bluuebunny/crossref_metadata_2025 huggingface dataset:
On the optimality of repair-cost-limit policies
Authors: Jiang Xiaoyue , Cheng Kan , Makis Viliam
Published: April 2003

An optimal repair/replacement problem for a single-unit repairable system with minimal repair and random repair cost is considered. The existence of the optimal policy is established using results of the optimal stopping theory, and it is shown that the optimal policy is a ‘repair-cost-limit’ policy, that is, there is a series of repair-cost-limit functions gn(t), n = 1, 2,…, such that a unit of age t is replaced at the nth failure if and only if the repair cost C(n, t) ≥ gn(t); otherwise it is minimally repaired. If the repair cost does not depend on n, then there is a single repair cost limit function g(t), which is uniquely determined by a first-order differential equation with a boundary condition.
Idle and busy periods in stable M/M/k queues
Authors: Daley D. J. , Servi L. D.
Published: April 2003

This paper finds the first and second moments of the number of arrivals in a stable M/M/k queue during an idle period, i.e. in a period when at least one server is idle. These and similar results are used along with renewal theory asymptotics to find the first and second moments of the proportion of arrivals occurring while there are at least ξ customers waiting for service. The asymptotics of the second moment for large ξ are established.
One-dimensional loss networks and conditioned M/G/∞ queues
Authors: Ferrari Pablo A. , Lopes Garcia Nancy
Published: April 2003

We study one-dimensional continuous loss networks with length distribution G and cable capacity C. We prove that the unique stationary distribution ηL of the network for which the restriction on the number of calls to be less than C is imposed only in the segment [−L,L] is the same as the distribution of a stationary M/G/∞ queue conditioned to be less than C in the time interval [−L,L]. For distributions G which are of phase type (= absorbing times of finite state Markov processes) we show that the limit as L → ∞ of ηL exists and is unique. The limiting distribution turns out to be invariant for the infinite loss network. This was conjectured by Kelly (1991).
Tight bound of random interval packing
Authors: Rhee Wansoo T.
Published: April 2003

Consider n random intervals I1, …, IN chosen by selecting endpoints independently from the uniform distribution. A packing of I1, …, IN is a disjoint sub-collection of these intervals: its wasted space is the measure of the set of points not covered by the packing. We investigate the random variable WN equal to the smallest wasted space among all packings. Coffman, Poonen and Winkler proved that EWN is of order (log N)2/N. We provide a sharp estimate of log P(WN ≥ t (log N)2 / N) and log P(WN ≤ t (log N)2 / N) for all values of t.
The output process of an MMPP/M/1 queue
Authors: Bean Nigel , Green David , Taylor Peter
Published: April 2003

Olivier and Walrand (1994) claimed that the departure process of an MMPP/M/1 queue is not an MAP unless the queue is a stationary M/M/1 queue. They also conjectured that the departure process of an MAP/PH/1 queue is not an MAP unless the queue is a stationary M/M/1 queue. We show that their proof of the first result has an algebraic error, which leaves open the above question of whether the departure process of an MMPP/M/1 can be an MAP.
Stochastic aspects of Lanchester's theory of warfare
Authors: Kingman J. F. C.
Published: April 2003

A Markov chain model for a battle between two opposing forces is formulated, which is a stochastic version of one studied by F. W. Lanchester. Solutions of the backward equations for the final state yield martingales and stopping identities, but a more powerful technique is a time-reversal analogue of a known method for studying urn models. A general version of a remarkable result of Williams and McIlroy (1998) is proved.
Inclusion-exclusion methods for treating annihilating and deposition processes
Authors: Sudbury Aidan
Published: April 2003

We consider one-dimensional processes in which particles annihilate their neighbours, grow until they meet their neighbours or are deposited onto surfaces. All of the models considered have the property that they are connected to exponential series often by an inclusion-exclusion argument.
On bounds for some optimal policies in reliability
Authors: Mi Jie
Published: April 2003

Often in the study of reliability and its applications, the goal is to maximize or minimize certain reliability characteristics or some cost functions. For example, burn-in is a procedure used to improve the quality of products before they are used in the field. A natural question which arises is how long the burn-in procedure should last in order to maximize the mean residual life or the conditional survival probability. In the literature, an upper bound for the optimal burn-in time is obtained by assuming that the underlying distribution of the products has a bathtub-shaped failure rate function; however, no lower bound is available. A similar question arises in studying replacement policy, warranty policy, and inspection models. This article gives a lower bound for the optimal burn-in time, and lower and upper bounds for the optimal replacement and warranty policies, under the same bathtub-shape assumption.
Discrete time analysis of a repairable machine
Authors: Alfa Attahiru Sule , Castro I. T.
Published: April 2003

We consider, in discrete time, a single machine system that operates for a period of time represented by a general distribution. This machine is subject to failures during operations and the occurrence of these failures depends on how many times the machine has previously failed. Some failures are repairable and the repair times may or may not depend on the number of times the machine was previously repaired. Repair times also have a general distribution. The operating times of the machine depend on how many times it has failed and was subjected to repairs. Secondly, when the machine experiences a nonrepairable failure, it is replaced by another machine. The replacement machine may be new or a refurbished one. After the Nth failure, the machine is automatically replaced with a new one. We present a detailed analysis of special cases of this system, and we obtain the stationary distribution of the system and the optimal time for replacing the machine with a new one.
Some bivariate notions of IFR and DMRL and related properties
Authors: Bassan Bruno , Kochar Subhash , Spizzichino Fabio
Published: April 2003

