bluuebunny/crossref_metadata_2025 huggingface dataset:
Left Heart Growth, Function, and Reintervention After Balloon Aortic Valvuloplasty for Neonatal Aortic Stenosis
Authors: McElhinney Doff B. , Lock James E. , Keane John F. , Moran Adrian M. , Colan Steven D.
Published: February 2005

Background—

Transcatheter balloon aortic valvuloplasty (BAVP) has become the first-line treatment for critical aortic stenosis (AS) in neonates. However, little is known about the growth and function of left heart structures or about patterns of reintervention on the left heart after neonatal BAVP.

Methods and Results—

Between 1985 and 2002, 113 patients underwent neonatal BAVP at ≤60 days of age. There were 16 early deaths (14%), with a significant decrease from 1985 to 1993 (22%) to 1994 to 2002 (4%), and 6 patients had successful early conversion to a univentricular circulation. In the short term, the mean relative gradient reduction was 54±26%, and significant aortic regurgitation (AR) developed in 15% of patients. The 91 early survivors with a biventricular circulation were followed up for 6.3±5.3 years, during which time there was a steady increase in the frequency of significant AR. Freedom from moderate or severe AR was 65% at 5 years. In almost all patients with a baseline aortic annulus
z
score less than −1, the annulus diameter increased to within the normal range within 1 to 2 years. Similarly, left ventricular (LV) end-diastolic dimension
z
scores, which ranged from −5 to 7.5 before BAVP, normalized within 1 to 2 years in nearly all patients with a predilation
z
score less than −1. Among early survivors with a biventricular circulation, reintervention-free survival on the LV outflow tract was 65% at 1 year and 48% at 5 years, with younger age, higher pre- and post-BAVP gradients, and a larger balloon-annulus diameter ratio associated with decreased reintervention-free survival (
P
<0.01). Seventeen surgical interventions were performed on the aortic valve in 15 patients, including replacement in 7. Survival free from aortic valve replacement was 84% at 5 years.

Conclusions—

BAVP for AS during the first 60 days of life results in short-term relief of AS in the majority of patients. Among early survivors, initially small left heart structures may be associated with worse subacute outcomes but typically normalize within 1 year. Reintervention for residual/recurrent AS or iatrogenic AR is relatively common, particularly during the first year after BAVP, but aortic valve replacement during early childhood is seldom necessary.
Chest Compression Rates During Cardiopulmonary Resuscitation Are Suboptimal
Authors: Abella Benjamin S. , Sandbo Nathan , Vassilatos Peter , Alvarado Jason P. , O’Hearn Nicholas , Wigder Herbert N. , Hoffman Paul , Tynus Kathleen , Vanden Hoek Terry L. , Becker Lance B.
Published: February 2005

Background—

Recent data highlight a vital link between well-performed cardiopulmonary resuscitation (CPR) and survival after cardiac arrest; however, the quality of CPR as actually performed by trained healthcare providers is largely unknown. We sought to measure in-hospital chest compression rates and to determine compliance with published international guidelines.

Methods and Results—

We developed and validated a handheld recording device to measure chest compression rate as a surrogate for CPR quality. A prospective observational study of adult cardiac arrests was performed at 3 hospitals from April 2002 to October 2003. Resuscitations were witnessed by trained observers using a customized personal digital assistant programmed to store the exact time of each chest compression, allowing offline calculation of compression rates at serial time points. In 97 arrests, data from 813 minutes during which chest compressions were delivered were analyzed in 30-second time segments. In 36.9% of the total number of segments, compression rates were <80 compressions per minute (cpm), and 21.7% had rates <70 cpm. Higher chest compression rates were significantly correlated with initial return of spontaneous circulation (mean chest compression rates for initial survivors and nonsurvivors, 90±17 and 79±18 cpm, respectively;
P
=0.0033).

Conclusions—

In-hospital chest compression rates were below published resuscitation recommendations, and suboptimal compression rates in our study correlated with poor return of spontaneous circulation. CPR quality is likely a critical determinant of survival after cardiac arrest, suggesting the need for routine measurement, monitoring, and feedback systems during actual resuscitation.
Phobic Anxiety and Risk of Coronary Heart Disease and Sudden Cardiac Death Among Women
Authors: Albert Christine M. , Chae Claudia U. , Rexrode Kathryn M. , Manson JoAnn E. , Kawachi Ichiro
Published: February 2005

Background—

High levels of phobic anxiety have been associated with elevated risks of coronary heart disease (CHD) death and sudden cardiac death (SCD) among men. To the best of our knowledge, no studies have looked at this association among women. Anxiety may influence CHD mortality by increasing the risk of ventricular arrhythmia and SCD.

