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1
Talebpour, Mansour. "Impunity and the International Criminal Court (ICC)." Thesis, SOAS, University of London, 2012. http://eprints.soas.ac.uk/15620/.
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2
De, la Barreda Solórzano Luis. "Temporary custody; Criminality; Human rights; Impunity; Torture." Derecho & Sociedad, 2017. http://repositorio.pucp.edu.pe/index/handle/123456789/117575.
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This article is about a pair of factors that cause the distress that can be observed within the mexican society: the overflowed criminality and the impunity, by virtue of which the State is not fullfiling its essential historical duty: to provide an aceptable level of public security. This has two sources that complement each other. One is the sensation we get when we face an unpredictable threat. It is caused by crime. The other is defencelessness or knowing that we can only rely in our own strength because there is no one willing to protect or assist us.<br>El artículo versa sobre el par de factores que provocan el malestar que se advierte en la sociedad mexicana: la criminalidad desbordada y la impunidad, en virtud de las cuales el Estado no está cumpliendo con su deber histórico fundamental: brindar un nivel aceptable de seguridad pública. Ésta tiene dos fuentes que se complementan entre sí. Una es la sensación que nace al enfrentarnos a un peligro imprevisible. Es suscitada por el crimen. La otra es la indefensión, o sea, el saber que sólo se cuenta con las propias fuerzas porque no hay nadie más dispuesto a protegernos o auxiliarnos.
3
Kronick, Ilana. "Indulging with "impunity": Compensatory intentions and diet-breaking behaviour." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=94936.
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The compensatory beliefs model proposes that when faced with temptation, people form intentions to behaviourally compensate for indulgence. Compensatory beliefs (CBs) are convictions that the consequences of engaging in an indulgent behaviour (eating cake) can be neutralized by the effects of another behaviour (skipping dinner). Compensatory intentions (CIs) are plans to compensate for indulgence that are based on the belief that compensatory behaviours can balance-out the effects of indulgence. I propose that compensatory thinking not only exists in dieters but that forming compensatory intentions results in both a decision to indulge and the act of indulging. The first manuscript shows that (1) dieters form compensatory intentions when experiencing the mental conflict of wanting to lose weight but also desiring to eat, and that (2) forming compensatory intentions results in the decision to indulge. These findings suggest that compensatory beliefs and intentions may be useful tools in helping predict whether or not dieters will adhere to their diets. Using experiential sampling methodology, the second manuscript shows that compensatory thinking contributes to the prediction of caloric intake. Implications of using CBs and CIs in weight loss scenarios are discussed, with particular emphasis on how they have been shown to be risky diet tools due to dieters' general failure to follow through with their intentions to compensate.<br>Le modèle de convictions compensateur propose que quand fait face avec la tentation, les gens forment des intentions de comportement compenser pour l'indulgence. Les convictions compensatrices sont des convictions que les conséquences de s'engager dans un comportement indulgent (mangeant le gâteau) peuvent être neutralisées par les effets d'un autre comportement (sautillant le dîner). Les intentions compensatrices sont des plans de compenser pour l'indulgence qui sont fondés sur la conviction que les comportements compensateurs peuvent équilibrer - des effets d'indulgence. Je propose que la réflexion compensatrice existe non seulement dans dieters, mais que la formation des intentions compensatrices s'ensuit tant dans une décision de céder que dans à l'acte du fait de céder. Le premier manuscrit montre (que 1) dieters forment des intentions compensatrices en connaissant le conflit mental du fait de vouloir maigrir, mais le fait de désirer aussi manger et (que 2) les intentions compensatrices se formant s'ensuivent dans la décision de céder. Ces conclusions suggèrent que les convictions compensatrices et les intentions peuvent être des instruments utiles dans l'aide prédisent si vraiment dieters adhérera à leurs régimes. En utilisant la méthodologie d'échantillonnage expérimentale, le deuxième manuscrit montre que la réflexion compensatrice contribue à la prédiction de consommation calorique. Les implications de former les intentions compensatrices dans les scénarios de perte de poids sont discutées, avec l'accentuation particulière sur comment les intentions compensatrices ont été montrées pour être des instruments de régime risqués en raison de l'échec général de dieter à l'achèvement avec leur intention de compenser.
4
Golab, Matthew Evans. "Guatemala's Fight Against Criminal Impunity: CICIG, A Hybrid Approach." Thesis, The University of Arizona, 2010. http://hdl.handle.net/10150/146833.
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The focus of this paper is CICIG, la Comision Internacional Contra la Impunidad en Guatemala (the International Commission against Impunity in Guatemala). Established through an agreement between the United Nations and Guatemalan government in 2006, CICIG is the first commission of its kind, functioning as a hybrid effort in the battle against Guatemalan criminal impunity. This paper will provide an overview of the multi-faceted problem of impunity within Guatemala. This investigation will also examine CICIG's establishment, structure, and goals. Furthermore, this paper will discuss the encouraging results that CICIG has achieved in its first two years of work, while also addressing the challenges that the commission has encountered. Finally, this paper will examine the future implications of CICIG within Guatemala, and also the implications of a possible replication effort of a CICIG-type commission in a different society, beyond Guatemala.
5
Muvumba, Sellström Angela. "Stronger than Justice : Armed Group Impunity for Sexual Violence." Doctoral thesis, Uppsala universitet, Institutionen för freds- och konfliktforskning, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-237114.
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What conditions lead to confidence among civil war combatants that they will not face accountability for perpetrating sexual violence? This study investigates the causes of impunity for sexual violence among armed actors. It develops a theoretical framework which identifies three explanations for armed group impunity for sexual violence, namely (1) flawed prohibitions inside an armed group; (2) negligent enforcement by its authorities; and (3) pardons in the form of amnesties during the peace process. Adopting a two-pronged approach, the study first explores the associations between amnesties arising from concluding peace agreements and post-settlement levels of sexual violence in Burundi, the Democratic Republic of Congo, Liberia, Mozambique, Sierra Leone and South Africa. A small-scale, events-based dataset of sexual violence by governments and rebel groups in the first three years after war was constructed. The second and main part of the study is a comparison between two rebel groups in Burundi’s civil war (1994-2008), CNDD-FDD (National Council for the Defence of Democracy-Forces for the Defence of Democracy) and Palipehutu-FNL (Palipehutu-Forces for National Liberation) and their practices of prohibition and punishment of wartime sexual violence, taking into account also the possible influence of amnesties. Based on original data from 19 focus groups of ex-combatants from these rebel organisations, it is found that flawed prohibitions and negligent authorities are the main explanations for armed group impunity. The findings do not support amnesties as a cause of armed group impunity for sexual violence. Moreover, additional findings suggest that accountability for sexual violence is triggered by dependency on civilian support, while impunity is facilitated by an armed group’s ability to secure recruits, material and other resources without the help of local communities.
