bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Adjuvant Endocrine Therapy for Early Breast Cancer
Authors: Stuart-Harris Robin , Davis Alison
Published: April 2010

Adjuvant endocrine therapy substantially reduces tumor recurrence and mortality in pre- and post-menopausal women with hormone receptor-positive early breast cancer but is ineffective in women with hormone receptor-negative tumors. Tamoxifen has been the standard adjuvant endocrine therapy for both pre- and post-menopausal women with hormone receptor-positive early breast cancer and remains the standard of care for premenopausal women. In addition to tamoxifen, ovarian ablation by surgery or radiotherapy remains an option for selected premenopausal women and trials are evaluating the role of ovarian function suppression using luteinizing hormone-releasing hormone agonists. For postmenopausal women, aromatase inhibitors are more effective than tamoxifen therapy and aromatase inhibitors and tamoxifen are regarded as standards of care. Prolonging adjuvant endocrine therapy in postmenopausal women by the sequencing of aromatase inhibitors and tamoxifen can improve outcomes further. Adjuvant endocrine therapy will probably be used for longer durations in selected postmenopausal women.
Some oscillation criteria for second-order delay dynamic equations
Authors: Higgins Raegan
Published: April 2010

We investigate the oscillation of second-order delay dynamic equations. Our results extend and improve known results for oscillation of second-order differential equations that have been established by Erbe [Canad. Math. Bull. 16:49-56 (1973)]. We apply results from the theory of upper and lower solutions and give some examples to illustrate the main results.
Regularization of some classes of ultradistribution semigroups and sines
Authors: Kostic Marko
Published: April 2010

We systematically analyze regularization of different kinds of ultradistribution semigroups and sines, in general, with nondensely defined generators and contemplate several known results concerning the regularization of Gevrey type ultradistribution semigroups. We prove that, for every closed linear operator A which generates an ultradistribution semigroup (sine), there exists a bounded injective operator C such that A generates a global differentiable C-semigroup (C-cosine function) whose derivatives possess some expected properties of operator valued ultradifferentiable functions. With the help of regularized semigroups, we establish the new important characterizations of abstract Beurling spaces associated to nondensely defined generators of ultradistribution semigroups (sines). The study of regularization of ultradistribution sines also enables us to perceive significant ultradifferentiable properties of higher-order abstract Cauchy problems.
Between Sacrifice and Indulgence: Nikolai Nekrasov as a Model for the Intelligentsia
Authors: Klioutchkine Konstantine
Published: April 2010

In this article, Konstantine Klioutchkine explores Nikolai Nekrasov's model of personality as it emerged at the intersection of his poetry, his public life, and his contemporaries’ accounts about him. The fascination with Nekrasov stemmed not so much from the veneration of his civic achievements as from the curiosity about his profligate lifestyle and glamorous ethical failures. Exemplary tensions within Nekrasov's lyric and public personae enabled his contemporaries to negotiate between the recognition of progressive values, the pursuit of unsanctioned pleasures, and the experience of moral infirmity. Discussions of Nekrasov's inherently contradictory personality suggested that, for members of the intelligentsia who came of age between the 1850s and 1880s, his personality symbolized what they had already sensed about the nature of their own selves but could not admit until later decades.
Unruly Felons and Civilizing Wives: Cultivating Marriage in the Siberian Exile System, 1822-1860
Authors: Schrader Abby M.
Published: April 2010

In the late eighteenth and early nineteenth centuries, Russian imperial authorities advocated colonizing Siberia and linking it to the center. This process was difficult: not only was the region remote, but it also had a reputation for lawlessness that was intensified by the 1822 expansion of the exile system. In this article, Abby M. Schrader examines one attempt that authorities undertook to civilize Siberia. Attributing much of the disorder that prevailed in Siberia to the region's severe gender imbalance and lack of stable households, officials sought to promote marriage among banished men. In doing so, authorities laid bare important preconceptions about Russian women's socio-sexual role. Rather than perceiving women as agents, they saw them as tools that could be deployed to enhance the larger social order. Placing stock in the potential for women to settle Siberia's exiles also provided authorities with an opportunity to displace blame for the failure of their policies upon women.
Looking for Solidarność in Central Asia: The Role of Human Rights Organizations in Political Change
Authors: Grodsky Brian
Published: April 2010

According to scholars of resource dependency, foreign funding can weaken rather than strengthen civil society abroad, ultimately impeding its effectiveness. Yet the spate of recent “democratic revolutions” in semiauthoritarian, postcommunist states suggests that pumping foreign money into the nongovernmental sphere can be an effective strategy. In this paper Brian Grodsky argues that a critical factor in assessing the likelihood that a given organizational movement will succumb to the ills of resource dependency is the type of politicization within that movement. Those organizations composed of members primarily motivated by ideology are logically less likely to succumb to resource dependency than those organizations dominated by political aspirants intent on converting democratization into their own political power. Two case studies, communist-era Poland and contemporary Uzbekistan, provide support for this theory.
The Dictatorship of Reason: Aleksandr Vol 'pin and the Idea of Rights under “Developed Socialism”
Authors: Nathans Benjamin
Published: April 2010