Methods and Results—

We prospectively examined the relationship between phobic anxiety, as measured by the Crown-Crisp index (CCI), and CHD among women participating in the Nurses’ Health Study. Among 72 359 women with no history of cardiovascular disease or cancer in 1988, 97 SCDs, 267 CHD deaths, and 930 nonfatal myocardial infarctions (MI) were documented over 12 years of follow-up. A higher score on the CCI was associated with an increased risk of SCD and fatal CHD but not of nonfatal MI in age-adjusted (
P
, trend ≤0.008) and in multivariable models excluding possible biological intermediaries (
P
, trend ≤0.03). Multivariable adjustment appeared to attenuate the relations; women who scored 4 or greater on the CCI were at a 1.59-fold (95% CI, 0.97 to 2.60) marginally increased risk of SCD and a 1.31-fold (95% CI, 0.97 to 1.75) marginally increased risk of fatal CHD compared with those who scored 0 or 1. After control for possible intermediaries (hypertension, diabetes, and elevated cholesterol), a trend toward an increased risk persisted for SCD (
P
=0.06).

Conclusions—

These prospective data suggest that high levels of phobic anxiety are associated with an increased risk of fatal CHD, particularly from SCD. Some but not all of this risk can be accounted for by CHD risk factors associated with phobic anxiety.
Opportunity for Intervention to Achieve American Heart Association Guidelines for Optimal Lipid Levels in High-Risk Women in a Managed Care Setting
Authors: Mosca Lori , Merz Noel Bairey , Blumenthal Roger S. , Cziraky Mark J. , Fabunmi Rosalind P. , Sarawate Chaitanya , Watson Karol E. , Willey Vincent J. , Stanek Eric J.
Published: February 2005

Background—

The American Heart Association (AHA) recently established evidence-based recommendations for cardiovascular disease (CVD) prevention in women, including lipid management. This study evaluated optimal lipid-level attainment and treatment patterns on the basis of these guidelines in high-risk women in a managed care setting.

Methods and Results—

We conducted a historical prospective cohort analysis of a 1.1-million-member, integrated, managed-care database. Eligible high-risk women were those with evidence of previous CVD or risk equivalent who had a full lipid panel available between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had a minimum of 12 months health plan eligibility preindex and postindex lipid panel. Optimal lipid levels were defined as LDL cholesterol (LDL-C) <100 mg/dL, HDL cholesterol (HDL-C) >50 mg/dL, non–HDL-C <130 mg/dL, and triglycerides <150 mg/dL. Laboratory values and lipid pharmacotherapy were assessed longitudinally over the postindex follow-up (up to 36 months). A total of 8353 high-risk women (mean age, 66±14 years) with a mean follow-up of 27±8 months were included. Only 7% attained optimal combined lipid levels initially, and this increased to 12% after 36 months. Lipid-modifying therapy was initiated in 32% of patients, including 35% of women with LDL-C ≥100 mg/dL and 15% with LDL-C <100 mg/dL.

Conclusions—

Among high-risk women, few attained the AHA’s standards for all lipid fractions, and only one third received recommended drug therapy, highlighting significant opportunities to apply evidence-based recommendations to manage lipid abnormalities in high-risk women.
National Study of Physician Awareness and Adherence to Cardiovascular Disease Prevention Guidelines
Authors: Mosca Lori , Linfante Allison H. , Benjamin Emelia J. , Berra Kathy , Hayes Sharonne N. , Walsh Brian W. , Fabunmi Rosalind P. , Kwan Johnny , Mills Thomas , Simpson Susan Lee
Published: February 2005

Background—

Few data have evaluated physician adherence to cardiovascular disease (CVD) prevention guidelines according to physician specialty or patient characteristics, particularly gender.

Methods and Results—

An online study of 500 randomly selected physicians (300 primary care physicians, 100 obstetricians/gynecologists, and 100 cardiologists) used a standardized questionnaire to assess awareness of, adoption of, and barriers to national CVD prevention guidelines by specialty. An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients. Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (
P
<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. After adjustment for risk assignment, the impact of patient gender on preventive care was not significant except for less aspirin (
P
<0.01) and more weight management recommended (
P
<0.04) for intermediate-risk women. Physicians did not rate themselves as very effective in their ability to help patients prevent CVD. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD.

Conclusions—

Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men. Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women.
Standards and Regulatory Capitalism: The Diffusion of Food Safety Standards in Developing Countries
Authors: Post Diahanna L.
Published: February 2005

Public health is a major area of social regulation, tied closely to the rise of the regulatory state. Among public health standards, food safety standards were some of the first to be globalized, through the Codex Alimentarius Commission established in 1963. With the establishment of the World Trade Organization (WTO), these international food safety standards have taken on even greater importance, serving as a reference point for the WTO in resolving disputes between countries over trade barriers. Have these international food safety standards influenced domestic policies and, if so, in which directions and why? This article considers how the Codex food additive standard has influenced policy in Argentina and the Dominican Republic. It looks at the role and interaction of international, regional, and domestic actors and top-down, bottom-up, and horizontal directions of policy diffusion. It also examines the role played by powerful states in shaping international standards.
The Institutional Foundations of Regulatory Capitalism: The Diffusion of Independent Regulatory Agencies in Western Europe
Authors: Gilardi Fabrizio
Published: February 2005

