The ancient Chinese I Ching, the Book of Changes, and the philosophy of the German philosopher Friedrich Nietzsche (1844-1900) both assert that the universe exists in a state of change. The I Ching, originally a book of divination, illustrates the changing phenomena of the natural world in terms of sixty-four hexagrams, which are figures composed of six lines  yielding and firm lines, representing actual conditions and relationships existing in the world and caused by the interplay between two primordial forces, yin and yang. The I Ching shows that on the macro level the Tao works in the universe, in heaven and on earth, and on the micro level it applies to man. The I Ching teaches harmony with Tao and its power (natural law and moral law), so that its reader may take appropriate action in any given situation with reference to the hexagrams and their appended judgments as revealed by the oracle. Nietzsche, however, regards the world as the Will to Power, ‘a monster of energy’, like a storming and flooding ocean eternally changing, where harmony and order seems impossible. His mouthpiece, Zarathustra, who teaches the Übermensch, encourages a war-like attitude towards life. Zarathustra’s second metamorphosis of an evolving spirit, the warrior lion, marks the difference between the Nietzschean Übermensch and the Chinese sage who attains harmony and balance within and without, a mysterious union with heaven. Zarathustra’s third metamorphosis, a playing child, creates itself as its own ‘bridge’ through a process of self-overcoming, whereas the I Ching indicates order to be the ‘bridge’ over chaos, the order of the human world being expressed in the five cardinal relationships. Whereas the I Ching advises its reader to follow their own nature and fate in order to lead a harmonious moral life, Nietzsche’s Übermensch is ‘the annihilator of morality’ and paradoxically ‘the designation of a type of supreme achievement’ (EH Books 1). With his idea of the Übermensch, Nietzsche indicates that morality is a pose (BGE 216). He seeks to make us become aware that we should invent our own virtue and create our own way in order to become what we are. He criticizes Christian morality, calling himself ‘the first immoralist’. His shocking approach attempts to make us become aware of the possibility that a ‘noble morality’ and ‘higher moralities’ ought to be possible. His Übermensch represents such a higher mode of existence. Zarathustra also teaches the doctrine of eternal recurrence, implying that moment is eternity, changelessness within change. Multifarious manifestations are the expression of the Tao. Everything is interconnected and interdependent. Whereas ordinary men see the continuity of phenomena as real, enlightened beings are aware of the transitory and illusive nature of the self and all things. The Nietzschean Übermensch embodies the characteristics of an enlightened being, a Buddha or Bodhisattva in Buddhist terms, characteristics such as wisdom and compassion. Therefore, the practice of the Bodhisattva is explored as a feasible way for actualizing the Nietzschean hypothetical Übermensch. / Thesis (DPhil)--University of Pretoria, 2009. / Philosophy / unrestricted

Objectives: The aims of this study were to: 1) Assess whether naturally induced anti-HPV antibodies are associated with subsequent acquisition of genital HPV 6, 11, 16, and 18 infections in men, 2) assess the recurrence (redetection) of genital HPV infections of the 9-valent vaccine HPV types and investigate factors associated with recurrent infections among men, and 3) assess the risk of type-specific sequential acquisition of anal HPV infection following a genital HPV infection of the 9-valent vaccine HPV types among men who have sex with women (MSW). Methods: 4,123 healthy men were followed every six months (median follow-up time 4.1 years). HPV antibodies were measured at baseline using a virus-like particle-based ELISA assay. Genital and anal HPV genotypes were detected using the Roche Linear Array assays. Kaplan-Meier curves and Cox models were developed to assess associations between serum anti-HPV antibody and subsequent incident HPV infections. Individual type analyses and grouped analyses were carried out to assess type-specific recurrence of the 9-valent vaccine HPV types. Risk of sequential anal HPV infection was assessed by examining incident rate ratios (IRR) and adjusted hazard ratios (aHR) among men with a prior genital HPV infection compared to men without a prior genital HPV infection. Results: 1) Significantly higher rates of incident infections were observed for HPV 16 among baseline HPV 16 seropositive men (aHR 1.37, 95% CI 1.01-1.86). Risk of persistent HPV 18 infection was significantly lower among HPV 18 seropositive men in unadjusted models, but not in the adjusted model, while incident and six-month persistent HPV 6 and 11 infections did not differ by baseline serostatus. 