"Fake News" bilden seit Menschengedenken ein zentrales Problem für die individuelle und öffentliche Meinungsbildung. Dabei wird die Wirkung verbreiteter Desinformation heutzutage durch die technischen Möglichkeiten im Bereich der Online-Kommunikation, etwa durch die Echokammern in sozialen Netzwerken oder den Einsatz künstlicher Meinungsverstärker, mitunter noch verstärkt. Effekte von einmal geäußerter Desinformation lassen sich aus kognitionswissenschaftlicher Perspektive nur noch sehr schwer korrigieren. Die Arbeit beschäftigt sich daher mit dem (kommunikations-)grundrechtlichen Schutz vo...
"Fake News" bilden seit Menschengedenken ein zentrales Problem für die individuelle und öffentliche Meinungsbildung. Dabei wird die Wirkung verbreiteter Desinformation heutzutage durch die technischen Möglichkeiten im Bereich der Online-Kommunikation, etwa durch die Echokammern in sozialen Netzwerken oder den Einsatz künstlicher Meinungsverstärker, mitunter noch verstärkt. Effekte von einmal geäußerter Desinformation lassen sich aus kognitionswissenschaftlicher Perspektive nur noch sehr schwer korrigieren. Die Arbeit beschäftigt sich daher mit dem (kommunikations-)grundrechtlichen Schutz vo...
The Philippines economy posted robust growth in early 2010, in part due to large one-off factors. As did many countries in the region, the Philippines benefited from a strong rebound in global trade. Manufacturing and investment activity expanded briskly as a result. Private consumption continued to expand, as consumer confidence improved. Growth also benefited from election-related spending. Expansionary (and now pro-cyclical) fiscal policy continued to support growth. Despite a withdrawal of liquidity-enhancing measures and a stronger peso, a closing output gap meant that monetary policy remained accommodative. A World Bank study of Philippines migration pattern during the global recession reveals that deployment of overseas foreign workers (OFWs) actually accelerated during the crisis. Partly this reflected the fact that the top OFW destinations were not as affected as the rest of the world. The most affected OFWs were males, production workers (especially construction workers) and new hires. By contrast, females, services workers, seafarers and rehires proved resilient to the crisis or even benefited from it. Globally, less tolerance towards weak public finances is expected, raising the need to introduce a credible medium-term fiscal consolidation plan for the Philippines. Running a pro-cyclical fiscal policy with relatively high debt and limited fiscal space-as undertaken in the first-half of 2010-raises risks and should be reverted. Credibility towards such a goal could be achieved, for example, by designing a comprehensive multi-year reform package. As the output gap closes, the accommodative monetary policy introduced in 2008 would need to be gradually unwound, starting by reaching a broadly neutral stance in 2010. An increase in policy rates currently negative or slightly positive could achieve such a goal.
A 2018 report from the Center for Strategic and International Studies, in partnership with computer security company McAfee, estimated that cybercrime costs the world almost $600 billion or .8% of the global Gross Domestic Product (CSIS, 2018, p. 4). In response to this booming element of transnational crime, states, private sector entities, non-governmental organizations, and individual citizens have sought to implement systems for the investigation, prosecution, and restitution of these crimes. One such solution is the development and enactment of international law. On December 27, 2019, the General Assembly of the United Nations passed Russia-led resolution A/74/401, entitled "Countering the use of information and communications technologies for criminal purposes (United Nations, 2019, Countering the use)." Vehemently opposed by Western states such as the United States, the resolution approved the establishment of a committee of experts to evaluate the potential for an international cybercrime treaty (United Nations). While international cooperation of this kind is commendable, Western states and human rights groups have professed concerns that the vague language of the resolution has the potential to erode the human rights protections afforded to citizens under international law (Hakmeh & Peters, 2020). The purpose of this paper is to identify the human rights concerns of Russia's proposed United Nations resolution and analyze the obligations the international community has to uphold relevant human rights protections while balancing international cooperation necessitated by international law and legal norms. The first section of this paper provides historical background on the relationship between cyber issues like cybercrime and international law. ; Winner of the 2020 Friends of the Kreitzberg Library Award for Outstanding Research in the College of Graduate and Continuing Studies Graduate category. ; Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 1 International Law & the Cyber Domain: Assessing the Human Rights Concerns of Cyber Legislation GD520 International Law and the International System Dr. John Becker Norwich University College of Graduate and Continuing Studies Kathryn R. Lamphere 23 May 2020 Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 2 Introduction A 2018 report from the Center for Strategic and International Studies, in partnership with computer security company McAfee, estimated that cybercrime costs the world almost $600 billion or .8% of the global Gross Domestic Product (CSIS, 2018, p. 4). In response to this booming element of transnational crime, states, private sector entities, non-governmental organizations, and individual citizens have sought to implement systems for the investigation, prosecution, and restitution of these crimes. One such solution is the development and enactment of international law. On December 27, 2019, the General Assembly of the United Nations passed Russia-led resolution A/74/401, entitled "Countering the use of information and communications technologies for criminal purposes (United Nations, 2019, Countering the use)." Vehemently opposed by Western states such as the United States, the resolution approved the establishment of a committee of experts to evaluate the potential for an international cybercrime treaty (United Nations). While international cooperation of this kind is commendable, Western states and human rights groups have professed concerns that the vague language of the resolution has the potential to erode the human rights protections afforded to citizens under international law (Hakmeh & Peters, 2020). The purpose of this paper is to identify the human rights concerns of Russia's proposed United Nations resolution and analyze the obligations the international community has to uphold relevant human rights protections while balancing international cooperation necessitated by international law and legal norms. The first section of this paper provides historical background on the relationship between cyber issues like cybercrime and international law. International Cyber Law Background The cyber domain is often presented as another realm, a world that exists outside of the mostly tidy borders the international community has used to separate themselves. Aligning with Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 3 this view is the notion that cyberspace cannot be regulated because it expands beyond the traditional idea of territorial sovereignty (Kanuck, 2010, p. 1573). These ideas raise two concerns over the identification and prosecution of cybercrime. The first concern is the conflict between "cybercrime, which is global in scale, and police activities that are confined to national borders (Cangemi, 2004, p. 166)." The conflict arises in the very structure of the Internet, which "can be characterized as a multitude of individual, but interconnected, electronic communications networks (Zekos, 2008, p. 30)." This interconnectedness has created a grey area within the legal system, where no one entity has regulatory control over what happens in that area. The second concern is far more technical and highlights the transient nature of information and data (Cangemi, 2004, p. 166). The source of information can be easily masked to hide its actual location, and data "may be amended, moved, or altered in a few seconds (p. 166)." The speed in which data travels presents a significant hurdle to the legal and law enforcement mechanisms typically used to investigate crimes. As Cangemi notes, this creates "an appreciable risk that the evidence of cyber-offences will disappear" long before implementing the required resources (p. 166). Nevertheless, despite these concerns, "nation-states do strive to exercise their sovereignty over cyberspace (Kanuck, 2010, p. 1573)." The physical elements of cybercrime, such as the location of the people perpetrating the crimes or the location of the hardware used to execute the crimes, are used as a connecting link to allow governments "to address cyber conflicts involving both state and nonstate actors as matters to be resolved by sovereign powers under their respective legal systems (p. 1573)." When evidence moves beyond territorial borders, states seek to invoke bilateral or international action to further pursue the crime. This model follows the same formula that society developed over time, whether it be in stopping crimes such as international drug trafficking or heinous acts of terrorism. The international community is well-Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 4 versed in this cycle, and the "nature of the international legal system affords this sovereign-centric approach primacy under the United Nations (U.N.) Charter regime (p. 1573)." If the international community is content in continuing to use this cycle, then "international legislation and action are essential to combat the phenomenon" of cybercrime (Pocar, 2004, 27). The essential requirement of international involvement and negotiation has rung true in the late 20th and early 21st centuries, as the international community takes steps to evolve international law to include cyber issues, specifically cybercrime. The 1980s introduced international consultation on cybercrime by multiple organizations. In 1983, the Organization for Economic Cooperation and Development (OECD) commissioned a two-year study focusing "on the possibility of harmonizing and internationalizing national cybercrime laws (Brenner, 2012, p. 133)." OECD later published a report in 1986 summarizing the results of the study and recommending countries criminalize certain cybercrimes. In 1985, the Council of Europe convened its own study, which involved a four-year focus on "the legal issues raised by cybercrime (p. 133)." In 1997, the Council of Europe convened another study tasked with "the drafting of a cybercrime treaty that would harmonize national laws dealing with cybercrime offenses and investigations (p. 133). In 2001, the study's efforts came to fruition in the creation of the Convention of Cybercrime. Also referred to as the Budapest Convention, the international treaty entered into law in July 2004 with the principle objective of "pursuing a common criminal policy aimed at the protection of society against cybercrime, especially by adopting appropriate legislation and fostering international co-operation (Council of Europe, 2001, Preamble)." As of 2018, 29 states have ratified the treaty, but the rapid development of technology has resulted in the convention becoming outdated, leaving governments and organizations calling for a new treaty (Murphy, 2018, p. 549) (Shackelford, 2014, p. 312). Russia's 2019 United Nations resolution is the latest attempt to modernize international cyber Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 5 law and has received much adulation despite its vague, concerning language and human rights implications. The next section of this paper addresses human rights and provides an overview of states' obligations to this arena as members of the international community. Human Rights & the International Community Modern international human rights law begins with the first article of the Charter of the United Nations (UN), which dictates that one of the purposes of the UN is to "achieve international cooperation…in promoting and encouraging "respect for human rights and for fundamental freedoms for all without distinction as to race, sex, language, or religion (Buergenthal, 2006, p. 785)." While the Charter provided minimal specificity as to what "respect for human rights" entailed, this provision and others within the Charter catalyzed a new international perspective on human rights. In joining the United Nations, members inherently accepted "the proposition that the Charter had internationalized the concept of human rights (p. 787)." Furthermore, the Charter insinuated that "states were deemed to have assumed some international obligations relating to human rights (p. 787)." Articles 55 and 56 of the Charter cemented the beginnings of these obligations, requiring member states to "take joint and separate action in co-operation with the Organization for the achievement of purposes" such as promoting "universal respect for, and observance of, human rights and fundamental freedoms for all (United Nations, 1945, Article 55, 56)." The specificity of human rights became more overt when the United Nations devoted the UN Commission on Human Rights to the task of drafting non-legally-binding human rights instrument. In December 1948, the UN General Assembly unanimously adopted the Universal Declaration on Human Rights (Murphy, 2018, p. 402). Composed of thirty articles, the declaration instituted vital human rights and eventually "served as a template for numerous subsequent treaties on human rights (p. 404)." As a result, the Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 6 Universal Declaration on Human Rights "has come to be accepted as a normative instrument in its own right (Buergenthal, 2006, p. 787)." Both documents uphold two pedestals of traditional international law as it pertains to human rights. The first pedestal retains responsibility for "the treatment by one state of another's nationals, an area known as state responsibility for injury to aliens (p. 389)." Although addressed at the state level, this notion asserts that individuals are afforded certain protections when in another state. The second pedestal, advanced by scholars such as Hugo Grotius, focuses on "the protection of persons against the acts of their own governments (p. 389)." It is this pedestal that introduces what is now known as humanitarian intervention, or the "idea of state intervening to protect the other state's nationals (p. 389)." Together, both the Charter of the United Nations and the Universal Declaration are "considered to spell out the general human rights obligations of all UN member states," of which there are now 193 (Buergenthal, 2006, p. 787) (Murphy, 2018, p. 59). Each international legal instrument has lent itself to the creation of international institutions dedicated to monitoring "compliance by the states parties with the obligations imposed by these instruments (Buergenthal, 2006, p. 788)." Such institutions include entities like the UN Human Rights Council and the Office of the United Nations High Commissioner for Human Rights (p. 788). Together, the instruments and institutions "laid the normative foundation of the contemporary international human rights revolution" and "influenced, in part at least, the contents of the legal norms under which international criminal tribunals operate today (p. 791)." The criticality of these elements to the international system, particularly as it pertains to international law, is justification for using each as measuring tools with which to judge the new UN cyber-focused resolution objectively. The third section of this paper will assess the purpose of the resolution and explain the supporting argument for its contents. Supporting Arguments & Analysis of A/74/401 Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 7 In order to truly understand the intent of international laws, it is crucial to develop an understanding of the stances actors take concerning the specific issues at hand. This understanding is of particular importance when discussing Resolution A/74/401 and the underlying views of cyberspace. Two opposing perspectives lie at the heart of debates surrounding the cyber domain and Internet governance and center around the notion of sovereignty. The first perspective is that "many governments are attempting to exert sovereignty in cyberspace in the same way as they do in physical domains (Nocetti, 2015, p. 111)." For these governments, the dominance of private sector institutions within cyberspace and "the unfettered internet access of their fellow citizens" are causes of concerns (p. 111). This sentiment is particularly true within the Russian government. Under its traditional views of governance, Russia "conceives of cyberspace as a territory with virtual borders corresponding to physical state borders, and wishes to see the remit of international laws extended to the internet space (p. 112)." Furthermore, Russia's domestic fears of an open Internet fuel its international concerns. Russia sees the Internet as "politically disruptive because it enables citizens to circumvent government-controlled 'traditional media (p. 113).'" It aligns this perspective "with the inherently authoritarian nature of the Russian regime (p. 114)." Russia's negative perception of the Internet as it is today ultimately lends itself to Russia's ideal mechanism of perpetuating its belief that "global internet governance is envisioned as an issue of high politics in which states - and the interstate balance of power-play – play an essential role (p. 116, 117)." Under this mechanism, it is little wonder that Russia has led international legal initiatives to refine control over the Internet since the Council of Europe's enactment of its Convention on Cybercrime. In a Ministry of Foreign Affairs press release following the General Assembly's adoption of Resolution A/74/401, Russia proclaimed that the "resolution shows that the world community urgently needs to develop a universal, comprehensive, and open-ended convention Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 8 on countering cybercrime (Ministry of Foreign Affairs, 2019)." The adopted resolution's language appears to align with this projected intent from Russia. The resolution stresses "the need to enhance coordination and cooperation among States in combating the use of information and communications technologies for criminal purposes" and notes "the importance of the international and regional instruments in the fight against cybercrime (United Nations, 2019, Countering the Use)." In order to fulfill these objectives, the resolution establishes an "intergovernmental committee of experts, representative of all regions" that will "elaborate a comprehensive international convention on countering the use of information and communications technologies for criminal purposes (United Nations, 2019)." Remarks of supporting nations support this appearance of cohesion. The representative from Nicaragua indicated the resolution would address cybercrime "in a more representative, democratic and transparent manner, taking into account the individual circumstances of developing and developed countries (Third Committee, 2019, Meetings Coverage)." China echoed this support, stating the resolution "is conducive to filling legal gaps in international cooperation (Third Committee)." At the same time, Belarus declared that "international cooperation is vital in investigating and combating cybercrime (Third Committee)." At face value, the resolution is a gesture of goodwill, a written contract to pursue options to disrupt cybercrime that will benefit all states. However, Russia's press release takes these notions a step further, realigning its message to its traditional view of international politics. It notes, "the resolution proposed by Russia essentially enhances states' digital sovereignty over their information space and ushers in a new page in the history of global efforts to counter cybercrime (Ministry of Foreign Affairs, 2019)." Furthermore, the press release dictates that the "convention must be based on the principles of respecting state sovereignty and non-interference in internal affairs (2019)." There are two Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 9 essential points within this statement that require further analysis. The first is the reassertion of the authoritarian construct with which Russia chooses to view cyberspace. In a press release initially dedicated to lauding the necessity of international cooperation, Russia simultaneously defaults to its traditional views of the international community and advocates for a "digital Westphalia (Nocetti, 2015, p. 117)." In recognizing sovereignty, Russia insinuates that the international community will successfully legislate mechanisms that will reduce cybercrime. A quick review of the supporting states in favor of the resolution upholds Russia's authoritarian views (United Nations, 2019, Countering the Use). In addition to China, Nicaragua, and Belarus, countries like Iran, Syria, Venezuela, Cuba, and the Democratic People's Republic of Korea are only some of the 88 Member States of the General Assembly who voted to adopt the resolution. Unsurprisingly, these states also abide by similar authoritarian perspectives on international law and sovereignty. China, for example, maintains a "comprehensive, multidimensional system that governs Internet infrastructure, commercial and social use as well as legal domains (Liang & Lu, 2010, p. 105)." This system supports "Internet censorship" and "China's single-party political system and its heavy intervention in Internet development (p. 105)." Given the nature and history of these states' political systems and methods of governance, the sudden focus on international cooperation generates questions of the underlying goals that may hide behind the official demands of the resolution. The second point requiring acknowledgment is the additional re-emphasis of sovereignty while also emphasizing non-interventionist beliefs in discussing non-interference in internal affairs. The resolution itself makes no mention of sovereignty or internal affairs beyond assisting countries with improving "national legislation and frameworks and build the capacity of national authorities" to deal with cybercrime (United Nations, 2019, Countering the Use). Despite the lack of language on this topic, the leading state on this initiative, Russia, felt the need Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 10 to emphasize its sovereignty in a press release about the resolution (Ministry of Foreign Affairs, 2019). Once again, Russia gives the impression that there may be a hidden desire layered within the words of the resolution. Additionally, the concept of non-interference within the international system is not without exceptions. The most critical exception being suspicion of human rights violations. As previously stated, humanitarian intervention and protecting citizens from their own government is a staple of international human rights law (Murphy, 2018, p. 389). Therefore, while non-interference in domestic matters is undoubtedly an essential tenet of international law, the resolution cannot call for international cooperation to combat cybercrime and simultaneously ignore the international cooperation required to maintain peace and security (United Nations, 1945, Charter of the United Nations). The next section of this paper will address these obligations to cooperation as it pertains to human rights while also highlighting the opposing arguments against Resolution A/74/401. Opposing Arguments for A/74/401 & Analysis of Human Rights Concerns The first perspective at the heart of the cyber domain debates, as described previously, is modeled after authoritarian beliefs and government control. The second perspective, modeled after a more Western approach to governance, is the belief of a free and open Internet that should remain decentralized and that "the best regulatory system is one that develops organically (Shackelford, 2013, p. 53)." A free Internet is more firmly the belief of the United States. This idea introduces the initial context necessary to understand the United States' opposition to the Russian-led cybercrime resolution. Even before the rapid development of the Internet, American foreign policy internalized the notion of "free flow of information internationally as an important element of national security (McCarthy, 2011, p. 92)." Former Secretary of State George Schultz argued that the free flow of information "undermined the Soviet Union and authoritarianism (p. 92, 93)." At its earliest beginnings, the Internet was a product of American ingenuity and, as a Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 11 result, built with a bias for "American libertarianism (p. 93)." In the present, the West has developed this concept in the "context of freedom expression, protection of intellectual property rights, and national security (Powers & Jablonski, 2015, p. 3)." As former Secretary of State Clinton asserted, the United States and other Western nations support the "freedom to connect" in opposition to efforts by states such as China, Iran, and Russia to create state-level information infrastructures designed for censorship (p. 3). The historical rivalry and disagreement between the two states on information, particularly as it pertains to cyberspace, only further roots the United States' opposition to the new United Nations cybercrime resolution. In its statement to the United Nations during the 49th & 50th meetings of the Third Committee, the United States expressed disappointment "with the decisions of the sponsors of this resolution to bring it to the Third Committee (United States Mission to the United Nations, 2019)." Contrary to the resolution's focus on cooperation, the United States' proclaimed the resolution would "drive a wedge between Member States and undermine international cooperation to combat cybercrime at a time when enhanced coordination is essential (United States Mission to the United Nations)." Furthermore, the United States asserted Russia's actions in introducing the resolution essentially bypass the "expert-driven, consensus-based process and therefore is not in line with their precedent (United States Mission to the United Nations)." Other Western states appear to agree with the United States assertions, as states such as the United Kingdom, Australia, France, Republic of Korea, and Germany composed part of the 58 Member States who opposed the adoption of the resolution (United Nations, 2019, Countering the Use). In a manner similar to the states in favor of the adoption, some opposed states made remarks in agreement with those of the United States during the Third Committee. Finland, on behalf of the European Union, remarked that "there is no consensus on the need for a new international instrument to fight cybercrime" and that the draft "represents a duplication of resources (Third Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 12 Committee, 2019, Meetings Coverage). Canada and Australia presented similar sentiments, remarking that "the Budapest Convention on Cybercrime is an important baseline for international cooperation" and that the new resolution "seeks to undercut consensus and will diminish existing global efforts that are already delivering results (Third Committee, 2019)." There is one remaining argument against the new cybercrime resolution: the potential that the document's vague language will create an environment where human rights will be more easily violated if left unchecked (Hakmeh & Peters, 2020). In a letter to the United Nations General Assembly, 37 organizations and six individuals expressed their concern for human rights protections as they pertain to the cybercrime resolution (Association for Progressive Communications (APC), 2019, Open Letter, p. 4). The first concern is a lack of clarity surrounding the scope of the "use of information and communications technologies for criminal purposes (APC, p. 1)." If left undefined, the language in the