bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory results for the features of body‐wave propagation in a transversely isotropic media
Authors: Chang Young‐Fo , Chang Chih‐Hsiung
Published: October 2002

Much of the earth’s crust appears to have some degree of elastic anisotropy (Crampin, 1981; Crampin and Lovell, 1991; Helbig, 1993). The phenomena of elastic wave propagation in anisotropic media are more complex than those in isotropic media. Shear‐wave propagation in an orthorhombic physical model is most complex when the direction of the wave is close to the neighborhood of the cusp on the group velocity surfaces (Brown et al., 1991). The first identification of singularities in wave propagation through sedimentary basins occurred in the examination of shear‐wave splitting in multioffset vertical seismic profiles (VSPs) at a borehole site in the Paris Basin (Bush and Crampin, 1991), where large variations in shear‐wave polarizations in propagation directions close to point singularities were observed. Computation of synthetic seismograms for layer sequences showed that the shear‐wave polarizations and amplitudes were irregular near point singularities (Crampin, 1991).
Generation of T-Cell Immunity to the HER-2/neu Protein After Active Immunization With HER-2/neu Peptide–Based Vaccines
Authors: Disis Mary L. , Gooley Theodore A. , Rinn Kristine , Davis Donna , Piepkorn Michael , Cheever Martin A. , Knutson Keith L. , Schiffman Kathy
Published: October 2002

PURPOSE: The HER-2/neu protein is a nonmutated tumor antigen that is overexpressed in a variety of human malignancies, including breast and ovarian cancer. Many tumor antigens, such as MAGE and gp100, are self-proteins; therefore, effective vaccine strategies must circumvent tolerance. We hypothesized that immunizing patients with subdominant peptide epitopes derived from HER-2/neu, using an adjuvant known to recruit professional antigen-presenting cells, granulocyte-macrophage colony-stimulating factor, would result in the generation of T-cell immunity specific for the HER-2/neu protein.

PATIENTS AND METHODS: Sixty-four patients with HER-2/neu–overexpressing breast, ovarian, or non–small-cell lung cancers were enrolled. Vaccines were composed of peptides derived from potential T-helper epitopes of the HER-2/neu protein admixed with granulocyte-macrophage colony-stimulating factor and administered intradermally. Peripheral-blood mononuclear cells were evaluated at baseline, before vaccination, and after vaccination for antigen-specific T-cell immunity. Immunologic response data are presented on the 38 subjects who completed six vaccinations. Toxicity data are presented on all 64 patients enrolled.

RESULTS: Ninety-two percent of patients developed T-cell immunity to HER-2/neu peptides (stimulation index, 2.1 to 59) and 68% to a HER-2/neu protein domain (stimulation index range, 2 to 31). Epitope spreading was observed in 84% of patients and significantly correlated with the generation of a HER-2/neu protein–specific T-cell immunity (P = .03). At 1-year follow-up, immunity to the HER-2/neu protein persisted in 38% of patients.

CONCLUSION: The majority of patients with HER-2/neu–overexpressing cancers can develop immunity to both HER-2/neu peptides and protein. In addition, the generation of protein-specific immunity, after peptide immunization, was associated with epitope spreading, reflecting the initiation of an endogenous immune response. Finally, immunity can persist after active immunizations have ended.
Use of Adjuvant Chemotherapy and Radiation Therapy for Rectal Cancer Among the Elderly: A Population-Based Study
Authors: Neugut Alfred I. , Fleischauer Aaron T. , Sundararajan Vijaya , Mitra Nandita , Heitjan Daniel F. , Jacobson Judith S. , Grann Victor R.
Published: October 2002

PURPOSE: Combined adjuvant fluorouracil (5-FU)–based chemotherapy with radiation is now the standard of care for locally advanced rectal cancer in the United States. We investigated the use of these treatments for stages II and III rectal cancer among the elderly and the effectiveness of these treatments on a population-based scale.

PATIENTS AND METHODS: The linked Surveillance, Epidemiology, and End-Results–Medicare database was used to identify 1,807 Medicare beneficiaries ≥ 65 years of age with stage II or III rectal cancer who underwent surgical resection between 1992 and 1996. We excluded members of a health maintenance organization in the 12 months before or 4 months after their diagnosis and those who died within 4 months of diagnosis. We used multivariate analysis to identify factors associated with combined 5-FU and radiation therapy, and propensity score methodology to determine survival benefit for those treated.

