This paper is concerned with an investigation of four Old English adverbials with respect to where they are base-generated within the substructure of clauses which serve as examples of Old English prose. There are three structures in which base-generation of clausal constituents is deemed to occur: the CP, the IP, and the VP. Function and derivational movement are the governing factors which regulate the possibility of base-generation occurring within a particular structure. The movements undergone by clausal constituents, from their places of origin within the ‘underlying structures’ to their syntactic realization in the ‘surface structures’ of Old English clauses, are founded upon the model outlined in Johannesson (2009a) which is based on the tenets of Government and Binding theory. As there are no native speakers of Old English, the functions of these adverbials within their clausal environments are determined by their Modern English interpretations. Due to time and space constraints, four Old English adverbials were analysed within the context of one-hundred and twenty clauses which were extracted from The Dictionary of Old English Corpus (2004). Cases deemed to be ambiguous are addressed and classified separately; only one such case was encountered in the course of this study. The results should exhibit proof that base-generation of the four Old English conjunct and disjunct adverbials investigated occurs within one of the aforementioned structures. Note that any conclusions drawn are based upon Modern English translations and that the results pertain to the genre of Old English prose.

Magister Legum - LLM / South Africa

Endokrin aktive Substanzen (EACs) sind exogene Substanzen natürlichen oder synthetischen Ursprungs, die mit der Feedbackregulation hormoneller Netzwerke interferieren können und somit deren Homöostase beeinflussen. Störungen der Hypothalamus-Hypophysen-Schilddrüsenachse (HPT-Achse) haben weitreichende Konsequenzen, da Schilddrüsenhormone essentiell für die Regulation von Entwicklung, Wachstum und Stoffwechsel sind. In der vorliegenden Arbeit wurde das Wirkprofil potenter Inhibitoren der thyreotropen Achse am Beispiel von 4-Methylbenzyliden-campher (4-MBC) und Genistein (GEN) untersucht. Der UV-Filter 4-MBC wurde in der ovariektomierten Ratte als goitrogene Substanz identifiziert. 4-MBC interferiert auf Ebene von Hypothalamus und Hypophyse mit der Expression Feedback-assoziierter Gene und beeinflusst daher die Feedbackregulation der thyreotropen Achse. Darüber hinaus wird die Biosynthese von Schilddrüsenhormonen durch Inhibition des Iodidtransports bei gleichzeitig erhöhter messenger RNA (mRNA)-Konzentration des Natrium-Iodid-Symporters (NIS) durch 4-MBC beeinträchtigt. Parallel dazu lässt die verstärkte Expression des Angiogenesemarkers vascular endothelial growth factor (VEGF) nach subakuter Exposition auf die Entstehung einer Hypothyreose schließen. Die damit einhergehenden Veränderungen sind auch in peripheren Organen durch die Analyse 3,3‘,5-Triiod-L-thyronin (T3)-regulierter Zielgene dokumentiert. Zudem wurden diese Effekte maßgeblich durch die Expositionszeit beeinflusst, da nach chronischer Exposition vermutlich auch kompensatorische Prozesse eine wichtige Rolle spielen. Die gezeigten speziesspezifischen Effekte lassen sich möglicherweise auf Unterschiede in der Pharmakokinetik zurückführen, z.B. in Folge differentieller Expression von Cytochrom P450-Genen. / Endocrine active compounds (EACs) can be of natural or synthetic origin and show hormone-like effects that interfere with feedback regulation of hormonal networks. Interferences with the hypothalamic-pituitary-thyroid axis (HPT-axis) result in extensive consequences as thyroid hormones are essential for regulation of development, growth, and metabolism. In the work presented here, the active profile of potent inhibitors of the HPT-axis namely 4-methylbenzylidene-camphor (4-MBC) and genistein (GEN) was investigated. 4-MBC, a UV filter used in sunscreens and various cosmetics, was identified as a goiter causing agent using ovariectomized rats. 4-MBC acts at the level of hypothalamus and pituitary gland by modulating the expression of thyrotropin-releasing hormone (TRH) as well as thyroid-stimulating hormone (TSH) that regulate feedback on the HPT-axis. Furthermore, biosynthesis of thyroid hormones was impaired by 4-MBC secondary to the inhibition of iodide transport with concomitantly increased messenger RNA (mRNA)-levels of the sodium-iodide symporter (NIS). In parallel expression of the angiogenesis marker vascular endothelial growth factor (VEGF) was increased, indicating hypothyroidism. After the application of 4-MBC the expression of L-3,3’,5-triiodothyronine (T3)-regulated target genes was reduced in the periphery both on the mRNA and protein level. The documented species-specific effects indicate a difference in pharmacokinetics, possibly secondary to differential expression of cytochrome P450 genes. GEN is contained in soy and red clover and its mechanistic analysis was carried out in thyroid hormone receptor (TR) deficient mice (TRα0/0). The gender-dependent effects of GEN on tissue specificity did not follow an obvious pattern and warrant continuative analysis. The work presented here supports the assumption that EACs can interfere with function and regulation of the HPT-axis at levels that were previously considered safe.

