Search

10.1080/03071847.2012.733104-F0001 10.1080/03071847.2012.733104-F0002 An AMISOM (African Union Mission in Somalia) soldier on duty at the front line at Maslah after a night of heavy fighting agains...

RESOLUTION 1973 (17 MARCH 2011) WAS THE FIRST TIME THE UNITED NATIONS Security Council authorized the use of military force for human protection purposes against a functioning de jure government. As such, it represents a significant development in the international politics of military force. But what are its likely consequences and how did it come about? We submit that Resolution 1973 and the subsequent enforcement operations, Odyssey Dawn and Unified Protector, were partly facilitated by the developing principle and practice of the Responsibility to Protect (R2P). Despite an increasing number of rhetorical commitments made by international institutions and many governments to prevent mass atrocities in the post--Cold War era, the use of force for human protection purposes remained severely constrained by principled objections rooted in international law and moral differences, the low political payoffs and potentially grave risks associated with humanitarian war, and the combination of difficult operational dilemmas and an absence of clear guidance about the strategies and tactics most likely to have positive effects in different circumstances. (1) Historically, these obstacles coalesced to produce a default policy environment that was strongly averse to the use of force to prevent or end the commission of genocide, war crimes, ethnic cleansing, or crimes against humanity (hereafter, genocide and mass atrocities). We submit that R2P has helped mitigate these three types of constraints, albeit unevenly, making UN-authorized humanitarian military intervention both politically possible in Libya and more likely in other similar cases. (2) First, R2P has largely resolved principled debate about whether international society should become engaged in such crises and replaced it with debates about how to best protect populations from grave abuses. Within international society, this principle is underscored by a widely shared understanding of the need for Security Council authorization for any use of military force. Second, R2P has helped to change international political calculations by establishing shared expectations and common interests, though of course national interests and domestic politics continue to shape decisions about using force. Third, it has provided a catalyst for more creative thinking about operational issues, most notably supporting moves toward using a broader range of measures to coerce and induce behavioral change and deepening understanding of the range of potential military measures and associated pitfalls. Nevertheless, while agreement on principles is important, reaching consensus on how to consistently apply those principles in response to specific cases is far more difficult, as the case of Syria in 2012 demonstrates only too well. (3) Moreover, while the use of force to protect populations from genocide and mass atrocities has become more likely, it is still rare and is likely to remain so for the foreseeable future. (4) To substantiate these claims, we begin this article by summarizing the road to the use of force in Libya, focusing on the forging of international consensus around Resolution 1973. Next, we contextualize Resolution 1973 by outlining the main principled, political, and prudential obstacles to using force for human protection purposes. In the final section, we revisit these obstacles and explore R2P's role in reshaping the way they are conceptualized and, in turn, the politics of using force to protect populations from genocide and mass atrocities. Libya: The Road to Humanitarian War On 19 March 2011, military forces from France, Canada, the United Kingdom, and the United States struck the air defenses and soldiers of Muammar Gaddafi's regime in Libya. These countries led a coalition of states with the expressed aim of enforcing the objectives set out by UN Security Council Resolution 1973, principally the operation of a no-fly zone over Libya, imposition of an arms embargo, and the protection of civilians on the ground. …

This article examines the UN mission in Côte d’Ivoire (UNOCI) by applying the framework set out by Paul Diehl and Dan Druckman. It does so in two main parts. The first describes the course and direction of UNOCI until the end of 2011. The second applies elements of the Diehl-Druckman framework to evaluate UNOCI. It argues that two particular issues stand out from the UNOCI case, and are reflected in the title of this essay. First, that in considering the evaluation of peacekeeping missions, the mandate itself needs to be front and centre and more thought needs to be given to the attribution of responsibility when the mandate calls for peacekeepers to ‘assist’ others. Second, peace processes involve multiple foreign actors and UN peace operations are only one part of the puzzle. Overlapping mandates and complex partnerships are becoming a more common feature of UN peace operations. Accounting for these in the evaluation of missions is one of the key challenges for the future.

C Couch, T Franxman, M Greenhawt. Ann Allergy Asthma Immunol. 2017;118(5):591–596.e3 To show characteristics and outcomes of oral food challenges (OFCs) in patients with tree nut (TN) sensitization with or without documented tree nut allergy and to help understand the relation between tree nut sensitization (by skin prick testing [SPT] and specific immunoglobulin E [sIgE]) and OFC outcomes. All open TN OFCs conducted at the University of Michigan Allergy and Immunology clinics between 2007 and 2015. Patients included in the study had a mean age of 4.5 years. Patients who had TN SPT and or …

In March 2011, the UN Security Council authorized the use of force to protect civilians in Libya. This was the first time that the Council has ever authorized the invasion of a functioning state for such purposes. International society's relatively decisive responses to recent crises in Cote d'Ivoire and Libya has provoked significant commentary, suggesting that something has changed about the way the world responds to violence against civilians. Focusing on these two cases, this article examines the changing practice of the UN Security Council. It argues that we are seeing the emergence of a new politics of protection, but that this new politics has been developing over the past decade. Four things are new about this politics of protection: protecting civilians from harm has become a focus for international engagement; the UN Security Council has proved itself willing to authorize the use of force for protection purposes; regional organizations have begun to play the role of ‘gatekeeper’; and major powers have exhibited a determination to work through the Security Council where possible. However, the cases of Cote d'Ivoire and Libya also help to highlight some key challenges that might halt or reverse progress. Notably, states differ in the way they interpret mandates; questions are being asked about the UN's authority to act independently of specific Security Council authorizations; the overlap of regional organizations sometimes sends conflicting messages to the Security Council; and there remains a range of difficult operational questions about how to implement protection mandates. With these in mind, this article concludes with some suggestions about how the future challenges might be navigated in order to maintain the progress that has been made in the past decade.