RESULTS: We found that 37% of patients received both adjuvant 5-FU and radiation therapy, 11% 5-FU alone, and 14% radiation alone. Decreasing age, increasing lymph node positivity, comorbid conditions, and nonblack race were associated with increased probability of treatment with 5-FU and radiation. Combined chemotherapy/radiation therapy was associated with improved survival for stage III (relative risk, 0.71; 95% confidence interval, 0.56 to 0.90), but not for stage II rectal cancer (relative risk, 0.89; 95% confidence interval, 0.70 to 1.14).

CONCLUSION: The association of combined treatment with improved survival in node-positive disease was similar to that observed in other studies. In the absence of data from well-designed randomized controlled trials, our observational data support efforts on the part of clinicians to make appropriate referrals and provide combined treatment for elderly patients with stage III rectal cancer.
Modulation of Irinotecan Metabolism by Ketoconazole
Authors: Kehrer Diederik F.S. , Mathijssen Ron H.J. , Verweij Jaap , de Bruijn Peter , Sparreboom Alex
Published: October 2002

PURPOSE: Irinotecan (CPT-11) is a prodrug of SN-38 and has been registered for the treatment of advanced colorectal cancer. It is converted by the cytochrome P450 3A4 isozyme (CYP3A4) into several inactive metabolites, including 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC). To investigate the role of CYP3A4 in irinotecan pharmacology, we evaluated the consequences of simultaneous treatment of irinotecan with a potent enzyme inhibitor, ketoconazole, in a group of cancer patients.

PATIENTS AND METHODS: A total of seven assessable patients was treated in a randomized, cross-over design with irinotecan (350 mg/m2 intravenously for 90 minutes) given alone and followed 3 weeks later by irinotecan (100 mg/m2) in combination with ketoconazole (200 mg orally for 2 days) or vice versa. Serial plasma, urine, and feces samples were obtained up to 500 hours after dosing and analyzed for irinotecan, metabolites (7-ethyl-10-hydroxycamptothecin [SN-38], SN-38 glucuronide [SN-38G], and APC), and ketoconazole by high-performance liquid chromatography.

RESULTS: With ketoconazole coadministration, the relative formation of APC was reduced by 87% (P = .002), whereas the relative exposure to the carboxylesterase-mediated SN-38 as expected on the basis of dose (area under the plasma concentration-time curve normalized to dose) was increased by 109% (P = .004). These metabolic alterations occurred without substantial changes in irinotecan clearance (P = .90) and formation of SN-38G (P = .93).

CONCLUSION: Inhibition of CYP3A4 in cancer patients treated with irinotecan leads to significantly increased formation of SN-38. Simultaneous administration of various commonly prescribed inhibitors of CYP3A4 can potentially result in fatal outcomes, and up to four-fold reductions in irinotecan dose are indicated.
Rituximab as First-Line and Maintenance Therapy for Patients With Indolent Non-Hodgkin’s Lymphoma
Authors: Hainsworth John D. , Litchy Sharlene , Burris Howard A. , Scullin Daniel C. , Corso Steven W. , Yardley Denise A. , Morrissey Lisa , Greco F. Anthony
Published: October 2002

PURPOSE: To evaluate response to single-agent rituximab in patients with indolent non-Hodgkin’s lymphoma (NHL) and no previous systemic therapy, and the feasibility, toxicity, and efficacy of maintenance rituximab, administered at 6-month intervals, in patients with objective response or stable disease after first-line rituximab therapy.

PATIENTS AND METHODS: Patients with indolent NHL (follicular or small lymphocytic subtypes) previously untreated with systemic therapy received rituximab 375 mg/m2 intravenously weekly for 4 weeks. Patients were restaged at week 6 for response; those with objective response or stable disease received maintenance rituximab courses (identical dose and schedule) at 6-month intervals. Maintenance was continued for a maximum of four rituximab courses or until progression. Between March 1998 and May 1999, 62 patients were entered onto this trial; minimum follow-up was 24 months.

RESULTS: Sixty patients (97%) completed the first 4-week course of rituximab and were assessable for response. All have now completed rituximab therapy; 36 (58%) received four courses at 6-month intervals. The objective response rate at 6 weeks was 47%; 45% of patients had stable disease. With continued maintenance, final response rate increased to 73%, with 37% complete responses. Response was similar in patients with follicular versus small lymphocytic subtypes (76% v 70%, respectively). Median actuarial progression-free survival was 34 months. Two patients experienced grade 3/4 toxicity with the first dose; one patient was removed from treatment. No cumulative or additional toxicities were seen with maintenance courses.