The Soviet mathematical logician Aleksandr Vol'pin is often credited with introducing the post-Stalin dissident strategy of attempting to hold the Soviet government to its own laws. In this article, Benjamin Nathans asks how Vol'pin himself arrived at the deceptively familiar rhetoric of civil rights and rule of law and how that rhetoric functioned in emerging dissident circles in the 1960s. Rather than approaching rights through classic liberal notions of social contract and self-interest, Vol'pin drew on the strikingly cosmopolitan and interdisciplinary ferment of Soviet intellectual life during the thaw years, putting logic, philosophy of language, and the burgeoning field of cybernetics to unexpected purposes. The result, Nathans suggests, was a counterintuitive blend of idealism and literalism that became an indispensable element of dissident thought and practice within late Soviet culture.
Remembering Romanian Communism
Authors: King Charles
Published: April 2010

The report of the Presidential Commission for the Analysis of the Communist Dictatorship in Romania, issued in December 2006, is the most serious attempt to understand Romania's communist experience ever produced. Coordinated by the American political scientist Vladimir Tismaneanu, the report covers virtually every aspect of communism as a lived system, from the installation of Communist Party officials during the postwar occupation, through the instruments of coercion, to the fate of religious institutions, the economy, national minorities, and education. The release of the report also contributed to a major political crisis, during which the parliament attempted to unseat the president, Traian Basescu, who had lauded the report and officially condemned communism as an illegitimate system. The question now is whether the commission's report will be used as yet another opportunity to reject history or as a way of helping Romanians learn, at last, how to own it.
Confronting Romania's Communist Past: A Response to Charles King
Authors: Tismaneanu Vladimir
Published: April 2010

The report of the Presidential Commission for the Analysis of the Communist Dictatorship in România, issued in December 2006, is the most serious attempt to understand România's communist experience ever produced. Coordinated by the American political scientist Vladimir Tismaneanu, the report covers virtually every aspect of communism as a lived system, from the installation of Communist Party officials during the postwar occupation, through the instruments of coercion, to the fate of religious institutions, the economy, national minorities, and education. The release of the report also contributed to a major political crisis, during which the parliament attempted to unseat the president, Traian Basescu, who had lauded the report and officially condemned communism as an illegitimate system. The question now is whether the commission's report will be used as yet another opportunity to reject history or as a way of helping Românians learn, at last, how to own it.
Less Than Zero?
Authors: Vázquez Carlos Manuel
Published: April 2010

Medellín v. Texas is the first case in which the Supreme Court has denied a treaty-based claim solely on the ground that the treaty relied upon was non-self-executing. In Foster v. Neilson, the only other case in which the Court had denied relief on this ground, the Court offered its view that the treaty was non-self-executing as an alternative ground for denying relief. The Court soon thereafter disavowed its conclusion that the treaty involved in Foster was non-selfexecuting, and, in the intervening years, it repeatedly declined invitations to deny relief on this or related grounds. Many observers (including me) thought that the Court would again skirt a ruling on non-self-execution in Medellín because the president had issued a memorandum ordering compliance with the judgment of the International Court of Justice (ICJ) in Avena. After all, the Court in American Insurance Ass’n v. Garamendi had recently struck down a California law on the ground that it conflicted with a “policy” reflected in certain sole executive agreements. The president in Medellín seemed to be standing on stronger ground, as he was insisting that state law give way to an obligation imposed by a treaty that had received the consent of the Senate and was accordingly the supreme law of the land. But the Court defied this expectation, with potentially regrettable results for the law of treaties.
On Proportionality of Countermeasures in International Law
Authors: Franck Thomas M.
Published: April 2010

In courts and tribunals, political arenas like the United Nations Security Council, and popular and scholarly journals, discursive recourse to the principle of proportionality has become frequent and vehement. It tends most audibly to arise in the midst of military conflicts pitting states against each other. But it also emerges in interstate trade disputes and when states, seeking to protect national security or public health, restrict internationally protected human rights.
The Governance of Kosovo: Security Council Resolution 1244 and the Establishment and Functioning of eulex
Authors: Wet Erika de
Published: April 2010

On February 4,2008, shortly before Kosovo's controversial unilateral secession from Serbia on February 17 of that year, the Council of the European Union (EU) adopted a Joint Action creating the European Union Rule of Law Mission in Kosovo/EULEX (hereinafter EULEX), the largest and most important mission thus far undertaken within the common European foreign and defense policy. Although EULEX is first and foremost a European undertaking, it is also strongly backed by the United States, which agreed to shoulder 25 percent of the operating costs while the remaining costs would be shared by European and other states. In October 2008, the U.S. Department of State further agreed to provide EULEX with eighty police officers and up to eight judges and prosecutors.
"Flying Home": Ralph Ellison, Richard Wright, and the Black Folk during World War II
Authors: Lucy Robin
Published: April 2010

