The Protection of Traditional Knowledge Associated with Genetic Resources: The Role of Databases and Registers

"The Protection of Traditional Knowledge Associated with Genetic Resources: The Role of Databases and Registers" ABSTRACT Yovana Reyes Tagle The misappropriation of TK has sparked a search for national and international laws to govern the use of indigenous peoples knowledge and protection against its commercial exploitation. There is a widespread perception that biopiracy or illegal access to genetic resources and associated traditional knowledge (TK) continues despite national and regional efforts to address this concern. The purpose of this research is to address the question of how documentation of TK through databases and registers could protect TK, in light of indigenous peoples increasing demands to control their knowledge and benefit from its use. Throughout the international debate over the protection of TK, various options have been brought up and discussed. At its core, the discussion over the legal protection of TK comes down to these issues: 1) The doctrinal question: What is protection of TK? 2) The methodological question: How can protection of TK be achieved? 3) The legal question: What should be protected? And 4) The policy questions: Who has rights and how should they be implemented? What kind of rights should indigenous peoples have over their TK? What are the central concerns the TK databases want to solve? The acceptance of TK databases and registers may bring with it both opportunities and dangers. How can the rights of indigenous peoples over their documented knowledge be assured? Documentation of TK was envisaged as a means to protect TK, but there are concerns about how documented TK can be protected from misappropriation. The methodology used in this research seeks to contribute to the understanding of the protection of TK. The steps taken in this research attempt to describe and to explain a) what has been done to protect TK through databases and registers, b) how this protection is taking place, and c) why the establishment of TK databases can or cannot be useful for the protection of TK. The selected case studies (Peru and Venezuela) seek to illustrate the complexity and multidisciplinary nature of the establishment of TK databases, which entail not only legal but also political, socio-economic and cultural issues. The study offers some conclusions and recommendations that have emerged after reviewing the national experiences, international instruments, work of international organizations, and indigenous peoples perspectives. This thesis concludes that if TK is to be protected from disclosure and unauthorized use, confidential databases are required. Finally, the TK database strategy needs to be strengthened by the legal protection of the TK itself.

Cystatin C, a measure of renal function, as prognostic risk marker in acute heart failure : Studies on the cardiorenal syndrome

Acute heart failure (AHF) is a complex syndrome associated with exceptionally high mortality. Still, characteristics and prognostic factors of contemporary AHF patients have been inadequately studied. Kidney function has emerged as a very powerful prognostic risk factor in cardiovascular disease. This is believed to be the consequence of an interaction between the heart and kidneys, also termed the cardiorenal syndrome, the mechanisms of which are not fully understood. Renal insufficiency is common in heart failure and of particular interest for predicting outcome in AHF. Cystatin C (CysC) is a marker of glomerular filtration rate with properties making it a prospective alternative to the currently used measure creatinine for assessment of renal function. The aim of this thesis is to characterize a representative cohort of patients hospitalized for AHF and to identify risk factors for poor outcome in AHF. In particular, the role of CysC as a marker of renal function is evaluated, including examination of the value of CysC as a predictor of mortality in AHF. The FINN-AKVA (Finnish Acute Heart Failure) study is a national prospective multicenter study conducted to investigate the clinical presentation, aetiology and treatment of, as well as concomitant diseases and outcome in, AHF. Patients hospitalized for AHF were enrolled in the FINN-AKVA study, and mortality was followed for 12 months. The mean age of patients with AHF is 75 years and they frequently have both cardiovascular and non-cardiovascular co-morbidities. The mortality after hospitalization for AHF is high, rising to 27% by 12 months. The present study shows that renal dysfunction is very common in AHF. CysC detects impaired renal function in forty percent of patients. Renal function, measured by CysC, is one of the strongest predictors of mortality independently of other prognostic risk markers, such as age, gender, co-morbidities and systolic blood pressure on admission. Moreover, in patients with normal creatinine values, elevated CysC is associated with a marked increase in mortality. Acute kidney injury, defined as an increase in CysC within 48 hours of hospital admission, occurs in a significant proportion of patients and is associated with increased short- and mid-term mortality. The results suggest that CysC can be used for risk stratification in AHF. Markers of inflammation are elevated both in heart failure and in chronic kidney disease, and inflammation is one of the mechanisms thought to mediate heart-kidney interactions in the cardiorenal syndrome. Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) correlate very differently to markers of cardiac stress and renal function. In particular, TNF-α showed a robust correlation to CysC, but was not associated with levels of NT-proBNP, a marker of hemodynamic cardiac stress. Compared to CysC, the inflammatory markers were not strongly related to mortality in AHF. In conclusion, patients with AHF are elderly with multiple co-morbidities, and renal dysfunction is very common. CysC demonstrates good diagnostic properties both in identifying impaired renal function and acute kidney injury in patients with AHF. CysC, as a measure of renal function, is also a powerful prognostic marker in AHF. CysC shows promise as a marker for assessment of kidney function and risk stratification in patients hospitalized for AHF.