CONCLUSION: Rituximab is highly active and extremely well tolerated as first-line single-agent therapy for indolent NHL. First-line treatment with scheduled maintenance at 6-month intervals produces high overall and complete response rates and a longer progression-free survival (34 months) than has been reported with a standard 4-week treatment.
Consultation Planning to Help Breast Cancer Patients Prepare for Medical Consultations: Effect on Communication and Satisfaction for Patients and Physicians
Authors: Sepucha Karen R. , Belkora Jeffrey K. , Mutchnick Stephanie , Esserman Laura J.
Published: October 2002

PURPOSE: To measure the prevalence of communication barriers between breast cancer patients and their physicians and to present the results of a study evaluating the impact of two visit preparation techniques on communication and satisfaction for breast cancer patients and their physicians.

PATIENTS AND METHODS: We recruited 132 breast cancer patients from two outpatient cancer centers in a sequential, controlled trial. Ninety-four consented and completed the trial. Patients were assigned to one of two visit preparation interventions before their appointment with either a surgeon or a medical oncologist. In the control intervention, called Productive Listening, a researcher listened to and prompted patients to reflect on their experiences communicating with physicians. In the experimental intervention, called Consultation Planning, a researcher elicited questions and concerns, generated a printed agenda for the upcoming consultation, and engaged patients in techniques to improve communication with their physicians. Valid and reliable surveys measured communication barriers, satisfaction with the intervention, and patients’ and physicians’ satisfaction with the consultation.

RESULTS: Sixty-four percent of the patients reported three or more communication barriers. Patients reported a significant reduction in communication barriers after both the intervention and the control session. Patients reported significantly higher satisfaction after the Consultation Planning sessions. Physicians reported significantly higher satisfaction with those patients who had participated in a Consultation Planning session.

CONCLUSION: Visit preparation sessions help patients prepare for medical consultations and reduce barriers to communication. Consultation Planning sessions, in which a researcher solicited the patient’s agenda, were more satisfying to patients and physicians than the Productive Listening sessions.
Tamoxifen, Radiation Therapy, or Both for Prevention of Ipsilateral Breast Tumor Recurrence After Lumpectomy in Women With Invasive Breast Cancers of One Centimeter or Less
Authors: Fisher Bernard , Bryant John , Dignam James J. , Wickerham D. Lawrence , Mamounas Eleftherios P. , Fisher Edwin R. , Margolese Richard G. , Nesbitt Lois , Paik Soonmyung , Pisansky Thomas M. , Wolmark Norman
Published: October 2002

PURPOSE: This trial was prompted by uncertainty about the need for breast irradiation after lumpectomy in node-negative women with invasive breast cancers of ≤ 1 cm, by speculation that tamoxifen (TAM) might be as or more effective than radiation therapy (XRT) in reducing the rate of ipsilateral breast tumor recurrence (IBTR) in such women, and by the thesis that both modalities might be more effective than either alone.

PATIENTS AND METHODS: After lumpectomy, 1,009 women were randomly assigned to TAM (n = 336), XRT and placebo (n = 336), or XRT and TAM (n = 337). Rates of IBTR, distant recurrence, and contralateral breast cancer (CBC) were among the end points for analysis. Cumulative incidence of IBTR and of CBC was computed accounting for competing risks. Results with two-sided P values of .05 or less were statistically significant.

RESULTS: XRT and placebo resulted in a 49% lower hazard rate of IBTR than did TAM alone; XRT and TAM resulted in a 63% lower rate than did XRT and placebo. When compared with TAM alone, XRT plus TAM resulted in an 81% reduction in hazard rate of IBTR. Cumulative incidence of IBTR through 8 years was 16.5% with TAM, 9.3% with XRT and placebo, and 2.8% with XRT and TAM. XRT reduced IBTR below the level achieved with TAM alone, regardless of estrogen receptor (ER) status. Distant treatment failures were infrequent and not significantly different among the groups (P = .28). When TAM-treated women were compared with those who received XRT and placebo, there was a significant reduction in CBC (hazard ratio, 0.45; 95% confidence interval, 0.21 to 0.95; P = .039). Survival in the three groups was 93%, 94%, and 93%, respectively (P = .93).