Advocates of moral hazard theory argue that the ‘responsibility to protect’ causes genocidal violence that would not otherwise occur. After summarizing the main elements of the moral hazard approach, this article demonstrates that there is no empirical evidence to support the general claim that the ‘responsibility to protect’ is a remote cause of genocide. This is followed by an analysis of the conflicts in Bosnia, Kosovo and Darfur which demonstrates that moral hazard does not provide a plausible account of the proximate causes of genocidal violence in these cases. We suggest that a major part of the explanation for why moral hazard theory performs so badly is its reductionist account of the dynamics of armed conflict and its simplistic understanding of the dynamics of provocation.

In bladder cancer, increased caveolin-1 (Cav-1) expression and decreased Src expression and kinase activity correlate with tumor aggressiveness. Here, we investigate the clinical and functional significance, if any, of this reciprocal expression in bladder cancer metastasis. We evaluated the ability of tumor Cav-1 and Src RNA and protein expression to predict outcome following cystectomy in 257 patients enrolled in two independent clinical studies. In both, high Cav-1 and low Src levels were associated with metastasis development. We overexpressed or depleted Cav-1 and Src protein levels in UMUC-3 and RT4 human bladder cancer cells and evaluated the effect of this on actin stress fibers, migration using Transwells, and lung metastasis following tail vein inoculation. Cav-1 depletion or expression of active Src in metastatic UMUC-3 cells decreases actin stress fibers, cell migration, and metastasis, while Cav-1 overexpression or Src depletion increased the migration of nonmetastatic RT4 cells. Biochemical studies indicated that Cav-1 mediates these effects via its phosphorylated form (pY14), whereas Src effects are mediated through phosphorylation of p190RhoGAP and these pathways converge to reduce activity of RhoA, RhoC, and Rho effector ROCK1. Treatment with a ROCK inhibitor reduced UMUC-3 lung metastasis in vivo, phenocopying the effect of Cav-1 depletion or expression of active Src. Src suppresses whereas Cav-1 promotes metastasis of bladder cancer through a pharmacologically tractable common downstream signaling pathway. Clinical evaluation of personalized therapy to suppress metastasis development based on Cav-1 and Src profiles seems warranted. Cancer Res; 71(3); 832–41. ©2010 AACR.

Although the Member States of the United Nations (UN) unanimously endorsed the 'responsibility to protect' (R2P) principle in October 2005, debates continue about its scope, potential impact and how it might be operationalised. This article examines one strand of the wider efforts to turn the responsibility to protect into a workable international agenda, namely, the 'responsibility not to veto'. This is the idea that the permanent five members of the UN Security Council (P5) should agree not to use their veto power to block action in response to genocide and mass atrocities which would otherwise carry a majority in the Council and where their own vital security interests are not engaged. It has been promoted in a variety of international forums for nearly a decade but has not been adopted by the P5. We argue that this idea deserves support although we acknowledge that it addresses only one part of the wider conundrum of preventing mass atrocities. Its primary limitation is that the problem veto abstention is designed to solve – situations where potential rescuers are blocked by a (threat of ) P5 veto – has been a rare occurrence in contemporary world politics. The more common scenario has been that cases of mass atrocities have not generated sufficient political will to mobilise an international military response. Consequently, the responsibility not to veto must form part of a broader range of R2Pfriendly measures to help prevent mass atrocities and rescue their victims should they occur.

Introduction: Recurrent somatic alterations associated with pediatric, childhood, and young adult cancers have not been as intensively studied as those associated with adult cancers. Consequently, whole-exome and transcriptome approaches are still being used to support discovery efforts. However, due to several initiatives aimed at profiling genomic alterations associated with childhood cancers, a set of recurrent somatic alterations has been defined. To accelerate research in this area, we have developed a novel targeted next-generation sequencing (NGS) assay to detect relevant somatic alterations previously reported in these cancer types. Methods: The assay was developed using Ion AmpliSeq targeted sequencing technology to cover the major gene variants associated with childhood cancers, including both solid tumor and hematologic cancer types. Over 200 gene targets were included on the basis of consultation with expert pediatric oncologists, literature review of the recent pediatric cancer genomic publications, as well as inclusion of relevant markers from adult cancers that are also observed in childhood cancers. Variant classes include mutations, copy number variations, gene fusions, and gene expression. Mutations in 130 genes, copy number variants in 28 genes, and over 1,400 distinct fusion isoforms in 88 fusion driver genes are analyzed. Variant calling algorithms for both DNA and RNA were optimized and combined into a single Ion Reporter workflow. Results: The assay generated an average read depth of >3,000 reads per DNA amplicon with high uniformity (>95%), when up to 7 sample DNA-RNA pairs were analyzed with the 540 chip of the Ion S5 sequencing instrument. Minimal allele frequency detected for key hotspots was 5%. Sensitive and reproducible detection of CNV and fusion variants associated with pediatric solid tumors (EWSR1-FL1 and KIAA1549-BRAF fusions, MYC and EGFR amplification) and hematologic cancers (ETV6-RUNX1 and PML-RARA fusions) was demonstrated in orthogonally profiled FFPE, blood, and bone marrow samples. Performance was robust across sample types. Similar results were observed with manual and automated library preparation. Conclusions: A novel NGS assay, designed specifically for pediatric, childhood, and young adult cancers, and capable of detecting relevant DNA and RNA alterations from the same sample, was developed and validated. The assay is useful for characterizing relevant alterations in a wide range of cancers, including childhood leukemias and lymphomas as well as solid tumors including neuroblastoma, rhabdomyosarcoma, retinoblastoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and brain and spinal cord tumors. A review of the analytical studies will be presented. Citation Format: Nickolay A. Khazanov, Chaitali Parikh, Habib Hamidi, Scott P. Myrand, Efren Ballesteros-Villagrana, Jingwei Ni, Paul D. Williams, Karen L. Clyde, Dinesh Cyanam, Armand Bankhead, III, Manimozhi Manivannan, Mark Tomilo, Susan Ewald, Jon K. Sherlock, Janice K. Au-Young, Jaclyn Biegel, Jonathan Buckley, Matthew Hiemenz, Dejerianne Ostrow, Alex Judkins, Xiaowu Gai, Tracy Busse, Alan Wayne, Deepa Bhojwani, Raca Gordana, Matthew Oberley, David Parham, Seth Sadis, Timothy Triche. Development of a next-generation sequencing (NGS) assay for pediatric, childhood, and young adult cancer research with comprehensive DNA and RNA variant detection [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr B45.

