A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25 mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25 mg dapivirine and various quantities of maraviroc (50– 400 mg) were manufactured and in vitro release assessed. The 25 mg dapivirine and 100 mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.

Using Non-Monetary Deprivation Indicators to Analyze Poverty and Social Exclusion: Lessons from Europe?

Non-monetary indicators of deprivation are now widely used in studying poverty in Europe. While measuring financial resources remains central, having reliable information about material deprivation adds to the ability to capture poverty and social exclusion. Non-monetary indicators can help improve the identification of those experiencing poverty and understand how it comes about. They are most productively used when multidimensionality is explicitly taken into account, both in framing the question and in empirical application. While serious methodological and measurement issues remain to be addressed, material deprivation indicators allow for new insights in making poverty comparisons across countries and analyzing changes over time. (C) 2010 by the Association for Public Policy Analysis and Management.

Does Affirmative Action Work? Evidence from the Operation of Fair Employment Legislation in Northern Ireland

An affirmative action programme, established by the Fair Employment (Northern Ireland) Act 1989, has been an important attempt to ensure ‘fair participation’ in employment for both Catholics and Protestants in Northern Ireland since 1990. The programme includes detailed monitoring of the community background of employees and requires employers to undertake remedial action where fair participation is not evident. Agreements were concluded between the regulatory agency and many employers specifying what affirmative action measures were required. Based on the annual monitoring returns submitted between 1990 and 2005, this article evaluates the effectiveness of the affirmative action programme in promoting fair employment participation using fixed effects models. The analysis shows that there has been a general shift towards workforce integration in Northern Ireland but the increase of under-represented groups in agreement concerns is greater than in concerns with no agreement. The success of agreements, however, is limited to certain industrial sectors and medium-sized enterprises.

Textbook (non-) adoption motives, legitimizing strategies and academic field configuration

Textbooks are an integral part of structured syllabus coverage in higher education. The argument advanced in this article is that textbooks are not simply products of inscription and embodied scholarly labour for pedagogical purposes, but embedded institutional artefacts that configure entire academic subject fields. Empirically, this article shows the various ways that motives of the (non-) adoption of textbooks have field institutional configuration effects. The research contribution of our study is threefold. First, we re-theorise the textbook as an artefact that is part of the institutional work and epistemic culture of academia. Second, we empirically show that the vocabularies of motive of textbook (non-) adoption and rhetorical strategies form the basis for social action and configuration across micro, meso and macro field levels. Our final contribution is a conceptualization of the ways that textbook (non-) adoption motives ascribe meaning to the legitimating processes in the configuration of whole subject fields.

The Terror that Underpins the “Peace”: The Political Economy of Colombia's Paramilitary Demobilization Process

Studies on terrorism have traditionally focused on non-state actors who direct violence against liberal states. These studies also tend to focus on political motivations and, therefore, have neglected the economic functions of terrorism. This article challenges the divorce of the political and economic spheres by highlighting how states can use terrorism to realise interconnected political and economic goals. To demonstrate this, we take the case of the paramilitary demobilisation process in Colombia and show how it relates to the US-Colombian free trade agreement. We argue that the demobilisation process fulfils a dual role. First, the process aims to improve the image of the Colombian government required to pass the controversial free trade agreement through US Congress to protect large amounts of US investment in the country. Second, the demobilisation process serves to mask clear continuities in paramilitary terror that serve mutually supportive political and economic functions for US investment in Colombia.

Potential Cellular Targets and Antibacterial Efficacy of Atmospheric Pressure Non-Thermal Plasma

Atmospheric pressure non-thermal plasma (APNTP) has been gaining increasing interest as a new alternative antibacterial approach. Although this approach has demonstrated promising antibacterial activity, its exact mechanism of action remains unclear. Mechanistic elucidation of the antimicrobial activity will facilitate development and rational optimisation of this approach for potential medical applications. In this study, the antibacterial efficacy of an in-house-built APNTP jet was evaluated alongside an investigation of the interactions between APNTP and major cellular components in order to identify the potential cellular targets involved in plasma-mediated bacterial destruction mechanisms. The investigated plasma jet exhibited excellent, rapid antibacterial activity against a selected panel of clinically significant bacterial species including Bacillus cereus, meticillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa, all of which were completely inactivated within 2 min of plasma exposure. Plasma-mediated damaging effects were observed, to varying degrees, on all of the investigated cellular components including DNA, a model protein enzyme, and lipid membrane integrity and permeability. The antibacterial efficacy of APNTP appears to involve a multiple-target mechanism, which potentially reduces the likelihood of emergence of microbial resistance towards this promising antimicrobial approach. However, cellular membrane damage and resulting permeability perturbation was found to be the most likely rate-determining step in this mechanism. Crown Copyright © 2013.

