Drug Analysis without Primary Reference Standards : Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material

Drug Analysis without Primary Reference Standards: Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material Primary reference standards for new drugs, metabolites, designer drugs or rare substances may not be obtainable within a reasonable period of time or their availability may also be hindered by extensive administrative requirements. Standards are usually costly and may have a limited shelf life. Finally, many compounds are not available commercially and sometimes not at all. A new approach within forensic and clinical drug analysis involves substance identification based on accurate mass measurement by liquid chromatography coupled with time-of-flight mass spectrometry (LC-TOFMS) and quantification by LC coupled with chemiluminescence nitrogen detection (LC-CLND) possessing equimolar response to nitrogen. Formula-based identification relies on the fact that the accurate mass of an ion from a chemical compound corresponds to the elemental composition of that compound. Single-calibrant nitrogen based quantification is feasible with a nitrogen-specific detector since approximately 90% of drugs contain nitrogen. A method was developed for toxicological drug screening in 1 ml urine samples by LC-TOFMS. A large target database of exact monoisotopic masses was constructed, representing the elemental formulae of reference drugs and their metabolites. Identification was based on matching the sample component s measured parameters with those in the database, including accurate mass and retention time, if available. In addition, an algorithm for isotopic pattern match (SigmaFit) was applied. Differences in ion abundance in urine extracts did not affect the mass accuracy or the SigmaFit values. For routine screening practice, a mass tolerance of 10 ppm and a SigmaFit tolerance of 0.03 were established. Seized street drug samples were analysed instantly by LC-TOFMS and LC-CLND, using a dilute and shoot approach. In the quantitative analysis of amphetamine, heroin and cocaine findings, the mean relative difference between the results of LC-CLND and the reference methods was only 11%. In blood specimens, liquid-liquid extraction recoveries for basic lipophilic drugs were first established and the validity of the generic extraction recovery-corrected single-calibrant LC-CLND was then verified with proficiency test samples. The mean accuracy was 24% and 17% for plasma and whole blood samples, respectively, all results falling within the confidence range of the reference concentrations. Further, metabolic ratios for the opioid drug tramadol were determined in a pharmacogenetic study setting. Extraction recovery estimation, based on model compounds with similar physicochemical characteristics, produced clinically feasible results without reference standards.

Monopolising Names? : The Protection of Geographical Indications in the European Community

Marketing of goods under geographical names has always been common. Aims to prevent abuse have given rise to separate forms of legal protection for geographical indications (GIs) both nationally and internationally. The European Community (EC) has also gradually enacted its own legal regime to protect geographical indications. The legal protection of GIs has traditionally been based on the idea that geographical origin endows a product exclusive qualities and characteristics. In today s world we are able to replicate almost any prod-uct anywhere, including its qualities and characteristics. One would think that this would preclude protec-tion from most geographical names, yet the number of geographical indications seems to be rising. GIs are no longer what they used to be. In the EC it is no longer required that a product is endowed exclusive characteristics by its geographical origin as long as consumers associate the product with a certain geo-graphical origin. This departure from the traditional protection of GIs is based on the premise that a geographical name extends beyond and exists apart from the product and therefore deserves protection itself. The thesis tries to clearly articulate the underlying reasons, justifications, principles and policies behind the protection of GIs in the EC and then scrutinise the scope and shape of the GI system in the light of its own justifications. The essential questions it attempts to aswer are (1) What is the basis and criteria for granting GI rights? (2) What is the scope of protection afforded to GIs? and (3) Are these both justified in the light of the functions and policies underlying granting and protecting of GIs? Despite the differences, the actual functions of GIs are in many ways identical to those of trade marks. Geographical indications have a limited role as source and quality indicators in allowing consumers to make informed and efficient choices in the market place. In the EC this role is undermined by allowing able room and discretion for uses that are arbitrary. Nevertheless, generic GIs are unable to play this role. The traditional basis for justifying legal protection seems implausible in most case. Qualities and charac-teristics are more likely to be related to transportable skill and manufacturing methods than the actual geographical location of production. Geographical indications are also incapable of protecting culture from market-induced changes. Protection against genericness, against any misuse, imitation and evocation as well as against exploiting the reputation of a GI seem to be there to protect the GI itself. Expanding or strengthening the already existing GI protection or using it to protect generic GIs cannot be justified with arguments on terroir or culture. The conclusion of the writer is that GIs themselves merit protection only in extremely rare cases and usually only the source and origin function of GIs should be protected. The approach should not be any different from one taken in trade mark law. GI protection should not be used as a means to mo-nopolise names. At the end of the day, the scope of GI protection is nevertheless a policy issue.