2) Up to 31% of prior prevalent and 20% of prior incident HPV infections recurred over time in individual type analyses. New female sexual partners, frequency of sexual intercourse with female partners, and new male sexual partners were associated with type-specific recurrence of HPV infections (HPV 6, 16, 31 and 58). In grouped analyses, lifetime number of male sexual partners (aOR = 2.40, 95% CI 1.19-4.84) and number of new male sexual partners (aOR 2.35, 95% CI 1.16-4.74) were associated with recurrence of HPV infections. 3) In individual type analyses, men with a prior HPV 16 genital infection had a significantly higher risk of subsequent anal HPV 16 infection (aHR=4.63, 95% CI 1.41-15.23). Significantly higher HRs were observed for any of the nine HPV types (aHR= 2.8, 95% CI1.32-5.99), high risk HPV types (aHR=2.65, 95% CI 1.26, 5.55) and low risk HPV types (aHR=5.89, 95% CI1.29, 27.01) in grouped analyses. Conclusion: Baseline seropositive status among men was not associated with a reduction in subsequent incident genital HPV 6, 11, and 16 infections, but with a possible protective effect for persistent HPV 18 infections. Men are also susceptible to recurrence of type-specific genital HPV infections, and recurrence of HPV infection was associated with high-risk sexual behaviors. MSW men with prior genital HPV infections are more likely to have a subsequent type-specific anal HPV infection than men who did not have prior genital HPV infections. Understanding the natural history of HPV infections among men is essential to control HPV associated diseases in both men and women.

Orientadores: Cármino Antonio de Souza, Afonso Celso Vigorito / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T14:24:56Z (GMT). No. of bitstreams: 1 Colella_MarcosPaulo_M.pdf: 4664560 bytes, checksum: ce76d7ca7d69ede5a86dc9fe14e7bbca (MD5) Previous issue date: 2014 / Resumo: O Transplante de Células Tronco Hematopoiéticas (TCTH) Alogênico representa uma possibilidade de cura para pacientes portadores de doenças hematológicas malignas e benignas. Porém, como qualquer modalidade de tratamento, apresenta efeitos adversos que podem ser graves, inclusive causando a morte. Com o intuito de se avaliar a influência que as comorbidades teriam na mortalidade não relacionada à recidiva (MNRR), foi criada uma ferramenta, o Índice de Comorbidade específico do Transplante de Células Tronco Hematopoiéticas (Hematopoietic Cell Transplant Specific Comorbidity Index - HCT-CI). Nossos objetivos, portanto, foram validar o HCT-CI na população de pacientes submetidos a TCTH Alogênico em nossa instituição, no período de 1993 a 2010, e avaliar outros fatores de riscos envolvidos na MNRR e na Sobrevida Global (SG). Os prontuários de 457 pacientes foram revistos e as informações referentes às comorbidades contidas no HCT-CI foram registradas. A maioria dos pacientes (59%) recebeu o índice 0, seguido de 30% de pacientes com índice de 1-2 e 11% com índice ? 3. Na análise univariada, os pacientes com HCT-CI igual a zero, comparados aos com HCT-CI ?1, apresentaram uma MNRR de 33% vs. 45% (p=0.01) e SG de 53% vs. 35% (p=0.001); nos pacientes que ao transplante apresentavam doença de baixo risco, comparados aos com doença de alto risco, a MNRR foi de 30% vs. 50% (p<0.0001) e SG de 57% vs. 27% (p<0.0001); o tipo de enxerto (medula óssea vs. sangue periférico) apresentou MNRR de 29% vs. 49% (p<0.0001) e SG de 56% vs. 34% (p<0.0001). A análise multivariada confirmou a influência do HCT-CI na MNRR e na SG, do risco da doença sobre a SG e do tipo de enxerto na MNRR. O tipo de condicionamento (baixa dose vs. alta dose) não teve influência na MNRR e SG, tanto na análise