CONCLUSION: In women with tumors ≤ 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, and TAM plus XRT when tumors are ER positive.
Novel Targets for Lung Cancer Therapy: Part I
Authors: Dy Grace K. , Adjei Alex A.
Published: October 2002

ABSTRACT: Lung cancer is the second most common form of cancer in the United States, and although it accounts for 15% of all cancers, it is the most lethal, accounting for approximately 28% of cancer deaths. In 2002, it is estimated that 177,000 new cases of lung cancer will be diagnosed in the United States, and an estimated 160,000 men and women will die from the disease. This mortality rate is greater than that attributable to colorectal, breast, and prostate cancer combined. Systemic treatments for lung cancer with standard chemotherapy agents are still relatively ineffective. Agents targeting novel proliferative and survival pathways in lung cancer are needed to improve treatment outcomes. In recent years, numerous agents inhibiting aberrant processes in tumor cells have undergone clinical evaluation. This review is the first of a two-part series that summarizes pertinent preclinical and clinical information on novel drugs that target critical abnormalities in lung cancer. In this article, agents inhibiting growth factor receptors and various molecules downstream of activated signaling cascades, such as cytoplasmic second messengers, are described.
Phase II Study of Carboplatin in Children With Progressive Low-Grade Gliomas
Authors: Gururangan Sridharan , Cavazos Christina M. , Ashley David , Herndon James E. , Bruggers Carol S. , Moghrabi Albert , Scarcella Deborah L. , Watral Melody , Tourt-Uhlig Sandra , Reardon David , Friedman Henry S.
Published: October 2002

PURPOSE: To assess the rate of tumor response and activity of carboplatin in stabilizing the growth of progressive low-grade gliomas.

PATIENTS AND METHODS: Eligible patients received carboplatin 560 mg/m2 intravenously every 4 weeks for 1 year after maximum tumor response or until disease progression or unacceptable toxicity.

RESULTS: Between October 1993 and October 2000, 81 children (median age, 79 months; range, 6 to 204) were enrolled onto this study. Patients received a median of 11 cycles of carboplatin (range, one to 29). Median follow-up from the time of enrollment was 55 months (range, 10 to 93). The overall objective response (complete response [CR] + partial response [PR] + minor response [MR]) and disease stabilization (CR + PR + stable disease + MR) rates to carboplatin treatment were 28% (95% confidence interval [CI], 18% to 38%) and 85% (95% CI, 74% to 93%), respectively. Eleven and 14 patients suffered progressive disease on study and after stopping therapy, respectively. Toxicity was predominantly myelosuppression and included grade 3/4 neutropenia in 56 patients and grade 3/4 thrombocytopenia in 40 patients. The 3-year failure-free survival (FFS) and overall survival (OS) for all patients were 64% (95% CI, 54% to 76%) and 84% (95% CI, 76% to 93%), respectively. Patients with diencephalic tumors had inferior FFS and OS compared with those with tumor at other sites (38% v 74% for FFS, P = .011; 54% v 91% for OS, P = .004). Neurofibromatosis type 1 patients with progressive low-grade glioma had a significantly better OS (95% v 80%; P = .052).

CONCLUSION: Carboplatin, in the schedule used in this study, produced disease stabilization or improvement in a majority of children with progressive low-grade glioma, with manageable toxicity. Improved treatment strategies are particularly required for patients with diencephalic tumors.
Evaluation of the inhibition effect of thiolated poly(acrylates) on vaginal membrane bound aminopeptidase N and release of the model drug LH-RH
Authors: Valenta Claudia , Marschütz Michaela , Egyed Christiane , Bernkop-Schnürch Andreas
Published: October 2002

The purpose of this study was to evaluate the inhibitory effect of thiolated carbopol 974P (carbcys) on the enzymatic activity of vaginal aminopeptidase N in-vitro. Mediated by a carbodiimide, L-cysteine was covalently linked to carbopol 974P. Depending on the weight ratio of polymer to cysteine during the coupling reaction, resulting conjugates displayed 31.3–54.4 μmol thiol groups per g polymer. The inhibitory effect of carb-cys conjugates was evaluated towards isolated aminopeptidase N and aminopeptidase-N-like activity of excised vaginal mucosa covered with native mucus, respectively. Enzymatic activity was assayed spectrophotometrically using L-leucine-p-nitroanilide (L-leu-pNA) as a synthetic substrate. Carb-cys thereby showed a significantly higher inhibitory effect than unmodified polymer towards both isolated enzyme and vaginal mucosa. Moreover, enzyme inhibition was strongly dependent on the amount of thiol groups being immobilised. The more thiol groups available the higher was the inhibitory effect. Due to its additional high cohesive properties and the possibility of a sustained drug release, which could be shown for the model drug LH-RH, carb-cys appears interesting for the development of vaginal peptide drug-delivery systems.
Optimization of inspection intervals based on cost
Authors: Badía F. G. , Berrade M. D. , Campos Clemente A.
Published: October 2002

We present a new inspection policy useful when testing is needed to detect failures of a single-unit system. It is supposed that tests may fail and give an erroneous result. The inspection policy minimizing cost per unit of time for an infinite time span is also discussed. In addition, we study the behaviour of the optimum policy for some time to failure distributions often assumed in reliability: exponential and Pareto.
Sequential games
Authors: Siegrist Kyle , Steele John
Published: October 2002

