bluuebunny/crossref_metadata_2025 huggingface dataset:
MODELLING USER UNCERTAINTY FOR DISCLOSURE RISK AND DATA UTILITY
Authors: TROTTINI MARIO , FIENBERG STEPHEN E.
Published: November 2002

In this paper we show how a simple model that captures user uncertainty can be used to define suitable measures of disclosure risk and data utility. The model generalizes previous results of Duncan and Lambert.1 We present several examples to illustrate how the new measures can be used to implement existing optimality criteria for the choice of the best form of data release.
SOFTWARE SYSTEMS FOR TABULAR DATA RELEASES
Authors: DOBRA ADRIAN , KARR ALAN F. , SANIL ASHISH P. , FIENBERG STEPHEN E.
Published: November 2002

We describe two classes of software systems that release tabular summaries of an underlying database. Table servers respond to user queries for (marginal) sub-tables of the "full" table summarizing the entire database, and are characterized by dynamic assessment of disclosure risk, in light of previously answered queries. Optimal tabular releases are static releases of sets of sub-tables that are characterized by maximizing the amount of information released, as given by a measure of data utility, subject to a constraint on disclosure risk. Underlying abstractions — primarily associated with the query space, as well as released and unreleasable sub-tables and frontiers, computational algorithms and issues, especially scalability, and prototype software implementations are discussed.
A CRITIQUE OF THE SENSITIVITY RULES USUALLY EMPLOYED FOR STATISTICAL TABLE PROTECTION
Authors: DOMINGO-FERRER JOSEP , TORRA VICENÇ
Published: November 2002

In statistical disclosure control of tabular data, sensitivity rules are commonly used to decide whether a table cell is sensitive and should therefore not be published. The most popular sensitivity rules are the dominance rule, the p%-rule and the pq-rule. The dominance rule has received critiques based on specific numerical examples and is being gradually abandoned by leading statistical agencies. In this paper, we construct general counterexamples which show that none of the above rules does adequately reflect disclosure risk if cell contributors or coalitions of them behave as intruders: in that case, releasing a cell declared non-sensitive can imply higher disclosure risk than releasing a cell declared sensitive. As possible solutions, we propose an alternative sensitivity rule based on the concentration of relative contributions. More generally, we suggest to complement a priori risk assessment based on sensitivity rules with a posteriori risk assessment which takes into account tables after they have been protected.
k-ANONYMITY: A MODEL FOR PROTECTING PRIVACY
Authors: SWEENEY LATANYA
Published: November 2002

Consider a data holder, such as a hospital or a bank, that has a privately held collection of person-specific, field structured data. Suppose the data holder wants to share a version of the data with researchers. How can a data holder release a version of its private data with scientific guarantees that the individuals who are the subjects of the data cannot be re-identified while the data remain practically useful? The solution provided in this paper includes a formal protection model named k-anonymity and a set of accompanying policies for deployment. A release provides k-anonymity protection if the information for each person contained in the release cannot be distinguished from at least k-1 individuals whose information also appears in the release. This paper also examines re-identification attacks that can be realized on releases that adhere to k-anonymity unless accompanying policies are respected. The k-anonymity protection model is important because it forms the basis on which the real-world systems known as Datafly, μ-Argus and k-Similar provide guarantees of privacy protection.
ACHIEVING k-ANONYMITY PRIVACY PROTECTION USING GENERALIZATION AND SUPPRESSION
Authors: SWEENEY LATANYA
Published: November 2002

Often a data holder, such as a hospital or bank, needs to share person-specific records in such a way that the identities of the individuals who are the subjects of the data cannot be determined. One way to achieve this is to have the released records adhere to k-anonymity, which means each released record has at least (k-1) other records in the release whose values are indistinct over those fields that appear in external data. So, k-anonymity provides privacy protection by guaranteeing that each released record will relate to at least k individuals even if the records are directly linked to external information. This paper provides a formal presentation of combining generalization and suppression to achieve k-anonymity. Generalization involves replacing (or recoding) a value with a less specific but semantically consistent value. Suppression involves not releasing a value at all. The Preferred Minimal Generalization Algorithm (MinGen), which is a theoretical algorithm presented herein, combines these techniques to provide k-anonymity protection with minimal distortion. The real-world algorithms Datafly and μ-Argus are compared to MinGen. Both Datafly and μ-Argus use heuristics to make approximations, and so, they do not always yield optimal results. It is shown that Datafly can over distort data and μ-Argus can additionally fail to provide adequate protection.
RE-IDENTIFYING REGISTER DATA BY SURVEY DATA USING CLUSTER ANALYSIS: AN EMPIRICAL STUDY
Authors: BACHER JOHANN , BRAND RUTH , BENDER STEFAN
Published: November 2002

More and more empirical researchers from universities or research centres like to use register or survey data collected by statistical agencies or the social security system, since these data can by used for several empirical studies, e.g. the analysis of special groups or quantitative effects of economic or social policies. Most of the data required have to be (factually) anonymised before they are disseminated to preserve confidentiality. In the area of statistics on households and individuals this path has been pursued in Germany for several years. The transmission of de facto anonymised datafiles has proved to be a good form of co-operation between scientists and statisticians.

