Some mechanisms of excitation of a railway wheel

Railway wheel vibrations are caused by a number of mechanisms. Two of these are considered: (a) gravitational load reaction acting on different points of the wheel rim, as the wheel rolls on, and (b) random fluctuating forces generated at the contact patch by roughness on the mating surfaces of the wheel and rail. The wheel is idealized as a thin ring, and the analysis is limited to a single wheel rolling on a rail. It is shown that the first mechanism results in a stationary pattern of vibration, which would not radiate any sound. The acceleration caused by roughness-excited forces is much higher at higher frequencies, but is of the same order as that caused by load reaction at lower frequencies. The computed acceleration level (and hence the radiated SPL) caused by roughness is comparable with the observed values, and is seen to increase by about 10 dB for a doubling of the wagon speed. The driving point impedance of the periodic rail-sleeper system at the contact patch, which is used in the analysis, is derived in a companion paper.

Paspalum vaginatum Swartz, Seashore Paspalum 'SDX-1'

‘SDX-1’ originated as an open-pollinated chance seeding in an old green of ‘Adalayd’ seashore paspalum (US Plant Patent 3939) surrounded by an undefined local ecotype of the same species. ‘SDX-1’ was finer textured and had a denser, more prostrate growth habit than its putative parents which are ‘Adalayd’ (maternal) and an undefined parental genotype growing among the surrounding local ecotype. ‘SDX-1’ was compared with other promising seedlings discovered similarly at the same time, and was selected on the basis of its dwarf growth habit, tolerance of low cutting height, turf density, fine-textured growth, and apparent salt tolerance under field conditions. Breeder: Stewart T Bennett, Paul H Tillman, Michael DePew, Enviro Turf LC, Terkonsha, MI, USA. PBR Certificate Number 3660, Application Number 2006/160, granted 16 December 2008.

Indigenous Intellectual Property: A Handbook of Contemporary Research

Taking an interdisciplinary approach unmatched by any other book on this topic, this thoughtful Handbook considers the international struggle to provide for proper and just protection of Indigenous intellectual property (IP). In light of the United Nations Declaration on the Rights of Indigenous Peoples 2007, expert contributors assess the legal and policy controversies over Indigenous knowledge in the fields of international law, copyright law, trademark law, patent law, trade secrets law, and cultural heritage. The overarching discussion examines national developments in Indigenous IP in the United States, Canada, South Africa, the European Union, Australia, New Zealand, and Indonesia. The Handbook provides a comprehensive overview of the historical origins of conflict over Indigenous knowledge, and examines new challenges to Indigenous IP from emerging developments in information technology, biotechnology, and climate change. Practitioners and scholars in the field of IP will learn a great deal from this Handbook about the issues and challenges that surround just protection of a variety of forms of IP for Indigenous communities. Preface The Legacy of David Unaipon Matthew Rimmer Introduction: Mapping Indigenous Intellectual Property Matthew Rimmer PART I INTERNATIONAL LAW 1. The United Nations Declaration on the Rights of Indigenous Peoples: A Human Rights Framework for Indigenous Intellectual Property Mauro Barelli 2. The WTO, The TRIPS Agreement and Traditional Knowledge Tania Voon 3. The World Intellectual Property Organization and Traditional Knowledge Sara Bannerman 4. The World Indigenous Network: Rio+20, Intellectual Property, Indigenous Knowledge, and Sustainable Development Matthew Rimmer PART II COPYRIGHT LAW AND RELATED RIGHTS 5. Government Man, Government Painting? David Malangi and the 1966 One-Dollar Note Stephen Gray 6. What Wandjuk Wanted Martin Hardie 7. Avatar Dreaming: Indigenous Cultural Protocols and Making Films Using Indigenous Content Terri Janke 8. The Australian Resale Royalty for Visual Artists: Indigenous Art and Social Justice Robert Dearn and Matthew Rimmer PART III TRADE MARK LAW AND RELATED RIGHTS 9. Indigenous Cultural Expression and Registered Designs Maree Sainsbury 10. The Indian Arts and Crafts Act: The Limits of Trademark Analogies Rebecca Tushnet 11. Protection of Traditional Cultural Expressions within the New Zealand Intellectual Property Framework: A Case Study of the Ka Mate Haka Sarah Rosanowski 12 Geographical Indications and Indigenous Intellectual Property William van Caenegem PART IV PATENT LAW AND RELATED RIGHTS 13. Pressuring ‘Suspect Orthodoxy’: Traditional Knowledge and the Patent System Chidi Oguamanam, 14. The Nagoya Protocol: Unfinished Business Remains Unfinished Achmad Gusman Siswandi 15. Legislating on Biopiracy in Europe: Too Little, too Late? Angela Daly 16. Intellectual Property, Indigenous Knowledge, and Climate Change Matthew Rimmer PART V PRIVACY LAW AND IDENTITY RIGHTS 17. Confidential Information and Anthropology: Indigenous Knowledge and the Digital Economy Sarah Holcombe 18. Indigenous Cultural Heritage in Australia: The Control of Living Heritages Judith Bannister 19. Dignity, Trust and Identity: Private Spheres and Indigenous Intellectual Property Bruce Baer Arnold 20. Racial Discrimination Laws as a Means of Protecting Collective Reputation and Identity David Rolph PART VI INDIGENOUS INTELLECTUAL PROPERTY: REGIONAL PERSPECTIVES 21. Diluted Control: A Critical Analysis of the WAI262 Report on Maori Traditional Knowledge and Culture Fleur Adcock 22. Traditional Knowledge Governance Challenges in Canada Jeremy de Beer and Daniel Dylan 23. Intellectual Property protection of Traditional Knowledge and Access to Knowledge in South Africa Caroline Ncube 24. Traditional Knowledge Sovereignty: The Fundamental Role of Customary Law in Protection of Traditional Knowledge Brendan Tobin Index