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Melvin, David J. "Ending impunity : establishing the legitimacy of the International Criminal Court." Honors in the Major Thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1114.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.<br>Bachelors<br>Sciences<br>Political Science
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Nichols, Lionel. "The International Criminal Court and the end of impunity in Kenya." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:34eab158-f675-492a-b844-f9a74e1a6ce6.
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This thesis considers the extent to which the International Criminal Court's Office of the Prosecutor ('OTP') has been successful in realising its self-defined mandate of ending impunity in Kenya. In particular, it focuses on the OTP's attempts to encourage domestic investigations and prosecutions as part of its strategy of positive complementarity. This strategy has been hailed as being the best and perhaps the only way that the OTP may use its finite resources to make a significant contribution to ending impunity. Despite this, no empirical study has been published that evaluates the effectiveness of this strategy and the impact that it has on ending impunity in the targeted situation country. This thesis seeks to address this gap in the literature by conducting a case study on the OTP's implementation of its strategy of positive complementarity in Kenya following that country's post-election violence in 2007/08. In doing so, I also hope to make a modest contribution to existing debates over the effectiveness of the ICC as an institution as well as international criminal justice and transitional justice more generally.
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Lafond, Geneviève. "The market of impunity: Why is international law fit for the job?" Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97097.
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This paper aims to demonstrate that corporations can be prosecuted under international law for forcing people to work in sweatshops. Indeed, as corporations are subject of international law they are subjected to international norms and should respect them. There is an emerging consensus about holding corporations liable for their human rights abuses. Submitting people to sweatshops conditions is one of the many ways corporations infringe human rights. In the worst cases, sweatshops fit the modern definition of slavery and slave-like practices such as forced labour. Corporations ought to be prosecuted either domestically using universal jurisdiction or at an international level for using forced labour. In doing so, the international community would send a strong message that sweatshops are unacceptable and eliminating them would certainly help eradicating poverty.<br>Cet article veut démontrer que les compagnies peuvent être poursuivies en vertu du droit international lorsqu'elles forcent des gens à travailler dans des ateliers de misère. En effet, comme les compagnies sont des sujets du droit international, elles sont assujetties aux normes internationales et se doivent de les respecter. Il y a un consensus émergeant à propos de la responsabilité des compagnies pour leurs violations des droits humains. Soumettre des gens aux conditions de travail présentes dans les ateliers de misère constitue une forme d'abus des droits humains dont les compagnies sont responsables. Dans les cas extrêmes, les conditions dans les ateliers de misère correspondent aux définitions modernes d'esclavage et de pratiques s'apparentant à l'esclavage tel le travail forcé. Les compagnies devraient être poursuivies soit par les tribunaux nationaux sous la juridiction universelle ou au niveau international lorsqu'elles utilisent du travail forcé. De cette façon, la communauté internationale enverrait un message clair à l'effet que les ateliers de misère sont inacceptables et leur élimination aiderait certainement à enrayer la pauvreté.
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Evans, Stephen. "Victim inequality and offender impunity : the asymmetric outcomes of motor insurance fraud." Thesis, University of Portsmouth, 2018. https://researchportal.port.ac.uk/portal/en/theses/victim-inequality-and-offender-impunity(21b058fd-1514-4b5e-9586-e544438318b5).html.
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This research examines whether the funding of IFED, a dedicated police unit, set up to deal exclusively with allegations of insurance fraud brought by those insurers providing the funding, has impacted the ability of non-insurer victims of insurance fraud to gain access to justice. The first stage of the research sought to identify and quantify the nature of fraud and its impact on both the insurance industry and on non-insurers. It included a desk-top review of the credit-hire sector, the local bus sector and large fleet-operators. The second stage involved a self-completion questionnaire to build econometric and experiential data from the credit-hire sector before effecting semi-structured interviews with twenty-nine witnesses working within or proximate to the area being investigated and conducting research and further interviews in respect of five case studies. An emergent theme was the use by the insurance industry of data, predominantly driven by uncorroborated estimates, that showed the industry to be impacted hugely by fraud, a conclusion that they had deployed to inspire a media and lobbying campaign to seek regulatory change protective of their business model whilst also gaining exclusive access to a dedicated police resource. Whilst no direct harm was reported by non-insurer victims because of the existence of IFED there was evidence of criminal offenders migrating to victims less capable of soliciting a police response and so gaming the system to gain impunity. The research posits an objective methodology for scoring the economic, societal or criminological validity of a privately-funded public-police initiatives with implications for future partnerships in other areas where business can contribute to the cost of law enforcement to assess whether enforcement success can feed directly through to the profit line but without inspiring victim inequality or offender impunity. Whilst the Police had, prior to the Fraud Review and the creation of IFED, demonstrated limited enthusiasm for investigating allegations of fraud, the creation of IFED, accompanied with the effects of austerity measures on policing, has had a meaningful and detrimental impact on the ability of certain non-insurers to deal with insurance fraud relative to the protection available to insurers. The identity of the victim made a difference. The partisan approach to a single victim-set may be contributing to the growth of insurance fraud facilitated by organised criminals and increasing the likelihood of impunity for offenders committing acquisitive vehicle offences involving the rental and credit-hire industries.
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Johnson, William. "A Critique of the International Anti-Corruption Debate: Lessons From El Salvador and Pakistan." Thesis, University of Oregon, 2014. http://hdl.handle.net/1794/18518.
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Corruption is an age-old problem that affects every society, government, and institution. In recent decades it has received considerable attention from scholars, development experts, and global policy-makers, and anti-corruption reforms now exist in nearly every country in the world. Unfortunately, decades of research and activism have created a proliferation of data and policy prescriptions that continue to follow a set of narrow, misguided assumptions about the causes and consequences of this serious problem. This is a critique of the perspective that has dominated the international anti-corruption debate. Building upon comparative research conducted in El Salvador and Pakistan, this thesis sheds light on how these narrow-minded assumptions lead to misguided and ineffective anti-corruption efforts in two distinct regions of the world.
11
Botte, Auriane. "Responsibility for core international crimes : connecting the dots toward a duty to end impunity." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/42395/.