Recently Bassan and Spizzichino (1999) have given some new concepts of multivariate ageing for exchangeable random variables, such as a special type of bivariate IFR, by comparing distributions of residual lifetimes of dependent components of different ages. In the same vein, we further study some properties of these concepts of IFR in the bivariate case. Then we introduce certain concepts of bivariate DMRL ageing and we develop a treatment that parallels those developed for bivariate IFR. For both the IFR and DMRL concepts, we analyse a weak and a strong version, and discuss some of the differences between them.
On the moment determinacy of the distributions of compound geometric sums
Authors: Lin Gwo Dong , Stoyanov Jordan
Published: April 2003

We deal with compound geometric sums of independent positive random variables and study the moment problem for the distributions of such sums (the Stieltjes moment problem). We find conditions under which the distributions are uniquely determined by their moments. We also treat related topics, including the Hamburger moment problem involving random variables on the whole real line. Some conjectures are outlined.
Stochastic orders in partition and random testing of software
Authors: Boland Philip J. , Singh Harshinder , Cukic Bojan
Published: April 2003

Testing in order to produce software of high reliability is an area of major concern in software engineering. In an effort to find efficient methods of testing, the comparison of partition and random sampling testing methods has received considerable attention in the literature. A standard criterion for comparisons between random and partition testing, based on their expected efficacy in program debugging, is the probability of detecting at least one failure causing input in the program's domain. However, the goal in software testing is usually to find as many faults as possible in a reasonable period of time, and therefore stochastic comparisons of the number of faults obtained in partition and random testing may provide more valuable information on which testing procedures to use. We establish various conditions which guarantee that the number of faults discovered in partition testing is stochastically greater than the number discovered in random testing (using a fixed total sample size) for many of the well-established stochastic orders (including the usual stochastic order, the hazard rate order, the likelihood ratio order, and the variability order). The results established also allow us to obtain both upper and lower bounds with these stochastic orders for the sum of n independent Bernoulli random trials (with varying probability of success) in terms of the binomial distribution with parameters n and p.
Doubly stochastic Hilbertian processes
Authors: Guillas Serge
Published: April 2003

In this paper, we consider a Hilbert-space-valued autoregressive stochastic sequence (Xn) with several regimes. We suppose that the underlying process (In) which drives the evolution of (Xn) is stationary. Under some dependence assumptions on (In), we prove the existence of a unique stationary solution, and with a symmetric compact autocorrelation operator, we can state a law of large numbers with rates and the consistency of the covariance estimator. An overall hypothesis states that the regimes where the autocorrelation operator's norm is greater than 1 should be rarely visited.
Some properties of two families of classes of life distributions
Authors: Mohan N. R. , Ravi S.
Published: April 2003

We study the closure properties of the family ℒ(α) of classes of life distributions introduced by Lin (1998) under general compounding. We define a discrete analogue of this family and study some properties.
The sojourn time distribution in an infinite server resequencing queue with dependent interarrival and service times
Authors: Huisman Tijs , Boucherie Richard J.
Published: April 2003

We consider an infinite server resequencing queue, where arrivals are generated by jumps of a semi-Markov process and service times depend on the jumps of this process. The stationary distribution of the sojourn time, conditioned on the state of the semi-Markov process, is obtained both for the case of hyperexponential service times and for the case of a Markovian arrival process. For the general model, an accurate approximation is derived based on a discretisation of interarrival and service times.
A matrix exponential form for hitting probabilities and its application to a Markov-modulated fluid queue with downward jumps
Authors: Miyazawa Masakiyo , Takada Hiroyuki
Published: April 2003

We consider a fluid queue with downward jumps, where the fluid flow rate and the downward jumps are controlled by a background Markov chain with a finite state space. We show that the stationary distribution of a buffer content has a matrix exponential form, and identify the exponent matrix. We derive these results using time-reversed arguments and the background state distribution at the hitting time concerning the corresponding fluid flow with upward jumps. This distribution was recently studied for a fluid queue with upward jumps under a stability condition. We give an alternative proof for this result using the rate conservation law. This proof not only simplifies the proof, but also explains an underlying Markov structure and enables us to study more complex cases such that the fluid flow has jumps subject to a nondecreasing Lévy process, a Brownian component, and countably many background states.
The waiting time analysis of a discrete-time queue with arrivals as a discrete autoregressive process of order 1
Authors: Hwang Gang Uk , Choi Bong Dae , Kim Jae-Kyoon
Published: April 2003