This article examines the theories of the black folk (those African Americans understood to constitute a folk group) as an economic, cultural, and literary category in the wartime writing of Richard Wright and Ralph Ellison. It rereads this work within the context of current scholarship that historicizes and contests the construction of the folk in folklore and literary theory and their applications. This article has a particular focus on the numerous and uncollected articles by Ellison and on the oral history narratives he recorded for the Federal Writers’ Project. While both writers initially adopted a Marxist perspective on the folk, as defined by Wright’s "Blueprint for Negro Writing" (1937), the work of Ellison and Wright diverged from this platform, though in radically different ways. Ellison’s perspective developed to encompass a cultural nationalist position that was, in turn, deeply embedded in a pluralist and syncretic vision of American culture. In African American folk culture, Ellison limned a political agenda for activism. Wright, in contrast, aligned himself with the views of Gunnar Myrdal, which Ellison disputed. Recovering and delineating the ways in which Ellison’s construction of the black folk ultimately diverges from that of Wright is a key element in the rereading of the cultural politics of wartime African American writing.
What’s in a Coin? Reading the Material Culture of Legend Tripping and Other Activities
Authors: Holly Donald H. , Cordy Casey E.
Published: April 2010

Several people accused of being vampires are buried in southern Rhode Island. Their legends are well known, and as a result some of the places where these people are buried are sites of considerable activity. Drawing primarily on material culture left behind by visitors, we attempt to identify activities that are taking place at these gravesites. Our observations suggest that vandalism, partying, legend tripping, tourism, and perhaps even magic and sorcery occur at the gravesites, presumably long after dark. Such activities speak to a wide range of intentions, beliefs, and experiences on the part of visitors. Taking a material culture approach to the study of graveyard practices, this article documents activities that would otherwise be difficult to observe.
Hair: From the West to the Middle East through the Mediterranean (The 2007 AFS Mediterranean Studies Section Address)
Authors: Bromberger Christian
Published: April 2010

From shaving to curling, from the concealment of hair to its ostentatious display, hair lends itself to a wide assortment of arrangements. It is uniquely suited for expressing status difference, relations among kin, group membership, and both the submission to and refusal of predominant social, political, and religious norms. Its fashioning entails, among other things, a striking aesthetic affinity with gardening and home decoration. From the West to the Middle East through the Mediterranean, this article explores the symbolic significances that societies attribute to this hotly debated physical characteristic and, more broadly, the interplay between voluntary social practices and culturally imposed rules of conduct.
Vernacular Health Moralities and Culinary Tourism in Newfoundland and Labrador
Authors: Everett Holly
Published: April 2010

This article addresses class-based moral judgments as a crucial aspect of both informal and consciously constructed kinds of culinary tourism in the Canadian province of Newfoundland and Labrador. Interview and survey data, as well as Internet travelogues, further reveal the development and negotiation of vernacular health moralities that influence the ways in which certain foods are culturally constructed to convey status.
Borat, Multiculturalism,Mnogonatsional'nost
Authors: Lee Steven S.
Published: April 2010

In this article, Sacha Baron Cohen'sBoratappears as just the latest in a decades- long exchange between American and Soviet models of minority uplift: on the one side, civil rights and multiculturalism; on the other,druzhba narodov(the friendship of peoples) andmnogonatsional'nost’(multi-national- ness). Steven S. Lee argues diat, with Borat, multiculturalism seems to have emerged as the victor in this exchange, but that the film also hearkens to a not-too-distant Soviet alternative. Part 1 shows how Borat gels with recent leftist critiques of multiculturalism, spearheaded by Slovenian philosopher Slavoj żižek. Part 2 relates Borat to a largely submerged history of American minorities drawing hope from mnogonatsional'nost', as celebrated in Grigorii Aleksandrov's 1936 filmCircus.The final part presents Borat as choosing neither multiculturalism nor mnogonatsional'nost', but rather the continued opposition of the two, if not a “third way.” For a glimpse of what this might look like, the paper concludes with a discussion ofAbsurdistan(2006) by Soviet Jewish American novelist Gary Shteyngart.
East and West Kiss: Gender, Orientalism, and Balkanism in Muslim-Majority Bosnia-Herzegovina
Authors: Helms Elissa
Published: April 2010

