bluuebunny/crossref_metadata_2025 huggingface dataset:
Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart
Authors: Wang Peipei , Chatham John C.
Published: April 2004

The aim of this study was to determine whether the transition from insulin resistance to hyperglycemia in a model of type 2 diabetes leads to intrinsic changes in the myocardium that increase the sensitivity to ischemic injury. Hearts from 6-, 12-, and 24-wk-old lean (Control) and obese Zucker diabetic fatty (ZDF) rats were isolated, perfused, and subjected to 30 min of low-flow ischemia (LFI) and 60 min of reperfusion. At 6 wk, ZDF animals were insulin resistant but not hyperglycemic. By 12 wk, the ZDF group was hyperglycemic and became progressively worse by 24 wk. In spontaneously beating hearts rate-pressure product (RPP) was depressed in the ZDF groups compared with age-matched Controls, primarily due to lower heart rate. Pacing significantly increased RPP in all ZDF groups; however, this was accompanied by a significant decrease in left ventricular developed pressure. There was also greater contracture during LFI in the ZDF groups compared with the Control group; surprisingly, however, functional recovery upon reperfusion was significantly higher in the diabetic 12- and 24-wk ZDF groups compared with age-matched Control groups and the 6-wk ZDF group. This improvement in recovery in the ZDF diabetic groups was independent of substrate availability, severity of ischemia, and duration of diabetes. These data demonstrate that, although the development of type 2 diabetes leads to progressive contractile and metabolic abnormalities during normoxia and LFI, it was not associated with increased susceptibility to ischemic injury.
Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-α, and FFAs to low-dose endotoxemia in humans
Authors: Krogh-Madsen Rikke , Møller Kirsten , Dela Flemming , Kronborg Gitte , Jauffred Sune , Pedersen Bente Klarlund
Published: April 2004

Insulin therapy to maintain euglycemia increases survival in critically ill patients. To explore possible mechanisms of action, we investigated the effect of endotoxin on circulating cytokines, free fatty acids (FFA), and leukocytes during manipulated plasma glucose and insulin concentrations. Ten volunteers underwent three trials each, receiving an intravenous bolus of endotoxin (0.2 ng/kg) during normoglycemia ( trial A, control), during a hyperglycemic clamp at 15 mM ( trial B), and during a hyperinsulinemic euglycemic clamp ( trial C). Endotoxin induced an increase in neutrophil count, a decrease in lymphocyte count, and an increase in serum levels of TNF-α, IL-6, and FFA. There was no difference in the TNF response between the three trials; the IL-6 levels were increased during the late phase of trials B and C compared with trial A. The endotoxin-induced elevation in FFA in trial A was suppressed during trials B and C. Clamping ( trials B and C) caused a reduction in lymphocyte count that persisted after endotoxin injection. We conclude that low-dose endotoxemia triggers a subclinical inflammatory response and an elevation in FFA. The finding that high insulin serum concentrations induce a more prolonged increase in the anti-inflammatory cytokine IL-6 and suppress the levels of FFA suggests that insulin treatment of patients with sepsis may exert beneficial effects by inducing anti-inflammation and protection against FFA toxicity, and thereby inhibit FFA-induced insulin resistance.
Osteogenic regulation of vascular calcification: an early perspective
Authors: Vattikuti Radhika , Towler Dwight A.
Published: April 2004

Cardiovascular calcification is a common consequence of aging, diabetes, hypercholesterolemia, mechanically abnormal valve function, and chronic renal insufficiency. Although vascular calcification may appear to be a uniform response to vascular insult, it is a heterogenous disorder, with overlapping yet distinct mechanisms of initiation and progression. A minimum of four histoanatomic variants—atherosclerotic (fibrotic) calcification, cardiac valve calcification, medial artery calcification, and vascular calciphylaxis—arise in response to metabolic, mechanical, infectious, and inflammatory injuries. Common to the first three variants is a variable degree of vascular infiltration by T cells and macrophages. Once thought benign, the deleterious clinical consequences of calcific vasculopathy are now becoming clear; stroke, amputation, ischemic heart disease, and increased mortality are portended by the anatomy and extent of calcific vasculopathy. Along with dystrophic calcium deposition in dying cells and lipoprotein deposits, active endochondral and intramembranous (nonendochondral) ossification processes contribute to vascular calcium load. Thus vascular calcification is subject to regulation by osteotropic hormones and skeletal morphogens in addition to key inhibitors of passive tissue mineralization. In response to oxidized lipids, inflammation, and mechanical injury, the microvascular smooth muscle cell becomes activated. Orthotopically, proliferating stromal myofibroblasts provide osteoprogenitors for skeletal growth and fracture repair; however, in valves and arteries, vascular myofibroblasts contribute to cardiovascular ossification. Current data suggest that paracrine signals are provided by bone morphogenetic protein-2, Wnts, parathyroid hormone-related polypeptide, osteopontin, osteoprotegerin, and matrix Gla protein, all entrained to endocrine, metabolic, inflammatory, and mechanical cues. In end-stage renal disease, a “perfect storm” of vascular calcification often occurs, with hyperglycemia, hyperphosphatemia, hypercholesterolemia, hypertension, parathyroid hormone resistance, and iatrogenic calcitriol excess contributing to severe calcific vasculopathy. This brief review recounts emerging themes in the pathobiology of vascular calcification and highlights some fundamental deficiencies in our understanding of vascular endocrinology and metabolism that are immediately relevant to human health and health care.
An Algorithm for the Detection of Faces on the Basis of Gabor Features and Information Maximization
Authors: Imaoka Hitoshi , Okajima Kenji
Published: April 2004