We consider a discrete-time queueing system with the discrete autoregressive process of order 1 (DAR(1)) as an input process and obtain the actual waiting time distribution and the virtual waiting time distribution. As shown in the analysis, our approach provides a natural numerical algorithm to compute the waiting time distributions, based on the theory of the GI/G/1 queue, and consequently we can easily investigate the effect of the parameters of the DAR(1) on the waiting time distributions. We also derive a simple approximation of the asymptotic decay rate of the tail probabilities for the virtual waiting time in the heavy traffic case.
Multivariate dispersive ordering of epoch times of nonhomogeneous Poisson processes
Authors: Belzunce Felíx , Ruiz José-María
Published: April 2003

In this paper we find conditions under which the epoch times of two nonhomogeneous Poisson processes are ordered in the multivariate dispersive order. Some consequences and examples of this result are given. These results extend a recent result of Brown and Shanthikumar (1998).
Probability distribution of the number of deceits in collective robotics
Authors: Murciano Antonio , Zamora Javier , Lopez-Sanchez Jesus , Rodriguez-Santamaria Emilia
Published: April 2003

The benefit obtained by a selfish robot by cheating in a real multirobotic system can be represented by the random variable Xn,q: the number of cheating interactions needed before all the members in a cooperative team of robots, playing a TIT FOR TAT strategy, recognize the selfish robot. Stability of cooperation depends on the ratio between the benefit obtained by selfish and cooperative robots. In this paper, we establish the probability model for Xn,q. If the values of the parameters n and q are known, then this model allows us to make predictions about the stability of cooperation. Moreover, if these parameters are modifiable, it is possible to tune them to guarantee the viability of cooperation.
Asymptotic independence and a network traffic model
Authors: Maulik Krishanu , Resnick Sidney , Rootzén Holger
Published: April 2003

The usual concept of asymptotic independence, as discussed in the context of extreme value theory, requires the distribution of the coordinatewise sample maxima under suitable centering and scaling to converge to a product measure. However, this definition is too broad to conclude anything interesting about the tail behavior of the product of two random variables that are asymptotically independent. Here we introduce a new concept of asymptotic independence which allows us to study the tail behavior of products. We carefully discuss equivalent formulations of asymptotic independence. We then use the concept in the study of a network traffic model. The usual infinite source Poisson network model assumes that sources begin data transmissions at Poisson time points and continue for random lengths of time. It is assumed that the data transmissions proceed at a constant, nonrandom rate over the entire length of the transmission. However, analysis of network data suggests that the transmission rate is also random with a regularly varying tail. So, we modify the usual model to allow transmission sources to transmit at a random rate over the length of the transmission. We assume that the rate and the time have finite mean, infinite variance and possess asymptotic independence, as defined in the paper. We finally prove a limit theorem for the input process showing that the centered cumulative process under a suitable scaling converges to a totally skewed stable Lévy motion in the sense of finite-dimensional distributions.
Dynamic models of long-memory processes driven by Lévy noise
Authors: Anh V. V. , Heyde C. C. , Leonenko N. N.
Published: April 2003

A class of continuous-time models is developed for modelling data with heavy tails and long-range dependence. These models are based on the Green function solutions of fractional differential equations driven by Lévy noise. Some exact results on the second- and higher-order characteristics of the equations are obtained. Applications to stochastic volatility of asset prices and macroeconomics are provided.
A family of densities derived from the three-parameter Dirichlet process
Authors: Carlton Matthew A.
Published: April 2003

The traditional Dirichlet process is characterized by its distribution on a measurable partition of the state space - namely, the Dirichlet distribution. In this paper, we consider a generalization of the Dirichlet process and the family of multivariate distributions it induces, with particular attention to a special case where the multivariate density function is tractable.
A generic property of phase-type representations
Authors: Commault Christian , Mocanu Stéphane
Published: April 2003

In this paper we introduce the notion of structured phase-type representations. A structured representation corresponds to a class of phase-type representations having the same graph but free parameters. We define a generic property for such a representation. Then we prove that, generically, an irreducible structured representation of a given order corresponds to a distribution whose degree is equal to this order.
On the class of controlled branching processes with random control functions
Authors: González M. , Molina M. , Del Puerto I.
Published: April 2003

In this paper, the class of controlled branching processes with random control functions introduced by Yanev (1976) is considered. For this class, necessary and sufficient conditions are established for the process to become extinct with probability 1 and the limit probabilistic behaviour of the population size, suitably normed, is investigated.
Moderate deviation for super-Brownian Motion with super-Brownian immigration
Authors: Hong Wen-Ming
Published: April 2003

Moderate deviation principles are established in dimensions d ≥ 3 for super-Brownian motion with random immigration, where the immigration rate is governed by the trajectory of another super-Brownian motion. It fills in the gap between the central limit theorem and large deviation principles for this model which were obtained by Hong and Li (1999) and Hong (2001).
On a new approach to calculating expectations for option pricing
Authors: Borovkov K. , Novikov A.
Published: April 2003

We discuss a simple new approach to calculating expectations of a specific form used for the pricing of derivative assets in financial mathematics. We show that in the ‘vanilla case’, the expectations can be found by simply integrating the respective moment generating function with a certain weight. In situations corresponding to barrier-type options, we just need to carry out one more integration. The suggested approach appears to be the first (and, apart from Monte Carlo simulation, the only) one to allow the pricing of discretely monitored exotic options when the underlying asset is modelled by a general Lévy process. We illustrate the method numerically by calculating the price of a discretely monitored lookback call option in the cases when the underlying follows the geometric Brownian and variance-gamma processes.
A note on level-crossing analysis for the excess, age, and spread distributions
Authors: Katayama Tsuyoshi
Published: April 2003

