INTRODUÇÃO: O tratamento padrão do Carcinoma Epidermoide do Ânus (CEDA) é a quimiorradioterapia ou radioterapia exclusiva. Os pacientes em que a terapêutica conservadora falha são tratados com Ressecção Abdominoperineal do Reto (RAP) de resgate. OBJETIVOS: Avaliar a sobrevivência com a RAP de resgate no CEDA, identificando os descritores favoráveis para sobrevivência maior e as características do agrupamento de variáveis relacionadas a descritores independentes de risco para mortalidade. MÉTODOS: Foram levantados dados através de 111 prontuários de portadores de CEDA, tratados inicialmente com quimiorradioterapia combinada ou radioterapia exclusiva e submetidos à RAP no período de outubro de 1982 a janeiro de 2011. RESULTADOS: A média de idade foi de 58 anos, 93 (83,8%) pacientes eram do sexo feminino e 80 (72,1%) da raça branca. O estadio cT3-4 compôs 66,7% e cN0 39,6% da casuística. A RAP foi indicada por persistência da doença (PD) em 61 (55%) pacientes e por recidiva (RD) em 50 (45%) pacientes. A ressecção cirúrgica sem resíduos tumorais (R0) foi realizada em 86 (77,5%) pacientes. O tempo médio de permanência hospitalar pós-operatório foi de 14 dias. A morbidade cirúrgica foi de 64,9%, sendo 78,3% dela devida às complicações da região perineal. Recidiva após RAP ocorreu em 68 (61,2%) pacientes, sendo 40 (58,8%) no primeiro ano do pós-operatório, a maioria locorregional (78%; 53/68). A mediana do seguimento foi de 16 meses (1,2-60 meses). Na análise multivariada, cirurgia R0 (p<0,001), invasão perineural vascular e/ou linfática negativa (p<0,0001) e linfonodo negativo na peça cirúrgica (p=0,03) foram estatisticamente associados à maior sobrevivência. CONCLUSÕES: A taxa de sobrevivência global estimada em cinco anos foi de 24,5%, com mediana de sobrevivência de 32 meses. O subgrupo de pacientes submetidos a cirurgias R0 em cujas peças cirúrgicas não foram encontrados invasão perineural vascular e/ou linfática nem linfonodos comprometidos apresentou taxa de sobrevivência estimada em três e cinco anos de 74,4% e 55,0%, respectivamente, com mediana de sobrevivência de 87 meses. Não houve diferença significativa entre pacientes que evoluíram com PD ou RD. Identificou-se a cirurgia R1-2, invasão perineural vascular e/ou linfática e linfonodo positivo na peça cirúrgica como fatores preditivos independentes de mortalidade / INTRODUCTION: The standard treatment for epidermoid carcinoma of the anus (ECA) is the association of chemotherapy (QT) and radiotherapy or exclusive radiotherapy (RT). When conservative treatment fails, patients are submitted to abdominoperineal resection of the rectum (APR). OBJECTIVES: To assess survival with salvage APR in ECA, identifying the most favorable independent descriptors for longer survival and the characteristics of the group of independent variables for mortality risk. METHODS: Data were collected from the medical records of 111 patients with ECA, initially treated with QT/RT or exclusive RT and later submitted to APR, from October 1982 to January 2011. RESULTS: Their mean age was 58 years, 93 (83.8%) patients were female, and 80 (72.1%) were Caucasian. The cT3-4 stage represented 66.7% of the case series and cN0, 39.6%. The APR was indicated due to persistence of disease (PD) in 61 (55%) patients and recurrence of disease (RD) in 50 (45%) patients. Surgical resection without residual tumor (R0) was performed in 86 (77.5%) patients. The mean postoperative hospital length of stay was 14 days. Surgical morbidity was 64.9%, of which, 78.3% related to perineal infection. Recurrence after APR was observed in 68 (61.2%) patients, 40 (58,8%; 40/68) of whom in the first postoperative year, mostly locoregional (78%; 53/68). The median follow-up was 16 months (1.2 - 60 months). On multivariate analysis, R0 surgery (p<0.001), absence of perineural and/or lymphovascular invasion (p<0.0001) and negative lymph node status in the surgical specimen (p=0.03) were associated with increased survival. CONCLUSION: Estimated overall survival rate in 5 years was 24.5%, with median survival of 32 months. There was no significant difference in survival after APR in patients who had PD or RD after conservative treatment. The subgroup of patients who underwent R0 and whose surgical specimen showed absence perineural and/or lymphovascular invasion and negative lymph nodes had an estimated survival rate at 3 and 5 years of 74,4% and 55,0%, respectively, with a median survival of 87 months. The following were identified as independent predictors of mortality: R1-2 surgery; presence perineural and/or lymphovascular invasion; and positive lymph node in the surgical specimen