resolution arguably "opens the door to criminalising ordinary online behaviour that is protected under international human rights law (APC, p. 1)." If steps to do so were taken as a result of the new resolution, they would be in direct violation of the United Nations High Commission for Human Rights; who stated in 2011 that "human rights are equally valid online as offline (Shackelford, 2019, p. 168)." The second concern offered by non-government entities is the increasing trend in "criminalising ordinary online activities of individuals and organisations through the application of cybercrime laws (APC, 2019, Open Letter, p. 1, 2)." The letter even goes so far as to quote the UN Special Rapporteur over these concerns, that the "surge in legislation and policies aimed at combating cybercrime has also opened the door to punishing and surveilling activists and protestors in many countries around the world (APC, p. 2)." If used in such a manner, these initiatives, in addition to the UN cybercrime resolution, are in direct violation of the Charter of United Nations and the Universal Declaration on Human Rights. Within the Charter of the United Nations, efforts to Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 13 restrict or punish opposition elements such as activists or protestors violates Articles 55 and 56, which requires states to cooperate with the UN in achieving the organizations' purposes such as promoting human rights (United Nations, 1945, Article 55, 56). The Universal Declaration on Human Rights provides more specific language with which to attribute potential violations. The open letter notes that legislation of this kind is used to "criminalise legitimate forms of online expression, association and assembly through vague and ill-defined terms that allow for arbitrary or discretionary application (APC, 2019, Open Letter, p. 2)." Immediately, legislation that allows for criminalization of these elements is in direct violation of Articles 18, 19, and 20, which declare "all persons have a right to freedom of thought, conscience, religion, and assembly (Murphy, 2018, p. 402)." Furthermore, violations such as these also violate article two, which guarantees people "the right to life, liberty, and security" and dictates that "these rights are to be held without discrimination of any kind (Murphy, p. 402, 403)." Upholding these rights within cyberspace continues to fall in line with the Western perspective on the Internet. As McCarthy quotes, "the Internet is arguably the greatest facilitator for freedom of expression and innovation in the world today (McCarthy, 2011, p. 94)." The status of the Universal Declaration on Human Rights as "legitimate norms within the international system" permits this interpretation and application of international law to future resolutions (p. 94). If states are signatories to the declaration, any future adoption of any resolution must adhere to the principles and freedoms guaranteed by it. Resolution A/74/401 does refer to human rights protections, "reaffirming the importance of respect for human rights and fundamental freedoms in the use of information and communication technologies (United Nations, 2019, Countering the Use)." However, the resolution's open language is in direct contradiction to this promise, if not clarified. As the open letter indicates, "simply reaffirming the importance of respect for human rights" is "insufficient to safeguard human rights while Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 14 countering cybercrime (APC, 2019, Open Letter, p. 2)." The final section of this paper recommends additional actions that may further unify opposing entities on this resolution while simultaneously addressing all human rights concerns. Recommendations The Russian-led supporters of the resolution and the United States-led opposition are unified in one common element, at least in writing. The element is that consensus and international cooperation are vital in addressing cybercrime (Ministry of Foreign Affairs, 2019) (United States Mission to the United Nations, 2019). This notion is in concert with the Council of Europe, who remains the only entity to successfully orchestrate an international cybercrime treaty (Council of Europe, 2004, Convention on Cybercrime). In 2001, the Council of Europe postulated that "solutions to the problems posed must be addressed by international law, necessitating the adoption of adequate international legal instruments" that can "ensure the necessary efficiency" required to combat cybercrime (Pocar, 2004, p. 28). If the international community determines that another cybercrime treaty is required within the intergovernmental committee of experts authorized by Resolution A/74/401, then the new treaty should consider the aims of the Council of Europe Convention on Cybercrime (United Nations, 2019, Countering the Use). In doing so, the United Nations should strive to create a "basic framework for the establishment by contracting states of domestic substantive and procedural laws" in a manner that allows states to "cooperate expeditiously with one another (Pocar, 2004, p. 30)." If successful, the United Nations will be able to "establish procedures for relevant international relations" and provide "forms of cooperation between national judicial authorities as many interact with each other both swiftly and efficiently (p. 31)." Furthermore, the necessity of these requirements is supported by the very nature of the "the world-wide dimension of the Internet," Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 15 which "implies that its illegal use and related offenses must prompt responses and concerted efforts from all relevant domestic and international authorities (p. 34)." The non-governmental organizations' open letter to the United Nations supports the need for cooperation but takes it one step further than the states themselves. In its current structure, the Internet is a public-private endeavor, with private entities dominating cyberspace (Nocetti, 2015, p. 111). The present language of the United Nations cybercrime resolution allows for an intergovernmental committee of experts. However, it does not expand on the actual composition of the committee (United Nations, 2019, Countering the Use). Noting that Russia and other authoritarian regimes prefer non-government entities to use the government as a proxy for communication, it can be inferred that a Russia-led resolution intends the committee to be comprised of only government entities (p. 117). The open letter rightly points out that collaboration on cyber issues must expand beyond state cooperation. Addressing cybercrime is "necessarily a multi-stakeholder endeavour" that "requires government officials and experts, members of the technical community, civil society, the private sector, and scientific and research institutions (APC, 2019, Open Letter, p. 4)." An assessment of this viewpoint reveals that a committee dedicated to combatting cybercrime cannot rely on government expertise alone. In order to accurately reflect the composition and requirements of a private-public Internet, all discussions surrounding this resolution should involve both private and public entities. Therefore, the committee should be reformed to more accurately reflect the Internet's users. In doing so, the United Nations breaches the divide between authoritarian and more democratic governments, further increasing cooperation on this resolution. However, increased cooperation through a broader, inclusive committee and implementation of lessons learned from the Council of Europe Convention on Cybercrime will not ensure that the future convention successfully resolves the resolution's weaknesses. In Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 16 modern-day, the international system emphasizes international human rights more than ever before, as "this branch of international law has experienced phenomenal growth over the past one hundred years (Buergenthal, 2006, p. 807)." This growth has contributed to the "growing political impact of human rights on the conduct of international relations and the behavior of governments (p. 807)." If real success is desired within international governance, then the committee established under the "Countering the use of information and communications technologies for criminal purposes" resolution must account for human rights protections when determining the requirements of the "comprehensive international convention (United Nations, 2019, Countering the Use)." As the representative from Costa Rica during the 49th and 50th meetings of the Third Committee, "the international community must protect and observe fundamental freedoms, including the right to privacy (Third Committee, 2019, Meeting Coverage)." Until there is consensus on "sensitive topics such as…State responsibility to prioritize and protect human rights," the future proposed convention will fall short of its goal of achieving complete international ratification (Third Committee). Conclusion As cyberspace expands in conjunction with the rapid advancement of technology, the fear of the unknown drives further division between already opposing states in the international system. Resolution A/74/401 is the latest testament to the evolution of politicization within Internet governance. In addressing a topic that impacts every Internet-accessible region of the world, the resolution simultaneously magnifies the opposing perspectives of states as it pertains to sovereignty within the cyber domain. Furthermore, it reignites the protracted debate over whether or not human rights obligations addressed in such documents as the Charter of the United Nations or Universal Declaration on Human Rights are legally binding. Preventing further polarization requires both an acknowledgment of a fracturing international system of Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 17 governance and a proposed solution to address the issue. While state-centric governance provides legitimacy and the potential for a higher allocation of resources dedicated to protecting the Internet, increased sovereignty also "risks sacrificing innovation, complicates the regulatory environment of cyberspace, and may threaten a positive vision of cyber peace (Shackelford, 2013, p. 50)." These risks are why an alternative method to an intergovernmental committee must develop in response to the resolution. This method should integrate a multi-stakeholder construct to more fully recognize the competing impacts of cybercrime and fairly address the allegations of human rights infringement. One such method is polycentric governance, a system composed of "diverse organizations and governments working at multiple levels" in order to "increase levels of voluntary cooperation or increase compliance with rules established by governmental authorities (p. 330)." Individually, each organization or type of government faces its own unique hurdles. Together, they "contribute to a governance regime that is multi-level, multi-purpose, multi-type, and multi-sectoral in scope that could complement the top-down governance model increasingly favored" by states such as Russia or China (p. 331). Implementing polycentric governance to more equitably debate the appropriate response to international cybercrime will create an international community willing to consider the developing convention. In doing so, the environment will be better suited to determining whether or not the international system can leverage international law to investigate and prosecute cybercrime. Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 18 References Association for Progressive Communications (APC). (2019). Open Letter to UN General Assembly: Proposed international convention on cybercrime poses a threat to human rights online. Retrieved from https://www.apc.org/sites/default/files/Open_letter_re_UNGA_cybercrime_resolution_0.pdf Brenner, S. (2012). Cybercrime and the Law: Challenges, Issues, and Outcomes. Northeastern University Press. Retrieved from https://ebookcentral.proquest.com/lib/norwich/reader.action?docID=1085118&ppg=124 Buergenthal, T. (2006). The Evolving International Human Rights System. The American Journal of International Law, 100(4), 783-807. Retrieved from https://www-jstor-org.library.norwich.edu/stable/pdf/4126317.pdf?refreqid=excelsior%3Ae4ea9f31648cbd83f8f97bc7dae8e67a Cangemi, D. (2004). Procedural Law Provisions of the Council of Europe Convention on Cybercrime. International Review of Law Computers & Technology, 18(2), 165-171. Retrieved from https://norwich.on.worldcat.org/oclc/5272830680 Center for Strategic & International Studies & McAfee. (2018). Economic Impact of Cybercrime – No Slowing Down. Retrieved from https://www.csis.org/analysis/economic-impact-cybercrime Council of Europe. (2004). Convention on Cybercrime. Retrieved from https://www.coe.int/en/web/conventions/full-list/-/conventions/treaty/185 Hakmeh, J. & Peters, A. (2020). A New UN Cybercrime Treaty? The Way Forward for Supporters of an Open, Free, and Secure Internet. Council on Foreign Relations. Retrieved from https://www.cfr.org/blog/new-un-cybercrime-treaty-way-forward-supporters-open-free-and-secure-internet Kanuck, S. (2010). Sovereign Discourse on Cyber Conflict Under International Law. Texas Law Review, 88, 1571-1597. Retrieved from https://www.law.upenn.edu/institutes/cerl/conferences/cyberwar/papers/reading/Kanuck.pdf Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 19 Liang, B., & Lu, H. (2010). Internet Development, Censorship, and Cyber Crimes in China. Journal of Contemporary Criminal Justice, 26(1), 103–120. Retrieved from https://norwich.on.worldcat.org/oclc/5322181473 McCarthy, D. (2011). Open Networks and the Open Door: American Foreign Policy and the Narration of the Internet. Foreign Policy Analysis, 7(1), 89-111. Ministry of Foreign Affairs of the Russian Federation. (2019, December). Press Release on the UN General Assembly Vote on the Russian Draft Resolution on Countering Cybercrime. Retrieved from https://www.mid.ru/en/foreign_policy/news/-/asset_publisher/cKNonkJE02Bw/content/id/3988579 Murphy, S. (2018). Principles of international law (3rd edition). West Academic Publishing. Nocetti, J. (2015). Contest and Conquest: Russia and Global Internet Governance. International Affairs, 91(1), 111-130. Retrieved from https://norwich.on.worldcat.org/oclc/5721220595 Pocar, F. (2004). New Challenges for International Rules Against Cyber-Crime. European Journal on Criminal Policy and Research, 10(1), 27-37. Retrieved from https://norwich.on.worldcat.org/oclc/5649374698 Powers, S. & Jablonski, M. (2015). The Real Cyber War: The Political Economy of Internet Freedom. University of Illinois Press. Retrieved from https://norwich.on.worldcat.org/oclc/903245891 Shackelford, S. J. (2013). Managing Cyber Attacks in International Law, Business, and Relations: In Search of Cyber Peace: Vol. Revised Edition. Cambridge University Press. Retrieved from https://norwich.on.worldcat.org/oclc/882104883 Shackelford, S. (2019). Should Cybersecurity Be a Human Right? Exploring the "Shared Responsibility" of Cyber Peace. Stanford Journal of International Law, 55(2), 155–184. Retrieved from https://norwich.on.worldcat.org/oclc/8185136062 United Nations General Assembly. (1945). Charter of the United Nations. Retrieved from https://www.un.org/en/charter-united-nations/index.html United Nations General Assembly. (2019). Countering the use of information and communications technologies for criminal purposes. Retrieved from https://www.undocs.org/A/74/401 United Nations Third Committee. (2019, November). Meetings Coverage Seventy-Fourth Session, 49th & 50th Meetings. Retrieved from https://www.un.org/press/en/2019/gashc4284.doc.htm United States Mission to the United Nations. (2019, November). Statement on Agenda Item 107 'Countering the use of information and communications technologies for criminal purposes.' Retrieved from https://usun.usmission.gov/statement-on-agenda-item-107-countering-the-use-of-information-and-communications-technologies-for-criminal-purposes/ Running head: INTERNATIONAL LAW & THE CYBER DOMAIN 20 Zekos, G. (2008). Electronic State Sovereignty. The Icfai University Journal of Cyber Law, 7(4), 30-60.
Rosa Ricci Summary of the PHD Dissertation: Religious Nonconformity and cultural Dynamics: The Case of the Dutch Collegiants There is ample reason to engage in research around the Collegiants, a minority religious movement in the Netherlands of the 17th century. An exploration of this topic can be interesting not only for a contribution to the history of Religion but also to understand the development of some central concept in the early modernity. Prominent, in this research, is the question that initially stirred my personal interest in the Collegiantism; i.e. to define and understand the religious and cultural background that represents the practical field of confrontation of Baruch Spinoza\''s philosophy. This historiographical question had the purpose of highlighting the relationship between Spinoza and the religious movements of his time in order to fully understand the public to whom he addressed his texts. Collegiants, however, constitute an interesting field of research not only for the study of Spinoza, but widely to understand the cultural and social dynamic of the Dutch Golden Age, a backdrop against which emerged a new idea of religion. This dissertation is not exploring a curiosity or an inconsistent exception in the history of the 17th century, but rather the centrality of a group that was influenced by and largely influenced its Dutch social, political and religious context. One of the major problems in capturing the significance of the Collegiants arises from the difficulty in defining this movement, which chose never to formulate a confession of faith and consciously refused to be classified within a specific Church, sect, or congregation. The name, Collegiants, was not the consequence of an active choice but a label that arose, together with that of Rijnsburgers, in the polemic pamphlets of the epoch. The difficulties to define such elusive religious group make, however, the Collegiants a fascinating field of research. In this dissertation the Collegaints are termed a "movement" in order to emphasize their explicit lacks of norms or model and to highlight the continual change and redefinition of their religious identity. This process can be properly defined using Deleuze\''s concept of becoming minorities: Les minorités et les majorités ne se distinguent pas par le nombre. Une minorité peut être plus nombreuse qu\''une majorité. Ce qui définit la majorité, c\''est un modèle auquel il faut être conforme [.] Tandis qu\''une minorité n\''a pas de modèle, c\''est un devenir, un processus [.] Quand une minorité se crée des modèles, c\''est parce qu\''elle veut devenir majoritaire, et c\''est sans doute inévitable pour sa survie ou son salut. This definition can help us to see both the positive and the productive side of the Collegiant movement, even thought it defined itself negatively in order to protest against the institutional Church and normative religion. The Collegiants were involved in this process of "devenir minoritaire" in a highly conscious way. They decided willfully to avoid strict affiliation to Churches or congregations and criticized explicitly the necessity of an identitarian definition. It can hardly be denied, indeed, that the religious reflection of the Collegiants was characterized by the conscientious refusal to construct a model or a norm to which they could refer. In this dissertation the term "minority" will therefore be used, always in reference to this concept, without drawing too much stress to the effective number of the Collegiants\'' members. This question appear, indeed, misleading because it does not take into account the position that Collegiants\'' member occupied in the economic, political and intellectual life of the United Provinces. It is the case of a group which, indeed, demonstrated in several occasions its deep influence in the Dutch religious life. Collegiants\'' continuous efforts towards de-institutionalization and their aspiration to an egalitarian and democratic religious life have to be conceived as an invitation to their coeval confessions, to undertake the way of evolving minorities renouncing whichever exclusivity and authority. The articulation of the Collegiants\'' proposal can be appreciated by studying the different lines of thought that emerged clearly from their texts. Most of Collegiants\'' publications were polemical or written to answer specific accusations. Within the enormous number of sources that can be included in Collegiants\'' works emerge a limited number of arguments. The question of religious organization, tolerance, freedom of speech and the epistemological approach in reading the Scriptures; these arguments can be taken as guidelines to understanding and defining the nature of the movement. These sources present arguments and concepts that we can take to be the Collegiants\'' stance on religious life and belief. Some arguments, however, emerged with particularly force because of the sanction of the Church orthodoxy. Tolerance, free-prophecy and egalitarian and anti-authoritarian tendencies were sensitive points to which the Church or Congregations reacted with particularly vehemence, sensing a threat to their institutional power. The Chapter 5 of this dissertation are dedicated to the enumeration of these arguments. Each chapter presents a specific theoretical core and question. However the chapters are not self-conclusive because the various problematics encountered in the study of Collegiants overlap each other in continuous cross-reference and this gives rise to a kaleidoscopic effect. The concepts debated in this dissertation can be fully understood only in relation to each other, as they emerge to construct a semantic constellation useful to their contextualization. Each chapter, furthermore, comes to focus on one or more texts that are considered exemplary or representative of a particular tendency in the Collegiants´history. This methodology wants to underline how the constant redefinition of the Collegiants\'' identity is always a matter of personal as well as collective choice, of internal debate and external polemic. An emphasis on the intentionality of Collegiants\'' behaviour is particularly important in understanding which specific choice they made to contrast the authoritarian and exclusive vision of the religious life. These choices are well reflected in the use of a specific vocabulary and in the emergence of specific concepts that can be considered as key guideline to identifying some stable points in the shifting nature of the Collegiants. The first chapter of this dissertation delineates an initial general history of the movement together with the ground on which the Collegiants built their vision of belief: the question about Church organization. The chapter refers directly to the practical organization of the Collegiant movement, an egalitarian and anti-charismatic religious life which involved considerations of power and identity. This specific position, with its high level of nonexclusivity and anticharismatic consciousness, makes Collegiants movement an exception in the pluralist world of 17th century Holland and marked their difference to the constellation of Dutch reformation. Although some Collegiants\'' demeanor mirrored the progressive individualization of cults and beliefs, they accorded central importance to the community, the context in which their religious ideal of confrontation and discussion was realized. The first attempt to write an exhaustive history of the rise and development of the Rijnsburgers was made by a Remonstrant preacher, Paschier de Fijne. He was the first opponent of the Collegiants; his book, Kort, waerachtigh, en getrouw Varhael van het eerste Begin en Opkomen van de Nieuwe Sekte der Propheten ofte Rynsburgers in het dorp Warmont anno 1619 en 1620 (Brief, truthful, and faithful history of the beginning and origin of the new sect of the Prophet of Rijnsburg in the village of Warmont), published anonymously in 1671 by his son, expresses his critical position vis à vis the Rijnsburgers. Besides representing the first opposition to the Collegiants, this work constitutes an important source because the author attended the first Collegiant\'' assembly (the Rijnsburgers\'' vergadering). In particular it describes the way in which this first meeting took place. For the first complete history of the Collegiant movement, however, we have to wait until 1775 when the Histoire der Rijnburgsche Vergadering (History of Rijnsburg\''s assembly), written by the Collegiant Elias van Nijmegen, appeared in Rotterdam. Both these sources are key instruments for reconstructing and understanding how Collegiants organized their assemblies, and how they achieved an acharismatic meeting, through debate and free-exegesis. These testimonies, which embrace a whole century, have, however, the demerit of representing the Collegiant\'' vergadering (assembly) as an eccentric but defined ritual. What emerges, on the other hand, from Collegiants internal debate is that the conduct of the meeting supper, the organization of religious life, the definition of free-exegesis and the limitation of free speech were all subject to constant argument and discussion inside the movement. These concerns emerge in a fragmentary way in the manifold sources that discuss the nature of free-prophecy, tolerance and ecclesiology. In the polemic with Bredenburg, the Bredenburgse twisten, the debate about tolerance involved the discussion of women's role in the vergadering and the reflections on free-prophecy indirectly interrogate the charismatic nature of the organization. Another important characteristic of the Collegiant\'' movement, delineate in the first chapter, is the autonomous and independent development of the single collegia. City autonomy and the different religious and social contexts in which the Rijnsburger vergadering took root led to large-scale differentiation. The capacity of Collegiants to survive for more than a century with their refusal of normativity and authoritarian organization was substantially due to the penetration of the Collegiants\'' arguments into the different confessions. This deep influence, in particular in the Mennonite and Remonstrant communities, defined the nature of the Collegiants, especially in some cities, as a stream inside institutionalized Churches. Because the collegia were open to all Christians, without limitation, even including Socinians and Catholics, most of the participants were also members of structured Churches, congregations or sects. In Amsterdam this phenomenon was particularly evident and the penetration of Collegiants\'' argument in the Flemish community through Galenus Abrahamsz led to one of the most important schisms in the Mennonite history in the United Provinces. In other cities such as Leiden or Haarlem, the existence of cultural circles and other forms of nonreligious association constituted the basis for the spread of Collegiantism. It was only in Rijnsburg, the village in which the movement first emerged, that a common house was built, after 1640, to host the twice yearly Collegiant national vergadering. The practical organization of the Collegiants, as has been stated, represents the foundation on which noncharismatic ecclesiology and anticonfessional ideals were constructed. With the historical background of the first chapter it is then possible to discuss the main religious and political tendencies inside the movement. The second chapter of this dissertation, following the issue of religious organization discussed in the first chapter, deals with the principles of free-prophecy, Biblical exegesis, and Collegiants ecclesiology. The central concept examined in this chapter is nonconformity analysed in its historical development of England and the Netherlands. This chapter suggests that nonconformity as religious phenomenon was an elaboration and transformation of the anti-confessional and anti-clerical thought that emerged in the 16th century with the radical Reformation. The inception of nonconformity in the Netherlands is indicated by the transformation of the debate about Nicodemism, following Coornhert\''s defense of religious dissimulation and