In this paper, we show that the time-average distributions of excess, age, and spread are given by the solution of first-order differential equations. These differential equations can be directly derived in a simple, unified way using a general level-crossing formula based on the balance of up and down crossings on sample paths, which may be helpful for the intuitive interpretation.
Path integrals for continuous-time Markov chains
Authors: Pollett P. K. , Stefanov V. T.
Published: April 2003

This note presents a method of evaluating the distribution of a path integral for Markov chains on a countable state space.
Losses per cycle in a single-server queue
Authors: Wolff Ronald W.
Published: April 2003

Several recent papers have shown that for the M/G/1/nqueue with equal arrival and service rates, the expected number of lost customers per busy cycle is equal to 1 for everyn≥ 0. We present an elementary proof based on Wald's equation and, for GI/G/1/n, obtain conditions for this quantity to be either less than or greater than 1 for everyn≥ 0. In addition, we extend this result to batch arrivals, where, for average batch size β, the same quantity is either less than or greater than β. We then extend these results to general ways that customers may be lost, to an arbitrary order of service that allows service interruption, and finally to reneging.
Base Generation by the Photolysis of an Amineimide with Triplet-sensitizers and Its Use for an Epoxide/Thiol Curing System
Authors: Katogi Shigeki , Yusa Masami , Shirai Masamitsu , Tsunooka Masahiro
Published: April 2003

Sensitized base generation from an amineimide is achieved by using triplet-sensitizers having a triplet energy of more than 289 kJ·mol−1, which enables the lower temperature curing of an epoxide/thiol system with a low UV dose.
Production of Hydrogen and Nanocarbon from Direct Decomposition of Undiluted Methane on High-nickeled Ni–Cu–Alumina Catalysts
Authors: Chen Jiuling , Li Xiumin , Li Yongdan , Qin Yongning
Published: April 2003

Very active and stable high-nickeled Ni–Cu–alumina catalysts were used to produce hydrogen and nanocarbon by direct decomposition of undiluted methane at 773–1013 K. The growth way of nanocarbon depends on reaction temperatures and may be related with the catalyst stability.
Genetic variants of serum butyrylcholinesterase in Chilean Mapuche Indians
Authors: Acuña M. , Eaton L. , Ramírez N.R. , Cifuentes L. , Llop E.
Published: April 2003

We estimated the frequencies of serum butyrylcholinesterase (BChE) alleles in three tribes of Mapuche Indians from southern Chile, using enzymatic methods, and we estimated the frequency of allele BCHE*K in one tribe using primer reduced restriction analysis (PCR‐PIRA). The three tribes have different degrees of European admixture, which is reflected in the observed frequencies of the atypical allele BCHE*A: 1.11% in Huilliches, 0.89% in Cuncos, and 0% in Pehuenches. This result is evidence in favor of the hypothesis that BCHE*A is absent in native Amerindians. The frequencies of BCHE*F were higher than in most reported studies (3.89%, 5.78%, and 4.41%, respectively). These results are probably due to an overestimation of the frequency of allele BCHE*F, since none of the 20 BCHE UF individuals (by the enzymatic test) individuals analyzed showed either of the two DNA base substitutions associated with this allele. Although enzymatic methods rarely detect the presence of allele BCHE*K, PCR‐PIRA found the allele in an appreciable frequency (5.76%), although lower than that found in other ethnic groups. Since observed frequencies of unusual alleles correspond to estimated percentages of European admixture, it is likely that none of these unusual alleles were present in Mapuche Indians before the arrival of Europeans. Am J Phys Anthropol 121:000–000, 2003. © 2003 Wiley‐Liss, Inc.
A study on the effect of new cyanate and phenoxy polymer on TGDDM/DDS/GMP formulations
Authors: Lakshmi M. Suguna , Srividhya M. , Reddy B. S. R.
Published: April 2003

An attempt was made on the modification of the tetraglycidyl‐4,4′‐diaminodiphenyl methane/diaminodiphenyl sulfone (TGDDM/DDS) system to improve properties for several industrial applications. Epoxy resins [TGDDM and 1‐glycidyloxy‐4‐methoxy phenol (GMP)] were synthesized in the laboratory. Also, a new cyanate ester and phenoxy polymer were synthesized and characterized by FTIR, 1H‐/13C‐NMR, and thermal studies. GMP was added as a diluent and a new cyanate ester (DCDPT) was introduced to reduce the tight crosslinking density. Further, a new phenoxy polymer was added to improve the toughness property. A variety of neat resin casts using different compositions of the blends were made and their physical, chemical, thermal, and mechanical properties were evaluated to study the effect of GMP as a diluent, cyanate ester as a comonomer, and phenoxy polymer as a toughener. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2963–2973, 2003
Crystal‐induced neutrophil activation: VIII. Immediate production of prostaglandin E2 mediated by constitutive cyclooxygenase 2 in human neutrophils stimulated by urate crystals
Authors: Gilbert Caroline , Poubelle Patrice E. , Borgeat Pierre , Pouliot Marc , Naccache Paul H.
Published: April 2003

Objective

To evaluate the impact of monosodium urate monohydrate (MSUM) crystals on the synthesis of prostaglandin E2 (PGE2) by human neutrophils, and to examine some of the mechanisms underlying these responses.