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This thesis begins with the observation that a gap exists between the universal consensus among all States regarding the criminalisation of genocide, crimes against humanity and war crimes on the one hand, and the prevalence of impunity on the other. It then puts forward the hypothesis that this gap may be explained by the unsuitability of the approach taken by the international community to address the issue of responsibility for core international crimes. In order to test this hypothesis, this thesis critically examines the different forms of responsibility for core international crimes available in International Law. One of the important characteristics that distinguish core international crimes from other international crimes or ordinary crimes is that they are often committed with the simultaneous participation of several actors, including individual perpetrators, the State and, in some instances, non-state actors. Addressing the impunity for the commission of core international crimes cannot, therefore, be limited to the lack of consequences for individual perpetrators. This thesis challenges the focus of International Criminal Justice on individual criminal responsibility and argues for a comprehensive approach to responsibility for international crimes, including State and collective responsibility, in order to convey the collective and political features of these crimes. The issue of responsibility for genocide, crimes against humanity and war crimes has been widely discussed in the scholarly literature, in particular with the development of International Criminal Law. One can observe, however, an imbalance between the amount of research dedicated to the issue of individual criminal responsibility for core international crimes and the issue of State responsibility for international crimes. This imbalance is partly due to the fact that the notion of State criminal responsibility was rejected by a large majority of States, and discussions on these issues were abandoned. The originality of this thesis comes from the broad approach it adopts to examine the issue of responsibility for core international crimes with the aim of bridging the gap between the distinct academic perspectives. It weaves together different approaches to responsibility, from individual responsibility to State responsibility, in order to identify the weaknesses of the current forms of responsibility and to highlight the complementary aspects of the main questions discussed in these different fields of law. The thesis goes beyond highlighting the complementary aspects of the different forms of responsibility for core international crimes and puts forward a concrete proposal to develop a comprehensive normative framework, based on the model of the Responsibility to Protect concept, to implement a comprehensive approach to responsibility. This framework relies on the emergence of a duty to end impunity that lies with the territorial State as well as the international community. The purpose of this comprehensive normative framework is to promote the cooperation and interactions between the different mechanisms available in International Law and designed to deal with issues of responsibility for core international crimes. The proposal is based on the assumption that including the different norms and measures which aim to end impunity within one framework would optimise their synergy to respond to core international crimes and protect the interests of humanity as a whole.
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Weski, Emelie. "Law+Impunity=Legitimacy? Rethinking liberal legitimacy of international law with a feminist critical approach." Thesis, Malmö högskola, Fakulteten för kultur och samhälle (KS), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-23954.
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In here, the criminalization of sexual violence is a manifestation of increased recognition of feminism, and proof of international law reaching at liberal criteria for legitimization. Though, in making conclusions other necessary criteria for fully recognized legitimacy are acknowledged (such as other types of rights, types of security and other levels for analysis). Though, from a strict feminist critical approach the criminalization of sexual violence, and the extent of such criminalization can by itself prove legitimacy or illegitimacy.The criminalizing of sexual violence took place over 100 years ago, yet the systematic use of it in warfare was not publicly condemned until the ICTR (International Criminal Tribunal of Rwanda) and the ICTY (International Criminal Tribunal of former Yugoslavia) (Buss, 2009, p. 356) took on the duty to prosecute and convict. Still today women’s security and sexual violence are research fields that awake a lot of hostile emotions.Findings show that there is few, if any, affects for those tribunals that fail to bring justice to rape victims; calling for an analysis of Walzer’s political fit. The international praxis of impunity supports feminism in an existing ‘male truth’ risking the security of women. The legitimacy of the institution of international law is, however, not dependent on one legal procedure.Liberalist and feminist different interpretations of adequate necessity to create peace frame after 15 224 words a utilitarian illusion which slows down the pace of the implementation of a feminist security agenda. However, the progress is still evidence of strife towards the Kantian society of states. An inconsistent moral consensus finally results in the conclusion that this thesis cannot confirm the institution of international law illegitimate, arguably validating legitimacy.
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Haque, Mahbubul Baker Iljas. "Impunity and Acid violence against women in Bangladesh : case studies in Satkhira and Sirajgonj districts /." Abstract, 2005. http://mulinet3.li.mahidol.ac.th/thesis/2548/cd383/4737344.pdf.
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Mazuel, Laurent. "Traitement de l'hétérogénéité sémantique dans les interactions humain-agent et agent-agent." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2008. http://tel.archives-ouvertes.fr/tel-00413004.
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Le thème général de cette thèse est le traitement de l'hétérogénéité sémantique dans les interactions humain-agent et agent-agent. Plus précisément, nous étudions le cas où un agent informatique muni d'un modèle de représentation de ses connaissances doit traiter des demandes envoyées par d'autres interlocuteurs, qu'il s'agisse d'utilisateurs humains ou d'agents informatiques.<br />La plupart des approches segmentent ce traitement en fonction de l'émetteur de la demande (humain ou agent). Nous pensons au contraire qu'il est possible de proposer un modèle d'interaction commun aux deux situations. Ainsi, nous présentons d'abord un algorithme d'interprétation sémantique de la commande indépendant du type d'interaction (humain-agent ou agent-agent). Cet algorithme considère le rapport entre « ce qui est compris » de la commande et « ce qui est possible » pour la machine. Ce rapport intervient dans un système de sélection de réponses basé sur une mesure de degré de relation sémantique. Nous proposons ensuite une telle mesure, conçue pour prendre en compte plus d'informations que la plupart des mesures actuelles.<br />Nous étudions ensuite les implémentations que nous avons faites dans les cadres humain-agent et agent-agent. Pour l'implémentation humain-agent, l'une des spécificités est l'utilisation d'une langue naturelle, impliquant le besoin d'utiliser des outils de modélisation de la langue. Pour l'implémentation agent-agent, nous proposerons une adaptation de notre architecture, en s'appuyant sur des protocoles d'interactions entre agents.
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Nkosi, Mfundo. "Prosecuting the three core crimes: Complementarity in light of Africa’s new international criminal Court." University of Western Cape, 2019. http://hdl.handle.net/11394/6990.
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Doctor Legum - LLD<br>The principle of complementarity forms the basis upon which the International Criminal Court
(ICC) exercises its jurisdiction. This principle of international law first appears in the Preamble
to the Rome Statute and then the admissibility provisions under Article 17 of the Rome Statute,
which outline that the Court will declare a case inadmissible where it is being investigated or
prosecuted by a state which has jurisdiction over it; unless the state is unwilling or unable to
genuinely carry out the investigation or prosecution. Alternatively where the case has been
investigated by a state which has jurisdiction over it and the state has decided not to prosecute
the person concerned, unless the decision resulted from the unwillingness or inability of the state
to genuinely prosecute. This principle implies that the ICC is a court of last resort and will
therefore not intervene in a case where the state of commission is either able or willing genuinely
to investigate and prosecute perpetrators of grave crimes.
It is common cause that Africa has been the staging area of mass atrocities for decades. The
indictment of Kenyan president Uhuru Kenyatta’s’ and his deputy William Ruto, Hissene Habre
case, and the indictment and issuance of an arrest warrant against the Sudanese President Omar
El-Bashir are instructive in this regard. The ICC’S actions created the perception of bias,
injustice and inequity. This prompted a sharp reaction from African states, which threated a mass
withdrawal from the Rome Statute in 2013. The one positive spin off from the AU reaction was
the expansion of the jurisdiction of the merged court to include a criminal chamber in 2014, thus
creating Africa’s first international criminal court, the African Criminal Court (ACC). This
development was the result of the discontent and frustration of the African continent towards the
work of the ICC, which was perceived as focusing only on African cases, whilst ignoring the
litany of cases coming from other regions of the world.
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Bergh, Niklas. "An autonomous multi-agent evacuation scenario using sight and agent-to-agent communication." Thesis, KTH, Optimeringslära och systemteori, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-147930.