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.

Use of Standards for CAD Layers in Building

One of the central issues in making efficient use of IT in the design, construction and maintenance of buildings is the sharing of the digital building data across disciplines and lifecycle stages. One technology which enables data sharing is CAD layering, which to be of real use requires the definition of standards. This paper focuses on the background, objectives and effectiveness of the International standard ISO 13567, Organisation and naming of layers for CAD. In particular the efficiency and effectiveness of the standardisation and standard implementation process are in focus, rather than the technical details. The study was conducted as a qualitative study with a number of experts who responded to a semi-structured mail questionnaire, supplemented by personal interviews. The main results were that CAD layer standards based on the ISO standard have been implemented, particularly in northern European countries, but are not very widely used. A major problem which was identified was the lack of resources for marketing and implementing the standard as national variations, once it had been formally accepted.

Corporate Governance in China (summary section only)

The negative relationship between economic growth and stock market return is not an anomaly according to evidence documented in many economies. It is argued that future economic growth is largely irrelevant for predicting future equity returns, since long-run equity returns depend mainly on dividend yields and the growth of per share dividends. The economic growth does result in a higher standard of living for consumers, but does not necessarily translate into higher returns for owners of the capital. The divergence in performance between the real sector and stock markets appears to support the above argument. However, this thesis strives to offer an alternative explanation to the apparent divergence within the framework of corporate governance. It argues that weak corporate governance standards in Chinese listed firms exacerbated by poor inventor protection results into a marginalized capital market. Each of the three essays in the thesis addresses one particular aspect of corporate governance on the Chinese stock market in a sequential way through gathering empirical evidence on three distinctive stock market activities. The first essay questions whether significant agency conflicts do exist by building a game on rights issues. It documents significant divergence in interests among shareholders holding different classes of shares. The second essay investigates the level of agency costs by examining value of control through constructing a sample of block transactions. It finds that block transactions that transfer ultimate control entail higher premiums. The third essay looks into possible avenues through which corporate governance standards could be improved by investigating the economic consequences of cross-listing on the Chinese stock market. It finds that, by adopting a higher disclosure standard through cross-listings, firms voluntarily commit themselves to reducing information asymmetry, and consequently command higher valuation than their counterparts.

Essays on Corporate Governance and the Quality of Disclosed Earnings: Across Transitional Europe