Methods

The amount of PGE2 released in the supernatants of stimulated human neutrophils was evaluated by enzyme immunoassay, and expression of cyclooxygenase 2 (COX‐2) was monitored by immunoblot on cell lysates, as well as by cytofluorometry of buffy‐coat cells.

Results

We observed that MSUM crystals rapidly stimulated the synthesis of PGE2, with levels peaking at 1 hour. This response was decreased by NS‐398, a specific inhibitor of COX‐2. We also detected a constitutive expression of COX‐2 in unstimulated and unprimed neutrophils. This rapid COX‐2–dependent PGE2 accumulation was independent of translation and transcription. We also observed that piceatannol, but not colchicine, blocked the synthesis of PGE2 stimulated by MSUM crystals.

Conclusion

These results show that the interaction of MSUM crystals with human neutrophils stimulates a significant synthesis of PGE2 mediated by constitutively expressed COX‐2. The results of this study emphasize the potential importance of the neutrophil as a source of PGE2, which may modulate, positively or negatively, the inflammatory response.
Lower prevalence of hand osteoarthritis among Chinese subjects in Beijing compared with white subjects in the United States: The Beijing Osteoarthritis Study
Authors: Zhang Yuqing , Xu Ling , Nevitt Michael C. , Niu Jingbo , Goggins Joyce P. , Aliabadi Piran , Yu Wei , Lui Li‐Yung , Felson David T.
Published: April 2003

Objective

Fewer Chinese subjects in Beijing have hip osteoarthritis (OA) compared with whites in the United States, but as many or more Chinese subjects have knee OA. If these differences are due to a systemic predilection for disease, then the prevalence of hand OA, the best indicator of generalized disease, should be different in China. The goals of this study were to estimate the prevalence of hand OA among elderly Chinese in Beijing, and to compare it with that among elderly whites in the United States.

Methods

We recruited a random sample of Beijing residents ages ≥60 years. Subjects answered questions on joint symptoms and provided posteroanterior radiographs of the hand. The protocol was identical to that used in the Framingham, Massachusetts OA Study. The hand radiographs from the Beijing OA Study were read intermingled with films from the Framingham OA Study. We defined a hand joint as having radiographic OA if it had a Kellgren and Lawrence grade ≥2. Symptomatic OA was present when both radiographic OA and self‐reported pain were present in the same joint. We classified a subject as having radiographic or symptomatic hand OA if at least 1 hand joint had radiographic or symptomatic OA. We estimated the prevalence of hand OA in elderly subjects in Beijing and compared it with the prevalence of hand OA in elderly subjects from Framingham, using an age‐standardized prevalence ratio.

Results

We obtained both symptom information and hand radiographs from 2,525 subjects. Despite the older age of the group, only 44.5% of men and 47.0% of women had radiographic hand OA. Symptomatic hand OA occurred in 3.0% of men and 5.8% of women. Compared with white men in Framingham, the Beijing Chinese men had a much lower prevalence of radiographic hand OA (age‐adjusted prevalence ratio 0.64, 95% confidence interval [95% CI] 0.58–0.70) and symptomatic hand OA (age‐adjusted prevalence ratio 0.25, 95% CI 0.16–0.34). The proportion of multiple hand joints affected by OA in Chinese men was also significantly lower than in white men. A similar magnitude of difference was also observed in the women. However, prevalence of symptomatic OA at the metacarpophalangeal (MCP) joints in Chinese men and prevalence of radiographic OA at the MCP joints in Chinese women were similar to those in their white counterparts in Framingham.

Conclusion

Elderly Chinese subjects in Beijing had a much lower prevalence of hand OA than did elderly whites in Framingham, Massachusetts. Coupled with the exceedingly low prevalence of hip OA in China, these results may suggest that the overall predilection for OA is less among subjects in China than among whites in the United States.
Rat embryos express transcripts for cyclooxygenase‐1 and carbonic anhydrase‐4, but not for cyclooxygenase‐2, during organogenesis
Authors: Streck Randal D. , Kumpf Steven W. , Ozolinš Terence R. S. , Stedman Donald B.
Published: April 2003

