bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Sectional Relations of Peripheral Microvascular Function, Cardiovascular Disease Risk Factors, and Aortic Stiffness
Authors: Mitchell Gary F. , Vita Joseph A. , Larson Martin G. , Parise Helen , Keyes Michelle J. , Warner Elaine , Vasan Ramachandran S. , Levy Daniel , Benjamin Emelia J.
Published: December 2005

Background—

Aortic stiffness and small-artery structure and function share various risk factors; however, relations between these 2 measures of vascular function are complex and incompletely understood.

Methods and Results—

We examined hyperemic forearm blood flow, an indicator of microvascular structure and function, and aortic stiffness in 2045 participants (1107 women, mean age 61±9 years) in the Framingham Heart Study offspring cohort. Using arterial tonometry, we evaluated 3 measures of aortic stiffness: brachial pulse pressure; carotid-femoral pulse wave velocity (CFPWV), which is related directly to aortic wall stiffness; and forward pressure wave amplitude (P
f
), which is related directly to aortic wall stiffness and inversely to aortic diameter. Using high-resolution ultrasound and Doppler, we evaluated brachial artery diameter, blood flow, and forearm vascular resistance (FVR) at baseline and during reactive hyperemia after 5 minutes of forearm ischemia. In multivariable models that adjusted for cardiovascular disease risk factors, local brachial pulse pressure, CFPWV, and P
f
, considered separately, were associated with increased baseline and hyperemic FVR (
P
<0.001). In models that further adjusted for mean arterial pressure, each measure of aortic stiffness was associated with reduced hyperemic flow (
P
<0.001). In risk factor–adjusted models that simultaneously considered CFPWV and P
f
, both were associated with increased FVR at baseline (
P
<0.01) and during hyperemia (
P
<0.001).

Conclusions—

Our findings indicate that abnormal aortic stiffness and increased pressure pulsatility are associated with blunted microvascular reactivity to ischemic stress that is in excess of changes attributable to conventional cardiovascular disease risk factors alone, including mean arterial pressure.
Correction of Defective Interdomain Interaction Within Ryanodine Receptor by Antioxidant Is a New Therapeutic Strategy Against Heart Failure
Authors: Yano Masafumi , Okuda Shinichi , Oda Tetsuro , Tokuhisa Takahiro , Tateishi Hiroki , Mochizuki Mamoru , Noma Toshiyuki , Doi Masahiro , Kobayashi Shigeki , Yamamoto Takeshi , Ikeda Yasuhiro , Ohkusa Tomoko , Ikemoto Noriaki , Matsuzaki Masunori
Published: December 2005

Background—Defective interdomain interaction within the ryanodine receptor (RyR2) seems to play a key role in the pathogenesis of heart failure, as shown in recent studies. In the present study we investigated the effect of oxidative stress on the interdomain interaction, its outcome in the cardiac function in heart failure, and the possibility of preventing the problem with antioxidants.

Methods and Results—Sarcoplasmic reticulum (SR) vesicles were isolated from dog left ventricular (LV) muscle (normal or rapid ventricular pacing for 4 weeks with or without the antioxidant edaravone). In the edaravone-treated paced dogs (EV+), but not in the untreated paced dogs (EV−), normal cardiac function was restored almost completely. In the SR vesicles isolated from the EV−, oxidative stress of the RyR2 (reduction in the number of free thiols) was severe, but it was negligible in EV+. The oxidative stress of the RyR2 destabilized interdomain interactions within the RyR2 (EV−), but its effect was reversed in EV+. Abnormal Ca2+leak through the RyR2 was found in EV− but not in EV+. The amount of the RyR2-bound FKBP12.6 was less in EV− than in normal dogs, whereas it was restored almost to a normal amount in EV+. The NO donor 3-morpholinosydnonimine (SIN-1) reproduced, in normal SR, several abnormal features seen in failing SR, such as defective interdomain interaction and abnormal Ca2+leak. Both cell shortening and Ca2+transients were impaired by SIN-1 in isolated normal myocytes, mimicking the pathophysiological conditions in failing myocytes. Incubation of failing myocytes with edaravone restored the normal properties.

Conclusions—During the development of heart failure, edaravone ameliorated the defective interdomain interaction of the RyR2. This prevented Ca2+leak and LV remodeling, leading to an improvement of cardiac function and an attenuation of LV remodeling.
Integrated Hemodynamic, Hormonal, and Renal Actions of Urocortin 2 in Normal and Paced Sheep
Authors: Rademaker Miriam T. , Cameron Vicky A. , Charles Christopher J. , Richards A. Mark
Published: December 2005

Background—

Urocortin 2 (Ucn2) has potent cardiovascular actions and may participate in the pathophysiology of heart failure (HF). The integrated hemodynamic, endocrine, and renal effects of Ucn2 are unknown.