L’histoire de l’intégration régionale dans les Grands Lacs est récente. Il faut attendre la colonisation pour voir le Burundi et le Rwanda entrer véritablement dans ce processus. Le mandat belge oriente les deux territoires vers le cœur de l’Afrique. Cette période va influencer la première intégration institutionnelle avec la Communauté Economique des Pays des Grands Lacs. Il convient toutefois de rester mesuré, puisque celle-ci est avant tout une intégration de papier. Elle est similaire aux autres adhésions des deux pays à cette période, qui se révèlent être en inadéquation avec leurs circuits commerciaux. Les organisations régionales sont également inefficaces pour régler la problématique des réfugiés. Les années 1993 et 1994 sont des ruptures internes pour le Burundi et le Rwanda. Elles provoquent également un renversement régional, avec la désintégration de l’Afrique des Grands Lacs : ce sont les guerres congolaises. Dans le même temps, les deux pays se réorientent vers l’Afrique de l’Est, où l’EAC leur permet enfin un réel désenclavement. L’intégration du Rwanda semble toutefois plus efficace que celle du Burundi. / The history of regional integration in the Great Lakes is recent. To see Burundi and Rwanda truly enter into this process you have to wait the colonization. The Belgian mandate turns the two territories to the heart of Africa. This period will influence the first institutional integration with the Economic Community of Great Lakes Countries. However, we should remain cautius, since it is primarily paper integration. It is similar to other memberships of the two countries in this period, which is proving to be inadequate with their commercial channels. Regional organizations are also ineffective to resolve the refugee issue. The years 1993 and 1994 are internal ruptures for Burundi and Rwanda. They also cause a regional reversal, with the disintegration of the African Great Lakes : these are the Congolese wars. At the same time, both countries are shifting towards East Africa, where the EAC finally allows them a real opening up. The integration of Rwanda, however, seems more effective than that of Burundi.

