bluuebunny/crossref_metadata_2025 huggingface dataset:
Durations and parametric model-checking in timed automata
Authors: Bruyère Véronique , Dall'olio Emmanuel , Raskin Jean-François
Published: April 2008

We consider the problem of model-checking a parametric extension of the logic TCTL over timed automata and establish its decidability. Given a timed automaton, we show that the set of durations of runs starting from a region and ending in another region is definable in Presburger arithmetic (when the time domain is discrete) or in a real arithmetic (when the time domain is dense). Using this logical definition, we show that the parametric model-checking problem for the logic TCTL can be solved algorithmically; the proof of this result is simple. More generally, we are able to effectively characterize the values of the parameters that satisfy the parametric TCTL formula with respect to the given timed automaton.
DirichletRank
Authors: Wang Xuanhui , Tao Tao , Sun Jian-Tao , Shakery Azadeh , Zhai Chengxiang
Published: April 2008

Link-based ranking algorithms are among the most important techniques to improve web search. In particular, the PageRank algorithm has been successfully used in the Google search engine and has been attracting much attention recently. However, we find that PageRank has a “zero-one gap” problem which, to the best of our knowledge, has not been addressed in any previous work. This problem can be potentially exploited to spam PageRank results and make the state-of-the-art link-based antispamming techniques ineffective. The zero-one gap problem arises as a result of the current ad hoc way of computing transition probabilities in the random surfing model. We therefore propose a novel
DirichletRank
algorithm which calculates these probabilities using Bayesian estimation with a Dirichlet prior. DirichletRank is a variant of PageRank, but does not have the problem of zero-one gap and can be analytically shown substantially more resistant to some link spams than PageRank. Experiment results on TREC data show that DirichletRank can achieve better retrieval accuracy than PageRank due to its more reasonable allocation of transition probabilities. More importantly, experiments on the TREC dataset and another real web dataset from the Webgraph project show that, compared with the original PageRank, DirichletRank is more stable under link perturbation and is significantly more robust against both manually identified web spams and several simulated link spams. DirichletRank can be computed as efficiently as PageRank, and thus is scalable to large-scale web applications.
Efficient guaranteed disk request scheduling with fahrrad
Authors: Povzner Anna , Kaldewey Tim , Brandt Scott , Golding Richard , Wong Theodore M. , Maltzahn Carlos
Published: April 2008

Guaranteed I/O performance is needed for a variety of applications ranging from real-time data collection to desktop multimedia to large-scale scientific simulations. Reservations on throughput, the standard measure of disk performance, fail to effectively manage disk performance due to the orders of magnitude difference between best-, average-, and worst-case response times, allowing reservation of less than 0.01% of the achievable bandwidth. We show that by reserving disk resources in terms of utilization it is possible to create a disk scheduler that supports reservation of nearly 100% of the disk resources, provides arbitrarily hard or soft guarantees depending upon application needs, and yields efficiency as good or better than best-effort disk schedulers tuned for performance. We present the architecture of our scheduler, prove the correctness of its algorithms, and provide results demonstrating its effectiveness.
GreenFS
Authors: Joukov Nikolai , Sipek Josef
Published: April 2008

Hard disks contain data - frequently an irreplaceable asset of high monetary and non-monetary value. At the same time, hard disks are mechanical devices that consume power, are noisy, and fragile when their platters are rotating.

In this paper we demonstrate that hard disks cause different kinds of problems for different types of computer systems and demystify several common misconceptions. We show that solutions developed to date are incapable of solving the power consumption, noise, and data reliability problems without sacrificing hard disk life-time, data reliability, or user convenience.

We considered data reliability, recovery, performance, user convenience, and hard disk-caused problems together at the enterprise scale. We have designed GreenFS: a fan-out stackable file system that offers all-time all-data run-time data protection, improves performance under typical user workloads, and allows hard disks to be kept off most of the time. As a result, GreenFS improves enterprise data protection, minimizes disk drive-related power consumption and noise and increases the chances of disk drive survivability in case of unexpected external impacts.
VPFS
Authors: Weinhold Carsten , Härtig Hermann
Published: April 2008

In this paper we present the lessons we learned when developing VPFS, a virtual private file system that is based on both a small amount of trusted storage and an untrusted legacy file system residing on the same machine. VPFS' purpose is to provide secure and reliable storage to highly sensitive applications running on top of a microkernel, which may concurrently execute untrusted software. The confidentiality and integrity guarantees of VPFS do not only apply to file contents, but also to all meta data including integrity of the directory structure.