BACKGROUND: Acetylsalicylic acid (ASA) is a rat teratogen, and exposures on gestational days (GDs) 9 and 10 induce diaphragm, cardiac, and midline defects. ASA inhibits members of the cyclooxygenase (COX) family and potentially members of the carbonic anhydrase (CA) family. The objective of this study was to determine whether the mRNA developmental expression pattern for any COX or CA isoform was consistent with a model in which ASA teratogenicity is mediated through direct interaction with one of these enzymes within embryos or within the adjacent ectoplacental cone (EPC) or yolk sac. METHODS: Staged embryos, over a range (GD 9.5–12) that included ASA‐sensitive and ASA‐insensitive stages of organogenesis, were assayed for COX and CA mRNA levels by three techniques: microarrays; in situ hybridization quantitated by a micro‐imager; and quantitative reverse transcription polymerase chain reaction. ASA‐ and vehicle‐treated embryos also were compared to determine whether inhibition led to upregulated COX or CA mRNA expression. RESULTS: COX‐2 mRNA was undetectable in embryos throughout organogenesis by any assay (although it was abundant in EPC). In contrast, COX‐1 mRNA was moderately abundant in embryos throughout organogenesis. One CA isoform, CA‐4, demonstrated developmentally regulated embryonic mRNA expression that coincided with ASA sensitivity. ASA exposure failed to induce upregulation of any of these mRNAs. CONCLUSIONS: Although ASA may affect the embryo indirectly through interaction with COX‐2 within EPC, failure to detect embryonic COX‐2 mRNA argues against COX‐2 functioning as a direct mediator of ASA teratogenic activity in induction of cardiac, diaphragm, and midline defects. Correlation of COX‐1 and CA‐4 expression with ASA sensitivity suggested that embryonic COX‐1 and possibly CA‐4 are much more likely candidates for mediators of ASA developmental toxicity. Birth Defects Research (Part B) 68:57–69, 2003. © 2003 Wiley‐Liss, Inc.
Prognostic significance of preoperative factors in localized prostate carcinoma treated with radical prostatectomy
Authors: Quinn David I. , Henshall Susan M. , Brenner Phillip C. , Kooner Raji , Golovsky David , O'Neill Gordon F. , Turner Jennifer J. , Delprado Warick , Grygiel John J. , Sutherland Robert L. , Stricker Phillip D.
Published: April 2003

BACKGROUND

Predicting outcome for men with clinically localized prostate carcinoma treated with curative intent remains imprecise and further evaluation of accepted and potential predictive factors is needed.

METHODS

The authors studied 696 men with localized prostate carcinoma diagnosed on transrectal biopsy and treated with radical prostatectomy at one institution between 1986 and 1999 to determine the relation between putative pretreatment prognostic factors and disease‐free survival. Clinical stage, Gleason score, perineural invasion, number of biopsies containing tumor, and serum prostate specific antigen (PSA) were evaluated as predictors of extracapsular extension, seminal vesicle involvement, lymph node metastases, and surgical margin involvement as well as outcome after surgery. Kaplan–Meier method and Cox regression analyses were used to evaluate the contribution of different factors to adverse pathologic features and relapse.

RESULTS

At mean follow‐up of 56.9 months (range, 1.0–177.9 months; median, 54.9 months), 26.1% (182 of 696 patients) of patients had developed a disease recurrence. Pretreatment serum PSA concentration, biopsy Gleason score, and clinical stage as well as number of biopsies involved with tumor as a percentage of the total number obtained were found to be independent predictors of outcome. In patients with PSA > 10 ng/mL, biopsy perineural invasion and percentage of biopsies containing tumor were found to independently predicted disease recurrent. Increased number of biopsies involved with tumor independently predicted extracapsular extension, margin involvement, seminal vesicle, and lymph node involvement.

CONCLUSIONS

This study demonstrated that the proportion of prostate biopsy cores containing tumor is an independent predictor of outcome after subsequent radical prostatectomy and suggested that perineural invasion has a predictive role in patients with a preoperative PSA > 10 ng/ml. Cancer 2003;97:1884–93. © 2003 American Cancer Society.

DOI 10.1002/cncr.11263
The sentinel lymph node: More than just another blue lymph node
Authors: Wagner Jeffrey D. , Sondak Vernon K.
Published: April 2003

DOI 10.1002/cncr.11270
Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors
Authors: Hinton Stuart , Catalano Paul J. , Einhorn Lawrence H. , Nichols Craig R. , David Crawford E. , Vogelzang Nicholas , Trump Donald , Loehrer Patrick J.
Published: April 2003

BACKGROUND

Various staging systems have been proposed for disseminated germ cell neoplasms. The Indiana University staging system was based on clinical and radiographic findings only, whereas the newly created International Germ Cell Cancer Collaborative Group (IGCCCG) staging system also utilized serum markers as a prognostic factor. This study updated the intergroup trial that compared the standard therapy of bleomycin, etoposide, and cisplatin (BEP) with etoposide, ifosfamide, and cisplatin (VIP) in advanced germ cell tumors and reanalyzed the results using the IGCCCG staging system.

METHODS

From October 1987 to April 1992, 304 patients with advanced‐stage germ cell tumors (using the Indiana University staging system) were randomized to receive four cycles of BEP or VIP. Two hundred and eighty‐six patients were eligible and fully evaluable. With a median follow‐up of 7.3 years, 283 of the 286 evaluable patients from the Eastern Cooperative Oncology Group protocol, E3887, were reclassified using the IGCCCG staging system. Progression‐free survival (PFS), overall survival (OS), and toxicity were assessed for the treatment arms.