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This report simulates an evacuation scenario in a crowded building and attempts to optimize the flow of agents during the process. Each agent is autonomous and assumed to know the map. Agents also have the ability to communicate between themselves, as well as using sight to perceive the environment around them. The purpose is to design a set of rules making the agents evacuate efficiently, which then can applied in real world situation for training people in evacuation strategies. The model used is a time and space discrete setting, where agents move in a discrete graph, and have several exits to choose between. The number of agents is large, making crowd control an important factor. The simulation is run with a number of numerical algorithms such as path planning and logical reasoning. The algorithms are programmed into a simulation program allowing the evacuation to be shown in real time. The results shows the importance of agents communicating, and clear paths to emergency exits.
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Kameldy, Neldjingaye. "Challenging impunity in northern Uganda : the tension between amnesties and the principle of international criminal responsibility." Diss., University of Pretoria, 2007. http://hdl.handle.net/2263/5448.
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This dissertation intends to analyse the practice of amnesties in the context of grave human rights violations using northern Uganda as a case study. It also examines its consistency with the obligation upon states to protect human rights through the prosecution of perpetrators of the said violations. It will, accordingly, analyse the
implications of the complementary mandate of the International Criminal Court (ICC) to national jurisdictions.
Furthermore, the author also explores the tension which results from national amnesties and the principle of international criminal responsibility, a principle that the ICC has the mandate
to enforce.<br>Thesis (LLM (Human Rights and Democratisation in Africa)) -- University of Pretoria, 2007.<br>A Dissertation submitted to the Faculty of Law University of Pretoria, in partial fulfilment of the requirements for the degree Masters of Law (LLM in Human Rights and Democratisation in Africa). Prepared under the supervision of Dr Ben Kiromba Twinomugisha of the Faculty of Law, Makerere University, Kampala, Uganda.<br>http://www.chr.up.ac.za<br>Centre for Human Rights<br>LLM
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Lindskog, Isabelle. "The gendered silence of international criminal law : Examining impunity for sexual violence through a feminist lens." Thesis, Uppsala universitet, Hugo Valentin-centrum, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-413208.
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MacManus, Thomas. "State-corporate crime and civil society : impunity, resistance and the commodification of victimhood in Ivory Coast." Thesis, King's College London (University of London), 2012. http://kclpure.kcl.ac.uk/portal/en/theses/statecorporate-crime-and-civil-society(bab993eb-766f-4cf4-a6c1-e2b2b04218cb).html.
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This thesis examines the specific criminogenic relationship between the state and corporation, and the state and civil society in the case of Trafigura’s dumping of toxic waste in Abidjan, Ivory Coast in August 2006. Research undertaken in London and Abidjan reveals that the impunity that was enjoyed by the Ivory Coast state and Trafigura for this state-corporate crime was underpinned by the power of the corporation and by failures of both domestic and international civil society organisations that might have been expected to have labelled and challenged the crimes. Moreover, the thesis reveals that in the case of this particular example of state-corporate crime, civil society as an agency of censure and sanction played a distinctly retrogressive role. Here, in fact, state crime facilitated organised crime’s insertion into civil society through a process I define as ‘the commodification of victimhood’ and, as a result, ensured that impunity was virtually guaranteed for corporation and government. The thesis also examines the failure of international and domestic legal measures to sanction the perpetrators. The thesis argues that a criminal state can act as a nexus for crimes by all three sectors of society, facilitating crime by actors in the state, the market and third spheres of society. Gramsci’s notion of civil society as an arena of struggle provides a theoretical framework to assist in understanding the complex relationships between civil society, the Ivorian state and Trafigura. The findings presented here suggest that scholars of state corporate crime should adopt a more cautionary approach to civil society’s capacity to label, censure and sanction than that suggested by Green and Ward (2004).
20
Xu, Ke. "Mobile agent security through multi-agent cryptographic protocols." Thesis, University of North Texas, 2004. https://digital.library.unt.edu/ark:/67531/metadc4473/.
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An increasingly promising and widespread topic of research in distributed computing is the mobile agent paradigm: code travelling and performing computations on remote hosts in an autonomous manner. One of the biggest challenges faced by this new paradigm is security. The issue of protecting sensitive code and data carried by a mobile agent against tampering from a malicious host is particularly hard but important. Based on secure multi-party computation, a recent research direction shows the feasibility of a software-only solution to this problem, which had been deemed impossible by some researchers previously. The best result prior to this dissertation is a single-agent protocol which requires the participation of a trusted third party. Our research employs multi-agent protocols to eliminate the trusted third party, resulting in a protocol with minimum trust assumptions. This dissertation presents one of the first formal definitions of secure mobile agent computation, in which the privacy and integrity of the agent code and data as well as the data provided by the host are all protected. We present secure protocols for mobile agent computation against static, semi-honest or malicious adversaries without relying on any third party or trusting any specific participant in the system. The security of our protocols is formally proven through standard proof technique and according to our formal definition of security. Our second result is a more practical agent protocol with strong security against most real-world host attacks. The security features are carefully analyzed, and the practicality is demonstrated through implementation and experimental study on a real-world mobile agent platform. All these protocols rely heavily on well-established cryptographic primitives, such as encrypted circuits, threshold decryption, and oblivious transfer. Our study of these tools yields new contributions to the general field of cryptography. Particularly, we correct a well-known construction of the encrypted circuit and give one of the first provably secure implementations of the encrypted circuit.
21
Blanchette, Andrew Michael. "Agent Brownie." Digital Commons at Loyola Marymount University and Loyola Law School, 2014. https://digitalcommons.lmu.edu/etd/50.
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22
Sedman, Dawn. "Challenging impunity? : the uneven exercise of criminal jurisdiction over individuals in international accountability mechanisms : a critical evaluation." Thesis, Keele University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534315.
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Rogowski, Adrian. "How to copy a song with impunity : a legal perspective on copyright infringement cases for musical works." Thesis, Stellenbosch : Stellenbosch University, 2015. http://hdl.handle.net/10019.1/97618.
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Thesis (LLM)--Stellenbosch Univeristy, 2015<br>ENGLISH ABSTRACT: Music has, and continues to play, an important role in society. It is therefore natural that more music composers enter the scene to capitalize upon this role that music has in society. It is however becoming more common place for music composers to start copying each other, either directly or indirectly. Fortunately, copyright laws have been developed to further protect the rights enjoyed by copyright holders, such as music composers, and these laws essentially protect the composers from the unlawful reproduction of their original music. Copying is, to some degree, inevitable, therefore, the question asked by this paper is to what extent is someone entitled to ‘copy’ from another person without it amounting to copyright infringement. In determining if there is copyright infringement, two tests must be applied and satisfied, namely, the causal connection test, and the substantial similarity test. Causal connection is usually met by establishing whether the alleged infringer had access to the original work. The substantial similarity test is the focus of this paper. The courts rely on this test to determine if that part which was reproduced from the original work is of substance i.e. if it is a part of the work which attributes uniqueness and quality to the original song. Of course, this test is notoriously difficult to understand and apply, hence the need for this paper to address the question on when there is substantial similarity in two works. This paper is of benefit to academics, authors (musicians) and lawyers, as not only is the substantial similarity test discussed from a theoretical point of view, but the question of when something is substantially similar is answered from a pragmatic point of view. It is hoped that this paper is used as a guideline in understanding and applying the substantial similarity test in music copyright infringement cases.<br>AFRIKAANSE OPSOMMING : Geen opsomming beskikbaar
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Tavares, Furtado Henrique. "Politics of impunity : rethinking the representations of violence through the disciplinary role of the Brazilian Truth Commission." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/politics-of-impunity-rethinking-the-representations-of-violence-through-the-disciplinary-role-of-the-brazilian-truth-commission(23959e88-7dbb-491a-b329-7330d8813deb).html.