We explored design alternatives that allow us to securely reuse untrusted infrastructure and thereby minimize the complexity that a file-system implementation adds to the trusted computing base. VPFS is split into two isolated components. A small trusted component implements all security-critical functionality, whereas the untrusted part reuses an existing file-system implementation provided by a virtualized legacy operating system that can be untrusted. In our VPFS prototype, alternative configurations of the trusted component comprise only between 4,000 and 4,600 lines of code, which is at least an order of magnitude smaller than existing commodity file-system stacks.
Towards cinematic internet video-on-demand
Authors: Cheng Bin , Stein Lex , Jin Hai , Zhang Zheng
Published: April 2008

Video-on-demand (VoD) is increasingly popular with Internet users. It gives users greater choice and more control than live streaming or file downloading. Systems such as MSN Video and YouTube deliver content at low bitrates. This may suit short clips, but great films and 5-minute bloopers are as different as symphonies and jingles. For cinema, poor quality and high jitter are less acceptable. Combining user control with high bitrate is compelling, but technically challenging.

VoD is expensive due to the load it places on video source servers. Many researchers have proposed using peer-to-peer (P2P) techniques to shift load from sources to peers (peer-assistance), yet none have implemented and deployed a system with the first purpose of openly and systematically evaluating this approach. To fill this void, we have built and deployed GridCast
1
. GridCast doubles the bitrates of current popular internet VoD systems, provides a full set of VCR
2
operations, and employs peer-assistance to improve scalability and continuity. GridCast has been live on CERNET
3
since May of 2006. In peak months, GridCast has served videos to approximately 23,000 users. From the beginning, we have gathered information to understand GridCast and improve its algorithms.

This paper introduces and evaluates GridCast. In May of 2007, we deployed multivideo caching, a major change to the caching algorithms. This paper analyzes scalability and continuity before and after this change. Our results contain several surprises and underline the importance of deployment to validate simulation results. We discuss what improvements can be developed beyond multivideo caching.
Protectit
Authors: Kong Jiantao , Schwan Karsten , Lee Min , Ahamad Mustaque
Published: April 2008

Protecting shared sensitive information is a key requirement for today's distributed applications. Our research uses virtualization technologies to create and maintain trusted data paths across distributed machines, for the services being run and their information exchanges. For trusted data paths, runtime protection methods control what data is visible to which distributed services operating on it, guided by online monitoring that determines the levels of trust inherent in the paths' machines, services, and service actions. This paper presents a key functional element of trusted data paths, which is the ProtectIT interception mechanism for controlling the data exchanges between the different virtual machines running trusted services. ProtectIT can be applied to any communication and/or I/O performed by virtual machines, and because ProtectIT does not require application, middleware, or operating system modifications, it can be used to construct trusted data paths without the knowledge or consent of such entities. Further, since ProtectIT operates in virtual machines isolated from those used by applications, it is not subject to the attacks faced by services exposed to the open Internet. ProtectIT's functionality consists of dynamic protection rules represented as data filters applied to virtual machines' communications. Examples presented in this paper include email services for which ProtectIT's filters control data visibility to mail servers and clients, and unsecured virtual machine communications morphed into secure ones via ProtectIT-based message interception.
Modeling viral economies for digital media
Authors: He Shan , Cattelan Renan G. , Kirovski Darko
Published: April 2008

Financial efficiency is the premier performance measure for most systems. Existing economic ecosystems for distribution of multimedia leave a lot to be desired: client-server platforms do not scale well resulting in substantial operational costs, whereas peer-to-peer platforms cannot police copyright control and are thus notorious for not being able to capitalize on its vast delivery potential. In this paper, we introduce an economic model that aims at predicting financial performance of both client-server and viral distribution systems for multimedia. The model consists of several probabilistic components: a global scale-free viral network of users and a localized user-behavior model that abstracts marketing, pricing, and executed transactions. The model uses simulation to predict relative economic behavior. In order to showcase our model, we compared the popular "on-line store" distribution system to the recently proposed off-line incentive-based viral ecosystem for multimedia. We also constructed an efficient dynamic pricing scheme and evaluated its performance in considered multimedia distribution scenarios.
BorderPatrol
Authors: Koskinen Eric , Jannotti John
Published: April 2008

Causal request traces are valuable to developers of large concurrent and distributed applications, yet difficult to obtain. Traces show how a request is processed, and can be analyzed by tools to detect performance or correctness errors and anomalous behavior.

We present BorderPatrol, which obtains precise request traces through suystems built from a litany of unmodified modules. Traced components include Apache, thttpd, PostgreSQL, TurboGears, BIND and notably Zeus, a closed-source event-driven web server. BorderPatrol obtains traces using active observation which carefully modifies the event stream observed by modules, simplifying precise observation. Protocol processors leverage knowledge about standard protocols, avoiding application-specific instrumentation.

BorderPatrol obtains precise traces for black-box systems that cannot be traced by any other technique. We confirm the accuracy of BorderPatrol's traces by comparing to manual instrumentation, and compare the developer effort required for each kind of trace. BorderPatrol imposes limited overhead on real systems (approximately 10-15%) and it may be enabled or disabled in at run-time, making it a viable option for deployment in production environments.
Documenting and automating collateral evolutions in linux device drivers
Authors: Padioleau Yoann , Lawall Julia , Hansen René Rydhof , Muller Gilles
Published: April 2008

The internal libraries of Linux are evolving rapidly, to address new requirements and improve performance. These evolutions, however, entail a massive problem of collateral evolution in Linux device drivers: for every change that affects an API, all dependent drivers must be updated accordingly. Manually performing such collateral evolutions is time-consuming and unreliable, and has lead to errors when modifications have not been done consistently.

