Deposition, imaging, and clearance: what remains to be done?

Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.

Securities: Its Conception and Protection of Interests of its Holders

Theoretical studies of the problems of the securities markets in the Russian Federation incline to one or other of the two traditional approaches. The first consists of comparing the definition of "valuable paper" set forth in the current legislation of the Russian Federation, with the theoretical model of "Wertpapiere" elaborated by German scholars more than 90 years ago. The problem with this approach is, in Mr. Pentsov's opinion, that any new features of the definition of "security" that do not coincide with the theoretical model of "Wertpapiere" (such as valuable papers existing in non-material, electronic form) are claimed to be incorrect and removed from the current legislation of the Russian Federation. The second approach works on the basis of the differentiation between the Common Law concept of "security" and the Civil Law concept of "valuable paper". Mr. Pentsov's research, presented in an article written in English, uses both methodological tools and involves, firstly, a historical study of the origin and development of certain legal phenomena (securities) as they evolved in different countries, and secondly, a comparative, synchronic study of equivalent legal phenomena as they exist in different countries today. Employing the first method, Mr. Pentsov divided the historical development of the conception of "valuable paper" in Russia into five major stages. He found that, despite the existence of a relatively wide circulation of valuable papers, especially in the second half of the 19th century, Russian legislation before 1917 (the first stage) did not have a unified definition of valuable paper. The term was used, in both theoretical studies and legislation, but it covered a broad range of financial instruments such as stocks, bonds, government bonds, promissory notes, bills of exchange, etc. During the second stage, also, the legislation of the USSR did not have a unified definition of "valuable paper". After the end of the "new economic policy" (1922 - 1930) the stock exchanges and the securities markets in the USSR, with a very few exceptions, were abolished. And thus during the third stage (up to 1985), the use of valuable papers in practice was reduced to foreign economic relations (bills of exchange, stocks in enterprises outside the USSR) and to state bonds. Not surprisingly, there was still no unified definition of "valuable paper". After the beginning of Gorbachev's perestroika, a securities market began to re-appear in the USSR. However, the successful development of securities markets in the USSR was retarded by the absence of an appropriate regulatory framework. The first effort to improve the situation was the adoption of the Regulations on Valuable Papers, approved by resolution No. 590 of the Council of Ministers of the USSR, dated June 19, 1990. Section 1 of the Regulation contained the first statutory definition of "valuable paper" in the history of Russia. At the very beginning of the period of transition to a market economy, a number of acts contained different definitions of "valuable paper". This diversity clearly undermined the stability of the Russian securities market and did not achieve the goal of protecting the investor. The lack of unified criteria for the consideration of such non-standard financial instruments as "valuable papers" significantly contributed to the appearance of numerous fraudulent "pyramid" schemes that were outside of the regulatory scheme of Russia legislation. The situation was substantially improved by the adoption of the new Civil Code of the Russian Federation. According to Section 1 of Article 142 of the Civil Code, a valuable paper is a document that confirms, in compliance with an established form and mandatory requisites, certain material rights whose realisation or transfer are possible only in the process of its presentation. Finally, the recent Federal law No. 39 - FZ "On the Valuable Papers Market", dated April 22 1996, has also introduced the term "emission valuable papers". According to Article 2 of this Law, an "emission valuable paper" is any valuable paper, including non-documentary, that simultaneously has the following features: it fixes the composition of material and non-material rights that are subject to confirmation, cession and unconditional realisation in compliance with the form and procedure established by this federal law; it is placed by issues; and it has equal amount and time of realisation of rights within the same issue regardless of when the valuable paper was purchased. Thus the introduction of the conception of "emission valuable paper" became the starting point in the Russian federation's legislation for the differentiation between the legal regimes of "commercial papers" and "investment papers" similar to the Common Law approach. Moving now to the synchronic, comparative method of research, Mr. Pentsov notes that there are currently three major conceptions of "security" and, correspondingly, three approaches to its legal definition: the Common Law concept, the continental law concept, and the concept employed by Japanese Law. Mr. Pentsov proceeds to analyse the differences and similarities of all three, concluding that though the concept of "security" in the Common Law system substantially differs from that of "valuable paper" in the Continental Law system, nevertheless the two concepts are developing in similar directions. He predicts that in the foreseeable future the existing differences between these two concepts will become less and less significant. On the basis of his research, Mr. Pentsov arrived at the conclusion that the concept of "security" (and its equivalents) is not a static one. On the contrary, it is in the process of permanent evolution that reflects the introduction of new financial instruments onto the capital markets. He believes that the scope of the statutory definition of "security" plays an extremely important role in the protection of investors. While passing the Securities Act of 1933, the United States Congress determined that the best way to achieve the goal of protecting investors was to define the term "security" in sufficiently broad and general terms so as to include within the definition the many types of instruments that in the commercial world fall within the ordinary concept of "security' and to cover the countless and various devices used by those who seek to use the money of others on the promise of profits. On the other hand, the very limited scope of the current definition of "emission valuable paper" in the Federal Law of the Russian Federation entitled "On the Valuable Papers Market" does not allow the anti-fraud provisions of this law to be implemented in an efficient way. Consequently, there is no basis for the protection of investors. Mr. Pentsov proposes amendments which he believes would enable the Russian markets to become more efficient and attractive for both foreign and domestic investors.