Methods and Results—

Eight sheep received incremental intravenous boluses of murine Ucn2 (10, 50, and 100 μg at 2-hour intervals) before (normal) and during pacing-induced HF. Compared with control data, Ucn2 induced rapid and dose-dependent increases in cardiac output (peak effects: normal 4.3±0.2 versus 6.1±0.2 L/min,
P
<0.001; HF 2.3±0.1 versus 4.5±0.2 L/min,
P
<0.001) and reductions in peripheral resistance (normal 20.2±1.0 versus 15.2±0.8 mm Hg/L per minute,
P
<0.01; HF 32.2±1.7 versus 13.6±0.5 mm Hg/L per minute,
P
<0.001) and left atrial pressure (normal 4.3±0.3 versus 0.5±0.2 mm Hg,
P
<0.01; HF 22.9±0.6 versus 5.1±1.8 mm Hg,
P
<0.001). Mean arterial pressure was minimally elevated in normals and decreased in HF (both
P
<0.01). In both states, Ucn2 reduced plasma atrial natriuretic peptide levels (normal 13±2 versus 10±2 pmol/L; HF 200±20 versus 72±10 pmol/L) and similarly increased corticotropin, cortisol, and Ucn1 (all
P
<0.001). In HF only, Ucn2 dose dependently decreased plasma vasopressin (3.09±0.36 versus 1.62±0.12 pmol/L,
P
<0.01), renin (2.98±1.17 versus 0.69±0.10 nmol/L per hour,
P
<0.001), aldosterone (1186±303 versus 364±122 pmol/L,
P
<0.001), endothelin-1 (3.39±0.23 versus 2.56±0.18 pmol/L,
P
<0.01), epinephrine (1633±260 versus 657±142 pmol/L,
P
<0.01), and brain natriuretic peptide (36±3 versus 18±4 pmol/L,
P
<0.001) concentrations. Renal effects, including increased urine volume (1.7-fold,
P
<0.05), sodium excretion (>12-fold,
P
<0.01), and creatinine excretion (1.3-fold,
P
<0.001), also occurred only in HF.

Conclusions—

Ucn2 has marked and beneficial hemodynamic, hormonal, and renal effects in experimental HF. These results support a role for Ucn2 in pressure/volume homeostasis in HF and suggest that the peptide may have therapeutic potential in this disease.
Influence of Ejection Fraction on Cardiovascular Outcomes in a Broad Spectrum of Heart Failure Patients
Authors: Solomon Scott D. , Anavekar Nagesh , Skali Hicham , McMurray John J.V. , Swedberg Karl , Yusuf Salim , Granger Christopher B. , Michelson Eric L. , Wang Duolao , Pocock Stuart , Pfeffer Marc A.
Published: December 2005

Background—

Left ventricular function is a principal determinant of cardiovascular risk in patients with heart failure. The growing number of patients with preserved systolic function heart failure underscores the importance of understanding the relationship between ejection fraction and risk.

Methods and Results—

We studied 7599 patients with a broad spectrum of symptomatic heart failure enrolled in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program. All patients were randomized to candesartan at a target dose of 32 mg once daily or matching placebo and followed up for a median of 38 months. We related left ventricular ejection fraction (LVEF), measured before randomization at the sites, to cardiovascular outcomes and causes of death. Mean LVEF in patients enrolled in CHARM was 38.8±14.9% (median LVEF 36%). Patients with lower LVEF tended to have higher baseline New York Heart Association class. The hazard ratio for all-cause mortality increased by 39% for every 10% reduction in ejection fraction below 45% (hazard ratio 1.39, 95% CI 1.32 to 1.46), with adjustment for baseline covariates. All-cause mortality, cardiovascular death, and all components of cardiovascular death declined with increasing ejection fraction until an ejection fraction of 45%, after which the risk of these outcomes remained relatively stable with increasing LVEF. The absolute change in rate per 100 patient-years for each 10% reduction in LVEF was greatest for sudden death and heart failure–related death. The effect of candesartan in reducing cardiovascular outcomes was consistent across LVEF categories.

Conclusions—

LVEF is a powerful predictor of cardiovascular outcome in heart failure patients across a broad spectrum of ventricular function. Nevertheless, once elevated to a range above 45%, ejection fraction does not further contribute to assessment of cardiovascular risk in heart failure patients.
Decreased Neurotrophin TrkB Receptor Expression Reduces Lesion Size in the Apolipoprotein E–Null Mutant Mouse
Authors: Kraemer Rosemary , Baker Peter James , Kent K. Craig , Ye Yuanfen , Han Jun Ji , Tejada Rafael , Silane Michael , Upmacis Rita , Deeb Ruba , Chen Yaoxin , Levine Daniel M. , Hempstead Barbara
Published: December 2005

Background—

Accumulation of macrophages and smooth muscle cells in the vascular wall is critical for the development of atherosclerotic lesions. Although much is known about the factors that regulate macrophage recruitment to the vascular wall, the ability of growth factors to regulate smooth muscle cell recruitment in lesion development in vivo is unclear. Our previous studies demonstrated that neurotrophins and their receptors, the Trk receptor tyrosine kinases, are potent chemotactic factors for smooth muscle cells, and the expression of brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, is upregulated in human atherosclerotic lesions.