Through an ethnographic analysis of public and “everyday” discourses in the Muslim-majority area of Bosnia-Herzegovina, this article shows how gender is frequently constitutive of orientalist and balkanist representations. Both orientalism and balkanism have recently undergone a shift, precisely in the ways in which they are gendered. Women have become more visible symbols of Balkan backwardness while orientalist depictions have moved from emphasizing erotic sexuality to a focus on heavily veiled and controlled women, symbolizing the political threat of the east/Islam. In examining the everyday workings of such discourses in a community straddling the imagined boundaries of east and west, Elissa Helms shows a range of competing (re) configurations of east/west and related dichotomies, which are reconfigured precisely through notions of gender. While some of these (re)articulations seem to challenge dominant orientalist and balkanist frameworks, Helms argues that they ultimately reproduce (gendered) notions of opposing east and west civilizations.
Visual Poetry after Modernism: Elizaveta Mnatsakanova
Authors: Sandler Stephanie
Published: April 2010

The impact of neither Andrei Belyi nor Velimir Khlebnikov has been fully comprehended, and their legacies are joined in unusual combination in the work of the contemporary visual poet Elizaveta Mnatsakanova. Her poetry appeals to both eye and ear, expanding on innovations introduced by Belyi and Khlebnikov, and it raises broad questions about the integration of sensory experiences by readers of visual poetry. Mnatsakanova uses illustrative handwriting, calligraphy, and images of a hand or a face in her one-of-a-kind albums and books, and her poems are set out in symmetrical columns or other spatial arrangements. Repetition is the central rhetorical device in her work, yet her unique albums emphasize individualized aesthetic production and anticipate highly charged reader reaction. Special attention is paid to “Das Hohelied,” a partof Das Buch Sabeth,which engages both the literary tradition and the immediacy of a reader's experience with the text.
Violating the Canon: Reading Der Nister with Vasilii Grossman
Authors: Murav Harriet
Published: April 2010

'Violating the Canon” makes the case for an alternative Jewish and literary space in the context of Soviet war literature by comparing works by Vasilii Grossman, Il'ia Erenburg, and the Yiddish author Der Nister. In this article, Harriet Murav distinguishes the question of literary value from the question of identity and separates out the problem of determining the typicality or representativeness of a work from the problem of engaging the complexity of its meanings. Jewish literature from the Soviet Union ought to be recovered from the constraints that subordinate it to Cold War-era sociological and political constraints. Mikhail Bakhtin, Werner Sollors, and Michael Warner provide approaches that allow access to more fluid and open-ended readings.
Freud, Tatlin, and the Tower: How Soviet Psychoanalysts Might Have Interpreted the Monument to the Third International
Authors: Kurbanovsky Alexei Alexeyevich
Published: April 2010

The first translations of Sigmund Freud's texts into Russian appeared in the early 1900s, and by the 1920s all important works were available; in Soviet Russia they stimulated wide discussion of various medical, pedagogical, and social problems as well as of developments in creative art. Alexei Kurbanovsky argues that “Freudianism” would have seemed very tempting to those early Soviet theorists who believed that they must appropriate the relevant discoveries of western psychology and adopt them for their own revolutionary ends: creating the “new communist man.” The application of Freudian techniques to the analysis of some classical Russian writers as well as painters is documented in writings from the 1920s by Ivan Ermakov; the artistic tendencies of the Russian avant-garde were quite often viewed as reflecting the latest achievements of science and technology. So aspiring Soviet critics might well have attempted psychoanalytical “readings“ of innovatory artifacts. Vladimir Tatlin stands as one of their possible model cases. Kurbanovsky argues that Tatlin's famous spiral tower could be psychoanalytically interpreted in reference to the Oedipal “refutation of father-figures.” Such an interpretation seems in tune with the general cultural climate where other phenomena (such as the October revolution) were seen as having a “hidden, Freudian aspect.” Examining the psychoanalytical underpinnings of the theory of Soviet avant-garde allows us to more fully appreciate its historical and cultural significance.
Art, Nationhood, and Display: Zinaida Volkonskaia and Russia's Quest for a National Museum of Art
Authors: Blakesley Rosalind P.
Published: April 2010

In 1831, the journalTeleskoppublished Princess Zinaida Volkonskaia's proposal for a national art museum in Moscow. Volkonskaia's project was progressive to a degree (Russia had no such museum at the time), yet the model she proposed was highly traditional. She excluded Russian art entirely, despite her support of modern Russian artists. Instead, Volkonskaia privileged classical and more recent western European art, underlining the deference to western practice that influenced cultural politics even as Russia moved toward a stronger national sense of self. Volkonskaia's project marks an important juncture in Russia's cultural history: the intersection of aristocratic female patronage and the institutionalization of academic procedure. It also provides a platform from which to consider Russia's self-image vis-à-vis Europe in the aftermath of the Napoleonic campaigns. By tracing an intricate dialogue in which national pride developed alongside continuing admiration for neoclassical ideals, Rosalind P. Blakesley addresses the paradoxes of Volkonskaia's project, and the difficulties of conceptualizing a “national” space of artistic display. Volkonskaia's project poses significant interpretive problems and her exclusion of Russian art prefigures the segregation of Russian and western art in Russian museums today, which has marginalized Russian art even within Russia itself. Volkonskaia's project thus has wide resonance, for the question of whether and how museums encapsulate national cultural identities remains an issue of great intellectual concern.
Models of Selfhood and Subjectivity: The Soviet Case in Historical Perspective
Authors: Chatterjee Choi , Petrone Karen
Published: April 2010