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This thesis is a critique of liberal humanitarian representations of violence in the context of Post-Conflict or Post-Authoritarian struggles against impunity. In particular, it addresses the argument of “cultures of impunity” whereby punishing perpetrators of violations of human rights in transitional societies prevents the endorsement of regimes of silence and the normalisation of wrongdoing. Drawing on a Deconstructivist and Disciplinary methodology this thesis argues that debates about punishment or forgiveness in the aftermath of systematic violence have a wider political meaning and a particular historical function. Instead of mere responses to an external reality “punishment vs. impunity” debates also have a productive facet: because they represent violence in a liberal humanitarian frame, they produce a postconflictual ethos that defines (1) the modes of acceptable political resistance in the present and (2) the achievable limits of justice in the future. In order to explain this wider “politics of impunity” this thesis focuses on the Brazilian transitional case, from the end of the Dirty War in the 1970s to the establishment of the National Truth Commission (2012-2014). As such, it rejects the explanation of Brazil as a quintessential “culture of impunity,” a reasoning that blames the amnesty of perpetrators after the militarised dictatorship (1964-1985) for instituting a regime of silence about the past and creating the conditions for an eternal state of exception in Brazil. Although it recognises the merits of this logic, this work argues against it, reassessing the question in a rather different perspective. First, the thesis suggests a methodological twist: moving focus away from the conditions of implementation of justice in post-conflict and post-authoritarian scenarios into the conditions of possibility of the promise of “never again”. This thesis analyses truth commissions, criminal tribunals, and reparation programmes as parts of a historically situated set of disciplines; that is, as the conjunction between a body of knowledge and modes of conduct centred on a specific representation of violence as an intentional, cyclical, and exceptional phenomenon. In other words, it is by narrowing down what violence is that struggles against impunity can promise a future of non-recurrence. Second, the thesis then describes how this representations of violence were mobilised in order to historically produce a postconflictual reality in Brazil. By analysing the trajectory of the memory struggles (1975-) I explain how this postconflictual reality redefined the meaning of political resistance after the Dirty/Cold War, and by looking at the work of the truth commission I describe in what sense it creates a parsimonious promise of justice.
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Logie, Robert. "A study of agent influence in nested agent interactions." Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520785.
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Hagmann, Mirjam. "Multinational Corporations: A case of impunity - An argumentation analysis on the parliamentary debate of the Swiss Business Initiative." Thesis, Malmö universitet, Fakulteten för kultur och samhälle (KS), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-21587.
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Non-governmental organizations (NGOs) and the media are constantly drawing attention to human rights violations caused by multinational corporations abroad (MNC). Due to the lack of an adequate framework to hold corporations accountable for their corporate misconduct across borders, there is a liability gap. Extensive research has been undertaken by political philosophers as well as lawyers attempting to fill the gap, leaving the question why it still exists. Currently, there is a debate in the Swiss parliament about the implementation of a constitutional law which could fill this gap. By conducting an argumentation analysis on the parliamentary debate about the Swiss Business Initiative (SBI), this thesis seeks to analyze how politicians are framing the debate, as well as what normative concerns of the academy have been discussed or left out. Finally, the paper concludes with seven findings that could be focused on more in praxis.
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Umana, Camilo. "Impunity:In the Search of a Socio-Legal Concept. Elucidations from a State Crime Case Study." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36916.
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In the contemporary world, the fight against impunity has become a fundamental political claim, a social goal and a main concern for human rights movements. However, it is unclear how we can delimit this fight, what are its aims and, ultimately, the remedies it proposes to overcome impunity. The academic studies and human rights mechanisms referring to this issue are not sufficiently clarifying. They often lack clear theoretical distinctions and stable empirical observations. Moreover, in social discourses impunity is employed with extremely vague connotations. This research addresses this lacuna, offering a conceptualization and characterization of impunity from a socio-legal perspective. With this purpose in mind, this work develops an analysis of impunity through the study of a particular kind of criminality. The study of state crime provides a prolific perspective for the analysis of the phenomenon of impunity, allowing to visualize the constitution of different blockages against the autonomous operation of the criminal justice. Particularly, this research studies an event of enforced disappearance initiated at the siege of the Colombian Palace of Justice in 1985, through a reconstruction focused on the perspective of the victims using a combination of qualitative methods. This field work, alongside different explorations of the sociological, human rights and criminological state of art of impunity, provides a sociological reflection on the concept of impunity. In the end, taking into account the problematization of the concept and its uses in social discourses, this work proposes a conceptualization apt for overcoming the vagueness of the definition of impunity as well as allowing a delimitation of the fight against it, leaving space for possible innovations on the penal rationality and possibly reinforcing a human rights agenda, concerned with the escalation of repression through punishment and committed with the restoration of social links and the victims’ rights.
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Helin, Heikki. "Supporting nomadic agent-based applications in the FIPA agent architecture." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/tieto/vk/helin/.
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Cederberg, Olle, and Nils Skogfeldt. "Call Forwarding Agent." Thesis, KTH, Skolan för informations- och kommunikationsteknik (ICT), 1998. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-61787.
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In today’s world of telecommunications there is an increasing problem with reaching people one wishes to speak to. People have several telephones and this makes the situation complex for the caller. Many phone calls are left unanswered. The Call Forwarding Agent is in this report presented as a solution to this reachability problem. The idea is to have an agent setting call forwards of all the users’ phones or numbers, towards the terminal where he is available. Later, when someone calls any of the users’ phones, the call will be terminated at the terminal where the user can receive it. The Call Forwarding Agent is compared to a number of similar services. The personal number service offers the same functionality as the Call Forwarding Agent, but the Call Forwarding Agent does not force the subscriber to change phone number and it also admits a simple call screening. We have implemented a prototype of the Call Forwarding Agent that can set call forwards of regular Public Service Telephony Network terminals and the Internet telephones in Ellemtel’s IP-phone system.
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Cuesta, Rivalta Patricia. "Mobile agent management." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/MQ57724.pdf.
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Gu, Gordon Ping. "Agent policy patterns." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0019/MQ57771.pdf.