This article studies the diffusion of the main institutional feature of regulatory capitalism, namely, independent regulatory agencies. While only a few such authorities existed in Europe in the early 1980s, by the end of the twentieth century they had spread impressively across countries and sectors. The analysis finds that three classes of factors (bottom-up, top-down, and horizontal) explain this trend. First, the establishment of independent regulatory agencies was an attempt to improve credible commitment capacity when liberalizing and privatizing utilities and to alleviate the political uncertainty problem, namely, the risk to a government that its policies will be changed when it loses power. Second, Europeanization favored the creation of independent regulators. Third, individual decisions were interdependent, as governments were influenced by the decisions of others in an emulation process where the symbolic properties of independent regulators mattered more than the functions they performed.
The Global Diffusion of Regulatory Instruments: The Making of a New International Environmental Regime
Authors: Busch Per-Olof , Jörgens Helge , Tews Kerstin
Published: February 2005

During the 1990s, a new regulatory pattern in domestic environmental policy making emerged. This pattern is largely a result of policy diffusion. In the absence of formal obligations, regulatory instruments that have been communicated internationally and were already being practiced elsewhere were voluntarily emulated and adopted by policy makers. While the international promotion of regulatory instruments often facilitated their diffusion, the instruments’ characteristics determined the extent and speed by which regulatory instruments spread across countries. The voluntary adoption of regulatory instruments cannot be exclusively explained by the rational motivation of policy makers to improve effectiveness. In addition, they were motivated by concerns of legitimacy and perceived pressure to conform with international norms.
The Global Diffusion of Regulatory Capitalism
Authors: Levi-Faur David
Published: February 2005

This article analyzes the rise and diffusion of the new order of regulatory capitalism. It offers an analytical and historical analysis of relations between capitalism and regulation and suggests that change in the governance of capitalist economy is best captured by reference to (1) a new division of labor between state and society (e.g., privatization), (2) an increase in delegation, (3) proliferation of new technologies of regulation, (4) formalization of interinstitutional and intrainstitutional arrangements of regulation, and (5) growth in the influence of experts in general, and of international networks of experts in particular. Regulation, though not necessarily directly by the state, seems to be on the increase despite efforts to redraw the boundaries between state and society.
On Waves, Clusters, and Diffusion: A Conceptual Framework
Authors: Elkins Zachary , Simmons Beth
Published: February 2005

This article makes a conceptual and theoretical contribution to the study of diffusion. The authors suggest that the concept of diffusion be reserved for processes (not outcomes) characterized by a certain uncoordinated interdependence. Theoretically, the authors identify the principal sources of clustered policy reforms. They then clarify the characteristics specific to diffusion mechanisms and introduce a categorization of such processes. In particular, they make a distinction between two types of diffusion: adaptation and learning. They argue that this categorization adds conceptual clarity and distinguishes mechanisms with distinct substantive consequences.
Regulatory Capitalism as a Networked Order: The International System as an Informational Network
Authors: Lazer David
Published: February 2005

This article conceptualizes the international system as an informational network—where the sovereign units in the system produce and process information, and linkages among units in the system are conduits for information. Building on a substantial literature that documents the diffusion of policies across nations, this article draws on concepts from network analysis to ask a critical question: what governance issues are raised by viewing the international system as an informational network? The author asserts that the core governance challenge is to balance the benefits of eliminating costly reinvention of the wheel, while maintaining continued innovation and minimizing the dissemination of welfare-reducing policies (fads). Increases in the linkages in the system, while improving the availability of information to all actors, may decrease innovation and increase fads.
Advancing Womanist Identity Development
Authors: Moradi Bonnie
Published: February 2005

Scholars have called for increased attention to within-group variability in models and measures of identity development. As a step toward responding to these calls, the current review focuses on the womanist identity development model as a model of gender-related identity development that has been argued to be applicable to women across racial/ethnic, class, and other groups. The review provides an introduction to the womanist identity development model and its operationalization, critically analyzes literature on the model and its measurement, and explores directions for further development of womanist identity development theory and research.
An Emancipatory Communitarian Approach to Vocational Development Theory, Research, and Practice
Authors: Blustein David L. , McWhirter Ellen Hawley , Perry Justin C.
Published: February 2005

Building on recent calls for a more explicit and intentional endorsement of social justice goals within counseling psychology and vocational psychology, this article proposes Prilleltensky’s (1997) emancipatory communitarian approach to psychological practice as a useful framework for vocational theory, practice, and research. Such a framework emphasizes the distinction between the concepts of work and career and illuminates the extent to which traditional vocational psychology has attended to the needs of the people who experience little, if any, volition in their choices of career or line of work. We present a rationale for integrating an emancipatory communitarian approach into vocational psychology theory and the implications of this approach for future research and practice.
Addressing Social Class and Classism in Vocational Theory and Practice
Authors: Liu William Ming , Ali Saba Rasheed
Published: February 2005