Introdução: O carcinoma epidermóide de cabeça e pescoço tem na cirurgia e na radioterapia, as principais modalidades terapêuticas iniciais. Nas recidivas loco-regionais, a cirurgia é a escolha padrão de tratamento. Objetivos: Identificação de fatores prognósticos clínicos, histopatológicos e biomoleculares e a avaliação da sobrevida após cirurgia de resgate. Casuística e Métodos: Estudo retrospectivo de pacientes submetidos a tratamento cirúrgico inicial, com revisão de variáveis histopatológicas e expressão imunohistoquímica de VEGF, ciclina d1 e EGF-R no tumor inicial e no resgate. Das recidivas, 10 eram de estádio clínico precoce (I e II) e 18, avançado (III e IV). O período de seguimento médio foi de 33,4 meses. Resultados: A comparação das variáveis histológicas e dos marcadores moleculares no tumor inicial e na recidiva não apresentou alterações estatisticamente significantes. A sobrevida global após cirurgia de resgate foi superior nas recidivas com diagnóstico após seis meses (p=0,02). Conclusões: Os achados sugerem que a expressão de VEGF superior a 75% é fator preditivo para controle da doença após a recidiva. A sobrevida entre o tempo decorrido do tratamento inicial e a recidiva foi estatisticamente significante / Introduction: The usual management of squamous cell carcinoma (SCC) head and neck is the surgery associated or not to post surgical radiotherapy. Salvage surgery is the first therapeutic option for recurrent tumors. Objective: The identification of prognostic factors and to assess survival interval after salvage surgery for SCC. Methods: Retrospective analysis of patients treated with surgery and review of histopathological variables and immunohistochemical expression of VEGF, EGF-R and Ciclina in the initial tumor and salvage surgery. Twenty eight patients were submitted salvage surgery with 10 were staged as early tumors (I and II) and 18 as advanced ones (III and IV). The average follow-up was 33.4 months. Results: The comparison of histopathologicals variables in the initial tumor and loco regional recurrence no statistically significant changes. Survival after salvage surgery was 70% in cases with recurrences diagnosed after six months of follow-up (p=0.02). Conclusions: The findings suggest that variables immunohistopathologicals in loco regional recurrence were of minor importance in prognosis. The time between the initial treatment and recurrence loco regional was independent variable of survival

Submitted by Marcia Silva (marcia@latec.uff.br) on 2016-07-15T20:00:32Z No. of bitstreams: 1 Dissert Luiz Claudio Dias Renato.pdf: 8269957 bytes, checksum: f96703b860281547900a8b1314416b9d (MD5) / Made available in DSpace on 2016-07-15T20:00:32Z (GMT). No. of bitstreams: 1 Dissert Luiz Claudio Dias Renato.pdf: 8269957 bytes, checksum: f96703b860281547900a8b1314416b9d (MD5) Previous issue date: 2016-03-18 / O presente trabalho apresenta os principais aspectos técnicos relacionados ao estudo e análise do contrato de salvamento LOF com a cláusula SCOPIC incorporada. O objetivo deste trabalho é fazer a análise do conceito de salvamento de embarcações no Transporte Marítimo, através de um contrato de salvamento Lloyd’s Open Form (LOF) com a cláusula SCOPIC (Special Conpensation P&I Clause) incorporada ao contrato. Uma vez que há um acidente que envolva um salvamento no mar, há todo um processo a ser seguido, o que envolve a retirada de declarações, a avaliação dos perigos, quer para nomear peritos, escolhendo testemunhas, cálculo dos valores do salvado, prêmio de salvamento, os valores do SCOPIC, desembolsos imediatos, a escolha do SCR (Shipowner Casualty Representative), nomeação dos advogados que representam os salvadores, seguradores de casco e máquinas, P&I e de carga, assim como, a utilização dos conceitos da Convenção Internacional de Salvamento no Mar (CISM 1989), em especial os Artigos 13 e 14. A opção metodológica adotada consistiu numa pesquisa qualitativa por instrumento de questionário eletrônico e levantamento exploratório. Como resultado da aplicação, foi possível verificar que os envolvidos em uma aventura marítima consideram o contrato de salvamento LOF, com a cláusula SCOPIC incorporada, importantíssimo para a atividade comercial de transporte marítimo. Dessa forma o trabalho contribui cientificamente para análises futuras dos valores envolvidos em um prêmio de salvamento, o problema da terceirização dos serviços de salvamento, o dilema do crescente gigantismo dos navios mercantes e suas cargas e uma possível avaliação equivocada das condições do navio na ocasião do salvamento. / This work highlights the main technical aspects related to the study and analysis of the LOF salvage contract with the SCOPIC clause. The objective of this work is to analyze the concept of salvage vessels in maritime transport through a salvage agreement Lloyd's Open Form (LOF) with SCOPIC clause (Special Conpensation P&I Clause) incorporated into the contract. Since there is an accident involving one salvage at sea, there is a whole process to be followed, which involves statements, the hazards assessment, in