Methods and Results—

TrkB
+/−
mice on a 129/B6 background were backcrossed to apolipoprotein E (ApoE)–null (
ApoE
−/−
) mice on the C57Bl/6 background for 6 to 8 generations. Immunohistochemical analysis demonstrated BDNF immunoreactivity in areas of macrophage and smooth muscle cell infiltration, whereas TrkB immunoreactivity was predominant in areas of neointimal smooth muscle cells. Moreover, haplodeficient expression of TrkB in
ApoE
−/−
mice was associated with a 30% to 40% reduction in lesion size compared with
ApoE
−/−
mice with normal expression of TrkB and a 45% decrease in smooth muscle cell accumulation in the lesions. Finally, reconstitution with bone marrow from
ApoE
−/−
mice with normal TrkB expression did not restore lesion development in
TrKB
+/−
/
ApoE
−/−
mice.

Conclusions—

These results suggest that TrkB expression on smooth muscle cells contributes to lesion development in the cholesterol-fed ApoE–null mutant mouse. These data demonstrate, for the first time, a role for the neurotrophin TrkB receptor in atherosclerotic lesion development.
Between Tolerance and Intolerance in Medieval Spain: An Historiographic Enigma
Authors: Novikoff Alex
Published: December 2005

The nature of what has been termed "tolerance" and "intolerance" in the historiography of medieval Iberia has, while rarely defined, continued to provide much-employed organizing categories for the field. This paper reviews one focus of that historiography from the nineteenth into the twenty-first century: the relations among Muslims, Jews, and Christians, with respect to tolerance/intolerance and related categories (notably, convivencia). It analyzes, among other factors, the impact on this historiography of the intellectual, cultural, and political movements which have affected historians of medieval Iberia. It makes a case for the importance for specialists in the field to be keenly aware of these aspects of historiography at a time when medieval Spain is seen as offering a unique opportunity for testing theories of interfaith relations and social interaction
Precipitation Shifts over Western North America as a Result of Declining Arctic Sea Ice Cover: The Coupled System Response
Authors: Sewall Jacob O.
Published: December 2005

Changes in Arctic sea ice cover have the potential to impact midlatitude climate. A previous sensitivity study utilizing the National Center for Atmospheric Research’s (NCAR) atmospheric general circulation model [AGCM; Community Climate Model, version 3 (CCM3)] to explore climate sensitivity to declining Arctic sea ice cover suggested that, as Arctic sea ice cover is reduced, precipitation patterns over western North America will shift toward dryer conditions in southwestern North America and wetter conditions in northwestern North America. Here, three complementary lines of research validate and explore the robustness of this possible climate change impact: 1) repetition of the previous sensitivity study (specified constant Arctic sea ice cover and atmospheric CO2) with an updated version of the NCAR AGCM [third Community Atmosphere Model (CAM3)], 2) investigation of the climate response to dynamically reduced Arctic sea ice cover (driven by a quadrupling of atmospheric CO2) in the coupled NCAR Community Climate System Model (CCSMv3), and 3) analysis of similar results from six other coupled climate system models. Results from the CAM3 sensitivity study are similar to those from the original study with declining Arctic sea ice cover driving up to 25% less mean annual precipitation (MAP) over southwestern North America and up to an 8% increase in MAP over northwestern North America. The seven coupled models also reproduce this same general pattern. At the time of CO2 quadrupling, Arctic sea ice cover is reduced (up to 90% in boreal winter) and MAP over southwestern North America decreases by up to 30% while MAP in northwestern North America increases by up to 40%. These results represent a significant shift in the precipitation pattern over western North America and support the findings of the original sensitivity study in suggesting that, as future reductions in Arctic sea ice cover take place, there will be a substantial impact on water resources in western North America.
Wage Differentials and Gender Discrimination
Authors: Johansson Mats , Katz Katarina , Nyman Håkan
Published: December 2005

The purpose of this article is to follow the development of the Swedish gender earnings gap through the 1980s and 1990s. We follow the changes in the wage gap and in factors to which it can be related year-by-year by analysing crosssectional data from Statistics Sweden (HEK) for the years 1981 and 1983–98. The results show that the unadjusted wage gap varied between 12 and 15 per cent of the average male wage up to 1989, when the differentials began to increase. During the 1990s the size of the gap was around 14–18 per cent. In a decomposition analysis we find that the measured differences in jobs and qualifications between women and men can account only for between two-fifths and three-fifths of the gender wage gap, if they are assumed to be rewarded according to the male wage function. If the female wage function is applied, even less of the differentials are explained. Differences in the educational requirements for jobs have contributed considerably to gender earnings inequality. The impact has decreased over the period studied, however, and is about half as large in the 1990s as it was in the 1980s.
Sociologists in Action
Authors: Brincker Benedikte , Gundelach Peter
Published: December 2005