The emancipatory communitarian approach to vocational development is congruent with previous calls to counseling psychologists to be oriented to social justice in their research and practice. However, even in the current emancipatory communitarian approach, an implicit upward mobility bias favors some vocations. To help understand how to better apply the emancipatory communitarian approach, a social class and classism framework is incorporated to explore how upward mobility bias distorts and ignores negative aspects of higher status and higher prestige jobs and does not recognize potential positive aspects of lower status and working-class jobs.
Advancing Social Justice in Vocational Theory, Research, and Practice
Authors: Borgen Fred H.
Published: February 2005

David Blustein, Ellen Hawley McWhirter, and Justin Perry present a social justice agenda for action in vocational psychology in their article “An Emancipatory Communitarian Approach to Vocational Development Theory, Research, and Practice.” They build on robust work in counseling psychology over recent decades by using the critical work of Isaac Prilleltensky as a fulcrum for advancing this agenda. Much of their case effectively argues that we should move beyond tradition to improve the working lives of our clients. While their arguments are powerful, I suggest several ways to expand their discourse.
Social Justice
Authors: Gainor Kathy A.
Published: February 2005

In response to the article “An Emancipatory Communitarian Approach to Vocational Development Theory, Research, and Practice” by David Blustein, Ellen Hawley McWhirter, and Justin Perry, this author discusses the moral imperative of a social justice approach to vocational psychology. Planning for and directly addressing the inevitable and necessary resistance to change are critical components of social justice work. Implications for vocational psychology theory, research, and training are discussed, including the application of social cognitive career theory.
Annunciation
Authors: McWhirter Ellen Hawley , Blustein David L. , Perry Justin C.
Published: February 2005

The informative and critical reactions from Fred Borgen; William Liu and Saba Rasheed Ali; Tod Sloan; and Kathy Gainor provide more reason and resolve to incorporate the emancipatory communitarian approach in vocational psychology. To move from a preoccupation with denunciation to the generation of solutions, or annunciation, we respond to each of the authors’ suggestions and comments. We highlight points raised by each author to clarify our rationale and intentions as well as to invite space for dialogue, disagreement, and growth among the many perspectives and values held within our field.
Marxian Theory of Competition and the Concept of Regulating Capital: Evidence from Greek Manufacturing
Authors: Tsoulfidis Lefteris , Tsaliki Persefoni
Published: February 2005

This article discusses the notion of competition as a process of rivalry between firms. This approach was developed initially by the classical economists and continued in the writings of Marx and Schumpeter. More specifically, this article sets out to show that on the one hand, this alternative notion of competition forms a theoretical framework for the understanding of many crucial aspects of modern economies; and on the other hand, on empirical grounds, one of the fundamental tenets of this theory, that is, the long-run tendential equalization of interindustry profit rates, holds true in the case of Greek manufacturing industries. The last objective is achieved with the introduction of the concept of regulating capital and with it the associated notion of the incremental rate of returns.
“Fiduciary Capitalism,” the “Political Model of Corporate Governance,” and the Prospect of Stakeholder Capitalism in the United States
Authors: Brennan David M.
Published: February 2005

As progressive pension reforms seek to increase the opportunities for stakeholder involvement, they confront an existing set of class relations that by design exclude workers, retirees, and the state from real economic participation. This article argues that pension reforms must explicitly recognize the class underpinnings that jeopardize their success; proposes a workable, class-sensitive orientation for pension reforms; and includes the legislative context for governance reforms.
Endogenous Social Preferences
Authors: Carpenter Jeffrey P.
Published: February 2005

A long-standing discussion in economics asks whether institutions affect people’s social predispositions. The current experiment tests whether different aspects of markets affect people’s social preferences. The results are that people are less socially minded in more anonymous settings. Additionally, market competition erodes social preferences through two mechanisms. First, market competition encourages opportunistic behavior, and second, the market institution itself decreases the other-regardingness of the participants.
From Additions and Withdrawals to Environmental Flows
Authors: Mol Arthur P. J. , Spaargaren Gert
Published: February 2005

Sociology is known for its academic debates. These debates are vehicles to accumulate understanding and interpretation of a constantly changing modern order. In the environmental social sciences, one of the axes of debate recently centered between Treadmill of Production ideas and Ecological Modernization perspectives. This article reviews the nature of that debate and aims to move beyond it. In using the sociology of networks and flows, the future research agenda for the environmental social sciences is reframed and reformulated.
Daily antibiotic cost of nosocomial infections in a Turkish university hospital
Authors: Inan Dilara , Saba Rabin , Gunseren Filiz , Ongut Gozde , Turhan Ozge , Yalcin Ata Nevzat , Mamikoglu Latife
Published: February 2005

Background

Many studies associated nosocomial infections with increased hospital costs due to extra days in hospital, staff time, extra investigations and drug treatment. The cost of antibiotic treatment for these infections represents a significant part of hospital expenditure. This prospective observational study was designed to determine the daily antibiotic cost of nosocomial infections per infected adult patient in Akdeniz University Hospital.