In this essay Choi Chatterjee and Karen Petrone examine some of the paradigms of selfhood that western scholars have used to understand Soviet subjectivity. They start with an analysis of how racialized western discourses about the backward Russian national character were transformed into representations of the totalitarian Soviet self seen as a passive receptacle for the ideological excesses of the regime. Revisionist historians have argued against this model and have shown how the pragmatic Soviet subject both internalized and resisted the Soviet norms of selfhood. In the third wave, scholars have used the model of the normative self to plot the internal processes through which citizens attempted to align their souls with the demands of Stalinist ideology. Chatterjee and Petrone conclude with the scholars’ analysis of the banal self, or the situation of Soviet selfhood in intimate and private spheres of existence that necessitated multiple negotiations and compromises with the theoretical norms of statesponsored subjectivity.
"With a Shade of Disgust": Affective Politics of Sexuality and Class in Memoirs of the Stalinist Gulag
Authors: Kuntsman Adi
Published: April 2010

This article addresses a topic seldom discussed in gulag studies: same-sex relations in the camps. In particular, it deals with affective politics of sexuality and class in gulag memoirs and the role of disgust in the formation of sexual and class boundaries. It approaches disgust as existing between the individual and the social, the subjective and the historical, the internal and the external, and traces the ways the gulag memoirs constitute the disgusting, the disgusted, and the boundary between them. At the center of the article are descriptions of same-sex relations in the Kolyma camps of the 1930s-1950s by Evgenia Ginzburg and Varlam Shalamov. Based on a critical reading of these and other memoirs, Adi Kuntsman reveals how same-sex relations among the common criminals are constructed by the memoirists as disgusting because they go against gender norms and against class perceptions of sexual morality. Kuntsman shows how these perceptions of the appropriate, embedded within the habitus of the intelligentsia, are transformed in the memoirs into the universal category of humanness, locating the common criminals, and, by association, anyone who engages in same-sex relations, beyond the bounds of humanity.
The Covert Design ofThe Brothers Karamazov:Alesha's Pathology and Dialectic
Authors: Rice James L.
Published: April 2010

A future revolutionary, Alesha Karamazov is, at nineteen, an inexperienced boy who lives in a monastery and who has been considered strange since birth. Fedor Dostoevskii endows him with hysteria—then a serious psychopathology with convulsions that were clinically seen as analogous to epilepsy, themorbus sacer fromwhich Dostoevskii himself suffered. Recognized as an epidemic problem, hysteria in this novel is elaborately deployed as a symbol of Russia's social ills and the underlying cause of farreaching personality changes in Alesha (for better or worse), preparing him for a heroic destiny. Although hysteria was soon altered and later eliminated as a clinical syndrome, James L. Rice enables us to read the novel for the first time in the light of documented medical history.
Pollution and Purification in the Moscow Human Rights Networks of the 1960s and 1970s
Authors: Walker Barbara
Published: April 2010

In this article Barbara Walker examines the theme of (samo)zhertvovanie in the Moscow human rights movement of the 1960s and 1970s. Some participants in that movement have expressed emotional satisfaction in the belief that they were motivated by the desire for self-giving; but that belief has sometimes been received with doubt. Walker uncovers the social phenomenon of a charity movement for the benefit of political prisoners that, she argues, lies near the social and emotional heart of the human rights movement. An important theme of the charity movement, whether real or constructed, is emotional purification of a sense of personal and social contamination stemming from participation in what some experienced as corruption in Soviet state and society. This article draws on ideas of spiritual atonement and salvation through altruism as explanatory cultural factors in this phenomenon.
Regulation of MafA Expression in Pancreatic β-Cells in db/db Mice With Diabetes
Authors: Matsuoka Taka-aki , Kaneto Hideaki , Miyatsuka Takeshi , Yamamoto Tsunehiko , Yamamoto Kaoru , Kato Ken , Shimomura Iichiro , Stein Roland , Matsuhisa Munehide
Published: April 2010

OBJECTIVE

Islet β-cells loose their ability to synthesize insulin under diabetic conditions, which is at least partially due to the decreased activity of insulin transcription factors such as MafA. Although an in vitro study showed that reactive oxygen species (ROS) decrease MafA expression, the underlying mechanism still remains unclear. In this study, we examined the effects of c-Jun, which is known to be upregulated by ROS, on the expression of MafA under diabetic conditions.

RESEARCH DESIGN AND METHODS

To examine the protein levels of MafA and c-Jun, we performed histological analysis and Western blotting using diabetic db/db mice. In addition, to evaluate the possible effects of c-Jun on MafA expression, we performed adenoviral overexpression of c-Jun in the MIN6 β-cell line and freshly isolated islets.

