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This article argues that, since the turn of the twenty-first century, fiction in Canada – whether by English-Canadian, Québécois, or Indigenous writers – has seen a re-emergence in the apocalyptic genre. While apocalyptic fiction also gained critical attention during the twentieth century, this initial wave was tied to disenfranchised, marginalized figures, excluded as failures in their attempts to reach a promised land. As a result, fiction at that time – and perhaps equally so in the divided English-Canadian and Québécois canons – was chiefly a (post)colonial, nationalist project. Yet, apocalyptic fiction in Canada since 2000 has drastically changed. 9/11, rapid technological advancements, a growing climate crisis, the Truth and Reconciliation Commission: these changes have all marked the fictions of Canada in terms of futurities. This article thus examines three novels – English-Canadian novelist Emily St. John Mandel’s Station Eleven (2014), Indigenous writer Thomas King’s The Back of the Turtle (2014), and Québécois author Nicolas Dickner’s Apocalypse for Beginners (2010) – to discuss the ways in which they work to bring about the destruction of nationalism in Canada through the apocalyptic genre and affectivity to envision new futures.

The development of neutralizing FVIII antibodies is the most serious complication of hemophilia A treatment. The currently known patient- and treatment-related risk factors for inhibitor development do not accurately predict this adverse event in all patients. The composition of the gut microbiota has been shown to influence immune-mediated diseases at distant anatomical sites (eg, lungs, brain, and joints). We demonstrate that a disrupted gut microbiota can be created in a mouse model of hemophilia A using a broad-spectrum antibiotic. Under controlled conditions, this sustained dysbiosis was associated with an increase in splenic B cells and the development of higher titer, FVIII-specific immunoglobulin G antibodies after FVIII challenge. Splenic and mesenteric lymph node cytokines, T cells, and dendritic cells were unaffected before administration of FVIII. However, the immune transcriptome of both aforementioned secondary lymphoid organs was significantly modified. Short-chain fatty acids (SCFAs), which are immunomodulatory microbial metabolites, were depleted in cecal contents of the dysbiotic mice. Furthermore, supplementation of the drinking water with butyrate, the most immunologically active SCFA, successfully achieved attenuation of the FVIII immune response. Collectively, data from this exploratory study suggest that the composition of the gut microbiota alters the FVIII immune response via the action of specific microbial metabolites on the immune cell transcriptome and that oral supplementation with butyrate effectively reduces the FVIII immune response.

Jaime Lannister is one of the most intriguing characters in HBO’s Game of Thrones due to his important role in the show’s chief area of conflict, King’s Landing, as well as his incestuous relationship with his sister and, because of this relationship, her strong influence on his character. What makes the dynamic of Jaime and Cersei’s relationship so compelling is the manner in which Cersei’s influence on Jaime seems to grow weaker or stronger depending on where he is travelling in Westeros, how far away he is from her, both physically and emotionally, and which characters he spends time with during these travels. An effective means of analyzing Jaime’s moral development in relation to his relationship with his sister is by way of affect theory—specifically the affect of proximity, which authors such as Sara Ahmed and Lauren Berlant discuss in The Promise of Happiness (2010) and Cruel Optimism (2011), respectively. By mapping out Jaime’s travels during the series, as well as through close reading of several key moments of his journey, I argue that Jaime’s ever-changing “affective proximity” to Cersei strongly affects his moral character, ultimately resulting in his heading to Winterfell to help fight the last war.

Anti-drug antibody formation following factor VIII (FVIII) replacement therapy is the most important treatment-related complication in patients with severe haemophilia A. A significant number of these antibodies show neutralising activity against FVIII and are referred to as FVIII inhibitors. Alloimmunity to FVIII, given the absence of endogenous circulating FVIII protein, may be predictable to some extent; however, only 30% of patients develop inhibitors. Genetic and environmental risk factors have been identified, contributing to the likelihood of inhibitor development. Multiple immunological theories have been proposed which in part explain the outcomes of many epidemiological studies. Significant differences exist among replacement therapies, including the source, FVIII sequence, glycosylation, formulation components, impurities and aggregation potential, which significantly complicate interpretation of the results from these studies. In this review, we present recent advances in the understanding of the cellular mechanisms of inhibitor formation and highlight some areas of uncertainty requiring further investigation.