In this paper, we present an automatic program transformation tool Coccinelle, for documenting and automating device driver collateral evolutions. Because Linux programmers are accustomed to manipulating program modifications in terms of patch files, this tool uses a language based on the patch syntax to express transformations, extending patches to semantic patches. Coccinelle preserves the coding style of the original driver, as would a human programmer.

We have evaluated our approach on 62 representative collateral evolutions that were previously performed manually in Linux 2.5 and 2.6. On a test suite of over 5800 relevant driver files, the semantic patches for these collateral evolutions update over 93% of the files completely. In the remaining cases, the user is typically alerted to a partial match against the driver code, identifying the files that must be considered manually. We have additionally identified over 150 driver files where the maintainer made an error in performing the collateral evolution, but Coccinelle transforms the code correctly. Finally, several patches derived from the use of Coccinelle have been accepted into the Linux kernel.
Manageable fine-grained information flow
Authors: Efstathopoulos Petros , Kohler Eddie
Published: April 2008

The continuing frequency and seriousness of security incidents underline the critical importance of application security. Decentralized information flow control (DIFC), a promising tool for improving application security, gives application developers fine-grained control over security policy and privilege management. DIFC developers can partition much application functionality into untrusted components bound by a kernel- or language-enforced security policy. Unless a (usually smaller and less exposed) trusted component is exploited, the effects of an application compromise are contained by the policy.

Although system-based DIFC can simultaneously achieve high performance and effective isolation, it offers a challenging programming model. Fine-grained policy specifications are spread over several application pieces. Common programming errors may be indistinguishable from policy exploit attempts, the system cannot expose developers to information about these errors, complicating debugging. Static checking (as in language based systems) and new system primitives can reduce these problems, but for dynamic applications like web servers, they do not eliminate them.

In this paper we propose subsystems that make decentralized information flow more manageable. First, a policy description language specifies an application-wide security policy in one localized place; communication restrictions are compiled into lower-level labels. Second, information flow-safe debugging mechanisms let developers debug DIFC applications without violating security policies. Although these mechanisms are preliminary, we demonstrate their effectiveness using applications similar to those developed for Asbestos and other DIFC systems.
Useful computations need useful numbers
Authors: Stoutemyer David R.
Published: April 2008

Most of us have taken the exact rational and approximate numbers in our computer algebra systems for granted for a long time, not thinking to ask if they could be significantly better. With exact rational arithmetic and adjustable-precision floating-point arithmetic to precision limited only by the total computer memory or our patience, what more could we want for such numbers? It turns out that there is much more that can be done that permits us to obtain exact results more often, more intelligible results, approximate results guaranteed to have requested error bounds, and recovery of exact results from approximate ones.
Fast algorithms, modular methods, parallel approaches and software engineering for solving polynomial systems symbolically
Authors: Xie Yuzhen
Published: April 2008

Symbolic methods are powerful tools in scientific computing. The implementation of symbolic solvers is, however, a highly difficult task due to the extremely high time and space complexity of the problem. In this thesis, we study and apply fast algorithms, modular methods, parallel approaches and software engineering techniques to improve the efficiency of symbolic solvers for computing triangular decomposition, one of the most promising methods for solving non-linear systems of equations symbolically.
Transactions are back---but are they the same?
Authors: Felber Pascal , Fetzer Christof , Guerraoui Rachid , Harris Tim
Published: April 2008

Transactions are back in the spotlight! They are emerging in concurrent programming languages under the name of transactional memory (TM). Their new role? Concurrency control on new multi-core processors. From afar they look the same as good ol' database transactions.
But are they really?

In this position paper, we reflect about the distinguishing features of these
memory transactions
with respect to their
database
cousins.

Disclaimer:
By its very nature, this position paper does not try to avoid subjectivity.
Database theory column
Authors: Vianu Victor
Published: April 2008

The 26th edition of the ACM SIGMOD-SIGACT-SIGART Symposium on Principles of Databases (PODS), took place from 11 to 13 June 2007. As usual since 1991, the symposium was organized jointly with the ACM SIGMOD International Conference on Management of Data. While SIGMOD focuses on practical aspects of database systems, PODS focuses on the theory of such systems. The joint organization stimulates interaction between systems and theory research. For the first time ever the joint SIGMOD/PODS conference was held in Asia: it took place in Beijing, China.
On-line bipartite matching made simple
Authors: Birnbaum Benjamin , Mathieu Claire
Published: April 2008

We examine the classic on-line bipartite matching problem studied by Karp, Vazirani, and Vazirani [8] and provide a simple proof of their result that the Ranking algorithm for this problem achieves a competitive ratio of 1 -- 1/
e
.
Future generation supercomputers II
Authors: Venkateswaran N. , Srinivasan Deepak , Manivannan Madhavan , Sai Sagar T P Ramnath , Gopalakrishnan Shyamsundar , Elangovan VinothKrishnan , M Arvind , Ramesh Prem Kumar , Ganesan Karthik , Krishnamurthy Viswanath , Sivaramakrishnan
Published: April 2008