There is enough evidence on how climate change consequences will adversely affect Africa despite the fact that it is the continent that has least contributed to the problem. The international climate change regime recognises Africa's vulnerability to climate change and provides for special treatment under the United Nations Framework Convention on Climate Change (the UNFCCC). Thus, the international climate change regime presents an opportunity for African countries to adapt and mitigate the consequences of climate change through the UNFCCC mechanism. However, the international climate change legal regime has not been able to adequately assist African countries to address the consequences of climate change under the vulnerability principle. Although the current international climate change regime requires developed countries to reduce their greenhouse gas (GHG) emissions, Africa needs to take steps itself to address the problem, because it is most vulnerable to the consequences of climate change. The African Union (AU) could play a great role in ensuring that the international climate change regime addresses the consequences of climate change in the region. This could be done through fostering strong African common positions during international climate change negotiations. A strong common position could strengthen African bargaining power and might result in more funding, capacity building and technology development and transfer for adaptation and mitigation programmes under the UNFCCC-Kyoto Conference of Parties. However, reaching a strong common position requires the cooperation of the AU member states. In this context, African regional integration is an opportunity for the AU to foster such cooperation among member states. The Treaty Establishing the African Economic Community (the Abuja Treaty), the Constitutive Act of the AU and the Protocol on the Relations between the AU and Regional Economic Communities (RECs) prioritise regional economic integration and call for states' cooperation, but the call has not yet been heeded. To realise deep and viable African integration, there must be a well-structured institutional and legal framework that defines the relationship between the AU, the AEC and the RECs. African regional integration is also seen as an avenue whereby the AU can create its own regional climate-change regime. In this regard, the AU's and RECs' normative framework on climate change is examined in order to assess whether it adequately integrates climate change issues. This study finds that although Africa is most vulnerable to the consequences of climate change, the AU's and RECs' normative framework on climate change is weak and inadequate to address the problem. The Framework should integrate climate change issues in order to achieve sustainable development. The AU should also ensure that member states ratify the relevant treaties and protocols (the Maputo Nature Convention and the Protocol establishing the African Court of Justice and Human Rights) that have not yet been ratified in order that they may become operational. The Maputo Nature Convention puts sustainable development in the forefront of attention as a reaction to the potentially conflicting environmental and developmental challenges facing the continent (such as climate change), but it is not yet in force. This work finds that human rights law can strengthen the AU's role in addressing climate change through its normative framework. The human rights approach to climate change under the African Charter on Human and Peoples' Rights (the Banjul Charter) is a viable avenue because human rights law forms the basis for states' responsibility based on human rights obligations and principles. The extraterritorial application of the Banjul Charter presents an avenue for AU institutions such as the Human Rights Commission and the African Human Rights Court to curb the effects of climate change through a human rights lens. The future of the AU is presented within the context of a set of recommendations that identify strong African regional integration as an avenue through which the AU can foster the cooperation of member states to address the consequences of climate change in the AU's and RECs' normative frameworks. General recommendations are made on the need for the international climate change regime to pay more attention to issues of funding, capacity building and technology development and transfer on the basis of the vulnerability principle and in relation to the principles of equity and common but differentiated responsibilities and respective capabilities. Also, the AU needs to strengthen its legal and institutional structures to ensure deep African integration that is capable of addressing common challenges such as the consequences of climate change. / PhD (Law), North-West University, Potchefstroom Campus, 2014

There is enough evidence on how climate change consequences will adversely affect Africa despite the fact that it is the continent that has least contributed to the problem. The international climate change regime recognises Africa's vulnerability to climate change and provides for special treatment under the United Nations Framework Convention on Climate Change (the UNFCCC). Thus, the international climate change regime presents an opportunity for African countries to adapt and mitigate the consequences of climate change through the UNFCCC mechanism. However, the international climate change legal regime has not been able to adequately assist African countries to address the consequences of climate change under the vulnerability principle. Although the current international climate change regime requires developed countries to reduce their greenhouse gas (GHG) emissions, Africa needs to take steps itself to address the problem, because it is most vulnerable to the consequences of climate change. The African Union (AU) could play a great role in ensuring that the international climate change regime addresses the consequences of climate change in the region. This could be done through fostering strong African common positions during international climate change negotiations. A strong common position could strengthen African bargaining power and might result in more funding, capacity building and technology development and transfer for adaptation and mitigation programmes under the UNFCCC-Kyoto Conference of Parties. However, reaching a strong common position requires the cooperation of the AU member states. In this context, African regional integration is an opportunity for the AU to foster such cooperation among member states. The Treaty Establishing the African Economic Community (the Abuja Treaty), the Constitutive Act of the AU and the Protocol on the Relations between the AU and Regional Economic Communities (RECs) prioritise regional economic integration and call for states' cooperation, but the call has not yet been heeded. To realise deep and viable African integration, there must be a well-structured institutional and legal framework that defines the relationship between the AU, the AEC and the RECs. African regional integration is also seen as an avenue whereby the AU can create its own regional climate-change regime. In this regard, the AU's and RECs' normative framework on climate change is examined in order to assess whether it adequately integrates climate change issues. This study finds that although Africa is most vulnerable to the consequences of climate change, the AU's and RECs' normative framework on climate change is weak and inadequate to address the problem. The Framework should integrate climate change issues in order to achieve sustainable development. The AU should also ensure that member states ratify the relevant treaties and protocols (the Maputo Nature Convention and the Protocol establishing the African Court of Justice and Human Rights) that have not yet been ratified in order that they may become operational. The Maputo Nature Convention puts sustainable development in the forefront of attention as a reaction to the potentially conflicting environmental and developmental challenges facing the continent (such as climate change), but it is not yet in force. This work finds that human rights law can strengthen the AU's role in addressing climate change through its normative framework. The human rights approach to climate change under the African Charter on Human and Peoples' Rights (the Banjul Charter) is a viable avenue because human rights law forms the basis for states' responsibility based on human rights obligations and principles. The extraterritorial application of the Banjul Charter presents an avenue for AU institutions such as the Human Rights Commission and the African Human Rights Court to curb the effects of climate change through a human rights lens. The future of the AU is presented within the context of a set of recommendations that identify strong African regional integration as an avenue through which the AU can foster the cooperation of member states to address the consequences of climate change in the AU's and RECs' normative frameworks. General recommendations are made on the need for the international climate change regime to pay more attention to issues of funding, capacity building and technology development and transfer on the basis of the vulnerability principle and in relation to the principles of equity and common but differentiated responsibilities and respective capabilities. Also, the AU needs to strengthen its legal and institutional structures to ensure deep African integration that is capable of addressing common challenges such as the consequences of climate change. / PhD (Law), North-West University, Potchefstroom Campus, 2014