order to appoint the surveyors and experts, choosing witnesses, calculation of the saved values, salvage award, SCOPIC of values, out of pockets, the choice of SCR (Shipowner Casualty Representatives), appointment of lawyers representing the salvors, H&M insurers (Hull and machinery), P&I Clubs and cargo, as well as the use of the International Convention’s Salvage at Sea (CISM 1989), in highlight the Articles 13 and 14. The method adopted. The methodological option adopted consisted of a search for "survey" and exploratory survey. As a result of the application, it found that those involved in a maritime adventure consider the LOF salvage contract with SCOPIC clause incorporated important to the shipping industry. This work contributes scientifically to further analyzes of the amounts involved in a salvage award, the problem of outsourcing of the salvage services, the dilemma of growing gigantism of merchant ships and their

To address the scale mountain pine beetle (MPB) outbreak in British Columbia, salvage has become fully integrated with timber supply strategies. The objective of this thesis is to assess the economic impact of different salvage strategies depending on different attack levels, decay rates, and stakeholder discount rates. The study area is located in N.E. British Columbia where the MPB has not yet reached its peak and where susceptible to attack stands account for 40% of the area. Salvage strategies were modelled with a timber supply model (Woodstock) which uses a linear programming type II optimization approach. Performance of the model was assessed over a range of indicators such as NPV, profit, salvage proportion, species composition, inventory levels, and non-recoverable volume. Sensitivity analyses were conducted on harvest flow, discount rate, and ending inventory. The model was very sensitive to the intensity of attack and less sensitive to the decay level. The high level of attack resulted in large volume losses, mostly as un-salvaged inventory. Although allowable annual cut (AAC) uplifts have an economic benefit, they do not necessarily maximize the salvage of pine. Non-pine species are an important component of the salvage and these species are also essential for the future timber supply. If the objective is to ensure quality and quantity of the future forest, policies have to complement AAC uplifts by strongly encouraging the salvage of mainly pine-leading stands and management options that minimize the “by-catch” of non-pine species and minimize destruction of advanced regeneration during salvage. However, this has an opportunity cost for the private industry where the objective is to maximize profit. If the salvage strategy focuses on decreasing the impact on cash flows, achieving desirable ending inventory levels, avoiding salvage of stands after shelf-life, and reducing impact on non-attack species, then the current harvest level will likely lead to a mid-term timber supply fall-down. Using the fibre for bioenergy production is an alternative if managing for bioenergy can be integrated into harvest operations. However, unlike mill residues, the bioenergy supply has to fully account for harvest and transportation costs of dead wood to the mill. / Forestry, Faculty of / Graduate

Municipal solid waste management is gradually becoming a major challenge that is confronting governments in all spheres. This can be attributed to urbanisation and startling population escalation. Each and every member in a community is a contributor to this dilemma and a generator of waste. The essence of this study is to investigate whether the utilisation of education programmes can assist to improve how communities handle and dispose their household waste and its contribution to the effectiveness of the integrated solid waste management system for the New Brighton Township in the Nelson Mandela Bay Municipality. A theoretical framework is developed using the systems theory in trying to address the challenge. The study used the qualitative research method. Data were gathered using questionnaires and face-to face interviews. The empirical survey was employed for the purposes of the study and the interpretation of the research findings were analysed and described. As a metropolitan municipality, it is envisaged that this research will assist the NMBM, to identify how to manage solid waste efficiently and effectively and thus enhancing service delivery that will ensure communities of their well-being and dignity. Various recommendations are presented, based on the findings of the study. It is hoped that these recommendations If are adopted, the NMBM will be able to deal more effectively and efficiently with the challenges that the NMBM is faced with in dealing with waste management issues thereby enabling the NMBM to deliver the most basic need to the communities of the New Brighton Townships.