RESULTS

MafA expression was markedly decreased in the islets of db/db mice, while in contrast c-Jun expression was increased. Costaining of these factors in the islets of db/db mice clearly showed that MafA and insulin levels are decreased in c-Jun–positive cells. Consistent with these results, overexpression of c-Jun significantly decreased MafA expression, accompanied by suppression of insulin expression. Importantly, MafA overexpression restored the insulin promoter activity and protein levels that were suppressed by c-Jun. These results indicate that the decreased insulin biosynthesis induced by c-Jun is principally mediated by the suppression of MafA activity.

CONCLUSIONS

It is likely that the augmented expression of c-Jun in diabetic islets decreases MafA expression and thereby reduces insulin biosynthesis, which is often observed in type 2 diabetes.
Impact of Common Variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the Risk of Type 2 Diabetes in 5,164 Indians
Authors: Chauhan Ganesh , Spurgeon Charles J. , Tabassum Rubina , Bhaskar Seema , Kulkarni Smita R. , Mahajan Anubha , Chavali Sreenivas , Kumar M.V. Kranthi , Prakash Swami , Dwivedi Om Prakash , Ghosh Saurabh , Yajnik Chittaranjan S. , Tandon Nikhil , Bharadwaj Dwaipayan , Chandak Giriraj R.
Published: April 2010

OBJECTIVE

Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case–control studies.

RESEARCH DESIGN AND METHODS

We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects.

RESULTS

We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 × 10−3 to 4.6 × 10−34). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71–2.09], P = 4.6 × 10−34). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of β-cell function (P = 6.9 × 10−8 and 3 × 10−4, respectively), which looked consistent with recessive and under-dominant models, respectively.

CONCLUSIONS

Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.
Associations Between Features of Glucose Exposure and A1C
Authors: Borg Rikke , Kuenen Judith C. , Carstensen Bendix , Zheng Hui , Nathan David M. , Heine Robert J. , Nerup Jorn , Borch-Johnsen Knut , Witte Daniel R. ,   on behalf of the ADAG Study Group
Published: April 2010

OBJECTIVE

Various methods are used to quantify postprandial glycemia or glucose variability, but few have been compared and none are standardized. Our objective was to examine the relationship among common indexes of postprandial glycemia, overall hyperglycemia, glucose variability, and A1C using detailed glucose measures obtained during everyday life and to study which blood glucose values of the day provide the strongest prediction of A1C.

RESEARCH DESIGN AND METHODS

In the A1C-Derived Average Glucose (ADAG) study, glucose levels were monitored in 507 participants (268 type 1 diabetic, 159 type 2 diabetic, and 80 nondiabetic subjects) with continuous glucose monitoring (CGM) and frequent self-monitoring of blood glucose (SMBG) during 16 weeks. We calculated several indexes of glycemia and analyzed their intercorrelations. The association between glucose measurements at different times of the day (pre- and postprandial) and A1C was examined using multiple linear regression.

RESULTS

Indexes of glucose variability showed strong intercorrelation. Among postprandial indexes, the area under the glucose curve calculated from CGM 2 h after a meal correlated well with the 90-min SMBG postprandial measurements. Fasting blood glucose (FBG) levels were only moderately correlated with indexes of hyperglycemia and average or postprandial glucose levels. Indexes derived with SMBG strongly correlated with those from CGM. Some SMBG time points had a stronger association with A1C than others. Overall, preprandial glucose values had a stronger association with A1C than postprandial values for both diabetes types, particularly for type 2 diabetes.

CONCLUSIONS

Indexes of glucose variability and average and postprandial glycemia intercorrelate strongly within each category. Variability indexes are weakly correlated with the other categories, indicating that these measures convey different information. FBG is not a clear indicator of general glycemia. Preprandial glucose values have a larger impact on A1C levels than postprandial values.
Leptin Deficiency Causes Insulin Resistance Induced by Uncontrolled Diabetes
Authors: German Jonathan P. , Wisse Brent E. , Thaler Joshua P. , Oh-I Shinsuke , Sarruf David A. , Ogimoto Kayoko , Kaiyala Karl J. , Fischer Jonathan D. , Matsen Miles E. , Taborsky Gerald J. , Schwartz Michael W. , Morton Gregory J.
Published: April 2010

OBJECTIVE

Depletion of body fat stores during uncontrolled, insulin-deficient diabetes (uDM) results in markedly reduced plasma leptin levels. This study investigated the role of leptin deficiency in the genesis of severe insulin resistance and related metabolic and neuroendocrine derangements induced by uDM.