EC Electronic Communications and Competition Law

Telecommunications have developed at an incredible speed over the last couple of decades. The decreasing size of our phones and the increasing number of ways in which we can communicate are barely the only result of this (r)evolutionary development. The latter has indeed multiple implications. The change of paradigm for telecommunications regulation, epitomised by the processes of liberalisation and reregulation, was not sufficient to answer all regulatory questions pertinent to communications. Today, after the transition from monopoly to competition, we are faced perhaps with an even harder regulatory puzzle, since we must figure out how to regulate a sector that is as dynamic and as unpredictable as electronic communications have proven to be, and as vital and fundamental to the economy and to society at large. The present book addresses the regulatory puzzle of contemporary electronic communications and suggests the outlines of a coherent model for their regulation. The search for such a model involves essentially deliberations on the question "Can competition law do it all?", since generic competition rules are largely seen as the appropriate regulatory tool for the communications domain. The latter perception has been the gist of the 2002 reform of the European Community (EC) telecommunications regime, which envisages a withdrawal of sectoral regulation, as communications markets become effectively competitive and ultimately bestows the regulation of the sector upon competition law only. The book argues that the question of whether competition law is the appropriate tool needs to be examined not in the conventional contexts of sector specific rules versus competition rules or deregulation versus regulation but in a broader governance context. Consequently, the reader is provided with an insight into the workings and specific characteristics of the communications sector as network-bound, converging, dynamic and endowed with a special societal role and function. A thorough evaluation of the regulatory objectives in the communications environment contributes further to the comprehensive picture of the communications industry. Upon this carefully prepared basis, the book analyses the communications regulatory toolkit. It explores the interplay between sectoral communications regulation, competition rules (in particular Article 82 of the EC Treaty) and the rules of the World Trade Organization (WTO) relevant to telecommunications services. The in-depth analysis of multilevel construct of EC communications law is up-to-date and takes into account important recent developments in the EC competition law in practice, in particular in the field of refusal to supply and tying, of the reform of the EC electronic communications framework and new decisions of the WTO dispute settlement body, such as notably the Mexico-Telecommunications Services Panel Report. Upon these building elements, an assessment of the regulatory potential of the EC competition rules is made. The conclusions drawn are beyond the scope of the current situation of EC electronic communications and the applicable law and explore the possible contours of an optimal regulatory framework for modern communications. The book is of particular interest to communications and antitrust law experts, as well as policy makers, government agencies, consultancies and think-tanks active in the field. Experts on other network industries (such as electricity or postal communications) can also profit from the substantial experience gathered in the communications sector as the most advanced one in terms of liberalisation and reregulation.

Evaluation and stages of surgical innovations

Surgical innovation is an important part of surgical practice. Its assessment is complex because of idiosyncrasies related to surgical practice, but necessary so that introduction and adoption of surgical innovations can derive from evidence-based principles rather than trial and error. A regulatory framework is also desirable to protect patients against the potential harms of any novel procedure. In this first of three Series papers on surgical innovation and evaluation, we propose a five-stage paradigm to describe the development of innovative surgical procedures.

Policy Contexts of Social Work in Britain: the wider implications of 'New' Labour and the 'New Legal Regime'