In part-I, a novel multi-core node architecture was proposed which when employed in a cluster environment would be capable of tackling computational complexity associated with wide class of applications. Furthermore, it was discussed that by appropriately scaling the architectural specifications, Teraops computing power could be achieved at the node level. In order to harness the computational power of such a node, we have developed an efficient application execution model with a competent cluster architectural backbone. In this paper we present the novel cluster paradigm, dealing with operating system design, parallel programming model and cluster interconnection network. Our approach in developing the competent cluster design revolves around an execution model to aid the execution of multiple applications simultaneously on all partitions of the cluster, leading to cost sharing across applications. This would be a major initiative towards achieving Cost-Effective Supercomputing.
Optimal pipeline depth with pipeline stage unification adoption
Authors: Yao Jun , Miwa Shinobu , Shimada Hajime , Tomita Shinji
Published: April 2008

To find the optimal pipeline design point by considering both performance and power objectives has been one focus of interest in recent researches. However, we found that previous papers did not consider deepening or shrinking pipeline depth dynamically during the program execution. In this paper, with the adoption of the earlier proposed Pipeline Stage Unification (PSU) method, we studied the relationship between power/performance and pipeline depth in processors with a pipeline of multi-usable depths. Our evaluation results of SPECint2000 benchmarks shown in this paper illustrate that the PSU adoption can achieve good efficiency for platforms which concern both energy and performance, even after the utilization of complex clock gating.
VCLEARIT
Authors: Lakshmikanthan Preetham , Nuñez Adrian
Published: April 2008

Leakage power loss is a major concern in deep-submicron technologies as it drains the battery even when a circuit is completely idle. In this paper, we first present a novel leakage reduction technique and then compare and contrast it with other well established leakage reduction techniques. Our leakage reduction technique achieves cancellation of leakage effects in both the pull-up network (PUN) as well as the pull-down network (PDN) for CMOS circuits. It involves voltage balancing in the PUN and PDN paths using a combination of high-
V

T

(high voltage threshold) and standard-
V

T

sleep transistors. Experiments conducted on a variety of multi-level combinational MCNC'91 benchmarks show significant savings in leakage power (upto 3 orders of magnitude), with lesser area and delay penalty using our leakage reduction technique when compared to other techniques.
Not multi-, but many-core
Authors: Maliţa Mihaela , Ştefan Gheorghe , Thiébaut Dominique
Published: April 2008

Recent embedded systems have switched to fully programmable parallel architectures. To make sure all corner cases usually present in real applications are supported and efficiently implemented in this switch of implementation, new solutions must be found. We introduce the
integral parallel architecture
(IPA) as a solution supporting intensive data computation in System-on-a-chip (Soc) implementations, fitting in a
small area
, and requiring
low power
. An IPA supports naturally all three possible styles of parallelism:
data, time
, and
speculative
.

As an illustrative example, we present the

BA1024

chip, a fully programmable SoC designed by
BrightScale, Inc.
for HDTV codecs. Its main performance figures include 60
GOPS/Watt
and 2
GOPS/mm
2
, representing an efficient IPA approach for embedded computation.
Aging of the Immune System as a Prognostic Factor for Human Longevity
Authors: Larbi Anis , Franceschi Claudio , Mazzatti Dawn , Solana Rafael , Wikby Anders , Pawelec Graham
Published: April 2008

Accumulating data are documenting an inverse relationship between immune status, response to vaccination, health, and longevity, suggesting that the immune system becomes less effective with advancing age and that this is clinically relevant. The mechanisms and consequences of age-associated immune alterations, designated immunosenescence, are briefly reviewed here.
Validity of Four Self-reported Colorectal Cancer Screening Modalities in a General Population: Differences over Time and by Intervention Assignment
Authors: Jones Resa M. , Mongin Steven J. , Lazovich DeAnn , Church Timothy R. , Yeazel Mark W.
Published: April 2008