Factual anonymity of the data depends on the costs and benefits of a potential re-identification. The paper assumes that the intruder only accepts low costs. Therefore he uses a cluster analysis module that is available in a standards statistical software package to re-identify persons. After a description of the method different factors influencing the re-identification risk are studied using German employment statistics (register data) and the German Life History Study (survey data). The factors are: sample fraction and number of (irrelevant) variables. The results show, that the number of identifiable persons is remarkable high. Furthermore it can be confirmed with the cluster analysis that the number of re-identifiable records increases with increasing sampling fraction and that irrelevant variables reduce this number.
USING COMPUTATION TREE LOGIC FOR INTELLIGENT INFORMATION SEARCH ON THE WEB
Authors: DI SCIASCIO EUGENIO , DONINI FRANCESCO M. , MONGIELLO MARINA
Published: November 2002

Web engines crawl hyperlinks to search for new documents; yet when they index discovered documents they basically revert to conventional information retrieval models and concentrate on the indexing of terms in a single document.

We propose to overcome such limits with an approach based on temporal logic. By modeling a web site as a finite state transition system we are able to define complex and selective queries over hyperlinks with the aid of Computation Tree Logic operators.

We deployed the proposed approach in a prototype system that allows users pose queries in natural language. Queries are automatically translated in Computation Tree Logic, and the answer returned by our system is a set of paths. Experiments carried out with the aid of human experts show improved retrieval effectiveness with respect to current search engines.
MINING WEB DATA USING CLUSTERING TECHNIQUE FOR WEB PERSONALIZATION
Authors: DE SUPRIYA KUMAR , RADHA KRISHNA P.
Published: November 2002

Clustering of data in a large dimension space is of great interest in many data mining applications. In this paper, we propose a method for clustering of web usage data in a high-dimensional space based on a concept hierarchy model. In this method, the relationship present in the web usage data are mapped into a fuzzy proximity relation of user transactions. We also described an approach to present the preference set of URLs to a new user transaction based on the match score with the clusters. The study demonstrates that our approach is general and effective for mining the web data for web personalization.
A SIMILARITY-BASED MODEL FOR TOPIC DISTILLATION
Authors: WANG XIAOYU , WU HONGWEI , WEI LI , ZHOU AOYING
Published: November 2002

Topic distillation is the process of finding representative pages relevant to a given query. Well-known topic distillation approaches such as the HITS algorithm have shown to be useful for topic distillation. Many succeeding researchers focus on augmenting HITS with further content analysis to alleviate the steady deterioration of distillation quality suffered by HITS. In this paper, we attempt to revisit the behavior of HITS from a different point of view. Namely, a similarity-based analysis model is applied to observing the distillation procedure. By defining a generalized similarity, an algorithm is proposed, which can improve the quality of distillation only using the information of hyperlinks. The experimental results reveal that the new algorithm improves distillation quality without utilizing any content information of pages.
IDENTIFYING TOPICS FOR WEB DOCUMENTS THROUGH FUZZY ASSOCIATION LEARNING
Authors: HARUECHAIYASAK CHOOCHART , SHYU MEI-LING , CHEN SHU-CHING
Published: November 2002

Due to the explosive growth of available information on the World Wide Web (WWW), users have suffered from the information overload. To alleviate this problem, there is a need for an intelligent tool to help the users screening and filtering for interesting and useful information. In this paper, a method of automatically identifying topics for Web documents via a classification technique is proposed. Topic identification can be applied as a filtering tool for recommender systems to prune down the number of documents to within some particular topics. We adopt the fuzzy association concept as a machine learning technique to classify the documents into some predefined categories or topics. Our approach is compared to the vector space model with the cosine coefficient using the data sets collected from three different Web portals: Yahoo!, Open Directory Project and Excite. The results show that our approach yields higher classification accuracy compared to the vector space model.
PREDICTION OF NAVIGATION PROFILES IN A DISTRIBUTED INTERNET ENVIRONMENT THROUGH LEARNING OF GRAPH DISTRIBUTIONS
Authors: KUKULENZ DIRK , PAULI JOSEF
Published: November 2002

Collaborative filtering techniques in the Internet are a means to make predictions about the behavior of a certain user based on the observation of former users. Frequently in literature the exploited information is contained in the access-log files of web servers storing requested data objects. However with additional effort on the server side it is possible to register, from which to which data object a client actually navigates. In this article the profile of a user in a distributed web environment will be modeled by the set of his navigation decisions between data objects. Such a set can be regarded as a graph with the nodes being the requested data objects and the edges being the decisions. A method is presented to learn the distribution of such graphs based on distance functions between graphs and the application of clustering techniques. The estimated distribution is used to predict future navigation decisions of new users. Results with randomly generated graphs show properties of the new algorithm. A measure to estimate the prediction quality for observed profiles is presented.
AUTOMATIC COMPETITOR IDENTIFICATION FROM PUBLIC INFORMATION SOURCES
Authors: ZELENKO DMITRY , SEMIN OLEG
Published: November 2002