Title: Analytical performance of a novel next generation sequencing assay for myeloid cancers Nick Khazanov, Wally Zhang, Dinesh Cyanam, Scott P. Myrand, Denis Kaznadzey, Paul Williams, Vinay Mittal, Dan Mazur, Sihong Chen, Jason Wustman, Efren Ballesteros-Villagrana, Goutam Nistala, Jon Sherlock, Michael Hogan, Jim Veitch, John Bishop, Seth Sadis Introduction: Myeloid malignancies contain a diverse and heterogeneous set of genomic alterations that include recurrent somatic mutations in key driver genes as well as frequent and diagnostic chromosomal rearrangements that generate a wide array of gene fusion products. To support clinical and translational research into precision oncology strategies for myeloid cancers, a next-generation sequencing (NGS) assay was generated to detect common and relevant somatic alterations. Methods: To define gene targets that were recurrently altered in myeloid cancers and relevant for clinical and translational research, an extensive survey of investigators at hematology oncology research labs was performed. The gene targets identified by researchers were complemented by a comprehensive survey of literature and genomic databases. Clinical guidelines for myeloid diseases in the US and in Europe were reviewed to ensure representation of relevant alterations. A targeted Ion AmpliSeq panel was generated to support the detection of recurrent single-nucleotide variants, insertions/deletions, and gene fusions from blood or bone marrow samples. The panel was developed for manual or automated library preparation and sequencing on the Ion Torrent PGM or Ion S5 instruments. Results: The Oncomine™ Myeloid Research Assay gene panel included 58 genes and generated an average read depth of >2,000 reads per targeted amplicon with an average uniformity of >95%. Important GC-rich targets such as CEBPA generated sufficient balanced read depth to support variant detection. A cohort of samples positive for FLT3 alterations was analyzed and successful detection of FLT3-internal tandem repeat variants was demonstrated. Several gene fusion transcripts common to myeloid cancers were detected. Comparable results were observed on Ion Torrent PGM and Ion S5 instruments. Conclusions: A novel myeloid specific NGS assay capable of detecting relevant DNA and RNA alterations from the same sample was developed. The assay is useful for characterizing relevant alterations in a range of myeloid diseases including acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, chronic myelogenous leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia. A review of the analytical studies will be presented. Citation Format: Nickolay Khazanov, Wally Zhang, Dinesh Cyanam, Scott P. Myrand, Denis Kaznadzey, Paul D. Williams, Vinay Mittal, Daniel J. Mazur, Sihong Chen, Jason Wustman, Efren Ballesteros-Villagrana, Goutam Nistala, Santhoshi Bandla, Jim Veitch, Jon Sherlock, John Bishop, Seth Sadis. Analytical performance of a novel next generation sequencing assay for myeloid cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3863.

The study tested the hypothesis that reduced intravaginal implant progesterone (P(4)) concentration to synchronise oestrus would increase pregnancy rates to fixed-time artificial insemination (FTAI) in Bos indicus heifers. Brahman heifers (n = 294; 2 year) were body condition scored (BCS), weighed and scanned for presence of a corpus luteum (CL). Only cyclic heifers were selected and allocated randomly within BCS and 25 kg bodyweight category to one of three P(4) treatment groups. On day 10, heifers received a P(4) implant (CueMate-1-pod, 0.78 g P(4); CueMate-2-pod, 1.56 g P(4); or CIDR-B, 1.9 g P(4)), 2 mg oestradiol benzoate (ODB) intramuscularly (i.m.) and 250 ug cloprostenol i.m.. At day 2, the implant was removed, 250 ug cloprostenol was injected i.m. and tail paint applied. The heifers received 1 mg ODB 24 h later and were FTAI 48-54 h after implant removal (day 0). Ten randomly selected heifers per group were blood sampled and scanned at days 10, 2, 0 and 6 to define the P(4) profiles pre- and post-FTAI. Heifers were heat-detected 18-20 days post-FTAI and oestrous heifers AI'd by the AM/PM rule. Bulls joined the heifers on day 27 post-FTAI. Transrectal ultrasonography estimated conception date on day 72. Statistical analysis examined the effects of treatment, technician, semen, ovarian status, BCS and liveweight, on pregnancy rate (PR) to FTAI. There was no significant difference (p = 0.362) in PR between treatment groups (CueMate 1-pod, 36.4%; CueMate 2-pod, 39.6%: CIDR-B, 28.3%), but PR was higher in those heifers with increased BCS between FTAI and pregnancy diagnosis (p = 0.005). Thirty-three per cent of monitor heifers had plasma P(4) concentrations of