indifferentism. Nicodemism was indeed considered, in the early 16th century, as necessary behavior to avoid pointless martyrdom and persecution, utilized especially by the crypto-reformed in Catholic countries such as Italy and Spain. The diffusion of this conduct among Catholics in reformed countries but, principally, the diffusion and justification of Nicodemism in the United Provinces, where inquisitorial control and confessional repression presented a relative risk after the revolt against Spain, testify of the new meaning that this behaviour took on in the late 16th century. Nicodemism, as Coornhert\''s position shows, became the justification of anticonfessionalism as conscious behaviour, with the possibility of openly criticizing rituals and ceremonies as for achieving salvation. In this chapter particular attention is paid to the consciousness and the open dimension of this behavior. The neglect of dissimulation and the necessity of making public personal religious sentiments, is one of the basic elements in the change between Nicodemism and nonconformity. The nonconformists acquired the anticonfessional and anticlerical content of Nicodemism, but added a principal characteristic: the veridiction. The veridiction represents the necessity of telling the truth about personal belief and religious conscience, but also institutes the core of reality in the conformity between internal belief and external behavior. These elements were present in both English and Dutch nonconformity, which developed, however, into different and sometimes opposite ecclesiology. In the English case, external nonconformity to the dominant Church and the necessity of openly showing belief led to a demand for exclusivity and a process of individualization rooted in the juridical meaning of nonconformity. Despite the turning of the debate around the necessity of free-conscience, the understanding of nonconformity as a refusal of secular world and the attempt of Baxter to disconnect the debate around nonconformity to a juridical question, the English debate never developed into a criticism of the Church\''s organization or in the necessity of a democratization of the religious life, which was, on the contrary, dominant among the Collegiants. The central text in the history of Collegiantism and in the Dutch definition of nonconformity is Galenus Abrahamsz and David Spruyt\''s XIX Artikelen. This text was conceived, from the very beginning, as a collective discussion about the nature and the sense of a religious community in the absence of Holy Gifts. Collegiants give to the term nonconformity a specific meaning which designates the absence of conformity to the first apostolic Church and the end of the extraordinaries gifts of the Holy Spirit. This radical statement caused a reaction among the orthodox members of the Mennonites and Quakers, which see in the absence of Holy inspiration a complete secularization of the religious community. Nonconformity assumed therefore for the Collegiants a double meaning: on one side it was an elaboration of anticonfessional criticism through the statement of the absence of holy influence on the religious life, on another side it represented a deep criticism of priestly authority conceived as a secularized power acting as constraint of consciences. The absence of Holy Gifts was, for the Collegiants, the demonstration that no Church or Congregation could pretend to be the true or original one. The reaction of Dutch orthodoxy appears, indeed, completely justified, because Collegiants\'' religious nonconformity presents itself not only as conscious antiauthoritarian criticism but also as a statement of the full secularization of the Church. Nonconformity was, for Abrahamsz and Spruyt, not only an unavoidable state, but also a necessary behavior to unmask the inauthentic religious life. This position represented the core of Collegiants\'' practice, the reason for their continuous redefinition and, on the same level, for their refusal of any type of identification. The recognition of the secularized status of common religious life arose among the Collegiants accompanied by an ample debate about free-prophecy and Bible exegesis, stressing the possibility of an individual form of salvation. A central role, in this direction, was played by reflection on the veridiction as a form of conformity between the inward conscience and the external behavior. Although there emerged from the sources a controversial statement about how to approach and read the Scriptures, through the free-prophecy the Collegiants organized a form of collective exegesis that had its principal aim to avoid charismatic and authoritarian leadership but also to realize a form of community close to the first apostolic Church. The communitarian discussion also involved a debate on salvation, which had no more to be tied to the simple membership in a confession but developed as an articulated discussion on the significance of the ethical and religious life. A good Christian had to reinterpret and bring alive the first teaching of the Gospel, which can be summarized as love for others and in the propagation of tolerance as ethical and interpersonal behavior. Collegiants\'' reflections on religious life, organization of communities, and their continuous effort to maintain equal relations in the absence of charismatic gifts in the Church institution, never turn to consideration of society or political forms. This absence was even more significant in a cultural and social context in which theological questions involved directly or indirectly political questions. In the same period, furthermore, Hobbes\'' reflections on jusnaturalism challenge for the first time the divine legitimacy of political power, establishing the basis of a new vision of the political community. Collegiants understood religious community as deprived from any form of divine inspiration and conceived it as a human association, nevertheless they never outline a political parallelism to this situation. The most evident reason of this absence is probably the lack of a strong monarchy in the 17th century United Provinces. However the relationship between secular and religious ideology did not fail and was well summarized by the situation after the Synod of Dordrecht, which created a rupture in Dutch society with the consequent convergence of the religious position with the political one. The intervention of Grotius in favor of the Arminian party testified to a clear identification between theological opposition to predestination (which meant a challenge to Calvinist orthodoxy) and antimonarchical opinion. This fracture remained invisible in Collegiants sources that debated the secularization of Churches and consider religious congregations as human institutions, but never tried to define the legitimacy of political institutions. It is possible, however, to find in the history of the Collegiants one significant exception: Cornelius Plockhoy\''s attempt to promote a religious-social project in the Dutch colonies of Delaware . Plockhoy\''s work illuminates the relationship and the fruitful parallels that it is possible to make between the United Provinces and England, especially during the time of the Cromwellian Commonwealth. Plockhoy\''s most significant works were written, indeed, in England, some years before the fail of Cromwell, and testify to a particular social and political engagement in the construction and definition of a community with a religious basis. It is interesting to note that only after the English experience did Plockhoy returned to Holland, following the end of the Commonwealth, to propose a similar project to the city of Amsterdam. This chapter suggests an analysis of his English and Dutch sources, stressing the differences and the modifications to his proposal. The importance of this author lies in the possibility of deducing from his position a possible Collegiant\'' thinking on politics and social organization. This contribution is certainly not descriptive of Collegiantism as a whole but represents the only explicit trace of the modification of Rijnsburger\''s religious reflections on the secular field. The description of Plockhoy\''s community in many respects echoes a certain irenicism sourced form the reading of Rosicrucian text; however it reflets and refers principally to his Collegiant experience . Although Plockhoy\''s account of the community project is never exclusively religious, the confessional element appears as prominently in both his Dutch and English projects. His religious and political project emerge clearly from his letters to Cromwell: it is essentially devoted to resolving the problem of religious conflict and the disturbance of social peace. It is, indeed, clear that Plockhoy\''s aim was not that of describing an ideal society or forming a separate community in order to conserve a purist religious ideal, but to propose a paradigmatic alternative to the religious turmoil and the social injustices of his time. The relation between political and religious arguments in Plockhoy\''s solution to religious turmoil highlights the interconnection between religious tolerance and colonial criticism, social injustice and authoritarianism. Plockhoy\''s meticulous pedagogic description of his project, his underlining of the necessity of economic independence for women and the possibility of them participating in collective work are expressions of an outlook that includes an aware judgment of his contemporary society. The last part of this chapter is dedicated to criticizes two approaches dominant in the literature about Plockhoy: one is the description of his project as a classical form of Utopia the other one is the reading of the Delaware religious community interpreted as a triumph of the work ethic. The third chapter of this dissertation deals with the tolerance, a fundamental and central concept to understand the nature of the Collegiants. It is our intention to show how during the 17th century there emerged in the Netherlands, in the religious context, a new concept of tolerance inspired by Castellio\''s works. The publication and translation, in the first half of the 17th century, of some of Castellio\''s work testify to the major interest that the French author had in the United Provinces, especially for the oppositors to the intolerant and orthodox Calvinist tradition. For the Collegiants, Castellio represented a predecessor in the struggle for religious peace. His work against the persecution of the heretics, supported by Biblical argumentation, represented a constant source of inspiration for the partisan of religious toleration. As suggested by Voogt , Castellio\''s deconstruction of the concept of heresy, as it was used by the Calvinist orthodoxy, in order to redefined it to signify a person who acts and believes differently from the mainstream, represented Collegiants\'' basis to rethink the concepts of rationality and truth. The peculiarity of the Dutch concept of vedraagzaamheid (tolerance), in opposition to how tolerance was defined and discussed in the European mainstream debate, was certainly due to the elements of reciprocity and mutuality that this particular form of tolerance included. In the 17th century, tolerance (especially religious tolerance) was used to label negative behavior, to identify indifferentism or libertinism, intolerance was, on the contrary, a sign of unity, integrity, and orthodoxy. Furthermore, arguments for religious intolerance were justified by the biblical example of the Mosaic theocracy, while religious tolerance represented the interests of the emerging mercantile elite, which supported the Republican experiment and advocated cities\'' autonomy. Tolerance became, in the 17th century, a concept contested because of its pejorative meaning; the progressive introduction of the pro-tolerance position, in order to contrast with this negative predominant vision, supported the idea that tolerance was not a menace to the integrity and peace of the Dutch Republic but the principal reason for its prosperity. The concept of tolerance became, afterwards, the battle-field on which the best juridical, economical and political form of the United Provinces was decided. The penetration of this debate about tolerance and intolerance in the Collegiants movement was adapted into an anticonfessional and irenic orientation focusing on religious and social peace. The defense of an unlimited and mutual tolerance represented, for the Collegiants, a proposal of pacification in the pluralistic dimension of the Dutch religious life, which was perceived, by their coeval, as a source of division and instability. The practice of nonexclusive tolerance and the extensive reception of different confessions inside the movement was a pragmatic attempt to find a solution to the problematic turbulence inside the Doopsgezinden and more generally to the religious disputations in the United Provinces. The central figure investigating the conduct and the limits of this debate inside the Collegiants was Jan Bredenburg. This chapter will, indeed, analyze the trouble arising from Bredenburg\''s position on tolerance and his extensive use of Spinozist concepts and language. This debate about the extension and the limits of tolerance involved, indirectly and directly, a discussion regarding religious organization, freedom of speech, and charismatic authority. In his works, Bredenburg, with his continuous redefinition of the discussion about tolerance, shows all the ambiguity and ambivalence of this term. Unlimited and mutual tolerance finds its limits in the continuous exigence of a normative delimitation of it, in the distinction of necessary and unnecessary dogma, but also, in a trivial way, in the impossibility of tolerating the intolerant. In the case of the Collegiants the adversaries of the unlimited and mutual tolerance undermined Collegiants\'' nonexclusivism with their proposals to identify with a confession of faith. Pressures in the direction of identification and exclusivism were, however, only a part of the tolerance problem. With the "Bredenburgse Twisten" (Bredenburg controversy) the limits and the ambiguities of the concept of tolerance and the limits of the penetration of Spinoza\''s philosophy in Collegiant\'' movement become clear. These limits concerned especially the necessity and priority of contrasting skeptical and atheist tendencies in the field of belief. The final chapter of this dissertation is dedicated to a question that underlines the problems of anticonfessionalism, tolerance, and secularization. The question asked in this conclusive part regards the possibility to trace the emergence of rational argument in Collegiants understanding of the divinity. To answer this question it was necessary to make some preliminary remarks about the diffusion and vernacularization of Descartes\'' and Spinoza\''s philosophies in the 17th century Netherlands. Short descriptions of the two most influential systems of thought of the epoch are two methodological steps useful in understanding not only the degree of penetration of these philosophies into Collegiants but also the nature and meaning of the concept of rationality at that time. The definition of the relationship with the divinity, after the XIX Arikelen\''s statement of the unholy Church, is represented, in the history of the Collegiant movement, by a precise moment: the discussion and dispute between the Rijnsburgers and the Quaker missionaries in the United Provinces. The debate with the Quakers assumes a specific meaning not only because it shows the proximity and similarity between the two religious movements but also because it testifies to the emergence of a central concept: the light. Central text to determine the nature of this relationship and to define the meaning that for the Collegiants had the concept of light, is Balling´s Het licht op den Kandelaar (The Light on the Candlestick). Balling\''s answer to Quakers represents a penetration of Spinozist language into the definition of religion as knowledge of God but also a singular affinity and fascination for the Quakers\'' concept of light. The question of contact with the divinity appears in the text as an individual experience, not mediated by any human instrument via language or the empirical experience. The approach to God is certainly described as an epistemological progression but the perfect comprehension of God is defined with the vocabulary of the affections rather than as full rational understanding. This text is certainly highly controversial and the continuous shift between philosophical and Quakers\'' language make its interpretation problematic. Het licht op den Kandelaar reflects Collegiants\'' position as a sum of philosophical argumentation, mysticism, and the irreconcilable reference to God as an infinite and unknowable creature. What emerges with force in the analysis of this source is the impossibility of understanding Balling\''s description of the relationship with God as purely rational. Balling, however, stresses the possibility of the constant perfectionism of human knowledge and self-emancipation and, furthermore, proposes new terms for religious thought. What he calls the "true religion" is described as ethical behavior constructed with the combination of tolerance, equal participation in the religious life, and the refusal to countenance formal conformism to Church institutions. Collegiants\'' acceptance of a Church without God does not necessary involve a pure absence of divine work, on the contrary, the proximity to God is progressively researched in an interior sphere which involve a process of knowledge. The legitimacy of the "Truth" is, then, given no more by the transcendental gift of the divinity but in the accordance of personal conviction and ethical behavior, the religion is, indeed, redefined according to these terms. True religion is, for Balling, a continuous inquiry into the natural and internal principle that each individual possesses in order to achieve full comprehension of God\''s word. This statement testify not only of a new conception of the Religion but also reaffirm the minoritaire core of Collegiants´nature; religion, in their understanding, is not more matter of concord, unity, orthodoxy but source of knowledge, problematization and continuous questioning about its own identity. Nonconformity and cultural dynamics: some preliminary remarks Before starting the presentation of the Collegiants\'' argument about tolerance, Church organization, and rationalism, to fully understand some choices and the approach of this dissertation, and to comprehend how Collegiants sources have been read, some methodological remarks are necessaries about the emergence and development of the historical phenomenon called nonconformity and how was it received and transformed in 17th century Holland. Nonconformity is, as will be shown, one of the central concepts developed by the Collegiants to justify their antiauthoritarianism and anticonfessionalism. The concept appears more interesting if we look at the number of meanings and social phenomena that it includes. It first developed in England in the juridical context and was named in the later 17th century as a defined religious movement that opposed the Act of Uniformity. In the English sources it is possible to retrace the history of this concept, demonstrating how the significance and arguments regarding nonconformity changed in one hundred years. Not far from England, in the United Provinces, the evolution of the concept of nonconformity follows another route, giving rise to radically different signification. Proposing a comparative study, between England and the United Provinces, of the development and semantic elaboration of the concept of nonconformity, is useful not only to understand the different expression of religious dissidence but also to detect cultural and social change in the approach to religion. Beyond the obvious differences between the two Countries, the different political, social and cultural history it is still possible and fruitful to compare how the concept of nonconformity developed in England and Netherlands because of the numerous contact between the Collegiants and the English religious dissident groups and because of the particular redefinition that the concept of nonconformity assumed in the United Provinces. The differentiation of English nonconformity (which dominates the European semantic field with direct and specific connotations of particular events with particular actors) from Dutch nonconformity, explains how historical agents using or interpreting a concept in a particular way can change its semantic connotation. The category of nonconformity, because of its shift from a juridical field to a social-religious one, indicates a semantic enrichment and a conceptual dynamic that can prove a sensible point to investigate structural changes. These case studies possess the necessary characteristics to be approached with the methodology developed by Koselleck and the Cambridge History of Ideas, because "society and language insofar belong among the meta-historical givens without which no narrative and no history are thinkable. For this reason, social historical and conceptual historical theories, hypotheses and methods are related to all merely possible regions of the science of history" . It is our intention to pay particular attention to the analysis of the sources and to their contextualization with the aim of constructing a map of nonconformity\''s semantic change via its arguments in pamphlets and polemical texts of the 17th century. It is our intention to investigate, through the study of the emergence of this concept, the tendencies of secularization, the development of arguments regarding religious indifferentism, and the renounciation of a religious life normalized by concrete institutions, rituals, and ceremonies. A semantic study of how the concept of nonconformity emerges, how it is filled with new meaning, and which new and old concepts intervene to define the religious and political field, is essential to explain and understand the Collegiants\'' mentality in 17th century Holland, to determine how they think, and in which ways they influence the cultural and social dynamic in a specific context. The production of new meaning and the continuous nomination of a cognitive world influence, in their turn, the production and development of new instruments of thinking. To understand the shift, the dynamics, and the changes in the cultural field, a rhetorical and semantic analysis is necessary. The arena of investigation is, however, limited to the religious sphere and the sources analyzed are, in a large majority, polemical pamphlets, which means that the question about the correlation between the emergence of a new concept and change in the mentality refers principally to the change in the perception of religion as a dogmatic and doctrinaire system. The concept of nonconformity is surrounded by many other concepts, which partly explain its nature and constitute its semantic field. In this dissertation we focus on different concepts (tolerance, anticonfessionalism, Utopia, mysticism, and millenarianism) because nonconformity emerges, from the analysis of different pamphlets and sources, as correlated with them. Dutch nonconformity involves, for example, a necessary reflection on Church form, the organization of religious life, exclusivism vs. non-exclusivism and a certain vision of the future that actualizes itself as Utopia or millenarian impulse. This constellation of concepts, which characterizes itself for semantic differentiation but also for their strict interrelation, is also useful in explaining the nature of a radical and dissident movement like the Collegiants and in understanding how the religion, understood as belief experience, was fulfilled by new themes, concepts, and meanings. Furthermore, to investigate this conceptual connection and contextualize the emergence and use of determined religious vocabulary, it is useful to understand the nature and presence, in the Dutch religious field, of the phenomenon of secularization especially in its particularly form which goes under the name of "rationalization of the world". The central question asked in this dissertation is, finally, not how it is possible to construct a category of nonconformity as an analytical concept that helps in understanding religious phenomena, but what is nonconformity and which kind of religious phenomenon it describes, how it has been used and with which consequences. The question regards how it is possible to detect structural change in the mentality while investigating conceptual change or emergence of a new concept. The cultural dynamic is, in this dissertation, understood as a semantic and cognitive phenomenon of mutual influence between emergence or nomination of new concepts and events historically determined. The History of Concepts approach privileges, as has been shown, the semantic field and text analysis for detecting changes in the mentality and in the social-cultural sphere. One more reason to find in this approach a fruitful method for understanding the Collegiants\'' universe is the particular interest that they reserved for the language. The Collegiants stressed the importance of the spread of vernacular Dutch with the compilation of grammars, dictionaries, and lexica . In 1654 the Collegiant Luidewijk Meijer published the Nederlandsche Woorden-Schat, with a new edition in 1658. The Woorden-Schat was a Latin-Dutch and French-Dutch dictionary and a guide to principal terms in Nederduitsche (Low Dutch), with particular attention paid to the basterdtwoorden (Bastard Words) and the konstwoorden beghrijpt (cultural and artistic concepts). Some Collegiants in Rotterdam, as well as in Amsterdam, were active participants in a cultural project that worked on the definition and elaboration of the Dutch language in poesy, theater, and literature. Rafael Camphuysen and Johachim Oudaan were appreciated poets and, in 1669, Luidewijk Meijer and Johannes Bouwmeester founded a cultural academy with the name Nil Volentibus Arduum (Nothing is arduous for the willing). Around the same time Adriaan Koerbagh published Een Bloemhof (A flower garden), a theological dictionary edited according to controversial philological criteria, with the explicit aim of explaining the origin of superstition and unmasking the authority of theologians\'' obscure and adulterated language . In 1706 William Sewel, a Flemish converted to Quakerism, wrote the Compendius Guide to the Low-Dutch Language, a Dutch grammar for English speakers. These sources and the presence in Collegiants\'' texts of a continuous debate about the language, testify to great awareness in their choice of terms and words. Collegiants often use italics to emphasize special concepts, or to introduce a neologism or Latin calque. In addition, they refer several times to their efforts to introduce a correct and transparent use of the language. The Collegiants were surprisingly familiar with the crystallizing power in a certain employment of discourse and language; they explicitly challenged the predominance of scholastic and theologian's terms, which substitute the direct and immediate experience of the religion with an intricate and abstract speculation on transcendence and divinity. Dutch grammar and dictionaries, work with the vernacular language in poetic or literary texts, and philological research on the origin of words, testify to a Collegiant Dutch language undertaking, an engagé project anything but neutral to democratize the discussion about religious matters and to guarantee egalitarian participation by both cultivated and uncultivated people. This effort is well represented by an emblematic figure in the Collegiants\'' sources; the founder of this religious movement, Van de Kodde, is several times described as a cultivated peasant able to speak French, Latin, Greek, in the same way the Philosopherenden Boer (Philosophizing peasant), described by Stol in 1676, extols the superiority of a simple peasant\'' reasonable pragmatism in comparison to the Cartesian\''s method and the Quaker\''s rhetoric. This was the essence of the Collegiants\'' anticonfessionalism and antiauthoritarianism, a campain with both Utopian and rational implications, aiming at a possible rethinking of religious experience outside normative structures.