Methods

All adult patients admitted to the ICUs between January 1, 2000, and June 30, 2003 who had only one nosocomial infection during their stay were included in the study. Infection sites and pathogens, antimicrobial treatment of patient and it's cost were recorded. Daily antibiotic costs were calculated per infected patient.

Results

Among the 8460 study patients, 817 (16.6%) developed 1407 episodes of nosocomial infection. Two hundred thirty three (2.7%) presented with only one nosocomial infection. Mean daily antibiotic cost was $89.64. Daily antibiotic cost was $99.02 for pneumonia, $94.32 for bloodstream infection, $94.31 for surgical site infection, $52.37 for urinary tract infection, and $162.35 for the other infections per patient. The treatment of Pseudomonas aeruginosa infections was the most expensive infection treated. Piperacillin-tazobactam and amikacin were the most prescribed antibiotics, and meropenem was the most expensive drug for treatment of the nosocomial infections in the ICU.

Conclusions

Daily antibiotic cost of nosocomial infections is an important part of extra costs that should be reduced providing rational antibiotic usage in hospitals.
Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients
Authors: Hashimoto Kenji , Engberg Göran , Shimizu Eiji , Nordin Conny , Lindström Leif H , Iyo Masaomi
Published: February 2005

Background

Recent magnetic resonance spectroscopy (MRS) studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF) of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients.

Method

Levels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography.

Results

The ratio (126.1 (median), 117.7 ± 27.4 (mean ± S.D.)) of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001) higher than that (81.01 (median), 89.1 ± 22.5 (mean ± S.D.)) of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls.

Conclusion

Our data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia.
Resection of small plexiform neurofibromas in neurofibromatosis type 1 children
Authors: Friedrich Reinhard E , Schmelzle Rainer , Hartmann Melanie , Fünsterer Carsten , Mautner Victor-F
Published: February 2005

Background

Plexiform neurofibromas (PNF) are benign tumors of the peripheral nerve which mostly develop in patients with neurofibromatosis type 1 (NF1). Surgical interventions are usually not applied to children with small tumors. These are rather restricted to debulking of larger tumors in adults that cause clinical complications or aesthetic disfigurement. In most cases, a total resection of PNF is not possible due to the network-like growth of the tumors.

Patients and methods

Early surgical intervention was carried out for 9 small PNFs in 7 NF1 children. Tumor resection was performed following the graphical delineation of the affected skin and according the MRI findings.

Results

Total resection was achieved for all 9 PNF without causing any neurological or organic deficit. Annual magnetic resonance tomography over a period of four years did not reveal any relapse of the tumors.

Conclusions

Early surgical intervention for small superficial PNFs in NF1 children have various advantages and may especially be considered a strategy to prevent progression.
Assessing post-traumatic stress disorder in South African adolescents: using the child and adolescent trauma survey (CATS) as a screening tool
Authors: Suliman S , Kaminer D , Seedat S , Stein DJ
Published: February 2005

Background

Several studies have demonstrated that South African children and adolescents are exposed to high levels of violent trauma with a significant proportion developing PTSD, however, limited resources make it difficult to accurately identify traumatized children.

Methods

A clinical interview (K-SADS-PL, selected modules) and self-report scale (CATS) were compared to determine if these different methods of assessment elicit similar information with regards to trauma exposure and post-traumatic stress disorder (PTSD) in adolescents. Youth (n = 58) from 2 schools in Cape Town, South Africa participated.

Results

91% of youth reported having been exposed to a traumatic event on self-report (CATS) and 38% reported symptoms severe enough to be classified as PTSD. On interview (K-SADS-PL), 86% reported exposure to a traumatic event and 19% were found to have PTSD. While there were significant differences in the rates of trauma exposure and PTSD on the K-SADS and CATS, a cut-off value of 15 on the CATS maximized both the number of true positives and true negatives with PTSD. The CATS also differentiated well between adolescents meeting DSM-IV PTSD symptom criteria from adolescents not meeting criteria.

Conclusions

Our results indicate that trauma exposure and PTSD are prevalent in South African youth and if appropriate cut-offs are used, self-report scales may be useful screening tools for PTSD.
Weight, Weight Gain, and Survival After Breast Cancer Diagnosis
Authors: Kroenke Candyce H. , Chen Wendy Y. , Rosner Bernard , Holmes Michelle D.
Published: February 2005

Purpose

To determine whether weight prior to diagnosis and weight gain after diagnosis are predictive of breast cancer survival.

Methods

Patients included 5,204 Nurses' Health Study participants diagnosed with incident, invasive, nonmetastatic breast cancer between 1976 and 2000; 860 total deaths, 533 breast cancer deaths, and 681 recurrences (defined as secondary lung, brain, bone, or liver cancer, and death from breast cancer) accrued to 2002. We computed the change in body mass index (BMI) from before to the first BMI reported ≥ 12 months after the date of diagnosis. Cox proportional hazards models were used to evaluate associations of categories of BMI before diagnosis and of BMI change with time to event. We stratified by smoking, menopausal status, and breast cancer–related variables.