We propose an algorithm for the detection of facial regions within input images. The characteristics of this algorithm are (1) a vast number of Gabor-type features (196,800) in various orientations, and with various frequencies and central positions, which are used as feature candidates in representing the patterns of an image, and (2) an information maximization principle, which is used to select several hundred features that are suitable for the detection of faces from among these candidates. Using only the selected features in face detection leads to reduced computational cost and is also expected to reduce generalization error. We applied the system, after training, to 42 input images with complex backgrounds (Test Set A from the Carnegie Mellon University face data set). The result was a high detection rate of 87.0%, with only six false detections. We compared the result with other published face detection algorithms.
Analysis of Sparse Representation and Blind Source Separation
Authors: Li Yuanqing , Cichocki Andrzej , Amari Shun-ichi
Published: April 2004

In this letter, we analyze a two-stage cluster-then-l1-optimization approach for sparse representation of a data matrix, which is also a promising approach for blind source separation (BSS) in which fewer sensors than sources are present. First, sparse representation (factorization) of a data matrix is discussed. For a given overcomplete basis matrix, the corresponding sparse solution (coefficient matrix) with minimum l1 norm is unique with probability one, which can be obtained using a standard linear programming algorithm. The equivalence of the l1—norm solution and the l0—norm solution is also analyzed according to a probabilistic framework. If the obtained l1—norm solution is sufficiently sparse, then it is equal to the l0—norm solution with a high probability. Furthermore, the l1—norm solution is robust to noise, but the l0—norm solution is not, showing that the l1—norm is a good sparsity measure. These results can be used as a recoverability analysis of BSS, as discussed. The basis matrix in this article is estimated using a clustering algorithm followed by normalization, in which the matrix columns are the cluster centers of normalized data column vectors. Zibulevsky, Pearlmutter, Boll, and Kisilev (2000) used this kind of two-stage approach in underdetermined BSS. Our recoverability analysis shows that this approach can deal with the situation in which the sources are overlapped to some degree in the analyzed
Lead Markets for Environmental Innovations: A New Role for the Nation State
Authors: Jänicke Martin , Jacob Klaus
Published: April 2004

The article discusses the role of the nation state in stimulating lead markets for green innovations. It is often feared that the nation state loses its capacity for action because of economic and political globalization. This article rejects this hypothesis. It argues that empirical research on actual environmental policies reveals that it is most often nation states that pioneer new approaches, push for advances in environmental policy, and serve as regional starting points for new ‘green’ technologies. The innovation and diffusion of environmental technologies and their support through national environmental policies bear the potential of a far-reaching ecological modernization.
A CLEAR AND PRESENT DANGER: "WAHHABISM" AS A RHETORICAL FOIL
Authors: Knysh Alexander
Published: April 2004

"We shall not return to the state anterior to discourse—in which nothing has yet been said, and in which things are only just beginning to emerge out of the grey light; and we shall not pass beyond discourse in order to rediscover the forms that it has created and left behind it; we shall remain, or try to remain, at the level of discourse itself…A task consists of not—of no longer—treating discourses as groups of signs (signifying elements referring to contents or representations) but as practices that systematically form the objects of which they speak."
Structure of a population of the lizard Podarcis bocagei in northwest Spain: variations in age distribution, size distribution and sex ratio
Authors: Galán Pedro
Published: April 2004

Mark-recapture techniques were used to investigate population size, age distribution, size distribution and sex ratio in a population of the lacertid lizard Podarcis bocagei in an abandoned gravel pit in northwest Spain. The study was carried out over a 2-year period. Despite relatively high maximum longevity, the population age distribution was characteristic of small, short-lived lizard species (i.e., there was a relatively high proportion of immature individuals). Population size declined over the study period, largely because of a drop in the number of immature animals: this may be partially attributable to density-dependent factors, but was probably due largely to a decline in habitat favourability as a result of colonisation of the study site by vegetation. The sex ratio was significantly female-biased in all cohorts studied, not only among adults but also among juveniles and sub-adults. However, sex ratio at hatching (as investigated by laboratory hatching of clutches laid by captured pregnant females) did not differ significantly from one-to-one. There was no difference found in survival probabilities between males and females. The observed bias in sex ratio must therefore be attributed to between-sex differences in net emigration.
Deciphering Sex Segregation
Authors: Charles Maria
Published: April 2004