Aptamers are known for their short in vivo circulating half-life and rapid renal clearance. Their conjugation to poly(ethylene glycol) (PEG) is a way to improve their residence in the body. Two aptamers (AptD and AptF), having a disulfide protected thiol modification on the 3′ end, have been conjugated to maleimide activated PEGs of various molecular weights and structures (linear PEG20; branched PEG20 and 40; PolyPEG17, 40, and 60 kDa). The high yield coupling (70−80% in most of the cases) could be achieved using immobilized tris[2-carboxyethyl]phosphine hydrochloride (TCEP) as reducing agent at pH 4. The affinity of PEGylated AptD for its target was reduced by conjugation to linear PEG20 and branched PEG40, but not to branched PEG20 and PolyPEGs. This work demonstrates an alternative approach to PEGylation of aptamers, and that the effect of PEG on the affinity for the target varies according to the structure and conformation of the synthetic polymer.

Between 2003 and 2008 the African Union deployed peace operations involving approximately 15,000 soldiers to four states: Burundi, Sudan, the Comoros, and Somalia. This represented a huge change of tempo from its predecessor, the Organization of African Unity. It also raises important questions about how successful these operations have been, what challenges they raise for the union's peacekeepers, and whether this tempo of operations is sustainable. This article addresses these questions by providing an overview of the African Union's peace operations and then reflecting on some of the general conclusions that can be drawn from the organization's first five years of peacekeeping.

How has the Peace and Security Council (PSC) of the African Union helped promote peace, security and stability on the African continent? This article assesses the PSC's activities in light of insights generated by the literature on international security institutions. After providing an overview of the immediate origins of the PSC, it discusses five elements of the Council's institutional design. It then evaluates the PSC's activities during its first five years (2004–9), by examining the Council's political relevance, its efficiency and productivity, and whether it is the institution best placed to deal with the continent's security problems. It concludes that the PSC's future will hinge on whether more of the African Union's members can be persuaded to devote more serious levels of resources (human and financial) to it.

Urinary biomarkers for the detection of bladder cancer have been developed, but no similar markers exist for prediction of clinical outcomes after receiving chemotherapy. Here we evaluate an approach that combines genomic, proteomic, and therapeutic outcome datasets to identify novel putative urinary biomarkers of clinical outcome after neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). Using this method, we identified gamma-glutamyl hydrolase (GGH), emmprin, survivin, and diazepam-binding inhibitor (DBI). Interestingly, GGH is a protein associated with methotrexate resistance, whereas emmprin, survivin, and DBI had been previously identified as predictors of outcome after platinum-containing chemotherapeutic regimens when assessed on tumor tissue. Using disease-free survival as a marker for clinical outcome, we evaluated the ability of GGH, emmprin, survivin, and DBI expression in tumor tissue to stratify 27 patients treated with neoadjuvant MVAC. DBI (P = 0.046) but not GGH (P = 0.190), emmprin (P = 0.066), or survivin (P = 0.393) successfully stratified patients. When GGH was used with DBI the significance of stratification improved (P = 0.024), whereas the addition of survivin or emmprin to this latter two-gene model reduced its significance (P = 0.036 and P = 0.040, respectively). Although these predictive results were obtained on tumor tissues, the presence of GGH and DBI in urine serves as a rationale for developing them as urinary markers of clinical outcomes for patients treated with neoadjuvant MVAC.

Conventional development of multivariate gene expression models (GEM) predicting therapeutic response of cancer patients is based on analysis of patients treated with specific regimens, which limits generalization to different or novel drug combinations. We overcome this limitation by developing GEMs based on in vitro drug sensitivities and microarray analyses of the NCI-60 cancer cell line panel. These GEMs were evaluated in blind fashion as predictors of tumor response and/or patient survival in seven independent cohorts of patients with breast (n = 275), bladder (n = 59), and ovarian (n= 143) cancer treated with multiagent chemotherapy, of which 233 patients were from prospectively enrolled clinical trials. In all studies, GEMs effectively stratified tumor response and patient survival independent of established clinical and pathologic tumor variables. In bladder cancer patients treated with neoadjuvant methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin, the 3-year overall survival for those with favorable GEM scores was 81% versus 33% for those with less favorable scores (P = 0.002). GEMs for breast cancer patients treated with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide and ovarian cancer patients treated with platinum-containing regimens also stratified patient survival [5-year overall survival 100% versus 74% (P = 0.05) and 3-year overall survival 68% versus 43% (P = 0.008), respectively]. Importantly, clinical prediction using our in vitro GEM was superior to that of conventionally derived GEMs. We show a facile yet effective approach to GEM derivation that identifies patients most likely to benefit from selected multiagent therapy. Use of such in vitro–based GEMs may provide a robust and generalizable approach to personalized cancer therapy. [Cancer Res 2009;69(21):8302–9]

The African Union mission in Somalia (AMISOM) endured a difficult first 30 months of operations. Deployed into an active war-zone, it was not long before an international debate began to revolve around how the mission should be brought to an end. This article analyses the main challenges as well as the most important local and international dynamics that affected the operation. It concludes that AMISOM was an ill-conceived mission that attracted few serious political champions partly because of the dangerous environment in which it operated and partly because of its lack of stable funding and capabilities. The predictable results were a dangerously under-resourced operation that placed peacekeepers in harm's way for morally and politically dubious reasons.