Results

In multivariate-adjusted analyses, weight before diagnosis was positively associated with breast cancer recurrence and death, but this was apparent only in never smokers. Similarly, among never-smoking women, those who gained between 0.5 and 2.0 kg/m2 (median gain, 6.0 lb; relative risk [RR], 1.35; 95% CI, 0.93 to 1.95) or more than 2.0 kg/m2 (median gain, 17.0 lb; RR, 1.64; 95% CI, 1.07 to 2.51) after diagnosis had an elevated risk of breast cancer death during follow-up (median, 9 years), compared with women who maintained their weight (test for linear trend, P = .03). Associations with weight were stronger in premenopausal than in postmenopausal women. Similar findings were noted for breast cancer recurrence and all-cause mortality.

Conclusion

Weight and weight gain were related to higher rates of breast cancer recurrence and mortality, but associations were most apparent in never-smoking women.
Meta-Analysis to Evaluate the Role of Interferon in Follicular Lymphoma
Authors: Rohatiner A.Z.S. , Gregory W.M. , Peterson B. , Borden E. , Solal-Celigny P. , Hagenbeek A. , Fisher R.I. , Unterhalt M. , Arranz R. , Chisesi T. , Aviles A. , Lister T.A.
Published: February 2005

Purpose

To determine whether interferon (IFN) -α2, when given with or following chemotherapy, influences response rate, remission duration, and survival in newly diagnosed patients with follicular lymphoma.

Patients and Methods

Ten phase III studies evaluating the role of IFN-α2 in 1,922 newly diagnosed patients with follicular lymphoma were analyzed. Updated individual patient data were used to perform meta-analyses for response, survival, and remission duration.

Results

The addition of IFN-α2 to initial chemotherapy did not significantly influence response rate. An overall meta-analysis for survival showed a significant difference in favor of IFN-α2, but also showed significant heterogeneity between studies. Further analyses were carried out in order to explain this heterogeneity, and to define the circumstances in which IFN-α2 prolonged survival. The survival advantage was seen when IFN-α2 was given: (1) in conjunction with relatively intensive initial chemotherapy (2P = .00005), (2) at a dose ≥ 5 million units (2P = .000002), (3) at a cumulative dose ≥ 36 million units per month (2P = .000008), and (4) with chemotherapy rather than as maintenance therapy (P = .004). With regard to remission duration, there was also a significant difference in favor of IFN-α2, irrespective of the intensity of chemotherapy used, IFN dose, or whether IFN was given as a maintenance strategy or with chemotherapy.

Conclusion

When given in the context of relatively intensive initial chemotherapy, and at a dose ≥ 5 million units (≥ 36 × 106 units per month), IFN-α2 prolongs survival and remission duration in patients with follicular lymphoma.
Quantification of Carbamylated LDL in Human Sera by a New Sandwich ELISA
Authors: Apostolov Eugene O , Shah Sudhir V , Ok Ercan , Basnakian Alexei G
Published: February 2005

Background: We previously suggested that increased carbamylated LDL (cLDL), a product of nonenzymatic modification of LDL in human serum by urea-derived cyanate, may cause cardiovascular complications in patients with chronic renal insufficiency. An assay for precise measurement of cLDL in serum was not previously available.

Methods: Polyclonal antibodies against human cLDL and nonmodified, native LDL (nLDL) were raised in rabbits and extensively purified by affinity chromatography. New sandwich ELISAs to measure cLDL and nLDL with use of these antibodies were developed. Serum concentrations of cLDL and nLDL were measured by the sandwich ELISAs in 41 patients with end-stage renal disease (ESRD) and 40 healthy controls.

Results: Both assays showed satisfactory reproducibility, linearity, and recovery. The assays could detect 2.7 mg/L cLDL with a linear detection range of 5–1000 mg/L and 5 mg/L nLDL with a linear detection range of 50–1000 mg/L. These measurements showed that patients with ESRD have significantly increased serum cLDL [281.5 (46.9) mg/L compared with 86.1 (29.7) mg/L in a control group; P <0.001]. There was no significant difference in nLDL concentrations between the groups.

Conclusions: These assays are a potentially valuable tool for cardiovascular research in renal patients and healthy individuals. The cLDL concentration appears to be the highest among all previously described modified LDL isoforms in both controls and ESRD patients.
Comparative approach of the solubility of protactinium oxy/hydroxides
Authors: Tarapcik P. , Fourest B. , Giffaut E.
Published: February 2005

The hydrolysis constants and the solubility products of the oxide/hydroxides of Pa(IV) and Pa(V) have been first reviewed and re-evaluated through the application of three comparative methods: the simple Hard Sphere Electrostatic model (HSE), the Brown and Wanner Theory (BWT) and the Correlation between Solubility and Complex stability constants of a metal ion (CSC). The latter method is the most empirical one, but it gives coherent results, in agreement with the few published experimental values, for all the possible aqua species of protactinium (Pa4+, Pa5+, PaO2+and PaO3+). The selected thermodynamic data have then been used to predict the protactinium solubility in non complexing media of various pH and redox potential.
Prognosticating the humic complexation for redox sensitive actinides through analogy, using the charge neutralisation model
Authors: Reiller Pascal
Published: February 2005

