bluuebunny/crossref_metadata_2025 huggingface dataset:
Salvation—Personal and Political
Authors: Newlands George
Published: September 2009

A great deal of human striving may be understood as a search for salvation, intellectual, physical, and emotional. This search generates stories, which are recorded in texts both sacred and secular. Religion, as part of human striving, searches for salvation through transcendence, and through the consequences for human life of divine action. This article focuses on Christian input into narratives of salvation, which is worked out in personal struggle, but also, as the tradition has shown, in community. It is this community element that is a recurring emancipatory theme. This may bring out the ecclesial dimensions of the Christian salvation theme: word and sacrament, participation and eucharist, worship and discipleship. Here too there are communities of damnation, where an irrational and wasteful dynamic tears communities apart, dragging individuals helplessly to destruction. The salvation theme is one of essential hope, but not an easy or unreflected hope.
Institutional Obstacles to Entrepreneurship
Authors: Fogel Kathy , Hawk Ashton , Morck Randall , Yeung Bernard
Published: September 2009

This article focuses on institutional obstacles to entrepreneurship. Entrepreneurs carry out a highly complicated composite act. They need intelligence to collect and digest information about business opportunities. They need foresight about the possibilities new technologies and other developments create. They need judgement and leadership skills to found a company and guide its growth. They need communication skills to enthuse financiers to back their vision. The number of active entrepreneurs therefore depends on how many individuals possess these skills. But skills are not endowments. Individuals decide to develop those skills that advance their well being and to forgo developing those that do not. The prospects of a career as an entrepreneur depend on the economic environment, which can be facilitative or detrimental. A multitude of factors determine this environment: rules and regulations, the quality of government, the availability of education, and the ambient culture.
Migration of Entrepreneurs
Authors: Godley Andrew
Published: September 2009

In the classical and neoclassical economists' development of the theory of entrepreneurship, little role was allocated to one of the more obvious empirical observations of entrepreneurial behaviour: entrepreneurs have always been highly mobile individuals. This omission may of course have been because the focus of so much attention among nineteenth-century economists was on the dramatic events then unfolding in the industrializing regions of Britain and the United States, before then spreading further afield. This article reviews the literature on immigrant entrepreneurship, focusing especially on recently published investigations of historic cases, before making some theoretical observations and suggesting areas for further research.
The Development of HRM in Historical and International Perspective
Authors: Kaufman Bruce E.
Published: September 2009

The human resource function in the business enterprise has its origins in the rise of modern industry in the late nineteenth century. This article provides a survey of its historical development both as a functional area of management practice and as an area of research and teaching in universities. Although, for reasons to be described, the bulk of attention is on the United States, The article endeavors to put the subject in an international context. Also provided is an account of the field's progress, shortcomings, and controversies.
HRM Systems and the Problem of Internal Fit
Authors: Kepes Sven , Delery John E.
Published: September 2009

Previous reviews of the fit perspectives in SHRM have had a pessimistic tone and concluded that there was little evidence of the assumption that ‘fit’ leads to organizational success, although most reviews did not specifically focus on internal fit. This article aims to revisit the theoretical foundation of internal fit and provide a review of the literature addressing this issue. Specifically, it sets out to explore the theory and research behind the internal fit perspective in an attempt to summarize and advance our knowledge behind HRM systems and internal fit. In doing so, it addresses the theory behind ‘fit’, the interplay between external and internal fit, issues of the level of abstraction (e.g. focus on HRM philosophies, policies, or practices in measuring HRM systems), different types of internal fit, problems stemming from levels of analysis issues, and the empirical evidence, before summarizing and concluding.
HRM and Knowledge Workers
Authors: Swart Juani
Published: September 2009

This article develops a definition of the knowledge worker and discusses the characteristics of knowledge workers and their work. It then shifts to the organizational level and takes a closer look at the characteristics of knowledge-based organizations and the management of knowledge work. Several managerial and theoretical challenges arise when we combine individual and organizational knowledge perspectives. Each of these challenges, together with relevant knowledge-focused HR practices, is discussed and presented in a table, which serves as a summary to the article. The final section looks toward the future and explores possible avenues for research, theory-building, and HRM policy and practice development.
HRM and Business Performance
Authors: Purcell John , Kinnie Nicholas
Published: September 2009

The search for causal links between strategic HRM and business performance has dominated both academic and practitioner debate for over two decades. This article poses fundamental questions such as what is meant by performance, how an HR system is to be configured, how the causal chain between HR practices and performance outcomes is to be modeled, and what this means for research in the area. Most importantly, it challenges what we mean by human resource management. Recent research is reviewed to argue that culture, leadership, line manager behaviour, and operational management all need to fall within this area of interest. Before getting into the substance of these points, the article says something about the type of problems that have bedeviled research in the area.
Family-Friendly, Equal-Opportunity, and High-Involvement Management in Britain
Authors: Wood Stephen , de Menezes Lilian M.
Published: September 2009