Turing and the Trans-Pacific Partnership: Intellectual Property, Public Health, and Access to Essential Medicines

A recent controversy in the United States over drug pricing by Turing Pharmaceuticals AG has raised larger issues in respect of intellectual property, access to medicines, and the Trans-Pacific Partnership (TPP). In August 2015, Turing Pharmaceuticals AG – a private biopharmaceutical company with offices in New York, the United States, and Zug, Switzerland - acquired the exclusive marketing rights to Daraprim in the United States from Impax Laboratories Incorporated. Martin Shkreli, Turing’s Founder and Chief Executive Officer, maintained: “The acquisition of Daraprim and our toxoplasmosis research program are significant steps along Turing’s path of bringing novel medications to patients with serious disorders, some of whom often go undiagnosed and untreated.” He emphasised: “We intend to invest in the development of new drug candidates that we hope will yield an even better clinical profile, and also plan to launch an educational effort to help raise awareness and improve diagnosis for patients with toxoplasmosis.” In September 2015, there was much public controversy over the decision of Martin Shkreli to raise the price of a 62 year old drug, Daraprim, from $US13.50 to $US750 a pill. The drug is particularly useful in respect to the treatment and prevention of malaria, and in the treatment of infections in individuals with HIV/AIDS. Daraprim is listed on the World Health Organization’s (WHO) List of Essential Medicines. In the face of much criticism, Martin Shkreli has said that he will reduce the price of Daraprim. He observed: “We've agreed to lower the price on Daraprim to a point that is more affordable and is able to allow the company to make a profit, but a very small profit.” He maintained: “We think these changes will be welcomed.” However, he has been vague and ambiguous about the nature of the commitment. Notably, the lobby group, Pharmaceutical Research and Manufacturers of America (PhARMA), disassociated itself from the claims of Turing Pharmaceuticals. The group said: “PhRMA members have a long history of drug discovery and innovation that has led to increased longevity and improved lives for millions of patients.” The group noted: “Turing Pharmaceutical is not a member of PhRMA and we do not embrace either their recent actions or the conduct of their CEO.” The biotechnology peak body Biotechnology Industry Organization also sought to distance itself from Turing Pharmaceuticals. A hot topic: United States political debate about access to affordable medicines This controversy over Daraprim is unusual – given the age of drug concerned. Daraprim is not subject to patent protection. Nonetheless, there remains a monopoly in respect of the marketplace. Drug pricing is not an isolated problem. There have been many concerns about drug pricing – particularly in respect of essential medicines for HIV/AIDS, tuberculosis, and malaria. This recent controversy is part of a larger debate about access to affordable medicines. The dispute raises larger issues about healthcare, consumer rights, competition policy, and trade. The Daraprim controversy has provided impetus for law reform in the US. US Presidential Candidate Hillary Clinton commented: “Price gouging like this in this specialty drug market is outrageous.” In response to her comments, the Nasdaq Biotechnology Index fell sharply. Hillary Clinton has announced a prescription drug reform plan to protect consumers and promote innovation – while putting an end to profiteering. On her campaign site, she has emphasised that “affordable healthcare is a basic human right.” Her rival progressive