Mehr Interaktion als geplant: Friedenseinsätze und Organisierte Kriminalität in fragilen Staaten

Fragile Staatlichkeit rangiert zu Recht hoch auf der Problemliste der internationalen Gemeinschaft. Während viele Herausforderungen schwacher Staaten erkannt sind, wird die Bedeutung der Organisierten Kriminalität und ihrer Verflechtungen mit lokalen und internationalen Akteuren noch oft unterschätzt. Gerade für VN-Friedenseinsätze, die zunehmend in fragilen Staaten operieren, wird häufig erst während der Mandatsumsetzung klar, wie sehr sie sich mit diesem Phänomen befassen müssen. Anhand konkreter Einsatzerfahrungen der Vereinten Nationen in Westafrika, Kosovo und Haiti untersucht Wibke Hansen die Schnittstellen zwischen Friedenseinsätzen und Organisierter Kriminalität. Dabei wird deutlich, dass die Auseinandersetzung mit Organisierter Kriminalität für Peacebuilding- und Statebuilding-Prozesse erfolgskritisch sein kann. Die Autorin schließt ihre policy-orientierte Arbeit mit Empfehlungen für einen strategischeren Umgang mit Organisierter Kriminalität im Kontext von Friedenseinsätzen. <br/

Missions in a changing world: the Bundeswehr and its operations abroad

Military operations abroad by the German Armed Forces are always a con­troversial instrument of German crisis management. Yet, such foreign deployments are likely to remain necessary for the foreseeable future while, at the same time, they are undergoing noticeable change. The conditions shaping this transformation can be captured in three dimensions of change: the change in war and violent conflict; the transformation of the inter­national political and legal context; and the shifting institutional frame­works for these operations. German policy-makers must address the related challenges - whether setting normative anchors and formats for operations, contributing to sta­bilisation in a context of continuing insecurity, building partners’ military capacities, dealing with transnational threats or using benchmarks for exiting. Yet, they only have limited influence over the described changes. Fundamentally, decisions about military operations abroad are taken within the triangle of pressing problems (crises and conflicts), responsibility (obli­gations under international law, alliances, political commitments), and the political situation and available capabilities in Germany itself. It is hard to predict the developments which will dictate the scope for action within this triangle. However, the worst possible approach would be to address the described challenges only from a short-term and ad-hoc perspective, especially since they do not exclusively concern operations abroad. In its 2017 Guidelines on crisis prevention and conflict resolution and 2016 White Paper, the German federal government outlined a frame­work for German engagement that it now has to fill. Furthermore, the expectations of Germany's partners within the EU, NATO and UN have grown - which will also require further military contributions. (author's abstract

Die Auslandseinsätze der Bundeswehr im Wandel

Die Auslandseinsätze der Bundeswehr sind ein immer wieder kontrovers diskutiertes Instrument des deutschen Krisenmanagements. Wie in einem Brennglas lassen sich an den Diskussionen die "Reifungsprozesse" sowie die Bruchlinien deutscher, europäischer und transatlantischer Sicherheitspolitik ablesen. Zwar dürften Auslandseinsätze noch lange notwendig bleiben, sie sind jedoch einem erkennbaren Wandel unterworfen. Die Rahmenbedingungen für ihre Weiterentwicklung lassen sich entlang von drei Dimensionen nachzeichnen: dem Wandel des Kriegsgeschehens, den Veränderungen des internationalen politischen und rechtlichen Kontexts sowie schließlich dem Wandel des institutionellen Rahmens für diese Einsätze. Mit all diesen Herausforderungen muss die deutsche Politik umgehen und kann gleichzeitig nur begrenzt Einfluss auf den beschriebenen Wandel nehmen. Grundsätzlich werden Entscheidungen über Auslandseinsätze in einem Dreieck aus Problemdruck (Krisen und Konflikte), Verantwortung (völkerrechtliche Verpflichtungen, Bündnisse, politische Bindungen) sowie der politischen Situation und Stimmung in Deutschland selbst getroffen. Die Entwicklungen, welche die Handlungsspielräume in diesem Dreieck bestimmen, mögen schwer abzusehen sein. Doch die schlechteste aller Lösungen wäre, sich nur anlassbezogen und kurzfristig mit den beschriebenen Herausforderungen auseinanderzusetzen, zumal sie nicht allein Auslandseinsätze betreffen. Mit den Leitlinien zum Krisenmanagement von 2017 und dem Weißbuch 2016 hat die Bundesregierung einen Rahmen für das deutsche Engagement gesetzt, den es nun zu füllen gilt. Zudem sind die Erwartungen der Partner Deutschlands in EU, Nato und UNO größer geworden, was auch weitere militärische Beiträge erfordern wird. (Autorenreferat