Several commentators have expressed disappointment with New Labour's apparent adherence to the policy frameworks of the previous Conservative administrations. The employment orientation of its welfare programmes, the contradictory nature of the social exclusion initiatives, and the continuing obsession with public sector marketisation, inspections, audits, standards and so on, have all come under critical scrutiny (c.f., Blyth 2001; Jordan 2001; Orme 2001). This paper suggests that in order to understand the socio-economic and political contexts affecting social work we need to examine the relationship between New Labour's modernisation project and its insertion within an architecture of global governance. In particular, membership of the European Union (EU), International Monetary Fund (IMF) and World Trade Organisation (WTO) set the parameters for domestic policy in important ways. Whilst much has been written about the economic dimensions of 'globalisation' in relation to social work rather less has been noted about the ways in which domestic policy agenda are driven by multilateral governance objectives. This policy dimension is important in trying to respond to various changes affecting social work as a professional activity. What is possible, what is encouraged, how things might be done, is tightly bounded by the policy frameworks governing practice and affected by those governing the lives of service users. It is unhelpful to see policy formulation in purely national terms as the UK is inserted into a network governance structure, a regulatory framework where decisions are made by many countries and organisations and agencies. Together, they are producing a 'new legal regime', characterised by a marked neo-liberal policy agenda. This paper aims to demonstrate the relationship of New Labour's modernisation programme to these new forms of legality by examining two main policy areas and the welfare implications they are enmeshed in. The first is privatisation, and the second is social policy in the European Union. Examining these areas allows a demonstration of how much of the New Labour programme can be understood as a local implementation of a transnational strategy, how parts of that strategy produce much of the social exclusion it purports to address, and how social welfare, and particularly social work, are noticeable by their absence within policy discourses of the strategy. The paper details how the privatisation programme is considered to be a crucial vehicle for the further development of a transnational political-economy, where capital accumulation has been redefined as 'welfare'. In this development, frameworks, codes and standards are central, and the final section of the paper examines how the modernisation strategy of the European Union depends upon social policy marked by an employment orientation and risk rationality, aimed at reconfiguring citizen identities.The strategy is governed through an 'open mode of coordination', in which codes, standards, benchmarks and so on play an important role. The paper considers the modernisation strategy and new legality within which it is embedded as dependent upon social policy as a technology of liberal governance, one demonstrating a new rationality in comparison to that governing post-Second World War welfare, and which aims to reconfigure institutional infrastructure and citizen identity.

Klassifizierung der Methoden eines Ganzheitlichen Produktionssystems unter Berücksichtigung der Anforderungen indirekter Bereiche

Seit den 50er Jahren des Zwanzigsten Jahrhunderts erfährt das Konzept der schlanken Produktion stetig Erweiterungen und Renaissancen [Fau09]. Zielt das Ursprungskonzept noch überwiegend auf eine Effizienzsteigerung im Bereich der Fertigung ab, so werden im Rahmen eines Ganzheitlichen Produktionssystems verstärkt auch die indirekten Bereiche, wie z. B. Konstruktion, Forschung und Entwicklung, Planung oder Vertrieb einbezogen. Im folgenden Beitrag werden die Rahmenbedingungen eines Produktionssystems im indirekten Bereich dargestellt und Empfehlungen hinsichtlich einer strukturellen Erweiterung aktuell bestehender Ordnungsrahmen gegeben.

Trade Versus Culture in the Digital Environment : An Old Conflict in Need of a New Definition

Following the recent UNESCO Convention on the Protection and Promotion of the Diversity of Cultural Expressions, the first wave of scholarly work has focused on clarifying the interface between the Convention and the WTO Agreements. Building upon these analyses, the present article takes however a different stance. It seeks a new, rather pragmatic definition of the relationship between trade and culture and argues that such a re-definition is particularly needed in the digital networked environment that has modified the ways markets for cultural content function and the ways in which cultural content is created, distributed and accessed. The article explores first the significance of the UNESCO Convention (or the lack thereof) and subsequently outlines a variety of ways in which the WTO framework can be improved in a ‘neutral’, not necessarily culturally motivated, manner to become more conducive to the pursuit of cultural diversity and taking into account the changed reality of digital media. The article also looks at other facets of the profoundly fragmented culture-related regulatory framework and underscores the critical importance of intellectual property rights and of other domains that appear at first sight peripheral to the trade and culture discussion, such as access to infrastructure, interoperability or net neutrality. It is argued that a number of feasible solutions exist beyond the politically charged confrontation of trade versus culture and that the new digital media landscape may require a readjustment of the priorities and the tools for the achievement of the widely accepted objective of cultural diversity.

The Law of the WTO and the Communications Law of the EC : On a Path of Harmony or Discord?

This paper presents an overview of the law of the World Trade Organization (WTO) relevant to telecommunications services and correlates this body of law with the current regulatory framework for electronic communications networks and services in the European Community. The latter has been adapted to meet the challenges of technological and market developments in communications, epitomized by the processes of digitization, enhanced transport networks and convergence. The novel solutions embodied in the EC electronic communications regime, notably, a new design of the Significant Market Power mechanism, a projected withdrawal of sector specific regulation and an affirmation of the principle of technological neutrality, pose interesting questions as to the conformity of this reformed EC communications law with the WTO rules on telecommunications services and the obligations of the European Communities and their Member States. Looking beyond the WTO legal compatibility test, essential questions regarding the need for evolution of the WTO telecommunications rules are raised. The present paper contributes to the ongoing debate in that context in light of the EC experience.