Family-friendly, equal-opportunity, and high-involvement initiatives have increasingly been at the forefront of discussions of human resource management since the 1990s. They are widely viewed by academics and policy makers as critical ways of simultaneously improving the well-being of workers and the efficiency of organizations. Moreover, they are often presented as related practices. This article first discusses how they are perceived to be related and the research thus far on their links to organizational performance. It then reports a study designed to test these associations.
Social Legitimacy of the HRM Profession: A US Perspective
Authors: Kochan Thomas A.
Published: September 2009

This article argues that HR professionals need to treat business strategy as an endogenous variable, be more externally focused and skilled at building networks and productive alliances with other groups and institutions, become more analytical and able to document the benefits associated with effective HR policies and practices to firms and employees, and be skilled at managing in an increasingly transparent society and information savvy workforce. The changing gender composition of the HR profession may affect its success in making these changes and meeting these challenges. Ironically, however, significant change in the status and legitimacy of the HR profession may require a rebalancing of power in employment relations.
Introduction
Authors: Dryzek John S. , Honig Bonnie , Phillips Anne
Published: September 2009

This introductory article explains the theme of this book, which is about political theory. It evaluates the impact of literature that proved especially influential in framing debate through the last decades of the twentieth century and opening years of the twenty-first and examines the historical work on political thought. It describes the combination of concerns that runs through the work of John Rawls, Ronald Dworkin, and the liberal egalitarian tradition and identifies areas of debate that have proved particularly fruitful over the last thirty years. It analyses political theory from a global perspective and discusses body politic.
Power After Foucault
Authors: Brown Wendy
Published: September 2009

This article examines changes in the conception of political power after Michel Foucault. It suggests that while Foucault has politicized certain practices and knowledge fields that were previously insulated from inquiry into the interests shaping them, such politicization need not be conflated with political life tout court. It argues that Foucault's formulations of power, and especially of government and governmentality, have made this distinction extremely difficult. However, rather than giving up the distinction on the one hand, or rejecting Foucault's problematization of it on the other, political theory after Foucault is faced with the task of delineating it anew.
Multiculturalism and Post‐colonial Theory
Authors: Gilroy Paul
Published: September 2009

This article looks at the relation between post-colonial theory and multiculturalism. It explains that post-colonial theory is built upon debates over the legitimacy of colonial power that stretch through the morality of European expansion and the consequent ethical and political problems associated with colonial administration. Multiculturalism, like post-colonialism, is often seen as a coded way of speaking about race and about the dangerous processes through which race becomes a matter of culture. Some of the most important and influential strains of political commentary on multiculturalism have arisen from negotiation with indigenous populations in various national states. Those debates have been focused on problems of recognition, reparation, and sovereignty.
New Technologies, Justice, and the Body
Authors: Fabre Cécile
Published: September 2009

This article examines the impact of medical technologies on the concept of justice and the human body. Traditionally, theories of justice require individuals to transfer material resources to other individuals who are needier or worse off. But three technologies, organ transplantation, genetic engineering, and artificial wombs, have changed our obligations to one another. It appears that justice now requires us to subject our body to sometimes invasive procedures should others need our bodily resources, particular genes, or nutrients which we no longer want to provide through our body itself.
The Public and its Policies
Authors: Goodin Robert , Rein Martin , Moran Michael
Published: September 2009

This article examines a story of the limits of high ambition in policy studies and policy making. It looks at the way those limits have been appreciated and how more modest ambitions have been made. The article also examines the difficulties of modest learning and reveals some of the most basic truths: policy and policy making is mostly a matter of persuasion and policy is not only about arguing, but also about bargaining. Networked governance, choices under constraint, and democratic politics are some of the other topics covered in this article.
Policy Analysis as Puzzle Solving
Authors: Winship Christopher
Published: September 2009

This article attempts to describe another form of rationality that complements standard instrumental rationality. The article proposes an approach to policy analysis that would help in dealing with multiple and conflicting ends. It presents an analysis of the phenomena of puzzle solving, instead of developing an elaborate theory. The main focus of this analysis is the example of an individual or a group attempting to solve a jigsaw puzzle. An analysis of the specifics of putting together a jigsaw puzzle may help in understanding the problems that are involved in the form of policy analysis.
Agenda Setting
Authors: Majone Giandomenico
Published: September 2009

This article discusses agenda setting, and is organized into four main sections. The first section looks at the possibility that some individual or institution may hold exclusive power over the agenda. This is a possibility that is usually overlooked by analysts situated outside the rational choice framework. The second section puts emphasis on the links between the study of agenda setting and democratic theory. This is followed by a discussion of another issue that is not sufficiently researched by students of agenda setting, namely: the selection of priorities within the decision agenda. The last section in the article highlights the growing impact of international factors on the formation of national agendas.
Learning in Public Policy
Authors: Freeman Richard
Published: September 2009