univariada quanto na multivariada. Quanto o grupo foi estratificado pelo HCT-CI (0 e ?1) o risco da doença ao transplante e o tipo de enxerto tiveram influência na MNRR e na SG, na análise univariada e multivariada, tanto nos pacientes com HCT-CI 0 e ?1. Não houve influência do tipo de condicionamento. O HCT-CI foi validado na nossa população de pacientes submetidos ao TCTH alogênico e identificamos outros fatores de risco que tiveram influência na MNRR e na SG. O HCT-CI, portanto, deve ser utilizado como guia no planejamento da estratégia terapêutica em pacientes portadores de comorbidades / Abstract: Allogeneic hematopoietic stem cell transplant is an important modality of treatment for patients bearing malignant and benign hematologic diseases, representing a chance of cure. As every treatment, it has a treatment-related mortality, possibly influenced by comorbidities. To better evaluate the influence of comorbidities on Non-Relapse Mortality (NRM) and Overall Survival (OS), the Hematopoietic Cell Transplant Specific Comorbidity Index (HCT-CI) was developed. Our objective was to apply the HCT-CI and to find risk factors for NRM and OS in patients who underwent an allogeneic hematopoietic stem cell transplant in our institution, between 1993 and 2010. Medical charts from 457 patients were reviewed. Most patients (59%) were classified in score 0, followed by 30% of cases with score 1-2 and 11% score 3-7. In a univariate analysis, patients with comorbidity score 0, compared with score ?1 had a NRM of 33% vs. 45% (p=0.01) and OS at 5 years of 53% vs. 35% (p=0.001); patients with low risk disease at transplant, compared with high risk disease, had a NRM of 30% vs. 50% (p<0.0001) and OS of 57% vs. 27% (p<0.0001); graft source (bone marrow vs. peripheral blood) had a NRM of 29% vs. 49% (p<0.0001) and OS 56% vs. 34% (p<0.0001). The multivariate analysis confirmed the influence of HCT-CI score on NRM and OS, disease risk at transplant on OS and graft source on NRM. The conditioning type (low dose vs. high dose) did not influence the NRM and OS in both univariate and multivariate analysis. When stratified by comorbidity (0 and ?1), disease status at transplant and graft source influenced NRM and OS in univariate and multivariate analysis, either in the group of patients with HCT-CI 0 and ?1. The conditioning type had no impact. Based on our data, we were able to validate de HCT-CI in our institution and to identify other risk factors with influence on NRM and OS. The HCT-CI, therefore, could be used to guide the treatment strategy of patients with comorbidities / Mestrado / Clinica Medica / Mestre em Clinica Medica

O objetivo deste estudo foi avaliar retrospectivamente, em longo-prazo, os preditores de recorrência de fibrilação atrial paroxística (FA) em 139 pacientes submetidos à ablação por radiofreqüência, através das técnicas ostial ou extraostial de abordagem do átrio esquerdo, associadas ou não à ablação do istmo cavo-tricuspídeo (ICT). Variáveis pré, intra e pós-ablação foram avaliadas por análise uni e multivariada, para determinar os preditores de recorrência da FA após um procedimento. Observou-se que maior tempo de história de FA, uso de mais antiarrítmicos e recorrência de FA dentro de 60 dias pós-procedimento, aumentaram o risco de recorrência de FA a longo-prazo. Por outro lado, a associação de flutter atrial e a ablação concomitante do ICT, reduziram o risco de recorrência ao final de 33 ±12 meses. / The objective of this study was to evaluate in retrospect, in long-term, the predictors of late recurrence of atrial fibrillation (AF) in 139 patients submitted to the ablation by radiofrequency, through the techniques ostial or extra-ostial of approach of the atrium left, associated or not to the ablation of the cavotricuspid isthmus(ICT). Variables pre, intra and post-ablation were appraised for analysis uni and multivariated, to determine the predictors of recurrence of AF after one procedure. It was observed that larger time of history of AF, use of more drugs and recurrence of AF within 60 days after procedure; they increased the risk of recurrence of AF in long-term. On the other hand, the association of atrial flutter and the concomitant ablation of ICT, they reduced the recurrence risk at the end of 33 ±12 months.