Little is known about the validity of self-reported colorectal cancer screening. To date, few published studies have validated all four screening modalities per recommended guidelines or included a general population-based sample, and none has assessed validity over time and by intervention condition. To estimate the validity of self-reported screening, a random sample of 200 adults, ages ≥50 years, was selected from those completing annual surveys on screening behavior as part of an intervention study. Approximately 60% of the validation sample authorized medical record review. Sensitivity, specificity, and positive and negative predictive values were calculated for baseline and year 1 follow-up reports for each test and for overall screening adherence. Sensitivity at baseline ranged from 86.9% (flexible sigmoidoscopy) to 100% (colonoscopy). Sensitivity at follow-up was slightly lower. Adjusting for validity measures, the sample overreported screening prevalence at baseline for each of the four modalities. At follow-up, overreporting was greatest for fecal occult blood test (13.0%). Overreporting across intervention conditions was highest for fecal occult blood test (10.8% for control; 24.8% for the most intense intervention) and overall screening adherence (10.9% for control; 14.3% for the most intense intervention). Sensitivity and specificity of self-reported colorectal cancer screening compared with medical records were high; however, adjusting self-reported screening rates based on relative error rates reduced screening prevalence estimates. Those exposed to more intense interventions to modify screening behavior seemed more likely to overestimate their screening rates compared with those who were not exposed. (Cancer Epidemiol Biomarkers Prev 2008;17(4):777–84)
Association of Mammographic Density with the Pathology of Subsequent Breast Cancer among Postmenopausal Women
Authors: Ghosh Karthik , Brandt Kathleen R. , Sellers Thomas A. , Reynolds Carol , Scott Christopher G. , Maloney Shaun D. , Carston Michael J. , Pankratz V. Shane , Vachon Celine M.
Published: April 2008

Background: Limited studies have examined the associations between mammographic density and subsequent breast tumor characteristics.

Methods: Eligible women were part of a case-control study of postmenopausal breast cancer, were 40 years or older and had a routine mammogram 4 years or more before their diagnosis. Mammographic density (percent density, dense area, and nondense area) was estimated using a computer-assisted thresholding program. At the time of cancer diagnosis, cases were classified as asymptomatic or symptomatic based on medical record review and breast imaging workup. Pathologic review was done blinded to the density status. Linear regression models and tests for trend examined the association between pathologic characteristics of the breast tumor and the components of density for all participants, and stratified by symptom status at diagnosis.

Results: Of the 286 eligible cases, 77% were 60 years or older and mean percent density was 29.5% (SD, 14.6%). Density was not significantly associated with tumor size (P = 0.22), histologic type (P = 0.77), estrogen receptor (P = 0.11) or progesterone receptor (P = 0.37) status, mitotic activity (P = 0.12), or nuclear pleomorphism (P = 0.09; P values for percent density). An inverse association was suggested between tumor grade and percent density (32.0%, 30.3%, 26.7% for grades 1-3; P = 0.06 for trend). The inverse association with tumor grade and its components (nuclear pleomorphism and tubular differentiation) was only evident among the 97 symptomatic women; positive associations of estrogen receptor (P = 0.009) and progesterone receptor (P = 0.04) were also seen with percent density only in this subgroup.

Conclusions: The inverse association between tumor grade and percent density in the symptomatic population could inform the biology of the association between mammographic density and breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(4):872–9)
Consumption of Raw Cruciferous Vegetables is Inversely Associated with Bladder Cancer Risk
Authors: Tang Li , Zirpoli Gary R. , Guru Khurshid , Moysich Kirsten B. , Zhang Yuesheng , Ambrosone Christine B. , McCann Susan E.
Published: April 2008

Cruciferous vegetables contain isothiocyanates, which show potent chemopreventive activity against bladder cancer in both in vitro and in vivo studies. However, previous epidemiologic studies investigating cruciferous vegetable intake and bladder cancer risk have been inconsistent. Cooking can substantially reduce or destroy isothiocyanates, and could account for study inconsistencies. In this hospital-based case-control study involving 275 individuals with incident, primary bladder cancer and 825 individuals without cancer, we examined the usual prediagnostic intake of raw and cooked cruciferous vegetables in relation to bladder cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with unconditional logistic regression, adjusting for smoking and other bladder cancer risk factors. We observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable intake (adjusted OR for highest versus lowest category = 0.64; 95% CI, 0.42-0.97), with a significant trend (P = 0.003); there were no significant associations for fruit, total vegetables, or total cruciferous vegetables. The associations observed for total raw crucifers were also observed for individual raw crucifers. The inverse association remained significant among current and heavy smokers with three or more servings per month of raw cruciferous vegetables (adjusted ORs, 0.46 and 0.60; 95% CI, 0.23-0.93 and 0.38-0.93, respectively). These data suggest that cruciferous vegetables, when consumed raw, may reduce the risk of bladder cancer, an effect consistent with the role of dietary isothiocyanates as chemopreventive agents against bladder cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(4):938–44)
Height, Body Mass Index, and Ovarian Cancer: A Pooled Analysis of 12 Cohort Studies
Authors: Schouten Leo J. , Rivera Christine , Hunter David J. , Spiegelman Donna , Adami Hans-Olov , Arslan Alan , Beeson W. Lawrence , van den Brandt Piet A. , Buring Julie E. , Folsom Aaron R. , Fraser Gary E. , Freudenheim Jo L. , Goldbohm R. Alexandra , Hankinson Susan E. , Lacey James V. , Leitzmann Michael , Lukanova Annekatrin , Marshall James R. , Miller Anthony B. , Patel Alpa V. , Rodriguez Carmen , Rohan Thomas E. , Ross Julie A. , Wolk Alicja , Zhang Shumin M. , Smith-Warner Stephanie A.
Published: April 2008

Background: Although many studies have investigated the association between anthropometry and ovarian cancer risk, results have been inconsistent.