Scholars and policy-makers increasingly treat occupational sex segregation as a generic indicator of female economic disadvantage. This view is difficult to reconcile with evidence that levels of sex segregation are lower in reputably ‘gender-traditional’ countries such as Italy, Japan, and Portugal than in ‘progressive’ Sweden and the United States. Understanding such seemingly anomalous patterns requires a two-dimensional conceptualization of occupational sex segregation - in particular, an analytical distinction between vertical and horizontal gender inequalities. Based on data from 10 industrialized countries, claims regarding (1) the hybrid nature of sex segregation and (2) the cultural and structural factors that influence its various components are empirically assessed. Results confirm that unequal distributions across the manual-non-manual divide (‘horizontal segregation’) and status differentials within these sectors (‘vertical segregation’) together account for a considerable share of occupational gender inequality. Gender-egalitarian cultural norms are associated with lower levels of vertical segregation in the non-manual sector, while postindustrial economic structures coincide with greater horizontal segregation (and more vertical segregation of non-manual occupations). The complex horizontal and vertical dynamics revealed here cast further doubt on unidimensional conceptualizations of sex segregation. They also provide the key for deciphering some long-standing empirical puzzles in the field.
The Role of Subjective Well-Being in Positive Youth Development
Authors: Park Nansook
Published: April 2004

Comprehensive perspectives on well-being that include positive aspects of human life such as subjective wellbeing have recently been proposed. Life satisfaction is the cognitive component of subjective well-being and plays an important role in positive development as an indicator, a predictor, a mediator/moderator, and an out-come. Whereas low life satisfaction is associated with psychological, social, and behavior problems, high life satisfaction is related to good adaptation and optimal mental health among youth. Life satisfaction and positive affect mitigate the negative effects of stressful life events and work against the development of psychological and behavioral problems among youth. Supportive parenting, engagement in challenging activities, positive life events, and high-quality interactions with significant others contribute to the development of life satisfaction. Further longitudinal research into the mechanisms of how life satisfaction plays its role in positive youth development is needed to promote the psychological wellbeing of all youth.
Character Strengths and Positive Youth Development
Authors: Park Nansook
Published: April 2004

The goal of positive youth development is to build and strengthen assets that enable youth to grow and flourish throughout life. In this article, the definition, origins, and assessment of character strengths and ways of fostering them are discussed. Character strengths are here defined as a family of positive traits reflected in thoughts, feelings, and behaviors. Character strengths are important in their own right, but they additionally promote well-being and buffer against psychological disorders among youth. Good parenting, close relationships with peer and family, positive role models, positive institutions, and various youth development programs play important roles in the development of character strengths. Character strengths exist in degrees, and they can be measured as individual differences. Future studies should approach character strengths as multidimensional constructs to understand better the structure and development of character, and how it contributes to positive youth development.
Youth as People: the Protective Aspects of Youth Development in After-School Settings
Authors: Nicholson Heather Johnston , Collins Christopher , Holmer Heidi
Published: April 2004

Youth development organizations have a common commitment to young people’s physical, emotional, and educational growth and development. A youth-centered atmosphere where young people feel supported and empowered by the community distinguishes successful programs from others that approach programming without considering young people the most important stake-holders. Programs serve youth best when the environments in which they function are intentionally inclusive, multicultural, and systematically nondiscriminatory. A safe and supportive place in which to develop an identity and confront the tough issues and extraordinary pressures of growing up is at the core of youth development environments that make a real difference. Some of the best youth development programs also make the successful link between volunteerism and positive mental health and support the concept that community service is an important component of subsequent civic engagement.
Research-Based Character Education
Authors: Berkowitz Marvin W. , Bier Melinda C.
Published: April 2004

Whereas character education is not new, scientific study of its effectiveness has been only sporadically implemented during the past thirty-five years. Much of the application of character education is therefore not informed by a scientific knowledge base. This article introduces a scientific perspective on character education and a summary of the research base examining the student impact of school-based character education. From this research base, general principles of effective practice are derived. This in turn is used to offer suggestions to practitioners and policy makers for the improvement of school-based character education.
Cultivating Optimism in Childhood and Adolescence
Authors: Gillham Jane , Reivich Karen
Published: April 2004

How do optimism and hope develop in young people? How can they be promoted? This article reviews research on the development of optimism and hope and interventions designed to build these qualities in youth. The Penn Resiliency Program is discussed as an example of a school-based intervention that may promote hope and prevent symptoms of depression and anxiety. Limits of existing studies and directions for future research are also discussed.
What is Wisdom and How Can We Develop It?
Authors: Sternberg Robert J.
Published: April 2004

Wisdom is the use of one’s intelligence and experience as mediated by values toward the achievement of a common good through a balance among (1) intrapersonal, (2) interpersonal, and (3) extrapersonal interests, over the (1) short and (2) long terms, to achieve a balance among (1) adaptation to existing environments, (2) shaping of existing environments, and (3) selection of new environments. This article discusses the balance theory of wisdom, and how wisdom can be assessed and developed.
Positive Stigma: Examining Resilience and Empowerment in Overcoming Stigma
Authors: Shih Margaret
Published: April 2004

