, and the proportion of holding share in supervisors and directors are significant variables on circulation period of convertible bonds. Apparently, the extent of debt and financial stability of issuers have significant effects on circulation period; the difference between stock price and conversion price, long-term debt ratio, total debt ratio and stock return rate contribute significantly on the timing of massive trading of convertible bonds. While the extent of debt and the return of stock hasten the hazard of the timing of massive trading. Furthermore, there are no significant differences between the survival curves evaluated at the average performance levels and the corresponding empirical survival curves, according to the results of Kolmogorov-Smirnov test. However, the differences between individual survival probabilities and overall empirical survival probabilities might be large, which indicates that the models incorporate companies’ performance overtime may provide a warning message for the termination of circulation or the timing of massive trading for a particular convertible bond.

BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. METHODS: We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma. / <p>De två första författarna delar förstaförfattarskapet.</p>

Background: When assessing the association between a factor X and a subsequent outcome Y in observational studies, the question that arises is what are the variables to adjust for to reduce bias due to confounding for causal inference on the effect of X on Y. Disregarding such factors is often a source of overestimation because these variables may affect both X and Y. On the other hand, adjustment for such variables can also be a source of underestimation because such variables may be the causal consequence of X and part of the mechanism that leads from X to Y. Methods: In this paper, we present a simple method to compute control variables in the presence of age at onset data on both X and a set of other variables. Using these age at onset data, control variables are computed that adjust only for conditions that occur prior to X. This strategy can be used in prospective as well as in survival analysis. Our method is motivated by an argument based on the counterfactual model of a causal effect. Results: The procedure is exemplified by examining of the relation between panic attack and the subsequent incidence of MDD. Conclusions: The results reveal that the adjustment for all other variables, irrespective of their temporal relation to X, can yield a false negative result (despite unconsidered confounders and other sources of bias).

Aquesta tesi avalua l'existència de diferencies per gènere en la relació entre discapacitat i mortalitat, i aspectes metodològics en l'anàlisi de supervivènciad'estudis de gent gran. Es van utilitzar les dades provinents d'una cohort de 1.315 subjectes amb edats superiors o iguals a 65 anys que van ser seguits durant un periode de 8 anys. La discapacitat es va mesurar mitjançant la capacitat que declarava l'individu per dur a terme activitats de la vida diària bàsiques. La discapacitat va evolucionar al llarg del temps empitjorant amb l'edat, però una proporció no menyspreable va ser capaç de recuperar-se. Es van observar diferències per gènere en l'evolució de la discapacitat: les dones tenien més dificultats en recuperar la seva capacitat funcional un cop esdevenien discapacitades. La força de l'associació entre la discapacitat i la mortalitat disminuia a edats avançades. Es van trobar diferencies per sexe: les dones depenents mostraven un risc de morir més alt que el homes depenents. Polítiques de salut dirigides a dones discapacitades haurien de ser implementades degut a la proporció més elevada de dones discapacitades, la probabilitat menor que tenen de recuperar la capacitat funcional, i el risc de morir més elevat que presenten comparat amb homes dicapacitats. / This thesis evaluates the existence of gender differences in the relationship between disability and mortality, as well as methodological aspects of the survival analysis for elderly studies. Data from a cohort of 1,315 subjects aged 65 years and older followed-up 8 years was used. Disability was assessed by self-reported difficulty to perform basic activities of daily living. Disability evolved over time worsening with age, but a non-negligible proportion was able to recover. There were gender differences in the evolution of disability: women were less able to regain functional capacity once they become disabled. The strength of the association between disability and mortality decreased in the older ages. But differences by gender were found: dependent elderly women showed a higher risk of dying compared to dependent men. Health policies focusing on disabled women should be implemented, due to the higher proportion of disabled women, the lower probability of regaining functional capacity, and their higher risk of dying compared to disabled men.

Fire is the primary natural disturbance vital to the ecological integrity of Quetico Provincial Park, Ontario, Canada. A new provincial park planning process (i.e., Class Environmental Assessment) has required the review of Quetico’s Fire Management Plan. To support this review, large and severe (stand-replacing) Quetico fires were studied using 1966 Ontario Ministry of Natural Resources (OMNR) forest resource inventory (FRI) mapping. A Geographic Information Systems (GIS) database of the FRI was created and updated with the OMNR digital fire atlas. This database was used as a time-since-fire and fire interval dataset to estimate fire frequency. It also served to archive the 1966 FRI for the largest protected area in the transition between the Boreal and Great Lakes-St. Lawrence forest regions. Non-parametric (Kaplan-Meier) survival analysis was used to estimate survival functions and mean fire intervals (i.e., the expected time between two consecutive stand-replacing fires for any location within the Park). Previous studies that have used Kaplan-Meier survival analysis methods have based fire frequency estimates solely on time-since-fire data. However, time-since-fire data cannot be equated with fire interval data when using non-parametric methods. At least one fire interval is required to obtain reliable results. The mean fire interval for the entire 475,782 ha Park between the years 1668 and 2007 was 230 years. Performing the analysis on various geographic and temporal partitions revealed fire frequency spatial and temporal variability. A constant (independent of time-since-fire) probability of burning was not observed for Quetico which is contrary to accepted conjecture for northwestern Ontario boreal/mixed-wood forests. A current fire cycle was also estimated for the Park (342 years) using the digital fire atlas. The results suggested that use of historical static fire frequency estimates as fire management prescriptions may not be justified given considerable fire frequency temporal variability. The observed fire frequency spatial variability suggests that studies should be undertaken at coarser scales than is the norm to characterise the regions fire regime in support of landscape level fire management planning.

Fire is the primary natural disturbance vital to the ecological integrity of Quetico Provincial Park, Ontario, Canada. A new provincial park planning process (i.e., Class Environmental Assessment) has required the review of Quetico’s Fire Management Plan. To support this review, large and severe (stand-replacing) Quetico fires were studied using 1966 Ontario Ministry of Natural Resources (OMNR) forest resource inventory (FRI) mapping. A Geographic Information Systems (GIS) database of the FRI was created and updated with the OMNR digital fire atlas. This database was used as a time-since-fire and fire interval dataset to estimate fire frequency. It also served to archive the 1966 FRI for the largest protected area in the transition between the Boreal and Great Lakes-St. Lawrence forest regions. Non-parametric (Kaplan-Meier) survival analysis was used to estimate survival functions and mean fire intervals (i.e., the expected time between two consecutive stand-replacing fires for any location within the Park). Previous studies that have used Kaplan-Meier survival analysis methods have based fire frequency estimates solely on time-since-fire data. However, time-since-fire data cannot be equated with fire interval data when using non-parametric methods. At least one fire interval is required to obtain reliable results. The mean fire interval for the entire 475,782 ha Park between the years 1668 and 2007 was 230 years. Performing the analysis on various geographic and temporal partitions revealed fire frequency spatial and temporal variability. A constant (independent of time-since-fire) probability of burning was not observed for Quetico which is contrary to accepted conjecture for northwestern Ontario boreal/mixed-wood forests. A current fire cycle was also estimated for the Park (342 years) using the digital fire atlas. The results suggested that use of historical static fire frequency estimates as fire management prescriptions may not be justified given considerable fire frequency temporal variability. The observed fire frequency spatial variability suggests that studies should be undertaken at coarser scales than is the norm to characterise the regions fire regime in support of landscape level fire management planning.