For its advocates, the 'responsibility to protect' (R2P) principle is clearly intended to be a universal concept, applicable equally to all parts of the globe. Yet recent literature examining the processes of norm diffusion in international relations has suggested that so-called universal norms do not automatically become embedded in different regions of the world and hence commitment to them varies depending on the local context. This article explores this issue with reference to how members of African international society have thought about the R2P idea. To do so it proceeds in two parts. The first summarises what I mean by African international society and the process of norm localization. In the second, I explore the current status of the R2P idea within the African society of states with reference to six illustrative episodes. These concern: 1) the building of Africa's new peace and security architecture; 2) the debate surrounding the adoption of the 2005 World Summit Outcome Document; 3) UN Security Council debates about the protection of civilians in armed conflict; 4) the African Union's response to the conflict in Darfur, Sudan; 5) the UN Secretary-General's appointment of a special adviser on R2P; and 6) African international society's response to the crisis in Zimbabwe. I conclude by reflecting upon what these episodes reveal about the current status of the R2P within African international society and the extent to which different camps are emerging that articulate different local positions on, and express varying degrees of skepticism about, the protection principle.

In recent years, senior UN officials have raised concerns about the decline of Western contributions to UN peace operations. Although this is a worrying trend for supporters of the UN, it does not mean that the West is playing a smaller role in peace operations per se. Instead, the West has increased its contribution to `hybrid' peace operations and missions that take place outside of the UN system. This article examines the West's contribution to both UN and non-UN peace operations since the Brahimi Report and assesses whether its contribution has markedly changed and what impact any changes have had on international peace and security. It proceeds in three sections. The first provides a historical overview of the West's ambivalent relationship with UN peace operations since 1948. The second analyses the West's contribution to UN, hybrid and non-UN peace operations. The final section explores what Western policies mean for international peace and security by assessing their impact on the UN's authority, the extent to which they save lives and their contribution to building stable peace. The article concludes that while in the short term the West's willingness to participate in hybrid operations displays a commitment to finding pragmatic solutions to some difficult problems, over the longer term this approach may weaken the UN's ability to maintain international peace and security.

This article seeks to contribute to debates about how regional arrangements construct and respond to threat agendas. It does so by using the literature on the concept of securitization to explore the processes through which the African Union (AU) and the Association of Southeast Asian Nations (ASEAN) have dealt with contemporary transnational challenges. After providing an overview of the Copenhagen School's (CS) understanding of securitization, we examine the main problems and limitations that emerge when attempting to apply the concept of securitization to regional arrangements in the developing world. The article explores in particular the extent to which the AU and ASEAN have securitized the transnational challenges on their agendas. We conclude that in both cases the impact of security culture as well as unresolved conceptual and methodological issues raise significant questions when seeking to apply securitization theory outside of Europe.

How do regional arrangements construct and respond to threat agendas, and to what extent can the existing literature on securitization theory help us understand this process? This article explores these questions by analyzing how the African Union (AU) has responded to contemporary transnational challenges. After providing an overview of the Copenhagen School's concept of securitization, the article discusses whether the known problems and limitations of securitization theory prevent this approach from being applied to regional arrangements. Arguing that they do not do so per se, the article then provides an overview of transnational challenges on the AU's agenda and explores the extent to which the organization has “securitized” them. It concludes that the AU has collectively securitized only a limited number of transnational challenges, particularly terrorism and HIV/AIDS, and that significant problems remain when attempting to apply the Copenhagen School's framework to regional arrangements.

The authors propose a semiparametric approach to modeling and forecasting age-specific mortality in the United States. Their method is based on an extension of a class of semiparametric models to time series. It combines information from several time series and estimates the predictive distribution conditional on past data. The conditional expectation, which is the most commonly used predictor in practice, is the first moment of this distribution. The authors compare their method to that of Lee and Carter. Prevision de taux de mortalite par la modelisation d'un rapport de densites Les auteurs proposent une methode semiparametrique pour la modelisation et la prevision de la mortalite par tranche d'ǎges aux Etats-Unis. Leur approche s'appuie sur la generalisation d'une classe de modeles semiparametriques au cas de series chronologiques. Elle exploite l'information provenant de plusieurs series et estime la loi predictive a partir du comportement passe. L'esperance conditionnelle, qui sert le plus souvent de predicteur en pratique, en est le premier moment. Les auteurs comparent leur methode a celle de Lee et Carter.

This special issue explores how one particular regional organisation, the Economic Community of West African States (ECOWAS), has defined certain transnational issues as security threats and how it has addressed them. In this introductory article, we begin by providing an overview and analysis of some of the most important transnational security challenges facing West Africa. Specifically, we discuss some of the problems raised by cross-border insurgencies, health challenges, organised criminal activities, terrorism and environmental degradation. We then examine the different levels at which actors have responded to these challenges. The section ‘Security culture: shaping the Economic Community of West African States (ECOWAS) response?’ sets out our approach to thinking about the concept of security culture and asks whether it might be relevant to understanding how and why ECOWAS has focused on responding to certain transnational security challenges and not to others. The final section provides a...

Drawing upon the various contributions to this special issue, this concluding article reflects upon the ways in which a shared security culture has influenced how the Economic Community of West African States (ECOWAS) has responded to transnational challenges. It then attempts to contextualise the ECOWAS approach by providing a brief comparative analysis of how other regional arrangements in Africa and Asia have addressed transnational challenges.