candidate, Bernie Sanders, was also concerned about the price hike. He wrote a letter to Martin Shkreli, complaining about the price increase for the drug Daraprim. Sanders said: “The enormous, overnight price increase for Daraprim is just the latest in a long list of skyrocketing price increases for certain critical medications.” He has pushed for reforms to intellectual property to make medicines affordable. The TPP and intellectual property The Daraprim controversy and political debate raises further issues about the design of the TPP. The dispute highlights the dangers of extending the rights of pharmaceutical drug companies under intellectual property, investor-state dispute settlement, and drug administration. Recently, the civil society group Knowledge Ecology International published a leaked draft of the Intellectual Property Chapter of the TPP. Knowledge Ecology International Director, James Love, was concerned the text revealed that the US “continues to be the most aggressive supporter of expanded intellectual property rights for drug companies.” He was concerned that “the proposals contained in the TPP will harm consumers and in some cases block innovation.” James Love feared: “In countless ways, the Obama Administration has sought to expand and extend drug monopolies and raise drug prices.” He maintained: “The astonishing collection of proposals pandering to big drug companies make more difficult the task of ensuring access to drugs for the treatment of cancer and other diseases and conditions.” Love called for a different approach to intellectual property and trade: “Rather than focusing on more intellectual property rights for drug companies, and a death-inducing spiral of higher prices and access barriers, the trade agreement could seek new norms to expand the funding of medical research and development (R&D) as a public good, an area where the US has an admirable track record, such as the public funding of research at the National Institutes of Health (NIH) and other federal agencies.” In addition, there has been much concern about the Investment Chapter of the TPP. The investor-state dispute settlement regime would enable foreign investors to challenge government policy making, which affected their investments. In the context of healthcare, there is a worry that pharmaceutical drug companies will deploy their investor rights to challenge public health measures – such as, for instance, initiatives to curb drug pricing and profiteering. Such concerns are not merely theoretical. Eli Lilly has brought an investor action against the Canadian Government over the rejection of its drug patents under the investor-state dispute settlement regime of the North American Free Trade Agreement (NAFTA). The Health Annex to the TPP also raises worries that pharmaceutical drug companies will able to object to regulatory procedures in respect of healthcare. It is disappointing that the TPP – in the leaks that we have seen – has only limited recognition of the importance of access to essential medicines. There is a need to ensure that there are proper safeguards to provide access to essential medicines – particularly in respect of HIV/AIDs, malaria, and tuberculosis. Moreover, there must be protection against drug profiteering and price gouging in any trade agreement. There should be strong measures against the abuse of intellectual property rights. The dispute over Turing Pharmaceuticals AG and Daraprim is an important cautionary warning in respect of some of the dangers present in the secret negotiations in respect of the TPP. There is a need to preserve consumer rights, competition policy, and public health in trade negotiations over an agreement covering the Pacific Rim.