Le 17 novembre 2016 a eu lieu la 3ème journée mondiale de lutte contre le cancer du pancréas.Cette prise en considération tardive rend compte de la dualité entre une incidence faible et un pronostic redoutable. Sa réputation de cancer rapidement mortel est attestée par un ratio incidence/mortalité proche de 1. Au 10ème rang en termes de localisations de cancers, il se hisse au 4ème rang en termes de mortalité par cancer et devrait devenir, en 2020, la 2ème cause de décès par cancer devant le cancer du côlon et juste après le cancer du poumon. Le taux de survie à 5 ans, tous stades confondus, est de 5% aux USA et en Europe.L’adénocarcinome canalaire pancréatique représente la tumeur la plus fréquente (80% des tumeurs pancréatiques exocrines). Sa localisation dans la glande pancréatique est céphalique dans 2/3 des cas.A ce jour, le traitement chirurgical reste le seul traitement potentiellement curatif. Celui-ci ne s’adresse qu’à une faible proportion de patients. En effet, seul 20% des patients présentant un adénocarcinome pancréatique céphalique sont effectivement résécables permettant d’obtenir un taux de survie globale à 5 ans d'environ 10 à 20% si la résection est suivie de chimiothérapie adjuvante ou non. Ces résultats modestes sont en outre à pondérer par la morbi-mortalité des résections pancréatiques céphaliques. Dans la série de l’Association Française de Chirurgie, reprenant les résections pancréatiques céphaliques réalisées en France entre 2004 et 2010, la mortalité était de 3,8% et la morbidité de 54%. Parmi les complications post-opératoires, la fistule pancréatique représente la principale complication en termes de mortalité (15 à 25%), génératrice de coût important dans les soins et d’une augmentation significative de la durée de séjour. La fistule pancréatique demeure la pierre angulaire de l’amélioration du pronostic des patients.L’objectif de ce travail sur l’adénocarcinome canalaire pancréatique céphalique traité chirurgicalement était d’analyser certains facteurs influençant la morbi-mortalité au trois temps de sa prise en charge :- Avant l’intervention, avec l’étude d’un facteur pronostic préopératoire, sur une cohorte de patients, pouvant influencer la survenue d’une fistule pancréatique et la mortalité- Pendant l’intervention, avec la réalisation d’une méta-analyse sur le type de reconstruction pancréatique et son influence sur la survenue d’une fistule pancréatique- Après l’intervention, avec l’étude de l’influence de la survenue d’une complication sévère sur la survie et la survie sans récidive.Au cours de cette thèse nous avons vu, que la réduction du taux de fistule pancréatique, par le seul biais de techniques peropératoires semble difficilement réalisable au regard de la multiplicité des techniques et de la difficulté à réaliser des études randomisées contrôlées méthodologiquement satisfaisantes. En revanche, la recherche des facteurs liés aux patients, prédisposant à la survenue d’une fistule pancréatique semble l’approche à privilégier. Ceci est d’autant plus primordial dès lors que nous avons mis en évidence un lien entre la survenue d’une complication sévère et la survie ou la récidive chez les patients réséqués. Ce travail souligne l’importance d’être capable d’identifier, dès la consultation, les patients à haut risque de complications sévères et de fistule post-opératoire d’une part, pour sélectionner les bons candidats à la chirurgie et d’autre part, pour être capable de leur apporter une information franche et loyale indispensable éthiquement au consentement éclairé. / The third World Day on pancreatic cancer took place the 17th November 2016. This late consideration is due to the duality between his relative scarcity and a dreadful prognosis.Its aggressiveness is underlined by a mortality rate equal to its incidence. Ranked 10th on cancer-related localization and 4th on cancer-related mortality, he will become the second cause of cancer-related deaths in 2020 just behind pulmonary cancer and before colorectal cancer. 5-yr survival rate is 5% irrespective of the stage.Pancreatic ductal adenocarcinoma is the most frequent form (80% of exocrine pancreatic tumors). He is localized in cephalic pancreas in 2/3 of cases.Although pancreatic resection provides the only chance of long-term survival, no more than 20% of patients will be eligible for surgery in curative intent leading to a 5-yr survival rate of 10 to 20%. Pancreaticoduodenectomy for pancreatic head, neck and uncinated process is still a challenging procedure. In the study of the French Surgery Association, mortality and morbidity rate were respectively 3.8% and 54%. Postoperative pancreatic fistula is considered as the Achilles’ heel of pancreaticoduodenectomy and is associated with increased post-operative mortality. Postoperative pancreatic fistula generates significant costs and prolonged hospital stay. Thus postoperative pancreatic fistula is the corner stone of patient’s prognosis improvement.The aim of this study on operated pancreatic ductal adenocarcinoma was to analyze several factors influencing morbidity and mortality.- Before surgery, by testing the impact of body surface area in a cohort of patients.- During surgery, by conducting a meta-analysis on reconstruction methods for pancreatic anastomosis.- After surgery, by evaluating the influence of severe complications on survival and recurrence.We show that the use of various surgical refinements, such as type of pancreatic anastomoses, are equivocal to decrease postoperative pancreatic fistula rate and that performing randomized controlled trials will be difficult. In contrast, the search for patient’s factors leading to postoperative pancreatic fistula seems to be the promising approach. This is of major concern as we demonstrated the causal link between the occurrence of severe postoperative complications and survival or recurrence. This work highlights the need for surgeons to distinguish during preoperative consultation high-risk patients in order to select the best candidates suitable for surgery as well as to give them a full and frank information ethically necessary for free and informed consent.