This article analyses the dominant patterns of political culture among West Africa's state elites in an attempt to understand what standards, beliefs and principles they cherish. We suggest that although there are significant differences across the region's states, the dominant political culture can be characterised as neopatrimonial, that is, systems based on personalised structures of authority where patron–client relationships operate behind a facade of ostensibly rational state bureaucracy. In order to explore these issues the article proceeds in four parts. After providing a definition of political culture and why it is an important topic of analysis, we examine the central characteristics of the political culture held by state elites in the Economic Community of West African States (ECOWAS) region. The section ‘The Nigerian factor’ briefly discusses some of the malign effects that this culture has had upon governance and political economy issues in the regional giant, Nigeria. The final sec...

Recent theory has examined the way in which vaccination strategies are expected to influence the evolution of parasite virulence. Most of this work has assumed that vaccination is imposed on a homogeneous host population. However, host populations are typically composed of different types of individuals, with each type responding differently to infection. Moreover, actual interventions often focus treatment on those hosts that are likely to suffer the most ill effects of a particular disease. Here we consider the epidemiological and evolutionary consequences of interventions that focus vaccination on individuals expressing the greatest susceptibility to infection and/or the greatest vulnerability to mortality once infected. Our results indicate that predictions are very sensitive to the nature and degree of heterogeneity in susceptibility and vulnerability. They further suggest that accounting for realistic kinds of heterogeneity when contemplating targeted treatment plans and policies might provide a new tool in the design of more effective virulence management strategies.

Since the early 1990s, a variety of African and Western governments alike have often suggested that finding “African solutions to African problems” represents the best approach to keeping the peace in Africa. Not only does the empirical evidence from post-Cold War Africa suggest that there are some fundamental problems with this approach, it also rests upon some problematic normative commitments. Specifically in relation to the problem of armed conflict, the “African solutions” logic would have at least three negative consequences: it would undermine the UN; it would provide a convenient excuse for powerful Western states that wished to avoid sending their own soldiers to peace operations in Africa; and it would help African autocrats fend off international, especially Western, criticism of their policies. After providing an overview of the constituent elements of the “African solutions” approach, this article sets out in general terms the central problems with it before turning to a specific illustration of how these problems affected the international responses to the ongoing war in Darfur, Sudan. Instead of searching for “African solutions”, policymakers should focus on developing effective solutions for the complex challenges raised by the issue of armed conflict in Africa. To this end, Western states in general and the P-3 in particular should give greater support to conflict management activities undertaken by the United Nations, develop clearer guidelines for how these should relate to regional initiatives, and facilitate the efforts of civic associations to build the foundations for stable peace in the continent's war zones.

The index of microcirculatory resistance (IMR), an invasive measure of microvascular function, has been shown to correlate with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study is to evaluate the predictive value of IMR on left ventricular recovery in patients undergoing a pharmacoinvasive strategy for STEMI.The index of microcirculatory resistance was assessed following percutaneous coronary intervention (PCI) in 31 patients with STEMI who were initially managed with thrombolysis. Other markers of microvascular function such as coronary flow reserve (CFR), TIMI flow grade, corrected TIMI frame count (cTFC), and ST-segment resolution were also recorded. All indices were evaluated against measures of left ventricular function and recovery 3 months postindex event.The IMR correlated with left ventricular function, as assessed by wall motion score and ejection fraction at 3-month follow-up (r = 0.652, P = 0.005; r = -0.452, P = 0.011, respectively). The traditional methods of assessing microvascular function, such as CFR, TIMI flow grade, cTFC, and ST-segment resolution did not correlate with wall motion score and ejection fraction at 3 months. Post-PCI IMR was significantly lower in those patients with left ventricular recovery at 3 months (18 U vs 39 U, P 0.001). The optimal cut-off value for post-PCI IMR and left ventricular recovery was 32 U. In patients in whom the IMR was greater than 32 U, the percent change in ejection fraction was significantly lower than in those patients in whom the IMR was less than 32 U (2 ± 11 vs 12 ± 8, P = 0.012).In patients presenting with STEMI initially managed with thrombolysis and subsequently undergoing PCI, IMR correlates with measures of left ventricular function and has the potential to predict left ventricular recovery at 3 months.

This article attempts to clarify some of the central questions and distinctions that provide the necessary backdrop for thinking in a sophisticated way about security in Africa. Drawing on the developing Critical Security Studies literature it suggests that an understanding of security based on people, justice and change offers the surest route to a stable future. It then sketches preliminary answers to some fundamental questions, namely: whose security should be prioritized? How have security dynamics in Africa been influenced by the wider processes driving world politics? What clusters of threats are the most salient? Where do such threats have the most pernicious effects? Which actors are best placed to alleviate those threats? And what sort of institutions should be built to assist in that process? The role of outsiders concerned with promoting security on the continent should be to try to ensure that as many Africans as possible are able to voice their opinions on these crucial issues.

This article employs the concepts of security culture and norm localization to explore some of the cultural dimensions of the African Union's (AU) security policies. After providing an overview of constructivist accounts of norm socialization in international relations, I use these insights to analyse the origins and development of the AU's security culture. The final two sections explore the ongoing process of norm localization in relation to the two most recent tenets of the AU's security culture: intolerance of unconstitutional changes of government and the responsibility to protect principle. An awareness of the uneven and contested nature of this process helps account for the fact that although these two transnational norms have been institutionalized in the AU Charter and endorsed by the United Nations, they have been internalized unevenly by the AU's member states. External advocates of these two norms would thus do well to help the continent's norm entrepreneurs build congruence between these norms and the AU's security culture.