This article discusses learning in public policy and aims to take stock of the different ways of thinking about learning in public policy. It examines the literature on convergence and diffusion between countries, which is important for distinguishing learning from other processes of development. The next topic discussed is Heclo's landmark study of political learning, which is described as ‘collective puzzling’. A third and different literature about learning as part of the ordinary business or practice of policy making is introduced. The article concludes with some reflections about the role of comparison in the process of learning across space and time.
The Tools of Government in the Information Age
Authors: Hood Christopher
Published: September 2009

This article studies the various tools of government in the Information Age. It identifies the three conventional approaches of the tools of government analysis: conceiving instruments as institutions, focusing on the politics of instrument selection, and cataloguing the tool kit in a more generic way than on the politics of instrument choice. It enumerates the three sets of issues related to the application of conventional analysis to Information-Age tools of government. Finally, the article tries to determine whether the Information Age has radically transformational or dynamic conservatism effects on the way government operates.
Historical Institutionalism
Authors: Sanders Elizabeth
Published: September 2009

This article studies the context where a new attention to institutional analysis emerged in the social sciences during the 1970s. It also examines the distinctions between historical institutionalism and its closest competitors — rational choice and quantitative cross-sectional analysis — as well as the search for agents of institutional maintenance and change. The last section of the article contains comments on the aspects of institutional development that have received too little attention.
Comparative Executive–Legislative Relations
Authors: Shugart Matthew S.
Published: September 2009

This article looks at comparative executive-legislative relations, beginning with early theoretical considerations and their modern application. It discusses the forms of constitutional structure and defines parliamentary, presidential, and hybrid systems. The next section pays attention to parliamentary systems, and this is followed by a detailed discussion of presidential and semi-presidential systems.
The Reach of Political Economy
Authors: Weingast Barry R. , Wittman Donald A.
Published: September 2009

This introductory article discusses a set of issues and approaches that have provided interesting results, and are most likely to prompt a number of researches in the next few years. It first looks at the research conducted on endogenous institutions, before focusing on legislative institutions. It looks at the revelation and aggregation of information, where the discussion is focused on the voters, particularly the voters who are uninformed in one way or another. One section covers the evolutionary models of human and political behaviour. The final section of the article discusses and considers the spread of political economy into new areas of research.
Legislatures and Parliaments in Comparative Context
Authors: Laver Michael
Published: September 2009

This article discusses legislatures and parliaments in a comparative context. The first section begins with a study of parliamentary politics. It then moves on to legislative politics in the separation-of-powers regimes. The final portion of the article revisits this distinction in the context of the different types of empirical technique that can be used to measure policy positions of elected politicians.
Capitalism and Democracy
Authors: Iversen Torben
Published: September 2009

This article discusses three different approaches to the study of democratic redistribution. It starts by considering the recent literature on capitalism as an economic system, and how the democratic and economic institutions may relate to each other. It then introduces the work that places coalitional politics at the very centre of the analysis.
Ethnic Mobilization and Ethnic Violence
Authors: Fearon James D.
Published: September 2009

This article studies ethnic mobilization and ethnic violence. It reviews some of the salient empirical patterns that concern cross-national and temporal variation in the politicization of ethnicity and ethnic violence. It also tries to explain the prevalence and variation of politicized ethnicity, and then arguments proposing to explain the occurrence of ethnic violence.
Youthful experts? A critical appraisal of children's emerging internet literacy
Authors: Livingstone Sonia
Published: September 2009

The growing importance of the Internet in today's lives raises many questions for social scientists, policy makers, and the public regarding the implications for work, education, community, politics, family life, and social relationships. Yet the research literature provides only moderate evidence that the Internet is bringing about any great changes; rather, the emerging picture stresses the (unequal) social conditions that influence how we fit the Internet into our lives. The contrast between the above quotations illustrates, the gap between the hopes held out for the Internet and the realities of people's experiences. As research, especially in industrialized countries, begins to shift its focus from questions of access and diffusion to questions about the nature and quality of Internet use, attention is being directed towards the skills and competence that ‘using’ the Internet implies.
Frege's Contribution to Philosophy of Language
Authors: Heck Richard G. , May Robert
Published: September 2009

Gottlob Frege's contributions to philosophy of language are so numerous and so fundamental that it is difficult to imagine the field without them. This article discusses Frege's apparently metaphysical doctrine that concepts are ‘unsaturated’. It argues that it is primarily a semantic thesis, an essential ingredient of Frege's conception of compositionality. It next discusses Frege's conception of truth. It argues that his seemingly puzzling doctrine that sentences denote objects, namely, truth-values, emerges from considerations about the logic of sentential connectives and the semantics of predicates and embodies an understanding of why, as Frege sees it, logic is so intimately concerned with the notion of truth. The article then turns to Frege's notion of a thought and, more generally, the distinction between sense and reference.
Conceptual Role Semantics
Authors: Greenberg Mark , Harman Gilbert
Published: September 2009