As a Caribbean institution of Higher Learning, the University of the West Indies is seen as a major contributor to integration efforts in the Region very often mandated by CARICOM to carry out educational missions to that effect. Working in a geographically fragmented and multilingual space, foreign language education is a major preoccupation for academic departments or sections in the respective campuses. The Mona Campus, based in Jamaica, was very one of the earliest to recognize the need to add LSP courses in its curriculum as electives (Business) or as 'service courses' for other programmes (Tourism and Hospitality Management). To these existing LSP courses, the French Section at the Mona Campus added in 2003 a new LSP course geared toward International Relation students. The originality of the course lays its chosen method of delivery by total simulation. The course was offered twice since its approval and under two different schedules (two-week intensive and semester-long). This chapter discusses the impact of these two schedules on the course delivery and learning process. The comparison shows the importance of student's motivation and learning autonomy. The study also comments on the use of blended learning (on-line module complementing face-to-face delivery) and suggests that virtual reality may offer a new addition to Total Simulation for LSP. ; To cite the digital version, add its Reference URL (found by following the link in the header above the digital file). ; TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 73 French for International Conference at The University of the West Indies, Mona: Total Simulation in the Teaching of Languages for Specific Purposes Marie-José Nzengou-Tayo The University of The West Indies, Mona Gilles Lubeth The University of The West Indies, Mona Abstract: As a Caribbean institution of Higher Learning, the University of the West Indies is seen as a major contributor to integration efforts in the Region very often mandated by CARICOM to carry out educational missions to that effect. Working in a geographically fragmented and multilingual space, foreign language education is a major preoccupation for academic departments or sections in the respective campuses. The Mona Campus, based in Jamaica, was very one of the earliest to recognize the need to add LSP courses in its curriculum as electives (Business) or as 'service courses' for other programmes (Tourism and Hospitality Management). To these existing LSP courses, the French Section at the Mona Campus added in 2003 a new LSP course geared toward International Relation students. The originality of the course lays its chosen method of delivery by total simulation. The course was offered twice since its approval and under two different schedules (two-week intensive and semester-long). This chapter discusses the impact of these two schedules on the course delivery and learning process. The comparison shows the importance of student's motivation and learning autonomy. The study also comments on the use of blended learning (on-line module complementing face-to-face delivery) and suggests that virtual reality may offer a new addition to Total Simulation for LSP. Keywords: CARICOM, French for international trade, international conferences, Language for Specific Purposes (LSP), methodology Introduction Language for Specific Purpose (LSP) has developed with the expansion of international trade and the development of multilingual and multicultural working teams. Short language courses are designed at the request of enterprises or institutions in order to meet the specific demands related to the work environment. Though LSP courses have been in existence for more than three decades, their introduction in the academic programs of language majors is quite recent and has been a hot debate for several years at MLA and ADFL meetings. In the Caribbean, with the development of integration, the need for LSP has been felt as the CARICOM (Caribbean Community) started to look beyond the English-speaking Caribbean and opened itself to non-English-speaking territories (Surinam and Haiti joined the organization in 1995 and 2002 respectively while Cuba and the Dominican Republic have observer status). These political trends impacted on our foreign language offerings, stressing the need to open our curriculum to professionally oriented courses. The Department of Modern Languages and Literatures and the language sections of the two other campuses TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 74 had various responses: at the St. Augustine Campus (Trinidad and Tobago), a Latin American Studies program was developed; at Cave Hill (Barbados), a cross-faculty program in Management Studies with a minor in a foreign language was approved; at Mona, LSP courses were developed and students from other faculties were allowed to declare minors in French or Spanish. In this article, we present the circumstances surrounding the design of the latest addition to French for Specific Purpose courses offered at the University of The West Indies, Mona (UWI, Mona), the methodological choices made and their implication for assessment. Because the course has been offered twice since its approval by the University Academic Quality Assurance Committee and with two different schedules, we will compare and discuss these two delivery modes. Language for Specific Purpose at the UWI, Mona At the UWI, Mona, the introduction of French for Special Purpose came out of a pragmatic approach at a time when high schools were experiencing a high turnover of French teachers and a reduction of schools offering A-level French (equivalent to the Baccalauréat). Noting that our graduates were being hired in the insurance and tourism industries, it was thought that equipping them with professional language skills would give a 'practical' touch to our program. The recruitment of a colleague with professional experience in translation led to discussions about a more professionally oriented program. "French for Business" was the first LSP course to be designed in 1991–1992 with the creation of a level III course of French for business or "Business French." The course was developed as an elective in response to a situation in which French graduates were moving toward the business sector instead of education. In the subsequent years, other LSP courses were introduced: "French for Hospitality" in 1998–1999 and "French for International Conferences" in 2003. The introduction of this last course coincided with a drastic overhaul of the French curriculum. The offering of "French for International Conferences" came at a time when the French section of the Department was repositioning itself and revising its offerings. The course was designed with a view to attracting International Relations (IR) students while capitalizing on the latest trend in French foreign language teaching methods. The decision was based on the fact that IR majors and French majors minoring in IR outnumbered students majoring in French only. It was taken at a time when the section was going into a survival mode, taking drastic measures and moving away from the traditional language curriculum (36 credits equally divided between language and literature). The section opted for a mix of language, literature, film and culture, and French for specific purpose courses. It was a drastic choice since the section was moving away of the traditional literary offerings. Though the section has not fully recovered, it has increased its numbers and the majority of students pursuing French are double majors (French and Spanish) with a professional objective of becoming translators or interpreters, followed by IR and Linguistics majors. Total Simulation in French Foreign Language Teaching and Learning Even though Total Simulation in French Foreign Language Education was initiated in the 1970s at the BELC (Bureau d'Enseignement de la Langue et de la Civilisation Françaises à l'Étranger / Office for the Teaching of French Language and Civilization TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 75 Abroad) it did not really become mainstream until the late eighties. This approach to language teaching evolved from role playing and the need to expand role playing over a longer period of time with a view to involving diverse aspects of communication (Yaiche, 1996). Total Simulation was borrowed from continuous professional education where staff received specific training to deal with job-related situations. Total Simulation for French Foreign Language Teaching was first conceptualized by Francis Debyser, a professor at the CIEP (Centre International d'Études Pédagogiques / International Center for Peda-gogical Studies). In the 1980s, Total Simulation became more broadly accepted and moved from experimental to established status. Publishers become interested and several textbooks were published by Hachette between 1980 and 1990 (Yaiche, 1996). By the 1990s, Total Simulation was redirected toward the teaching of French for Specific Purpose (Business French, French for International Relations, Hospitality French). Total Simulation benefits today from IT and its use in the classroom. It is still at the experimental stage as is the case of 'Virtual Cabinet' for the teaching of English, which has been developed by Masters' students at University of Lyon II (http://sites.univ-lyon2.fr/vcab/demo/) or 'L'auberge' developed by University Lille III for incoming French Foreign Language Students (http://auberge.int.univ-lille3.fr/). Characteristics of a Total Simulation Course in Foreign Language Learning Total Simulation in Foreign Language Teaching and Learning could be considered revolutionary in its approach and methodology. First, the role of the teacher is transformed as he or she becomes a facilitator and a participant in the simulation instead of an instructor. For instance, in the International Conference Simulation, the teacher plays the part of the Secretariat. He or she compiles and archives the material needed for the progress of the conference. He or she also provides documents and the linguistic tools needed for the project. Secondly, simulation follows a set pattern of five stages (See Bourdeau, Bouygue, & Gatein, 1992; Yaiche, 1996). The first stage is the creation of the setting. In the case of the International Conference, it means, choosing the theme and the place of the conference. The second stage is to identify the participants. At this point, the role playing starts as the learners have to choose an identity and the country that they will represent. Learners will have to play several roles: delegates from their chosen countries (Minister of Foreign Affairs or High Ranking Civil Servant or Ambassador). At one point, they also play the part of journalists. The countries are fictitious but based on the characteristics of real countries. During this stage, learners choose their identity and civil status; they invent a short biography indicating two physical, moral, psychological, intellectual characteristics, two distinctive objects, (Yaiche, 1996). The third and fourth stages consist in conducting the simulation: the official opening ceremony and the working sessions. At this point, learners are to present their country's respective position paper. Interaction takes place as well as negotiations for a common position and action plan. During this stage, the facilitator plays an important part in ensuring the archiving of all productions and the elaboration of a data bank for the progress of the conference. Students are provided with documents and assisted in acquiring the mastery of the linguistic tools needed for the exercise (e.g., mastery of high language register for official speeches; mastery of diplomatic lexicon for the phrasing of the final resolution and the press release, TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 76 ability to write an abstract or a synthetic report from a news article, etc.). The final stage is geared toward ending the simulation. In the case of the International Conference, it is marked by the writing of the final resolution and a press conference. Since IR students are to be prepared to face and manage diplomatic incidents/crisis during negotiations, elements that could lead to such incident are introduced between the fourth and fifth stage of the simulation when students are drafting the final resolution of the conference. Students are expected to draw on their negotiating skills in order to solve the problem or assuage the potential conflict and bring the conference to a positive closing ceremony. Assessment is blended in the simulation: oral expression is assessed during the opening ceremony (a five-minute presentation) and during the press conference. Students are video recorded and marking takes place afterwards. (See evaluation sheet in appendix B). Both examiners are present to abide by University Examination Regulations. Writing proficiency is assessed through a press release and the conference final resolution, which is done individually during a traditional in-class test. It is also assessed 'outside' of the simulation through the submission of a take-home assignment, the format of which is either a précis writing or a critical review of a newspaper article related to the theme of the conference. Students are provided with a choice of articles from Le Monde Diplomatique, a well-established and recognized reference journal from which they will select an article for review or summary. LSP and Total Simulation in Jamaica and at the UWI, Mona French teachers in Jamaica were introduced to Total Simulation in 1993 thanks to a new French Linguistics Attaché who was also appointed at The University of the West Indies from 1992–1997. A specialist in Total Simulation, she organized two workshops for the Jamaica Association of French Teachers and one for the Tourism Product Development Company (TPDCo), a Jamaican state agency responsible for the training of the workforce in the tourism sector. The co-authors received additional training at the annual training seminar organized by the Centre International d'Études Pédagogiques (CIEP) held in Caen in July 1996 (Nzengou-Tayo) and July 2009 (Lubeth) respectively. The first total simulation course at the UWI was developed in 2003. Two factors contributed to the choice of this methodology. One was the renewed interest in LSP with the review of the French program. After a quality assurance review in 2003, the French section, threatened by low numbers in registration, revised its program with a stronger professional component (introduction of an additional LSP course and translation modules). The second was the institutionalization of summer courses, which offered the possibility of using an intensive format. The idea was to design a course that could imitate a real life situation: an international conference taking into account that such an event is usually limited over a period of time (1–2 weeks) and requires a full work day. The course was submitted to the University Quality Assurance Committee for approval (See course proposal in Appendix A). In the initial submission, evaluation was by 50% coursework and 50% final examination (Appendix A). However, when the course was first taught in 2006, we requested a change of the evaluation scheme to 100% coursework (50% oral presentation and 50% written assignment). The reason for this change was directly related to the philosophy behind total simulation, which required a formative form of assessment that would blend seamlessly in the simulation. TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 77 Case Study: The 2006 and 2009 Experiences Since its creation, French for International Conferences (FREN 3118) has been offered twice: first, in 2006 as an intensive summer course over two weeks, and secondly, in 2009 as a regular semester course over thirteen weeks. These two modes of delivery will be compared and discussed in this section. Course delivery schedule. In 2005–2006, during the two-week period during which the course was offered, the timetable averaged 25 hours per week with 5 daily contact hours. FREN 3118 was the only course attended by the students. Students were put in an immersion situation as they interacted with a native speaker of French during the week. During the second week, ten hours were set aside for independent research in an attempt to give students an opportunity to develop learning autonomy. In 2009–2010, the course was taught during the first semester according to the regular schedule. The timetable featured 3 one-hour sessions per week. In addition to FREN 3118, students were simultaneously registered for four other courses whose demands were competing with the French course. The fast pace of the semester (13 weeks) did not allow for a scheduled independent research. Students had to use their free time for independent research to develop their learning autonomy. The difference between the schedules of the 2006 and 2009 course delivery had an impact on the course management as well as the students' learning experience. It is evident that 2009 students did not have the same learning stimulus as the 2006 ones. They had the pressure of their other courses in term of time and workload. In addition, regular attendance was an issue since students sometimes missed classes either due to timetable clashes or assignment deadlines to meet in other courses. The running of the course was affected as each student had a part to play in the progress of the simulation and absence from class meetings affected the proceedings of the conference. Student profile and number. The course targets third-year students and requires a general language module at level III as a co-requisite. However, the co-requisite can be waived depending on the level of the students. For instance, when the course was offered during the summer 2006, it was waived for second-year students who had received a B+ in the two modules of the level II language courses. In 2009, a third-year International Relations student who had completed level I of the French language courses with A and was reading the level II language course was allowed to register. The waiver was granted based on his outstanding results at level I and also after an interview in which he demonstrated a high level of motivation and learning autonomy. In 2006, the course was offered with 9 students and in 2009 there were 14 registered students. Numbers can be an issue for conducting a total simulation course. For instance, our experience taught us that, even though Cali, Cheval, & Zabardi (1992) suggest a number of 20 participants divided according to a ratio by type of countries1 in La Conférence Internationale et ses Variantes, country-ratio balance can still be observed TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 78 with lesser numbers. Based on our 2006 experience, we recommend a minimum of 8 students. Indeed, a lesser number would not allow their distribution according to the recommended country ratio. In addition, work in commissions, which is part of the simulation process, would be less productive. Similarly, 20 is the maximum manageable number of students during total simulation. The attention to be devoted to students' progress and the group dynamics become a challenge with larger numbers. Therefore, beyond 20, the group would be divided and two concurrent simulations conducted, provided that staffing is not an issue for the institution. Topics and scenarios. On both occasions, the theme of the conference was inspired by current affairs relevant to the Caribbean region. In 2006, the conference was titled "Libre circulation des travailleurs à l'échelle mondiale: Faisabilité et conditions" (Feasibility and Conditions for a Global Free Movement of Labour). The theme was inspired by discussions taking place in the media about the Caribbean Single Market and Economy (CSME) put in place by CARICOM countries that year. The scenario was developed to involve a group of 9 countries, members of a regional organization seeking to achieve integration through free movement of workers. The 2009 edition of the conference, "Réchauffement climatique: Stratégies et équité" (Global Warming: Strategies and Equity) was inspired by the then ongoing international negotiations on global warming. The course started in September, just three months before the Copenhagen Summit. The scenario was based on the creation of an international organization, the Group of 14 (G14) specially dedicated to addressing the issue of global warming, and therefore holding its first conference accordingly. The choice of topics related to current international or regional issues stimulates the students' interest as they can have access to current reference material. They develop their critical thinking as they are exposed to various diverging opinions and asked to present their country's position at the start of the conference. For example, at the 2009 conference, the delegate of "Bonangue" expressed the country's position as follows: Conscient des graves effets [du réchauffement climatique] sur l'environnement, nous tenons à prendre action immédiatement parce que les effets poseront un problème pour le pays. Par le passé, la Bonangue a donné priorité aux revenus, dans certains cas, au détriment de l'environnement. Le pays est disposé à porter [sic] les changements nécessaires. The delegate of "Kalasie," on the contrary, indicated, "La Kalasie est favorable au recours aux crédits d'émission de gaz utilisables par les investisseurs." Another delegate from "Lisérbie" chose to stress the social impact and the importance to reach a consensus on the matter. The multiple and sometimes diverging country positions will contribute to the life of the conference as the objective is to find a common ground and sign a final resolution, which would bring the conference to a close. TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 79 Resources and methods. The course outline was developed in accordance with the prescribed textbook La Conférence Internationale et ses Variantes (Cali et al., 1992). The authors' recom-mendations were followed with some adjustments, which will be presented below. Since countries have to be fictitious to respect the principle of Total Simulation, two websites, CIA: The World Factbook, and Quid were used to establish the profile of these invented countries.2 Using the principle of 'mots-valises' students invented the name of the countries they were representing. For instance, "Lisérbie," "Kalasie" or "Dukenyah" were obviously created in reference to existing countries or regions. Other names were arbitrary and left to the students' imagination as "Cadeaux d'Ouest," "Amapour" or "Kadia." Other web resources were used in accordance with the theme of the conference and a companion website was developed on the University Virtual Learning Environment (OurVLE) (UWI, Mona "Virtual Learning Environment") to take advantage of information technology at our disposal at the Mona Campus. The 2006 intensive format. We introduced some slight variations from the standard format of the simulation. First, the course started with a screening of the French movie Saint-Germain ou la Négociation (2003) with Jean Rochefort. The objective was to highlight the objectives, modalities of diplomatic negotiations as well as to insist on the high-language register used during negotiations, which the students would have to use. Despite the historical context (the 16th century), the film was particularly suitable as it showed protocol and behind-the-scene events taking place during political negotiations. Secondly, students were given an introductory lecture on the processes of international conferences coupled with a tour of the Jamaica Conference Centre in Kingston. This was facilitated by a colleague and professional translator who worked at international conferences and was familiar with the facility. Various documents were made available online on a range of topics: international organizations pursuing regional integration through implementation of free movement of labor (the European Union, CARICOM) and a compilation of documents on immigration and globalization. In 2006, the course page on OurVLE was used only for archival purposes. The instructor, playing the part of the conference Secretary, uploaded for future reference documents that had been identified as relevant to the conference. Since the students' time were dedicated to the course, it was easy to simulate the rhythm of a conference with meetings in commission and plenary sessions. The course outline was design to be the "agenda" of the conference. The intensive format helped to develop a group dynamic based on solidarity and conviviality, which stimulated weaker students to make efforts to improve their proficiency. The 2009 semester-long format. The semester-long delivery of FREN 3118 differed from the intensive summer course on some points. The presentation by the guest lecturer and the film screening were maintained, but, due to timetable constraints, the tour of the Conference Centre did not take place. The main innovation was in the extensive use of the online module and the exploration of the functionalities offered by the Moodle platform supporting OurVLE TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 80 where all the material necessary for the presentation of the theme and the conduct of the activities of the conference were uploaded. All documents were made available online via OurVLE, expanding from print and website links to audio and video. Students' productions were added to the resources identified by the instructor. The instructor/facilitator provided the following resources: explanatory documents on global warming (its geopolitical implications and the negotiation process); documents with terminology used in diplomatic language; and audiovisual documents from France2, France3, and YouTube. A link to Yann Arthus-Bertrand's documentary Home (2009) was also put on the course portal. As Secretariat, the instructor/facilitator uploaded reports of sessions held during the preparatory phase (the preconference meetings). These reports gave students a regularly updated overview of progress made, a review of notions covered as well as the calendar of events (the schedule of meetings). Using the functionalities offered by Moodle, students were able to contribute to the development of the course portal. Using the 'upload a single file' and the forum features, they uploaded their own production, including country and delegate profiles, reports resulting from the sessions in commission and plenary sessions, and draft resolutions. The course portal was useful for archiving the various activities conducted during the course. Students were able to refer to a central repository outside of the contact hours. This tool also had financial and ecological benefits as it reduced the cost of photocopying. Indeed, whereas all documents had to be printed in 2006, only documents produced during the conference (student-generated commission and plenary reports, agenda and list of speakers) were printed for circulation in 2009. Because of the discontinuity of the timetable (3 hours spread over 13 weeks), the 2009 conference did not flow as harmoniously as the 2006 one. With competing interests, students found it difficult to dedicate themselves to the conference. Running from one class to another, they sometimes lost track of the conference objectives, which in turn had an impact on the group dynamics and progress as indicated by the results of the continuous assessment (i.e., the coursework). Evaluation and students' results. As mentioned earlier, the course assessment was done by 100% coursework. The percentage was equally divided between oral and writing proficiency (50% each). Oral proficiency was assessed as follows: delegate's address at the opening ceremony weighting 25%; delegate's interview at the press conference (15%); and one intervention as a journalist interviewing the delegates at the