We present an automatic system that discovers competing companies from public information sources. The system extracts data from text, uses transformation-based learning to obtain appropriate data normalization, combines structured and unstructured information sources, uses probabilistic modelling to represent models of linked data, and succeeds in autonomously discovering competitors. We also introduce the iterative graph reconstruction process for inference in relational data, and show that it leads to improvements in performance. We validate system results and deploy it on the web as a powerful analytic tool for individual and institutional investors.
APPROXIMATE INFORMATION FILTERING WITH MULTIPLE CLASSIFICATION HIERARCHIES
Authors: STUCKENSCHMIDT HEINER
Published: November 2002

Web page categorization is an approach for improving precision and efficiency of information retrieval on the web by filtering out irrelevant pages. Current approaches to information filtering based on categorization assume the existence of a single classification hierarchy used for filtering. In this paper, we address the problem of filtering information categorized according to different classification hierarchies. We describe a method for approximating Boolean queries over class names across different class hierarchies.
AN EVOLUTIONARY APPROACH TO MINING ROBUST MULTI-RESOLUTION WEB PROFILES AND CONTEXT SENSITIVE URL ASSOCIATIONS
Authors: NASRAOUI OLFA , KRISHNAPURAM RAGHU
Published: November 2002

We present a technique for simultaneously mining Web navigation patterns and maximally frequent context-sensitive itemsets (URL associations) from the historic user access data stored in Web server logs. A new hierarchical clustering technique that exploits the symbiosis between clusters in feature space and genetic biological niches in nature, called Hierarchical Unsupervised Niche Clustering (H-UNC) is presented. We use H-UNC as part of a complete system of knowledge discovery in Web usage data. Our approach does not necessitate fixing the number of clusters in advance, is insensitive to initialization, can handle noisy data, general non-differentiable similarity measures, and automatically provides profiles at multiple resolution levels. Our experiments show that our algorithm is not only capable of extracting meaningful user profiles on real Web sites, but also discovers associations between distinct URL pages on a site, with no additional cost. Unlike content based association methods, our approach discovers associations between different Web pages based only on the user access patterns and not on the page content. Also, unlike traditional context-blind association discovery methods, H-UNC discovers context-sensitive associations which are only meaningful within a limited context/user profile.
AN ARCHITECTURE OF e-BUTLER: A CONSUMER-CENTRIC ONLINE PERSONALIZATION SYSTEM
Authors: ADOMAVICIUS GEDIMINAS , TUZHILIN ALEXANDER
Published: November 2002

This paper presents an architecture of the e-Butler service, i.e. a personalized consumer-centric infomediary delivering a broad range of shopping-related services to consumers. In order to provide these services effectively, e-Butler should be "intelligent". This paper describes how a certain level of intelligence can be achieved through the utilization of a broad range of technologies, including data mining, personalization, profiling, recommender systems, data warehousing, Web proxy servers, data monitoring and XML-based technologies, that are integrated into a unique architecture of e-Butler.
SUPPLY CHAIN FORMATION IN OPEN, MARKET-BASED MULTI-AGENT SYSTEMS
Authors: EASWARAN ANEURIN M. , PITT JEREMY
Published: November 2002

Efficient allocation of services to form a supply chain to solve complex tasks is a crucial problem. Optimal service allocation based on a single criterion is NP-Complete. Furthermore, complex tasks in general have multiple criteria that may be conflicting and non-commensurable. This paper presents a two-stage brokering algorithm for optimal anytime service allocation based on multiple criteria. In the first stage, a hierarchical task network planner is used to identify the services required to solve a task. In the second stage, a genetic algorithm (GA) determines service providers based on multiple criteria to provide the services identified by the planner. We present our algorithm and results from various experiments conducted to analyze the effect of various parameters that influence the complexity of the problem. In general, the results show the GA finds optimal solutions much quicker than a standard search algorithm. The empirical results also indicate the performance of the algorithm is sub-linear or polynomial time for various parameters. The algorithm has the ability to deal with any number of criteria. By addressing this problem, we expand the range of problems being addressed to any that require simultaneous optimization of multiple criteria and/or planning.
XML QUERY BY EXAMPLE
Authors: ZHANG SEN , WANG JASON T. L. , HERBERT KATHERINE G.
Published: November 2002

XML's tree structure provides a rich background for complicated structural searches. In this paper we present a new system, called XML Query by Example (XML QBE) that allows the user to query XML documents exploiting their inherent tree structure. We present some interesting queries and describe the underlying query processing algorithms. We also describe the system's architecture and report its implementation status. Finally we conclude the paper by pointing out some future work.
Functional P2Y
2
Nucleotide Receptors Mediate Uridine 5′-Triphosphate–Induced Intimal Hyperplasia in Collared Rabbit Carotid Arteries
Authors: Seye Cheikh I. , Kong Qiongman , Erb Laurie , Garrad Richard C. , Krugh Brent , Wang Meifang , Turner John T. , Sturek Michael , González Fernando A. , Weisman Gary A.
Published: November 2002

Background—

Extracellular uridine 5′-triphosphate (UTP) induces mitogenic activation of smooth muscle cells (SMCs) through binding to P2Y
2
nucleotide receptors. P2Y
2
receptor mRNA is upregulated in intimal lesions of rat aorta, but it is unclear how this G-protein–coupled receptor contributes to development of intimal hyperplasia.