Conceptual role semantics (CRS) is the view that the meanings of expressions of a language (or other symbol system) or the contents of mental states are determined or explained by the role of the expressions or mental states in thinking. The theory can be taken to be applicable to language in the ordinary sense, to mental representations, conceived of either as symbols in a ‘language of thought’ or as mental states such as beliefs, or to certain other sorts of symbol systems. CRS rejects the competing idea that thoughts have intrinsic content that is prior to the use of concepts in thought. According to CRS, meaning and content derive from use, not the other way round.
Predicate Reference
Authors: MacBride Fraser
Published: September 2009

Whether a predicate is a referential expression depends upon what reference is conceived to be. Even if it is granted that reference is a relation between words and worldly items, the referents of expressions being the items to which they are so related, this still leaves considerable scope for disagreement about whether predicates refer. One of Frege's great contributions to the philosophy of language was to introduce an especially liberal conception of reference relative to which it is unproblematic to suppose that predicates are referring expressions. According to this liberal conception, each significant expression in a language has its own distinctive semantic role or power, a power to effect the truth-value of the sentences in which it occurs.
Speech Acts and Performatives
Authors: Hornsby Jennifer
Published: September 2009

This article aims to connect Austin's seminal notion of a speech act with developments in philosophy of language over the last forty odd years. It starts by considering how speech acts might be conceived in Austin's general theory. Then it turns to the illocutionary acts with which much philosophical writing on speech acts has been concerned, and finally to the performatives which Austin's own treatment of speech as action took off from.
World Politics
Authors: Weiss Thomas G. , Daws Sam
Published: September 2009

This article discusses world politics and international relations, with a primary focus on the United Nations Organization. It enumerates the four most relevant changes within the United Nations (UN), namely: the emergence of a single ‘hyper-power’, the emergence of threats, the reformulation of state sovereignty, and the increasing role of nonstate actors. It evaluates the efforts of the UN at problem-solving, discusses the concepts of global governance and US hegemony, and enumerates three analytical problems.
Secretary‐General
Authors: Newman Edward
Published: September 2009

This article discusses the intricacies of trying to be a Secretary-General. It describes the evolution of the roles of the Office of Secretary-General in the context of international politics. The article also provides an outline of the articles of the Charter that relate to the Secretary-General, the evolution of the office during the Cold War, and how the office has encountered challenges in the ‘new era’.
Peaceful Settlement of Disputes and Conflict Prevention
Authors: Mani Rama
Published: September 2009

This article examines the issues traditionally dealt with by the Secretary-General of the UN. These issues are negotiations, fact-finding, mediation, good offices, conciliation, and arbitration. More recent inventions such as international tribunals and regional arrangements are studied as well. The concept of ‘culture of prevention’ is introduced in this article.
The Way We Reason Now: Reflective Equilibrium in Bioethics
Authors: Arras John D.
Published: September 2009

This article begins with some preliminary remarks about the general features and basic varieties of reflective equilibrium (RE) in moral reflection. It then considers a couple of preliminary doubts about this method. One of these doubts claims that the most plausible interpretation of RE is so comprehensive that it risks paralyzing our thinking, while the other claims that this same version of RE is insufficiently determinate in practical contexts and will thus fail to be sufficiently action-guiding. The article then explicates the sense in which RE qualifies as a coherence theory of justification, and considers several objections to RE that flow from its reliance on the putative connection between coherence and moral justification.
‘Reinventing’ the Rule of Double Effect
Authors: Sulmasy Daniel P.
Published: September 2009

The Rule of Double Effect has played an important role in bioethics, especially during the last fifty years. Its major application in bioethics has been in providing physicians who are opposed to euthanasia with a moral justification for using opioid analgesics in treating the pain of patients whose death might thereby be hastened. It has also prominently been applied to certain obstetric cases. The scope of application of double effect is actually much broader than medical ethics, extending to cover such topics as strategic bombing in warfare. This article, while general in theory, concentrates on its applications in medical ethics.
Is the Science of Comparative Politics Possible?
Authors: Przeworski Adam
Published: September 2009

This article provides an overview of the issues needed in making causal inferences, when the generated data come from processes that are not controlled by the researcher. This overview serves as an introduction to the issues that have been discussed in detail by other researchers. This article emphasizes that the possible causes of these issues may include events, institutions, and policies. It also tries to determine if the science of comparative politics exists, by identifying the problem, the kinds of data, and the potential biases. Several historical studies are also provided.
Collective Action Theory
Authors: Ostrom Elinor
Published: September 2009