In this article, we argue that Alain Touraine's method of intervention is a way of conducting sociological analysis of collective action and social change, but that it must be developed in different ways. We place the intervention method within the context of Touraine's works on social movements and offer a detailed account. Drawing on the works of Pierre Bourdieu and Alberto Melucci we provide the basis for critically engaging with the method. We explore the methodological rules and procedures and the role of the researcher, and suggest a relatively more open understanding of the method.
The Structure and Operation of China's Diplomatic System
Authors: Rana Kishan
Published: December 2005

Diplomacy is now under rapid evolution. This means ever-widening international contacts by official agencies other than the foreign ministry, the sub-state agencies, and non-state actors; the impact of information and communication revolution; and gradual ‘democratisation’, via institutional plurality, emerging public-private partnerships and a stronger role of home publics. Most foreign ministries now pursue reform as a continuous activity. China is one such example. The evolution in China's diplomatic system since 1949 demonstrates how professional expertise challenges ideological commitment, though both criteria remain relevant. On strategic policy issues, this system is highly efficient, and coordinated through the ‘leading small group’ mechanism operating under the Party Politburo. Yet inter-ministry harmonisation in routine issues is often blocked, thanks to the entrenched old vertical hierarchies. This limits in and out placements of officials, except within set parameters. Political diplomacy is today innovative and supple in its execution. The practice of economic diplomacy remains low key, with embassies less engaged in ‘marketing’ projects, compared with Western counterparts. Cultural diplomacy is shifting to high gear, and will be a major theme at the 2008 Olympics. Domestic public diplomacy, outreach to home publics has become a top priority. The foreign ministry makes effective use of think tanks and retired envoys to provide inputs into the policy process, and is far ahead of India in the multiple policy options that this plural process generates, though policy formulation remains tightly guarded and secretive. China's diplomatic service has unique features— a single class hierarchy; ruthless fast-track implementation that propels the talented to high office at early age; a major problem of attrition, with many quitting in the first few years; an excellent system of language and area specialisation; continuous gender inequality. We may count on continuing refinement and improvement of the Chinese diplomatic process.
Sino-Indian Friendship in the Nehru Era
Authors: Quanyu Shang
Published: December 2005

This paper focuses on Sino-Indian relations in the early Nehru era, i.e., the friendly relations between China and India from 1947 to 1958. It reveals that in the early part of Nehru's period, China and India had intimate bilateral relations characterised by mutual support and cooperation in many decisive national, regional and international issues, such as establishment of diplomatic relations, admission of PRC to the United Nations, the Korean crisis, friendly exchanges in the Initiation Phase from 1947 to 1953 and the Panchsheel Agreement, Indo-China issue, Asian-African conference, Taiwan and Goa questions, and mutual visits of high-ranking leaders in the Honeymoon Phase from 1954 to 1958. Furthermore, it discusses the factors contributing to the intimacy and cordiality of Sino-Indian relations in the early years of the Nehru era. These include the internal context, external context and personal factor. The internal context comprises both the historical conditions and the existing realistic situation that China and India faced. The external context was constituted by the circumstances of the global Cold War, marked by the American-Pakistani alliance, American-Chinese enmity, and Indo-Pakistani hostility, whereby Sino-Indian friendship came into being logically. The personal factor stemmed from Nehru's ideas and his stand on Sino-Indian friendship.
Unlocking the Hegemonic Power of ‘The People's Democratic Dictatorship’
Authors: Hampton Andrea Fehr
Published: December 2005

This article explores the relationship between the Chinese state and civil society by juxtaposing the experiences of the Uygur ethnic group of Xinjiang province against the country's environmentally focused social organisations. It analyses the reasons behind the failure or success of each movement as defined by their ability to create a counter-hegemony, where subordinate groups challenge a system in which the interests of one section of society organise, in Gramscian terms, the majority of people's common sense. This article bases the creation of successful counter-hegemony on two premises: first is the suggestion that the key to developing an effective civil society is its contribution to the prevailing political agenda. The second premise is the implication that if a social movement is to succeed against a prevailing hegemonic power, it must in some capacity, align itself with the prevailing interests and then co-opt them to forward its own agenda, constructing ‘good sense’ from ‘common sense’. Both the Uygur and the green movements are reviewed in their capacity to align with the interests of the Chinese Communist Party-led state, of which three components are identified: (1) the party line; (2) national security; and (3) prevailing international power structures. In identifying these three factors that shape the interests of the state, they become focal points around which social groups can adapt and manipulate to create a counter-hegemony. Thus, these three features become prongs of a key that can unlock the hegemonic power of the Chinese state. The implication of this article is that there are certain avenues for creating successful counter-hegemonic civil society movements, even where the state is most repressive.
Identifying Mutual Interest Areas at WTO
Authors: Chaisse Julien , Chakraborty Debashis
Published: December 2005