Methods and Results—

This study used a silicone collar placed around rabbit carotid arteries to induce vascular injury and intimal thickening. Collar placement caused rapid upregulation of P2Y
2
receptor mRNA in medial SMCs before appearance of neointima. Fura-2 digital imaging of single SMCs was used to measure changes in myoplasmic calcium concentration (Ca
m
) in response to P2Y receptor agonists. In contrast to UDP, activation by UTP or adenosine 5′-triphosphate (ATP) greatly increased Ca
m
, which indicates upregulation of functional P2Y
2
receptors at which UTP and ATP are equipotent agonists. The number of responsive cells was significantly greater for freshly dispersed SMCs from collared arteries than for controls. Perivascular infusion of UTP (100 μmol/L) within the collar significantly enhanced neointimal development. Intimas that resulted from UTP exposure were infiltrated by macrophages. Moreover, increased expression of osteopontin occurred in response to in situ application of UTP. ATP or UTP also stimulated osteopontin expression in cultured SMCs in a dose-dependent manner. Furthermore, P2Y
2
antisense oligonucleotide inhibited osteopontin expression induced by UTP.

Conclusions—

These findings indicate for the first time a role for the UTP/ATP receptor, P2Y
2
, in development of intimal hyperplasia associated with atherosclerosis and restenosis.
Cytosolic Heat Shock Protein 60, Hypoxia, and Apoptosis
Authors: Gupta S. , Knowlton A.A.
Published: November 2002

Background—

Heat shock protein (HSP)60 is an abundant protein found primarily in the mitochondria, though 15% to 20% is found in the cytosol. Previously we observed that HSP60 complexes with bax in the cytosol. Reduction in HSP60 precipitates translocation of bax to the mitochondria and apoptosis. We hypothesized that HSP60 would decrease with hypoxia/reoxygenation and that this would precipitate bax translocation to the mitochondria and release of cytochrome c.

Methods and Results—

Adult rat cardiac myocytes were studied at end-hypoxia and at 10 and 24 hours of reoxygenation. HSP60 levels were unchanged at end-hypoxia and decreased 33% and 40% at 10 and 24 hours of reoxygenation, whereas HSP72 increased 80% and 110%. Bax and bcl-2 decreased during reoxygenation. However, cytochrome c release occurred at end-hypoxia, before reoxygenation. Cell fractionation was done to analyze this further. In normal myocytes, bax and HSP60 were present in the cytosol, and bax coimmunoprecipitated with cytosolic HSP60. At end-hypoxia, mitochondrial HSP60 was unchanged, but cytosolic HSP60 had disappeared and was now in the plasma membrane fraction. Concurrently, bax was no longer in the cytosol but now in the mitochondria. Thus, although total HSP60 remained the same, it no longer complexed with bax, and bax was free to translocate to the mitochondria and precipitate apoptosis. Reduction in ATP had a similar effect.

Conclusions—

These studies show that hypoxia results in disassociation of the HSP60-bax complex with translocation of cytosolic HSP60 to the plasma membrane and bax to the mitochondria. This is sufficient to trigger apoptosis.
Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Limits Progression and Destabilization of Established Atherosclerosis in Apolipoprotein E–Knockout Mice
Authors: Inoue Shujiro , Egashira Kensuke , Ni Weihua , Kitamoto Shiro , Usui Makoto , Otani Kisho , Ishibashi Minako , Hiasa Ken-ichi , Nishida Ken-ichi , Takeshita Akira
Published: November 2002

Background—

Monocyte infiltration into the arterial wall and its activation is the central event in atherogenesis. Thus, monocyte chemoattractant protein-1 (MCP-1) might be a novel therapeutic target against atherogenesis. We and others recently reported that blockade or abrogation of the MCP-1 pathway attenuates the initiation of atheroma formation in hypercholesterolemic mice. It remains unclear, however, whether blockade of MCP-1 can limit progression or destabilization of established lesions.

Methods and Results—

We report here that blockade of MCP-1 by transfecting an
N
-terminal deletion mutant of the MCP-1 gene limited progression of preexisting atherosclerotic lesions in the aortic root in hypercholesterolemic mice. In addition, blockade of MCP-1 changed the lesion composition into a more stable phenotype, ie, containing fewer macrophages and lymphocytes, less lipid, and more smooth muscle cells and collagen. This strategy decreased expression of CD40 and the CD40 ligand in the atherosclerotic plaque and normalized the increased chemokine (RANTES and MCP-1) and cytokine (tumor necrosis factor α, interleukin-6, interleukin-1β, and transforming growth factor β
1
) gene expression. These data suggest that MCP-1 is a central mediator in the progression and destabilization of established atheroma.

Conclusions—

The results of the present study suggest that the inflammatory responses mediated by MCP-1 are important in atherosclerosis and its complications.
Adrenocortical, Autonomic, and Inflammatory Causes of the Metabolic Syndrome
Authors: Brunner E.J. , Hemingway H. , Walker B.R. , Page M. , Clarke P. , Juneja M. , Shipley M.J. , Kumari M. , Andrew R. , Seckl J.R. , Papadopoulos A. , Checkley S. , Rumley A. , Lowe G.D.O. , Stansfeld S.A. , Marmot M.G.
Published: November 2002

Background—

The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS.