Down, You Vagabond of a Heart! : Romance and Created Personas in the Journals of L. M. Montgomery

Kanadalainen kirjailija L. M. (Ludy Maud) Montgomery (1874-1942) tunnetaan parhaiten lasten ja nuorten kirjallisuudestaan, erityisesti Anne of Green Gables -romaanistaan (suom. Annan nuoruusvuodet). Graduni tutkii kuitenkin Montgomeryn vähemmän tunnettua omaelämäkerrallista tuotantoa, hänen päiväkirjojaan, jotka on julkaistu viidessä osassa (1985-2004). Keskityn romanssin kuvaukseen Montgomeryn päiväkirjojen ensimmäisessä osassa ja tutkin, millaisia tekstuaalisia persoonia (personas) kertoja luo autobiografisessa prosessissa. Tähän narratiiviseen prosessiin vaikuttavat erityisesti päiväkirjan yleisö tai lukijat (audience), samoin kuin fiktiiviset esikuvat ja fiktiivisesti kirjoittaminen (fictionalisation) sekä kysymys päiväkirjan kertovasta ja kerrotusta minästä (narrated and narrating I). Romanssi on pääosassa Montgomeryn päiväkirjojen ensimmäisessä julkaistussa osassa, joka kuvaa hänen teini- ja varhaisaikuisuusvuosiaan. Väitän, että vaikka päiväkirjateksti saattaa vaikuttaa rehelliseltä ja todenmukaiselta kuvaukselta elämästä, varsinkin Montgomeryn tapauksessa kyseessä on silti läpikotaisin editoitu ja muokattu teksti, jota päiväkirjan tekijä hallitsee rautaisella otteella ja joka käyttää hyväkseen fiktiivisiä keinoja. Aineistonani käytän sekä Montgomeryn julkaistuja että julkaisemattomia päiväkirjoja, joita säilytetään University of Guelphin arkistoissa, Kanadan Ontariossa. Päiväkirjat ovat moneen kertaan sekä Montgomeryn että julkaistujen päiväkirjojen editoijien muokkaamia, joten niiden tutkiminen lähilukemalla (close-reading) ja eri versioita vertaillen on erityisen tärkeää. Teorian osalta keskityn lähinnä Pohjois-Amerikassa kirjoitettuun autobiografia- ja (naisten) päiväkirjatutkimukseen. Väitän gradussani, että Montgomeryn kuvaus heteroseksuaalisesta romanssista välttää tarjoamasta lukijalle romanssijuonen tyypillistä katharsista. Montgomeryn romanttiset persoonat ovat yllättävän epäromanttisia ja ristiriidassa keskenään. Romantiikan traditiolle tyypillistä kieltä ja personifikaatiota käytetään joko korostetun liioitellusti tai humoristisesti ja parodioiden.