press conference (10%). Writing proficiency was assessed through a press release (10%), an individual proposal for the final resolution (15%), and one précis writing/critical review of document(s) (25%). Students' oral and written productions were graded using a criterion-referenced assessment grid (See Appendix B for details). In 2006, we got a 100% pass rate with results ranging from A+ to C. In 2009, the pass rate was 71.42%. With the intensive format, students demonstrated their mastery of high-level register. Students who were considered 'weak' based on their low grade in the general language courses, managed to improve their proficiency level and achieve acceptable performances in oral presentations. In 2009, there was a large gap between the TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 81 best and the weakest students (2 students got As, 4 students failed, and 8 students' grades ranged from B+ to D). Group average was 49.79%. When comparing the two groups' results, we have to admit that we had some doubts initially about the intensive format because of the limited time given to students to properly absorb the notions and the various tasks required in the course. Yet, it appears that stretching the process over a semester is not a decisive factor for improved performance. The role of group dynamics in total simulation is yet to be measured though it is generally recognized in class interaction and learning. During the regular semester, the group dynamics did not play a cohesive role as it did in the summer course where more proficient students helped to strengthen the weaker ones. Competing academic interests and irregular attendance during the regular semester also had an impact on students' low performance. Conclusion At the UWI, Mona, we introduced LSP courses in our academic programs as part of our major from a pragmatic standpoint in reviewing our curriculum. Though we are aware that LSP courses generally target professionals already in the field, as a result, the design and offering of such courses is usually preceded by a need analysis and the identification of the language processes (i.e., register, lexicon, syntax, speech acts) needed to achieve the requested proficiency (Mangiante & Parpette, 2004). Both "Business French" and "French for International Conferences" count toward the major, though only one can be taken as a core course, the other being an elective. Because LSP courses have a professional orientation, they give undergraduates the impression of being prepared for the world of work. The use of total simulation comforts this impression because of its task-based approach and the fact that it recreates a work environment with its idiosyncrasies. Combined with information technology (OurVLE), it becomes an original and valuable method. The dual-mode adds flexibility to the course and expands access to authentic material. However, success depends heavily on students' learning autonomy, which is enhanced by a tool like OurVLE. Motivation and participation are essential for the success of students as evidenced by the results of the third-year student who was accepted while doing the first module of level II French and was one of the top two students in the course. Our experience suggests that the intensive format yields better results because it reinforces student concentration, dedication, and performance, which also benefit from the positive impact of the group dynamics. Recent development in the field shows an orientation toward multimedia and information technology to create virtual worlds where Total Simulation is made possible on a large scale. The combination of the two is very promising for language learning and teaching but presents new challenges to foreign language teachers and course developers. Notes 1Cali, Cheval, & Debardi (1992) identify the following categories: developing countries, developed countries, least developed countries, and Central or Eastern European countries in transition towards market economy. The latter category being now obsolete, the decision was made to replace it with countries in the same geographical region. TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 82 2See https://www.cia.gov/library/publications/the-world-factbook/ and http://www.quid.fr. References Arthus-Bertrand, Y. (2009). Home. Home Project. Retrieved (September–November 2009) from http://www.youtube.com/homeprojectFR L'auberge. Retrieved February 21, 2010 from http://auberge.int.univ-lille3.fr/ Bourdeau, M., Bouygue, & M., Gatein, J. J. (1992). Le congrès médical: Simulation globale sur objectifs spécifiques. Ministère des affaires étrangères, sous direction de la coopération linguistique et éducative, CIEP-BELC, 1991/92. Sèvres: CIEP. Cali, C., Cheval, M., & Zabardi, A. (1992). La conférence internationale et ses variantes. Paris: Hachette, Français langue étrangère. Mangiante, J. M., & Parpette, C. (2004). Le français sur objectifs spécifiques: De l'analyse des besoins à l'élaboration d'un cours. Paris: Hachette. Le Monde Diplomatique. 2009. Paris: Editions "Le Monde." Retrieved from http://www.monde-diplomatique.fr/ Virtual Cabinet. Retrieved February 21, 2010 from http://sites.univ-lyon2.fr/vcab/demo/ Yaiche, F. (1996). Les simulations globales: Mode d'emploi. Paris: Hachette, Français langue étrangère. TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 83 APPENDICES Appendix A Original submission to the Academic Quality Assurance Committee of the UWI, Mona Campus in 2003–2004. The assessment was subsequently modified to 100 percent coursework in 2005–2006. DEPARTMENT OF MODERN LANGUAGES & LITERATURES COURSE PROPOSAL Course Title: French for International Conferences Course Code: FREN 3118 Level: 3 Semester: 1 Credits: 3 Prerequisite: A Pass in F24A (FREN 2001) Co-requisite: F34A (FREN 3001) Contact hours: 4 hours per weeks (1 lecture, 1 writing tutorial, 1 oral expression, 1 listening comprehension) Rationale: French is one of the major languages of the United Nations and other inter-national institutions. In response to increased demand for specialized foreign language courses, this course will introduce students to the technical French of international relations and negotiations Course description: This course is designed to reproduce an international conference setting during which various aspects of diplomatic negotiations will be envisaged with a view to using French at the formal/foreign affairs level. Objectives: At the end of the course students should be able to Demonstrate understanding of French spoken in a formal/diplomatic setting Read articles in French on international issues. Write press reviews, press releases in French about an international issue. Express a personal view about a topical International issue in French Express a simulated official view about a topical International issue in French Simulate an official address in French Simulate a press conference in French TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 84 ASSESSMENT 50% in-course: 3 one-hour in-class tests: Reading comprehension (15%); Writing (20%); Listening comprehension (15%) 50% Final Examination: Oral presentation (25%) and 2-hour written examination (25%) TEXTS La Conférence Internationale et ses Variantes. Chantal Cali, Mireille Cheval and Antoinette Zabardi. Paris: Hachette Livre, Français Langue Étrangère, 1995. Audio-visual material from TV5 (such as Kiosque, Une fois par mois, Le dessous des cartes). Articles from journals such as Le monde diplomatique. REFERENCES Plaisant, François. (2000). Le ministère des affaires étrangères. Toulouse: Editions Milan, Les Essentiels Milan, 2000. Kessler, Marie-Christine. (1998). La politique étrangère de la France. Paris: Presses de Sciences-Po. http://www.france.diplomatie.gouv.fr Appendix 2. Assessment grid for oral presentation Official Address: (5-minute presentation at the Opening Ceremony). Press Conference Part 1 and 2: Presentation of Country Position followed by Questions and Answer session). Students plays the country official and then the journalist parts. FREN 3118: Oral Presentation Assessment Grid NAME: Grade Comments Relevance of Arguments /5 Fluency /5 Consistent use of high-language register /3 Communicative skills /2 Accuracy and richness of vocabulary /5 Accuracy and use of complex syntactic structures /5 Accurate pronunciation /5 FINAL GRADE (25%) /25 TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 85 FREN 3118: Press Conference Assessment Grid—Presenter NAME: Grade Comments Relevance of Arguments (5 pts. x 3 = 15) Presentation Answer (1) Answer (2) Fluency (5 pts. x 3 = 15) Presentation Answer (1) Answer (2) Consistent Use of High Language Register (3 pts. x 3 = 9) Presentation Answer (1) Answer (2) Communicative skills (2 pts. x 3 = 6) Presentation Answer (1) Answer (2) Accuracy and Richness of Vocabulary (5 pts. x 3 = 15) Presentation Answer (1) Answer (2) Accuracy and Use of Complex Syntactic Structures (5 pts. x 3 = 15) Presentation Answer (1) Answer (2) Accurate Pronunciation /5 marks x 3 = 15 Presentation Answer (1) Answer (2) Unconverted Total (90 pts.) / FINAL GRADE (15%) TOTAL SIMULATION IN TEACHING LSP Scholarship and Teaching on Languages for Specific Purposes (2013) 86 FREN 3118: Press Conference Assessment Grid—Journalist NAME: Grade Comments Relevance of question (5 pts. x 4 = 20) Question 1 (Name) Question 2 (Name) Question 3 (Name) Question 4 (Name) Fluency (5 pts. x 4 = 20) Question 1 (Name) Question 2 (Name) Question 3 (Name) Question 4 (Name) Consistent use of high-language register (3 pts. x 4 = 12) Question 1 (Name) Question 2 (Name) Question 3 (Name) Question 4 (Name) Accuracy and richness of vocabulary (5 pts. x 4 = 20) Question 1 (Name) Question 2 (Name) Question 3 (Name) Question 4 (Name) Accuracy and use of complex syntactic structures (5 pts. x 4 = 20) Question 1 (Name) Question 2 (Name) Question 3 (Name) Question 4 (Name) Accurate pronunciation (5 marks x 4 = 20) Question 1 (Name) Question 2 (Name) Question 3 (Name) Question 4 (Name) Unconverted Total (112 pts.) FINAL GRADE (10%)
L'arròs (Oryza sativa L.) és un dels cultius alimentaris més importants del món, sent Colòmbia el segon productor d'arròs d'Amèrica Llatina, després del Brasil. L'arròs es classifica com el tercer producte agrícola en extensió de país, després del cafè i el blat de moro. En el present estudi es va determinar la qualitat de l'arròs cultivat i comercialitzat a Colòmbia, atenent a paràmetres microbiològics, fisicoquímics i toxicològics (presència de micotoxines), i es va plantejar com a objectiu general estudiar la incidència d'aflatoxines, zearalenona i desoxinivalenol en l'arròs produït a les principals zones arrosseres de Colòmbia. Durant l'any 2017 es van prendre 62 mostres d'arròs paddy cultivades per sistemes "reg" i "secà", procedents de les principals zones arrosseres de Colòmbia. L'any 2018, el nombre de mostres recollides va ser de 58, provinents dels dos sistemes de cultiu. Aquestes mostres es van analitzar microbiològicament (coliformes totals, Escherichia coli, i Fongs i Llevats) i es van determinar les seves característiques fisicoquímiques (pH, activitat d'aigua -Aw- i contingut d'humitat). Finalment, les mostres van ser analitzades per a la detecció i quantificació d'aflatoxines (AF) (B1, B2, G1 i G2), zearalenona (ZEA) i desoxinivalenol (DO). Per fer això, es van aplicar tècniques analítiques estandarditzades reconegudes per l'Associació Oficial de Química Analítica dels Estats Units (AOAC). Dels resultats obtinguts, en les mostres recollides durant l'any 2017, es va observar una incidència global del 46% de coliformes totals (CT) en les mostres procedents de sistema "reg" de totes les zones arrosseres. En les mostres de sistema "secà", la incidència observada va ser del 50 %. La incidència de Fongs i Llevats (F i Ll) va ser alta, i va oscil·lar entre el 96 i el 100 %, sense importar el sistema de cultiu emprat. Escherichia coli va presentar una incidència de el 8 % en el sistema "reg", mentre que no es va detectar la seva presència en les mostres cultivades pel sistema "secà". En l'arròs conreat l'any 2018 pel sistema "reg" la càrrega microbiana, tant de bacteris com de fongs, va disminuir considerablement; només el 13 % de les mostres van presentar recomptes de CT. Els fongs van estar presents en el 76 % de les mostres. Pel que fa a el sistema "secà", el 23 % de les mostres van presentar contaminació amb CT, i el 54 % amb F i Ll. La presència de fongs en el gra en cultiu va ser molt elevada a tot el país, tot i que l'any 2018, es va apreciar una disminució generalitzada en la incidència en totes les zones arrosseres. En relació a les variables fisicoquímiques, les mostres procedents de sistema "reg", van presentar durant 2017 valors mitjans de pH entre 6,39 i 6,75, i de 0,65 i 0,74 d'Aw, amb uns valors d' humitat entre 7,48 i 11,74 %. Les mostres cultivades pel sistema "secà" van evidenciar valors mitjans de pH entre 6,72 i 7,00, de 0,70 i 0,75 de Aw, i humitats compreses entre 6,87 i 10,09 %. En les mostres procedents de sistema "reg" de l'any 2018, els valors de pH van oscil·lar entre 6,68 i 7,37, els de Aw entre 0,71 - 0,74, i els d'humitat entre 7,78 i 10,12 %, mentre que les de sistema "secà" van presentar valors de pH entre 6,44 i 6,75, de 0,65 i 0,74 d' Aw, i entre 7,11 i 8,39 % d'humitat. Aquestes propietats fisicoquímiques i les seves interaccions són els principals determinants etiològics en la regulació del creixement fúngic i de la producció de metabòlits secundaris. L'any 2017, la micotoxina de major incidència al país va ser AF, seguida de ZEA. La zona més crítica per la presència d'AF va ser la zona "Nord". Al 2018, ZEA passar a ser la micotoxina de major incidència, especialment en el sistema de cultiu "reg". En contrast, DO va ser la micotoxina de menor incidència. Sense distinció de sistema de cultiu aplicat, en les mostres recollides durant els dos anys, no es va evidenciar la presència de AFG1 i AFG2. En les mostres cultivades pel sistema "reg" en 2017, la presencia d'AF va correspondre al 15 % de les mostres, amb concentracions que van variar entre 0,1 mg/kg i 1,83 mg/kg, mentre que la ZEA es va detectar en un 13 % de les mostres, amb concentracions entre 53, 5 mg/kg i 2,57 mg/kg. No es va detectar la presència de DO en cap mostra. En les mostres procedents de sistema "secà", es va observar la presència d'AF en un 43 % de les mostres (2,1 - 119,5 mg/kg) i ZEA en un 7 % (271,9 mg/kg). La incidència d'AF en l'arròs conreat pel sistema "reg" l'any 2018 es va reduir en comparació amb l'any anterior, amb presència només en un 2 % de les mostres (0,9 mg/kg). No obstant això, es va denotar una major incidència de ZEA, present en el 31 % de les mostres (98 µg/kg - 5,19 mg/kg). En aquest cas, va ser destacable l'aparició de DO en el 7 % de les mostres analitzades (0,87 - 5,86 mg / kg), procedents de les zones "Centre" i "Plans Orientals" del país. En les mostres obtingudes pel sistema "secà" es va detectar la presència d'AF i de ZEA, però no es va observar DO en cap zona. La incidència d'AF va ser del 31 % (1,6 - 22,4 mg / kg) i la de ZEA del 15 % (67 mg / kg). Dels aïllaments fúngics obtinguts a partir de les mostres d'arròs en cultiu corresponents al mostreig de l'any 2017, Aspergillus va ser el gènere amb més freqüència (74 %) seguit de Penicillium (20 %). Es van aïllar 19 soques de fongs aïllades de l'arròs conreat l'any 2017, caracteritzant-les fenotípica i molecularment. Disset d'elles van correspondre a Aspergillus flavus. El 52 % de les soques van presentar fluorescència UV a ALC i es va verificar la seva capacitat aflatoxigénica. No es va detectar la presència ni de CT ni tampoc d'E. Coli en cap de les 16 mostres d'arròs comercial analitzades, procedents de les diferents zones arrosseres de Colòmbia, però sí es va detectar la presència de F i Ll. La incidència d'AF en aquestes mostres va ser del 50 % (2,4 - 93,9 mg/kg) i la de DO del 6 % (128 mg/kg), superant-se en el 31 % de les mostres el valor màxim permissible establert per les legislacions colombiana i europea. No es va evidenciar la presència de ZEA en cap de les mostres analitzades. ; "El arroz (Oryza sativa L.) es uno de los cultivos alimentarios más importantes del mundo, siendo Colombia el segundo productor de arroz de América Latina, después de Brasil. El arroz se clasifica como el tercer producto agrícola en extensión del país, después del café y el maíz. En el presente estudio se determinó la calidad del arroz cultivado y comercializado en Colombia, atendiendo a parámetros microbiológicos, fisicoquímicos y toxicológicos (presencia de micotoxinas), y se planteó como objetivo general estudiar la incidencia de aflatoxinas, zearalenona y desoxinivalenol en el arroz producido en las principales zonas arroceras de Colombia. Durante el año 2017 se tomaron 62 muestras de arroz paddy cultivadas por sistemas "riego" y "secano", procedentes de las principales zonas arroceras de Colombia. En el año 2018, el número de muestras recogidas fue de 58, provenientes de los dos sistemas de cultivo. Estas muestras se analizaron microbiológicamente (Coliformes Totales, Escherichia coli y Mohos y Levaduras) y se determinaron sus características fisicoquímicas (pH, actividad de agua -Aw- y contenido de humedad). Finalmente, las muestras fueron analizadas para la detección y cuantificación de aflatoxinas (AF) (B1, B2, G1 y G2), zearalenona (ZEA) y desoxinivalenol (DON). Para ello, se aplicaron técnicas analíticas estandarizadas reconocidas por la Asociación Oficial de Química Analítica de los Estados Unidos (AOAC). De los resultados obtenidos, en las muestras recolectadas durante el año 2017, se observó una incidencia global del 46 % de Coliformes Totales (CT) en los granos procedentes del sistema "riego" de todas las zonas arroceras. En las muestras del sistema "secano", la incidencia observada fue del 50 %. La incidencia de Mohos y Levaduras (M y L) fue alta, osciló entre el 96 y el 100 %, independientemente del sistema de cultivo empleado. Escherichia coli presentó una incidencia del 8 % en el sistema "riego", mientras que no se detectó su presencia en las muestras cultivadas por el sistema "secano". En el arroz cultivado en el año 2018 por el sistema "riego" la carga microbiana, tanto de bacterias como de hongos, disminuyó considerablemente; sólo el 13 % de las muestras presentaron recuentos de CT. Los mohos estuvieron presentes en el 76 % de las muestras. En cuanto al sistema "secano", el 23 % de las muestras presentaron contaminación con CT y el 54 % de M y L. La presencia de hongos en el grano en cultivo fue muy elevada en todo el país, aunque en el año 2018, se apreció una disminución generalizada en la incidencia en todas las zonas arroceras. Con relación a las variables fisicoquímicas, las muestras procedentes del sistema "riego", presentaron durante 2017 valores promedio de pH entre 6,39 y 6,75, y de 0,65 y 0,74 de Aw, con unos valores de humedad entre 7,48 y 11,74 %. Las muestras cultivadas por el sistema "secano" evidenciaron valores promedios de pH entre 6,72 y 7,00, de 0,70 y 0,75 de Aw, y humedades comprendidas entre 6,87 y 10,09 %. En las muestras procedentes del sistema "riego" del año 2018, los valores de pH oscilaron entre 6,68 y 7,37, los de Aw entre 0,71 - 0,74, y los de humedad entre 7,78 y 10,12 %, mientras que las del sistema "secano" presentaron valores de pH entre 6,44 y 6,75, de 0,65 y 0,74 de Aw, y entre 7,11 y 8,39 % de humedad. Estas características fisicoquímicas y sus interacciones son los principales determinantes etiológicos en la regulación del crecimiento fúngico y la producción de metabolitos secundarios. En el año 2017, la micotoxina de mayor incidencia en el país fue AF, seguida de ZEA. La zona más crítica por la presencia de AF fue la zona "Norte". En el 2018, ZEA pasó a ser la micotoxina de mayor incidencia, especialmente en el sistema de cultivo "riego". En contraste, DON fue la micotoxina de menor incidencia. Sin distinción del sistema de cultivo aplicado, en las muestras recolectadas durante los dos años, no se evidenció la presencia de AFG1 y AFG2. En las muestras cultivadas por el sistema "riego", se detectó la presencia de AF en el 15 % de las muestras, con concentraciones que variaron entre 0,1 µg/kg y 1,83 mg/kg, mientras que la ZEA se detectó en un 13 % de las muestras, con concentraciones entre 53,5 µg/kg y 2,57 mg/kg. No se detectó la presencia de DON en ninguna muestra. En las muestras procedentes del sistema "secano", se observó la presencia de AF en un 43 % de las muestras (2,1 - 119,5 µg/kg) y ZEA en el 7 % (271,9 µg/kg). La incidencia de AF en el arroz cultivado por el sistema "riego" en el año 2018 se redujo en comparación con el año anterior, detectándose solo en un 2 % de las muestras (0,9 µg/kg). No obstante, se denotó una mayor incidencia de ZEA, presente en el 31 % de las muestras (98 µg/kg - 5,19 mg/kg). Fue destacable la aparición de DON en el 7 % de las muestras analizadas (0,87 - 5,86 mg/kg), procedentes de las zonas "Centro" y "Llanos Orientales" del país. En las muestras obtenidas por el sistema "secano", se detectó la presencia de AF y de ZEA, pero no se detectó DON en ninguna zona. La incidencia de AF fue del 31 % (1,6 - 22,4 µg/kg) y la de ZEA del 15 % (67 µg/kg). De los aislamientos fúngicos obtenidos a partir de las muestras de arroz en cultivo correspondientes al muestreo del año 2017, Aspergillus fue el género aislado con mayor frecuencia (74 %) seguido de Penicillium (20 %). Se aislaron 19 cepas de moho aisladas del arroz cultivado en el año 2017, caracterizándolas fenotípica y molecularmente; 17 de ellas correspondieron a Aspergillus flavus. El 52 % de las cepas presentaron fluorescencia UV en ALC y se verificó la capacidad aflatoxigénica de las mismas. No se detectó la presencia ni de CT ni tampoco de E. coli en ninguna de las 16 muestras de arroz comercial analizadas, procedentes de las diferentes zonas arroceras de Colombia, pero sí se detectó la presencia de M y L. La incidencia de AF en estas muestras fue del 50 % (2,4 - 93,9 µg/kg) y la de DON fue del 6 % (128 µg/kg), superándose en el 31 % de las muestras el valor máximo permisible establecido por las legislaciones colombiana y europea. Sin embargo, no se evidenció la presencia de ZEA. ; Rice (Oryza sativa L.) is one of the most important food crops in the world, with Colombia being the second largest rice producer in Latin America, after Brazil. Rice has been classified as the third largest agricultural product in the country, behind coffee and corn, respectively. In the present study, the quality of rice grown and commercialized in Colombia was determined, taking into account microbiological, physicochemical, and toxicological parameters (presence of mycotoxins); furthermore, the general objective of this inquiry was to study the incidence of aflatoxins, zearalenone, and deoxynivalenol in rice produced in the main rice-growing areas of Colombia. During 2017, 62 samples of paddy rice grown by "irrigation" and "dry" systems were taken, from the main rice-growing areas of Colombia. In 2018, the number of samples collected was 58, from the two cultivation systems. These samples were microbiologically analyzed (Total Coliforms, Escherichia coli and Molds and Yeasts) and their physicochemical characteristics (pH, water activity -Aw- and moisture content) were determined. Finally, the samples were analyzed for the detection and quantification of aflatoxins (AF) (B1, B2, G1 and G2), zearalenone (ZEA) and deoxynivalenol (DON). For this reason, standardized analytical techniques recognized by the Official Association of Analytical Chemistry of the United States (AOAC) were conducted. The results obtained from the samples collected during 2017, a global incidence of 46 % of Total Coliforms (CT) was observed in the grains from the "irrigation" system all over the rice-growing areas. Regarding the "dry" sample system, the observed incidence was about the 50 %. The incidence of Molds and Yeasts (M and L) was high, ranging between 96 and 100 %, regardless of the culture system used. Escherichia coli presented an incidence of 8 % in the "irrigation" system, while its presence was not detected in the samples grown by the "dry" system. In the rice cultivated in 2018 by the "irrigation" system, the microbial load (both of bacteria and fungi) decreased considerably, in which only 13 % of the samples had CT counts. Molds were present in 76 % of the samples. Comcerning the "dry" system, 23 % of the samples presented contamination with CT and 54 % with M and L. The presence of fungi in cultivated grain was very high throughout the country, although in 2018 there was a generalized decrease in the incidence in all rice-growing areas. In relation to the physicochemical variables, the samples from the "irrigation" system presented during 2017 average pH values between 6,39 and 6,75, and of 0,65 and 0,74 of Aw, with values of humidity between 7,48 and 11.74 %. The samples cultivated by the "dry" system showed average values of pH between 6,72 and 7,00, of 0,70 and 0,75 of Aw, and humidity between 6,87 and 10,09 %. In the samples from the "irrigation" system in 2018, the pH values ranged between 6,68 and 7,37, those of Aw between 0,71 - 0,74, and those of humidity between 7,78 and 10, 12 %, while those of the "dry" system presented pH values between 6,44 and 6,75, of 0.65 and 0,74 of Aw, and between 7,11 and 8.39 % moisture. These physicochemical characteristics and their interactions are the main etiological determinants in the regulation of fungal growth and the production of secondary metabolites. In 2017, the mycotoxin with the highest incidence in the country was AF, followed by ZEA. The most critical area for the presence of AF was the "North" one. In 2018, ZEA became the mycotoxin with the highest incidence, especially in the "irrigation" cultivation system. In contrast, DON was the mycotoxin with the lowest incidence. Regardless of the cultivation system applied, in the samples collected during the two years, the presence of AFG1 and AFG2 was not evidenced. In the samples cultivated by the "irrigation" system, the presence of AF was detected in 15 % of the samples, with concentrations that varied between 0,1 µg/kg and 1,83 mg/kg, while the ZEA was detected in 13 % of the samples, with concentrations between 53,5 µg/kg and 2,57 mg/kg. The presence of DON was not detected in any sample. In the samples from the "dry" system, the presence of FA was observed in 43 % of the samples (2,1 - 119,5 µg/kg) and ZEA in 7 % (271,9 µg/kg). The incidence of AF in rice cultivated by the "irrigation" system in 2018 was reduced compared to the previous year, being detected only in 2 % of the samples (0,9 µg/kg). However, a higher incidence of ZEA was found present in 31 % of the samples (98 µg/kg - 5.19 mg/kg). The appearance of DON was remarkable in 7 % of the samples analyzed (0,87 - 5,86 mg/kg), coming from the "Central" and "Llanos Orientales" areas of the country. In the samples obtained by the "dry" system, the presence of AF and ZEA was detected, but DON was not detected in any area. The incidence of AF was 31 % (1,6 - 22,4 µg/kg) and that of ZEA was 15 % (67 µg/kg). About the fungal isolates obtained from the cultured rice samples corresponding to the sampling of the year 2017, Aspergillus was the genus isolated with the highest frequency (74 %) followed by Penicillium (20 %). 19 strains of mold isolated from rice grown in 2017 were isolated, characterizing them phenotypically and molecularly; 17 of them corresponded to Aspergillus flavus. 52 % of the strains showed UV fluorescence in ALC and their aflatoxigenic capacity was verified. The presence of CT or E. coli was not detected in any of the 16 commercial rice samples analyzed, from the different rice-growing areas of Colombia, but the presence of M and L was detected. The incidence of AF in these samples were 50 % (2,4 - 93,9 µg/kg) and that of DON was 6 % (128 µg/kg), exceeding the maximum permissible value established by Colombian legislation in 31 % of the samples and European. However, the presence of ZEA was not evidenced.