Trotz der zunehmenden Bedeutung von freien Lappenplastiken stellen gefäßgestielte Suralis-Lappenplastiken weiterhin eine zuverlässige Methode zur Defektdeckung an der unteren Extremität dar. In der Arbeit werden 19 Fälle untersucht, bei denen eine Suralis-Lappenplastik durchgeführt wurde. Die Patientenzufriedenheit wird anhand funktioneller und ästhetischer Gesichtspunkte mittels eines standardisierten Fragebogens erfasst. Aus der ärztlichen Dokumentation werden notwendige Revisionseingriffe, stationäre und ambulante Behandlungszeiten, Nebenerkrankungen und die Erlössituation im DRG-System ausgewertet. Zudem wird im Rahmen einer anatomischen Studie an einem Leichenpräparat ein Suralis-Lappen gehoben und eine Fotodokumentation angefertigt.:1. Einleitung 2. Grundlagen 3. Material und Methoden 4. Ergebnisse 5. Diskussion 6. Zusammenfassung 7. Literaturverzeichnis 8. Anhang / Although the increasing meaning of free flaps the pedicled sural flap is a save method of covering defect wounds on lower limbs. In this report 19 cases of sural flap coverage are examined. The level of satisfaction of patients is measured by functional and aesthetic aspects using a standardised survey. Number of necessary revision operations, time of treatment, side diseases, and DRG based profit is determinded by the medical documentation. Furthermore an anatomic study is done showing the surgical raising of a sural flap.:1. Einleitung 2. Grundlagen 3. Material und Methoden 4. Ergebnisse 5. Diskussion 6. Zusammenfassung 7. Literaturverzeichnis 8. Anhang

NAMPT (Nicotinamide phosphoribosyltransferase) catalyses the rate-limiting step in the NAD biosynthesis from nicotinamide and thereby regulates the activity of NAD-dependent enzymes. Cancer cells are highly dependent on NAD for energy and DNA repair processes and are assumed to be more susceptible to an inhibition of NAD synthesis than non-transformed cells. We aimed to investigate whether or not inhibition of NAMPT with its specific inhibitor FK866 can sensitize leukemia cells for chemotherapeutic agents. NAMPT protein abundance, enzymatic activity and NAD concentrations were significantly higher in Jurkat and Molt-4 leukemia cell lines compared to normal peripheral blood mononuclear cells. Combination of etoposide and FK866 caused increased cell death in leukemia cell lines compared to etoposide alone. Etoposide decreased protein abundance of NAD-dependent deacetylases SIRTUIN1. After combining etoposide and FK866 treatment SIRTUIN2 was further decreased and accumulation and acetylation of the downstream target p53 was further enhanced in MOLT4 cells. Concomitantly, protein abundance of p21 and cleaved BAX was increased. Targeting NAMPT could be a novel therapeutic strategy to enhance the efficacy of chemotherapeutic agents such as etoposide against leukemia.