Methods and Results—

This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both −0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (
r
=−0.19;
P
=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences.

Conclusions—

Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.
Poly(ADP-Ribose) Polymerase Is Activated in Subjects at Risk of Developing Type 2 Diabetes and Is Associated With Impaired Vascular Reactivity
Authors: Szabó Csaba , Zanchi Anne , Komjáti Katalin , Pacher Pál , Krolewski Andrzej S. , Quist William C. , LoGerfo Frank W. , Horton Edward S. , Veves Aristidis
Published: November 2002

Background—

We have previously shown that endothelial function is impaired not only in diabetes but also in subjects at risk of developing type 2 diabetes. We hypothesized that changes in the expression or activity of the endothelial isoform of nitric oxide synthase (eNOS), the receptor for advanced glycation end products (RAGE), and poly(ADP-ribose) polymerase (PARP) are related to this impairment.

Methods and Results—

We included a control group of 21 healthy subjects, a group of 22 healthy individuals with parental history of type 2 diabetes, a group of 23 subjects with impaired glucose tolerance, and a group of 21 type 2 diabetic patients. Two 2-mm forearm skin biopsies were taken from each participant and used for measurements. The percentage of PARP-positive endothelial nuclei was higher in the group with parental history of type 2 diabetes and diabetic patients compared with the controls (
P
<0.001). Immunoreactivity for nitrotyrosine (a marker of reactive nitrogen species) was higher in the diabetic group compared with all other groups (
P
<0.01). No differences in the expression of eNOS and RAGE were found among all 4 groups. The polymorphism of the eNOS gene was also studied and was not found to influence eNOS expression or microvascular functional measurements.

Conclusions—

PARP activation is present in healthy subjects at risk of developing diabetes as well as in established type 2 diabetic patients, and it is associated with impairments in the vascular reactivity in the skin microcirculation.
Hemodynamic and Neurohumoral Effects of Selective Endothelin A (ET
A
) Receptor Blockade in Chronic Heart Failure
Authors: Lüscher Thomas F. , Enseleit Frank , Pacher Richard , Mitrovic Veselin , Schulze Matthias R. , Willenbrock Roland , Dietz Rainer , Rousson Valentin , Hürlimann David , Philipp Sebastian , Notter Thomas , Noll Georg , Ruschitzka Frank
Published: November 2002

Background—

The endothelin (ET-1) system is activated in chronic heart failure (CHF). Whether, what type, and what degree of selective ET blockade is clinically beneficial is unknown. We investigated hemodynamic and neurohumoral effects of 3 weeks of treatment with various dosages of the orally available ET
A
antagonist darusentan in addition to modern standard therapy in patients with CHF.

Methods and Results—

A total of 157 patients with CHF (present or recent NYHA class III of at least 3 months duration), pulmonary capillary wedge pressure ≥12 mm Hg, and a cardiac index ≤2.6 L · min
−1
· m
−2
were randomly assigned to double-blind treatment with placebo or darusentan (30, 100, or 300 mg/d) in addition to standard therapy. Short-term administration of darusentan increased the cardiac index, but this did not reach statistical significance compared with placebo. The increase in cardiac index was significantly more pronounced after 3 weeks of treatment (
P
<0.0001 versus placebo). Pulmonary capillary wedge pressure, pulmonary arterial pressure, pulmonary vascular resistance, and right atrial pressure remained unchanged. Heart rate, mean artery pressure, and plasma catecholamines remained unaltered, but systemic vascular resistance decreased significantly (
P
=0.0001). Higher dosages were associated with a trend to more adverse events (including death), particularly early exacerbation of CHF without further benefit on hemodynamics compared with moderate dosages.

Conclusions—

This study demonstrates for the first time in a large patient population that 3 weeks of selective ET
A
receptor blockade improves cardiac index in patients with CHF. However, long-term studies are needed to determine whether ET
A
blockade is beneficial in CHF.
Outcomes After Aortic Valve Replacement in Patients With Severe Aortic Regurgitation and Markedly Reduced Left Ventricular Function
Authors: Chaliki Hari P. , Mohty Dania , Avierinos Jean-Francois , Scott Christopher G. , Schaff Hartzell V. , Tajik A. Jamil , Enriquez-Sarano Maurice
Published: November 2002

Background—

Left ventricular dysfunction is an indication for aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR). However, the postoperative outcome of patients with severe AR and a markedly low ejection fraction (EF) is not known.

