This thesis argues that the International Criminal Court (ICC) brings a new more deontological paradigm to international interventions, founded upon the universal application of legal principle, and displacing consequentialist notions of justice linked to human rights. Based upon the Court’s Statute and mode of operations, it is argued that this is associated with assumptions concerning the ICC’s primacy, military enforcement, and theory of change. The consequences of this development in volatile contexts are demonstrated. The case study, founded upon analysis from the war-affected community, examines the impact of the International Criminal Court in the Lord’s Resistance Army war, and reveals the relationship between criminal justice enforcement, and community priorities for peace and human rights. On the basis of evidence, and contrary to narratives repeated but unsubstantiated in the literature, it demonstrates that in this case these two imperatives were in opposition to one another. The Court’s pursuit of retributive legal principle was detrimental to the community’s interests in peace and human rights. The subsequent failure of the ICC’s review process to interrogate this important issue is also established. The research establishes that statutory and operational assumptions upon which Court interventions are based do not hold in volatile contexts. For the case study community and elsewhere, this has had adverse impacts, with significant implications for the ICC. The findings indicate that if these issues are not fundamentally addressed, principled international criminal justice enforcement in volatile environments will continue to have profoundly negative human rights consequences.

Graft-versus-host disease (GvHD) is a frequent, and often life-threatening, complication after an allogeneic, hematopoietic stem cell transplantation (allo-SCT). It can appear in an acute or a chronic form and presents different grades of severity. Particularly, the severe forms of GvHD are often responsible for a change of the curative intent for allo-SCT into a palliative goal of care. For this non-systematic review, we conducted a focused literature search in the MEDLINE database via PubMed to examine whether patients with severe forms of GvHD might have special needs and burdens from a supportive and palliative care perspective. To draw a comprehensive picture of this patient group, we included findings on quality of life (QoL) and physical symptoms and function as well as psychological and spiritual well-being. In most domains, patients with severe forms of GvHD showed greater impairment and a higher symptom burden compared to patients with milder forms of GvHD. However, we could not identify any studies that specifically investigated patients with severe forms of GvHD. Further research in this field is necessary to guarantee the highest standard of care for this very special patient group.

Detta examensarbete grundades på en kvalitativ och empirisk studie. Målsättningen har varit att utröna vilka teorier och faktorer som kunde bidra till elevers motivation och lärande, och hur lärare verksamma i undervisningen av naturvetenskapliga ämnen ser på möjligheterna att kunna påverka denna. En annan viktig aspekt i studien kretsar kring frågeställningen om ”tvålärarskapet”; som kortfattat innebär att två lärare arbetar parallellt i klassrummet. Har lärare som arbetar enligt denna metod en möjlighet att underlätta och entusiasmera inlärningen och motivationen? Finns det eventuellt några nackdelar? Förutom kontakten med en svensk förgrundsgestalt bakom undervisningsformen; tvålärarskapet, används djupintervjuer med sammanlagt sex lärare, samt diskussioner och två mer omfattande intervjuer med elever som grund. Studien har funnit att bland de viktigaste teorierna för att främja motivationen och lärandet återfanns teorin om Tron på sin egen kapacitet, Sociala relationer, Förväntningar och värden, samt Inre motivation, yttre motivation. Tvåläraskapet kan ha ett samband med teorin om Sociala relationer vilket skulle kunna ha implikationer på dess inverkan på motivationen och lärandet. / This thesis was based on a qualitative and empirical study. The objective was to discover which theories and factors could contribute to students' motivation and learning, and how teachers active in the teaching of science subjects see the possibilities of being able to influence this. A very important aspect of the study revolves around the question of "co-teaching"; which in short means that two teachers work in parallel in the classroom. Do teachers working according to this method have an opportunity to facilitate and encourage the learning and motivation? Are there any downsides? In addition to the contact with one of the most outspoken Swedish professionals behind the educational method of co-teaching, in-depth interviews with a total of six teachers are used, as well as discussions and two more extensive interviews with common students as a basis. The study has found that among the most important theories to promote motivation and learning were the theories of Self-Efficacy, Social Relations, Expectations and Values, and Intrinsic motivation, extrinsic motivation. Co-teaching may be related to the Social Relationship theory, which could have implications for its impact on motivation and learning.