I marknadsrapporter går att läsa att samhällsfastigheter är en lågriskplacering där investerare söker säker hamn när det börjar blåsa. I Catella Property Forecast (2019) bedöms samhällsfastigheter som låg risk med medel-till-hög avkastning. Den underliggande efterfrågan på samhällsfastigheter i Sverige drivs av den demografiska utvecklingen och framgent behövs stora investeringar för att möta behovet bland landets kommuner och landsting. Hos investerarkollegiet har samhällsfastigheter seglat upp som ett alltmer populärt segment och i en marknadsrapport från Pangea Property Partners kommuniceras att samhällsfastigheter är den mest eftertraktade produkten bland institutionella investerare på fastighetsmarknaden i Sverige (Pangea Institutional Outlook, 2019). På grund av dess beskaffenhet bedöms risk och osäkerhet för investeringar i samhällsfastigheter som relativt låg under kontraktsperioden där ekonomiskt stabila hyresgäster säkerställer ett kassaflöde under långa hyresförhållanden. Hyresgästrisken och vakansrisken är i princip obefintlig under de långa hyreskontraktens löptid. Dock behäftas fastigheterna alltid, likt alla fastigheter, med en viss risk som kan härledas till exempelvis teknisk risk och miljörisk. Utöver dessa tillkommer även politisk risk samt juridiska risker. Specifikt för samhällsfastigheter är att de, per definition, är specialanpassade för verksamheten vilket kraftigt begränsar dess alternativa användning. Alla ovan nämnda parametrar ska speglas i en marknadsvärdesbedömning utförd av en registrerad värderare. Marknadsvärdesbedömningar är centrala i beslutsfattandet vilket föranleder att det är av största vikt att de är rättvisande. Då investerare känner komfort för de förhållanden som råder under löptiden för de långa avtalen är det intressant att granska synen på dessa fastigheter då kontrakten har löpt ut. Syftet med denna fallstudie är att genomlysa hur restvärdet för samhällsfastigheter bedöms av värderare med hänsyn till osäkerhet och risk. Värdering av fastigheter sker vanligen med kassaflödesmetoden som bygger på att framtida driftnetton under en given kalkylperiod diskonteras. Till detta värde adderas ett diskonterat restvärde som ska motsvara fastighetens värde vid slutet av kalkylperioden vilket ofta sammanfaller med att hyreskontraktet löper ut. Metoden bygger till stor del på prognostisering av framtiden. Följaktligen är värderingar behäftade med osäkerhet. Hur riskerna och osäkerheterna behandlas i värderingen kommer att framgå av resultatet. Studien visar att värderanas syn på restvärdesrisken för samhällsfastigheter är nästintill enhetlig och bygger ur teoretisk synvinkel på en objektiv bedömning av värderingsobjektets egenskaper och förutsättningar vid kalkylperiodens slut. Här bedöms ingående parametrar så som geografiskt läge, fastighetens kvalitet och standard men även politisk risk och vad byggnaden är anpassad till i dagsläget. Det framkommer även hur centralt sambandet mellan initial direktavkastning, exit yield och marknadens avkastningskrav är i bedömningen. Studien visar även att värderare bedömer att investerare inte fullt ut tar hänsyn till restvärdesrisken på de nivåer som transaktioner sker till i dagsläget. / Currently, there is strong investor demand for public property in Sweden with yields declining for both prime and secondary segments of the market. The underlying demand for properties relating to education and elderly care is expected to be high for years to come as a result of a growing population and other demographic changes. Investments in public property is considered low risk due to the long-term leases with financially strong and stable tenants. The occupancy rate for public property is high, partly due to the fact that single tenant properties are a regular occurrence and partly because the high demand. All investments are associated with risk, the character of which varies depending on the type of property and various other factors. Technical risk, political risk and environmental risks to name a few. Public properties are, per definition, properties that primarily houses tax-financed operators and that is customized for public services. Because of the specialized nature of these assets and the fact that they are difficult to convert to other uses the question of risk and uncertainty arise at the end of the lease period. When valuing a property using the discounted cash flow method this moment in time in when the terminal value is evaluated. The aim of this case study is to examine how valuers assess the risk and uncertainty associated with the terminal value of public property in Sweden. Through analysis of the external valuations that have been undertaken at one of Sweden’s largest owner of public properties for the end of year 2018 the objective is to find factors related to the terminal value that differ between properties intended for educational purposes and those for elderly care. By conducting interviews with external valuers, the report will outline what aspects of a property valuers examine in determining the terminal value. Information gathered in the interviews will be used to analyze the valuations that were carried out for the end of year reporting of Sweden’s largest owner of public property. The report starts with a review of the fundamentals of valuation which later in the report will be applied to the empirical data to create a framework from which determination of the risk associated with the terminal value of public property can be judged. Furthermore, the report will seek to understand the bridge between theory and practice in the subject.