Climate Change, national politics and grassroots action: an introduction

Climate change continues to dominate academic work within green/environmental politics. Indeed, there appears to be almost an inverse relationship between the lack of political leadership on tackling climate change and the growth in ever more sophisticated academic analyses of this complex and multifaceted problem. There is an increasing disjunction between the growth in our knowledge and understanding of the ethical, political, economic, sociological, cultural, and psychological aspects of climate change and the lack of political achievement in putting in place clear and binding targets, an agreed decarbonisation roadmap, and associated regulatory and policy instruments with enforcement. This gap might be taken as evidence that we do not need more reports on climate change. To quote that most unlikely of green politicians, Arnold Schwarzenegger, former Governor of California: ‘The debate is over. We know the science. We see the threat. And we know that the time for action is now’ (California Energy Commission 2007, p. 1). This special issue focuses on a variety of ways in which climate change is conceptualised in normative political and ethical theory, and addressed in policy and regulations.

Religiosity, Political Orientation, and Consequentialist Moral Thinking

Three studies demonstrated that the moral judgments of religious individuals and political conservatives are highly insensitive to consequentialist (i.e., outcome-based) considerations. In Study 1, both religiosity and political conservatism predicted a resistance toward consequentialist thinking concerning a range of transgressive acts, independent of other relevant dispositional factors (e.g., disgust sensitivity). Study 2 ruled out differences in welfare sensitivity as an explanation for these findings. In Study 3, religiosity and political conservatism predicted a commitment to judging “harmless” taboo violations morally impermissible, rather than discretionary, despite the lack of negative consequences rising from the act. Furthermore, non-consequentialist thinking style was shown to mediate the relationship religiosity/conservatism had with impermissibility judgments, while intuitive thinking style did not. These data provide further evidence for the influence of religious and political commitments in motivating divergent moral judgments, while highlighting a new dispositional factor, non-consequentialist thinking style, as a mediator of these effects.

Non-apologies and prolonged silences in post-conflict settings: The case of post-colonial Cyprus

Despite the growing use of apologies in post-conflict settings, cases of non-apology remain unaddressed and continue to puzzle scholars. This article focuses on the absence of apology by non-state and anti-state actors by examining the case of the Cypriot armed group EOKA, which has refused to offer an apology to the civilian victims of its ‘anti-colonial’ struggle (1955–1959). Using field data and parliamentary debates, and drawing on comparisons, this article analyses the factors that contributed to a lack of apology. It is argued that the inherited timelessness of Greek nationalism, and the impression of a perpetual need for defence, set up textbook conditions for the development of a hegemonic discourse and prevented an apology for human rights violations.

Borders, Asylum and Global Non-Citizenship: The Other Side of the Fence

The experience of border crossing for refugees and irregular migrants challenges global border and migration controls in multiple contexts. Using qualitative field research in Tanzania, Spain, Morocco and Australia, Heather Johnson asks how a global regime of migration management and control can be perceived through the dynamics of particular border spaces: refugee camps, border zones and detention centres. She explores how irregular migrants are impacted by the increasingly security-oriented practices of border control, and how they confront these practices. Johnson rejects the characterization of border spaces as exceptional, abject and exclusionary, arguing instead for an understanding of politics as everyday contestation that reveals a radical political agency, re-imagining the global non-citizen as a transgressive and powerful figure. Building on recent scholarship that rethinks irregularity and non-citizenship, her conclusions have broad implications for how we understand irregular migration from a position of dialogue and solidarity.

