229 research outputs found

    The formation of Croatian national identity: a centuries-old dream?

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    This volume assesses the formation of Croatian national identity in the 1990s. It develops a novel framework calling into question both primordial and modernist approaches to nationalism and national identity before applying that framework to Croatia. In doing so it provides a new way of thinking about how national identity is formed and why it is so important. An explanation is given of how Croatian national identity was formed in the abstract, via a historical narrative that traces centuries of yearning for a national state. The book shows how the government, opposition parties, dissident intellectuals and diaspora groups offered alternative accounts of this narrative in order to legitimise contemporary political programmes based on different visions of national identity. It then looks at how these debates were manifested in social activities as diverse as football and religion, economics and language. This volume marks an important contribution to both the way we study nationalism and national identity, and our understanding of post-Yugoslav politics and society

    The formation of Croatian national identity: A centuries-old dream?

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    This volume assesses the formation of Croatian national identity in the 1990s. It develops a novel framework calling into question both primordial and modernist approaches to nationalism and national identity before applying that framework to Croatia. In doing so it provides a new way of thinking about how national identity is formed and why it is so important. An explanation is given of how Croatian national identity was formed in the abstract, via a historical narrative that traces centuries of yearning for a national state. The book shows how the government, opposition parties, dissident intellectuals and diaspora groups offered alternative accounts of this narrative in order to legitimise contemporary political programmes based on different visions of national identity. It then looks at how these debates were manifested in social activities as diverse as football and religion, economics and language. This volume marks an important contribution to both the way we study nationalism and national identity, and our understanding of post-Yugoslav politics and society

    Globalisation, Security and International Order after September 11

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    Although there is some agreement about the sorts of underlying forces that gave rise to the events of September 11, the theoretical and policy implications that flow from them remain contentious - the US's overwhelmingly military response notwithstanding. In contrast to much of the orthodoxy that characterises contemporary theoretical and policy debates, we argue that there should be a recognition that the pursuit of security is a complex, multi-dimensional enterprise. We contend that unless security studies and practice begins to incorporate a more complex understanding of the contemporary international system, it will continue to be incapable of addressing many of the potential threats that confront even the most powerful states. The first part of this paper looks at the contested notion of 'globalisation', and the way that international society has been conceptualised in both the conventional security studies/international relations literature, and in the field of international political economy (IPE). The second part of the paper looks at the continuing influence of state-centric security discourses and highlights their inability to provide a conceptual framework for security provision in a global era

    Reconsidering the Cases of Humanitarian Intervention

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    Justice Beyond Borders? Australia and the International Criminal Court

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    The International Criminal Court (ICC) came into being on 1 July 2002. A four-person team opened an office in The Hague and will collect reports and allegations of genocide, war crimes and crimes against humanity until judges and a prosecutor are appointed towards the end of 2003. Although the court was heralded by many states and international lawyers as the most important positive development in international law since the formation of the United Nations, it did not get off to an auspicious start. The Bush administration was concerned that US military forces operating overseas would be particularly vulnerable to what it described as 'politicised' prosecutions. It therefore insisted that not only would it not be a part of the ICC, but also that it would not sanction the continuation of UN peacekeeping operations. Closer to home, the Australian Senate only ratified the ICC's founding treaty, the Rome Statute, after a bitter debate that split both the Liberal and National parties. This was the case even though the Howard government-and Foreign Minister Alexander Downer in particular-had been a leading advocate of the court and ratification of the Rome Statute had been a Liberal Party election promise in 2001. The cost that Downer, and pro-ICC Attorney-General Daryl Williams had to pay in order to appease restive conservative backbenchers, the National Party, and an increasingly reluctant (and pro-US) Prime Minister and secure the ratification was a declaration that reaffirmed the primacy of the Australian judicial system over the ICC. The declaration insisted that no Australian would be prosecuted by the court without the consent of the Attomey-General, and asserted Australia's right to define what is meant by the crimes of genocide, war crimes, and crimes against humanity. We argue that although Downer and Williams should be commended for their commitment to international justice, the declaration attached to Australia's ratification was unnecessary and unhelpful. The first and third aspects of the declaration were unnecessary: the principle of complementarity enshrined in the Rome Statute means that the ICC already recognises the primacy of domestic jurisdiction, and the crimes covered are already considered to fall under universal jurisdiction, as the Nuremberg, Tokyo and more recent Pinochet trials showed (see Weller 1999). The second is unhelpful because it contravenes both the letter and the spirit of the Rome Statute. We will begin, then, by tracing the development of the ICC debate in Australian politics. In 1998, the government was an enthusiastic advocate of the court but by 2002 an alliance of an ardently pro-US Prime Minister, vocal right-wing parliamentarians and their supporters, and The Australian (and its foreign affairs editor Greg Sheridan in particular) combined to put ratification in doubt. Contrary to Prime Minister John Howard's claims, this debate was not well informed. Instead, it was characterised by hearsay, inaccuracy and scare-mongering. The subsequent section of the article demonstrates this by focusing on the background to, and creation of, the Rome Statute

    Evolving norms of protection: China, Libya and the problem of intervention in armed conflict

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    This article examines the influence of civilian protection norms on China’s response to the 2011 crisis in Libya. It argues that Responsibility to Protect—an emerging norm commonly associated with the Libyan case—did not play a major role in China’s abstention on Resolution 1973 (2011) authorizing international intervention in Libya. For China, Responsibility to Protect is merely a concept and could not serve as the basis for intervention. Instead, Protection of Civilians in Armed Conflict, as a normative foundation for civilian protection endorsed by China, offers a more appropriate lens for understanding China’s vote. Protection of Civilians, however, does not accommodate China’s unprecedented evacuation of Chinese nationals from Libya. This operation proceeded from a third logic of Protection of Nationals Abroad, which poses dilemmas for China’s strict adherence to the principles of sovereignty and non-interference and brings to bear domestic interests and notions of protection

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

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    Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

    Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

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    CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology
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