EC Electronic Communications and Competition Law

Telecommunications have developed at an incredible speed over the last couple of decades. The decreasing size of our phones and the increasing number of ways in which we can communicate are barely the only result of this (r)evolutionary development. The latter has indeed multiple implications. The change of paradigm for telecommunications regulation, epitomised by the processes of liberalisation and reregulation, was not sufficient to answer all regulatory questions pertinent to communications. Today, after the transition from monopoly to competition, we are faced perhaps with an even harder regulatory puzzle, since we must figure out how to regulate a sector that is as dynamic and as unpredictable as electronic communications have proven to be, and as vital and fundamental to the economy and to society at large. The present book addresses the regulatory puzzle of contemporary electronic communications and suggests the outlines of a coherent model for their regulation. The search for such a model involves essentially deliberations on the question "Can competition law do it all?", since generic competition rules are largely seen as the appropriate regulatory tool for the communications domain. The latter perception has been the gist of the 2002 reform of the European Community (EC) telecommunications regime, which envisages a withdrawal of sectoral regulation, as communications markets become effectively competitive and ultimately bestows the regulation of the sector upon competition law only. The book argues that the question of whether competition law is the appropriate tool needs to be examined not in the conventional contexts of sector specific rules versus competition rules or deregulation versus regulation but in a broader governance context. Consequently, the reader is provided with an insight into the workings and specific characteristics of the communications sector as network-bound, converging, dynamic and endowed with a special societal role and function. A thorough evaluation of the regulatory objectives in the communications environment contributes further to the comprehensive picture of the communications industry. Upon this carefully prepared basis, the book analyses the communications regulatory toolkit. It explores the interplay between sectoral communications regulation, competition rules (in particular Article 82 of the EC Treaty) and the rules of the World Trade Organization (WTO) relevant to telecommunications services. The in-depth analysis of multilevel construct of EC communications law is up-to-date and takes into account important recent developments in the EC competition law in practice, in particular in the field of refusal to supply and tying, of the reform of the EC electronic communications framework and new decisions of the WTO dispute settlement body, such as notably the Mexico-Telecommunications Services Panel Report. Upon these building elements, an assessment of the regulatory potential of the EC competition rules is made. The conclusions drawn are beyond the scope of the current situation of EC electronic communications and the applicable law and explore the possible contours of an optimal regulatory framework for modern communications. The book is of particular interest to communications and antitrust law experts, as well as policy makers, government agencies, consultancies and think-tanks active in the field. Experts on other network industries (such as electricity or postal communications) can also profit from the substantial experience gathered in the communications sector as the most advanced one in terms of liberalisation and reregulation.

European Community Communications Law : An Introduction

The present article is an abridged version of a chapter to the book EC Electronic Communications and Competition Law (London: Cameron May, 2007). It provides an introduction to the rules at the European Community level governing the electronic communications sector (previously and more traditionally referred to as telecommunications). Such an introduction encompasses essentially an enquiry into the relevant competition law rules, of which here particular attention is paid to abuse of dominant position and the essential facilities doctrine, as well as an analysis of the EC sector specific regulatory framework, which has substantially evolved since the liberalisation of the telecommunications sector back in the beginning of the 1990s. It is the objective of the article to explore to what extent both regulatory tools could deal with the specificities of communications markets, and where they may fail to do so.

Typology of the Tools of EC Communications Regulation

The present article is an abridged version of a chapter to the book EC Electronic Communications and Competition Law (London: Cameron May 2007). It explores in a neutral manner the pros and cons of the currently applied toolkit of European Community communications law, i.e. the generic competition law rules and the sector specific regulatory framework. A number of criteria are introduced and these tools are then tested as to their efficiency and efficacy.

Orphan drugs and paediatric medicinal products

While the safety and availability of medicinal products for the majority of adult patients has steadily improved in recent decades, for children and people suffering from rare diseases (orphan diseases) there is a lack of approved medicinal products for these patient populations. Since the research and development of medicinal products is associated with high costs, the costs for paediatric medicinal products and medicines for rare diseases (orphan drugs) may barely be covered under normal market conditions due to the small patient populations. In order to prevent the continued exclusion of children and persons suffering from rare diseases from medical progress and to eliminate the deficits in the research and development of medicinal products for these patient groups, the European Union created, along the lines of the U.S. model, a system of incentives and constraints. Since 2000, under Regulation (EC) No. 141/2000 (Orphan Drug Regulation) there has been an incentive system to encourage the research and development of orphan drugs. With the goal of improving the health of children in Europe, Regulation (EC) No. 1901/2006 (Paediatric Regulation) combines economic incentives with the requirement to conduct paediatric studies. This article explains and comments on the specific regulatory framework for orphan drugs and paediatric medicinal products in the European Union.