The traditional literature on stigma focuses on identifying factors contributing to the harmful impact of stigmas on the lives of stigmatized individuals. This focus, however, cannot explain the many cases of individuals possessing a stigmatized identity flourishing in our society. This article investigates the processes that successful stigmatized individuals use to overcome the harmful consequences of stigmatization. Specifically, this article reviews three processes: (1) compensation; (2) strategic interpretations of the social environment; and (3) focusing on multiple identities that have been identified in the literature to help stigmatized individuals handle prejudice and discrimination. Moreover, successful individuals adopt an “empowerment” model as opposed to a “coping” model when dealing with stigma. In other words, successful individuals view overcoming the adversities associated with stigma as an empowering process, as opposed to a depleting process. This discussion underscores the importance of adopting a new approach to gain a fuller understanding of the experience of being stigmatized.
The Art of Good Hope
Authors: McGeer Victoria
Published: April 2004

What is hope? Though variously characterized as a cognitive attitude, an emotion, a disposition, and even a process or activity, hope, more deeply, a unifying and grounding force of human agency. We cannot live a human life without hope, therefore questions about the rationality of hope are properly recast as questions about what it means to hope well. This thesis is defended and elaborated as follows. First, it is argued that hope is an essential and distinctive feature of human agency, both conceptually and developmentally. The author then explores a number of dimensions of agency that are critically implicated in the art of hoping well, drawing on several examples from George Eliot’s Middlemarch. The article concludes with a short section that suggests how hoping well in an individual context may be extended to hope at the collective level.
Hope and Its Place in Mind
Authors: Pettit Philip
Published: April 2004

People may have open minds on whether a life-extending drug or technology is going to be developed before their sixties and may strongly desire that development. Do they therefore hope that it occurs? Do they hope for it in the substantive sense of “pinning their hopes” on the development? No, they do not. Hoping for a prospect in that sense certainly presupposes having an open mind on whether it will occur and having a desire for its occur-rence. But, more crucially, it means investing the prospect with a characteristic, galvanizing, and orientating role: it involves setting aside doubts about the possible nonoccurrence of the prospect and acting accordingly. This article offers a characterization of hope in that substantive sense and argues both that it can be rational and that it is ubiquitous.
The Hope Process and Social Inclusion
Authors: Braithwaite Valerie
Published: April 2004

The psychology of individual hope has been well articulated through the work of Seligman and Snyder, but scholars have done little to extend this model to under-stand how individuals engage in collective hope. This article develops a model of the collective hope process that emphasizes the importance of principles of social inclusion, open contestation of goals, and transparent pathways to give certainty to the belief that the public is important to the process, even if the same public is uncertain and divided about the outcomes. The study is based on a survey of 2,040 Australians who shared their hopes, fears, and actions in relation to the Australian taxation system in 2000.
Science and Politics in Police Research: Reflections on Their Tangled Relationship
Authors: Walker Samuel
Published: April 2004

Police research in the United States has been heavilyinfluenced by external politics. This influence isagendasetting rather than truth-suppressing. Agenda-settinginfluence occurs where external political influencecauses researchers to undertake research on a subject orsubjects they had previously neglected. The influence ofpolitics on research has, in some very importantrespects, greatly enriched social science research on thepolice, forcing scholars to confront subjects andmethodological issues they had previously neglected. Therelationship between police research and the externalpolitical environment is extremely complex and is by nomeans simple or one-directional. There are also someimportant examples, notably, community policing, ofwhere research findings have influenced the politicalagenda.
Trends in the Policing Industry
Authors: Maguire Edward R. , King William R.
Published: April 2004

Fairness and Effectiveness in Policing: The Evidencedoes a terrific job of discussing the limited research on trends in the policing industry, but what it does not include is perhaps as informative. Large gaps in the body of research limit our ability to make definitive inferences about how the policing industry is changing. These gaps result in part from a lack of systematic, standardized, longitudinal data collection and analysis on the nature and outputs of police organizations in the United States. As a result, we know little about basic descriptive features of policing and how these features are changing over time. Lacking the ability to track even the most basic descriptive trends, the police research industry is at even more of a loss in developing careful empirical explanations of these trends. This article discusses some of these trends, summarizes what we know and what we do not know about them, and provides some recommendations for how the police research industry can do a better job of describing and explaining trends in the police industry.
War, Exile, Moral Knowledge and the Limits of Psychiatric Understanding: A Clinical Case Study of a Bosnian Refugee in London
Authors: Summerfield Derek
Published: April 2004

Background: This paper describes a Bosnian refugee, a survivor of war and ethnic cleansing, during a 3-year follow-up in a psychiatry clinic.