China and India, in spite of being signatory members of GATT (General Agreement on Tariffs and Trade, 1948), witnessed a dissimilar experience in the arena of multilateral negotiations and trade. China lost its membership after the withdrawal of Taiwan from GATT in 1950, but gained steady access in the global market since the late 80s. India, on the other hand, in spite of maintaining the membership of GATT, never focused on export promotion strategies before late 80s. Both the countries expect further growth in their exports in coming future, as the tariff and non-tariff barriers (NTBs) in member countries are likely to go down in the post-transitory phase of the World Trade Organization (WTO), which started from 1 January 2005 onwards. However, the WTO-compatibilities of several domestic policies of both China and India have been questioned by their trade partners on various occasions and the debate is likely to continue in the future. Moreover, the exports of both of them are subject to various NTBs in principal markets, which are likely to intensify in the coming days. This bears serious implications on the export potentials of the two countries. Considering the domestic policies of China and India as well as the barriers on them, this article attempts to identify material and institutional areas where the two countries could jointly negotiate at the multilateral forum. It argues that collective bargaining by the two countries on key issues is likely to provide them an edge in future negotiations.
Fraternity Row, The Student Ghetto, and the Faculty Enclave
Authors: Gumprecht Blake
Published: December 2005

The unusual demographic characteristics of college towns, and the social differences that exist within student populations, have led to the emergence in college communities of several distinctive types of residential districts. Using Ithaca, New York, as an example, this study examines the origins and evolution of three such districts—the Greek-housing district sometimes called “fraternity row,” the student rental area often known as the student ghetto, and the faculty enclave. Together such districts help to make the American college town a unique type of urban place.
Pediatric Procedural Pain
Authors: Blount Ronald L. , Piira Tiina , Cohen Lindsey L. , Cheng Patricia S.
Published: December 2005

This article reviews the various settings in which infants, children, and adolescents experience pain during acute medical procedures and issues related to referral of children to pain management teams. In addition, self-report, reports by others, physiological monitoring, and direct observation methods of assessment of pain and related constructs are discussed and recommendations are provided. Pharmacological, other medical approaches, and empirically supported cognitive behavioral interventions are reviewed. Salient features of the interventions are discussed, and recommendations are made for necessary components of effective treatment interventions.
Recurrent Abdominal Pain
Authors: Banez Gerard A. , Gallagher Heather M.
Published: December 2005

The purpose of this article is to provide an empirically informed but clinically oriented overview of behavioral treatment of recurrent abdominal pain. The epidemiology and scope of recurrent abdominal pain are presented. Referral process and procedures are discussed, and standardized approaches to assessment are summarized. Treatment protocols developed by Sanders and colleagues and by Finney and colleagues are described, followed by a review of treatment efficacy. The article concludes with practice recommendations that emphasize the importance of reassurance and education, appropriate and realistic treatment goals, the child's daily functional status, and treatment plans tailored to match the child and family's presentation.
Ozone and Climate
Authors: Grundmann Reiner
Published: December 2005

This article compares the cases of ozone layer protection and climate change. In both cases, scientific expertise has played a comparatively important role in the policy process. The author argues that against conventional assumptions, scientific consensus is not necessary to achieve ambitious political goals. However, the architects of the Intergovernmental Panel on Climate Change operated under such assumptions. The author argues that this is problematic both from a theoretical viewpoint and from empirical evidence. Contrary to conventional assumptions, ambitious political regulations in the ozone case were agreed under scientific uncertainty, whereas the negotiations on climate change were much more modest albeit based on a large scientific consensus. On the basis of a media analysis, the author shows that the creation of a climate of expectation plus pressure from leader countries is crucial for success.
Public Housing and Family Life in East Asia: Housing History and Social Change in Hong Kong, 1953-1990
Authors: Lee James , Ngai-ming Yip
Published: December 2005

This article attempts to contribute to an emerging literature on the link between housing history and society. For Hong Kong, it has always been argued that much of its socioeconomic successes in the past five decades have been heavily attributed to orchestrated public housing policy since 1953. Although this argument is popular, micro evidence to support this thesis is scant. Most studies focus mainly on describing the macro effects of housing policy with little link to the actual household experiences of public housing tenants. The purpose of this article is to make explicit that link through various individual housing trajectories.
“His Brain was Wrong, His Mind Astray”: Families and the Language of Insanity in New South Wales, Queensland, and New Zealand, 1880s-1910
Authors: Coleborne Catharine
Published: December 2005