This is the preliminary publication of the collection of artefacts found in the burial ground near to Komarovka of the Ulyanovsk region. The items came from a cremation burial destroyed by treasure-hunters. A long single-edged blade, a spearhead and a combat knife, as well as elements of horse harness, and garnets, form the set of artefacts. As it is clear from their condition, the grave goods were intentionally damaged in the past as a part of the rite. We date this artefact complex to the middle or to the second half of the 6th c. CE. The fact that the burial includes a blade, as well as some specifi cities of the funeral rite, makes it unique for the Imen'kovo culture. Northern Caucasus and the Danube are the regions where one can fi nd the analogues for the artifacts included in Komarovka burial set. We suggest their introduction to the Middle Volga could be related to cultural interactions of when the Avarian and Turkic Khaganates established. The same processes started the formation of new military equipment of the Imen'kovo population which included melee weapons and plate armor as well, in addition to bow and arrows. ; Статья посвящена предварительной публикации набора артефактов из грунтового могильника у с. Комаровка Ульяновской области. Предметы происходят из разрушенного несанкционированными раскопками погребения, совершенного по обряду кремации с преднамеренным повреждением погребального инвентаря. В состав анализируемого комплекса входят длинный однолезвийный клинок, наконечник копья и боевой нож, а также предметы конского снаряжения, украшения и детали костюма. Вероятная датировка комплекса - середина - вторая половина VI в. н.э. Наличие клинкового оружия и особенности погребального обряда делают публикуемый комплекс уникальным для именьковской культуры. Аналогии составляющим его артефактам обнаруживаются в материалах Северного Кавказа и Подунавья, а также Западной Сибири. 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Esta tesis doctoral se ha realizado dentro del marco de un acuerdo de co-tutela entre la Universidad de Zaragoza (Universidad de origen), la Universidad de Calabria (Universidad anfitriona) y la Facultad de Ciencias y Tecnología de la Universidad NOVA de Lisboa (FCT NOVA) (Universidad anfitriona). El trabajo de investigación se ha llevado a cabo dentro del programa de Doctorado en Ingeniería de Membranas Erasmus Mundus (EUDIME), (FPA 2011-0014), financiado por la Unión Europea. La tesis se centró principalmente en el uso de la técnica de electrohilado para producir diferentes tipos de membranas que puedan ser utilizadas en distintas aplicaciones biomédicas. Se sintetizaron y produjeron nanopartículas orgánicas e inorgánicas para ser utilizadas como rellenos o como portadores (sistema de administración de fármacos), así como membranas nanofibrosas electrohiladas. Este trabajo se llevó a cabo en el Instituto de Nanociencia de Aragón (INA), específicamente en el grupo de Nanostructured Films and Particles (NFP) bajo la supervisión de la profesora Silvia Irusta y la Dra. Gracia Mendoza. Una parte importante de la caracterización físico-química se realizó en el INA. En la Universidad de Calabria se trabajó bajo la supervisión de la Dra. Loredana de Bartolo en el Instituto de Tecnología de Membranas (ITM). Allí se utilizaron técnicas específicas tanto para la caracterización como para estudiar diferentes señales biológicas producidas por las membranas sintetizadas, bajo la supervisión. Por otro lado, la movilidad llevada a cabo en la Facultad de Ciencias y Tecnología (FCT NOVA) de la Universidade NOVA (FCT NOVA) bajo la supervisión de la profesora Ana Isabel Aguiar-Ricardo, permitió realizar una caracterización completa de dos membranas asimétricas siguiendo diferentes Normas Internacionales que establecen diferentes ensayos a realizar en apósitos primarios utilizados en heridas. El desarrollo de nuevos scaffolds cargados con proteínas morfogenéticas o antibióticos es de gran interés en el campo de la ingeniería de tejidos óseos. Scaffolds electrohilados con una microporosidad mejorada puede ser beneficioso para mejorar la viabilidad celular debido a que una alta porosidad junto a la presencia de microporos puede proporcionar un entorno tridimensional (3D) que no solamente facilita la siembra y difusión celular sino también proporciona una mejor difusión de los nutrientes y residuos a través del scaffolds. La adición de cerámica de fosfato de calcio ha sido ampliamente investigada para fabricar scaffolds altamente porosos para la ingeniería de tejidos óseos debido a que presentan una composición muy similar al hueso, incluyendo excelentes propiedades de biocompatibilidad, osteoinductivas y osteoconductoras. Partículas cargadas con proteínas morfogenéticas de hueso distribuidas homogéneamente en el scaffolds podrían asegurar una liberación continua del factor de crecimiento proporcionando de esta forma las señales bioquímicas necesarias para la reparación y regeneración ósea. Los scaffolds cargados con antibióticos pueden proporcionar una liberación sostenida del fármaco en el sitio de interés, así como el mantenimiento de propiedades osteogénicas mejoradas para la regeneración exitosa del hueso. Evitando de esta forma que se alcancen niveles de toxicidad o niveles ineficaces en la zona de interés, así como la aparición de efectos secundarios indeseados en los pacientes que provocan un rechazo a los tratamientos prolongados de fármacos por vía sistemática (vía oral e intravenosa). Otra aplicación biomédica interesante de las membranas electrohiladas es la fabricación de apósitos inteligentes eficientes para el tratamiento de heridas. Para lograr una curación rápida de la herida es necesario desarrollar membranas apropiadas con poros interconectados capaces de prevenir la deshidratación rápida y la penetración de bacterias. Para mantener un ambiente húmedo en el lecho de la herida se necesita una alta capacidad de absorción y una adecuada transmisión de vapor de agua. Además, si la membrana electrohilada presenta propiedades bactericidas facilitará el proceso de curación. El objetivo principal de esta tesis fue el desarrollo mediante electrohilado de membranas fibrosas con las características apropiadas para ser utilizadas en la ingeniería de tejidos óseos o como apósito para heridas. En los Capítulos II al V se plantean una serie de objetivos específicos con el fin de cumplir el objetivo principal. Este documento de tesis se dividió en las siguientes secciones: CAPÍTULO I, corresponde a la introducción general donde se describen los conceptos de biomateriales, scaffolds, ingeniería de tejidos y el objetivo principal de los sistemas de liberación de fármacos. Así como, la clasificación de los biomateriales y la ingeniería de tejidos según el origen de los materiales. Además se ponen de manifiesto todos los factores que deben tenerse en cuenta para desarrollar y aplicar adecuadamente los apósitos para heridas. Se mencionaron las diferentes técnicas utilizadas en la literatura haciendo énfasis en el uso de electrohilado y electropulverización para producir scaffolds o membranas para su uso en la ingeniería del tejido óseo y como apósitos para heridas. CAPÍTULO II, se enfoca en el desarrollo y mejora de andamios 3D capaces de promover una eficiente regeneración ósea junto con la liberación de antibióticos dirigidos para prevenir la colonización de bacterias. El objetivo de este trabajo fue sintetizar y caracterizar un sistema de liberación de fármacos que consiste en nanofibras electrohiladas de policaprolactona (PCL) decoradas con partículas de poli (ácido láctico-coglicólico) (PLGA) cargadas con rifampicina (RFP). Este material debe promover la reparación ósea evitando el deterioro del scaffolds provocado por una infección. Se realizó la evaluación in vitro de la capacidad bactericida del material electrohilado sintetizado contra bacterias Gram positivas (Staphylococcus aureus) y Gram negativas (Escherichia coli), así como su citocompatibilidad en cultivos 3D con osteoblastos humanos. Estos resultados se enviaron a la Revista de farmacia "International Journal of Pharmaceuitics" para su publicación en formato de artículo y está bajo revisión. CAPÍTULO III, se describe la síntesis y caracterización de membranas con estructura de núcleo-envoltura de PCL y acetato de polivinilo (PVAc) obtenidas por electrohilado. Las fibras se cargaron con nanopartículas de hidroxiapatita sintética (HAn) para aumentar la bioactividad de los materiales. Los scaffolds desarrollados se trataron con ablación láser para crear características topográficas deseadas a nivel micrométrico con el objetivo de favorecer la adhesión y crecimiento celular. Todas las membranas obtenidas presentaron una estructura de poros tridimensionalmente interconectados y el tratamiento con láser provocó un aumento en la viabilidad y densidad celular. Además, el aumento en la biocompatibilidad de los scaffolds sugiere que los microporos pequeños favorecen la adhesión y proliferación celular. Estos resultados fueron publicados en el artículo titulado "Laser-treated electrospun fibers loaded with nano-hydroxyapatite for bone tissue engineering". Javier Aragon, Nuria Navascues, Gracia Mendoza, Silvia Irusta. International Journal of Pharmaceutics 525,112–122, 2017. DOI:10.1016/j.ijpharm.2017.04.022. CAPÍTULO IV, se refiere al desarrollo de un scaffold electrohilado compuesto por fibras con estructura de núcleo-cubierta de PCL o PCL/PVAc cargado con HAn sintética. Estas fibras se decoraron con partículas de PLGA cargadas con proteína morfogenética ósea 2 (BMP2) mediante el uso simultaneo de electrohilado coaxial y electropulverización. El objetivo de este trabajo fue evaluar las propiedades estructurales y físico-químicas así como el proceso de biodegradación de los nuevos scaffolds desarrollados y su capacidad para abordar las características arquitectónicas, bioquímicas y funcionales del tejido óseo. Para esto, se probó la bioactividad del scaffold mediante el cultivo de osteoblastos humanos sobre ellos y se monitoreo de la viabilidad celular durante 4 semanas. Se evaluó la actividad osteogénica in vitro de las células sembradas sobre los scaffolds determinando la actividad de la fosfatasa alcalina (ALP) y la expresión de osteocalcina (OCN) y osteopontina (OPN) como proteínas osteogénicas. Estos resultados fueron publicados en el artículo titulado "Polymeric electrospun scaffolds for bone morphogenetic protein 2 delivery in bone tissue engineering". Javier Aragón, Simona Salerno, Loredana De Bartolo, Silvia Irusta and Gracia Mendoza. Journal of Colloid and Interface Science, 531 (2018) 126–137. DOI:10.1016/j.jcis.2018.07.029. El CAPÍTULO V, describe la síntesis de un apósito antimicrobiano para heridas, con una resistencia mecánica adecuada que es capaz de absorber exudados y evitar la deshidratación rápida de una herida. Se prepararon membranas asimétricas de PCL/PVAc cargadas con carvacrol (CRV) mediante el uso simultáneo de electrohilado y electropulverización. Las membranas constan de dos capas; la primera es una capa de PCL electrohilado; la segunda, una lámina de PVAc que estaría en contacto con la piel liberando a su vez el compuesto antimicrobiano. Se demostró que el uso de diferentes disolventes pueden dar lugar a la obtención de diferentes morfologías de la capa PVAc-CRV. Los valores obtenidos de elongación máxima de las membranas antes de romperse son adecuados para ser utilizados como apósitos para heridas ya que están en el mismo rango reportado de elongaciones en la piel humana. Las membranas presentan una tasa óptima de Transmisión de vapor de agua (WVTR) con valores que se encuentran en el rango requerido para mantener un buen balance entre humedad y pérdida de agua en la herida. En la primera semana, se liberó más del 60 % del CRV cargado, mientras que después de tres semanas, las membranas liberaron entre el 85 y el 100 % del CRV cargado mediante la contribución de un proceso de difusión de tipo Fickiano y la relajación delas cadenas poliméricas. Las membranas sintetizadas son candidatas potenciales para ser utilizadas como apósitos para heridas. El manuscrito que resume estos resultados se envió a la revista "Materials Science and Engineering C" y está bajo revisión (MSEC_2018_3013). CAPÍTULO VI, resume las conclusiones generales del trabajo de tesis. APÉNDICE 1, describe las principales técnicas de caracterización y los métodos para evaluar diferentes propiedades en función de las posibles aplicaciones. APÉNDICE 2, resume los artículos publicados y la participación en foros científicos durante el período de tesis. 1 The current Doctoral Thesis work has been performed under a co-supervision agreement between University of Zaragoza (Home University), University of Calabria (Host University) and Faculty of Sciences and Technology of the NOVA University of Lisbon (FCT NOVA) (Host University). This research has been carried out inside the Erasmus Mundus Doctorate in Membrane Engineering program (EUDIME), (FPA 2011-0014), funded by the European Union. This thesis focused mainly on the use of the electrospinning technique to produce different kind of membranes for biomedical applications. In particular, it described the synthesis and production of inorganic and organic nanoparticles to be used as fillers or as carriers (drug delivery system) as well as the production of electrospun nanofibrous membranes. This work was carried out within the Institute of Nanoscience of Aragon (INA), specifically in the Nanostructured Films and Particles (NFP) group under the supervision of the Professor Silvia Irusta and Dr Gracia Mendoza. Also an important part of the physico-chemical characterization was done at INA. The study of different biological signals and the use of specific techniques for membrane characterization were acquired at the University of Calabria under the supervision of Dr. Loredana De Bartolo in the Institute on Membrane Technology of the National Research Council of Italy (ITM-CNR). On the other hand, the mobility carried out at the Faculty of Sciences and Technology (FCT NOVA) of Universidade NOVA (FCT NOVA) under the supervision of Professor Ana Isabel Aguiar-Ricardo, allowed a total characterization of two asymmetric membranes following different International Standards to accomplish testing for primary wound dressing. The development of novel membranes loaded with morphogenetic proteins or antibiotic are of great interest in the field of bone tissue engineering. To promote the cellular viability and extracellular matrix production, electrospun membranes with enhanced porosity and micro-scale pores could be beneficial since increased porosity and pore size can provide a three-dimensional (3D) environment that not only facilitates cell seeding/diffusion but also provides better diffusion of nutrients and waste throughout the membranes. The addition of calcium phosphate ceramics has been extensively investigated to fabricate highly porous membranes to bone tissue engineering due to their close similar composition of bone, including excellent biocompatibility, osteoinductive and osteoconductive properties. A homogeneous distribution of the bone morphogenetic protein-loaded particles along the entire membrane could be ensuring a continuous release of the growth factor to provide the necessary biochemical cues for bone repair and regeneration. Antibiotic-loaded membranes may provide drug targeted and sustained release, avoiding the long-term oral and intravenous systematic multidrug administration, which implies toxic side effects, low delivery to the target site and low patient adherence to the treatment. Therefore, membranes loaded with antibiotics can overcome the drawbacks of the traditional therapy sustaining enhanced osteogenic properties for the successful regeneration of the bone. Another interesting biomedical application of electrospun membranes is the fabrication of efficient smart dressings for the treatment of wounds. A rapid wound healing requires developing appropriate membranes with interconnected pores that allow the oxygen diffusion and transport of metabolic waste, as well as an adequate pore size to prevent rapid dehydration and bacteria penetration. A high absorption capacity and adequate water vapor transmission will be necessary to keep a moist environment in the wound bed. Besides, if the electrospun membrane has some bactericidal properties will be better for the healing process. The main goal of this thesis was the development of fibrous membranes by electrospinning with the appropriate characteristics to be used in bone tissue engineering or as wound dressing materials. To achieve this target, several specific objectives were defined, which are described in Chapters II to V. The thesis was divided in the following sections: CHAPTER I, is an introduction where the concepts of biomaterials, scaffolds and tissue engineering and the main target of drug delivery systems are described. The chapter includes the classification of biomaterials according to the origin of the materials and tissue engineering is also described as well as all the factors that must be taken into account to develop and properly apply a wound dressing are discussed. Different kind of techniques used in the literature to produce scaffolds or membranes for bone tissue engineering and wound dressings are mentioned, focusing on the use of electrospinning and electrospray to produce them. CHAPTER II, focuses on the development of enhanced 3D membranes able to promote efficient bone regeneration together with targeted antibiotic release to prevent bacteria colonization. The aim of this work was to synthesize and characterize a drug delivery system consisting of polycaprolactone (PCL) electrospun nanofibers decorated with rifampicin (RFP) loaded into poly(lactic-coglicolic acid) (PLGA) particles. This material would promote bone repair avoiding the impairment of the membrane mediated by infection. The bactericidal ability of the synthesized electrospun material was assessed In vitro against gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria, as well as its cytocompatibility in human osteoblasts 3D cultures. These results are included in the accepted article entitled "Composite scaffold obtained by electro-hydrodynamic technique for infection prevention and treatment in bone repair". Javier Aragon, Sergio Feoli, Gracia Mendoza, Silvia Irusta. International Journal of Pharmaceutics. CHAPTER III, describes the synthesis and characterization of core-shell membranes of PCL and polyvinyl acetate (PVAc) obtained by electrospinning. The fibers were loaded with synthetic hydroxyapatite nanoparticles (HAn) to increase the bioactivity of the materials. The prepared membranes were then treated by laser ablation to create desired microscale topographical features in order to favor cell adhesion and growth. All prepared membranes exhibited a three-dimensional network structure with interconnected pores; the laser treatment has modified the structural characteristics of the membrane causing an increase the cell viability and cell density. The materials biocompatibility is affected by the structural properties of the membranes, indeed smaller micropore sizes favor cell adhesion and proliferation. These results are published in the article entitled "Laser-treated electrospun fibers loaded with nano-hydroxyapatite for bone tissue engineering". Javier Aragon, Nuria Navascues, Gracia Mendoza, Silvia Irusta. International Journal of Pharmaceutics 525,112–122, 2017. DOI:10.1016/j.ijpharm.2017.04.022. CHAPTER IV, refers to the development of a composite electrospun membrane of PCL or PCL/PVAc core–shell fibers loaded with synthetic HAn. These fibers were decorated with bone morphogenetic protein 2 (BMP2) loaded in/into PLGA particles via simultaneous electrospraying and coaxial electrospinning. The aim of this study was to evaluate the structural and physico-chemical properties and biodegradation processes of the newly developed membranes assessing their ability to address the architectural, biochemical, and functional features of bone tissue. For this purpose, the membrane bioactivity was tested by culturing human osteoblasts on the membranes and by monitoring cell viability up to 4 weeks. The In vitro osteogenic activity of cells seeded onto the membranes was evaluated by assessing alkaline phosphatase (ALP) activity and the expression of osteogenic proteins osteocalcin (OCN) and osteopontin (OPN). These results are published in the article "Polymeric electrospun scaffolds for bone morphogenetic protein 2 delivery in bone tissue engineering". Javier Aragón, Simona Salerno, Loredana De Bartolo, Silvia Irusta and Gracia Mendoza. Journal of Colloid and Interface Science, 531 (2018) 126–137. DOI:10.1016/j.jcis.2018.07.029. CHAPTER V, describes the synthesis of an antimicrobial wound dressing material, with appropriate mechanical resistance avoiding rapid dehydration and absorbing exudates. PCL/PVAc asymmetric membranes loaded with carvacrol (CRV) were prepared by electrospinning and electrospraying simultaneously. The membranes consist of two layers: the first is an electrospun PCL sheet, the second a PVAc sheet that would be in contact with the skin releasing the antimicrobial compound. The use of different solvents results in different morphologies for the PVAc-CRV layer. The membranes exhibit mechanical properties with strain to failure values that are in the range of human skin, being adequate to be deposited over a wound surface. The samples present Water Vapor Transmission (WVTR) values in the required range to keep good moisture balance with water loss from the wound at the optimal rate. In the first week, more than 60 % of the loaded CRV was released while after three weeks membranes released between 85 to 100 % of the loaded CRV through a Fickian diffusion and diffusion due to polymer relaxation. The synthesized membranes are potential candidates to be used for wound dressing applications. The manuscript summing up these results has been submitted to a scientific journal and is currently under review. GENERAL CONCLUSIONS, summarizes the conclusions of the thesis work. APPENDIX 1, describes the main characterization techniques and the methods to evaluate different properties according to the possible applications. APPENDIX 2, summarizes the articles published and the participation in scientific forums during the thesis period.
In my postgraduate formation during the last years of the 80's, we had close to thirty hospital beds in a pavilion called "sépticas" (1). In Colombia, where abortion was completely penalized, the pavilion was mostly filled with women with insecure, complicated abortions. The focus we received was technical: management of intensive care; performance of hysterectomies, colostomies, bowel resection, etc. In those times, some nurses were nuns and limited themselves to interrogating the patients to get them to "confess" what they had done to themselves in order to abort. It always disturbed me that the women who left alive, left without any advice or contraceptive method. Having asked a professor of mine, he responded with disdain: "This is a third level hospital, those things are done by nurses of the first level". Seeing so much pain and death, I decided to talk to patients, and I began to understand their decision. I still remember so many deaths with sadness, but one case in particular pains me: it was a woman close to being fifty who arrived with a uterine perforation in a state of advanced sepsis. Despite the surgery and the intensive care, she passed away. I had talked to her, and she told me she was a widow, had two adult kids and had aborted because of "embarrassment towards them" because they were going to find out that she had an active sexual life. A few days after her passing, the pathology professor called me, surprised, to tell me that the uterus we had sent for pathological examination showed no pregnancy. She was a woman in a perimenopausal state with a pregnancy exam that gave a false positive due to the high levels of FSH/LH typical of her age. SHE WAS NOT PREGNANT!!! She didn't have menstruation because she was premenopausal and a false positive led her to an unsafe abortion. Of course, the injuries caused in the attempted abortion caused the fatal conclusion, but the real underlying cause was the social taboo in respect to sexuality. I had to watch many adolescents and young women leave the hospital alive, but without a uterus, sometime without ovaries and with colostomies, to be looked down on by a society that blamed them for deciding to not be mothers. I had to see situation of women that arrived with their intestines protruding from their vaginas because of unsafe abortions. I saw women, who in their despair, self-inflicted injuries attempting to abort with elements such as stick, branches, onion wedges, alum bars and clothing hooks among others. Among so many deaths, it was hard not having at least one woman per day in the morgue due to an unsafe abortion. During those time, healthcare was not handled from the biopsychosocial, but only from the technical (2); nonetheless, in the academic evaluations that were performed, when asked about the definition of health, we had to recite the text from the International Organization of Health that included these three aspects. How contradictory! To give response to the health need of women and guarantee their right when I was already a professor, I began an obstetric contraceptive service in that third level hospital. There was resistance from the directors, but fortunately I was able to acquire international donations for the institution, which facilitated its acceptance. I decided to undertake a teaching career with the hope of being able to sensitize health professionals towards an integral focus of health and illness. When the International Conference of Population and Development (ICPD) was held in Cairo in 1994, I had already spent various years in teaching, and when I read their Action Program, I found a name for what I was working on: Sexual and Reproductive Rights. I began to incorporate the tools given by this document into my professional and teaching life. I was able to sensitize people at my countries Health Ministry, and we worked together moving it to an approach of human rights in areas of sexual and reproductive health (SRH). This new viewpoint, in addition to being integral, sought to give answers to old problems like maternal mortality, adolescent pregnancy, low contraceptive prevalence, unplanned or unwanted pregnancy or violence against women. With other sensitized people, we began with these SRH issues to permeate the Colombian Society of Obstetrics and Gynecology, some universities, and university hospitals. We are still fighting in a country that despite many difficulties has improved its indicators of SRH. With the experience of having labored in all sphere of these topics, we manage to create, with a handful of colleagues and friend at the Universidad El Bosque, a Master's Program in Sexual and Reproductive Health, open to all professions, in which we broke several paradigms. A program was initiated in which the qualitative and quantitative investigation had the same weight, and some alumni of the program are now in positions of leadership in governmental and international institutions, replicating integral models. In the Latin American Federation of Obstetrics and Gynecology (FLASOG, English acronym) and in the International Federation of Obstetrics and Gynecology (FIGO), I was able to apply my experience for many years in the SRH committees of these association to benefit women and girls in the regional and global environments. When I think of who has inspired me in these fights, I should highlight the great feminist who have taught me and been with me in so many fights. I cannot mention them all, but I have admired the story of the life of Margaret Sanger with her persistence and visionary outlook. She fought throughout her whole life to help the women of the 20th century to be able to obtain the right to decide when and whether or not they wanted to have children (3). Of current feminist, I have had the privilege of sharing experiences with Carmen Barroso, Giselle Carino, Debora Diniz and Alejandra Meglioli, leaders of the International Planned Parenthood Federation – Western Hemisphere Region (IPPF-RHO). From my country, I want to mention my countrywoman Florence Thomas, psychologist, columnist, writer and Colombo-French feminist. She is one of the most influential and important voices in the movement for women rights in Colombia and the region. She arrived from France in the 1960's, in the years of counterculture, the Beatles, hippies, Simone de Beauvoir, and Jean-Paul Sartre, a time in which capitalism and consumer culture began to be criticized (4). It was then when they began to talk about the female body, female sexuality and when the contraceptive pill arrived like a total revolution for women. Upon its arrival in 1967, she experimented a shock because she had just assisted in a revolution and only found a country of mothers, not women (5). That was the only destiny for a woman, to be quiet and submissive. Then she realized that this could not continue, speaking of "revolutionary vanguards" in such a patriarchal environment. In 1986 with the North American and European feminism waves and with her academic team, they created the group "Mujer y Sociedad de la Universidad Nacional de Colombia", incubator of great initiatives and achievements for the country (6). She has led great changes with her courage, the strength of her arguments, and a simultaneously passionate and agreeable discourse. Among her multiple books, I highlight "Conversaciones con Violeta" (7), motivated by the disdain towards feminism of some young women. She writes it as a dialogue with an imaginary daughter in which, in an intimate manner, she reconstructs the history of women throughout the centuries and gives new light of the fundamental role of feminism in the life of modern women. Another book that shows her bravery is "Había que decirlo" (8), in which she narrates the experience of her own abortion at age twenty-two in sixty's France. My work experience in the IPPF-RHO has allowed me to meet leaders of all ages in diverse countries of the region, who with great mysticism and dedication, voluntarily, work to achieve a more equal and just society. I have been particularly impressed by the appropriation of the concept of sexual and reproductive rights by young people, and this has given me great hope for the future of the planet. We continue to have an incomplete agenda of the action plan of the ICPD of Cairo but seeing how the youth bravely confront the challenges motivates me to continue ahead and give my years of experience in an intergenerational work. In their policies and programs, the IPPF-RHO evidences great commitment for the rights and the SRH of adolescent, that are consistent with what the organization promotes, for example, 20% of the places for decision making are in hands of the young. Member organizations, that base their labor on volunteers, are true incubators of youth that will make that unassailable and necessary change of generations. In contrast to what many of us experienced, working in this complicated agenda of sexual and reproductive health without theoretical bases, today we see committed people with a solid formation to replace us. In the college of medicine at the Universidad Nacional de Colombia and the College of Nursing at the Universidad El Bosque, the new generations are more motivated and empowered, with great desire to change the strict underlying structures. Our great worry is the onslaught of the ultra-right, a lot of times better organized than us who do support rights, that supports anti-rights group and are truly pro-life (9). Faced with this scenario, we should organize ourselves better, giving battle to guarantee the rights of women in the local, regional, and global level, aggregating the efforts of all pro-right organizations. We are now committed to the Objectives of Sustainable Development (10), understood as those that satisfy the necessities of the current generation without jeopardizing the capacity of future generations to satisfy their own necessities. This new agenda is based on: - The unfinished work of the Millennium Development Goals - Pending commitments (international environmental conventions) - The emergent topics of the three dimensions of sustainable development: social, economic, and environmental. We now have 17 objectives of sustainable development and 169 goals (11). These goals mention "universal access to reproductive health" many times. In objective 3 of this list is included guaranteeing, before the year 2030, "universal access to sexual and reproductive health services, including those of family planning, information, and education." Likewise, objective 5, "obtain gender equality and empower all women and girls", establishes the goal of "assuring the universal access to sexual and reproductive health and reproductive rights in conformity with the action program of the International Conference on Population and Development, the Action Platform of Beijing". It cannot be forgotten that the term universal access to sexual and reproductive health includes universal access to abortion and contraception. Currently, 830 women die every day through preventable maternal causes; of these deaths, 99% occur in developing countries, more than half in fragile environments and in humanitarian contexts (12). 216 million women cannot access modern contraception methods and the majority live in the nine poorest countries in the world and in a cultural environment proper to the decades of the seventies (13). This number only includes women from 15 to 49 years in any marital state, that is to say, the number that takes all women into account is much greater. Achieving the proposed objectives would entail preventing 67 million unwanted pregnancies and reducing maternal deaths by two thirds. We currently have a high, unsatisfied demand for modern contraceptives, with extremely low use of reversible, long term methods (intrauterine devices and subdermal implants) which are the most effect ones with best adherence (14). There is not a single objective among the 17 Objectives of Sustainable Development where contraception does not have a prominent role: from the first one that refers to ending poverty, going through the fifth one about gender equality, the tenth of inequality reduction among countries and within the same country, until the sixteenth related with peace and justice. If we want to change the world, we should procure universal access to contraception without myths or barriers. We have the moral obligation of achieving the irradiation of extreme poverty and advancing the construction of more equal, just, and happy societies. In emergency contraception (EC), we are very far from reaching expectations. If in reversible, long-term methods we have low prevalence, in EC the situation gets worse. Not all faculties in the region look at this topic, and where it is looked at, there is no homogeneity in content, not even within the same country. There are still myths about their real action mechanisms. There are countries, like Honduras, where it is prohibited and there is no specific medicine, the same case as in Haiti. Where it is available, access is dismal, particularly among girls, adolescents, youth, migrants, afro-descendent, and indigenous. The multiple barriers for the effective use of emergency contraceptives must be knocked down, and to work toward that we have to destroy myths and erroneous perceptions, taboos and cultural norms; achieve changes in laws and restrictive rules within countries, achieve access without barriers to the EC; work in union with other sectors; train health personnel and the community. It is necessary to transform the attitude of health personal to a service above personal opinion. Reflecting on what has occurred after the ICPD in Cairo, their Action Program changed how we look at the dynamics of population from an emphasis on demographics to a focus on the people and human rights. The governments agreed that, in this new focus, success was the empowerment of women and the possibility of choice through expanded access to education, health, services, and employment among others. Nonetheless, there have been unequal advances and inequality persists in our region, all the goals were not met, the sexual and reproductive goals continue beyond the reach of many women (15). There is a long road ahead until women and girls of the world can claim their rights and liberty of deciding. Globally, maternal deaths have been reduced, there is more qualified assistance of births, more contraception prevalence, integral sexuality education, and access to SRH services for adolescents are now recognized rights with great advances, and additionally there have been concrete gains in terms of more favorable legal frameworks, particularly in our region; nonetheless, although it's true that the access condition have improved, the restrictive laws of the region expose the most vulnerable women to insecure abortions. There are great challenges for governments to recognize SRH and the DSR as integral parts of health systems, there is an ample agenda against women. In that sense, access to SRH is threatened and oppressed, it requires multi-sector mobilization and litigation strategies, investigation and support for the support of women's rights as a multi-sector agenda. Looking forward, we must make an effort to work more with youth to advance not only the Action Program of the ICPD, but also all social movements. They are one of the most vulnerable groups, and the biggest catalyzers for change. The young population still faces many challenges, especially women and girls; young girls are in particularly high risk due to lack of friendly and confidential services related with sexual and reproductive health, gender violence, and lack of access to services. In addition, access to abortion must be improved; it is the responsibility of states to guarantee the quality and security of this access. In our region there still exist countries with completely restrictive frameworks. New technologies facilitate self-care (16), which will allow expansion of universal access, but governments cannot detach themselves from their responsibility. Self-care is expanding in the world and can be strategic for reaching the most vulnerable populations. There are new challenges for the same problems, that require a re-interpretation of the measures necessary to guaranty the DSR of all people, in particular women, girls, and in general, marginalized and vulnerable populations. It is necessary to take into account migrations, climate change, the impact of digital media, the resurgence of hate discourse, oppression, violence, xenophobia, homo/transphobia, and other emergent problems, as SRH should be seen within a framework of justice, not isolated. We should demand accountability of the 179 governments that participate in the ICPD 25 years ago and the 193 countries that signed the Sustainable Development Objectives. They should reaffirm their commitments and expand their agenda to topics not considered at that time. Our region has given the world an example with the Agreement of Montevideo, that becomes a blueprint for achieving the action plan of the CIPD and we should not allow retreat. This agreement puts people at the center, especially women, and includes the topic of abortion, inviting the state to consider the possibility of legalizing it, which opens the doors for all governments of the world to recognize that women have the right to choose on maternity. This agreement is much more inclusive: Considering that the gaps in health continue to abound in the region and the average statistics hide the high levels of maternal mortality, of sexually transmitted diseases, of infection by HIV/AIDS, and the unsatisfied demand for contraception in the population that lives in poverty and rural areas, among indigenous communities, and afro-descendants and groups in conditions of vulnerability like women, adolescents and incapacitated people, it is agreed: 33- To promote, protect, and guarantee the health and the sexual and reproductive rights that contribute to the complete fulfillment of people and social justice in a society free of any form of discrimination and violence. 37- Guarantee universal access to quality sexual and reproductive health services, taking into consideration the specific needs of men and women, adolescents and young, LGBT people, older people and people with incapacity, paying particular attention to people in a condition of vulnerability and people who live in rural and remote zone, promoting citizen participation in the completing of these commitments. 42- To guarantee, in cases in which abortion is legal or decriminalized in the national legislation, the existence of safe and quality abortion for non-desired or non-accepted pregnancies and instigate the other States to consider the possibility of modifying public laws, norms, strategies, and public policy on the voluntary interruption of pregnancy to save the life and health of pregnant adolescent women, improving their quality of life and decreasing the number of abortions (17).