Discussion: This case throws light on the tension between medicotherapeutic and sociomoral ways of understanding the effects of such experiences, and of the limitations of morally and politically neutral psychiatric categories and technologies. Suffering always invokes questions of values: in this case the clinical picture represented a moral protest at what had been done with such impunity, and a refusal to accommodate to a world which now seemed unintelligible. The clinical picture also embodied the collective outrage, and sense of unfinished business, which many back in Bosnia itself were carrying in the wake of the 1995 Dayton peace accords which effectively legitimised the lines of ethnic cleansing.

Conclusions: DSM or ICD diagnoses of depressive disorder or post-traumatic stress disorder turned out to lack validity and explanatory power. Claims that victims of war and atrocity typically have an unmet need for mental health services are overstated. Recovery from the effects of war may depend on reestablishing a sense of intelligibility, a task that must primarily go on in social space rather than mental space.
Measuring Community Mental Health in Developing Societies: Evaluation of a Checklist Format in Nepal
Authors: Tausig Mark , Subedi Sree , Broughton C. L. , Subedi Janardan , Williams-Blangero Sarah
Published: April 2004

Background: There is growing recognition of the importance of mental health problems in developing countries. In large part, however, we have very limited epidemiological data at national and/or community levels about the prevalence of mental illnesses.

Aims: The purpose of this paper is to describe the reliability and validity characteristics of an assessment tool that may be useful for conducting community-level surveys (particularly in rural communities of developing countries) to obtain prevalence rates of mental illnesses.

Methods: We used a sample of adults residing in a rural village in Nepal to assess disorders with a modified version of the DSM-III-R Checklist. We evaluated construct validity, scale reliability, convergent validity and discriminant validity.

Results: There is strong evidence for the construct validity of generalized anxiety and depression in our sample. By contrast, the symptoms associated with mania and schizophrenia were not empirically distinct. Convergent validity is acceptable. As a test of validity characteristics, the pattern of sociodemographic correlations suggests that the specific social origins of disorder in Nepal will require further investigation.

Conclusion: The first step in obtaining high quality information on the distribution of mental illness in developing countries is to establish some reliable and valid indicators of disorder. The checklist format for assessing disorder appears to meet this objective and offers the possibility that community-level prevalence studies can be reasonably conducted.
British Romantic Melancholia
Authors: Dolan Elizabeth A.
Published: April 2004

In the context of increasing British discomfort with the cult of sensibility in the 1790s, medical writers redefined the profile of the melancholic as a highly rational, rather than emotional, literary man. Charlotte Smith’s representation of melancholia in her Elegiac Sonnets returns to the mid-eighteenth-century understanding of the illness, which portrayed the melancholic as a person of both sensibility and rationality. In her attempt to claim melancholia and its association with literary genius, Smith profoundly influenced the content of what was to be called Romantic poetry.
In The Name of the Other I... GÉRard De Nerval
Authors: Froment Meurice Marc
Published: April 2004

What was the French poet Gérard de Nerval thinking, when he wrote under his too realistic portrait: ‘I am the other’? In attempting to distance himself from his reputation as a madman, he deprived himself of a proper self-identity. This essay approaches melancholy from the point of view of the (proper) name–its malefic power and the strategies to inscribe/erase its destabilizing virtues.
Corrections
Authors: Toal Catherine
Published: April 2004

This paper examines the effect on contemporary American literature of a popular discourse on depression, looking at Rick Moody’s memoir The Black Veil , and two novels, Jonathan Franzen’s The Corrections and David Foster Wallace’s Infinite Jest . It argues that, despite their differences in style and genre, the three texts gesture towards a shared set of preoccupations regarding the culture of depression, associating it (either critically or inadvertently) with the absence of coherent forms of cultural authority and processes of formation, and with a threat to masculinity.
German Anti-Americanism in Context
Authors: Berendse Gerrit-Jan
Published: April 2004

The anti-American rhetoric which suddenly emerged in Western Europe’s intellectual discourse during the showdown of the Second Gulf War in 2002–3 is more than a political act. The new patterns of antagonism are symptoms of a process of cultural emancipation that commenced in the 1990s. Surprisingly, the rationale behind the growing demise of the project of Americanization which dominated the Cold War is a critical examination of Europe’s entanglement in a postmodern culture industry and its global markets. In the aftermath of unification, Germany’s cultural scene has been meticulously scrutinized by its own intellectuals, who perceived the cultural imperialism of the USA as a threat. To some extent based on anti-American traditions that originate in Germany’s period of Romanticism, contemporary intellectuals are acting as the guardians of the cultural values of so- called ‘Old Europe’. However, it will be argued that the appraisal of the political and cultural intimacy of both continents will not only result in a schism but will also foster new and exciting transatlantic liaisons.
Absence of a Pharmacokinetic Interaction between Etanercept and Warfarin
Authors: Zhou Honghui , Patat Alain , Parks Virginia , Buckwalter Mary , Metzger Deborah , Korth‐Bradley Joan
Published: April 2004

Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr) fusion protein, is effective and well tolerated in the treatment of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between a single dose of Rand S‐enantiomers of warfarin and multiple doses of etanercept after administration of warfarin and etanercept alone and together. In a nonrandomized, three‐period study, 12 healthy male subjects received a single oral 25‐mg dose of warfarin after an overnight fast, followed by twice‐weekly 25‐mg subcutaneous doses of etanercept for seven doses. The last dose of etanercept was administered concurrently with a second dose of warfarin. Serial blood samples for plasma warfarin concentration measurement and international normalized ratio (INR) assessment were collected before and up to 144 hours after dose administration. Serial blood samples for serum etanercept concentration measurement were collected before and up to 60 hours after the sixth dose and 264 hours after the seventh dose. Etanercept did not affect the pharmacokinetics and pharmacodynamics of warfarin. All ratios of maximum serum concentration (Cmax) and area under the serum concentration versus time curve (AUC) for pharmacokinetics (R‐ and S‐enantiomers of warfarin) and INR fell within the confidence interval of 0.8 to 1.25. Warfarin also did not cause a clinically significant alteration in the pharmacokinetics of etanercept. In conclusion, coadministration of etanercept and warfarin would not be expected to change the pharmacokinetics of either medication; therefore, no dosage adjustment is needed in cases in which warfarin and etanercept are coadministered.
Multiple‐Dose FTY720: Tolerability, Pharmacokinetics, and Lymphocyte Responses in Healthy Subjects
Authors: Kovarik John M. , Schmouder Robert , Barilla Denise , Riviere Gilles‐Jacques , Wang Yibin , Hunt Thomas
Published: April 2004

FTY720 is a sphingosine‐1‐phosphate receptor agonist being developed as an immunomodulator for acute rejection prophylaxis after organ transplantation. This study was performed to characterize the pharmacokinetics of and lymphocyte response to multiple‐dose FTY720. In this randomized, double‐blind study, three groups of 20 healthy subjects each received either placebo, 1.25 mg/day FTY720, or 5 mg/day FTY720 for 7 consecutive days. FTY720 blood concentrations and lymphocyte counts were assessed over the weeklong treatment phase and over a month‐long washout phase. The relationship between FTY720 blood concentrations and lymphocyte counts was explored by an inhibitory Emax model. First‐dose exposure was consistent with dose proportionality between the low‐ and high‐dose groups. Blood levels accumulated fivefold over the treatment period. Exposure on day 7 was dose proportional for Cmax (5.0 ± 1.0 vs. 18.2 ± 4.1 ng/mL) and for AUC (109 ± 24 vs. 399 ±85 ng•h/ mL). Washout pharmacokinetics after the last dose indicated an elimination half‐life averaging 8 days. Lymphocyte counts decreased by 80% in subjects receiving the lower dose to a nadir of 0.4 ± 0.1 × 109/L and by 88% in subjects receiving the upper dose to a nadir of 0.2 ±0.1 ×109/L. Descriptive exposure‐response modeling estimated that the lymphocyte response at 5 mg/day is near the maximal response achievable. By the end‐of‐study evaluation on day 35, lymphocyte counts had recovered to within 75% and 50% of baseline in the low‐ and high‐dose groups, respectively. In summary, systemic exposure to FTY720 was consistent with dose‐proportionality after both single‐ and multiple‐dose administration. Total lymphocyte counts decreased from baseline by 80% and 88% at regimens of 1.25 and 5 mg/day, respectively. Exposure‐response modeling provided evidence that 5 mg/day FTY720 resulted in a near‐maximal dynamic effect of this drug on lymphocytes.
Pharmacokinetic and Safety Evaluation of Palonosetron, a 5‐Hydroxytryptamine‐3 Receptor Antagonist, in U.S. and Japanese Healthy Subjects
Authors: Stoltz Randall , Cyong Jong‐Chol , Shah Ajit , Parisi Simona
Published: April 2004