The complexation of redox sensitive elements by humic acid (HA), described through the charge neutralisation model (CNM), has been reviewed in order to have a comprehensive scope. The data acquired in HUMICS program on thorium(IV), and data available in the literature, were reinterpreted according to the CNM, and adapted to uranium(IV), neptunium(IV) and plutonium(IV) through analogy in order to draw a boundary prediction. Otherwise, available data obtained in the framework of the CNM were used, or adapted if necessary, for other redox states when the analogy is justified,i.e.Am3+-Cm3+for Pu3+, NpO2+for PuO2+and UO22+for PuO22+.

The obtained speciation diagrams indicate that, when (HA)=100 mg/L, redox sensitive actinides should be reduced to their +IV state whenEh≤650 mV/SHE for plutonium,Eh≤100 mV/SHE for neptunium andEh≤-20 mV/SHE for U. Plutonium could be present as mixtures of plutonium(III) and (IV) depending on the pH value in reducing ground waters -150 ≤Eh(mV/SHE) ≤ 150. The known reduction of neptunium(V) to neptunium(IV) in Gorleben ground waters seems also well represented, so is the stability of uranium(VI) in humic solution whenEh≥ 100 mV/SHE. Conversely, the known association of plutonium(VI) in marine systems is not satisfactorily represented, so does is the uranium behaviour under reducing conditions. Experiments under well-controlled conditions are still needed to ascertain the plutonium and uranium comportment in the presence of humic acid.
Sorption and transport behavior of radionuclides in the proposed low-level radioactive waste disposal facility at the Hanford site, Washington
Authors: Um Wooyong , Serne R. Jeffrey
Published: February 2005

A series of batch sorption and column experiments was conducted to investigate sorption and transport behavior of99Tc,129I,79Se, and90Sr on and through borehole sediments collected from the proposed low-level radioactive waste disposal facility at the Hanford Site (200 East Area). Batch sorption experiments were conducted on Hanford sediment using uncontaminated Hanford groundwater and simulated glass leachates spiked with individual radionuclides. Strongest sorption occurred for90Sr, while79Se sorption was intermediate, and129I and99Tc showed the least sorption affinities on Hanford sediment among these radionuclides studied. The results of column experiments that measured transport behavior of these radionuclides through Hanford sediment were similar to the mobility that can be calculated from the batch sorption results, that is high mobility for99Tc and129I compared to the intermediate and strong retardation for79Se and90Sr, respectively. These contaminant sorption data on sediments from below the proposed disposal facility, especially the tests using simulated glass leachate, corroborate values obtained for sediments collected in the past from near by locations and for generic solutions such as regional groundwater. These new data should provide more technical defensibility for past performance assessment predictions that did not use site-specific sediments and leachates. Further, the new data will be incorporated into future performance assessment activities that will update and improve past predictions.
A Genetic and Molecular Characterization of Two Proximal Heterochromatic Genes on Chromosome 3 of Drosophila melanogaster
Authors: Schulze Sandra R , Sinclair Donald A R , Fitzpatrick Kathleen A , Honda Barry M
Published: February 2005

Heterochromatin comprises a transcriptionally repressive chromosome compartment in the eukaryotic nucleus; this is exemplified by the silencing effect it has on euchromatic genes that have been relocated nearby, a phenomenon known as position-effect variegation (PEV), first demonstrated in Drosophila melanogaster. However, the expression of essential heterochromatic genes within these apparently repressive regions of the genome presents a paradox, an understanding of which could provide key insights into the effects of chromatin structure on gene expression. To date, very few of these resident heterochromatic genes have been characterized to any extent, and their expression and regulation remain poorly understood. Here we report the cloning and characterization of two proximal heterochromatic genes in D. melanogaster, located deep within the centric heterochromatin of the left arm of chromosome 3. One of these genes, RpL15, is uncharacteristically small, is highly expressed, and encodes an essential ribosomal protein. Its expression appears to be compromised in a genetic background deficient for heterochromatin protein 1 (HP1), a protein associated with gene silencing in these regions. The second gene in this study, Dbp80, is very large and also appears to show a transcriptional dependence upon HP1; however, it does not correspond to any known lethal complementation group and is likely to be a nonessential gene.
Flexibility in a Gene Network Affecting a Simple Behavior in Drosophila melanogaster
Authors: van Swinderen Bruno , Greenspan Ralph J
Published: February 2005

Gene interactions are emerging as central to understanding the realization of any phenotype. To probe the flexibility of interactions in a defined gene network, we isolated a set of 16 interacting genes in Drosophila, on the basis of their alteration of a quantitative behavioral phenotype—the loss of coordination in a temperature-sensitive allele of Syntaxin1A. The interactions inter se of this set of genes were then assayed in the presence and in the absence of the original Syntaxin1A mutation to ask whether the relationships among the 16 genes remain stable or differ after a change in genetic context. The pattern of epistatic interactions that occurs within this set of variants is dramatically altered in the two different genetic contexts. The results imply considerable flexibility in the network interactions of genes.
Evolution of Recombination Due to Random Drift
Authors: Barton N H , Otto Sarah P
Published: February 2005