A Transatlantic Trade and Investment Partnership Agreement: Implications for Swiss Agriculture

To say that regionalism is gaining momentum has become an understatement. To mourn the lack of progress in multilateral trade rule-making is a commonplace in the discourse of politicians regretting the WTO negotiation standstill, and of “know-what-to-do” academics. The real problem is the uneven level-playing field resulting from increasing differences of rules and obligations. The Transatlantic Trade and Investment Partnership Agreement (TTIP) is a very ambitious project. WTI studies in 2014 have shown that the implications for Switzerland could be enormous. But even the combined market power of the two TTIP participants – the EU and the USA – will not level the playing field impairing the regulatory framework, and the market access barriers for trade in agriculture. Such differences will remain in three areas which, incidentally, are also vital for a global response to the food security challenge to feed 9 billion people before the year 2050: market access, non-tariff barriers, and trade-distorting domestic support programmes. This means that without multilateral progress the TTIP and other so-called mega-regionals, if successfully concluded, will exacerbate rather than lessen trade distortions. While this makes farmers in rich countries safer from competition, competitive production in all countries will be hampered. Consequently, and notwithstanding the many affirmations to the contrary, farm policies worldwide will continue to only address farmer security without increasing global food security. What are the implications of the TTIP for Swiss agriculture? This article, commissioned by Waseda University in Tokyo, finds that the failure to achieve further reforms – including a number of areas where earlier reforms have been reversed – is presenting Switzerland and Swiss agriculture with a terrible dilemma in the eventuality of a successful conclusion of the TTIP. If Swiss farm production is to survive for more than another generation, continuous reform efforts are required, and over-reliance on the traditional instruments of border protection and product support is to be avoided. Without a substantial TTIP obliging Switzerland to follow suit, autonomous reforms will remain extremely fragile.

The Optimal Capital Structure of Banks: Balancing Deposit Insurance, Capital Requirements and Tax-Advantaged Debt

The capital structure and regulation of financial intermediaries is an important topic for practitioners, regulators and academic researchers. In general, theory predicts that firms choose their capital structures by balancing the benefits of debt (e.g., tax and agency benefits) against its costs (e.g., bankruptcy costs). However, when traditional corporate finance models have been applied to insured financial institutions, the results have generally predicted corner solutions (all equity or all debt) to the capital structure problem. This paper studies the impact and interaction of deposit insurance, capital requirements and tax benefits on a bankÇs choice of optimal capital structure. Using a contingent claims model to value the firm and its associated claims, we find that there exists an interior optimal capital ratio in the presence of deposit insurance, taxes and a minimum fixed capital standard. Banks voluntarily choose to maintain capital in excess of the minimum required in order to balance the risks of insolvency (especially the loss of future tax benefits) against the benefits of additional debt. Because we derive a closed- form solution, our model provides useful insights on several current policy debates including revisions to the regulatory framework for GSEs, tax policy in general and the tax exemption for credit unions.

La acción pública en el espacio urbano : debates y reflexiones en torno a la noción de política urbana

En este artículo se propone reflexionar sobre un conjunto de herramientas conceptuales que permitan analizar los modos en los cuales se configura la acción pública en el espacio urbano. Para ello se revisan una serie de contribuciones de la teoría política que consideran al aparato burocrático, en tanto objetivación de las instituciones estatales, como garante de las relaciones de producción hegemónicas. Y, al mismo tiempo, se supone que el ámbito intraestatal posee una dinámica específica, constituyéndose como un espacio de disputa política entre diversos actores. Teniendo en cuenta este escenario, el análisis de las políticas públicas implica una lectura dinámica acerca de la articulación de las relaciones sociales en el ámbito estatal, que exige indagar las estrategias y los intereses de los actores que se organizan en torno a redes o entramados según las cuestiones socialmente problematizadas que logran permear la agenda pública. Desde esta perspectiva se propone elaborar una definición de política urbana y delimitar una serie de interrogantes básicos para su abordaje. Para tal fin, se consideran ciertas particularidades que asume la política urbana como una política pública de fuerte impronta territorial. Además, se reconocen distintas formas de intervención estatal en el espacio urbano y ciertos nudos problemáticos que hacen a la definición de la cuestión urbana en la actualidad, escenario de la sanción de un nuevo marco normativo en la provincia de Buenos Aires.