Family and friends made descriptions of the behavior of individuals at the time of their committal to institutions for the insane in Australasian colonies, including Gladesville Hospital for the Insane, Sydney, New South Wales; Goodna Hospital for the Insane, near Brisbane in Queensland; and the Auckland Mental Hospital in New Zealand’s North Island, in the late nineteenth and early twentieth centuries. These lay descriptions of insanity, gleaned from those close to patients by doctors during initial interviews at the stage of asylum committal, eventually became marginal notes in clinical patient cases. This article seeks to understand this interplay between lay descriptions by family and friends and the asylum’s use of these descriptions in its profiling and diagnosis of patients. It argues that patient case notes should be reexamined as rich sources of information about families, households, and, most importantly, the language used by ordinary people to describe mental states.
Was Ancient Rome a Dead Wives Society? What did the Roman Paterfamilias Get Away With?
Authors: Thompson Steven
Published: December 2005

Until recently, descriptions of the Roman family routinely attributed to the head of household the right of life and death over his wife, children of any age, and slaves, and assumed he exercised it. Challenges to this position by Roman law specialists have gradually affected the way this right and its exercise are described by historians of the family. This article surveys these challenges, tracks their uptake by historians of the family, and notes the emerging consensus answer to the question What did the Roman father get by with? Relevant ancient sources are quoted and placed in context, and previously unexamined evidence from Roman playwrights and satirists is offered to support the emerging consensus answer, which is that he did not get away with murder.
Leveraging Knowledge
Authors: Pillania Rajesh K.
Published: December 2005

Knowledge has emerged as the most critical resource for wealth creation and sustainable competitive advantage. I conducted research to study what Indian firms are doing to leverage knowledge, especially to gauge their expectations and the problems they are facing. To have a macro view of the situation, I asked experts from industry, academia and policy makers about knowledge management (KM) strategies in Indian companies. To have the micro view, I selected five firms each from two industries: software and pharmaceuticals, and four firms from the petroleum marketing sector, thus covering both the private and public sectors. Though Indian firms expect a lot of benefits out of KM, there are obstacles to its implementation particularly due to lack of awareness of KM and knowledge-hoarding culture. Indian firms, especially those in the public sector, need to invest and leverage knowledge resources for competing in this era of privatization, liberalization and globalization.
Individuality or Cultural Reproduction?
Authors: Skille Eivind Åsrum
Published: December 2005

The Norwegian Government initiated the Sports City Program (SCP) in 1992 in an attempt to encourage inactive segments of the urban population to become more active. The program was implemented by the Norwegian Olympic Committee and Confederation of Sports and is designed to provide sporting activities for those who are not involved in conventional sports. Through a survey in one of the cities where the SCP is most developed, this study examines the degree to which adolescents (age 16-19) participate in SCP activities. Drawing on the work of Bourdieu, I argue first, that a considerable overlap between participants in conventional sports and SCP activities indicates that the new sport activities, to a considerable extent, provide further opportunities for those who already participate in the sporting field. Second, however, the Sports City Program also seems to attract a different type of adolescent, in terms of social class, compared to those who participate in conventional sports. For these two rather different groups, their habitus for participation in sport is influenced by their family members’ and peers’ relation to sport, though in different ways.
Updating the Mathematical Model of a Structure Using Vibration Data
Authors: Bagchi Ashutosh
Published: December 2005

Model updating is an important step for correlating the mathematical model of a structure to the real one. There are a variety of techniques available for model updating using dynamic and static measurements of the structure’s behavior. This paper concentrates on the model updating techniques using the natural frequencies or frequencies and mode shapes of a structure. An iterative technique is developed based on the matrix update method. The method hasbeenappliedtothefiniteelement models of a three span continuous steel free deck bridge located in western Canada. The finite element models of the bridge have been constructed using three-dimensional beam and facet shell elements and the models have been updated using the measured frequencies. From the study it is clear that the initial model needs to be built such that it represents the actual structure as closely as possible. The results demonstrate that the difference between the modal parameters from the model and field tests affect the quality of the model updating process.
The Effect of Private School Competition on Public School Performance in Georgia
Authors: Geller Christopher R. , Sjoquist David L. , Walker Mary Beth
Published: December 2005

This article presents estimates of the effect of private school competition on public school performance. Using data on school districts in Georgia, the authors estimate models relating tenth- and third-grade test scores for either reading or mathematics to the level of private school competition. Test scores are not measurably or significantly higher in areas with greater private school competition, a result robust through multiple estimations using three measures of private school competition and a variety of control variables. The authors address the possible endogeneity between test scores and private school competition using instrumental variables estimators, with percentage of the population that is Catholic, county population in 1980, lagged competition, and various other measures as alternative instruments.
Partnership working between university researchers and self-advocacy organizations
Authors: Schoeters Ludo , Schelfhout Patrick , Roets Griet , Van Hove Geert , Townson Louise , Chapman Rohhss , Buchanan Ian
Published: December 2005

