Understanding the power of the prime minister : structure and agency in models of prime ministerial power

Understanding the power of the prime minister is important because of the centrality of the prime minister within the core executive of British government, but existing models of prime ministerial power are unsatisfactory for various reasons. This article makes an original contribution by providing an overview and critique of the dominant models of prime ministerial power, highlighting their largely positivist bent and the related problem of the prevalence of overly parsimonious conceptions of the structural contexts prime ministers face. The central argument the paper makes is that much of the existing literature on prime ministerial power is premised on flawed understandings of the relationship between structure and agency, that this leads to misunderstandings of the real scope of prime ministerial agency, as well as its determinants, and that this can be rectified by adopting a strategic-relational view of structure and agency

Correction: Bioinformatics and Multiepitope DNA Immunization to Design Rational Snake Antivenom

Correction: Bioinformatics and Multiepitope DNA Immunization to Design Rational Snake Antiveno

Bioinformatics and Multiepitope DNA Immunization to Design Rational Snake Antivenom

BACKGROUND: Snake venom is a potentially lethal and complex mixture of hundreds of functionally diverse proteins that are difficult to purify and hence difficult to characterize. These difficulties have inhibited the development of toxin-targeted therapy, and conventional antivenom is still generated from the sera of horses or sheep immunized with whole venom. Although life-saving, antivenoms contain an immunoglobulin pool of unknown antigen specificity and known redundancy, which necessitates the delivery of large volumes of heterologous immunoglobulin to the envenomed victim, thus increasing the risk of anaphylactoid and serum sickness adverse effects. Here we exploit recent molecular sequence analysis and DNA immunization tools to design more rational toxin-targeted antivenom. METHODS AND FINDINGS: We developed a novel bioinformatic strategy that identified sequences encoding immunogenic and structurally significant epitopes from an expressed sequence tag database of a venom gland cDNA library of Echis ocellatus, the most medically important viper in Africa. Focusing upon snake venom metalloproteinases (SVMPs) that are responsible for the severe and frequently lethal hemorrhage in envenomed victims, we identified seven epitopes that we predicted would be represented in all isomers of this multimeric toxin and that we engineered into a single synthetic multiepitope DNA immunogen (epitope string). We compared the specificity and toxin-neutralizing efficacy of antiserum raised against the string to antisera raised against a single SVMP toxin (or domains) or antiserum raised by conventional (whole venom) immunization protocols. The SVMP string antiserum, as predicted in silico, contained antibody specificities to numerous SVMPs in E. ocellatus venom and venoms of several other African vipers. More significantly, the antiserum cross-specifically neutralized hemorrhage induced by E. ocellatus and Cerastes cerastes cerastes venoms. CONCLUSIONS: These data provide valuable sequence and structure/function information of viper venom hemorrhagins but, more importantly, a new opportunity to design toxin-specific antivenoms—the first major conceptual change in antivenom design after more than a century of production. Furthermore, this approach may be adapted to immunotherapy design in other cases where targets are numerous, diverse, and poorly characterized such as those generated by hypermutation or antigenic variation

Linking working memory and long-term memory: A computational model of the learning of new words

The nonword repetition (NWR) test has been shown to be a good predictor of children’s vocabulary size. NWR performance has been explained using phonological working memory, which is seen as a critical component in the learning of new words. However, no detailed specification of the link between phonological working memory and long-term memory (LTM) has been proposed. In this paper, we present a computational model of children’s vocabulary acquisition (EPAM-VOC) that specifies how phonological working memory and LTM interact. The model learns phoneme sequences, which are stored in LTM and mediate how much information can be held in working memory. The model’s behaviour is compared with that of children in a new study of NWR, conducted in order to ensure the same nonword stimuli and methodology across ages. EPAM-VOC shows a pattern of results similar to that of children: performance is better for shorter nonwords and for wordlike nonwords, and performance improves with age. EPAM-VOC also simulates the superior performance for single consonant nonwords over clustered consonant nonwords found in previous NWR studies. EPAM-VOC provides a simple and elegant computational account of some of the key processes involved in the learning of new words: it specifies how phonological working memory and LTM interact; makes testable predictions; and suggests that developmental changes in NWR performance may reflect differences in the amount of information that has been encoded in LTM rather than developmental changes in working memory capacity. Keywords: EPAM, working memory, long-term memory, nonword repetition, vocabulary acquisition, developmental change

Liberal intervention in the foreign policy thinking of Tony Blair and David Cameron