Palonosetron (Aloxi™, Onicit®) is a selective 5‐HT3 receptor antagonist recently approved by the Food and Drug Administration for the prevention of acute and delayed chemotherapy‐induced nausea and vomiting. This study was performed to determine the pharmacokinetics and assess the safety and tolerability of intravenous (IV) palonosetron in healthy U.S. and Japanese subjects. Subjects were administered a single IV dose of palonosetron, ranging from 0.3 to 90 μg/kg in either of two randomized, double‐blind, placebo‐controlled, ascending‐dose studies (n = 80 and n = 32, respectively). Serial blood samples were obtained in both studies to evaluate the pharmacokinetics of palonosetron and its N‐oxide metabolite, M9. Intravenous palonosetron was well tolerated across a wide range of doses in both studies. The incidence and severity of adverse events (AEs) were similar between subjects receiving palonosetron and those receiving placebo, with no dose‐dependent incidences. The most frequently reported AEs were headache, transient elevation of liver enzymes, and constipation. Systemic exposure (AUC and Cmax) for palonosetron generally increased with increasing dose. Mean total body clearance, elimination half‐life, and apparent volume of distribution ranged from 1.11 to 3.90 mL/min/kg, 33.7 to 54.1 hours, and 3.85 to 12.6 L/kg, respectively, in U.S. subjects and from 2.58 to 3.50 mL/min/kg, 30.8 to 36.8 hours, and 6.96 to 9.85 L/kg, respectively, in Japanese subjects. The pharmacokinetics of palonosetron appeared to be independent of dose, with no dose adjustment required in Japanese subjects. The plasma concentration profile of palonosetron, as represented by a half‐life of approximately 40 hours, may provide a clinical advantage over other 5‐HT3 antagonists.
Pharmacokinetics and Pharmacodynamics of a Novel Depot Formulation of Abarelix, a Gonadotropin‐Releasing Hormone (GnRH) Antagonist, in Healthy Men Ages 50 to 75
Authors: Wong Shekman L. , Lau David T.‐W. , Baughman Sharon A. , Fotheringham Nick , Menchaca Dora , Garnick Marc B.
Published: April 2004

This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel depot formulation of abarelix, a new gonadotropin‐releasing hormone (GnRH) antagonist. This was an open‐label, sequential two‐phase study in healthy male subjects ages 50 to 75. Subjects received a single intramuscular (IM) dose of 15 μg/kg abarelix injectable solution, followed by a 21‐day washout period and a subsequent intramuscular dose of 100 mg abarelix depot. The PK and the hormonal suppression effects of abarelix were evaluated based on testosterone (T), dihydrotestosterone (DHT), follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) levels. Abarelix provides immediate competitive blocking of the GnRH receptors on pituitary gonadotropes without causing release of gonadotropins, and these effects are reversible. The mean IC50s of abarelix for T, DHT, FSH, and LH were 2.08, 3.42, 6.43, 4.25 ng/mL, respectively. The mean relative bioavailability of the depot formulation in reference to the injectable solution was 0.52. The mean tmax and terminal t1/2 for abarelix after administration of abarelix injectable solution and abarelix depot injection were 1 hour and 3 days and 0.22 days (5.3 h) and 13.2 days, respectively. The novel abarelix depot formulation used in this study significantly improved the duration of abarelix delivery and pharmacological activities compared to the injectable formulation, without causing any safety issues.
Strategic Choice and the Nature of the Chinese Family Business: An Exploratory Study of the Hong Kong Watch Industry
Authors: Davies Howard , Ma Catherine
Published: April 2004

This study examines the relationship between the nature of the Chinese Family Business (CFB) and the business strategies adopted, in the setting of the Hong Kong watch industry. The nature of the CFB is conceptualized and measured as a set of sub-dimensions, represented by continuous variables. It is hypothesized that ‘ CFBness’ is positively associated with ‘traditional’ business strategies, but inhibitive of ‘upgrading’. The results show that the hypotheses are partially supported. While the findings support the view that firms’ strategic choices are constrained by material and ideational influences in their environment, only a small proportion of the variation in business strategies is accounted for by ‘CFB-ness’, leaving ample room for human agency. Overall, the results support a ‘middle view’ between the deterministic and voluntaristic perspectives, whereby firms exercise strategic choice within an environment that predisposes, but does not fix, their behaviour.
The History of Organizational Renewal: Evolutionary Models of Spanish Savings and Loans Institutions
Authors: ¡lvarez Valle Santos , Merino Teresa GarcÌa
Published: April 2004

This study is aimed at, first, gaining a better understanding of organizational evolutionary processes and, second, their adaptation mechanisms. The research on selection makes it clear that different evolutionary patterns can be characterized, particularly if resources and capabilities are considered. By applying this theoretical model to the population of Spanish savings and loans entities, we have found not only diverse adaptation mechanisms, but also the important role played by strategic behaviour in achieving internal adaptation. In addition, we have also found that each organizational evolution is clearly influenced by resources and capabilities. Hence, the process of organizational evolution appears complex and dependent on environmental dynamics. In sum, it can be concluded that the process of organizational renewal faced by Spanish savings and loans institutions led to different adaptation mechanisms, mechanisms which were strongly influenced by organizational resources and capabilities.
Dialectical Tensions and Rhetorical Tropes in Negotiations
Authors: Putnam Linda L.
Published: April 2004

This article reviews and critiques traditional approaches to the study of discourse in negotiations. Then, drawing from an ethnographic study, it contrasts different ways in which discourse either constrains disputants or enables them to transform issues and the very nature of their disputes. Through an analysis of two rhetorical tropes used in the discourse, it examines the way in which bargainers enact tacit norms, use bargaining formulas, and define the nature of their interdependence. The article then draws from the textual analysis of negotiation to contrast different ways that meanings and organizational understandings are produced and reproduced through social interaction.
The Cross-National Diffusion of Work Systems: Translation of Japanese Operations in the UK
Authors: Saka Ayse
Published: April 2004