Complex Interactions between Dioxin-Like and Non-Dioxin-Like Compounds for in Vitro Cellular Responses: Implications for the Identification of Dioxin Exposure Biomarkers

Despite considerable advances in reducing the production of dioxin-like toxicants in recent years, contamination of the food chain still occasionally occurs resulting in huge losses to the agri-food sector and risk to human health through exposure. Dioxin-like toxicity is exhibited by a range of stable and bioaccumulative compounds including polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), produced by certain types of combustion, and man-made coplanar polychlorinated biphenyls (PCBs), as found in electrical transformer oils. While dioxinergic compounds act by a common mode of action making exposure detection biomarker based techniques a potentially useful tool, the influence of co-contaminating toxicants on such approaches needs to be considered. To assess the impact of possible interactions, the biological responses of H4IIE cells to challenge by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in combination with PCB-52 and benzo-a-pyrene (BaP) were evaluated by a number of methods in this study. Ethoxyresorufin-O-deethylase (EROD) induction in TCDD exposed cells was suppressed by increasing concentrations of PCB-52, PCB-153, or BaP up to 10 mu M. BaP levels below 1 mu M suppressed TCDD stimulated EROD induction, but at higher concentrations, EROD induction was greater than the maximum observed when cells were treated with TCDD alone. A similar biphasic interaction of BaP with TCDD co-exposure was noted in the AlamarBlue assay and to a lesser extent with PCB-52. Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) profiling of peptidomic responses of cells exposed to compound combinations was compared. Cells co-exposed to TCDD in the presence of BaP or PCB-52 produced the most differentiated spectra with a substantial number of non-additive interactions observed. These findings suggest that interactions between dioxin and other toxicants create novel, additive, and non-additive effects, which may be more indicative of the types of responses seen in exposed animals than those of single exposures to the individual compounds.

Victimhood and Attitudes towards Dealing with the Legacy of the Past: Northern Ireland as a Case Study

Research Highlights and Abstract: Using Northern Ireland as a case study, this article provides the first nationally representative and systematic study of victims' views on how to deal with the past; Focusing specifically on Northern Ireland, it both investigates and provides a comprehensive account of the marked divisions between the various religious groupings-Protestants, Catholics and the non-affiliated-in terms of a range of truth recovery mechanisms to deal with legacy of its violent past; It empirically investigates and validates two key predictors-perceptions of victimhood and general attitudes towards the past-in determining the source of these divisions It outlines the implications of our findings for other societies emerging from conflict. Truth recovery mechanisms have become a cornerstone of peacebuilding efforts in societies emerging from conflict. Yet, to date, the view of victims in post-conflict societies concerning such arrangements remains highly anecdotal and often second-hand in nature. Mindful of this omission and using Northern Ireland as a case study, this article investigates the views of victims towards a range of mechanisms to deal with the legacy of Northern Ireland's violent past. Based on the 2011 Northern Ireland Social and Political Attitudes Survey, the results suggest some marked divisions in relation to this issue, with victims within the Catholic community being significantly more supportive of such initiatives than either Protestants or those with no religion. Moreover, while perceptions of victimhood emerge as the key predictor of attitudes among Protestants and the non-affiliated, general opinions on how to deal with the past are the key determinant of views among members of the Catholic community

Non-governmental Organizational Accountability: Talking the Talk and Walking the Walk?

Concern for NGO accountability has been intensified in recent years, following the growth in the size of NGOs and their power to influence global politics and curb the excesses of globalization. Questions have been raised about where the sector embraces the same standards of accountability that it demands from government and business. The objective of this paper is to examine one aspect of NGO accountability, its discharge through annual reporting. Using Habermas’ (1984; 1987) theory of communicative action, and specifically its validity claims, the research investigates whether NGOs use their annual reporting process to account to the host societies in which they operate or steer stakeholder actions toward their own self-interests. The results of the study indicate that efforts by organizations to account are characterized by communicative action through the provision of truthful disclosures, generally appropriate to the discharge of accountability and in a manner intended to improve their understandability. At the same time, however, some organizations exhibit strategically oriented behaviors in which the disclosure content is guided by the opportunity to present organizations in a particular light and there appears a lack of rhetor authenticity. The latter findings cast doubt on the ethical inspiration of NGOs and the values they demand from business communities, and questions arise as to why such practices exist and what lessons can be learnt from them.