We give a general construction of sequential games among multiple players, as well as a construction of the composition of sequential games. We obtain new properties of the optimal class of win-by-kgames, including closure under composition and independence between the winner of the game and the number of points played. We obtain new results on the asymptotic efficiency of then-point, win-by-kgames.
Geometric inequalities for the eigenvalues of concentrated Markov chains
Authors: François Olivier
Published: October 2002

This article describes new estimates for the second largest eigenvalue in absolute value of reversible and ergodic Markov chains on finite state spaces. These estimates apply when the stationary distribution assigns a probability higher than 0.702 to some given state of the chain. Geometric tools are used. The bounds mainly involve the isoperimetric constant of the chain, and hence generalize famous results obtained for the second eigenvalue. Comparison estimates are also established, using the isoperimetric constant of a reference chain. These results apply to the Metropolis-Hastings algorithm in order to solve minimization problems, when the probability of obtaining the solution from the algorithm can be chosen beforehand. For these dynamics, robust bounds are obtained at moderate levels of concentration.
A perturbation method for the structured coalescent with strong migration
Authors: Notohara Morihiro
Published: October 2002

By applying a perturbation method to the structured coalescent process in population genetics theory, we obtain the approximate solutions of the moment generating functions for the total coalescence time, the number of segregating sites among sampled DNA sequences and the number of allele types in a sample in the case of strong migration.
Poisson limits and nonparametric estimation for pairwise interaction point processes
Authors: Chang Wei-Bin , Gubner John A.
Published: October 2002

The distribution of the interpoint distance process of a sequence of pairwise interaction point processes is considered. It is shown that, if the interaction function is piecewise-continuous, then the sequence of interpoint distance processes converges weakly to an inhomogeneous Poisson process under certain sparseness conditions. Convergence of the expectation of the interpoint distance process to the mean of the limiting Poisson process is also established. This suggests a new nonparametric estimator for the interaction function if independent identically distributed samples of the point process are available.
A note on bias optimality in controlled queueing systems
Authors: Lewis Mark E. , Puterman Martin L.
Published: October 2002

The use of bias optimality to distinguish among gain optimal policies was recently studied by Haviv and Puterman [1] and extended in Lewis et al. [2]. In [1], upon arrival to an M/M/1 queue, customers offer the gatekeeper a reward R. If accepted, the gatekeeper immediately receives the reward, but is charged a holding cost, c(s), depending on the number of customers in the system. The gatekeeper, whose objective is to ‘maximize’ rewards, must decide whether to admit the customer. If the customer is accepted, the customer joins the queue and awaits service. Haviv and Puterman [1] showed there can be only two Markovian, stationary, deterministic gain optimal policies and that only the policy which uses the larger control limit is bias optimal. This showed the usefulness of bias optimality to distinguish between gain optimal policies. In the same paper, they conjectured that if the gatekeeper receives the reward upon completion of a job instead of upon entry, the bias optimal policy will be the lower control limit. This note confirms that conjecture.
Random and Poisson paced record models in theFαsetup
Authors: Hofmann Glenn , Nagaraja H. N.
Published: October 2002

We study a random record model where the observationXihas continuous distribution functionFαi(αi> 0) and the number of available observations is random and independent of the observations. We obtain the joint distribution of the record values and inter-record times for our model. We investigate the distribution of the number of records when the number of observations has one of the common distributions and the α's increase geometrically or linearly. A particularly interesting case arises when the observations arrive at time points paced by a Poisson point process. For this model we obtain distributional results for the inter-arrival times of records for a large class of combinations of α structures and intensity functions.
Filtering equations for the conditional law of residual lifetimes from a heterogeneous population
Authors: Gerardi A. , Spizzichino F. , Torti B.
Published: October 2002

We consider a probabilistic model of a heterogeneous populationPsubdivided into homogeneous sub-cohorts. A main assumption is that the frailties give rise to a discrete, exchangeable random vector. We put ourselves in the framework of stochastic filtering to derive the conditional distribution of residual lifetimes of surviving individuals, given an observed history of failures and survivals. As a main feature of our approach, this study is based on the analysis of behaviour of the vector of ‘occupation numbers’.
A Monte Carlo approach to calculating probabilities for continuous identity by descent data
Authors: Browning Sharon
Published: October 2002