This article discusses collective action theory and focuses on three broad tropics. It first examines the growing and extensive theoretical literature that posits a host of structural variables presumed to affect the likelihood of individuals achieving collective action to overcome social dilemmas. It studies how a theory of boundedly rational, norm-based human behaviour is a better foundation for explaining collective action than a model of maximizing material payoffs to self. The article also discusses the link between structural measures and core individual relationships. It ends by reflecting on the challenge that political scientists face in testing collective action theory in light of the large number of variables posited to affect outcomes.
The Emergence of Parties and Party Systems
Authors: Boix Carles
Published: September 2009

This article discusses the emergence of parties and party systems. It summarizes the two main competing explanations of party systems, which are the neo-institutionalist research agenda and the historical-sociological literature. It then evaluates their strengths and limitations. The last two sections are focused on a new method of restructuring the way people think about how parties emerged. This method eventually integrates both approaches within a broad analytical framework.
Comparative Studies of the Economy and the Vote
Authors: Duch Raymond M.
Published: September 2009

This article looks at comparative studies of the economy and the vote and is divided into three major parts. The first portion provides a summary of the four important contributions of economic voting research. This is where the work on the American economic vote and economic voting are reviewed. The second portion suggests one methodological approach for analyzing the numerous existing surveys, modeling cross-national variation, and measuring the magnitude of the economic vote. The third and final portion provides a brief summary of the contextual theory of the economic vote from Duch and Stevenson, which builds the assumption of instrumentally rational voters.
The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects
Authors: Stavros Fiona , Kramer William G. , Wilkins Martin R.
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Endothelin‐A receptor antagonists (ETRAs) and phosphodiesterase‐type 5 inhibitors are approved monotherapies for the treatment of pulmonary arterial hypertension; combining agents from these two drug classes could be beneficial.

• There is a significant pharmacokinetic (PK) interaction between the ETRA bosentan and the phosphodiesterase‐type 5 inhibitor sildenafil.

• This study assessed whether the ETRA sitaxentan similarly impacts the PK of sildenafil.

WHAT THIS STUDY ADDS

• This study demonstrates that sitaxentan has little effect on sildenafil PK and pharmacodynamics and that no dose adjustment of either agent is required upon co‐administration of sildenafil with sitaxentan.

AIMS This study evaluated the effects of sitaxentan on the pharmacodynamic [systemic blood pressure (BP)] and pharmacokinetic (PK) parameters of sildenafil in healthy volunteers.

METHODS Healthy subjects (18–60 years, n= 24) were randomized into two sequence groups. Group 1 received sitaxentan sodium 100 mg daily (7 days), followed by placebo (7 days). Group 2 received placebo (7 days), followed by sitaxentan sodium 100 mg (7 days). On day 7 of each treatment period, participants received sildenafil 100 mg. PK parameters and BP were analysed on day 7 in each treatment period.

RESULTS Sildenafil exposure was slightly higher [AUC∞ geometric mean ratio (GMR), 128%] when co‐administered with sitaxentan 100 mg vs. placebo, demonstrating a weak, but statistically significant interaction (90% confidence interval 115.5%, 141.2%). The mean maximum positive (Emax+) and maximum negative (Emax–) changes from baseline in both systolic and diastolic BP were comparable for sitaxentan and placebo (range 4.8–7.3 mmHg) with three of four geometric mean ratios falling within the equivalence window, suggesting that the drug interaction was not clinically significant. Adverse events were similar between sitaxentan 100 mg (39%) and placebo (30%). No deaths or serious adverse events occurred during the study.

CONCLUSION The dose of sildenafil does not need to be adjusted when co‐administered with sitaxentan.
Inhibition of oral midazolam clearance by boosting doses of ritonavir, and by 4,4‐dimethyl‐benziso‐(2H)‐selenazine (ALT‐2074), an experimental catalytic mimic of glutathione oxidase
Authors: Greenblatt David J. , Peters Diane E. , Oleson Lauren E. , Harmatz Jerold S. , MacNab Malcolm W. , Berkowitz Noah , Zinny Miguel A. , Court Michael H.
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The viral protease inhibitor ritonavir is known to inhibit clearance of intravenous midazolam.

• ALT‐2074, a catalytic mimic of glutathione oxidase, inhibits human cytochrome P450 3A (CYP3A) isoformsin vitro.

WHAT THIS STUDY ADDS

• Short‐term administration of low‐dose ritonavir increases area under the plasma concentration curve following oral midazolam by a factor of 28.

• Therefore ritonavir is an appropriate positive control inhibitor for clinical drug interaction studies involving CYP3A substrates.

• Midazolam clearance is weakly inhibited by ALT‐2074, consistent with itsin vitroprofile.

AIMSWe evaluated whether ‘boosting’ doses of ritonavir can serve as a positive control inhibitor for pharmacokinetic drug–drug interaction studies involving cytochrome P450 3A (CYP3A). The study also determined whether 4,4‐dimethyl‐benziso‐(2H)‐selenazine (ALT‐2074), an investigational organoselenium compound that acts as a catalytic mimic of glutathione oxidase, inhibits CYP3A metabolismin vivo.