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Brusewitz, Collin Emanuel, and Andreas Svensson. "The principal agent." Thesis, Högskolan Kristianstad, Sektionen för hälsa och samhälle, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-12765.
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Problem: How can segments on Aktietorget explain how a lemon market can not only survive but grow? Purpose: The purpose is to try to explain how Aktietorget can grow under lemon market conditions by gauging investor groupings investment tendencies. Method: Quantitative archival study regarding returns and price per share depending on investor identity. Conclusion: Finance industry investor yields higher returns, which implicates the possibility of rational investing. This is attributed to either identity inherited capabilities or them being agents in the place of the principal. The private investor on the other hand is full principals and has a tendency towards low price per share. All other capital on Aktietorget conforms to the lottery characteristics of Aktietorget.
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Cuesta, Rivalta Patricia Carleton University Dissertation Engineering Systems and Computer. "Mobile agent management." Ottawa, 2000.
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Gu, Gordon Ping Carleton University Dissertation Computer Science. "Agent policy patterns." Ottawa, 2000.
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Passi, Emilio C. "Bloom's taxonomy agent /." View online record:, 2000. http://srproj.lib.calpoly.edu/projects/csc/Passi%5FEmilio/.
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Rochford, Damien (Damien Joseph). "Agent and environment." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/84421.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Linguistics and Philosophy, 2013.<br>Cataloged from PDF version of thesis.<br>Includes bibliographical references (pages 65-67).<br>This paper is about how agents learn. There is a picture of learning that is very influential in epistemology; I call it 'the Classical Picture'. As influential as it is, it is a flawed picture of learning, and epistemology is distorted by it. In this paper, I offer an alternative: the Calibration Picture. It is based on an extended analogy between agents and measuring devices. Epistemology looks very different from the Calibration point of view. Distinctions that are absolute, given the Classical Picture, are relative, given the Calibration Picture. These include the distinction between enabling and justifying roles of experience, the distinction between a priori and a posteriori knowledge, and the distinction between irrationality and ignorance. The beautiful thing about the Calibration Picture is that it gives you a precise way to characterise what is absolute, and a precise way to recover Classical distinctions from that absolute thing, relative to a context. In this way, the Calibration Picture enables you to recover much of the power of the Classical Picture, while offering a new way to understand its significance.<br>by Damien Rochford.<br>Ph.D.
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Kitchen, Ashley D. "When Laws and Representation Are Not Enough: Enduring Impunity and Post-Conflict Sexual Violence in Liberia and Sierra Leone." Wright State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=wright1363784056.
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Johnston, Sharon 1972. "Double agent dilemma : the Canadian physician: patient advocate and social agent." Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30308.
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This thesis considers the rationalization of health care in Canada. It focuses on the conflicting roles modern physicians play in our system, acting as both patient advocate and social agent. It begins by tracing the origin of both of these duties. It then examines the ethical, professional, and legal issues which arise in the limited circumstances where front-line physicians must participate in the rationing of health care. It offers a framework for resolving the double agent dilemma and states five interlocking recommendations which are the building blocks of the resolution.
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Johnston, Sharon. "Double agent dilemma, the Canadian physician : patient advocate and social agent." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ64284.pdf.
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Cardoso, Rafael Cau? "A decentralised online multi-agent planning framework for multi-agent systems." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2018. http://tede2.pucrs.br/tede2/handle/tede/8048.
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Previous issue date: 2018-03-27<br>Sistemas multiagentes freq?entemente cont?m ambientes complexos e din?micos,
nos quais os planos dos agentes podem falhar a qualquer momento durante a execu??o
do sistema. Al?m disso, novos objetivos podem aparecer para os quais n?o existem
nenhum plano dispon?vel. T?cnicas de planejamento s?o bem adequadas para lidar com
esses problemas. H? uma quantidade extensa de pesquisa em planejamento centralizado
para um ?nico agente, por?m, at? ent?o planejamento multiagente n?o foi completamente
explorado na pr?tica. Plataformas multiagentes tipicamente proporcionam
diversos mecanismos para coordena??o em tempo de execu??o, frequentemente necess?rios
em planejamento online. Neste contexto, planejamento multiagente descentralizado
pode ser eficiente e eficaz, especialmente em dom?nios fracamente acoplados, al?m de
garantir algumas propriedades importantes em sistemas de agentes como privacidade
e autonomia. N?s abordamos esse problema ao apresentar uma t?cnica para planejamento
multiagente online que combina aloca??o de objetivos, planejamento individual
utilizando rede de tarefas hier?rquicas (HTN), e coordena??o em tempo de execu??o
para apoiar a realiza??o de objetivos sociais em sistemas multiagentes. Especificamente,
n?s apresentamos um framework chamado Decentralised Online Multi-Agent Planning
(DOMAP). Experimentos com tr?s dom?nios fracamente acoplados demonstram que DOMAP
supera quatro planejadores multiagente do estado da arte com respeito a tempo
de planejamento e tempo de execu??o, particularmente nos problemas mais dif?ceis.<br>Multi-agent systems often contain dynamic and complex environments where agents? course of action (plans) can fail at any moment during execution of the system. Furthermore, new goals can emerge for which there are no known plan available in any of the agents? plan library. Automated planning techniques are well suited to tackle both of these issues. Extensive research has been done in centralised planning for singleagents, however, so far multi-agent planning has not been fully explored in practice. Multi-agent platforms typically provide various mechanisms for runtime coordination, which are often required in online planning (i.e., planning during runtime). In this context, decentralised multi-agent planning can be efficient as well as effective, especially in loosely-coupled domains, besides also ensuring important properties in agent systems such as privacy and autonomy. We address this issue by putting forward an approach to online multi-agent planning that combines goal allocation, individual Hierarchical Task Network (HTN) planning, and coordination during runtime in order to support the achievement of social goals in multi-agent systems. In particular, we present a planning and execution framework called Decentralised Online Multi-Agent Planning (DOMAP). Experiments with three loosely-coupled planning domains show that DOMAP outperforms four other state-of-the-art multi agent planners with regards to both planning and execution time, particularly in the most difficult problems.
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Fraser, Samuel. "The Catastrophe Artists: Understanding America’s Unaccountable Foreign Policy Elite." Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/cmc_theses/2158.
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The 2003 U.S. invasion of Iraq was a foreign policy action that violated international law, was based on false premises, and came to represent a clear and costly political disaster for the United States and Iraq. Why then, did none of the top policymakers responsible for the decision to invade face meaningful consequences – be they professional consequences, or legal ones? Why too have so many of the media figures who helped sell this war to the American public remained in their prestigious positions, with massive platforms to influence the American people?
This paper argues that the above groups, referred to as the foreign policy elite or foreign policy establishment, are granted a general impunity for their actions. It seeks to explain this condition of elite impunity, and how it operates, through Robert Putnam’s theory of “elite integration.” It also examines the role of congressional marginalization and public disengagement in enabling the foreign policy elite to escape accountability. The subsequent chapters offer case studies of how each of these factors has helped advance and preserve the careers of two prominent members of the foreign policy elite, Elliott Abrams and Henry Kissinger. Finally, the conclusion explores further questions on the matter of elite impunity, and offers some basic steps towards creating a more accountable foreign policy elite.