The Trans-Pacific partnership protects old companies at the expense of the new

Under this trade agreement, intellectual property will be transformed into a means of protecting the investments of multinational companies in culture, advertising, and medicine, writes Matthew Rimmer. The Trans-Pacific Partnership (TPP) is a blockbuster trade deal, which will transform the intellectual property of the Pacific Rim. The Australian Prime Minister Malcolm Turnbull has argued the trade agreement is a "gigantic foundation stone" for the country's future prosperity. Nonetheless, though the final text remains unreleased, it's clear from what we do know that the Intellectual Property Chapter is set to protect legacy intellectual property industries - rather than support disruptive technologies and dynamic innovation.

Save Left Shark: Katy Perry, Intellectual Property, and 3D Printing

There has been much interest in how intellectual property law, policy and practice will adapt to the emergence of 3D printing and the maker movement. Intellectual property lawyers will have to grapple with the impact of additive manufacturing upon a variety of forms of intellectual property — including copyright law, trade mark law, designs law, patent law and trade secrets. The disruptive technology of 3D printing will both pose opportunities and challenges for legal practitioners and policy makers.A performance by pop princess Katy Perry at the 2015 Super Bowl has sparked a public controversy over intellectual property, internet memes and 3D printing.

Inventing the Future: Intellectual Property and 3D Printing

A new technology – 3D printing – has the potential to make radical changes to aspects of the way in which we live. Put simply, it allows people to download designs and turn them into physical objects by laying down successive layers of material. Replacements or parts for household objects such as toys, utensils and gadgets could become available at the press of a button. With this innovation, however, comes the need to consider impacts on a wide range of forms of intellectual property, as Dr Matthew Rimmer explains. 3D Printing is the latest in a long line of disruptive technologies – including photocopiers, cassette recorders, MP3 players, personal computers, peer to peer networks, and wikis – which have challenged intellectual property laws, policies, practices, and norms. As The Economist has observed, ‘Tinkerers with machines that turn binary digits into molecules are pioneering a whole new way of making things—one that could well rewrite the rules of manufacturing in much the same way as the PC trashed the traditional world of computing.’

Legislating on biopiracy in Europe: too little, too late?

This Handbook considers the international struggle to provide for proper and just protection of Indigenous intellectual property. Leading scholars consider legal and policy controversies over Indigenous knowledge in the fields of international law, copyright law, trademark law, patent law, trade secrets law, and cultural heritage. This collection examines national developments in Indigenous intellectual property from around the world. As well as examining the historical origins of conflicts over Indigenous knowledge, the volume examines new challenges to Indigenous intellectual property from emerging developments in information technology, biotechnology, and climate change.

Extract from plants

An extract of organic material from a species selected from the tribe Nicotianeae that comprises a mixture of C26 to C33 alkanes at a purity of at least 90% by volume of total extract.

Cardiac function before and after treatment for various types of loading conditions and in myocardial restriction : A prospective study on pediatric patients with two- and three-dimensional echocardiography and measurement of serum natriuretic peptides