When sharing becomes a liability: An intellectual capital approach to describing the dichotomy of knowledge protection versus sharing in intra- and interorganizational relationships

The tension created when companies are collaborating with competitors – sometimes termed co-opetition - has been subject of research within the network approach. As companies are collaborating with competitors, they need to simultaneously share and protect knowledge. The opportunistic behavior and learning intent of the partner may be underestimated, and collaboration may involve significant risks of loss of competitive edge. Contrastingly, the central tenet within the Intellectual Capital approach is that knowledge grows as it flows. The person sharing does not lose the knowledge and therefore knowledge has doubled from a company’s point of view. Value is created through the interplay of knowledge flows between and within three forms of intellectual capital: human, structural and relational capital. These are the points of departure for the research conducted in this thesis. The thesis investigates the tension between collaboration and competition through an Intellectual Capital lens, by identifying the actions taken to share and protect knowledge in interorganizational collaborative relationships. More specifically, it explores the tension in knowledge flows aimed at protecting and sharing knowledge, and their effect on the value creation of a company. It is assumed, that as two companies work closely together, the collaborative relationship becomes intertwined between the two partners and the intellectual capital flows of both companies are affected. The research finds that companies commonly protect knowledge also in close and long-term collaborative relationships. The knowledge flows identified are both collaborative and protective, with the result that they sometimes are counteracting and neutralize each other. The thesis contributes to the intellectual capital approach by expanding the understanding of knowledge protection in interorganizational relationships in three ways. First, departing from the research on co-opetition it shifts the focus from the internal view of the company as a repository of intellectual capital onto the collaborative relationships between competing companies. Second, instead of the traditional collaborative and sharing point of departure, it takes a competitive and protective perspective. Third, it identifies the intellectual capital flows as assets or liabilities depending on their effect on the value creation of the company. The actions taken to protect knowledge in an interorganizational relationship may decrease the value created in the company, which would make them liabilities.

Molecular mechanisms of hypertension-induced heart failure : Experimental studies with special emphasis on local renin-angiotensin system, cardiac metabolism and levosimendan

Hypertension is a major risk factor for stroke, ischaemic heart disease, and the development of heart failure. Hypertension-induced heart failure is usually preceded by the development of left ventricular hypertrophy (LVH), which represents an adaptive and compensatory response to the increased cardiac workload. Biomechanical stress and neurohumoral activation are the most important triggers of pathologic hypertrophy and the transition of cardiac hypertrophy to heart failure. Non-clinical and clinical studies have also revealed derangements of energy metabolism in hypertensive heart failure. The goal of this study was to investigate in experimental models the molecular mechanisms and signalling pathways involved in hypertension-induced heart failure with special emphasis on local renin-angiotensin-aldosterone system (RAAS), cardiac metabolism, and calcium sensitizers, a novel class of inotropic agents used currently in the treatment of acute decompensated heart failure. Two different animal models of hypertensive heart failure were used in the present study, i.e. hypertensive and salt-sensitive Dahl/Rapp rats on a high salt diet (a salt-sensitive model of hypertensive heart failure) and double transgenic rats (dTGR) harboring human renin and human angiotensinogen genes (a transgenic model of hypertensive heart failure with increased local RAAS activity). The influence of angiotensin II (Ang II) on cardiac substrate utilization and cardiac metabolomic profile was investigated by using gas chromatography coupled to time-of-flight mass spectrometry to detect 247 intermediary metabolites. It was found that Ang II could alter cardiac metabolomics both in normotensive and hypertensive rats in an Ang II receptor type 1 (AT1)-dependent manner. A distinct substrate use from fatty acid oxidation towards glycolysis was found in dTGR. Altered cardiac substrate utilization in dTGR was associated with mitochondrial dysfunction. Cardiac expression of the redox-sensitive metabolic sensor sirtuin1 (SIRT1) was increased in dTGR. Resveratrol supplementation prevented cardiovascular mortality and ameliorated Ang II-induced cardiac remodeling in dTGR via blood pressure-dependent pathways and mechanisms linked to increased mitochondrial biogenesis. Resveratrol dose-dependently increased SIRT1 activity in vitro. Oral levosimendan treatment was also found to improve survival and systolic function in dTGR via blood pressure-independent mechanisms, and ameliorate Ang II-induced coronary and cardiomyocyte damage. Finally, using Dahl/Rapp rats it was demonstrated that oral levosimendan as well as the AT1 receptor antagonist valsartan improved survival and prevented cardiac remodeling. The beneficial effects of levosimendan were associated with improved diastolic function without significantly improved systolic changes. These positive effects were potentiated when the drug combination was administered. In conclusion, the present study points to an important role for local RAAS in the pathophysiology of hypertension-induced heart failure as well as its involvement as a regulator of cardiac substrate utilization and mitochondrial function. Our findings suggest a therapeutic role for natural polyphenol resveratrol and calcium sensitizer, levosimendan, and the novel drug combination of valsartan and levosimendan, in prevention of hypertension-induced heart failure. The present study also provides a better understanding of the pathophysiology of hypertension-induced heart failure, and may help identify potential targets for novel therapeutic interventions.

