Negotiating Uncertainty in the Right to Asylee Status

The asylum system regards asylum seekers as actors with privilege and resources, and expects them to present sound cases documenting their rights to asylee status. However, the asylum system fails to consider the lack of autonomy of asylum seekers, as they must manage trauma, lack of resources, new host societies, and the asylum process. Based on interviews (n=14) with asylum seekers, general findings reveal that inherent barriers within the asylum system position asylum seekers into a context of insecurity that undermines their agency and ability to achieve asylee status. The examination of asylum seekers interacting with the United States asylum system offers a unique vantage point for exploring the relationship between structure and agency. Asylum seekers’ agency is theoretically reconfigured in an inclusive abstract action model that validates their negotiation process in mitigating vulnerability from persecution through the asylum process. However, due to asylum seekers limited agency and the structural barriers involved in attaining asylee status, structure is theorized as minimizing agency aims. I propose a revised concept of agency to account for asylum seekers’ uncertainty in securing asylee statu

Refugees, Sexual Violence, and Armed Conflict: The Nuances between Victims and Agents

The examination of forced migration of political refugees from sexual violence in armed conflict offers a unique vantage point for exploring the relationship between structure and agency. While it is significant to acknowledge the lack of autonomy accessible to political refugees, simultaneously, it is problematic to assume that their actions do not qualify as agency. I argue that it is possible on one hand to address the lack of agency related to the imposed structure, while on the other hand, to theorize marginalized actors’ form of agency based on their ability to actively negotiate forced conditions in order to secure their own and their families’ safety. This theoretical shift in re-conceptualizing agency from the perspective of political refugees reveals that despite, international human rights efforts, in practice these policies may deter and marginalize refugees. Inherent gender bias and exclusion in human rights agendas serve to undermine the rights and security of refugees. Incorporating refugees’ experiences negotiating conditions of violence facilitates the ability to critique and transform Western perspectives of human rights, particularly deterrent measures and individual-responsibility policies that require refugees to provide justification of their rights to security

Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System

Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia

Genetic errors of immunity distinguish pediatric non-malignant lymphoproliferative disorders

Background Pediatric non-malignant lymphoproliferative disorders (PLPD) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD. Objective The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes. Methods PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant EBV infection. Fifty-one subjects from 47 different families with PLPD were analyzed using whole exome sequencing (WES). Results WES identified likely genetic errors of immunity in 51% to 62% of families (53% to 65% of affected children). Presence of a genetic etiology was associated with younger age and hemophagocytic lymphohistiocytosis. Ten-year survival for the cohort was 72.4%, and patients with viable genetic diagnoses had a higher survival rate (82%) compared to children without a genetic explanation (48%, p = 0.03). Survival outcomes for individuals with EBV-associated disease and no genetic explanation were particularly worse than outcomes for subjects with EBV-associated disease and a genetic explanation (17% vs. 90%; p = 0.002). Ascertainment of a molecular diagnosis provided targetable treatment options for up to 18 individuals and led to active management changes for 12 patients. Conclusion PLPD therefore defines children with high risk for mortality, and WES informs clinical risks and therapeutic opportunities for this diagnosis