Background: The incidence of all forms of congenital heart defects is 0.75%. For patients with congenital heart defects, life-expectancy has improved with new treatment modalities. Structural heart defects may require surgical or catheter treatment which may be corrective or palliative. Even those with corrective therapy need regular follow-up due to residual lesions, late sequelae, and possible complications after interventions. Aims: The aim of this thesis was to evaluate cardiac function before and after treatment for volume overload of the right ventricle (RV) caused by atrial septal defect (ASD), volume overload of the left ventricle (LV) caused by patent ductus arteriosus (PDA), and pressure overload of the LV caused by coarctation of the aorta (CoA), and to evaluate cardiac function in patients with Mulibrey nanism. Methods: In Study I, of the 24 children with ASD, 7 underwent surgical correction and 17 percutaneous occlusion of ASD. Study II had 33 patients with PDA undergoing percutaneous occlusion. In Study III, 28 patients with CoA underwent either surgical correction or percutaneous balloon dilatation of CoA. Study IV comprised 26 children with Mulibrey nanism. A total of 76 healthy voluntary children were examined as a control group. In each study, controls were matched to patients. All patients and controls underwent clinical cardiovascular examinations, two-dimensional (2D) and three-dimensional (3D) echocardiographic examinations, and blood sampling for measurement of natriuretic peptides prior to the intervention and twice or three times thereafter. Control children were examined once by 2D and 3D echocardiography. M-mode echocardiography was performed from the parasternal long axis view directed by 2D echocardiography. The left atrium-to-aorta (LA/Ao) ratio was calculated as an index of LA size. The end-diastolic and end-systolic dimensions of LV as well as the end-diastolic thicknesses of the interventricular septum and LV posterior wall were measured. LV volumes, and the fractional shortening (FS) and ejection fraction (EF) as indices of contractility were then calculated, and the z scores of LV dimensions determined. Diastolic function of LV was estimated from the mitral inflow signal obtained by Doppler echocardiography. In three-dimensional echocardiography, time-volume curves were used to determine end-diastolic and end-systolic volumes, stroke volume, and EF. Diastolic and systolic function of LV was estimated from the calculated first derivatives of these curves. Results: (I): In all children with ASD, during the one-year follow-up, the z score of the RV end-diastolic diameter decreased and that of LV increased. However, dilatation of RV did not resolve entirely during the follow-up in either treatment group. In addition, the size of LV increased more slowly in the surgical subgroup but reached control levels in both groups. Concentrations of natriuretic peptides in patients treated percutaneously increased during the first month after ASD closure and normalized thereafter, but in patients treated surgically, they remained higher than in controls. (II): In the PDA group, at baseline, the end-diastolic diameter of LV measured over 2SD in 5 of 33 patients. The median N-terminal pro-brain natriuretic peptide (proBNP) concentration before closure measured 72 ng/l in the control group and 141 ng/l in the PDA group (P = 0.001) and 6 months after closure measured 78.5 ng/l (P = NS). Patients differed from control subjects in indices of LV diastolic and systolic function at baseline, but by the end of follow-up, all these differences had disappeared. Even in the subgroup of patients with normal-sized LV at baseline, the LV end-diastolic volume decreased significantly during follow-up. (III): Before repair, the size and wall thickness of LV were higher in patients with CoA than in controls. Systolic blood pressure measured a median 123 mm Hg in patients before repair (P < 0.001) and 103 mm Hg one year thereafter, and 101 mm Hg in controls. The diameter of the coarctation segment measured a median 3.0 mm at baseline, and 7.9 at the 12-month (P = 0.006) follow-up. Thicknesses of the interventricular septum and posterior wall of the LV decreased after repair but increased to the initial level one year thereafter. The velocity time integrals of mitral inflow increased, but no changes were evident in LV dimensions or contractility. During follow-up, serum levels of natriuretic peptides decreased correlating with diastolic and systolic indices of LV function in 2D and 3D echocardiography. (IV): In 2D echocardiography, the interventricular septum and LV posterior wall were thicker, and velocity time integrals of mitral inflow shorter in patients with Mulibrey nanism than in controls. In 3D echocardiography, LV end-diastolic volume measured a median 51.9 (range 33.3 to 73.4) ml/m² in patients and 59.7 (range 37.6 to 87.6) ml/m² in controls (P = 0.040), and serum levels of ANPN and proBNP a median 0.54 (range 0.04 to 4.7) nmol/l and 289 (range 18 to 9170) ng/l, in patients and 0.28 (range 0.09 to 0.72) nmol/l (P < 0.001) and 54 (range 26 to 139) ng/l (P < 0.001) in controls. They correlated with several indices of diastolic LV function. Conclusions (I): During the one-year follow-up after the ASD closure, RV size decreased but did not normalize in all patients. The size of the LV normalized after ASD closure but the increase in LV size was slower in patients treated surgically than in those treated with the percutaneous technique. Serum levels of ANPN and proBNP were elevated prior to ASD closure but decreased thereafter to control levels in patients treated with the percutaneous technique but not in those treated surgically. (II): Changes in LV volume and function caused by PDA disappeared by 6 months after percutaneous closure. Even the children with normal-sized LV benefited from the procedure. (III): After repair of CoA, the RV size and the velocity time integrals of mitral inflow increased, and serum levels of natriuretic peptides decreased. Patients need close follow-up, despite cessation of LV pressure overload, since LV hypertrophy persisted even in normotensive patients with normal growth of the coarctation segment. (IV): In children with Mulibrey nanism, the LV wall was hypertrophied, with myocardial restriction and impairment of LV function. Significant correlations appeared between indices of LV function, size of the left atrium, and levels of natriuretic peptides, indicating that measurement of serum levels of natriuretic peptides can be used in the clinical follow-up of this patient group despite its dependence on loading conditions.