ABSTRACT External otitis and its treatment. Is a group III steroid without antibiotics sufficient therapy? – Experimental and clinical studies Per Emgård, Department of Otorhinolaryngology, University of Umeå and Ystad Hospital, Umeå and Ystad, Sweden External otitis is one of the most common ear, nose and throat (ENT) diagnoses in out-patient clinics. The clinical course of external otitis includes itching, pain, redness, swelling and effusion of the external auditory canal (EAC) with normal tympanic membrane status. The inflammatory condition is often associated with infection by bacteria, e.g. Pseudomonas aeruginosa, or skin bacteria such as Staphylococcus species. Fungi are present only in a low percentage of cases and if present Candida albicans infection is the most frequent in northern countries such as Sweden and the UK. Topical therapy is recommended in most countries and dominates the therapy in most studies. Topical drugs used are usually a combination of antibiotics and a steroid. However, external otitis is treated with surprisingly many strategies – eleven different ones in Sweden, for example, and 18 in the UK. The aims of the present studies were to – -establish an animal model, infected and uninfected, suitable for testing various treatment strategies of external otitis; and -perform a clinical study in patients to elucidate whether a group III steroid alone is as efficient for treatment of external otitis as is the commonly used topical drug containing a combination of a steroid and antibiotics. The animal model was established through mechanical irritation of the external ear canal skin of Sprague-Dawley rats. An evaluation scale for characterization of the clinical status of the ear canal was introduced, recording redness, swelling and occurrence of effusion in a standardized way. Specimens of the ear canal skin were analysed by histological techniques. A topical solution of 0.05% bethametasone dipropionate (BD) was compared with a 1% hydrocortisone solution with antibiotics oxytetracycline and polymyxin B added (HCPB), administered in the external otitis model infected or non-infected with bacteria (P. aeruginosa) and a fungus (C. albicans). The same drugs were tested in a randomized parallel-group multi-centre study in 51 patients. The clinical status of the external otitis patients was evaluated on a similar scale as used in the animal model. Early normalization of the ear canal skin status and frequency of relapses during the 6-month follow-up period were used as end-points of the study. The studies showed the following: -An animal model for external otitis, infected or uninfected, could be established. -A new scale for evaluation of the external ear canal status with regard to redness, swelling and occurrence of effusion was introduced for the animal model as well as for the investigations in patients. -Treatment with a group III steroid topical solution without antibiotics was superior to treatment with a group I steroid with antibiotics added in achieving resolution of external otitis. -The effectiveness of the topical drugs in the clinical studies in external otitis patients was similar to that in animal external otitis models. We conclude that a group III steroid solution cures external otitis more effectively than does a solution containing a group I steroid combined with antibiotics, whether infected by bacteria or by fungi. No difference was evident regarding adverse effects. Furthermore, costs favour a solution without any antibiotic components. In view of these observations a group III steroid solution is preferred for remedy of external otitis in the clinical situation. Key words: external otitis, external auditory canal (EAC), animal model, treatment, betamethasone, hydrocortisone, antibiotics, human study, Pseudomonas aeruginosa, Candida albicans.