To evaluate the feasibility and safety of direct transcatheter aortic valve implantation (TAVI) by the transfemoral approach without balloon pre-dilatation using the Edwards SapienXT valve.TAVI is established in selected high-risk patients with severe aortic stenosis. Balloon aortic valvuloplasty (BAV) is recommended prior to valve implantation, but may contribute to procedural risk. It is unknown whether this is necessary for successful passage and deployment of the device.81 patients (mean age 84 [95%CI:82-85.8], 62% male, median EuroScore 22.8% [95%CI:20.5-27]) undergoing transfemoral TAVI (35 by direct implantation [direct group]; 46 with balloon pre-dilatation [balloon group]) between 2010 and 2013 were analyzed for efficacy and safety endpoints.Procedural success was 100%. Pre and post-procedural peak gradients in the direct group were 66mmHg (95%CI:59-72.8) and 14mmHg (95%CI:12-17.8)(P 0.0001) compared to 76.5mmHg (95%CI:73.7-94.0) and 17mmHg (95%CI:16-19)(P 0.0001) in the balloon group. Post-dilatation was performed in 4/35(11.4%) of the direct group and 3/46(6.5%) of the balloon group (P = 0.83). Post procedure moderate AR was present in 1/35(2.9%) in the direct group and none in the balloon group. In-hospital mortality (2.9% direct vs. 0% balloon group), stroke (2.9% vs. 4.4%), tamponade (2.9% vs. 2.2%), major vascular complications (2.9% vs. 8.7%) and new permanent pacing (2.2% vs. 0) were similar. Pacing time, inflations, radiation dose and contrast use were all significantly lower in the direct group.Direct implantation of the Edwards SapienXT valve during TAVI by the transfemoral route appears safe, efficacious and feasible in those without extreme calcification. © 2016 Wiley Periodicals, Inc.

Objectives. Primary immunodeficiency diseases (PIDDs) are caused by inherent deficits in immune defenses that result in abnormal susceptibility to infection. In most cases, early and appropriate diagnosis can improve patient outcomes. The objective of this study was to evaluate understanding, recognition, and diagnosis of PIDD among pediatricians. Methods. A mail survey sent to a sample of pediatricians obtained from the American Medical Association and American Osteopathic Association. Results were compared with a similar survey of specialists who are members of the American Academy of Asthma, Allergy and Immunology. Results. More than a third (35%) of pediatricians were uncomfortable with the recognition and diagnosis of PIDD despite 95% having ordered screening tests or referring patients to specialists to be evaluated for PIDD, and 77% having followed at leastone patient with PIDD. In all, 84% of pediatricians were unaware that professional guidelines for PIDD exist. Conclusions. Patients with PIDD would benefit from improved recognition of the diseases by pediatricians in order to facilitate earlier diagnosis and optimize ongoing therapy.

A central prediction of classical theories of senescence states that environments posing a high risk of mortality favor the evolution of rapid intrinsic deterioration, or ageing. Although widely cited as being largely corroborated by existing data, empirical support for this prediction has been mixed. Recent theory suggests that this expectation should only be realized under particular circumstances, and this could account for the equivocal empirical findings. Here, we highlight the salient features of some of the recent developments in this field and suggest some ways in which progress might be made. We argue that it is necessary to move beyond the simplistic classical expectation and to take a more comprehensive and precise approach to studies of senescence, both theoretically and empirically.

This article explores the different moral and legal arguments used by protagonists in the debate about whether or not to conduct a humanitarian intervention in Darfur. The first section briefly outlines four moral and legal positions on whether there is (and should be) a right and/or duty of humanitarian intervention: communitarianism, restrictionist and counter-restrictionist legal positivism and liberal cosmopolitanism. The second section then provides an overview of the Security Council's debate about responding to Darfur's crisis, showing how its policy was influenced by both normative concerns and hard-nosed political calculations. The article concludes by asking what Darfur's case reveals about the legitimacy and likelihood of humanitarian intervention in such catastrophes and the role of the UN Security Council as the primary authorising body for the use of international force. The authors argue that this case demonstrates that for the cosmopolitan/counter-restrictionist case to prevail pivotal states need to put humanitarian emergencies on the global agenda and express a willingness to act without Council authorisation, though the question of how to proceed in cases where the Council is deadlocked remains vexed.

This article explores the role that military force might play in responding to the mass killing of civilians, through a discussion of the international response to the crisis in Darfur, Sudan. It contends that international society supported a weak military response in Darfur that left civilian protection to a hopelessly small, under-funded and unprepared African Union force. The first section provides an overview of the possible military options available to international society to respond to instances of mass killing. The second discusses the military response to the Darfur crisis, which came primarily in the form of the African Union's Mission in Sudan (AMIS). The third section offers a preliminary assessment of AMIS in terms of its international legitimacy, its effectiveness in achieving its mandate and its ability to foster stable peace in Darfur. The conclusion reflects upon the extent of change in international society's response to the mass killing of civilians since the 1994 Rwandan genocide.

Recent research has attempted to clarify the contributions of several mutational processes, such as substitutions or homologous recombination. Simplistic, tractable protein models, which determine the compact native structure phenotype from the sequence genotype, are well-suited to such studies. In this paper, we use a lattice-protein model to examine the effects of point mutation and homologous recombination on evolving populations of proteins. We find that while the majority of mutation and recombination events are neutral or deleterious, recombination is far more likely to be beneficial. This results in a faster increase in fitness during evolution, although the final fitness level is not significantly changed. This transient advantage provides an evolutionary advantage to subpopulations that undergo recombination, allowing fixation of recombination to occur in the population.