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Fazekas-Amphoux, Tünde. "L'héxaméthylène-bisacétamide (HMBA) et les cellules thyroïdiennes humaines et animales en culture : agent de prolifération, agent de différenciation, mode d'action ? : agent de prolifération, agent de différenciation, mode d'action ?" Aix-Marseille 2, 1997. http://www.theses.fr/1997AIX20660.
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Gill, Martin L. "Combining MAS and P2P systems : the Agent Trees Multi-Agent System (ATMAS)." Thesis, University of Stirling, 2005. http://hdl.handle.net/1893/108.
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The seamless retrieval of information distributed across networks has been one of the key goals of many systems. Early solutions involved the use of single static agents which would retrieve the unfiltered data and then process it. However, this was deemed costly and inefficient in terms of the bandwidth since complete files need to be downloaded when only a single value is often all that is required. As a result, mobile agents were developed to filter the data in situ before returning it to the user. However, mobile agents have their own associated problems, namely security and control. The Agent Trees Multi-Agent System (AT-MAS) has been developed to provide the remote processing and filtering capabilities but without the need for mobile code. It is implemented as a Peer to Peer (P2P) network of static intelligent cooperating agents, each of which control one or more data sources. This dissertation describes the two key technologies have directly influenced the design of ATMAS, Peer-to-Peer (P2P) systems and Multi-Agent Systems (MAS). P2P systems are conceptually simple, but limited in power, whereas MAS are significantly more complex but correspondingly more powerful. The resulting system exhibits the power of traditional MAS systems while retaining the simplicity of P2P systems. The dissertation describes the system in detail and analyses its performance.
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Hoegh, Julie E. "Agent of change : the literary agent and contemporary British publishing and bookselling." Thesis, King's College London (University of London), 2004. https://kclpure.kcl.ac.uk/portal/en/theses/agent-of-change--the-literary-agent-and-contemporary-british-publishing-and-bookselling(ecf174ac-58aa-4b2b-9650-9b42ddaed129).html.
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Mattiasson, Nazar Alexander. "Place, youth and memory as resistance : An ethnographic case study of discussions about impunity at Londres 38,espacio de memorias." Thesis, Stockholms universitet, Statsvetenskapliga institutionen, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-171553.
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” You don’t talk about politics or football around the dining table” is a Chilean expression that well describes how the dictatorship (1973–1990) is attached to the societal soul, with people’s diversifiedrelationships to its legacy. For the outside world, Chile is a thriving democracy that got out of Pinochet’s iron grip, but for many Chileans, the transition to democracy has excluded demands for justice and a real influence. How is it to be born into democracy and grow up in a society where the struggle for memory is a struggle for the future? Where you did not live the terrible years but live with its consequences? This study is interested in how the younger generation breaks a generational silence and actively participates in politicizing memory. With a political-ethnographic approach and a customized discourse analytical tool, these processes are captured through an extensive case study of the memory site Londres 38, espacio de memorias. In conversations about impunity with the memory site’s young representatives and the school and university class’s diversified reflections on the subject during participating visits, present research shows how the place becomes a democratic deliberative platform, in contrast to prevailing power relations, giving voice and perspective to a new generation.
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Amponsah-Frimpong, Samuel. "Truth commissions and the perpetuation of the culture of impunity in Africa : a case study of Ghana and South Africa." Diss., University of Pretoria, 2003. http://hdl.handle.net/2263/982.
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"It is noted that special measures are always necessary in post-conflict situations to bring about the restoration of normalcy to societies. Truth commissions have been identified as a key to uniting, reconciling and helping the people to confidently deal with their past. Whilst these are noble notions, practically, truth commissions face serious challenges. The dissertation shall seek to highlight these problems and offer recommendations. ... The dissertation is divided into five chapters. Chapter one is the general introduction. It gives a brief political history of Ghana and South Africa and their impact on the enjoyment of human rights. The chapter shall also discuss the need for national reconciliation in both countries. Chapter two discusses truth commissions in contemporary societies. It briefly discusses the establishment of national reconciliaton commissions and their mandates. Chapter three focuses on the laws establishing the TRC and NRC of South Africa and Ghana respectively. These legislation shall be considered in detail in order to analyse their objectives to know whether or not thet are achievable within their stated mandates. Chapter four discusses the challenges truth commission poses to international law and its implications on rule of law. The chapter shall discuss the issue of amnesty to perpetrators of gross human rights and the perpetuation of the culture of impunity in the light of international law. Chapter five considers the way forward and suggest recommendations." -- Chapter 1.<br>Thesis (LLM (Human Rights and Democratisation in Africa))--University of Pretoria, 2003.<br>http://www.chr.up.ac.za/academic_pro/llm1/dissertations.html<br>Centre for Human Rights<br>LLM
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Lipperts, Steffen Richard Goswin. "Mobile agent support services." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=964753065.
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Braña, García Irene. "Anticancer targeted agent combination." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/457506.
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Las toxicidades limitantes de dosis fuero una neutropenia febril grado 4 (en el brazo de docetaxel) y una neutropenia grado 3 en el brazo de gemcitabina. La combinación de carlumab no tuvo un impacto
El cáncer es una enfermedad altamente frecuente y con alta mortalidad. El desarrollo de fármacos contra el cáncer se ha caracterizado por su ineficiencia, con una de las tasas de aprobación de fármacos más baja entre las diferentes especialidades médicas. El principal motivo de esta baja tasa de éxito es la falta de eficacia de los nuevos fármacos que entran al desarrollo clínico. Se han planteado diferentes estrategias para mejorar la eficiencia del desarrollo de fármacos, incluyendo la combinación de fármacos antitumorales, el desarrollo en paralelo de biomarcadores y la optimización del diseño de los ensayos clínicos usando modelización basada en farmacocinética y farmacodinamia
Esta tesis es un compendio de dos artículos que evalúan estrategias para optimizar el desarrollo de fármacos mediante la combinación de agentes antitumorales. El primer proyecto es la evaluación preclínica en xenoinjertos derivados de pacientes (PDX) la combinación de inhibidores de PI3K-mTOR con diferentes agentes antitumorales y el segundo es el ensayo clínico fase I evaluando carlumab, un anticuerpo anti CCL2, en combinación con diferentes quimioterapias en pacientes con tumores sólidos avanzados.
Proyecto 1: se seleccionaron tres modelos de PDX con deficiencia en PTEN: un PDX de cáncer de mama triple negativo (TNBC), otro de carcinoma de ovario de bajo grado KRAS G12R mutado y otro de adenocarcinoma de pulmón con mutaciones en KRAS G12C y TP53 R181P. En estos modelos se evaluaron dos inhibidores de PI3K-mTOR—PF-04691502 and PF-05212384— en combinación con cisplatino, paclitaxel o dacomitinib.