RESULTS

With a longer follow‐up of 7.3 years and using the Indiana University staging system, the PFS rates were 64% versus 58% and the OS rates were 69% versus 67% in the VIP and BEP arms, respectively. For patients reclassified with the IGCCCG staging system, the PFS rates were 81%, 72%, and 54% and the OS rates were 89%, 81%, and 60% for good, intermediate, and poor‐risk patients, respectively. Differences in OS (VIP, 62%; BEP, 57%) and PFS (VIP, 56%; BEP, 49%) for the subset of patients reclassified as poor risk by the IGCCCG staging system were not significantly different. More toxicity, primarily hematologic toxicity, occurred on the VIP arm.

CONCLUSIONS

With a median follow‐up of 7.3 years and with a reclassification based on the IGCCCG, OS and PFS rates were comparable between BEP and VIP. Toxicity, primarily hematologic, was modestly greater with the ifosfamide‐containing arm. The VIP regimen may be considered a treatment alternative for patients with underlying pulmonary disease. In most patients with poor and intermediate‐risk germ cell tumors, four cycles of BEP remain the standard therapy. Cancer 2003;97:1869–75. © 2003 American Cancer Society.

DOI 10.1002/cncr.11271
Prostate cancer: Biology, diagnosis, and management
Authors: D'Amico Anthony V.
Published: April 2003

DOI 10.1002/cncr.11276
Primary transcrotal excision for paratesticular rhabdomyosarcoma
Authors: Dall'Igna Patrizia , Bisogno Gianni , Ferrari Andrea , Treuner Jörn , Carli Modesto , Zanetti Ilaria , Guglielmi Maurizio , Cecchetto Giovanni
Published: April 2003

BACKGROUND

To evaluate the role of primary reexcision (PRE) with scrotal resection in patients with paratesticular rhabdomyosarcoma enrolled in the German‐Italian Cooperative Studies. The authors compared patients who underwent this procedure, according to the protocol guidelines, with those who did not.

METHODS

In 32 of 198 patients with localized disease, the primary surgery was performed through a noncorrect scrotal approach. Twenty‐four patients underwent PRE as recommended by the protocol guidelines (Group A) and 8 did not receive this treatment (Group B). The Group B patients were treated with the same chemotherapeutic regimens as the Group A patients and no radiotherapy was given to either group.

RESULTS

After PRE, residual tumor was not detected in 21 of the 24 Group A patients. Twenty patients are alive in first complete remission 26–250 months after diagnosis (median, 40 months), 2 are alive in second complete remission at 3 and 9 months from diagnosis of lymph node and lung recurrence, and 2 died of disease after lymph node and distant metastases at 16 and 13 months from diagnosis. Three‐fourths of these patients were older than 10 years old and the tumor was larger than 5 cm. The eight Group B patients are all alive in first complete remission 24–250 months since diagnosis.

CONCLUSIONS

The data on the eight patients who obtained local control without PRE or radiotherapy warrant further investigation. Because of the supposed high risk of contamination with subsequent microscopic residual tumor after a transcrotal approach, we emphasize the utility of PRE with hemiscrotectomy. Cancer 2003;97:1981–4. © 2003 American Cancer Society.

DOI 10.1002/cncr.11284
Expression and localization of GLUT1 and GLUT12 in prostate carcinoma
Authors: Chandler Jenalle D. , Williams Elizabeth D. , Slavin John L. , Best James D. , Rogers Suzanne
Published: April 2003

BACKGROUND

Increased glucose consumption is a characteristic of malignant cells and in prostate carcinoma is associated with the proliferation of both androgen‐dependent and independent cells. Transport of polar glucose across the nonpolar membrane relies on glucose transporter proteins, known as GLUTs. Increased expression of GLUT1 is a characteristic of many malignant cells. The authors characterized and cloned the cDNA for a novel glucose transporter, GLUT12, which was identified initially in malignant breast epithelial cells. To the authors' knowledge, there have been no reports on the expression of glucose transporters in the human prostate or human prostate carcinoma cells. The authors evaluated GLUT1 and GLUT12 expression in human prostate carcinoma cells.

METHODS

Reverse transcription‐polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4‐2, and C4‐2B using primers to amplify GLUT1, GLUT12, or the housekeeping gene, 36B4. Total protein extracted from prostate carcinoma cell lines was assessed for GLUT12 protein by Western blot analysis. Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy. Sections of benign prostatic hyperplasia and human prostate carcinoma were stained for immunohistochemical detection of GLUT1 and GLUT12.

RESULTS

GLUT1 and GLUT12 mRNA and protein were detected in all cell lines evaluated. Immunofluorescence staining demonstrated both GLUT1 and GLUT12 on the plasma membrane and in the cytoplasm in all cultured prostate carcinoma cell lines, with GLUT1 but not GLUT12 appearing to colocalize with the Golgi. Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12. Malignant tissue stained for GLUT12 but was negative for GLUT1.

CONCLUSIONS

GLUT1 and GLUT12 are expressed in human prostate carcinoma cells. One possible rationale for the GLUT1 Golgi association is that it may supply glucose to the Golgi for byproduct incorporation into the prostatic secretory fluid. Further work will investigate the importance of glucose transport and GLUT1 and GLUT12 in prostate carcinoma cell growth. Cancer 2003;97:2035–42. © 2003 American Cancer Society.