<p>The rapid growth in the number of regional trade agreements (RTAs) has led to concern about the weakening of the multilateral trading system. This thesis examines the spread of such agreement and the extent to which they pose a threat to the multilateral system. Regionalism and multilateralism are complimentary as shown in the case study of the East African Community. The current regional trade agreement management rules are weak and ambiguous and possible amendments for these rules are proposed</p>

<p>The rapid growth in the number of regional trade agreements (RTAs) has led to concern about the weakening of the multilateral trading system. This thesis examines the spread of such agreement and the extent to which they pose a threat to the multilateral system. Regionalism and multilateralism are complimentary as shown in the case study of the East African Community. The current regional trade agreement management rules are weak and ambiguous and possible amendments for these rules are proposed</p>

Les eczémas [eczéma allergique de contact (EAC) et l'eczéma atopique (EA)] sont des dermatoses inflammatoires fréquentes des pays industrialisés. Elles sont induites suite au recrutement et à l'activation dans la peau de lymphocytes T spécifiques d'allergènes, qui sont présents dans notre environnement, et qui sont habituellement très bien tolérés par la majoritédes individus exposés. Ce travail de thèse porte sur un aspect novateur de la physiopathologie des eczémas, à savoir : la contribution des lymphocytes T mémoires résidants (LTrm) dans la peau à la chronicité et à la sévérité de ces maladies.Capitalisant sur des modèles précliniques pertinents ainsi que sur des échantillons cliniques prélevés chez les patients, ce travail a permis d'acquérir de nouvelles connaissances : (i) de nombreux LTrm CD8+ spécifiques colonisent les lésions d'eczéma (ii) ils s'accumulent avecla persistance de l'allergène dans la peau, (iii) ils jouent un rôle majeur dans les récidives de la maladie, mais (iv) ils expriment à leur surface divers récepteurs inhibiteurs, tels que PD-1 ou TIM-3, qui empêchent la survenue de réponses allergiques excessives.Ces travaux apportent donc des informations majeures sur la nature unique des LTrm CD8+ spécifiques d'allergènes et des mécanismes qui contrôlent leur réactivation, afin de préserver l'intégrité de la peau et la survenue de réactions chroniques sévères. Le développement des nouvelles stratégies thérapeutiques ciblant la réactivation des LTrm via leurs récepteursinhibiteurs pourrait permettre de restaurer la tolérance chez les individus allergiques / Allergic contact dermatitis (ACD) and atopic dermatitis (AD), also referred to contact or atopic eczema, are frequent skin inflammatory diseases with increasing prevalence and high socioeconomic impact in Western countries. Eczemas are the prototype of skin delayed-type hypersensitivity reactions. Skin lesions are induced by the recruitment and activation in the skin of effector/memory T cells specific for environmental antigens that are innocuous to healthy non-allergic individuals.The aim of this work was to better understand the pathophysiology of eczemas by a comprehensive analysis of the contribution of skin resident memory T cells (Trm) to the chronicity and severity of these diseases.Capitalizing on relevant preclinical eczema models and on clinical samples collected from allergic patients, this work showed that: (i) numerous allergen-specific CD8+Trm colonize the eczema lesion, (ii) they accumulate in the epidermis in response to the long-term persistence of the allergen in the skin, (iii) they are instrumental for the recurrence of eczema, but (iv) theyexpress several inhibitory check point receptors (ICRs, such as PD-1, TIM-3) at their surface, which keep them in check to prevent the development of severe immunopathology.Thus, our work provides important information for considering the unique nature of hapteninduced CD8+ Trm and the mechanisms that prevent their unwanted reactivation and subsequent development of chronic or severe skin allergy. The development of therapeutic strategies targeting the reactivation of skin Trm in situ via their ICRs should open new avenues to restore tolerance in allergic individuals