Methods: The associations of height, body mass index (BMI), and ovarian cancer risk were examined in a pooled analysis of primary data from 12 prospective cohort studies from North America and Europe. The study population consisted of 531,583 women among whom 2,036 epithelial ovarian cancer cases were identified. To summarize associations, study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model.

Results: Women with height ≥1.70 m had a pooled multivariate RR of 1.38 [95% confidence interval (95% CI), 1.16-1.65] compared with those with height <1.60 m. For the same comparison, multivariate RRs were 1.79 (95% CI, 1.07-3.00) for premenopausal and 1.25 (95% CI, 1.04-1.49) for postmenopausal ovarian cancer (Pinteraction = 0.14). The multivariate RR for women with a BMI ≥30 kg/m2 was 1.03 (95% CI, 0.86-1.22) compared with women with a BMI from 18.5 to 23 kg/m2. For the same comparison, multivariate RRs were 1.72 (95% CI, 1.02-2.89) for premenopausal and 1.07 (95% CI, 0.87-1.33) for postmenopausal women (Pinteraction = 0.07). There was no statistically significant heterogeneity between studies with respect to height or BMI. BMI in early adulthood was not associated with ovarian cancer risk.

Conclusion: Height was associated with an increased ovarian cancer risk, especially in premenopausal women. BMI was not associated with ovarian cancer risk in postmenopausal women but was positively associated with risk in premenopausal women. (Cancer Epidemiol Biomarkers Prev 2008;17(4):902–12)
Evaluation of Claims, Medical Records, and Self-report for Measuring Fecal Occult Blood Testing among Medicare Enrollees in Fee for Service
Authors: Schenck Anna P. , Klabunde Carrie N. , Warren Joan L. , Peacock Sharon , Davis William W. , Hawley Sarah T. , Pignone Michael , Ransohoff David F.
Published: April 2008

Background: There is no agreement on the best data source for measuring colorectal cancer (CRC) screening. Medicare claims have been used to measure CRC testing but the validity of using claims to measure fecal occult blood tests (FOBT) has not been established.

Methods: We compared ascertainment of FOBT among three data sources: self-reports, Medicare claims, and medical records. Data were collected on FOBT use during the study window (1/1/1998 – 12/31/2002). Our study was conducted with North Carolina Medicare enrollees (N = 561) who had previously responded to a telephone survey on CRC tests. FOBT information was abstracted from respondents' physician office medical records and compared with self-reported FOBT use and Medicare claims for FOBT. Data sources were assessed for accuracy and completeness of FOBT reporting using sensitivity, specificity, positive predictive value, negative predictive value, and agreement.

Results: Reporting of FOBT use in the prior year in medical records and Medicare claims agreed 82% of the time [95% confidence interval (95% CI), 79-85%]. FOBT 1-year use rates from self-report agreed with test use found in medical records 70% of the time (95% CI, 66-74%). The lowest agreement was between self-reported 1-year FOBT use and Medicare claims, which agreed 67% of the time (95% CI, 63-71%).

Conclusions: No data source could be established as providing complete and valid information about FOBT use among Medicare enrollees, showing the difficulty of ascertaining test use rates for noninvasive, low-cost procedures conducted in multiple settings. Caution should be used when attempting to measure FOBT use with self-report, Medicare claims, or medical records. (Cancer Epidemiol Biomarkers Prev 2008;17(4):799–804)
Validation of Self-reported Colorectal Cancer (CRC) Screening in a Study of Ethnically Diverse First-Degree Relatives of CRC Cases
Authors: Bastani Roshan , Glenn Beth A. , Maxwell Annette E. , Ganz Patricia A. , Mojica Cynthia M. , Chang L. Cindy
Published: April 2008

Background: Evidence about the accuracy of self-reports of colorectal cancer (CRC) screening is lacking. We conducted a validation protocol in a randomized trial to increase CRC screening among high-risk individuals.

Methods: First-degree relatives (n = 1,280) of CRC cases who were due for CRC screening were included in the parent trial. All subjects who completed the follow-up interview (n = 948) were asked to participate in validation activities. Self-reports of receipt of CRC screening during the 12-month study period were verified via physicians.

Results: Although 60% (n = 567) verbally agreed, only 171 subjects (18% of original sample) returned the signed validation form with the physician name and contact information and a medical information release statement. The signed forms were mailed to physicians with a $10 incentive and the request to list the dates of recent CRC screening tests. One hundred twenty-three physicians (72% of physicians contacted, 13% of original sample) returned completed validation forms. Rates of agreement were low across all three screening types with physicians verifying self-reported screening for 29% of fecal occult blood testing, 56% of sigmoidoscopy, 55% of colonoscopy, and 57% of any screening test.