This research aims to know the potential effect of Intellectual Capital Performance (ICP) to the intensity of Intellectual Capital Disclosure (ICD). The independent variables used in this research are the components of ICP that consists of Value Added Human Capital (VAHU), Value Added Capital Employed (VACA), and Structural Capital Value Added (SCVA) that is measured by using the Value Added Intellectual Coefficient (VAIC™). While, the dependent variable used in this research is ICD that measured by a disclosure index and relevant scoring system. Company size and leverage are also used in the regression model as moderating variables. One year annual reports (2017) of banking sector companies registered on the Indonesia Stock Exchange (IDX) are analyzed in quantitative research type. The samples that listed on the IDX in 2017 are selected by using purposive sampling method with certain criteria and 33 banking sector companies are obtained. The analysis is made by multiple regression analysis and the data testing is conducted by using SPSS 22 and Eviews 9 which previously has been carried out the classic assumption test first. Results of this study indicate that: (1) Simultaneously, ICP component significantly affect ICD. However, each component of VAHU and SCVA does not significantly affect the ICD, only VACA significantly affects the ICD; (2) Simultaneously, with the moderation of company size, ICP does not significantly affect the ICD. Similarly, each component of VAHU, VACA and SCVA does not significantly affect ICD; and (3) Simultaneously, with the moderation of company leverage, ICP significantly affects ICD. 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Social innovations are activities aiming at implementation of social objectives, including mainly the improvement of life of individuals and social groups, together with public policy and management objectives. The essay indicates and discusses the most important contemporary problems, solving of which requires social innovations.
Social innovations precondition the progress of civilisation. The world needs not only new technologies, but also new solutions of social and institutional nature that would be conducive to achieving social goals.
Social innovations are experimental social actions of organisational and institutional nature that aim at improving the quality of life of individuals, communities, nations, companies, circles, or social groups. Their experimental nature stems from the fact of introducing unique and one-time solutions on a large scale, the end results of which are often difficult to be fully predicted. For example, it was difficult to believe that opening new labour markets for foreigners in the countries of the European Union, which can be treated as a social innovation aiming at development of the international labour market, will result in the rapid development of the low-cost airlines, the offer of which will be available to a larger group of recipients. In other words, social innovations differ from economic innovations, as they are not about implementation of new types of production or gaining new markets, but about satisfying new needs, which are not provided by the market. Therefore, the most important distinction consists in that social innovations are concerned with improving the well-being of individuals and communities by additional employment, or increased consumption, as well as participation in solving the problems of individuals and social groups [CSTP, 2011]. In general, social innovations are activities aiming at implementation of social objectives, including mainly the improvement of life of individuals and social groups together with the objectives of public policy and management [Kowalczyk, Sobiecki, 2017]. Their implementation requires global, national, and individual actions. This requires joint operations, both at the scale of the entire globe, as well as in particular interest groups.
Why are social innovations a key point for the progress of civilisation? This is the effect of the clear domination of economic aspects and discrimination of social aspects of this progress. Until the 19th century, the economy was a part of a social structure. As described by K. Polanyi, it was submerged in social relations [Polanyi, 2010, p. 56]. In traditional societies, the economic system was in fact derived from the organisation of the society itself. The economy, consisting of small and dispersed craft businesses, was a part of the social, family, and neighbourhood structure. In the 20th century the situation reversed – the economy started to be the force shaping social structures, positions of individual groups, areas of wealth and poverty. The economy and the market mechanism have become independent from the world of politics and society. Today, the corporations control our lives. They decide what we eat, what we watch, what we wear, where we work and what we do [Bakan, 2006, p. 13].
The corporations started this spectacular "march to rule the world" in the late 19th century. After about a hundred years, at the end of the 20th century, the state under the pressure of corporations and globalisation, started a gradual, but systematic withdrawal from the economy, market and many other functions traditionally belonging to it. As a result, at the end of the last century, a corporation has become a dominant institution in the world. A characteristic feature of this condition is that it gives a complete priority to the interests of corporations. They make decisions of often adverse consequences for the entire social groups, regions, or local communities. They lead to social tensions, political breakdowns, and most often to repeated market turbulences. Thus, a substantial minority (corporations) obtain inconceivable benefits at the expense of the vast majority, that is broad professional and social groups. The lack of relative balance between the economy and society is a barrier to the progress of civilisation.
A growing global concern is the problem of migration. The present crisis, left unresolved, in the long term will return multiplied. Today, there are about 500 million people living in Europe, 1.5 billion in Africa and the Middle East, but in 2100, the population of Europe will be about 400 million and of the Middle East and Africa approximately 4.5 billion. Solving this problem, mainly through social and political innovations, can take place only by a joint operation of highly developed and developing countries. Is it an easy task? It's very difficult. Unfortunately, today, the world is going in the opposite direction. Instead of pursuing the community, empathic thinking, it aims towards nationalism and chauvinism. An example might be a part of the inaugural address of President Donald Trump, who said that the right of all nations is to put their own interests first. Of course, the United States of America will think about their own interests. As we go in the opposite direction, those who deal with global issues say – nothing will change, unless there is some great crisis, a major disaster that would cause that the great of this world will come to senses.
J.E. Stiglitz [2004], contrary to the current thinking and practice, believes that a different and better world is possible. Globalisation contains the potential of countless benefits from which people both in developing and highly developed countries can benefit. But the practice so far proves that still it is not grown up enough to use its potential in a fair manner. What is needed are new solutions, most of all social and political innovations (political, because they involve a violation of the previous arrangement of interests). Failure to search for breakthrough innovations of social and political nature that would meet the modern challenges, can lead the world to a disaster. Social innovation, and not economic, because the contemporary civilisation problems have their roots in this dimension.
A global problem, solution of which requires innovations of social and political nature, is the disruption of the balance between work and capital. In 2010, 400 richest people had assets such as the half of the poorer population of the world. In 2016, such part was in the possession of only 8 people. This shows the dramatic collapse of the balance between work and capital. The world cannot develop creating the technological progress while increasing unjustified inequalities, which inevitably lead to an outbreak of civil disturbances. This outbreak can have various organisation forms. In the days of the Internet and social media, it is easier to communicate with people. Therefore, paradoxically, some modern technologies create the conditions facilitating social protests. There is one more important and dangerous effect of implementing technological innovations without simultaneous creation and implementation of social innovations limiting the sky-rocketing increase of economic (followed by social) diversification. Sooner or later, technological progress will become so widespread that, due to the relatively low prices, it will make it possible for the weapons of mass destruction, especially biological and chemical weapons, to reach small terrorist groups. Then, a total, individualized war of global reach can develop. The individualisation of war will follow, as described by the famous German sociologist Ulrich Beck.
To avoid this, it is worth looking at the achievements of the Polish scientist Michał Kalecki, who 75 years ago argued that capitalism alone is not able to develop. It is because it aggressively seeks profit growth, but cannot turn profit into some profitable investments. Therefore, when uncertainty grows, capitalism cannot develop itself, and it must be accompanied by external factors, named by Kalecki – external development factors. These factors include state expenses, finances and, in accordance with the nomenclature of Kalecki – epochal innovations. And what are the current possibilities of activation of the external factors? In short – modest. The countries are indebted, and the basis for the development in the last 20 years were loans, which contributed to the growth of debt of economic entities. What, then, should we do? It is necessary to look for cheaper solutions, but such that are effective, that is breakthrough innovations. These undoubtedly include social and political innovations. Contemporary social innovation is not about investing big money and expensive resources in production, e.g. of a very expensive vaccine, which would be available for a small group of recipients. Today's social innovation should stimulate the use of lower amounts of resources to produce more products available to larger groups of recipients.
The progress of civilisation happens only as a result of a sustainable development in economic, social, and now also ecological terms. Economic (business) innovations, which help accelerate the growth rate of production and services, contribute to economic development. Profits of corporations increase and, at the same time, the economic objectives of the corporations are realised. But are the objectives of the society as a whole and its members individually realised equally, in parallel? In the chain of social reproduction there are four repeated phases: production – distribution – exchange – consumption. The key point from the social point of view is the phase of distribution. But what are the rules of distribution, how much and who gets from this "cake" produced in the social process of production? In the today's increasingly global economy, the most important mechanism of distribution is the market mechanism. However, in the long run, this mechanism leads to growing income and welfare disparities of various social groups. Although, the income and welfare diversity in itself is nothing wrong, as it is the result of the diversification of effectiveness of factors of production, including work, the growing disparities to a large extent cannot be justified. Economic situation of the society members increasingly depends not on the contribution of work, but on the size of the capital invested, and the market position of the economic entity, and on the "governing power of capital" on the market. It should also be noted that this diversification is also related to speculative activities. Disparities between the implemented economic and social innovations can lead to the collapse of the progress of civilisation.
Nowadays, economic crises are often justified by, indeed, social and political considerations, such as marginalisation of nation states, imbalance of power (or imbalance of fear), religious conflicts, nationalism, chauvinism, etc. It is also considered that the first global financial crisis of the 21st century originated from the wrong social policy pursued by the US Government, which led to the creation of a gigantic public debt, which consequently led to an economic breakdown. This resulted in the financial crisis, but also in deepening of the social imbalances and widening of the circles of poverty and social exclusion. It can even be stated that it was a crisis in public confidence. Therefore, the causes of crises are the conflicts between the economic dimension of the development and its social dimension.
Contemporary world is filled with various innovations of economic or business nature (including technological, product, marketing, and in part – organisational). The existing solutions can be a source of economic progress, which is a component of the progress of civilisation. However, economic innovations do not complete the entire progress of civilisation moreover, the saturation, and often supersaturation with implementations and economic innovations leads to an excessive use of material factors of production. As a consequence, it results in lowering of the efficiency of their use, unnecessary extra burden to the planet, and passing of the negative effects on the society and future generations (of consumers). On the other hand, it leads to forcing the consumption of durable consumer goods, and gathering them "just in case", and also to the low degree of their use (e.g. more cars in a household than its members results in the additional load on traffic routes, which results in an increase in the inconvenience of movement of people, thus to the reduction of the quality of life).
Introduction of yet another economic innovation will not solve this problem. It can be solved only by social innovations that are in a permanent shortage. A social innovation which fosters solving the issue of excessive accumulation of tangible production goods is a developing phenomenon called sharing economy. It is based on the principle: "the use of a service provided by some welfare does not require being its owner". This principle allows for an economic use of resources located in households, but which have been "latent" so far. In this way, increasing of the scope of services provided (transport, residential and tourist accommodation) does not require any growth of additional tangible resources of factors of production. So, it contributes to the growth of household incomes, and inhibition of loading the planet with material goods processed by man [see Poniatowska-Jaksch, Sobiecki, 2016]. Another example: we live in times, in which, contrary to the law of T. Malthus, the planet is able to feed all people, that is to guarantee their minimum required nutrients. But still, millions of people die of starvation and malnutrition, but also due to obesity. Can this problem be solved with another economic innovation? Certainly not! Economic innovations will certainly help to partially solve the problem of nutrition, at least by the new methods of storing and preservation of foods, to reduce its waste in the phase of storage and transport. However, a key condition to solve this problem is to create and implement an innovation of a social nature (in many cases also political). We will not be able to speak about the progress of civilisation in a situation, where there are people dying of starvation and malnutrition.
A growing global social concern, resulting from implementation of an economic (technological) innovation will be robotisation, and more specifically – the effects arising from its dissemination on a large scale. So far, the issue has been postponed due to globalisation of the labour market, which led to cheapening of the work factor by more than ten times in the countries of Asia or South America. But it ends slowly. Labour becomes more and more expensive, which means that the robots become relatively cheap. The mechanism leading to low prices of the labour factor expires. Wages increase, and this changes the relationship of the prices of capital and labour. Capital becomes relatively cheaper and cheaper, and this leads to reducing of the demand for work, at the same time increasing the demand for capital (in the form of robots).
The introduction of robots will be an effect of the phenomenon of substitution of the factors of production. A cheaper factor (in this case capital in the form of robots) will be cheaper than the same activities performed by man. According to W. Szymański [2017], such change is a dysfunction of capitalism. A great challenge, because capitalism is based on the market-driven shaping of income. The market-driven shaping of income means that the income is derived from the sale of the factors of production. Most people have income from employment. Robots change this mechanism. It is estimated that scientific progress allows to create such number of robots that will replace billion people in the world. What will happen to those "superseded", what will replace the income from human labour? Capitalism will face an institutional challenge, and must replace the market-driven shaping of income with another, new one. The introduction of robots means microeconomic battle with the barrier of demand. To sell more, one needs to cut costs. The costs are lowered by the introduction of robots, but the use of robots reduces the demand for human labour. Lowering the demand for human labour results in the reduction of employment, and lower wages. Lower wages result in the reduction of the demand for goods and services. To increase the demand for goods and services, the companies must lower their costs, so they increase the involvement of robots, etc.
A mechanism of the vicious circle appears
If such a mass substitution of the factors of production is unfavourable from the point of view of stimulating the development of the economy, then something must be done to improve the adverse price relations for labour. How can the conditions of competition between a robot and a man be made equal, at least partially? Robots should be taxed. Bill Gates, among others, is a supporter of such a solution. However, this is only one of the tools that can be used. The solution of the problem requires a change in the mechanism, so a breakthrough innovation of a social and political nature. We can say that technological and product innovations force the creation of social and political innovations (maybe institutional changes). Product innovations solve some problems (e.g. they contribute to the reduction of production costs), but at the same time, give rise to others.
Progress of civilisation for centuries and even millennia was primarily an intellectual progress. It was difficult to discuss economic progress at that time. Then we had to deal with the imbalance between the economic and the social element. The insufficiency of the economic factor (otherwise than it is today) was the reason for the tensions and crises. Estimates of growth indicate that the increase in industrial production from ancient times to the first industrial revolution, that is until about 1700, was 0.1-0.2 per year on average. Only the next centuries brought about systematically increasing pace of economic growth. During 1700- 1820, it was 0.5% on an annual average, and between 1820-1913 – 1.5%, and between 1913-2012 – 3.0% [Piketty, 2015, p. 97]. So, the significant pace of the economic growth is found only at the turn of the 19th and 20th century. Additionally, the growth in this period refers predominantly to Europe and North America. The countries on other continents were either stuck in colonialism, structurally similar to the medieval period, or "lived" on the history of their former glory, as, for example, China and Japan, or to a lesser extent some countries of the Middle East and South America. The growth, having then the signs of the modern growth, that is the growth based on technological progress, was attributed mainly to Europe and the United States.
The progress of civilisation requires the creation of new social initiatives. Social innovations are indeed an additional capital to keep the social structure in balance. The social capital is seen as a means and purpose and as a primary source of new values for the members of the society. Social innovations also motivate every citizen to actively participate in this process. It is necessary, because traditional ways of solving social problems, even those known for a long time as unemployment, ageing of the society, or exclusion of considerable social and professional groups from the social and economic development, simply fail. "Old" problems are joined by new ones, such as the increase of social inequalities, climate change, or rapidly growing environmental pollution. New phenomena and problems require new solutions, changes to existing procedures, programmes, and often a completely different approach and instruments [Kowalczyk, Sobiecki, 2017].