Countdown im Sudan: Zwischen Kompromiss und Krieg - Szenarien bis 2011

Wibke Hansen; Annette Webe

Combination of nanoparticle-based therapeutic vaccination and transient ablation of regulatory T cells enhances anti-viral immunity during chronic retroviral infection.

Regulatory T cells (Tregs) have been shown to limit anti-viral immunity during chronic retroviral infection and to restrict vaccine-induced T cell responses. The objective of the study was to assess whether a combinational therapy of nanoparticle-based therapeutic vaccination and concomitant transient ablation of Tregs augments anti-viral immunity and improves virus control in chronically retrovirus-infected mice. Therefore, chronically Friend retrovirus (FV)-infected mice were immunized with calcium phosphate (CaP) nanoparticles functionalized with TLR9 ligand CpG and CD8(+) or CD4(+) T cell epitope peptides (GagL85-93 or Env gp70123-141) of FV. In addition, Tregs were ablated during the immunization process. Reactivation of CD4(+) and CD8(+) effector T cells was analysed and the viral loads were determined

Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection

T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP) nanoparticle (NP)-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I) are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8+ T cells (CTL) and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR−/−) or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections

data_sheet_1_Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8+ T Cell Responses During Chronic Retroviral Infection.PDF

<p>T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP) nanoparticle (NP)-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8⁺ T cell response and improve the eradication of virus infected cells. However, the mechanisms underlying this effect were largely unclear. While type I interferons (IFNs I) are considered to drive T cell exhaustion by persistent immune activation during chronic viral infection, we here describe an indispensable role of IFN I induced by therapeutic vaccination to efficiently reinforce cytotoxic CD8⁺ T cells (CTL) and improve control of chronic retroviral infection. The induction of IFN I is CpG dependent and leads to significant IFN signaling indicated by upregulation of IFN stimulated genes. By vaccinating chronically retrovirus-infected mice lacking the IFN I receptor (IFNAR^−/−) or by blocking IFN I signaling in vivo during therapeutic vaccination, we demonstrate that IFN I signaling is necessary to drive full reactivation of CTLs. Surprisingly, we also identified an impaired suppressive capability of regulatory T cells in the presence of IFNα, which implicates an important role for vaccine-induced IFNα in the regulation of the T cell response during chronic retroviral infection. Our data suggest that inducing IFN I signaling in conjunction with the presentation of viral antigens can reactivate immune functions and reduce viral loads in chronic infections. Therefore, we propose CaP NPs as potential therapeutic tool to treat chronic infections.</p

A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern

BACKGROUND:: The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable and mutations have been described in syndromatic cases. OBJECTIVE:: To conduct a meta-analysis of genome-wide association studies (GWAS) to identify common genetic variants influencing ERP. METHODS:: We ascertained ERP based on electrocardiograms in three large community-based cohorts from Europe and the US: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed GWAS in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached p=1x10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages. RESULTS:: Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9\ub18.9 years, 30.3\% women; ERP negative: 47.5\ub19.4 years, 54.2\% women). After meta-analysis, eight single nucleotide polymorphisms reached p=1x10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95\% confidence interval 0.36-0.61; p=6.9x10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95\% confidence interval 1.25-1.69; p=8.5x10(-7)). In the replication step (7151 individuals), none of the eight variants replicated, and combined meta-analysis results failed to reach genome-wide significance. CONCLUSIONS:: In a GWAS, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations