1,179 research outputs found

    U.S. Standing in the World: Causes, Consequences, and the Future

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    America’s global standing has become a central concern of U.S. leaders and citizens. U.S. leaders, regardless of party, pledge to “restore U.S. standing” as a central goal of America’s foreign policy agenda. Standing has been the subject of widespread public discussion and intellectual debate. Yet despite all this attention, three issues fundamental to standing have been relatively ignored: -What is standing and how has it varied?-What causes standing to rise and fall?-What impact does standing have on U.S. foreign policy?This task force answers these questions by synthesizing what we now know about U.S. standing and/or identifying what we need to know to understand better a topic of clear national and international importance

    Condom use and the risk of HIV infection: who is being protected?

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    A study/survey done on condom use among Zimbabwean men in Zimbabwe.Descriptive baseline data at enrolment into a cohort of male factory workers who were tested for HIV serology and monitored for sero-con version over time, were analysed for condom use. At recruitment, the 1 146 men were asked about their sexual behaviour, history of sexually transmitted diseases (STDs), condom use and circumstances under which condoms were used. HIV seroprevalence in the cohort was 18,2 pc. Self reported use of condoms was low, with only 5 pc of the men reporting using them all the time. Forty four pc reported that they had never used a condom, 11,5 pc tried a condom only once, and 30,5 pc used condoms less than half the time. HIV positive men were more likely (Odds Ratio [OR]= 2,2 95 pc Cl: 1,3 — 3,3) to use condoms than those who tested negative. Men using a condom more than once were younger and had more education (p values < 0,0005). Univariate analysis showed that men with self reported risk factors for HIV infection were more likely to use condoms. Significantly more condom users reported paying for sex, multiple sex partners or (for married men) a girlfriend (p < 0,005). Condom users also more often had a history of genital ulcers, urethral discharge or other STDs. Few married men (24 pc) reported using a condom with their wives. Condom use was more commonly reported with commercial sex workers (44 pc) or other extramarital partners (36 pc). Some risk factors for HIV infection were also present amongst men who reported that they did not use condoms. Independent determinants of condom use identified by stepwise logistic regression analysis included young age, having a girlfriend (OR = 2,2; 95 pc Cl: 1,47 — 3,3), number of sex partners in the last year (OR = 1,27; 95 pc Cl: 1,06 —1,51 per partner), and paying for sex in the preceding year (OR = 1,74; 95 pc Cl: 1,06 — 2,83). The results show that men use condoms with partners considered risky, such as prostitutes or girlfriends but use condoms less often with their wives. The results underscore theneedfor health education for behavioural change that promotes universal, consistent use of condoms or monogamous partnership

    The Alternative for Germany’s radicalization in historical-comparative perspective

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    This article chronicles the AfD’s rightward repositioning and compares it with the programmatic development of three postwar German parties on the ideological wings. By highlighting factors that tilt the balance of power away from moderate reformers towards hardliners, this comparative analysis sheds light on the conditions that lead a relatively successful party on the ideological wings, such as the AfD, to radicalize its programme. Four variables stand out: whether party hardliners take the blame for the recent election loss; whether they offer a convincing programmatic and strategic alternative to the reformers; whether changes in party composition strengthen hardliners; and whether external factors enhance their weight within the party. The essay concludes that the AfD’s radicalization was unusual, but not exceptional. It is however too early to conclude that the Federal Republic’s distinctive institutions and political culture no longer impose significant costs on parties that shift their programmes away from the centre

    HIV seroconversion among factory workers in Harare: who is getting newly infected?

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    A clinical report on the impact of HIV/AIDS among factory workers in Zimbabwe's industrial areas of Harare.It was estimated that by the of 1996 more than 8.4 million AIDS cases had occurred worldwide.1 Because of the long and variable duration between infection with the human immunodeficiency virus (HIV) and the ultimate development of AIDS, a more useful indication of current trends in the epidemic is the number of new infections with HIV. Twenty eight million people from 190 countries across the world were HIV positive by mid 1996.Composed of distinct epidemics, each with its own features, degree and extent, the pandemic has had a disproportionately severe impact on the developing world. Despite wide information on HIV prevention, 3.1 million new infections occurred during 1996. Up to 93% of the HIV infections recorded in 1996 were from developing countries with 68% from sub-Saharan Africa.2 Developing countries, who have weaker economic structures, continue to bear the greatest burden of HIV infections. HIV infection appears be spreading much faster in Southern Africa than anywhere else

    In Vitro HIV-1 Evolution in Response to Triple Reverse Transcriptase Inhibitors & In Silico Phenotypic Analysis

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    Background Effectiveness of ART regimens strongly depends upon complex interactions between the selective pressure of drugs and the evolution of mutations that allow or restrict drug resistance. Methods Four clinical isolates from NRTI-exposed, NNRTI-naive subjects were passaged in increasing concentrations of NVP in combination with 1 µM 3 TC and 2 µM ADV to assess selective pressures of multi-drug treatment. A novel parameter inference procedure, based on a stochastic viral growth model, was used to estimate phenotypic resistance and fitness from in vitro combination passage experiments. Results Newly developed mathematical methods estimated key phenotypic parameters of mutations arising through selective pressure exerted by 3 TC and NVP. Concentrations of 1 µM 3 TC maintained the M184V mutation, which was associated with intrinsic fitness deficits. Increasing NVP concentrations selected major NNRTI resistance mutations. The evolutionary pathway of NVP resistance was highly dependent on the viral genetic background, epistasis as well as stochasticity. Parameter estimation indicated that the previously unrecognized mutation L228Q was associated with NVP resistance in some isolates. Conclusion Serial passage of viruses in the presence of multiple drugs may resemble the selection of mutations observed among treated individuals and populations in vivo and indicate evolutionary preferences and restrictions. Phenotypic resistance estimated here “in silico” from in vitro passage experiments agreed well with previous knowledge, suggesting that the unique combination of “wet-” and “dry-lab” experimentation may improve our understanding of HIV-1 resistance evolution in the future

    Convergence towards a European strategic culture? A constructivist framework for explaining changing norms.

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    The article contributes to the debate about the emergence of a European strategic culture to underpin a European Security and Defence Policy. Noting both conceptual and empirical weaknesses in the literature, the article disaggregates the concept of strategic culture and focuses on four types of norms concerning the means and ends for the use of force. The study argues that national strategic cultures are less resistant to change than commonly thought and that they have been subject to three types of learning pressures since 1989: changing threat perceptions, institutional socialization, and mediatized crisis learning. The combined effect of these mechanisms would be a process of convergence with regard to strategic norms prevalent in current EU countries. If the outlined hypotheses can be substantiated by further research the implications for ESDP are positive, especially if the EU acts cautiously in those cases which involve norms that are not yet sufficiently shared across countries

    Economic globalization and decentralization : a centrifugal or centripetal relationship?

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    One of the most significant economic trends in the last decades has been the integration of countries in international markets. What have been the consequences of global economic integration upon the territorial organization of the states? Has it contributed to centralize powers or to further decentralization? The literature so far has provided inconclusive evidence. In this paper we shed new light on the relationship between economic globalization and territorial politics by using a varied source of data such as the Regional Authority Index, and the KOF indices of globalization for the period 1970-2010. Results show that economic globalization is positively associated to decentralization, particularly in those countries with more regionalist parties and where levels of inequality are lower. Conversely, higher levels of regional inequality can revert the effect

    Zidovudine (AZT) Monotherapy Selects for the A360V Mutation in the Connection Domain of HIV-1 Reverse Transcriptase

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    Background: We previously demonstrated in vitro that zidovudine (AZT) selects for A371V in the connection domain and Q509L in ribonuclease H (RNase H) domain of HIV-1 reverse transcriptase (RT) which, together with the thymidine analog mutations D67N, K70R and T215F, confer greater than 100-fold AZT resistance. The goal of the current study was to determine whether AZT monotherapy in HIV-1 infected patients also selects the A371V, Q509L or other mutations in the C-terminal domains of HIV-1 RT. Methodology/Principal Findings: Full-length RT sequences in plasma obtained pre- and post-therapy were compared in 23 participants who received AZT monotherapy from the AIDS Clinical Trials Group study 175. Five of the 23 participants reached a primary study endpoint. Mutations significantly associated with AZT monotherapy included K70R (p = 0.003) and T215Y (p = 0.013) in the polymerase domain of HIV-1 RT, and A360V (p = 0.041) in the connection domain of HIV-1 RT. HIV-1 drug susceptibility assays demonstrated that A360V, either alone or in combination with thymidine analog mutations, decreased AZT susceptibility in recombinant viruses containing participant-derived full-length RT sequences or site-directed mutant RT. Biochemical studies revealed that A360V enhances the AZT-monophosphate excision activity of purified RT by significantly decreasing the frequency of secondary RNase H cleavage events that reduce the RNA/DNA duplex length and promote template/primer dissociation. Conclusions: The A360V mutation in the connection domain of RT was selected in HIV-infected individuals that received AZT monotherapy and contributed to AZT resistance. © 2012 Brehm et al

    Nucleic Acid Template and the Risk of a PCR-Induced HIV-1 Drug Resistance Mutation

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    The HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses.We performed ultra-deep pyrosequencing (UDPS) and clonal dideoxynucleotide sequencing of plasma virus samples to assess the prevalence of minority K65R variants in subtype B and C viruses from untreated individuals. Although UDPS of plasma samples from 18 subtype C and 27 subtype B viruses showed that a higher proportion of subtype C viruses contain K65R (1.04% vs. 0.25%; p<0.001), limiting dilution clonal sequencing failed to corroborate its presence in two of the samples in which K65R was present in >1.5% of UDPS reads. We therefore performed UDPS on clones and site-directed mutants containing subtype B- and C-specific patterns of silent mutations in the conserved KKK motif encompassing RT codons 64 to 66 and found that subtype-specific nucleotide differences were responsible for increased PCR-induced K65R mutation in subtype C viruses.This study shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques. However, the study is also consistent with the subtype C nucleotide template being inherently responsible for increased polymerization-induced K65R mutations in vivo
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