The struggle for protection of environmental refugees: who's responsibility? Discourses from the United Nations and Non-governmental organizations

This thesis identifies, examines and problematizes some of the discourses that have so far come to light on the issue of protection for environmental refugees. By analyzing the discourses produced by the United Nations Office of the High Commissioner for Refugees (UNHCR) and two non-governmental organizations - the Environmental Justice Foundation (EJF) and Equity and Justice Working Group Bangladesh (EquityBD), I examine the struggling discourses that have emerged about how protection for environmental refugees has been interpreted. To do this, I rely on Ernesto Laclau and Chantal Mouffe's theory and method of discourse analysis. The results show that responsibilization is the main point of struggle in the discussions on the protection of environmental refugees. As a floating signifier, it was utilized by the discourses produced by the UNCHR and the selected NGOs in contingent ways and with different political objectives. The UNHCR discourse responsibilized both the environmental refugees for their own protection and the individual states. The EJF and EquityBD, by contrast, allocated responsibility for the protection of environmental refugees to the international community. These contingent understandings of responsibilization necessitated different justifications. While the EJF discourse relied on humanitarianism for the assistance of environmental refugees, the EquityBD discourse constructed a rights based, more permanent solution. The humanitarian based discourse of the EJF was found to be inextricably linked with the neoliberal discourse produced by the UNHCR. Both these discourses encouraged environmental refugees to stay in their homelands, undermining the politics of protection. Another way in which protection was undermined was by UNHCR's discourse on securitization. In this context, climate change induced displacement became threat to developed countries, the global economy and transnational classes. The struggling discourses about who/what has been allocated responsibility for the protection of environmental refugees also meant that identities of the displaced be constructed in specific ways. While the UNHCR discourse constructed as voluntary migrants and predators, the EJF and EquityBD discourses portrayed them as victims. However, even though the EJF discourse constructed them as victims, their reliance on humanitarianism could also be interpreted as a way of giving the environmental refugee a predator like identity. These discourses on responsibilization and identity formation clashed with each other in the aim of achieving a hegemonic position in discussions and debates about the protection of environmental refugees.

The struggle for protection of environmental refugees: who's responsibility? Discourses from the United Nations and Non-governmental organizations

This thesis identifies, examines and problematizes some of the discourses that have so far come to light on the issue of protection for environmental refugees. By analyzing the discourses produced by the United Nations Office of the High Commissioner for Refugees (UNHCR) and two non-governmental organizations - the Environmental Justice Foundation (EJF) and Equity and Justice Working Group Bangladesh (EquityBD), I examine the struggling discourses that have emerged about how protection for environmental refugees has been interpreted. To do this, I rely on Ernesto Laclau and Chantal Mouffe's theory and method of discourse analysis. The results show that responsibilization is the main point of struggle in the discussions on the protection of environmental refugees. As a floating signifier, it was utilized by the discourses produced by the UNCHR and the selected NGOs in contingent ways and with different political objectives. The UNHCR discourse responsibilized both the environmental refugees for their own protection and the individual states. The EJF and EquityBD, by contrast, allocated responsibility for the protection of environmental refugees to the international community. These contingent understandings of responsibilization necessitated different justifications. While the EJF discourse relied on humanitarianism for the assistance of environmental refugees, the EquityBD discourse constructed a rights based, more permanent solution. The humanitarian based discourse of the EJF was found to be inextricably linked with the neoliberal discourse produced by the UNHCR. Both these discourses encouraged environmental refugees to stay in their homelands, undermining the politics of protection. Another way in which protection was undermined was by UNHCR's discourse on securitization. In this context, climate change induced displacement became threat to developed countries, the global economy and transnational classes. The struggling discourses about who/what has been allocated responsibility for the protection of environmental refugees also meant that identities of the displaced be constructed in specific ways. While the UNHCR discourse constructed as voluntary migrants and predators, the EJF and EquityBD discourses portrayed them as victims. However, even though the EJF discourse constructed them as victims, their reliance on humanitarianism could also be interpreted as a way of giving the environmental refugee a predator like identity. These discourses on responsibilization and identity formation clashed with each other in the aim of achieving a hegemonic position in discussions and debates about the protection of environmental refugees.