METHODSThirteen healthy volunteers received single 3‐mg oral doses of midazolam on three occasions: in the control condition, during co‐treatment with low‐dose ritonavir (three oral doses of 100 mg over 24 h), and during co‐treatment with ALT‐2074 (three oral doses of 80 mg over 24 h).

RESULTSRitonavir increased mean (±SE) total area under the curve (AUC) for midazolam by a factor of 28.4 ± 4.2 (P< 0.001), and reduced oral clearance to 4.2 ± 0.5% of control (P< 0.001). In contrast, ALT‐2074 increased midazolam AUC by 1.25 ± 0.11 (P< 0.05), and reduced oral clearance to 88 ± 8% of control.

CONCLUSIONSLow‐dose ritonavir produces extensive CYP3A inhibition exceeding that of ketoconazole (typically 10‐ to 15‐fold midazolam AUC enhancement), and is a suitable positive control index inhibitor for drug–drug interaction studies. ALT‐2074 inhibits CYP3A metabolism to a small degree that is of uncertain clinical importance.
Contributions of climatic and crop varietal changes to crop production in the North China Plain, since 1980s
Authors: LIU YUAN , WANG ENLI , YANG XIAOGUANG , WANG JING
Published: September 2009

The North China Plain (NCP) is the most important agricultural production area in China. Crop production in the NCP is sensitive to changes in both climate and management practices. While previous studies showed a negative impact of climatic change on crop yield since 1980s, the confounding effects of climatic and agronomic factors have not been separately investigated. This paper used 25 years of crop data from three locations (Nanyang, Zhengzhou and Luancheng) across the NCP, together with daily weather data and crop modeling, to analyse the contribution of changes in climatic and agronomic factors to changes in grain yields of wheat and maize. The results showed that the changes in climate were not uniform across the NCP and during different crop growth stages. Warming mainly occurred during the vegetative (preflowering) growth stage of wheat and maize, while there was a cooling trend or no significant change in temperatures during the postflowering stage of wheat (spring) or maize (autumn). If varietal effects were excluded, warming during vegetative stages would lead to a reduction in the length of the growing period for both crops, generally leading to a negative impact on crop production. However, autonomous adoption of new crop varieties in the NCP was able to compensate the negative impact of climatic change. For both wheat and maize, the varietal changes helped stabilize the length of preflowering period against the shortening effect of warming and, together with the slightly reduced temperature in the postflowering period, extend the length of the grain‐filling period. The combined effect led to increased wheat yield at Zhengzhou and Luancheng; increased maize yield at Nanyang and Luancheng; stabilized wheat yield at Nanyang, and a slight reduction in maize yield at Zhengzhou, compared with the yield change caused entirely by climatic change.
Genetic relatedness in wintering groups of house sparrows (Passer domesticus)
Authors: LIKER A. , BÓKONY V. , KULCSÁR A. , TÓTH Z. , SZABÓ K. , KAHOLEK B. , PÉNZES Z.
Published: September 2009

Social behaviour of group‐living animals is often influenced by the relatedness of individuals, thus understanding the genetic structure of groups is important for the interpretation of costs and benefits of social interactions. In this study, we investigated genetic relatedness in feeding aggregations of free‐living house sparrows (Passer domesticus) during the nonbreeding season. This species is a frequent model system for studies of social behaviour (e.g. aggression, social foraging), but we lack adequate information on the kin structure of sparrow flocks. During two winters, we ringed and observed sparrows at feeding stations, and used resightings to identify stable flock‐members and to calculate association indices between birds. We genotyped the birds using seven highly polymorphic microsatellite loci, and estimated pairwise relatedness coefficients and relatedness categories (close kin vs. unrelated) by maximum likelihood method. We found that most birds were unrelated to each other in the flocks (mean ± SE relatedness coefficient: 0.06 ± 0.002), although most individuals had at least a few close relatives in their home flock (14.3 ± 0.6% of flock‐mates). Pairwise association between individuals was not significantly related to their genetic relatedness. Furthermore, there was no difference between within‐flock vs. between‐flock relatedness, and birds had similar proportions of close kin within and outside their home flock. Finally, relatedness among members of different flocks was unrelated to the distance between their flocks. Thus, sparrow flocks were not characterized by association of relatives, nevertheless the presence of some close kin may provide opportunity for kin‐biased behaviours to evolve.
Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus, metabolic syndrome or neither
Authors: Conard S. , Bays H. , Leiter L. A. , Bird S. , Lin J. , Hanson M. E. , Shah A. , Tershakovec A. M.
Published: September 2009

Aim: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both associated with increased risk for atherosclerotic coronary heart disease (CHD). Thus, it is useful to know the relative efficacy of lipid‐altering drugs in these patient populations.