Two related individuals are identical by descent at a genetic locus if they share the same gene copy at that locus due to inheritance from a recent common ancestor. We consider idealized continuous identity by descent (IBD) data in which IBD status is known continuously along chromosomes. IBD data contains information about the relationship between the two individuals, and about the underlying crossover processes. We present a Monte Carlo method for calculating probabilities for IBD data. The method is not restricted to Haldane's Poisson process model of crossing-over but may be used with other models including the chi-square, Kosambi renewal and Sturt models. Results of a simulation study demonstrate that IBD data can be used to distinguish between alternative models for the crossover process.
Cell loss probability for M/G/1 and time-slotted queues
Authors: McDonald David , Théberge François
Published: October 2002

It is common practice to approximate the cell loss probability (CLP) of cells entering a finite buffer by the overflow probability (OVFL) of a corresponding infinite buffer queue, since the CLP is typically harder to estimate. We obtain exact asymptotic results for CLP and OVFL for time-slotted queues where block arrivals in different time slots are i.i.d. and one cell is served per time slot. In this case the ratio of CLP to OVFL is asymptotically (1-ρ)/ρ, where ρ is the use or, equivalently, the mean arrival rate per time slot. Analogous asymptotic results are obtained for continuous time M/G/1 queues. In this case the ratio of CLP to OVFL is asymptotically 1-ρ.
Age-replacement policy and optimal work size
Authors: Mi Jie
Published: October 2002

Suppose that there is a sequence of programs or jobs that are scheduled to be executed one after another on a computer. A program may terminate its execution because of the failure of the computer, which will obliterate all work the computer has accomplished, and the program has to be run all over again. Hence, it is common to save the work just completed after the computer has been working for a certain amount of time, say y units. It is assumed that it takes a certain time to perform a save. During the saving process, the computer is still subject to random failure. No matter when the computer failure occurs, it is assumed that the computer will be repaired completely and the repair time will be negligible. If saving is successful, then the computer will continue working from the end of the last saved work; if the computer fails during the saving process, then only unsaved work needs to be repeated. This paper discusses the optimal work size y under which the long-run average amount of work saved is maximized. In particular, the case of an exponential failure time distribution is studied in detail. The properties of the optimal age-replacement policy are also derived when the work size y is fixed.
Breakage and restoration in recursive trees
Authors: Tetzlaff Guillermo Tomás
Published: October 2002

Uniform sequential tree-building aggregation of n particles is analyzed together with the effect of the avalanche that takes place when a subtree rooted at a uniformly chosen vertex is removed. For large n, the expected subtree size is found to be ≃ logn both for the tree of size n and the tree that remains after an avalanche. Repeated breakage-restoration cycles are seen to give independent avalanches which attain size k(1 ≤ k ≤ n-1) with probability (k(k+1))-1 and restored trees that are recursive.
On the convexity of loss probabilities
Authors: Wolff Ronald W. , Wang Chia-Li
Published: October 2002

For the M/G/c loss system, it is well known that Erlang's loss probability is convex in the number of servers. We extend this result firstly to renewal arrivals and exponential service, then to regenerative arrivals and exponential service, and finally to an arbitrary arrival process with i.i.d. service times that are independent of the arrival process.
Distribution of the number of customers served in an M/G/1 retrial queue
Authors: Lopez-Herrero M. J.
Published: October 2002

We present a recursive method of computation for the probability that at mostkcustomers were served during the busy period of an M/G/1 retrial queue.
The stochastic equationYt+1=AtYt+Btwith non-stationary coefficients
Authors: Horst Ulrich
Published: October 2002

In this paper, we consider the stochastic sequence {Yt}t∊ℕdefined recursively by the linear relationYt+1=AtYt+Btin a random environment which is described by the non-stationary process {(At,Bt)}t∊ℕ. We formulate sufficient conditions on the environment which ensure that the finite-dimensional distributions of {Yt}t∊ℕconverge weakly to the finite-dimensional distributions of a unique stationary process. If the driving sequence {(At,Bt)}t∊ℕbecomes stationary in the long run, then we can establish a global convergence result. This extends results of Brandt (1986) and Borovkov (1998) from the stationary to the non-stationary case.
Geometric renewal convergence rates from hazard rates
Authors: Berenhaut Kenneth S. , Lund Robert
Published: October 2002

This paper studies the geometric convergence rate of a discrete renewal sequence to its limit. A general convergence rate is first derived from the hazard rates of the renewal lifetimes. This result is used to extract a good convergence rate when the lifetimes are ordered in the sense of new better than used or increasing hazard rate. A bound for the best possible geometric convergence rate is derived for lifetimes having a finite support. Examples demonstrating the utility and sharpness of the results are presented. Several of the examples study convergence rates for Markov chains.
Analysis of the busy period for the M/M/c queue: an algorithmic approach
Authors: Artalejo J. R. , Lopez-Herrero M. J.
Published: October 2002