Locally recurrent renal cell carcinoma and multiple pulmonary metastases were successfully resected in a patient 20 years after nephrectomy. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Die vorliegende retrospektive Studie untersuchte die lokale Rezidiv- und Überlebensrate von Patienten mit Plattenepithelkarzinomen in Abhängigkeit vom Randstatus und Resektionsabstand der Tumorresektion sowie von der postoperativen Therapie. Dabei wurden Daten von 351 Patienten mit Plattenepithelkarzinomen des Oropharynx, Hypopharynx und Larynx ausgewertet, welche zwischen 2005 und 2009 reseziert wurden. Der gesundheitliche Zustand der Patienten wurde anschließend bis Dezember 2011 beobachtet. Im Ergebnis konnte kein Einfluss des Randstatus und des Resektionsabstandes auf die lokale Rezidivrate nachgewiesen werden. Beide Faktoren hatten jedoch einen signifikanten Einfluss auf die Letalitätsrate. Die postoperative Therapie zeigte einen positiven Einfluss auf die lokale Rezidivrate. Sie konnte aber die negativen Prognosefaktoren, die eine Indikation dieser Therapie darstellen, bezüglich der Letalitätsrate nicht ausgleichen. Weiterhin war ein positiver Einfluss der postoperativen Therapie auf das rezidivfreie Überleben (DFS-disease-free survival) sowohl uni- als auch multivariat nachweisbar. Die Gesamtüberlebensrate (OS-overall survival) wurde signifikant positiv durch einen geringeren Randstatus und einen zunehmenden Resektionsabstand (ASR Klassifikation) beeinflusst. Das krankheitsspezifische Überleben (DSS-disease-specific survival) sank bei Auftreten eines lokalen Rezidivs. Aus diesen Ergebnissen kann geschlussfolgert werden, dass eine postoperative Therapie zur Kontrolle lokaler Rezidive von hoher Bedeutung ist. Da lokale Rezidive die Überlebensrate signifikant senken, hat die postoperative Therapie indirekt einen positiven Effekt auf das Überleben. Des Weiteren zeigt sich bei Patienten mit freien Resektionsrändern die höchste Überlebensrate, wobei diese mit zunehmendem Abstand des Karzinoms vom Resektionsrand steigt.

Due to the high survival rates of many young cancer patients and a high risk of second tumors, fear of cancer recurrence (FCR) can cause serious impairment for adolescent and young adult (AYA) cancer patients. The aim of this study is to analyze the structure of the Fear of Disease Progression Questionnaire (FoP-Q-12) to better understand the construct of FCR.We performed a cross-sectional survey on a sample of AYA patients aged 15–39 years with different tumor entities. FCR was measured using the FoP-Q-12, and a network analysis was conducted to examine the relationship of FCR symptoms. The importance of individual items in the network was determined using centrality analyses. A total of 247 AYA patients (81.8% female, median age 31.0 years) participated in the study. The mean FCR score in the sample was 35.9 (SD = 9.9). The majority of patients reported having high FCR (59.5%), according to the established cut-off. The two questionnaire items with the strongest association related to fears about work, and the most central symptom was the fear of serious medical interventions. The centrality of emotional issues in the sample indicates that these symptoms should be prioritized in the development of interventions targeting FCR. Further research should address this topic with larger samples of patients in other age groups and in longitudinal studies.

<div>In this thesis we study two different types of self-interacting random walks. First, we study excited random walk in a deterministic, identically-piled cookie environment under the constraint that the total drift contained in the cookies at each site is finite. We show that the walk is recurrent when this parameter is between -1 and 1 and transient when it is less than -1 or greater than 1. In the critical case, we show that the walk is recurrent under a mild assumption on the environment. We also construct an environment where the total drift per site is 1 but in which the walk is transient. This behavior was not present in previously-studied excited random walk models.</div><div><br></div><div>Second, we study the "have your cookie and eat it'' random walk proposed by Pinsky, who already proved criteria for determining when the walk is recurrent or transient and when it is ballistic. We establish limiting distributions for both the hitting times and position of the walk in the transient regime which, depending on the environment, can be either stable or Gaussian.</div>

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