A growing body of empirical research examines the structure and effectiveness of corporate governance systems around the world. An important insight from this literature is that corporate governance mechanisms address the excessive use of managerial discretionary powers to get private benefits by expropriating the value of shareholders. One possible way of expropriation is to reduce the quality of disclosed earnings by manipulating the financial statements. This lower quality of earnings should then be reflected by the stock price of firm according to value relevance theorem. Hence, instead of testing the direct effect of corporate governance on the firm’s market value, it is important to understand the causes of the lower quality of accounting earnings. This thesis contributes to the literature by increasing knowledge about the extent of the earnings management – measured as the extent of discretionary accruals in total disclosed earnings - and its determinants across the Transitional European countries. The thesis comprises of three essays of empirical analysis of which first two utilize the data of Russian listed firms whereas the third essay uses data from 10 European economies. More specifically, the first essay adds to existing research connecting earnings management to corporate governance. It testifies the impact of the Russian corporate governance reforms of 2002 on the quality of disclosed earnings in all publicly listed firms. This essay provides empirical evidence of the fact that the desired impact of reforms is not fully substantiated in Russia without proper enforcement. Instead, firm-level factors such as long-term capital investments and compliance with International financial reporting standards (IFRS) determine the quality of the earnings. The result presented in the essay support the notion proposed by Leuz et al. (2003) that the reforms aimed to bring transparency do not correspond to desired results in economies where investor protection is lower and legal enforcement is weak. The second essay focuses on the relationship between the internal-control mechanism such as the types and levels of ownership and the quality of disclosed earnings in Russia. The empirical analysis shows that the controlling shareholders in Russia use their powers to manipulate the reported performance in order to get private benefits of control. Comparatively, firms owned by the State have significantly better quality of disclosed earnings than other controllers such as oligarchs and foreign corporations. Interestingly, market performance of firms controlled by either State or oligarchs is better than widely held firms. The third essay provides useful evidence on the fact that both ownership structures and economic characteristics are important factors in determining the quality of disclosed earnings in three groups of countries in Europe. Evidence suggests that ownership structure is a more important determinant in developed and transparent countries, while economic determinants are important determinants in developing and transitional countries.

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.

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.

Nationalism Circumscribed : Transnational Governance of Minority Rights in Post-Cold War Europe

For the past two centuries, nationalism has been among the most influential legitimizing principles of political organization. According to its simple definition, nationalism is a principle or a way of thinking and acting which holds that the world is divided into nations, and that national and political units should be congruent. Nationalism can thus be divided into two aspects: internal and external. Internally, the political units, i.e., states, should be made up of only one nation. Externally each nation-state should be sovereign. Transnational national governance of rights of national minorities violates both these principles. This study explores the formation, operation, and effectiveness of the European post-Cold War minorities system. The study identifies two basic approaches to minority rights: security and justice. These approaches have been used to legitimize international minority politics and they also inform the practice of transnational governance. The security approach is based on the recognition that the norm of national self-determination cannot be fulfilled in all relevant cases, and so minority rights are offered as a compensation to the dissatisfied national groups, reducing their aspiration to challenge the status quo. From the justice perspective, minority rights are justified as a compensatory strategy against discrimination caused by majority nation-building. The research concludes that the post-Cold War minorities system was justified on the basis of a particular version of the security approach, according to which only Eastern European minority situations are threatening because of the ethnic variant of nationalism that exists in that region. This security frame was essential in internationalising minority issues and justifying the swift development of norms and institutions to deal with these issues. However, from the justice perspective this approach is problematic, since it justified double standards in European minority politics. Even though majority nation-building is often detrimental to minorities also in Western Europe, Western countries can treat their minorities more or less however they choose. One of the main contributions of this thesis is the detailed investigation of the operation of the post-Cold War minorities system. For the first decade since its creation in the early 1990s, the system operated mainly through its security track, which is based on the field activities of the OSCE that are supported by the EU. The study shows how the effectiveness of this track was based on inter-organizational cooperation in which various transnational actors compensate for each other s weaknesses. After the enlargement of the EU and dissolution of the membership conditionality this track, which was limited to Eastern Europe from the start, has become increasingly ineffective. Since the EU enlargement, the focus minorities system has shifted more and more towards its legal track, which is based on the Framework Convention for the Protection of National Minorities (Council of Europe). The study presents in detail how a network of like-minded representatives of governments, international organizations, and independent experts was able strengthen the framework convention s (originally weak) monitoring system considerably. The development of the legal track allows for a more universal and consistent, justice-based approach to minority rights in contemporary Europe, but the nationalist principle of organization still severely hinders the materialization of this possibility.

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.

Water quality assessment in water protection planning

Yhteenveto: Veden laadun arviointi vesiensuojelun suunnittelussa