This article investigates the process of the cross-national diffusion of work systems to the affiliate firms of three Japanese multinational companies in the UK. It examines the degree to which structural, cultural, and control-related work systems of the source company are adopted by the recipient. The case studies highlight the interplay between institutional forces and organizational action through a process of work-systems translation. The study is based on a systematic comparative analysis of the ways in which Japanese work systems are implemented and sustained in the given firms. It concludes that firms attempt to translate alternative work systems rather than submit to environmental pressures toward isomorphism. The process of diffusing work systems is not driven by pre-existing legacies alone. There is room for social action in that actors, through their interaction, contribute actively to shaping the work organization.
A Dual-Motor, Constructive Process Model of Organizational Transition
Authors: Cule Paul E. , Robey Daniel
Published: April 2004

The hyper-competitive global business environment of the information age has challenged many companies to transform their business models and organizational forms. Drawing from the theoretical models of Van de Ven and Poole, we propose a process theory of organizational transition that incorporates two generative mechanisms, or ‘motors’. At the individual level, we employ a teleological motor, which captures the managerial actions undertaken to promote transformation. At the organizational level, we employ a dialectic motor, which captures forces both promoting and opposing change. The model consists of three sequential phases of transition: creation, destruction, and unification. The model is grounded in an empirical study of a large company undergoing a major transition in business model and organization structure during the decade of the 1990s.
Narrative Temporality: Implications for Organizational Research
Authors: Cunliffe Ann L. , Luhman John T. , Boje David M.
Published: April 2004

Our aim is to stimulate critical reflection on an issue that has received relatively little attention: how alternative presuppositions about time can lead to different narrative ways of researching and theorizing organizational life. Based on two amendments to Paul Ricoeur’s work in Time and Narrative, we re-story narrative research in organizations as Narrative Temporality (NT). Our amendments draw upon the temporality perspective of Jean-Paul Sartre in order to reframe narrative research in organizations as a fluid, dynamic, yet rigorous process open to the interpretations (negotiated) of its many participants (polyphonic) and situated in the context and point of enactment (synchronic). We believe an approach to narrative organizational research grounded in NT can open up new ways of thinking about experience and sense-making, and help us take reflexive responsibility for our research.
Field Approaches to Institutional Change: The Evolution of the National Collegiate Athletic Association 1906–1995
Authors: Washington Marvin
Published: April 2004

This article uses qualitative and quantitative data to examine the institutional change of an interest association. Interest associations are unique institutions in that they may be more concerned with membership growth than with economic gain. However, these associations play a vital role in the social control and evolution of organizational fields. After a discussion of the theoretical literature on institutional change, I examine the change of the National Collegiate Athletic Association (NCAA) as it competed for dominance in the US collegiate athletic field with a contender institution, the National Association of Intercollegiate Athletics. I hypothesize, and find support for the claim that to contend with the competing institution, the NCAA changed by changing its membership criteria. In the early period of the NCAA, it was a place for only high-status schools. After 1952, the NCAA attracted lower-status schools, which were previously not interested in joining the NCAA. This study advances institutional theory using qualitative and quantitative evidence to examine how a major interest association emerged and transformed itself in order to maintain control over field structuration.
Learning Groups: What Types are there? A Theoretical Analysis and an Empirical Study in a Consultancy Firm
Authors: Bogenrieder Irma , Nooteboom Bart
Published: April 2004

This article attempts to unpack the notion of ‘communities of practice’, in more detail than has been done before, and looks more generally at intra-organizational groups for learning. First, it gives a theoretical analysis of the relevant characteristics of learning groups which affect the possibilities and conditions for the sharing and joint development of knowledge. These characteristics include opportunities for learning (on the ‘competence’ side of relations), relational risk (on the ‘governance’ side of relations), and the effects on both from the ‘structural features’ of groups. On the competence side, it analyses the implications of different types of knowledge and learning, and the trade-off between stability of relations (for the sake of mutual understanding and trust) and flexibility of relations (for the sake of variety as a source of learning). On the structural side, it considers the effects on competence and governance of network density, the strength of ties, structural holes, and stability of group membership. On the governance side, it considers psychological risk, in loss of reputation or legitimation, career risk and risk of competition, and risk of lock-in into the group. Trust yields one basis for dealing with such risks, and the article discusses what that means and how trust develops. Next, the analysis is used in an exploratory empirical study of a consultancy company, to see if the theoretical framework can explain the occurrence, structure, functioning, and performance of learning groups found in practice.
Custom and Law Practices in Central India
Authors: Holden Livia S.
Published: April 2004

This article features qualitative case law studies based on extensive fieldwork in rural Madhya Pradesh in India. It focuses on perceptions of law in the dispute-settlement process at the grassroots level, highlighting the features of legal consciousness especially in relation to forum-shopping strategies between traditional and official jurisdiction. It shows that at the local level customs are reinterpreted in the light of modern values. Yet they remain the main reference point in the struggle between official law and traditional law.