Methods: A double‐blind, parallel group trial of adult patients with hypercholesterolaemia at high‐CHD risk receiving atorvastatin 40 mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent change from baseline at week 6 was assessed for LDL‐C, total cholesterol, HDL‐C , non‐HDL‐C , Apo A‐I, Apo B and triglycerides. Safety was monitored through clinical and laboratory adverse events (AEs).

Results: Compared with doubling atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL‐C, triglycerides, Apo B, non‐HDL‐C, total cholesterol and lipid ratios in the T2DM, MetS and neither groups. Treatment effects were of similar magnitude across patient groups with both treatments, except triglycerides, which were slightly greater in the T2DM and MetS groups vs. neither group. Changes in HDL‐C , Apo A‐I and high sensitivity C‐reactive protein (hs‐CRP) were comparable for both treatments in all three groups. Safety and tolerability profiles were generally similar between treatments and across patient groups, as were the incidence of liver and muscle AEs.

Conclusions: Compared with doubling atorvastatin to 80 mg, addition of ezetimibe to atorvastatin 40 mg produced greater improvements in multiple lipid parameters in high‐CHD risk patients with T2DM, MetS or neither, consistent with the significantly greater changes observed in the full study cohort (clinical trial # NCT00276484).
Open‐label study to assess the safety and pharmacodynamics of five oral insulin formulations in healthy subjects
Authors: Eldor R. , Kidron M. , Arbit E.
Published: September 2009

Aim: Orally delivered insulin is predicted to bear therapeutic advantages in diabetes management when compared to injectable insulin, because of its ability to mimic the natural route of endogenous insulin secreted by the pancreas into the portal vein and directly to the liver. Oramed Pharmaceuticals is developing an oral insulin product which consists of unmodified recombinant human insulin combined with adjuvants that protect it from enzymatic degradation in the gastrointestinal tract and promote its absorption from the gut. The aim was to determine the optimal adjuvants to insulin ratio which can provide for the best pharmacodynamic profile, while maintaining the safety of the product.

Methods: Eight healthy, male volunteers participated in this open‐label study which included five independent visits. During each visit, subjects were administered one of the five encapsulated oral insulin formulations which contained equal amounts of insulin but varying proportions of adjuvants. Parameters measured included safety, Cmax and Tmax for insulin and Cmin, Tmin and area under the curve (AUC) for glucose and c‐peptide. Comparisons were made between formulations and between post‐treatment time periods within each visit.

Results: All five oral insulin formulations were well tolerated and no serious adverse events were reported. All formulations resulted in a significant response in the response period (60–300 min) in comparison to baseline (0–60 min); this was captured both in the c‐peptide response and the glucose response (all five formulations p < 0.05). However, none of the formulations turned out significantly different in response over the other. Formulation 5 showed the most profound reduction in c‐peptide when AUC0–60 (baseline) was compared to AUC60–300 (p < 0.007).

Conclusions: All five oral insulin formulations resulted in glucose and c‐peptide reductions, where formulation 5 demonstrated the most pronounced effect on c‐peptide concentration reduction. This formulation was deemed the lead formulation to be advanced to future clinical studies. This study also reinforces the notion that oral insulin can maintain its biological activity after delivery, suggesting a potential role for this product in management of diabetes.
Combination treatment with alogliptin and voglibose increases active GLP‐1 circulation, prevents the development of diabetes and preserves pancreatic beta‐cells in prediabetic db/db mice
Authors: Moritoh Y. , Takeuchi K. , Hazama M.
Published: September 2009

Aim: Alogliptin, a dipeptidyl peptidase‐4 (DPP‐4) inhibitor, and voglibose, an alpha‐glucosidase inhibitor, have different but complementary mechanisms of action on glucagon‐like peptide‐1 (GLP‐1) regulation and glucose‐lowering effects. The present study evaluated the chronic effects of combination treatment with alogliptin and voglibose in prediabetic db/db mice.

Methods: Alogliptin (0.03%) and voglibose (0.001%) alone or in combination were administered in the diet to prediabetic db/db mice.

Results: After 3 weeks, voglibose treatment increased GLP‐1 secretion (voglibose alone, 1.6‐fold; alogliptin plus voglibose, 1.5‐fold), while it decreased plasma glucose‐dependent insulinotropic polypeptide (GIP) (voglibose alone, −30%; alogliptin plus voglibose, −29%). Alogliptin, voglibose and combination treatment decreased plasma DPP‐4 activity by 72, 15 and additively by 80%, respectively, and increased plasma active GLP‐1 levels by 4.5‐, 1.8‐ and synergistically by 9.1‐fold respectively. Combination treatment increased plasma insulin by 3.6‐fold (alogliptin alone, 1.3‐fold; voglibose alone, 1.8‐fold), decreased plasma glucagon by 30% (alogliptin alone, 11%; voglibose alone, 8%), and prevented the development of diabetes, much more effectively than either agent alone. After 4 weeks, alogliptin, voglibose and combination treatment increased pancreatic insulin content by 1.6‐, 3.4‐ and synergistically by 8.5‐fold respectively. Furthermore, combination treatment resulted in an increased expression of insulin, pancreatic and duodenal homeobox 1 (PDX1) and glucose transporter 2 (GLUT2), and maintenance of normal beta/alpha‐cell distribution in the pancreatic islet.