David Cameron was a critic of Tony Blair’s doctrine of the international community, which was used to justify war in Kosovo and more controversially in Iraq, suggesting caution in projecting military force abroad while in opposition. However, and in spite of making severe cuts to the defence budget, the Cameron-led Coalition government signed Britain up to a military intervention in Libya within a year of coming into office. What does this say about the place liberal interventionism occupies in contemporary British foreign policy? To answer this question, this article studies the nature of what we describe as the ‘bounded liberal’ tradition that has informed British foreign policy thinking since 1945, suggesting that it puts a distinctly UK national twist on conventional conservative thought about international affairs. Its components are: scepticism of grand schemes to remake the world; instinctive Atlanticism; security through collective endeavour; and anti-appeasement. We then compare and contrast the conditions for intervention set out by Tony Blair and David Cameron. We explain the similarities but crucially also the vital differences between the two leaders’ thinking on intervention, with particular reference to Cameron’s perception that Downing Street needed to loosen its control over foreign policy-making after Iraq. Our argument is that policy substance, policy style and party political dilemmas prompted Blair and Cameron to reconnect British foreign policy with its ethical roots, ingraining a bounded liberal posture to British foreign policy after the moral bankruptcy of the John Major years. This return to a patient, pragmatic and ethically informed foreign policy meant that military operations in Kosovo and Libya were undertaken in quite different circumstances, yet came to be justified by similar arguments from the two leaders

Randomised Controlled Double-Blind Non-Inferiority Trial of Two Antivenoms for Saw-Scaled or Carpet Viper (Echis ocellatus) Envenoming in Nigeria

Snake bite threatens millions of poor rural folk throughout Africa. In Nigeria, as in many countries of sub-Saharan Africa, it takes a terrible toll on human life and limb. Over the years, the news for those exposed to snake bite has been generally bad: withdrawal of antivenom manufacturers, increasing cost and, most recently, the marketing of ineffective or fake antivenoms in the region. Our paper reports encouraging results achieved by two antivenoms created as a direct consequence of the present crisis in antivenom supply for Africa. They have been assessed in the most powerful trial ever attempted in this field. The trial showed that in people with non-clotting blood following carpet viper bite, the commonest cause of snake bite morbidity and mortality in the West African savannah, administration of the antivenoms- EchiTAb G and EchiTAb Plus-ICP led to permanent restoration of blood clotting in 76% and 83% of the patients within 6 hours, respectively. Generally mild early adverse reactions were recorded in 19% and 26%, respectively. Both antivenoms proved effective and acceptably safe and can be recommended for treating carpet viper envenoming in Nigeria

Distinguishing Financialization from Neoliberalism

This article contends that neoliberalism and financialization, although sharing much in common, are not synonymous developments. Not only do strongly financialized nations display structural, economic differences, they are also directed by alternative economic epistemologies, cultures and practices. The argument is made by examining the financialization of the UK economy since the mid-1970s. This shift was not simply part of a broad transition away from Keynesianism and towards free market fundamentalism. It was also one very much guided by the particular economic paradigm, discursive practices and devices of the City of London as financial elites took up influential positions in the Thatcher government. The discussion and case example highlight five epistemological elements specific to finance: the creation of money in financial markets, the transactional focus of finance, the centrality of financial markets to economic management, the orthodoxy of shareholder value, and the intense microeconomic approach to financial calculation. Such elements, in conjuction with neoliberalism’s reliance upon finance-blind neoclassical economics, lies at the cultural and epistemological distinction between fiancialization and neoliberalism. Identifying such distinctions opens up new possibilities for understanding financialization, elites, and the neoliberal condition that brought about the financial crash of 2007-08, as well as the political and economic crises that have followed

Morphological variation and sensitivity to frequency of forms among native speakers of Czech

This article looks at inter-speaker variation in two environments: the genitive and locative singular cases of masculine ‘hard inanimate’ nouns in Czech, using a large-scale survey of native speakers that used two tasks to test their preferences for certain forms (acceptability) and their choices (gap filling). Our hypothesis that such variation exists was upheld, but only within limited parameters. Most biographical data (age, gender, education) played no role in respondents’ choices or preferences. Their region of origin played a small but significant role, although not the one expected. Relating the two types of tasks to each other, we found that respondents’ use of the ratings scale did not correlate to their choice of forms, but their overall strength of preference for one form over another did correlate with their choices. Inter-speaker variation does thus go some way to explaining the persistent diversity in this paradigm and arguably may contribute to its maintenance

Comparing different models of the development of verb inflection in early child Spanish

How children acquire knowledge of verb inflection is a long-standing question in language acquisition research. In the present study, we test the predictions of some current constructivist and generativist accounts of the development of verb inflection by focusing on data from two Spanish-speaking children between the ages of 2;0 and 2;6. The constructivist claim that children's early knowledge of verb inflection is only partially productive is tested by comparing the average number of different inflections per verb in matched samples of child and adult speech. The generativist claim that children's early use of verb inflection is essentially error-free is tested by investigating the rate at which the children made subjectverb agreement errors in different parts of the present tense paradigm. Our results show: 1) that, although even adults ' use of verb inflection in Spanish tends to look somewhat lexically restricted, both children's use of verb inflection was significantly less flexible than that of their caregivers, and 2) that, although the rate at which the two children produced subjectverb agreement errors in their speech was very low, this overall error rate hid a consistent pattern of error in which error rates were substantially higher in low frequency than in high frequency contexts, and substantially higher for low frequency than for high frequency verbs. These results undermine the claim that children's use of verb inflection is fully productive from the earliest observable stages, and are consistent with the constructivist claim that knowledge of verb inflection develops only gradually