This paper presents an algorithmic analysis of the busy period for the M/M/c queueing system. By setting the busy period equal to the time interval during which at least one server is busy, we develop a first step analysis which gives the Laplace-Stieltjes transform of the busy period as the solution of a finite system of linear equations. This approach is useful in obtaining a suitable recursive procedure for computing the moments of the length of a busy period and the number of customers served during it. The maximum entropy formalism is then used to analyse what is the influence of a given set of moments on the distribution of the busy period and to estimate the true busy period distribution. Our study supplements a recent work of Daley and Servi (1998) and other studies where the busy period of a multiserver queue follows a different definition, i.e., a busy period is the time interval during which all servers are engaged.
Some new results involving the NBU(2) class of life distributions
Authors: Li Xiaohu , Kochar Subhash C.
Published: October 2002

Some new results about the NBU(2) class of life distributions are obtained. Firstly, it is proved that the decreasing with time of the increasing concave ordering of the excess lifetime in a renewal process leads to the NBU(2) property of the interarrival times. Secondly, the NBU(2) class of life distributions is proved to be closed under the formation of series systems. Finally, it is also shown that the NBU(2) class is closed under convolution operation.
The equilibrium distribution for a generalized Sankoff-Ferretti model accurately predicts chromosome size distributions in a wide variety of species
Authors: De Arkendra , Ferguson Michael , Sindi Suzanne , Durrett Richard
Published: October 2002

Sankoff and Ferretti (1996) introduced several models of the evolution of chromosome size by reciprocal translocations, where for simplicity they ignored the existence of centromeres. However, when they compared the models to data on six organisms they found that their short chromosomes were too short, and their long chromosomes were too long. Here, we consider a generalization of their proportional model with explicit chromosome centromeres and introduce fitness functions based on recombination probabilities and on the length of the longest chromosome arm. We find a simple formula for the stationary distribution for our model which fits the data on chromosome lengths in many, but not all, species.
Late infantile neuronal ceroid lipofuscinosis: Quantitative description of the clinical course in patients with CLN2 mutations
Authors: Steinfeld Robert , Heim Peter , von Gregory Henning , Meyer Kerstin , Ullrich Kurt , Goebel Hans H. , Kohlschütter Alfried
Published: October 2002

We examined 26 individuals with clinical and electron microscopic signs of late infantile neuronal ceroid lipofuscinosis (LINCL). In 22 cases, we found both pathogenic alleles. Sixteen patients exclusively carried either one or a combination of the two common mutations R208X and IVS5–1G > C. In the remaining cases, four missense mutations could be detected, of which R127Q, N286S, and T353P represent novel, previously not described alleles. A clinical performance score was developed by rating motor, visual, and verbal functions and the incidence of cerebral seizures in 3‐month intervals during the course of the disease. A Total Disability Score was derived by summing up the single scores for motor, visual, and verbal functions. The 16 individuals with the two common mutations were grouped together (referred to as standard patients), and the 5th, 50th, and 95th centiles were calculated and graphically depicted over time. The scores for motor function and language ability dropped earliest and progressed very similarly in the standard patients. The performance curves of two children with the N286S mutation slightly diverged from the 95th centile. However, the performance curves of one patient with atypical LINCL carrying the R127Q mutation fell far beyond the 95th centile. The presented performance rating clearly and quantitatively delineates the disease course of the LINCL patients and hence offers a useful tool for clinical evaluation of future therapeutic interventions. In addition, the described performance score system can be applied to other types of neuronal ceroid lipofuscinoses and could be adapted to various other neurodegenerative diseases of childhood. © 2002 Wiley‐Liss, Inc.
How does interferon work? Does it even matter?
Authors: Sondak Vernon K.
Published: October 2002

Adjuvant therapy for patients with melanoma using interferon α remains controversial despite numerous randomized clinical trials. In the current study, Kirkwood et al. present the results of a biologic companion trial to Intergroup Trial E1690, which compared high‐dose and low‐dose interferon α2b with observation after surgery. The implications for current practice and future clinical trials are discussed.

See also pages 1102‐12.
Role of metallothioneins in irradiated human rectal carcinoma
Authors: Bouzourene Hanifa , Chaubert Pascal , Gebhard Sandra , Bosman Fred T. , Coucke Philippe
Published: October 2002

BACKGROUND

Metallothioneins (MT) are low‐molecular weight, metal‐binding proteins that play a role in cellular proliferation and differentiation, as well as in cellular defense mechanisms. They act as scavengers of free radicals produced by irradiation. A number of in vitro and in vivo studies have linked overexpression of cellular MT with tumor cell resistance to radiation. This is the first study that investigates whether MT expression is involved in the radioresistance of rectal carcinoma.