Trade wars in the TRIPS Council: Intellectual property, technology transfer, and climate change

This Chapter considers the geopolitical conflicts in respect of intellectual property, trade, and climate change in the TRIPS Agreement 1994 under the World Trade Organization (WTO). In particular, it focuses upon debates in the TRIPS Council on the topic of patent law and clean energy in 2013 and 2014. The chapter highlights the development agenda of a number of developing countries who are keen for access to clean energy to combat climate change and global warming. It also considers the mixed contributions of members of the BRICS/ BASIC group – including Brazil, India, China, and South Africa. This chapter highlights the intellectual property maximalist position of a number of developed countries on intellectual property, climate change, and trade. Seeking to overcome this conflict and stalemate, this Chapter puts forward both procedural and substantial reform options in respect of intellectual property, trade, and climate change in the TRIPS Council and the WTO. It also flags that the TRIPS Agreement 1994 could well be displaced by the rise of mega-regional trade agreements – such as the Trans-Pacific Partnership (TPP), and the Trans-Atlantic Trade and Investment Partnership (TTIP).

Knowledge Transfer within Western Multinationals' Subsidiary Units in China and Finland - The Impact of Headquarter Control Mechanisms, Subsidiary Location and Social Capital (summary section only)

It is suggested that the ability and practices of how the multinational corporation (MNC) manages knowledge transfer among its geographically dispersed subsidiary units are crucial for the building and development of firm competitive advantage. However, cross-border transfer of valuable organizational knowledge is likely to be problematic and laborious, especially within diversified and differentiated MNCs. Using data collected from 164 western multinational companies’ subsidiary units located in China and Finland, this study aims to investigate cross-border knowledge transfer within the MNC. It explores a number of factors that influence the transfer of knowledge among units in the differentiated MNC. The study consists of five individual papers. Paper 1 investigates a range of organizational mechanisms that may positively influence a subsidiary’s propensity to undertake knowledge transfers to other parts of the corporation. Paper 2 explores the impact of subsidiary location on the motivational dispositions of knowledge receiving units to value and accept knowledge from subsidiaries located in economically less advanced countries. Paper 3 examines the influence of social capital variables on knowledge transfer in dyadic relationships between foreign-owned subsidiaries and their sister and patent units. Paper 4 provides some initial insights into potentially different effects of trust and shared vision in intra-organizational vs. inter-organizational relationships. Using a case study setting, Paper 5 explores means and mechanisms used in transferring human resource management practices to Western MNCs’ business units in China from a cultural perspective. The results of the study show that MNC management through choices regarding organizational controls can encourage and enhance corporate-internal knowledge transfer. It also finds evidence that more knowledge is transferred from subsidiaries located in an industrialized country (e.g., Finland) than subsidiaries located in a developing country (e.g., China). While the study has highlighted the importance of social capital in promoting knowledge transfer, it has also uncovered some new findings that the effect of trust and shared vision may be contingent upon different contexts. Finally, in Paper 5, a number of mechanisms used in transferring selected HRM practices and competences to the Chinese business units have been identified. The findings suggest that cultural differences should be taken into consideration in the choice and use of different transfer mechanisms.