This article gives accounts of differing experiences of self-advocate partnerships in research with universities in England and Flanders. In England the partnership grew up within a local People First group built upon a personal working relationship with one support person. It is focused almost exclusively on empirical research and, because it is aimed at influencing policy and practice, questions of funding and control are to the fore. In Flanders the partnership is closely linked with the development of a national movement of self-advocates in which the university was a close ally. Research is important in both contexts but in Flanders the university is more clearly identified with the wider movement. Partnerships have their ups and downs but in both countries researchers with the label ‘learning difficulties’ wish to set their own agendas and place great importance on trust in their work with their support worker (England) or ally (Flanders).
Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies
Authors: O'Connor Owen A. , Heaney Mark L. , Schwartz Lawrence , Richardson Stacie , Willim Robert , MacGregor-Cortelli Barbara , Curly Tracey , Moskowitz Craig , Portlock Carol , Horwitz Steven , Zelenetz Andrew D. , Frankel Stanley , Richon Victoria , Marks Paul , Kelly William K.
Published: December 2005

Purpose

To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies.

Patients and Methods

Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both trials, dose escalation was performed in parallel and independently in patients with solid tumors and hematologic malignancies. Eligible patients were required to have adequate hepatic and renal function, an absolute neutrophil count ≥ 500/μL and a platelet count more than 25,000/mL. All patients provided informed consent for study inclusion.

Results

A total of 39 patients with hematologic malignancy were enrolled (14 on IV SAHA and 25 on oral SAHA), of whom 35 were treated. The spectrum of diseases included patients with diffuse large B-cell lymphoma (n = 12), Hodgkin's disease (HD; n = 12), multiple myeloma (n = 2), T-cell lymphoma (n = 3), mantle cell lymphoma (n = 2), small lymphocytic lymphoma (n = 2), and myeloid leukemia (n = 2). Major adverse events with the oral formulation included fatigue, diarrhea, anorexia, and dehydration, whereas myelosuppression and thrombocytopenia were more prominent with the IV formulation. Typically, the hematologic toxicities resolved shortly after SAHA was stopped. There was no neutropenic fever or neutropenic sepsis. Reduction in measurable tumor was observed in five patients. One patient with transformed small lymphocytic lymphoma met criteria for complete response, whereas another met the criteria for partial response (PR). One patient with refractory HD had a PR, whereas three patients had stable disease for up to 9 months.

Conclusion

These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.
Array-Based Comparative Genomic Hybridization Analysis Reveals Recurrent Chromosomal Alterations and Prognostic Parameters in Primary Cutaneous Large B-Cell Lymphoma
Authors: Dijkman Remco , Tensen Cornelis P. , Jordanova Ekaterina S. , Knijnenburg Jeroen , Hoefnagel Juliette J. , Mulder Aat A. , Rosenberg Carla , Raap Anton K. , Willemze Rein , Szuhai Károly , Vermeer Maarten H.
Published: December 2005

Purpose

To evaluate the clinical relevance of genomic aberrations in primary cutaneous large B-cell lymphoma (PCLBCL).

Patients and Methods

Skin biopsy samples of 31 patients with a PCLBCL classified as either primary cutaneous follicle center lymphoma (PCFCL; n = 19) or PCLBCL, leg type (n = 12), according to the WHO–European Organisation for Research and Treatment of Cancer (EORTC) classification, were investigated using array-based comparative genomic hybridization, fluorescence in situ hybridization (FISH), and examination of promoter hypermethylation.

Results

The most recurrent alterations in PCFCL were high-level DNA amplifications at 2p16.1 (63%) and deletion of chromosome 14q32.33 (68%). FISH analysis confirmed c-REL amplification in patients with gains at 2p16.1. In PCLBCL, leg type, most prominent aberrations were a high-level DNA amplification of 18q21.31-q21.33 (67%), including the BCL-2 and MALT1 genes as confirmed by FISH, and deletions of a small region within 9p21.3 containing the CDKN2A, CDKN2B, and NSG-x genes. Homozygous deletion of 9p21.3 was detected in five of 12 patients with PCLBCL, leg type, but in zero of 19 patients with PCFCL. Complete methylation of the promoter region of the CDKN2A gene was demonstrated in one PCLBCL, leg type, patient with hemizygous deletion, in one patient without deletion, but in zero of 19 patients with PCFCL. Seven of seven PCLBCL, leg type, patients with deletion of 9p21.3 and/or complete methylation of CDKN2A died as a result of their lymphoma.

Conclusion

Our results demonstrate prominent differences in chromosomal alterations between PCFCL and PCLBCL, leg type, that support their classification as separate entities within the WHO-EORTC scheme. Inactivation of CDKN2A by either deletion or methylation of its promoter could be an important prognostic parameter for the group of PCLBCL, leg type.
Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non–Small-Cell Lung Cancer Tumors
Authors: Tsurutani Junji , Fukuoka Junya , Tsurutani Hiroko , Shih Joanna H. , Hewitt Stephen M. , Travis William D. , Jen Jin , Dennis Phillip A.
Published: December 2005

Purpose

Akt is a serine/threonine kinase that has been implicated in lung tumorigenesis and lung cancer therapeutic resistance. Full activation of Akt requires two phosphorylation events, but only one site of phosphorylation (S473) has been evaluated thus far in clinical non–small-cell lung cancer (NSCLC) specimens, which has resulted in conflicting results regarding the prognostic significance of Akt activation in NSCLC. In this study, we sought to determine whether evaluation of Akt phosphorylation at T308 would improve prognostic accuracy.