As doenças de origem alimentar continuam a ser um problema comum em todo o mundo. Ainda que possam ser provocadas por diversos agentes, são as bactérias, os vírus ou os parasitas a principal causa das infeções alimentares. O consumo ou processamento de alimentos contaminados têm sido descritos como as principais vias de transmissão para os humanos. Campylobacter jejuni e Campylobacter coli têm sido descritos como a principal causa de gastroenterite bacteriana em seres humanos em todo o mundo e em 2013, na União Europeia, a campilobacteriose, infeção causada por Campylobacter, foi a zoonose mais relatada. Nos seres humanos, as espécies de Campylobacter têm sido associadas a uma variedade de condições gastrointestinais, tais como gastroenterite, doenças inflamatórias do intestino, cancro colon-rectal, síndrome do intestino irritável, entre outras e também podem provocar manifestações extra-gastrointestinais, como bacteremia, infeções pulmonares e abcessos. As complicações pós-infeção por este microrganismo incluem a artrite reativa e podem conduzir a doenças auto-imunes, tais como a síndrome de Guillain-Barré. A maioria das infeções por Campylobacter não necessita de intervenção terapêutica sendo apenas necessária reidratação. No entanto, em pacientes imunodeprimidos, pacientes cujos sintomas são severos ou persistentes e aqueles com infeções extra-intestinais é utilizado tratamento antimicrobiano, sendo os antibióticos mais utilizados a eritromicina e a ciprofloxacina. No entanto, em todo o Mundo tem-se verificado que as estirpes de Campylobacter são cada vez mais resistentes a antibióticos, incluindo os usados em humanos. Para além disso também têm sido descritas estirpes de Campylobacter resistentes a desinfetantes, o que se deve, principalmente, à sua capacidade de formar biofilmes. Estes biofilmes são um problema emergente na indústria alimentar, aumentando a possibilidade de contaminações ao longo da cadeia alimentar. Assim, e como os estudos relativos a Campylobacter são escassos, é da maior relevância estudar a epidemiologia de espécies de Campylobacter isoladas em Portugal, a sua resistência a antibióticos e procurar alternativas, aos antimicrobianos convencionais, para o seu controlo. Devido à escassez de estudos relativos à epidemiologia de Campylobacter em Portugal procedeu-se neste trabalho ao estudo da distribuição epidemiológica de isolados de Campylobacter de seres humanos, entre 2009 e 2012, em Portugal. Para isso, foram analisadas 837 estirpes obtidas através do Instituto Nacional de Saúde Dr. Ricardo Jorge. Destas 837 estirpes, 84,5% foram identificados como C. jejuni, 14,8% como C. coli, 0,2% como C. upsaliensis, 0,1% como C. concisus e 0,2% das amostras foram identificadas como Arcobacter butzleri. Em relação à sua distribuição por faixas etárias, observou-se que 61,5% das estirpes pertenciam ao grupo com idades entre 1 e 15 anos. Após este estudo preliminar, a partir deste grupo de isolados humanos, escolheram-se aleatoriamente 125 estirpes de Campylobacter (C. jejuni e C. coli) isoladas de seres humanos. A este grupo de estirpes, adicionaram-se 39 isolados de retalho alimentar e 32 de animais. As 196 amostras foram então caracterizadas através da tipagem por sequenciamento multilocus e da tipagem do gene flaA. Através destes métodos de tipagem, observou-se que as estirpes de C. coli eram geneticamente mais conservadas do que C. jejuni e que dentro de cada espécie, existiam isolados geneticamente relacionados provenientes de fontes diferentes. Em seguida, o fenótipo de resistência ao ácido nalidíxico, amoxicilina, ciprofloxacina, eritromicina, gentamicina e tetraciclina foi avaliado pelo método de diluição em agar. Observaram-se elevadas taxas de resistência para todos os antibióticos com exceção à gentamicina, incluindo para os antibióticos utilizados no tratamento de campilobacteriose grave em humanos. Além disso, observou-se um fenótipo de resistência a múltiplos antibióticos (resistência a 3 ou mais classes de antibióticos) em 86% dos isolados. Perante os elevados níveis de resistência observados, estudaram-se os mecanismos moleculares subjacentes a essas resistências. Verificou-se que todos os isolados resistentes à ciprofloxacina possuíam a mutação Thr-Ile-86 na região que determina resistências às quinolonas no gene gyrA. Para a resistência à eritromicina apenas foi detetada a mutação A2075G no gene 23S rRNA. Em relação à resistência à gentamicina, observou-se que as três estirpes resistentes à gentamicina possuíam o marcador de resistência aos aminoglicosídeos aphA-3, sendo que uma das estirpes tinha uma mutação neste marcador. Foi ainda evidenciado neste estudo, que as bombas de efluxo cmeABC também podem desempenhar um papel na resistência a múltiplas drogas e no fenótipo da resistência a gentamicina. Assim, neste estudo foi possível obter uma visão geral da epidemiologia de Campylobacter em Portugal e descrever pela primeira vez a elevada taxa de multirresistência a antibióticos, assim como realçar o surgimento de estirpes de Campylobacter resistentes aos antibióticos de uso humano. Com base nos resultados deste estudo foram selecionadas estirpes com diferentes perfis genéticos e de resistência a antibióticos para serem utilizadas no decurso deste trabalho. Como o género Campylobacter é a principal causa de gastroenterite bacteriana e a via alimentar é a principal via de contaminação, a elevada percentagem de estirpes resistentes a antibióticos aumenta o potencial zoonótico da infeção com estirpes multirresistentes. Logo, torna-se necessário controlar o crescimento de Campylobacter nas vias mais comuns de contaminação, que são os alimentos. Assim, o objetivo seguinte deste trabalho foi avaliar o potencial do resveratrol para controlar as estirpes de Campylobacter previamente caracterizadas. Apesar do resveratrol possuir várias propriedades biológicas, incluindo antimicrobianas, a sua baixa solubilidade em água e alta instabilidade comprometem a sua aplicação. Assim, para ultrapassar estes problemas, estudou-se o encapsulamento do resveratrol com metil-β-ciclodextrina. Verificou-se que a complexação do resveratrol com esta ciclodextrina provocou um aumento de 400 vezes na sua solubilidade. Em seguida o complexo de inclusão foi caracterizado através de Espectroscopia de Infravermelho por Transformada de Fourier (FTIR), Calorimetria Exploratória Diferencial (DSC), Difração de Raios-X (XRD) e Microscopia Eletrónica de Varrimentos (SEM), confirmando-se efetivamente a sua formação. Seguidamente foram avaliadas algumas propriedades biológicas do resveratrol e do seu complexo de inclusão com metil-β-ciclodextrina, tendo-se verificado que ambos os compostos tinham atividade antioxidante muito forte, baixa toxicidade e ainda capacidade de reduzir a viabilidade das células Caco-2 (linha celular constituída por células epiteliais de adenocarcinoma colorectal heterogéneo). Além disso, também foi demonstrada a sua atividade antibacteriana contra estirpes de Campylobacter previamente selecionadas: duas estirpes de referência (C. jejuni ATCC 33560 e C. coli ATCC 33559), duas estirpes isoladas de fezes de pacientes com gastroenterite aguda (C. coli 53 e C. coli 873) e duas estirpes isoladas de carne de aves fresca (C. jejuni 225421 e C. coli 219872). Estes resultados sugerem que o resveratrol e o seu complexo de inclusão podem ser usados para controlar Campylobacter e que o resveratrol encapsulado em metil-β-ciclodextrina mantem as suas propriedades antioxidantes e antibacterianas. Uma vez que os resultados com o resveratrol e o complexo de inclusão foram bastante promissores, estudou-se ainda outro complexo de inclusão (resveratrol-hidroxipropil-γ-ciclodextrina), previamente formado e caraterizado pelo grupo de investigação, que revelou ainda ter um potencial antimicrobiano mais elevado contra Campylobacter e A. butzleri, um patogéneo de origem alimentar relacionado a Campylobacter. Dado isto, inicialmente avaliou-se a atividade antibacteriana em células planctónicas e mostrou-se que tanto o resveratrol como o complexo de inclusão têm um efeito bactericida contra as estirpes multirresistentes C. coli 873 e C. jejuni 225421. Com o objetivo de esclarecer o potencial mecanismo de ação do complexo de inclusão do resveratrol em hidroxipropil-γ-ciclodextrina sobre as estirpes de Campylobacter, começou por se avaliar a despolarização das membranas celulares e a atividade metabólica por citometria de fluxo. Através desta técnica, observou-se que complexo de inclusão pode atuar induzindo a despolarização da membrana e afetando a atividade metabólica das células. Dado que os biofilmes bacterianos são um problema emergente na indústria alimentar, também foi avaliado o potencial destes dois compostos para inibir a formação de biofilmes e eliminar biofilmes estabelecidos. Tanto o resveratrol como o complexo de inclusão foram capazes de inibir a formação de biofilmes e diminuir biofilmes previamente estabelecidos, mesmo em concentrações sub-inibitórias. O sistema quorum sensing (QS) tem sido associado à resistência antimicrobiana e formação de biofilmes, portanto, o potencial anti-QS destes dois compostos também foi estudado através da utilização de uma estirpe biossensor (Chromobacterium violaceum ATCC 12472). Verificou-se que ambos, o resveratrol e o complexo de inclusão, foram capazes de inibir o sistema QS, o que pode explicar o efeito anti-biofilme destes compostos. Assim, nestes estudos foram demonstradas as propriedades antimicrobianas e anti-biofilme do resveratrol e complexo de inclusão em estirpes de Campylobacter. Este aspeto associado ao facto de o resveratrol ser um composto de origem natural, e de também apresentar forte atividade antioxidante, encorajam futuros estudos com vista à sua aplicação como potencial conservante alimentar. Finalmente, uma vez que tem havido um interesse crescente na utilização de compostos naturais para aplicação em produtos alimentares, também foi avaliado o potencial do óleo essencial de coentros (Coriandrum sativum L.) e do seu principal composto, o linalool, para controlar Campylobacter. Ambos os compostos exibiram um efeito bactericida contra as quatro estirpes testadas (C. jejuni ATCC 33560, C. coli ATCC 33559, C. jejuni 225421 e C. coli 873) com valores de concentração mínima inibitória entre 0,5 e 1 μL/mL e observou-se que os compostos voláteis do óleo essencial de coentros também inibiram o crescimento de Campylobacter. Observou-se ainda que ambos os compostos inibiram a formação de biofilmes e promoveram a dispersão de biofilmes de Campylobacter. Como descrito anteriormente, também foi estudado o efeito destes compostos sobre o sistema QS. Foi demonstrada a atividade anti-QS do óleo essencial de coentros e do linalool através da inibição da produção de violaceína pela estirpe biossensor C. violaceum. Assim, mais uma vez, esta atividade anti-QS pode estar associada com a atividade anti-biofilme dos compostos, uma vez que o QS tem um papel importante na regulação da formação e desenvolvimento de biofilmes. Para além do potencial anti-bacteriano e anti-biofilme do óleo essencial e do linalool, também se avaliou a sua atividade antioxidante, uma vez que o processo de oxidação está relacionado com a perda da qualidade dos alimentos. Assim, observou-se que ambos os compostos têm uma elevada capacidade para inibir a peroxidação de lípidos. Em suma, os resultados demonstraram que estes compostos naturais podem ser utilizado para controlar Campylobacter e também como agentes antioxidantes para melhorar a qualidade dos alimentos. Em conclusão, neste trabalho, foram apresentados, dados recentes referentes à epidemiologia de Campylobacter em Portugal, bem como a sua diversidade genética e respetivos perfis de resistência a antibióticos. Diante disto, são necessários novos agentes antimicrobianos para controlar este patogéneo emergente de origem alimentar. Neste trabalho mostrou-se que o resveratrol e o óleo essencial de coentros, ambos compostos naturais, têm a capacidade de reduzir células planctónicas e biofilmes de Campylobacter, possuindo também várias atividades biológicas, incluindo propriedades antioxidantes. Este trabalho permitiu alargar o conhecimento sobre a epidemiologia e taxas resistência de estirpes de Campylobacter isoladas em Portugal e desenvolver novas estratégias de controlo deste microrganismo baseadas na utilização de compostos de origem natural. ; Foodborne diseases remain common around the world and can be caused by a variety of agents, being bacteria, viruses or parasites the main causes of such infections. Moreover, the major cause of foodborne diseases is consumption or handling of contaminated food. Campylobacter jejuni and Campylobacter coli are the major cause of bacterial gastroenteritis in humans worldwide and are increasingly resistant to antimicrobial agents mainly due to its ability to form biofilms. Furthermore, campylobacteriosis was the most commonly reported zoonosis in the European Union in 2013. So, the main objective of this work was to study the epidemiology of Campylobacter species in Portugal and to explore the potential of natural compounds as new antibacterials to control this foodborne pathogen and to increase the shelf life of food products. We started this work with an epidemiological study of Campylobacter in Portugal. Firstly we studied the epidemiological distribution of Campylobacter isolates from humans, between 2009 and 2012, in Portugal. For this, 837 strains from the National Institute of Health Dr Ricardo Jorge were analyzed, of which 84.5% were identified as C. jejuni, 14.8% as C. coli, 0.2% as C. upsaliensis, 0.1% as C. concisus and 0.2% of the samples were identified as Arcobacter butzleri. Concerning the distribution per age groups, we observed that 61.5% of the strains belonged to the group aged between 1 and 15 years. Afterward, from the group of 837 strains, we randomly choose 125 Campylobacter isolates from humans. In addition to these isolates, we added strains isolated from different sources: 39 from retail food and 32 from animals. All the 196 strains were then characterized by multilocus sequence typing (MLST) and flaA typing. We found that the C. coli isolates were genetically more conserved than C. jejuni, and within each species, genetically related isolates were recovered from different sources. Then, the resistance phenotype to six antibiotics was evaluated by the agar dilution method. We observed high resistance rates to several antibiotics, including the ones used in the treatment of severe campylobacteriosis. We also identified a multidrug resistance phenotype in 86% of the isolates. Once this high resistance to antibiotics was confirmed, we decided to study the underlying molecular mechanisms. In all the ciprofloxacin resistant isolates we found the Thr-86-Ile mutation in the quinolone-resistance-determining regions (QRDR) in the DNA gyrase gene (gyrA). For the erythromycin resistance only the mutation A2075G was detected. Regarding gentamicin resistance, we found the three gentamicin-resistant isolates harboured the aphA-3 aminoglycoside resistance marker, with one strain having a point mutation. In addition, we showed that cmeABC efflux pumps may also play a role in the multidrug resistance phenotype and in the gentamicin resistance. In sum, the results obtained in this first part of the study gave an overview of the Campylobacter epidemiology in Portugal and worrying antibiotic multi-resistance rate. This part also highlighted the emergence of Campylobacter strains resistant to antibiotics commonly used in humans. Then, we select a group of strains with different genetic and antibiotic profiles to be used in the subsequent steps of our work. Since the main source of Campylobacter infection is through contaminated food, it is necessary to find new strategies to control the growth of Campylobacter in the most common way of contamination, which are foods. So, in the next step we assessed the potential of resveratrol to control the strains of Campylobacter that were characterized previously. However, despite resveratrol having several biological properties, its low aqueous solubility and high instability compromise its application. So, to overcome these limitations, we studied the encapsulation of resveratrol with a methyl-β-cyclodextrin. We found that resveratrol complexation caused a 400 fold improvement in its solubility. The inclusion complex was characterized by several techniques. After the formation of the inclusion complex, we compared the biological properties of resveratrol and its inclusion complex. We showed that both compounds had very strong antioxidant activity and low toxicity, together with the ability to reduce the viability of Caco-2 cells (heterogeneous human epithelial colorectal adenocarcinoma cell line). In addition, we also demonstrated their antibacterial activity against the previously selected Campylobacter strains. These results suggest that resveratrol and its inclusion complex can be used to control Campylobacter, since the biological properties are maintained. Due to the very good results obtained with resveratrol and this inclusion complex, we decided to study another inclusion complex (resveratrol-hydroxypropyl-γ-cyclodextrin) and its potential to control Campylobacter and A. butzleri, a closely related foodborne pathogen. Firstly we evaluated the antibacterial activity against planktonic cells, demonstrating that both resveratrol and inclusion complex have a bactericidal effect against the two microorganisms. The inclusion complex may act by inducing membrane depolarization and by affecting the metabolic activity of the cells. Since bacterial biofilms are an emerging problem in the food industry, we also evaluated the potential of these two compounds against biofilms. We showed that resveratrol and the inclusion complex inhibit biofilm formation and diminish established biofilms, even at sub-inhibitory concentrations. Since the quorum sensing (QS) system has been associated with the antimicrobial resistance and biofilm formation, we also evaluated the potential anti-QS effect of these two compounds by using a biosensor strain. We found that both resveratrol and inclusion complex were able to inhibit the QS system, which could explain their anti-biofilm effect. The results showed that resveratrol could be used as antibacterial and anti-biofilm agent in the food industry, allowing an improve shelf life and an increase in food safety. Finally, since there has been a growing interest in the use of natural compounds for application in food products, we also evaluated the potential of coriander (Coriandrum sativum L.) essential oil and its major compound linalool to control Campylobacter. Both compounds showed a bactericidal effect against all the tested strains and we observed that the volatile compounds of the coriander essential oil also inhibited the growth of Campylobacter. Then, since biofilms are a growing problem in the food industry, we also evaluated the anti-biofilm activity of these compounds. Both coriander oil and linalool inhibited biofilm formation and promoted biofilm dispersion of Campylobacter biofilms. As previously described, we also studied the effect of these compounds on the QS system and we observed an anti-QS activity by inhibiting the violacein production. So, once more, this anti-QS activity could be associated with the anti-biofilm activity, since QS has been described to regulate the biofilm formation and development. Moreover, in addition to the antibacterial and anti-biofilm potential, we evaluated the antioxidant activity of coriander oil and linalool, since the oxidation process is also associated with the loss of food quality. We observed that both compounds showed an exceptional ability to inhibit lipid peroxidation. Those results demonstrate that these natural compounds could be used to control Campylobacter and as antioxidant to enhance food quality. In sum, in this thesis, we described the recent epidemiology of Campylobacter in Portugal, as well as its genetic diversity and worrying antibiotic resistance rates. In addition, we also demonstrated that resveratrol and coriander essential oil, which are both natural compounds, have the ability to reduce planktonic cells and biofilms of Campylobacter, including the multiresistant strains characterized in the first part of the work. Clearly, the results obtained in this work encourage the future use of these natural compounds to control Campylobacter.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease ; The i-Select chips was funded by the French National Foundation on Alzheimer's disease and related disorders. The French National Fondation on Alzheimer's disease and related disorders supported several I-GAP meetings and communications. Data management involved the Centre National de Génotypage,and was supported by the Institut Pasteur de Lille, Inserm, FRC (fondation pour la recherche sur le cerveau) and Rotary. This work has been developed and supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease) and by the LABEX GENMED grant (Medical Genomics). The French National Foundation on Alzheimer's disease and related disorders and the Alzheimer's Association (Chicago, Illinois) grant supported IGAP in-person meetings, communication and the Alzheimer's Association (Chicago, Illinois) grant provided some funds to each consortium for analyses. EADI The authors thank Dr. Anne Boland (CNG) for her technical help in preparing the DNA samples for analyses. This work was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille and the Centre National de Génotypage. The Three-City Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Agence Nationale de la Recherche, ANR supported the COGINUT and COVADIS projects. Fondation de France and the joint French Ministry of Research/INSERM «Cohortes et collections de données biologiques» programme. Lille Génopôle received an unconditional grant from Eisai. The Three-city biological bank was developed and maintained by the laboratory for genomic analysis LAG-BRC - Institut Pasteur de Lille. Belgium sample collection: The patients were clinically and pathological characterized by the neurologists Sebastiaan Engelborghs, Rik Vandenberghe and Peter P. De Deyn, and in part genetically by Caroline Van Cauwenberghe, Karolien Bettens and Kristel Sleegers. Research at the Antwerp site is funded in part by the Belgian Science Policy Office Interuniversity Attraction Poles program, the Foundation Alzheimer Research (SAO-FRA), the Flemish Government initiated Methusalem Excellence Program, the Research Foundation Flanders (FWO) and the University of Antwerp Research Fund, Belgium. Karolien Bettens is a postdoctoral fellow of the FWO. The Antwerp site authors thank the personnel of the VIB Genetic Service Facility, the Biobank of the Institute Born-Bunge and the Departments of Neurology and Memory Clinics at the Hospital Network Antwerp and the University Hospitals Leuven. Finish sample collection: Financial support for this project was provided by the Health Research Council of the Academy of Finland, EVO grant 5772708 of Kuopio University Hospital, and the Nordic Centre of Excellence in Neurodegeneration. Italian sample collections: the Bologna site (FL) obtained funds from the Italian Ministry of research and University as well as Carimonte Foundation. The Florence site was supported by grant RF-2010-2319722, grant from the the Cassa di Risparmio di Pistoia e Pescia (Grant 2012) and the Cassa di Risparmio di Firenze (Grant 2012). The Milan site was supported by a grant from the «fondazione Monzino». The authors thank the expert contribution of Mr. Carmelo Romano. The Roma site received financial support from Italian Ministry of Health, Grant RF07-08 and RC08-09-10-11-12. The Pisa site is grateful to Dr. Annalisa LoGerfo for her technical assistance in the DNA purification studies. Spanish sample collection: the Madrid site (MB) was supported by grants of the Ministerio de Educación y Ciencia and the Ministerio de Sanidad y Consumo (Instituto de Salud Carlos III), and an institutional grant of the Fundación Ramón Areces to the CBMSO. The authors thank I. Sastre and Dr. A. Martínez-García for the preparation and control of the DNA collection, and Drs. P. Gil and P. Coria for their cooperation in the cases/controls recruitment. The authors are grateful to the Asociación de Familiares de Alzheimer de Madrid (AFAL) for continuous encouragement and help. Swedish sample collection: Financially supported in part by the Swedish Brain Power network, the Marianne and Marcus Wallenberg Foundation, the Swedish Research Council (521-2010-3134), the King Gustaf V and Queen Victoria's Foundation of Freemasons, the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and the Karolinska Institutet, the Swedish Brain Foundation and the Swedish Alzheimer Foundation. CHARGE AGES: The AGES-Reykjavik Study is funded by National Institutes of Health (NIH) contract N01-AG-12100 (National Institute on Aging (NIA) with contributions from the National Eye Institute, National Institute on Deafness and Other Communication Disorders and National Heart, Lung, and Blood Institute (NHLBI)), the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). ASPS/PRODEM: The Austrian Stroke Prevention Study and The Prospective Dementia Register of the Austrian Alzheimer Society was supported by The Austrian Science Fond (FWF) grant number P20545-P05 (H. Schmidt) and P13180; The Austrian Alzheimer Society; The Medical University of Graz. Cardiovascular Health Study (CHS): This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and HHSN268200960009C; and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629, AG15928, AG20098, AG027058 and AG033193 (Seshadri) from the NIA. A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Framingham Heart Study (FHS): This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with A_ymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This study as also supported by grants from the National Institute on Aging: AG08122 and AG033193 (Seshadri). Drs. Seshadri and DeStefano were also supported by additional grants from the National Institute on Aging: (R01 AG16495; AG031287, AG033040), the National Institute of Neurological Disorders and Stroke (R01 NS17950), and the National Heart, Lung and Blood Institute (U01 HL096917, HL093029 and K24HL038444, RC2-HL102419 and UC2 HL103010. Fundació ACE would like to thank patients and controls who participated in this project. This work has been funded by the Fundación Alzheimur (Murcia), the Ministerio de Educación y Ciencia (PCT-010000-2007-18), (DEX-580000-2008-4), (Gobierno de España), Corporación Tecnológica de Andalucía (08/211) and Agencia IDEA (841318) (Consejería de Innovación, Junta de Andalucía). The authors thank to Ms. Trinitat Port-Carbó and her family for their generous support of Fundació ACE research programs. The Rotterdam Study: The Rotterdam Study was funded by Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission;and the Municipality of Rotterdam; by grants from the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), Internationale Stichting Alzheimer Onderzoek, Hersenstichting Nederland, the Netherlands Genomics Initiative–Netherlands Organization for Scientific Research (Center for Medical Systems Biology and the Netherlands Consortium for Healthy Aging), the Seventh Framework Program (FP7/2007-2013), the ENGAGE project (grant agreement HEALTH-F4-2007-201413), MRACE-grant from the Erasmus Medical Center, the Netherlands Organization for Health Research and Development (ZonMW Veni-grant no. 916.13.054). ARIC: The Atherosclerosis Risk in Communities Study (ARIC) is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01- HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022 and grants R01-HL087641, RC2-HL102419 (Boerwinkle, CHARGE-S), UC2 HL103010, U01-HL096917 (Mosley) and R01-HL093029; NHGRI contract U01- HG004402; and NIH contract HHSN268200625226C and NIA: R01 AG033193 (Seshadri). Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. GERAD Cardiff University was supported by the Wellcome Trust, Medical Research Council (MRC), Alzheimer's Research United Kingdom (ARUK) and the Welsh Government. ARUK supported sample collections at the Kings College London, the South West Dementia Bank, Universities of Cambridge, Nottingham, Manchester and Belfast. The Belfast group acknowledges support from the Alzheimer's Society, Ulster Garden Villages, N. Ireland R & D Office and the Royal College of Physicians/Dunhill Medical Trust. The MRC and Mercer's Institute for Research on Ageing supported the Trinity College group. DCR is a Wellcome Trust Principal Research fellow. The South West Dementia Brain Bank acknowledges support from Bristol Research into Alzheimer's and Care of the Elderly. The Charles Wolfson Charitable Trust supported the OPTIMA group. Washington University was funded by NIH grants, Barnes Jewish Foundation and the Charles and Joanne Knight Alzheimer's Research Initiative. Patient recruitment for the MRC Prion Unit/UCL Department of Neurodegenerative Disease collection was supported by the UCLH/UCL Biomedical Centre and their work was supported by the NIHR Queen Square Dementia BRU. LASER-AD was funded by Lundbeck SA. The Bonn group would like to thank Dr. Heike Koelsch for her scientific support. The Bonn group was funded by the German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant number 01GI0102, 01GI0711, 01GI0420. The AgeCoDe study group was supported by the German Federal Ministry for Education and Research grants 01 GI 0710, 01 GI 0712, 01 GI 0713, 01 GI 0714, 01 GI 0715, 01 GI 0716, 01 GI 0717. The Homburg group was funded by the German Federal Ministry of Education and Research (BMBF): German National Genome Research Network (NGFN); Alzheimer's disease Integrated Genome Research Network; AD-IG: 01GS0465. Genotyping of the Bonn case-control sample was funded by the German centre for Neurodegenerative Diseases (DZNE), Germany. The GERAD Consortium also used samples ascertained by the NIMH AD Genetics Initiative. Harald Hampel was supported by a grant of the Katharina-Hardt-Foundation, Bad Homburg vor der Höhe, Germany. The KORA F4 studies were financed by Helmholtz Zentrum München; German Research Center for Environmental Health; BMBF; German National Genome Research Network and the Munich Center of Health Sciences. The Heinz Nixdorf Recall cohort was funded by the Heinz Nixdorf Foundation (Dr. Jur. G.Schmidt, Chairman) and BMBF. Coriell Cell Repositories is supported by NINDS and the Intramural Research Program of the National Institute on Aging. The authors acknowledge use of genotype data from the 1958 Birth Cohort collection, funded by the MRC and the Wellcome Trust which was genotyped by the Wellcome Trust Case Control Consortium and the Type-1 Diabetes Genetics Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development and Juvenile Diabetes Research Foundation International. The Nottingham Group (KM) are supported by the Big Lottery. MRC CFAS is part of the consortium and data will be included in future analyses. ADGC The National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIA LOAD, U24 AG026395, R01 AG041797; MIRAGE R01 AG025259; Banner Sun Health Research Institute P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01AG33193; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG06781, UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, and UL1 RR029893; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653, AG041718; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant # NS39764, NIMH MH60451 and by Glaxo Smith Kline. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG034504 to AJM, The Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr. Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer's Research Trust (ART), BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona. Marcelle Morrison-Bogorad, PhD., Tony Phelps, PhD and Walter Kukull PhD are thanked for helping to co-ordinate this collection. ADNI Funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, Glaxo-SmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and by the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, K01 AG030514. Data collection and sharing for this project was funded by the ADNI (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. The authors thank Drs. D. Stephen Snyder and Marilyn Miller from NIA who are ex-o_cio ADGC members. Support was also from the Alzheimer's Association (LAF, IIRG-08-89720; MP-V, IIRG-05-14147) and the United States Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. Peter St George-Hyslop is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health