S-Adenosyl-L-methionine (SAM) is an essential metabolite for all domains of life. SAM- dependent reactions result in three major metabolites: S-adenosyl-L-homocysteine (SAH), methylthioadenosine (MTA), and 5'-deoxyadenosine (5'-dA). Each of these has been demonstrated to be feedback inhibitors of SAM dependent enzymes. Thus, each metabolite has a pathway to prevent inhibition through the salvage of nucleoside and ribose moieties. However, these salvage pathways are not universally conserved. In the anaerobic archaeal organism Methanocaldococcus jannaschii, the salvage of SAH, MTA, and 5'-dA, proceeds first via deamination to S-inosylhomocysteine (SIH), methylthioinosine (MTI), and 5'-deoxyinosine (5'-dI). The annotated SAH hydrolase from M. jannaschii is specific for SIH and the hydrolyzed product homocysteine is then methylated to methionine. The salvage of MTA is known to proceed through the methionine salvage pathway, however, an anaerobic route for the salvage of MTA is still mostly unknown. Only two enzymes from the methionine salvage pathway are annotated in M. jannaschii's proteome, a methylthioinosine phosphorylase (MTIP) and methylthioribose 1-phosphate isomerase (MTRI). These enzymes were shown to produce methylthioribulose 1-phosphate from MTI. Unfortunately, how MTI is converted to either 2-keto-(4-methylthio)butyrate or methionine remains unknown. The two enzymes involved in the salvage of MTI have also been demonstrated to be involved in the salvage of 5'-dI. Interestingly, there is little information on how 5'-dA or 5'-dI is recycled and it is proposed here to be the source of deoxysugars for the production methylglyoxal, a precursor for aromatic amino acids. MTIP and MTRI were demonstrated to produce 5-deoxyribulose 1-phosphate from 5'-dI. Additionally, two enzymes annotated as part of the pentose phosphate pathway, ribulose 5-phosphate 3-epimerase and transketolase, were able to convert 5-deoxyribulose 1-phosphate to lactaldehyde. Lactaldehyde was then reduced to methylglyoxal by an essential enzyme in methanogenesis, N5, N10-methylenetetahydromethanopterin reductase with NADPH. These results further demonstrate a novel route for the biosynthesis of methylglyoxal. Lastly, hypoxanthine produced from phosphorolysis of inosine, MTI, and 5'-dI was demonstrated to be reincorporated through the hypoxanthine/guanine phosphoribosyltransferase (Hpt) to IMP. Together these reactions represent novel pathways for the salvage of the SAM nucleoside and ribose moieties in M. jannaschii. / Ph. D.

Principe de droit coutumier longtemps honoré, le droit de refuge n’est plus. Les catastrophes de l’« Erika » et du « Prestige », et entre les deux, le périple du « Castor », ont largement mis en lumière cette réalité. À l’origine de ce déclin, les progrès techniques. Certains ayant permis la sauvegarde des marins en perdition sans nécessiter le déroutement du navire vers un abri. D’autres ayant eu pour conséquence de rendre dangereux et polluants la navigation.Le phénomène dit de « lèpre maritime » fut la constante, la pratique adoptée par les États côtiers confrontés à des navires en difficulté susceptibles de porter atteinte à leurs intérêts. Décrit ainsi, le réflexe se perçoit comme légitime. Mais voilà, l’automatisme peut pousser à l’absurde alors que les progrès, encore eux mais a contrario cette fois-ci, permettent de mesurer et tempérer les risques et ainsi revenir vers la voie naturelle du refuge même en présence de navires potentiellement dangereux et/ou polluants / Principle of customary international law which was honored a long time, the right of refuge for ships in distress is in the present day eroded. The disasters of the « Erika » and the « Prestige », and between these two, the event of the « Castor », have largely emphasized this reality.At the origin of this decline, we found technical progresses. Some having permitted rescue of the sailors in distress without requiring the ship to be granted a safe haven. Others having had for consequence to make navigation dangerous and pollutant.The phenomenon known as of « maritime lepers » has been the constant, the practice adopted by the coastal States confronted with ships in distress likely to threaten their interests. Described in this manner, the reflex can be perceived like legitimate. But, the automatism can conduct to the absurdity whereas progresses, but a contrario this time, make possible to measure and moderate the risks and, in consequence, to return towards the natural way of the refuge even in the presence of potentially dangerous and/or polluting ships