Patients and Methods

Phosphospecific antibodies against T308 and S473 were validated and used in an immunohistochemical analysis of tissue microarray slides containing NSCLC specimens (n = 300) and surrounding lung tissue specimens (n = 100).

Results

Phosphorylation of either S473 or T308 was positive in most NSCSLC specimens, but was detected rarely in surrounding normal tissues. When Akt activation was defined by using both sites of phosphorylation, Akt activation was specific for NSCLC tumors versus surrounding tissue (73.4% v 0%; P < .05), was higher in adenocarcinoma than in squamous cell carcinoma (78.1% v 68.5%; P = .040), and was associated with shorter overall survival for all stages of disease (log-rank P = .041). In multivariate analyses, increased phosphorylation of T308 alone was a poor prognostic factor for stage I patients or for tumors < 5 cm (log-rank P = .011 and P = .015, respectively).

Conclusion

These results suggest that monitoring phosphorylation of Akt at T308 improves the assessment of Akt activation, and show that Akt activation is a poor prognostic factor for all stages of NSCLC.
Impact of the Year 2000 Medicare Policy Change on Older Patient Enrollment to Cancer Clinical Trials
Authors: Unger Joseph M. , Coltman Charles A. , Crowley John J. , Hutchins Laura F. , Martino Silvana , Livingston Robert B. , Macdonald John S. , Blanke Charles D. , Gandara David R. , Crawford E. David , Albain Kathy S.
Published: December 2005

Purpose

A prior analysis by the Southwest Oncology Group (SWOG) showed that women and African American patients were adequately represented on cancer clinical treatment trials but that older patients were substantially underrepresented. Twenty-five percent of patients ≥ 65 years old were enrolled onto SWOG trials from 1993 to 1996, whereas 63% of all patients with cancer were ≥ 65 years old. Recognition of this under-representation led to a change in Medicare policy in 2000 to include coverage of routine patient care costs of clinical trials. We conducted an updated analysis of accrual trends.

Methods

The proportions of enrollment onto SWOG treatment trials by sex, race/ethnicity, and age (≥ 65 years) were computed for the years 1997 to 2000; corresponding rates in the United States were derived from US Census and National Cancer Institute Surveillance, Epidemiology, and End Results data. Additionally, method of payment data were analyzed over time (1993 to 2003) to assess whether patterns in method of payment changed with the new Year 2000 Medicare policy on clinical trials coverage.

Results

The results showed continued adequate representation by sex and race/ethnicity. Older patient accrual on SWOG trials increased significantly since 2000, with 31% of patients ≥ 65 years old enrolled from 1997 to 2000 and 38% enrolled from 2001 to 2003 (v 25% from 1993 to 1996). The percentage of patients using Medicare plus supplemental insurance also increased beginning in 2000, whereas the percentage of patients using Medicare alone remained the same.

Conclusion

Method of payment analyses provided evidence that the Year 2000 Medicare policy change had a positive impact, but only for those patients with supplemental private coverage of coinsurance costs. Improvements in the Medicare payment structure could further increase older patient participation in clinical trials.
A Pilot Study of an Investigational Testosterone Transdermal Patch System in Young Women with Spontaneous Premature Ovarian Failure
Authors: Kalantaridou Sophia N. , Calis Karim A. , Mazer Norman A. , Godoy Heidy , Nelson Lawrence M.
Published: December 2005

Context: Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women.

Objective: The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone.

Design: This was an open-label study (2-month baseline period followed by 2-month treatment period).

Patients: Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded.

Intervention: Four consecutive 28-d cycles of transdermal estradiol (E2; 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 μg/d) was applied twice weekly to the abdomen.

Main Outcome Measures: Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied.

Results: The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9–9.9) pg/ml; 26.0 (17.2–34.6) pmol/liter (with E2), and 6.9 (4.9–8.8) pg/ml; 23.9 (17.2–30.5) pmol/liter (with E2 and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 pg/ml (23.5 pmol/liter), although the mean values are slightly above this.

Conclusions: The addition of TTP to cyclic E2/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress.
Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men
Authors: van den Beld Annewieke W. , Visser Theo J. , Feelders Richard A. , Grobbee Diederick E. , Lamberts Steven W. J.
Published: December 2005

Context: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly.

Objective: We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men.

Design: A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr.

Participants: Four hundred three independently and ambulatory living men (aged 73–94 yr) participated.

Main Outcome Measures: The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality.

Methods: TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition.

Results: Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality.

Conclusions: In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.