Levosimendaanin vaikutusmekanismi ja nykyinen merkitys sydämen vajaatoiminnan hoidossa

Sydämen vajaatoiminta on erilaisista sydän- ja verisuonisairauksista aiheutuva monimuotoinen oireyhtymä, johon sairastuneiden ja kuolleiden potilaiden määrä on yhä suuri. Sen patofysiologiaan voi kuulua muun muassa sympaattisen hermoston ja reniini-angiotensiini-aldosteroni–järjestelmän aktiivisuutta, huonosti supistuva vasen kammio, sydämen uudelleenmuokkautumista, muutoksia [Ca2+]i:n säätelyssä, kardiomyosyyttien apoptoosia sekä systeeminen tulehdustila. Johonkin osaan sairauden patofysiologiasta eivät nykyiset lääkehoidot riittävästi vaikuta. Klassiset inotroopit lisäävät sydämen supistusvireyttä kasvattamalla solunsisäistä Ca2+-pitoisuutta, mutta ne lisäävät rytmihäiriöriskiä, sydämen hapenkulutusta sekä heikentävät ennustetta. Levosimendaani, kalsiumherkistäjä, lisää sydämen supistusvoimaa [Ca2+]i:ta kohottamatta herkistämällä sydänlihaksen kalsiumin vaikutuksille. Lisäksi levosimendaani avaa sarkolemmaalisia ja mitokondriaalisia K+-kanavia, jotka välittävät vasodilataatiota ja kardioprotektiota. Suurilla annoksilla levosimendaani on selektiivinen PDE3-estäjä. Levosimendaania suositellaan äkillisesti pahentuneen sydämen vajaatoiminnan hoitoon, mutta muitakin lupaavia indikaatioita sille on keksitty. Esimerkiksi kroonisesti annosteltu oraalinen levosimendaani on suojannut kardiovaskulaarijärjestelmää ja parantanut selviytymistä in vivo. Erikoistyössä selvitettiin kroonisesti annostellun oraalisen levosimendaanin, valsartaanin ja näiden kombinaatioterapian vaikutuksia selviytymiseen, verenpaineeseen sekä sydämen hypertrofioitumiseen Dahlin suolaherkillä (Dahl/Rapp) rotilla. Levosimendaanin suojavaikutus ilmeni vähäisempänä kuolleisuutena, mutta ero ei ollut tilastollisesti merkitsevä kontrolliryhmään nähden. Kombinaatioterapia suojasi rottia kardiovaskulaarikuolleisuudelta ja vähensi todennäköisesti verenpaineesta riippuvaisesti sydämen hypertofioitumista niin sydän/kehonpaino–suhteen kuin ultraäänitutkimuksenkin perusteella arvioituna paremmin kuin kumpikaan lääke monoterapiana. Lääkekombinaatio alensi additiivisesti hypertensiota kaikissa mittauspisteissä. Sydämen systolista toimintaa levosimendaani kohensi vain vähäisesti. Dahl/Rapp-rotille kehittyikin pääosin hypertension indusoimaa diastolista sydämen vajaatoimintaa kohonneen IVRT-arvon perusteella. Levosimendaani sekä monoterapiana että kombinaatioterapiana valsartaanin kanssa vähensi sydämen diastolista vajaatoimintaa.