Methods and Results—

The study group consisted of a total of 450 patients who had AVR for isolated AR between 1980 and 1995. Patients with markedly reduced left ventricular function (EF <35%, LoEF, n=43) were compared with those with moderate reduction in left ventricular function (EF 35% to 50%, MedEF, n=134) and those with normal left ventricular function (EF ≥50%, Nl EF, n=273). The operative mortality rate was higher with LoEF (14%) than with MedEF and Nl EF (6.7% and 3.7%, respectively,
P
=0.02). At 10 years, 41%±9% of LoEF patients had survived compared with 56%±5% and 70%±3% of MedEF and Nl EF patients, respectively (
P
<0.0001). Congestive heart failure occurred at 10 years in 25%±9% with LoEF compared with 17%±4% and 9%±2% with MedEF and NL EF, respectively (
P
<0.003). Postoperative EF improved by 4.9%±13.8% in the LoEF group and by 4%±11.9% in the MedEF group compared with −2.3%±10.9% in the Nl EF group (
P
<0.002 and
P
<0.0001, respectively).

Conclusions—

Patients with severe AR and markedly low EF incur excess operative mortality rates, postoperative mortality rates, and congestive heart failure after AVR. However, postoperative EF improves markedly, and most patients enjoy a long postoperative survival without recurrence of heart failure after AVR; thus they should not be denied the benefits of AVR.
Effect of β-Blocking Therapy on Outcome in the Multicenter UnSustained Tachycardia Trial (MUSTT)
Authors: Ellison Kristin E. , Hafley Gail E. , Hickey Kathleen , Kellen Joyce , Coromilas James , Stein Kenneth M. , Lee Kerry L. , Buxton Alfred E.
Published: November 2002

Background—

β-Blockers are known to reduce total mortality and sudden death in survivors of recent myocardial infarction. The effects of these agents in patients at high risk for sudden death with remote infarction are not clear.

Methods and Results—

We analyzed the effect of β-blockers on outcomes in 2096 patients with coronary artery disease, ejection fraction ≤40%, and spontaneous nonsustained ventricular tachycardia enrolled in the Multicenter UnSustained Tachycardia Trial (MUSTT). Forty-five percent of 702 patients with inducible sustained ventricular tachyarrhythmia and 35% of 1394 patients without inducible tachycardia were discharged from hospital receiving β-blockers. Patients treated with β-blockers were younger and had higher ejection fractions, higher rates of recent angina, and more recent infarction. β-Blockers were associated with decreased total mortality for the entire study population (5-year mortality 50% with β-blockers versus 66% without β-blockers; adjusted
P
=0.0001). The mortality benefit associated with β-blockers was present in patients with and without inducible tachycardia, except those treated with implantable defibrillators. There was no significant effect of β-blocker therapy on the rate of arrhythmic death or cardiac arrest (adjusted
P
=0.2344).

Conclusions—

β-Blocking agents have beneficial effects on survival of patients having characteristics of those enrolled in the MUSTT trial. These effects do not appear to be due to a specific antiarrhythmic effect of β-blockers. The beneficial effects of β-blockers were demonstrable in all patients except those treated with implantable defibrillators.
E2F-1 Regulates Nuclear Factor-κB Activity and Cell Adhesion
Authors: Chen Min , Capps Carrie , Willerson James T. , Zoldhelyi Pierre
Published: November 2002

Background—

The transcription factor E2F-1 promotes vascular smooth muscle cell apoptosis and is reported to inhibit apoptosis induced by tumor necrosis factor (TNF)-α in endothelial cells. Whether E2F-1 overexpression exerts potentially antiinflammatory effects in endothelial cells is not known.

Methods and Results—

By immunoblotting and immunofluorescence, TNF-α treatment of human aortic endothelial cells (HAECs) with the control vector Ad.null was followed by rapid nuclear translocation of nuclear factor (NF)-κB p65, whereas nuclear translocation of p65 was markedly reduced in HAECs overexpressing E2F-1. Electrophoretic mobility shift assay and gel shift analysis of nuclear cell extracts confirmed that HAECs treated with a recombinant adenovirus encoding E2F-1 failed to associate with the binding domain of p65. Stimulation of the Ad.null-infected endothelial cells with TNF-α resulted in enhanced expression of endothelial intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and E-selectin and enhanced adhesion of monocytic U937 cells to the HAECs. Adhesion molecule expression and cell adhesion were reduced in E2F-1–transduced HAECs, associated with a marked decrease in phosphorylated IκB-α, required for nuclear translocation of NF-κB p65.

Conclusions—

These findings suggest that E2F-1 stabilizes IκB and thereby may inhibit NF-κB–dependent processes involved in atherogenesis, including endothelial expression of E-selectin, vascular cellular adhesion molecule-1, and intracellular adhesion molecule-1 and cell adhesion to perturbed endothelial cells.
Coronary Bypass Graft Patency in Patients With Diabetes in the Bypass Angioplasty Revascularization Investigation (BARI)
Authors: Schwartz Leonard , Kip Kevin E. , Frye Robert L. , Alderman Edwin L. , Schaff Hartzell V. , Detre Katherine M.
Published: November 2002

Background—

Few studies have compared long-term status of bypass grafts between patients with and without diabetes, and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG.