Conclusions: Chronic treatment with alogliptin in combination with voglibose concurrently increased active GLP‐1 circulation, increased insulin secretion, decreased glucagon secretion, prevented the onset of the disease, and preserved pancreatic beta‐cells and islet structure in prediabetic db/db mice.
Modulation of nutrient sensing nuclear hormone receptors promotes weight loss through appetite suppression in mice
Authors: Perreault M. , Will S. , Panza D. , Gareski T. , Harding K. , Kubasiak D. , Jalenak M. , Gartrell K. , Wang S. , Bollag G. , Artis D. R. , Ibrahim P. N. , Womack P. , Lin J. J. , Saiah E. , Mansour T. S. , Vlasuk G. P. , Erbe D. V. , Tobin J. F.
Published: September 2009

Aim: Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in glucose and lipid metabolism. Three isoforms of PPARs have been identified with different tissue distribution and biological functions. Although the pharmacology of each receptor is well studied, the physiological effect of simultaneous activation of PPARα, γ and δ is only starting to emerge. We sought to determine the biological effects of a novel PPAR pan activator and elucidate the physiological mechanisms involved.

Methods:
Ob/ob, diet‐induced obese (DIO) or PPARα knockout mice were administered a novel agonist that activates all PPARs to various degrees to determine the effect on body weight, body composition, food intake and energy expenditure. In addition, serum parameters including glucose, insulin, triglycerides and ketone bodies as well as tissue acylcarnitine were evaluated. The effect of the novel agonist on liver and skeletal muscle histopathology was also studied.

Results: We report that simultaneous activation of all PPARs resulted in substantial weight loss in ob/ob and DIO mice. Consistent with known PPAR pharmacology, we observed that agonist treatment increased lipid oxidation, although appetite suppression was mainly responsible for the weight loss. Agonist‐induced weight loss was completely absent in PPARα knockout mice suggesting that PPARα pharmacology was the major contributor to weight regulation in mice.

Conclusions: Our work provides evidence that simultaneous activation of PPARα, γ and δ decreases body weight by regulating appetite. These effects of the pan agonist were completely absent in PPARα knockout mice, suggesting that PPARα pharmacology was the major contributor to weight loss.
Colestilan monotherapy significantly improves glycaemic control and LDL cholesterol levels in patients with type 2 diabetes: a randomized double‐blind placebo‐controlled study
Authors: Kondo K. , Kadowaki T.
Published: September 2009

Aim: To evaluate the plasma glucose‐reducing activity and safety of colestilan, a bile acid sequestrant, in patients with type 2 diabetes.

Methods: Patients with fasting plasma glucose (FPG) 7.2–11.1 mmol/l and HbA 1c≥7.0% were randomly allocated in double‐blind manner to receive colestilan or placebo therapy for 12 weeks.

Results: A total of 183 patients entered the double‐blind treatment phase. At 12 weeks, colestilan significantly reduced HbA 1c and FPG vs. placebo by 0.9% and 1.2 mmol/l respectively (both p < 0.001). A significant (p < 0.001) 22.5% reduction of LDL cholesterol was also observed in the 172 patients evaluated (colestilan group: n = 86; placebo group: n = 86). However, no significant reduction of fasting insulin was observed (p = 0.087). No incidence of hypoglycaemia was reported in this study.

Conclusion: Colestilan improved glycaemic control and reduced LDL cholesterol levels in patients with type 2 diabetes.
Outside Directors on Korean Boards: Governance and Institutions
Authors: Chizema Amon , Kim Jootae
Published: September 2009

abstract

Drawing on institutional theory, this study examines the factors that pressured Korean firms to appoint outside directors to their boards. While this practice could be considered to be a management innovation in Korea, in the Anglo‐American corporate governance system it has long been used as one of several mechanisms to mitigate agency costs between management and shareholders. As such, this response by Korean firms, following the 1997–98 currency crisis in Asia, could be seen as an example of corporate governance convergence on the Anglo‐American model, where higher levels of outside director representation on the board are the norm. We examine the antecedents of having a higher proportion of outside directors on Korean boards. Our findings indicate that larger firms that are under stricter control by the government have higher representation of outside directors on the board. We also find a positive and significant relationship between the proportion of outside directors and business group affiliation, poor prior firm performance, higher levels of debt and foreign ownership.