Conclusion: Validation of self-report using the type of protocol we used for subjects receiving medical care in many community settings may be unfeasible and cost inefficient. Given the overall low participation rate in validation activities and considerable challenges in collecting high quality data, conclusions about the accuracy of self-reported CRC screening are difficult to make based on the results of this study. (Cancer Epidemiol Biomarkers Prev 2008;17(4):791–8)
Accuracy of Self-Reported Cancer-Screening Histories: A Meta-analysis
Authors: Rauscher Garth H. , Johnson Timothy P. , Cho Young Ik , Walk Jennifer A.
Published: April 2008

Background: Survey data used to study trends in cancer screening may overestimate screening utilization while potentially underestimating existing disparities in use.

Methods: We did a literature review and meta-analysis of validation studies examining the accuracy of self-reported cancer-screening histories. We calculated summary random-effects estimates for sensitivity and specificity, separately for mammography, clinical breast exam (CBE), Pap smear, prostate-specific antigen testing (PSA), digital rectal exam, fecal occult blood testing, and colorectal endoscopy.

Results: Sensitivity was highest for mammogram, CBE, and Pap smear (0.95, 0.94, and 0.93, respectively) and lowest for PSA and digital rectal exam histories (0.71 and 0.75). Specificity was highest for endoscopy, fecal occult blood testing, and PSA (0.90, 0.78, and 0.73, respectively) and lowest for CBE, Pap smear, and mammogram histories (0.26, 0.48, and 0.61, respectively). Sensitivity and specificity summary estimates tended to be lower in predominantly Black and Hispanic samples compared with predominantly White samples. When estimates of self-report accuracy from this meta-analysis were applied to cancer-screening prevalence estimates from the National Health Interview Survey, results suggested that prevalence estimates are artificially increased and disparities in prevalence are artificially decreased by inaccurate self-reports.

Conclusions: National survey data are overestimating cancer-screening utilization for several common procedures and may be masking disparities in screening due to racial/ethnic differences in reporting accuracy. (Cancer Epidemiol Biomarkers Prev 2008;17(4):748–57)
A Prospective Evaluation of Insulin and Insulin-like Growth Factor-I as Risk Factors for Endometrial Cancer
Authors: Gunter Marc J. , Hoover Donald R. , Yu Herbert , Wassertheil-Smoller Sylvia , Manson JoAnn E. , Li Jixin , Harris Tiffany G. , Rohan Thomas E. , Xue XiaoNan , Ho Gloria Y.F. , Einstein Mark H. , Kaplan Robert C. , Burk Robert D. , Wylie-Rosett Judith , Pollak Michael N. , Anderson Garnet , Howard Barbara V. , Strickler Howard D.
Published: April 2008

Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HRq4-q1), 2.33; 95% confidence interval (95% CI), 1.13-4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HRq4-q1, 0.53; 95% CI, 0.31-0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HRq4-q1, 4.30; 95% CI, 1.62-11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data. (Cancer Epidemiol Biomarkers Prev 2008;17(4):921–9)
Transcription Factor 7–like 2Polymorphism and Colon Cancer
Authors: Slattery Martha L. , Folsom Aaron R. , Wolff Roger , Herrick Jenifer , Caan Bette J. , Potter John D.
Published: April 2008

Polymorphisms of the transcription factor 7–like 2 (TCF7L2) gene have been associated with insulin sensitivity and diabetes, and the TCF7L2 gene is involved in the Wnt/β-catenin signaling pathway, all factors thought to be important in the etiology of colon cancer. In this confirmatory study, we evaluated the rs7903146 TCF7L2 polymorphism with colon cancer using previously collected data on 1,578 cases and 1,966 controls. We did not observe a statistically significant association between the rs7903146 polymorphisms and risk of colon cancer [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 0.98-1.28] when evaluating the total population. We did, however, observe a statistically significant interaction between the rs7903146 TCF7L2 polymorphism and recent use of aspirin/nonsteroidal anti-inflammatory drugs (NSAID; P = 0.001). Increased colon cancer risk associated with the T allele was restricted to those without recent use of aspirin/NSAIDs (OR, 1.65; 95% CI, 1.35-2.02, relative to recent aspirin users, i.e., use of aspirin/NSAIDS within the 2 years before diagnosis, with the CC genotype). Among individuals who reported recent use of aspirin/NSAIDs, the T allele reduced risk of colon cancer (OR, 0.78; 95% CI, 0.62-0.98) in a dose-response fashion (P for linear trend across genotypes = 0.03). These data suggest that colon cancer risk associated with the rs7903146 TCF7L2 polymorphism is modified by use of aspirin/NSAIDs. (Cancer Epidemiol Biomarkers Prev 2008;17(4):978–82)
Detection and Quantitation ofN′-Nitrosonornicotine in Human Toenails by Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry
Authors: Stepanov Irina , Hecht Stephen S.
Published: April 2008