Lojalitet i licensavtal

Loyalty in Licensing Agreements The purpose of the dissertation is to analyse the impact of the principle of loyalty on licensing agreements from the viewpoint of Finnish law using the traditional legal method (Rechtsdogmatik) combined with empirical data in the form of licensing agreements. The need for good licensing agreements is crucial. One should avoid mechanical and stereotyped agreements in favour of more conscious and goal-oriented ones. When the parties' will and goals have been made clear, the drafting technique should be chosen accordingly. The importance of the principle of loyalty in the interpretation of licensing agreements varies according to their degree of relationality. This is a concept originating in the relational contract theory, more precisely Ian Macneil's spectrum of contracts, where contracts can be placed on an axis according to their degree of relationality. In the dissertation different factors are used to conclude whether the licensing agreement at hand is to be placed on the axis closer to the transactional pole or closer to the relational pole. A conclusion of the dissertation is that few licensing agreements can be placed so close to the transactional pole, that the principle of loyalty lacks importance altogether. The impact of the principle of loyalty the main focus of which is on fostering the contracting parties to behave in accordance with best practices, not for example on altering contract terms is analysed in different situations where the parties' interests typically collide. These situations are discussed from the point of view of three patent and knowhow licensing agreements that differ as to their degree of relationality. A balance needs to be struck between freedom of contract and relational needs. Especially when interpreting more modern licensing agreements, one should not focus on the written document alone, as is often recommended in the literature on Nordic intellectual property law. Neither is the principle of caveat emptor a proper starting point. Moreover, where the parties are of equal bargaining power, one should not assume that the grants in licensing agreements are to be interpreted narrowly. Focus in the interpretation should instead be on the entirety of the circumstances.

Patents, Ethics and Stem Cell Research : The Case of hESC Innovation in Australia, Europe and the United States