RESEARCH DESIGN AND METHODS

Adult male Wistar rats remained nondiabetic or were injected with the β-cell toxin, streptozotocin (STZ) to induce uDM and subsequently underwent subcutaneous implantation of an osmotic minipump containing either vehicle or leptin at a dose (150 μg/kg/day) designed to replace leptin at nondiabetic plasma levels. To control for leptin effects on food intake, another group of STZ-injected animals were pair fed to the intake of those receiving leptin. Food intake, body weight, and blood glucose levels were measured daily, with body composition and indirect calorimetry performed on day 11, and an insulin tolerance test to measure insulin sensitivity performed on day 16. Plasma hormone and substrate levels, hepatic gluconeogenic gene expression, and measures of tissue insulin signal transduction were also measured.

RESULTS

Physiologic leptin replacement prevented insulin resistance in uDM via a mechanism unrelated to changes in food intake or body weight. This effect was associated with reduced total body fat and hepatic triglyceride content, preservation of lean mass, and improved insulin signal transduction via the insulin receptor substrate–phosphatidylinositol-3-hydroxy kinase pathway in the liver, but not in skeletal muscle or adipose tissue. Although physiologic leptin replacement lowered blood glucose levels only slightly, it fully normalized elevated plasma glucagon and corticosterone levels and reversed the increased hepatic expression of gluconeogenic enzymes characteristic of rats with uDM.

CONCLUSIONS

We conclude that leptin deficiency plays a key role in the pathogenesis of severe insulin resistance and related endocrine disorders in uDM. Treatment of diabetes in humans may benefit from correction of leptin deficiency as well as insulin deficiency.
Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial
Authors: Riddle Matthew C. , Ambrosius Walter T. , Brillon David J. , Buse John B. , Byington Robert P. , Cohen Robert M. , Goff David C. , Malozowski Saul , Margolis Karen L. , Probstfield Jeffrey L. , Schnall Adrian , Seaquist Elizabeth R. ,   for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Investigators
Published: April 2010

OBJECTIVE

Randomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality.

RESEARCH DESIGN AND METHODS

Participants with type 2 diabetes (n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.1%) were randomly assigned to treatment strategies targeting either A1C <6.0% (intensive) or A1C 7.0–7.9% (standard). Data obtained during 3.4 (median) years of follow-up before cessation of intensive treatment were analyzed using several multivariable models.

RESULTS

Various characteristics of the participants and the study sites at baseline had significant associations with the risk of mortality. Before and after adjustment for these covariates, a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year. Higher average A1C was associated with greater risk of death. The risk of death with the intensive strategy increased approximately linearly from 6–9% A1C and appeared to be greater with the intensive than with the standard strategy only when average A1C was >7%.

CONCLUSIONS

These analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.
Aldose Reductase Gene Polymorphisms and Diabetic Retinopathy Susceptibility
Authors: Abhary Sotoodeh , Burdon Kathryn P. , Laurie Kate J. , Thorpe Stacey , Landers John , Goold Lucy , Lake Stewart , Petrovsky Nikolai , Craig Jamie E.
Published: April 2010

OBJECTIVE

Aldose reductase (ALR) is involved in diabetic microvascular damage via the polyol pathway. A recent meta-analysis found genetic variation in the ALR gene (AKR1B1) to be significantly associated with diabetic retinopathy (DR). We investigated the genetic association of AKR1B1 with DR.

RESEARCH DESIGN AND METHODS

The study enrolled 909 individuals with diabetes. Participants were genotyped for an AKR1B1 (CA)n microsatellite and 14 tag single nucleotide polymorphisms, and ophthalmological assessment was performed.

RESULTS

A total of 514 individuals were found to have DR. rs9640883 was significantly associated with DR (P = 0.0005). However, AKR1B1 variation was not independently associated with DR development after adjusting for relevant clinical parameters. rs9640883 was associated with duration of diabetes (P = 0.002).

CONCLUSION

Many previous reports have failed to account for known risk factors for DR. The commonly reported association of AKR1B1 with DR may be due to an association of the gene with younger age at onset of diabetes.
Dietary Phylloquinone and Menaquinones Intakes and Risk of Type 2 Diabetes
Authors: Beulens Joline W.J. , van der A Daphne L. , Grobbee Diederick E. , Sluijs Ivonne , Spijkerman Annemieke M.W. , van der Schouw Yvonne T.
Published: April 2010

OBJECTIVE

To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS

We used data from a prospective cohort study in 38,094 Dutch men and women, aged 20–70 years. Dietary phylloquinone and menaquinones intakes were assessed using a validated food frequency questionnaire. Diabetes case patients were ascertained mainly via self-report and verified against medical records.

RESULTS

During 10.3 years of follow-up, 918 incident cases of diabetes were documented. In a multivariate model adjusting for diabetes risk factors and dietary factors, phylloquinone intake tended to be associated (P = 0.08) with a reduced risk of type 2 diabetes with a hazard ratio (HR) of 0.81 (95% CI 0.66–0.99) for the highest versus the lowest quartile. For menaquinones intake, a linear, inverse association (P = 0.038) with risk of type 2 diabetes was observed with an HR of 0.93 (0.87–1.00) for each 10-μg increment in the multivariate model.