This article examines the recommendations contained within the Commission for Africa's report Our Common Interest, and asks what they might mean for the UK's Africa policies. After discussing the choice of the Commissioners and summarising the main recommendations made in their report, the article identifies some of the central problems raised but not resolved by the Commission in the relation to issues of security, political economy and governance. The article concludes that the Commission's report raised the profile of an important set of issues but neither resolved them conceptually nor set out a persuasive plan to implement its numerous recommendations. In particular, the Commission did not convincingly explain how neo-patrimonial regimes in Africa could be reformed to ensure that they pursue genuinely national development policies instead of the current strategies that benefit their supporters and weaken their political opponents.

A flurry of activity in the ‘official’ and ‘unofficial’ Commonwealths in the 1990s failed to translate into media recognition in the UK. A commitment to the organization from the incoming Labour government has so far failed to deliver the concrete action demanded by the Foreign Affairs Committee. But the Commonwealth has contributed to the UK's foreign policies in three main areas: peace and security, political economy and issues of governance. This paper examines each area in detail but concludes that the official Commonwealth remains “an institution relegated to the back burner”.

The article proceeds in four parts. In the opening section we discuss the debates generated by non-UN peace operations during the Cold War and in more recent years, and briefly highlight the limitations imposed by thinking of these developments in terms of regionalization. The second section develops a typology of non-UN peace operations according to the different actors conducting and authorizing them, namely, individual states, coalitions of the willing, and regional arrangements. The third section develops criteria to evaluate these operations in terms of their legitimacy, success in accomplishing the mandate, and contribution to stable peace and security. We then use these criteria to assess a contemporary example of each type of non-UN peace operation, namely, British operations in Sierra Leone, the Australian-led coalition in the Solomon Islands, and the African Union’s mission in Burundi.

Governments that have endorsed the ‘sovereignty as responsibility’ approach have shown little inclination to protect civilians suffering at the hands of their own government in the Sudanese province of Darfur. After providing an overview of Darfur’s crisis and international society’s feeble response, we explore why the strongest advocates of ‘sovereignty as responsibility’, the NATO and EU states, failed to seriously contemplate military intervention. We suggest that three main factors help explain the West’s unwillingness to intervene in Darfur: increased scepticism about the West’s humanitarian interventionism, especially after the invasion of Iraq; Western strategic interests in Sudan; and the relationship between the crisis in Darfur and Sudan’s other civil wars. We conclude that the emerging norm of humanitarian intervention remains weak and strongly contested, and that advocates of the ‘responsibility to protect’ approach have yet to persuade their governments to help save populations in danger.

The prevailing viewpoint in the study of sperm competition is that male sperm-allocation strategies evolve in response to the degree of sperm competition an ejaculate can expect to experience within a given mating. If males cannot assess the degree of sperm competition their ejaculate will face and/or they are unable to facultatively adjust sperm investment in response to perceived levels of competition, high sperm allocation (per mating) is predicted to evolve in the context of high sperm competition. An implicit assumption of the framework used to derive this result is that the degree of sperm competition is unaffected by changes in sperm-allocation strategies. We present theory based on an alternative perspective, in which the degree of sperm competition and the sperm-allocation strategy are coupled traits that coevolve together. Our rationale is that the pattern of sperm allocation in the population will, in part, determine the level of sperm competition by affecting the number of ejaculates per female in the population. In this setting, evolution in sperm-allocation strategies is driven by changes in underlying environmental parameters that influence both the degree of sperm competition and sperm allocation. This change in perspective leads to predictions that are qualitatively different from those of previous theory.

Collaboration between hospitals and community organisations has been promoted over the past 20 years by various levels of government, hospital associations, health promotion advocates, and others at the state/province, national and international levels as a way to improve the 'efficiency of the system', reduce duplication, enhance effectiveness and service coordination, improve continuity of care, and enhance community capacity to address complex issues. Nevertheless, and despite a growing literature on interagency collaboration, systematic documentation and empirical analysis of hospital-community collaboration (HCC) is almost completely lacking in the literature, particularly as regards collaborations that address the determinants of health beyond the hospital walls. In this paper, we describe the methodology and key findings from a research study of HCC. The Hospital Involvement in Community Action (HICA) study undertook detailed qualitative case studies (in four urban, suburban, rural and northern locations) and a telephone survey (of 139 community organisations in a large urban centre) in order to learn about the range of collaborations and working relationships that exist between hospitals and community agencies in the province of Ontario (Canada), and the factors that influenced (enabled and/or hindered) HCC. Particular attention was paid to barriers and enablers at three nested levels of context (policy, hospital and community) and, drawing primarily on the qualitative case studies, it is this aspect that is the focus of this paper. That such collaborations continue to be widespread despite a generally unfavourable policy environment and hospital institutional culture that poses significant barriers, suggests that the extent to which HCC flourishes (or exists at all) crucially depends on the presence and ongoing enthusiasm/commitment of one or more 'champions' within the hospital, and the commitment of both parties to overcome the marked cultural differences between hospital and community. We conclude with a discussion of implications for policy and practice.

Coronary artery embolus is a rare and potentially under- recognised cause of acute myocardial infarction. We describe the case of an 80-year-old woman presenting with an acute coronary syndrome secondary to coronary artery embolus associated with atrial fibrillation, which was successfully treated with the use of a thrombectomy aspiration catheter.