La adición de los inhibidores de PI3K-mTOR a cisplatino o paclitaxel aumentó la actividad de la quimioterapia en los modelos de TNBC y LGSOC; sin embargo, no se objetivó este efecto en modelo de adenocarcinoma de pulmón con mutación de KRAS y TP53. Se objetivó modulación farmacodinámica de pAKT y pS6 en los grupos tratados con inhibidores de PI3K-mTOR.
Nuestra investigación sugiere que añadir un inhibidor de PI3K-mTOR puede aumentar el efecto inhibitorio sobre el crecimiento de la quimioterapia en modelos PDX con deficiencia en PTEN. Sin embargo, este beneficio no se observó en el modelo de adenocarcinoma KRAS y TP53 mutado. En el futuro se deberá ahondar en el papel de la pérdida de PTEN en la actividad de estas combinaciones.
Proyecto 2: se trata de un ensayo clínico fase Ib evaluando carlumab, un anticuerpo monoclonal contra CCL-2, en combinación con cuatro regímenes de quimioterapia (docetaxel, gemcitabina, carboplatino + paclitaxel y doxorrubicina liposomal pegilda (PLD). En este estudio participaron 53 pacientes en los que o bien los agentes quimioterápicos eran parte del tratamiento convencional o no tenían otras opciones de tratamiento convencional: docetaxel (n=15), gemcitabina (n=12), carboplatino + paclitaxel (n=12) y PLD (n=14).
Las toxicidades limitantes de dosis incluyeron una neutropenia febril grado 4 (en el brazo de docetaxel) y una neutropenia grado 3 (en el brazo de gemcitabina). De acuerdo a los brazos de tratamiento, las toxicidades grado 3 o mayores más frecuentes fueron: neutropenia (6/15) y neutropenia febril (4/15) en el brazo de docetaxel, neutropenia (2/12) en el brazo de gemcitabina, neutropenia (4/12), trombocitopenia (4/12) y anemia (2/12) en el brazo de carboplatino-paclitaxel y anemia (3/14) y mucositis (2/14) en el brazo de PLD. Se objetivo una respuesta parcial y 18 estabilizaciones de la enfermedad (38%).
La adición de carlumab no tuvo cambios relevantes en el perfil farmacocinético de ninguna de las quimioterapias evaluadas. Los niveles de CCL2 libres descendieron inmediatamente tras el tratamiento con carlumab, pero aumentaron con las administraciones posteriores, sugiriendo que carlumab secuestraba CCL2 de manera temporal. No se objetivaron anticuerpos anti-droga que justificasen dicho efecto. No se objetivaron cambios en las células tumorales circulantes ni en las células circulantes endoteliales. En 3 de 19 pacientes evaluables se objetivó una reducción del 30% en los niveles de N-telopeptido de colágeno tipo I en orina (uNTx).
Carlumab es seguro administrado a dosis de 10 o 15 mg/kg en combinación con quimioterapia convencional y tiene buena tolerancia. Sin embargo, no se alcanza una inhibición sostenida de CCL2, ni se han objetivado un número de respuestas significativas.<br>Cancer is a highly frequent disease associated to high mortality. Drug development in Oncology has shown to be inefficient, having one of the lowest success rate of drugs entering in phase I trials that finally achieves marketed authorization. The main reason for this high failure rate is lack of efficacy. Different strategies have been adopted to improved anti-cancer drug development with the aim of improving patient care. This strategies include the combinatorial use of agents, biomarker co-development, and optimization of clinical trial design with the use of pharmacokinetic-pharmacodynamic modeling.
This thesis is presented as compendium of work integrating two projects; the first project preclinically evaluates the combination of two PI3K-mTOR inhibitors and chemotherapy or the pan-HER inhibitor dacomitinib in patient derived xenografts. The second project evaluates de monoclonal antibody anti-CCL2 carlumab in patient derived xenografts.
Project 1: Three PDXs were selected for their lack of PTEN expression by immunohistochemistry: a triple-negative breast cancer (TNBC), a KRAS G12R low-grade serous ovarian cancer (LGSOC), and KRAS G12C and TP53 R181P lung adenocarcinoma (LADC). Two dual PI3K-mTOR inhibitors were evaluated—PF-04691502 and PF-05212384—in combination with cisplatin, paclitaxel, or dacomitinib.
The addition of PI3K-mTOR inhibitors to cisplatin or paclitaxel increased the activity of chemotherapy in the TNBC and LGSOC models; whereas no added activity was observed in the LADC model. Pharmacodynamic modulation of pS6 and pAKT was observed in the group treated with PI3K-mTOR inhibitor.
Our research suggests that the addition of a PI3K-mTOR inhibitor may enhance tumor growth inhibition when compared to chemotherapy alone in PTEN-deficient PDXs. However, this benefit was absent in the KRAS and TP53 mutant LADC model. The role of PTEN deficiency in the antitumor activity of these combinations should be further investigated in the clinic.
Project 2 is a first-in-human phase 1b study of carlumab with one of four chemotherapy regimens (docetaxel, gemcitabine, paclitaxel+carboplatin, and pegylated liposomal doxorubicin HCl [PLD]). Fifty-three patients with advanced solid tumors for which ≥1 of these regimens was considered standard of care or for whom no other treatment options existed participated in the study: docetaxel (n=15), gemcitabine (n=12), paclitaxel or carboplatin (n=12), or PLD (n=14).
Dose-limiting toxicities included one grade 4 febrile neutropenia (docetaxel arm) and one grade 3 neutropenia (gemcitabine arm). The most common drug-related grade ≥3 adverse events were docetaxel arm—neutropenia (6/15) and febrile neutropenia (4/15); gemcitabine arm—neutropenia (2/12); paclitaxel+carboplatin arm—neutropenia, thrombocytopenia (4/12 each), and anemia (2/12); and PLD arm—anemia (3/14) and stomatitis (2/14). One partial response and 18 (38 %) stable disease responses were observed.
Combination treatment with carlumab had no clinically relevant pharmacokinetic effect on any of the chemotherapeutic agents tested. Free CCL2 declined immediately post-treatment with carlumab but increased with further chemotherapy administrations in all arms, suggesting that carlumab could sequester CCL2 for only a short time. Neither antibodies against carlumab nor consistent changes in circulating tumor cells (CTCs) or circulating endothelial cells (CECs) enumeration were observed. Three of 19 evaluable patients showed a 30 % decrease from baseline urinary cross-linked N-telopeptide of type I collagen (uNTx).
Carlumab could be safely administered at 10 or 15 mg/kg in combination with standard-of-care chemotherapy and was well-tolerated, although no long-term suppression of serumCCL2 or significant tumor responses were observed.
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Steindórsson, Ólafur B. "Kollektivet som autonom agent." Thesis, Linköping University, Department of Culture and Communication, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-58973.
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Uchyigit, G. "Agent-based recommender systems." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429341.
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