CONCLUSIONS

This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes.
Cardiovascular Disease Mortality in Europeans in Relation to Fasting and 2-h Plasma Glucose Levels Within a Normoglycemic Range
Authors: Ning Feng , Tuomilehto Jaakko , Pyörälä Kalevi , Onat Altan , Söderberg Stefan , Qiao Qing ,   for the DECODE Study Group
Published: April 2010

OBJECTIVE

To study mortality in relation to fasting plasma glucose (FPG) and 2-h plasma glucose levels within the normoglycemic range.

RESEARCH DESIGN AND METHODS

Data from 19 European cohorts comprising 12,566 men and 10,874 women who had FPG <6.1 mmol/l and 2-h plasma glucose <7.8 mmol/l at baseline examination were analyzed. Multivariate-adjusted hazard ratios (HRs) and 95% CIs for deaths from cardiovascular disease (CVD), non-CVD, and all causes were estimated for individuals whose 2-h plasma glucose > FPG (group II) compared with those whose 2-h plasma glucose ≤ FPG (group I).

RESULTS

A total of 827 (246) CVD and 611 (351) non-CVD and 1,438 (597) all-cause deaths occurred in men (women). Group II was older and had higher BMI, blood pressure, and fasting insulin than group I. The multivariate-adjusted HRs (95% CIs) for CVD, non-CVD, and all-cause mortality were 1.22 (1.05–1.41), 1.09 (0.92–1.29), and 1.16 (1.04–1.30) in men and 1.40 (1.03–1.89), 0.99 (0.79–1.25), and 1.13 (0.94–1.35) in women, respectively, for group II as compared with group I. HRs were 1.25 (1.05–1.50), 1.09 (0.89–1.34), and 1.18 (1.03–1.35) in men and 1.60 (1.03–2.48), 1.05 (0.78–1.42), and 1.18 (0.93–1.51) in women, respectively, after additional adjustment for fasting insulin in a subgroup of individuals.

CONCLUSIONS

In individuals with both FPG and 2-h plasma glucose within the normoglycemic range, high 2-h plasma glucose was associated with insulin resistance and increased CVD mortality.
Exenatide Affects Circulating Cardiovascular Risk Biomarkers Independently of Changes in Body Composition
Authors: Bunck Mathijs C. , Diamant Michaela , Eliasson Bjorn , Cornér Anja , Shaginian Rimma M. , Heine Robert J. , Taskinen Marja-Riitta , Yki-Järvinen Hannele , Smith Ulf
Published: April 2010

OBJECTIVE

To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers.

RESEARCH DESIGN AND METHODS

Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured.

RESULTS

Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight.

CONCLUSIONS

Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.
Diabetic Foot Prevention
Authors: Lavery Lawrence A. , Hunt Nathan A. , LaFontaine Javier , Baxter Cory L. , Ndip Agbor , Boulton Andrew J.M.
Published: April 2010

OBJECTIVE

To evaluate the frequency of foot prevention strategies among high-risk patients with diabetes.

RESEARCH DESIGN AND METHODS

Electronic medical records were used to identify 150 patients on dialysis and 150 patients with previous foot ulceration or amputation with 30 months follow-up to determine the frequency with which patients received education, podiatry care, and therapeutic shoes and insoles as prevention services.

RESULTS

Few patients had formal education (1.3%), therapeutic shoes/insoles (7%), or preventative podiatric care (30%). The ulcer incidence density was the same in both groups (210 per 1,000 person-years). In contrast, the amputation incidence density was higher in the dialysis group compared with the ulcer group (58.7 vs. 13.1 per 1,000 person-years, P < 0.001). Patients on dialysis were younger and more likely to be of non-Hispanic white descent (P = 0.006) than patients with a previous history of ulcer or amputation.

CONCLUSIONS

Prevention services are infrequently provided to high-risk patients.
The Effect of Diversification on Performance Revisited: How the Dominance of Diversifiers Versus Specialists Drives the Diversification‐Performance Relationship
Authors: Becerra Manuel , Santaló Juan
Published: April 2010

In this paper, we argue that the effect of diversification on performance is not homogeneous across industries, as previously assumed in the literature on diversification in strategy and finance. We provide empirical evidence that some industries are more friendly environments for diversified firms than for specialists, and vice versa. The implications of this qualification for the diversification‐performance relationship are investigated in this study. The results show that the number of specialists in an industry is an important moderator of the diversification‐performance relationship, and it determines the existence of a positive, negative, or curvilinear relationship. Diversification has a more negative impact on performance as the number of specialized firms in the industries in the sample increases. Although we find clear evidence of the curvilinear relationship between diversification and performance frequently found in strategy research, the relationship seems to be the result of not accounting for the relative dominance of diversifiers versus specialists in the industries in the sample.