Methods and Results—

Among 1526 patients in BARI who underwent CABG as initial revascularization, 99 of 292 (34%) with treated diabetes mellitus (TDM) (those on insulin or oral hypoglycemic agents) and 469 of 1234 (38%) without TDM had follow-up angiography. Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention (mean 3.9 years) were reviewed. An average of 3.0 grafts were placed at initial CABG for patients with TDM (n=297; internal mammary artery [IMA], 33%) and 2.9 grafts for patients without TDM (n=1347; IMA, 34%). Patients with TDM were more likely than those without to have small (<1.5 mm) grafted distal vessels (29% versus 22%) and vessels of poor quality (9% versus 6%). On follow-up angiography, 89% of IMA grafts were free of stenoses ≥50% among patients with TDM versus 85% among patients without TDM (
P
=0.23). For vein grafts, the corresponding percentages were 71% versus 75% (
P
=0.40). After statistical adjustment, TDM was unrelated to having a graft stenosis ≥50% (adjusted odds ratio, 0.87; 95% CI, 0.58 to 1.32).

Conclusions—

Despite diabetic patients’ having smaller distal vessels and vessels judged to be of poorer quality, diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up. Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes.
Impairment in Cardiac Autonomic Regulation Preceding Arterial Hypertension in Humans
Authors: Lucini Daniela , Mela Giuseppe Sandro , Malliani Alberto , Pagani Massimo
Published: November 2002

Background—

Subjects in the upper-normal range of arterial pressure have an excess cardiovascular risk, which suggests that other factors, such as impaired autonomic regulation, might be implicated. This study was designed to assess whether noninvasive markers of cardiac and vascular autonomic regulation might already be altered in subjects with high-normal arterial pressure levels.

Methods and Results—

We performed an observational study on a population comprising 300 subjects of both sexes with arterial pressure ranging from 90/60 to 210/120 mm Hg, who were divided into 3 groups (each n=100) with average systolic pressures of 103, 133, and 163 mm Hg. Autonomic regulation was inferred from spectral analysis of RR interval and systolic arterial pressure variability, considering rest and stand-induced changes, to account for sympathetic excitatory components. Significant alterations in markers of sinoatrial regulation (increased low-frequency normalized units, reduced high-frequency normalized units, and α-index) were already apparent in subjects in the second tertile, ie, those with arterial pressure within normal limits. Markers of vascular regulation instead showed significant alterations in the third (hypertensive) tertile. In response to standing, changes in markers of sinoatrial modulations were gradually reduced, whereas those of vascular regulation were increased. A tight link between progression of arterial pressure and the continuum of changes in autonomic markers as shown by simple correlation analysis appeared strongly affected by age and was spread across many spectral analysis–derived variables. Hypertensive autonomic dysregulation was particularly apparent in the youngest group.

Conclusions—

RR-variability parameters might prove useful to assess, with longitudinal studies, the mechanistic role of autonomic impairment in the increased risk of prehypertensive conditions.
Vasodilator Response Assessment in Porcine Myocardium With Magnetic Resonance Relaxometry
Authors: Foltz Warren D. , Huang Hong , Fort Stephen , Wright Graham A.
Published: November 2002

Background—

This research describes an early preclinical study of the biophysical mechanisms governing changes in myocardial T
2
during vasodilation in normal myocardium.

Methods and Results—

Theoretical modeling and experimental studies in an instrumented pig model (n=7) provided measures of changes in myocardial T
2
, relative blood volume (BV), and microcirculation oxygen levels (%O
2
) during intracoronary adenosine infusion. Intracoronary adenosine increases perfusion without increasing blood volume or cardiac metabolic rate; thus, T
2
elevations should reflect elevated microcirculation oxygen levels. Robust strategies were used for magnetic resonance imaging (MRI) data collection. Measures of myocardial and vascular T
1
before and after Clariscan (Amersham Health) injection provided blood volume assessment. Changes in microcirculation oxygen levels were estimated via direct blood sampling from the left anterior descending (LAD) coronary vein. Perfusion changes were monitored using a Doppler flow wire within the left main coronary artery. Myocardial T
2
elevations (ΔT
2
=17±8%) within the LAD arterial perfusion bed were related to elevations in perfusion (coronary velocity reserve=3.2±0.4) and coronary venous %O
2
[Δ(LAD CV%O
2
) =56±11%], whereas blood volume (ΔBV=0 ±2%) and cardiac metabolic rate [Δ(heart rate x blood pressure) = −4±11%] remained constant.

Conclusions—

Myocardial T
2
elevation during intracoronary adenosine infusion was significant and repeatable, caused by increases in microcirculation oxygen levels. Changes in microcirculation oxygen levels of approximately 40%O
2
should be detectable by this technique. This sensitivity should suffice for differentiating normal from abnormal myocardium via measurement of myocardial perfusion reserve.
Lack of Association Between Serum Immunoreactivity and
Chlamydia pneumoniae
Detection in the Human Aortic Wall
Authors: Porqueddu Massimo , Spirito Rita , Parolari Alessandro , Zanobini Marco , Pompilio Giulio , Polvani Gianluca , Alamanni Francesco , Stangalini Davide , Tremoli Elena , Biglioli Paolo
Published: November 2002

Background—

Only a few studies have focused the attention on the relation between elevated anti–
Chlamydia pneumoniae
(CP) antibodies and the detection of CP in the arterial wall. The aim of our study is thus to investigate the relationship between immune response to CP and detection of CP in the aortic walls of patients with abdominal aortic aneurysm.