In finite populations subject to selection, genetic drift generates negative linkage disequilibrium, on average, even if selection acts independently (i.e., multiplicatively) upon all loci. Negative disequilibrium reduces the variance in fitness and hence, by Fisher's (1930) fundamental theorem, slows the rate of increase in mean fitness. Modifiers that increase recombination eliminate the negative disequilibria that impede selection and consequently increase in frequency by “hitchhiking.” Thus, stochastic fluctuations in linkage disequilibrium in finite populations favor the evolution of increased rates of recombination, even in the absence of epistatic interactions among loci and even when disequilibrium is initially absent. The method developed within this article allows us to quantify the strength of selection acting on a modifier allele that increases recombination in a finite population. The analysis indicates that stochastically generated linkage disequilibria do select for increased recombination, a result that is confirmed by Monte Carlo simulations. Selection for a modifier that increases recombination is highest when linkage among loci is tight, when beneficial alleles rise from low to high frequency, and when the population size is small.
Roles of RAD6 Epistasis Group Members in Spontaneous Polζ-Dependent Translesion Synthesis in Saccharomyces cerevisiae
Authors: Minesinger Brenda K , Jinks-Robertson Sue
Published: February 2005

DNA lesions that arise during normal cellular metabolism can block the progress of replicative DNA polymerases, leading to cell cycle arrest and, in higher eukaryotes, apoptosis. Alternatively, such blocking lesions can be temporarily tolerated using either a recombination- or a translesion synthesis-based bypass mechanism. In Saccharomyces cerevisiae, members of the RAD6 epistasis group are key players in the regulation of lesion bypass by the translesion DNA polymerase Polζ. In this study, changes in the reversion rate and spectrum of the lys2ΔA746 −1 frameshift allele have been used to evaluate how the loss of members of the RAD6 epistasis group affects Polζ-dependent mutagenesis in response to spontaneous damage. Our data are consistent with a model in which Polζ-dependent mutagenesis relies on the presence of either Rad5 or Rad18, which promote two distinct error-prone pathways that partially overlap with respect to lesion specificity. The smallest subunit of Polδ, Pol32, is also required for Polζ-dependent spontaneous mutagenesis, suggesting a cooperative role between Polδ and Polζ for the bypass of spontaneous lesions. A third error-free pathway relies on the presence of Mms2, but may not require PCNA.
Persistence and Loss of Meiotic Recombination Hotspots
Authors: Pineda-Krch Mario , Redfield Rosemary J
Published: February 2005

The contradiction between the long-term persistence of the chromosomal hotspots that initiate meiotic recombination and the self-destructive mechanism by which they act strongly suggests that our understanding of recombination is incomplete. This “hotspot paradox” has been reinforced by the finding that biased gene conversion also removes active hotspots from human sperm. To investigate the requirements for hotspot persistence, we developed a detailed computer simulation model of their activity and its evolutionary consequences. With this model, unopposed hotspot activity could drive strong hotspots from 50% representation to extinction within 70 generations. Although the crossing over that hotspots cause can increase population fitness, this benefit was always too small to slow the loss of hotspots. Hotspots could not be maintained by plausible rates of de novo mutation, nor by crossover interference, which alters the frequency and/or spacing of crossovers. Competition among hotspots for activity-limiting factors also did not prevent their extinction, although the rate of hotspot loss was slowed. Key factors were the probability that the initiating hotspot allele is destroyed and the nonmeiotic contributions hotspots make to fitness. Experimental investigation of these deserves high priority, because until the paradox is resolved all components of the mechanism are open to doubt.
Bacterial Persistence
Authors: Kussell Edo , Kishony Roy , Balaban Nathalie Q , Leibler Stanislas
Published: February 2005

The persistence phenotype is an epigenetic trait exhibited by a subpopulation of bacteria, characterized by slow growth coupled with an ability to survive antibiotic treatment. The phenotype is acquired via a spontaneous, reversible switch between normal and persister cells. These observations suggest that clonal bacterial populations may use persister cells, whose slow division rate under growth conditions leads to lower population fitness, as an “insurance policy” against antibiotic encounters. We present a model of Escherichia coli persistence, and using experimentally derived parameters for both wild type and a mutant strain (hipQ) with markedly different switching rates, we show how fitness loss due to slow persister growth pays off as a risk-reducing strategy. We demonstrate that wild-type persistence is suited for environments in which antibiotic stress is a rare event. The optimal rate of switching between normal and persister cells is found to depend strongly on the frequency of environmental changes and only weakly on the selective pressures of any given environment. In contrast to typical examples of adaptations to features of a single environment, persistence appears to constitute an adaptation that is tuned to the distribution of environmental change.