Embryonic stem cells offer potentially a ground-breaking insight into health and diseases and are said to offer hope in discovering cures for many ailments unimaginable few years ago. Human embryonic stem cells are undifferentiated, immature cells that possess an amazing ability to develop into almost any body cell such as heart muscle, bone, nerve and blood cells and possibly even organs in due course. This remarkable feature, enabling embryonic stem cells to proliferate indefinitely in vitro (in a test tube), has branded them as a so-called miracle cure . Their potential use in clinical applications provides hope to many sufferers of debilitating and fatal medical conditions. However, the emergence of stem cell research has resulted in intense debates about its promises and dangers. On the one hand, advocates hail its potential, ranging from alleviating and even curing fatal and debilitating diseases such as Parkinson s, diabetes, heart ailments and so forth. On the other hand, opponents decry its dangers, drawing attention to the inherent risks of human embryo destruction, cloning for research purposes and reproductive cloning eventually. Lately, however, the policy battles surrounding human embryonic stem cell innovation have shifted from being a controversial research to scuffles within intellectual property rights. In fact, the ability to obtain patents represents a pivotal factor in the economic success or failure of this new biotechnology. Although, stem cell patents tend to more or less satisfy the standard patentability requirements, they also raise serious ethical and moral questions about the meaning of the exclusions on ethical or moral grounds as found in European and to an extent American and Australian patent laws. At present there is a sort of a calamity over human embryonic stem cell patents in Europe and to an extent in Australia and the United States. This in turn has created a sense of urgency to engage all relevant parties in the discourse on how best to approach patenting of this new form of scientific innovation. In essence, this should become a highly favoured patenting priority. To the contrary, stem cell innovation and its reliance on patent protection risk turmoil, uncertainty, confusion and even a halt on not only stem cell research but also further emerging biotechnology research and development. The patent system is premised upon the fundamental principle of balance which ought to ensure that the temporary monopoly awarded to the inventor equals that of the social benefit provided by the disclosure of the invention. Ensuring and maintaining this balance within the patent system when patenting human embryonic stem cells is of crucial contemporary relevance. Yet, the patenting of human embryonic stem cells raises some fundamental moral, social and legal questions. Overall, the present approach of patenting human embryonic stem cell related inventions is unsatisfactory and ineffective. This draws attention to a specific question which provides for a conceptual framework for this work. That question is the following: how can the investigated patent offices successfully deal with patentability of human embryonic stem cells? This in turn points at the thorny issue of application of the morality clause in this field. In particular, the interpretation of the exclusions on ethical or moral grounds as found in Australian, American and European legislative and judicial precedents. The Thesis seeks to compare laws and legal practices surrounding patentability of human embryonic stem cells in Australia and the United States with that of Europe. By using Europe as the primary case study for lessons and guidance, the central goal of the Thesis then becomes the determination of the type of solutions available to Europe with prospects to apply such to Australia and the United States. The Dissertation purports to define the ethical implications that arise with patenting human embryonic stem cells and intends to offer resolutions to the key ethical dilemmas surrounding patentability of human embryonic stem cells and other morally controversial biotechnology inventions. In particular, the Thesis goal is to propose a functional framework that may be used as a benchmark for an informed discussion on the solution to resolving ethical and legal tensions that come with patentability of human embryonic stem cells in Australian, American and European patent worlds. Key research questions that arise from these objectives and which continuously thread throughout the monograph are: 1. How do common law countries such as Australia and the United States approach and deal with patentability of human embryonic stem cells in their jurisdictions? These practices are then compared to the situation in Europe as represented by the United Kingdom (first two chapters), the Court of Justice of the European Union and the European Patent Office decisions (Chapter 3 onwards) in order to obtain a full picture of the present patenting procedures on the European soil. 2. How are ethical and moral considerations taken into account at patent offices investigated when assessing patentability of human embryonic stem cell related inventions? In order to assess this part, the Thesis evaluates how ethical issues that arise with patent applications are dealt with by: a) Legislative history of the modern patent system from its inception in 15th Century England to present day patent laws. b) Australian, American and European patent offices presently and in the past, including other relevant legal precedents on the subject matter. c) Normative ethical theories. d) The notion of human dignity used as the lowest common denominator for the interpretation of the European morality clause. 3. Given the existence of the morality clause in form of Article 6(1) of the Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions which corresponds to Article 53(a) European Patent Convention, a special emphasis is put on Europe as a guiding principle for Australia and the United States. Any room for improvement of the European morality clause and Europe s current manner of evaluating ethical tensions surrounding human embryonic stem cell inventions is examined. 4. A summary of options (as represented by Australia, the United States and Europe) available as a basis for the optimal examination procedure of human embryonic stem cell inventions is depicted, whereas the best of such alternatives is deduced in order to create a benchmark framework. This framework is then utilised on and promoted as a tool to assist Europe (as represented by the European Patent Office) in examining human embryonic stem cell patent applications. This method suggests a possibility of implementing an institution solution. 5. Ultimately, a question of whether such reformed European patent system can be used as a founding stone for a potential patent reform in Australia and the United States when examining human embryonic stem cells or other morally controversial inventions is surveyed. The author wishes to emphasise that the guiding thought while carrying out this work is to convey the significance of identifying, analysing and clarifying the ethical tensions surrounding patenting human embryonic stem cells and ultimately present a solution that adequately assesses patentability of human embryonic stem cell inventions and related biotechnologies. In answering the key questions above, the Thesis strives to contribute to the broader stem cell debate about how and to which extent ethical and social positions should be integrated into the patenting procedure in pluralistic and morally divided democracies of Europe and subsequently Australia and the United States.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.