Methods and Results—

A specimen of aortic wall was obtained from 102 consecutive patients who underwent abdominal aneurysm repair. The possible presence of CP was studied by polymerase chain reaction and confirmed by nonradioactive DNA hybridization. Antibody response to CP was studied (IgG, IgA titers). We found 33 patients (32.4%) with CP DNA+. No correlation between CP DNA detection and antibody titers was found (IgG
P
=0.52, IgA
P
=0.66). High correlation between IgG and IgA titer was observed (
P
<0.01). Endovascular presence of CP and antibody titers was not related to the age of the patient.

Conclusions—

CP antibody titers are not associated with the presence of CP in the aortic wall of patients with abdominal aortic aneurysm.
Mechanism of Late In-Stent Restenosis After Implantation of a Paclitaxel Derivate–Eluting Polymer Stent System in Humans
Authors: Virmani Renu , Liistro Francesco , Stankovic Goran , Di Mario Carlo , Montorfano Matteo , Farb Andrew , Kolodgie Frank D. , Colombo Antonio
Published: November 2002

Background—

We recently reported delayed angiographic restenosis in 15 patients who received 7-hexanoyltaxol (QP2)–eluting polymer stents (QuaDS) for the treatment of in-stent restenosis. This study presents the histological findings of atherectomy specimens from a subset of these patients receiving implants.

Methods and Results—

Between October and December 2001, 5 patients treated with QuaDS-QP2 stents underwent directional coronary atherectomy at 11.2±1.0 months for recurrent in-stent restenosis. Restenotic lesion composition was assessed with special stains, immunohistochemistry with quantitative image analysis, and, in one specimen, transmission electron microscopy. Atherectomy specimens contained fibrin interspersed in a smooth muscle cell–rich neointima with proteoglycan matrix. In 2 of 5 specimens, large aggregates of macrophages and T-lymphocytes were noted. These areas of active inflammation demonstrated a relatively high proliferation index by Ki-67 antibody staining, whereas the proliferation index in smooth muscle cell–rich restenotic areas was low.

Conclusion—

Restenotic lesions from QuaDS-QP2–eluting stents at 12 months show persistent fibrin deposition with varying degrees of inflammation. These pathological changes, representing delayed healing, are usually observed up to only 3 months in human coronary arteries with stainless steel balloon-expandable stents. The nonreabsorbable polymer alone may have induced chronic inflammation.
WHAT IS THE FIFTH SIBYLLINE ORACLE ?
Authors: Felder Stephen
Published: November 2002

Can The Fifth Sibylline Oracle be useful for the study of Second Temple Judaism? J.J. Collins thought so, and John M.G. Barclay has attempted to use it in his construction of Jewish life and thought in the Mediterranean Diaspora. But David S. Potter and Erich Gruen have cautioned that because the Sibylline Oracles were preserved by Christians and subjected to extensive redaction and interpolation, they cannot be dated with any certainty and therefore cannot be reliably used for the study of Second Temple Judaism. In this article I attempt to identify and date two clear strata in The Fifth Sibylline Oracle, explaining how the document came into its final, or near-final form. Then I make some preliminary suggestions regarding what The Fifth Sibylline Oracle may tell us about Second Temple Judaism.
The spleen is a major site of megakaryopoiesis following transplantation of murine hematopoietic stem cells
Authors: Slayton William B. , Georgelas Ann , Pierce L. Jeanne , Elenitoba-Johnson Kojo S. , Perry S. Scott , Marx Melissa , Spangrude Gerald J.
Published: November 2002

The stem cell pool can be fractionated by using the mitochondrial dye, rhodamine-123, into Rholow hematopoietic stem cells and Rhohigh progenitors. Rholow stem cells permanently engraft all lineages, whereas Rhohighprogenitors transiently produce erythrocytes, without substantial platelet or granulocyte production. We hypothesized that the inability of the Rhohigh cells to produce platelets in vivo was due to the fact that these cells preferentially engraft in the spleen and lack marrow engraftment. Initially, we demonstrated that Rhohigh progenitors produced more megakaryocytes in vitro than Rholow stem cells did. To study the activity of the Rholow and Rhohighsubsets in vivo, we used mice allelic at the hemoglobin and glucose phosphate isomerase loci to track donor-derived erythropoiesis and thrombopoiesis. Rholow stem cells contributed to robust and long-term erythroid and platelet engraftment, whereas Rhohigh progenitors contributed only to transient erythroid engraftment and produced very low numbers of platelets in vivo. Donor-derived megakaryopoiesis occurred at higher densities in the spleen than in the bone marrow in animals receiving Rholowstem cells and peaked around day 28. Blockade of splenic engraftment using pertussis toxin did not affect the peak of splenic megakaryopoiesis, supporting the hypothesis that these megakaryocytes were derived from progenitors that originated in the bone marrow. These data emphasize that in vitro behavior of hematopoietic progenitor cell subsets does not always predict their behavior following transplantation. This study supports a major role for the spleen in thrombopoiesis following engraftment of transplanted stem cells in irradiated mice.