CD2 is a transmembrane molecule and a “non-canonical” member of the signaling lymphocyte activation molecule (SLAM) family of receptors that is expressed on T cells and NK cells. Its ligands, mouse CD48 and human CD58, are widely expressed on hematopoietic cells including antigen-presenting cells (APCs) and T cells. Previous studies indicated that CD2 promotes T-cell receptor (TCR) signaling when it is engaged by its ligands displayed on APCs. However, the supporting experimental data were rather controversial, and there is no general agreement about the role of CD2 in T cell activation. To study the function of CD2 and its ligands in T cells, we examined T cell functions in newly generated mouse strains lacking CD2 or CD48 in the C57BL/6 background. Compared to wild-type (WT) mice, T cells from CD2-deficient (“knock-out”; KO) mice had severe activation defects. Surprisingly, expression of CD48 on T cells, not on APCs, was also necessary for optimal T cell responses. We found evidence of CD2 interacted with CD48 in cis on T cells and observed their co-localization by confocal microscopy and fluorescence resonance energy transfer (FRET). The only exception was CD2-dependent cytotoxicity, which required CD48 both on T cells and on APCs. Mechanistic studies using mass spectrometry and structure-function analyses revealed that the cis interactions between CD2 and CD48 on T cells boosted TCR signaling, an effect that correlated with the capacity of CD2 to recruit the kinase Lck. Similarly, our further study revealed that the cis interactions between CD2 and CD58 on human T cells were also necessary for maximal TCR signaling and T cell activation. Taken together, our studies provide clear evidence that cis interactions between CD2 and its ligands on T cells are important in TCR signaling and T cell activation. Modulation of these cis interactions can be a promising approach to suppress or enhance T cell activation in a therapeutic setting. / CD2 est une molécule transmembranaire et un membre “ non-canonique ” de la famille de la famille SLAM (« signaling lymphocyte activation molecule ») exprimée à la surface des lymphocytes T et des cellules NK (« natural killer »). Les ligands de CD2, CD48 chez la souris et CD58 chez l’humain, sont exprimés de manière ubiquitaire sur les cellules hématopoïétiques, y compris sur les cellules présentatrices d’antigène (CPA) et lymphocytes T. Des études antérieures ont indiqué que CD2 est impliqué dans la signalisation des récepteurs TCR (« T-cell receptor ») en réponse à son engagement par CD48 sur le CPA; cependant, les données expérimentales qui supportent ce modèle sont plutôt contradictoires et aucun accord n’a été trouvé sur les rôle de CD2 dans l’activation de lymphocytes T. Pour étudier la fonction de CD2 et ses ligands, nous avons examiné les fonctions des lymphocytes T chez des souches de souris dépourvues de CD2 ou CD48 nouvellement générées à partir du “fond génétique” C57BL/6. Par rapport aux souris de type sauvage (WT; « wild-type »), les lymphocytes T de souris CD2-déficientes (« knock-out »; KO) présentent des sévères défauts d’activation. Il est intéressant de noter que l’expression de CD48 sur les lymphocytes T, mais non sur les CPA, était aussi nécessaire pour les réponses des lymphocytes T. Nous avons également démontré que CD2 interagit en cis avec CD48 sur les cellules T et avons observé leur co-localisation par microscopie confocale et FRET (« fluorescence resonance energy transfer) ». La seule exception était la cytotoxicité CD2- dépendante, qui nécessitait l’expression de CD48 à la fois sur les lymphocytes T et sur les CPA. L’étude des mécanismes par la spectrométrie de masse et les analyses structurefonction ont démontré que les interactions en cis entre CD2 et CD48 permettent de stimuler la signalisation du TCR, ce qui corrèle avec la capacité de CD2 à recruter la kinase Lck. De manière similaire, notre étude plus approfondie a démontré que les interactions en cis entre CD2 et CD58 sur les lymphocytes T humains sont nécessaires pour la signalisation maximale du TCR et l’activation cellulaire T. L’ensemble de nos études ont mis en évidence que les interactions en cis entre CD2 et ses ligands sur les lymphocytes T jouent un rôle important dans la signalisation du TCR et l’activation de ces cellules. La modulation de ces interaction en cis pourrait être une approche potentielle pour augmenter ou interférer avec l’activation des lymphocytes T dans un contexte thérapeutique.

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001–2013) with either rituximab (R-RIC-9%) or nonrituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1–77.3) and 43.2 months (range 0.3–179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study.

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