Specific biomarkers of tobacco carcinogen uptake are critical for investigations of the role of tobacco smoke exposure in human cancers. Two new biomarkers of human exposure to tobacco-specific carcinogens have been recently developed by our research group: urinary N′-nitrosonornicotine (NNN) and toenail 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In this study, we report the presence of NNN in human toenails. Toenails of 17 smokers were analyzed for total NNN. Mean total NNN level in these samples was 4.63 ± 6.48 fmol/mg toenail and correlated with previously reported total NNAL (r = 0.96; P < 0.0001), total nicotine (r = 0.48; P < 0.05), and total cotinine (r = 0.87; P < 0.0001). An interesting finding was that amounts of NNN in smokers' toenails were generally higher than those of total NNAL. The ratio of toenail NNN to NNAL averaged 2.8, whereas the previously reported ratio between these biomarkers in smokers' urine was 0.1. NNN was also found in toenail samples from 12 nonsmokers, averaging 0.35 ± 0.16 fmol/mg and positively correlating with toenail cotinine (r = 0.58; P = 0.05). The results of this study show the feasibility of quantifying NNN in human toenails, providing a potentially useful new biomarker of tobacco carcinogen exposure. (Cancer Epidemiol Biomarkers Prev 2008;17(4):945–8)
Prognostic Significance of Cadherin-Based Adhesion Molecules in Cutaneous Malignant Melanoma
Authors: Kreizenbeck Gretchen M. , Berger Aaron J. , Subtil Antonio , Rimm David L. , Gould Rothberg Bonnie E.
Published: April 2008

Background: The need for novel molecular prognostic markers that can supplement validated clinicopathologic correlates for cutaneous malignant melanoma is well recognized. Proteins that mediate the epithelial-mesenchymal transition, the process by which a cancer cell disengages from its parent tumor, are important candidates.

Methods: The prognostic relevance of E-cadherin, N-cadherin, and P-cadherin, calcium-dependent transmembrane glycoproteins that regulate cell-cell adhesion, and their adaptors, α-catenin, β-catenin, and p120-catenin, was evaluated on a cohort of 201 primary and 274 metastatic melanoma tumors using fluorescence-based immunohistochemical methods and Automated Quantitative Analysis of protein expression on digitally captured photomicrographs.

Results: Increasing levels of N-cadherin expression improved overall survival (log-rank = 7.31; P = 0.03) but did not retain significance following adjustment for established clinicopathologic correlates (P = 0.50). Higher levels of E-cadherin approached significance for favorable prognosis on both univariate (P = 0.13) and multivariable (P = 0.10) analyses. Hierarchical clustering of the composite profiles for all six markers identified four unique clusters that yielded differential overall survival (log-rank = 10.54; P = 0.01). Cluster 4, expressing high E-cadherin and N-cadherin levels, possessed the most favorable outcome and cluster 2, featuring low E-cadherin and α-catenin but modest N-cadherin, showed least favorable outcomes. Cluster 2 remained significant on multivariable analysis (hazard ratio, 3.29; 95% confidence interval, 1.50-7.19; P = 0.003).

Conclusions: Although none of the cadherin-based adhesion molecules were independently prognostic, multimarker profiles were significant. Similar to epithelial-derived tumors, loss of E-cadherin correlates with poor outcome. In contrast, for neural crest–derived cutaneous malignant melanoma, N-cadherin overexpression can be associated with either a successful epithelial-mesenchymal transition or a favorably differentiated tumor. Additional cadherin profiles are needed to discriminate these distinctive phenotypes. (Cancer Epidemiol Biomarkers Prev 2008;17(4):949–58)
Line Region Hypomethylation Is Associated with Lifestyle and Differs by Human Papillomavirus Status in Head and Neck Squamous Cell Carcinomas
Authors: Furniss C. Sloane , Marsit Carmen J. , Houseman E. Andres , Eddy Karen , Kelsey Karl T.
Published: April 2008

Genomic hypomethylation is a hallmark of essentially all cancers, but the degree of this hypomethylation differs among individual tumors. Little work has explored what leads to these differences and or asked whether they are clinically meaningful. In this study of head and neck squamous cell carcinoma, we assessed hypomethylation in tumors using a semiquantitative fragment analysis approach to determine the relative methylation status of the line retroviral element LRE1 (Line-1.2). Because this is an established marker of genomic methylation status, we examined the relationship between the relative methylation, patient demographics, and other risk factors for head and neck squamous cell carcinoma. We determined relative methylation status for 303 patients, 193 of which had complete data for all variables of interest. Using a generalized linear model, we found that patient body mass index was significantly positively associated with tumor LRE1 methylation level. Smoking duration, particularly in tumors lacking human papillomavirus (HPV) DNA, was significantly negatively associated with relative methylation level. Having previously assessed relative methylation in blood-derived DNA, we compared tumor with the blood DNA methylation level and observed these to be independent. Finally, the lower LRE1 methylation in patients whose tumors were HPV DNA negative was associated with poorer patient survival (hazard ratio, 1.6; 95% confidence interval, 1.0-2.6). These findings suggest that HPV-associated tumors differ molecularly from those arising after heavy tobacco use and that this epigenetic alteration may affect survival in HPV-negative patients already exhibiting a more aggressive disease. (Cancer Epidemiol Biomarkers Prev 2008;17(4):966–71)