DOI 10.1002/cncr.11293
Image‐guided and intensity‐modulated radiosurgery for patients with spinal metastasis
Authors: Ryu Samuel , Fang Yin Fang , Rock Jack , Zhu Jingeng , Chu Archie , Kagan Eduard , Rogers Lisa , Ajlouni Munther , Rosenblum Mark , Kim Jae Ho
Published: April 2003

BACKGROUND

Radiosurgery can deliver a single, large radiation dose to a localized tumor using a stereotactic approach and hence, requires accurate and precise delivery of radiation to the target. Of the extracranial organ targets, the spine is considered a suitable site for radiosurgery, because there is minimal or no breathing‐related organ movement. The authors studied spinal radiosurgery in patients with spinal metastases to determine its accuracy and precision.

METHODS

The spinal radiosurgery program was based on an image‐guided and intensity‐modulated, shaped‐beam radiosurgical unit. It is equipped with micromultileaf collimators for beam shaping and radiation intensity modulation and with a noninvasive, frameless positioning device that uses infrared, passive marker technology together with corroborative image fusion of the digitally reconstructed image from computed tomography (CT) simulation and orthogonal X‐ray imagery at the treatment position. These images were compared with the port films that were taken at the time of treatment to determine the accuracy of the isocenter position. Clinical feasibility was tested in 10 patients who had spinal metastasis with or without spinal cord compression. The patients were treated with fractionated external beam radiotherapy followed by single‐dose radiosurgery as a boost (6–8 grays) to the most involved portion of the spine or to the site of spinal cord compression.

RESULTS

The accuracy for the isocenter was within 1.36 mm ± 0.11 mm, as measured by image fusion of the digitally reconstructed image from CT simulation and the port film. Clinically, the majority of patients had prompt pain relief within 2–4 weeks of treatment. Complete and partial recovery of motor function also was achieved in patients with spinal cord compression. The radiation dose to the spinal cord was minimal. The maximum dose of radiation to the anterior edge of the spinal cord within a transverse section, on average, was 50% of the prescribed dose. There was no acute radiation toxicity detected clinically during the mean follow‐up of 6 months.

CONCLUSIONS

Image‐guided, shaped‐beam spinal radiosurgery is accurate and precise. Rapid clinical improvement of pain and neurologic function also may be achieved. The results indicate the potential of spinal radiosurgery in the treatment of patients with spinal metastasis, especially those with solitary sites of spine involvement, to increase the prospects of long‐term palliation. Cancer 2003;97:2013–8. © 2003 American Cancer Society.

DOI 10.1002/cncr.11296
Screening nasopharyngeal carcinoma by detection of the latent membrane protein 1 (LMP‐1) gene with nasopharyngeal swabs
Authors: Hao Sheng‐Po , Tsang Ngan‐Ming , Chang Kai‐Ping
Published: April 2003

BACKGROUND

Nasopharyngeal carcinoma (NPC) is a common head and neck cancer in Taiwan. The goals of the current study were to investigate whether a nasopharyngeal swab technique could provide enough DNA for polymerase chain reaction (PCR) analysis of the Epstein–Barr virus (EBV)–derived latent membrane protein 1 (LMP‐1) gene and to determine the feasibility and reliability of diagnosing NPC by detection of LMP‐1 in the nasopharynx.

METHODS

320 adults underwent nasopharyngoscopy and nasopharyngeal swab to obtain cells for the LMP‐1 PCR assay; some patients also underwent nasopharyngeal biopsy.

RESULTS

An amount of DNA that was sufficient for PCR was extracted from 96.3% of the swab samples. By detecting LMP‐1 in nasopharyngeal swabs, NPC was diagnosed with a false positive rate of 12.7% (7 of55 patients), a false negative rate of 1.6% (4 of 253 patients), sensitivity of 87.3% (48 of 55 patients), specificity of 98.4% (249 of 253 patients), a positive predictive value of 92.3% (48 of 52 patients), and a negative predictive value of 97.3% (249/256 patients). NPC was diagnosed by nasopharyngoscopy with a false positive rate of 38% (30 of 79 patients), a false negative rate of 0.4% (1 of 241 patients), sensitivity of 62% (49 of 79 patients), specificity of 99.6% (240 of 241 patients), a positive predictive value of 98% (49 of 50 patients), and a negative predictive value of 88.9% (240 of 270 patients). Only 7 (0.2%) of 256 patients with a diagnosis other than NPC had LMP‐1 detected in the nasopharyngeal space.

CONCLUSIONS

Detecting EBV genomic LMP‐1 by nasopharyngeal swab diagnosed NPC with 87.3% sensitivity and 98.4% specificity. EBV genomic DNA usually is not detected by PCR‐based methods in the nasopharyngeal space. Its incidence is estimated to be as low as 0.2% among the general population. The nasopharyngeal swab coupled with PCR‐based EBV LMP‐1 detection could serve as part of a screening program for high‐risk populations. Cancer 2003;97:1909–13. © 2003 American Cancer Society.

DOI 10.1002/cncr.11312
American Cancer Society Atlas of Clinical Oncology: Lung cancer
Authors: Masters Gregory A.
Published: April 2003

DOI 10.1002/cncr.11333