METHODS

Using a mouse monoclonal antibody, MT expression was analyzed by immunohistochemistry on surgical samples (n = 85) from 85 patients with locally advanced rectal carcinoma who were treated preoperatively with a hyperfractionated and accelerated radiotherapy schedule and on tumor biopsies (n = 13) obtained before treatment. The potential correlations between MT expression and pathologic variables and survival were examined.

RESULTS

MT were expressed strongly in both the cytoplasm and nucleus of tumor cells in 7 biopsy and 42 surgical samples. A comparison of MT expression in biopsy and surgical specimens showed that MT expression did not change after irradiation in most cases. Against all expectations, MT were expressed more frequently in tumors from responders than in those from the nonresponders (P = 0.02). There was no correlation between MT expression and tumor stage, histology after radiotherapy, or survival.

CONCLUSION

These findings do not support the hypothesis that MT overexpression at the end of radiotherapy is a marker for radiation resistance. Cancer 2002;95:1003–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10780
Salvage chemotherapy for recurrent spinal cord ependymona
Authors: Chamberlain Marc C.
Published: October 2002

BACKGROUND

Ependymomas are reported to constitute 4% of all primary central nervous system (CNS) malignancies in adults, 30% of which occur in the spinal cord. A prospective Phase II study to determine toxicity and response to chronic oral etoposide in patients with recurrent low‐grade intramedullary spinal cord ependymoma (SCE) was conducted.

METHODS

Ten patients (6 males and 4 females with a median age of 30 years) with recurrent SCE were treated with oral etoposide (50mg/m2/day given daily for 21 days followed by a 14‐day break and then repeated constituted a cycle of therapy). All patients had failed surgery and radiotherapy and four patients had failed one prior chemotherapy. Blood counts were obtained weekly, and neurologic examination and a chemistry panel were performed monthly. Contrast‐enhanced magnetic resonance imaging of the spine was performed every 8 weeks after a cycle of etoposide and before the next cycle of chemotherapy was initiated.

RESULTS

Treatment‐related complications included alopecia in 9 patients, nonbloody diarrhea in 6 patients, a baseline weight loss of > 10% in 5 patients, Grade (according to the National Cancer Institute Common Toxicity Scale) 3‐4 neutropenia in 3 patients, Grade 3‐4 thrombocytopenia in 3 patients, and Grade 3‐4 anemia in 2 patients. There were no treatment‐related deaths reported. After 1 cycle of etoposide, 3 patients (30%) demonstrated progressive disease, 2 patients (20%) achieved a partial response, and 5 patients (50%) maintained stable disease. The overall median response or stable disease duration (disease‐free progression) was 15 months (range, 2.5–45+ months). The overall median survival was 17.5 months (range, 3–45+ months).

CONCLUSIONS

Chronic oral etoposide appears to be well tolerated, has modest toxicity, and had apparent activity in the small cohort of adults in the current study with surgically and medically refractory, recurrent, intradural intramedullary SCE. Cancer 2002;95:997–1002. © 2002 American Cancer Society.

DOI 10.1002/cncr.10826
A generalized lot sizing model for the process cycling problem
Authors: Matthews John P.
Published: October 2002

Most scheduling/lot sizing models for the single‐machine problem assume that aggregate demand equals aggregate production; and that backorders are to be avoided. Where working inventories are low, the scheduler may wish to avoid short production runs and willingly incur some backorder penalties so as to increase the length of production runs and reduce setup costs per unit of time. The model proposed here identifies optimal lot sizes with respect to the backorder/setup cost relationships. Use of the model will result in an optimally balanced inventory even when aggregate inventory levels are changing.
Load‐limited order release in job shop scheduling systems
Authors: Kanet John J.
Published: October 2002

This report examines the practice of using work load limits to control the release of orders to a job shop. Load limits function in the following general way. Whenever the inventory of work at a work center exceeds some critical value (its “load limit”), further release of orders which are routed to that work center are blocked from entering the shop. After the inventory is “worked off,” release of work to the shop gateways is again permitted. Load‐limited order release is intuitively appealing because it appears to be a method for reducing system inventory and flow times. The practice of load limiting order release is becoming popularized by some of the recent production planning software products now on the market. A notable example is OPT. In this report, analytical results for an M/M/1 queueing model, along with existing simulation studies of multi‐machine job shops are interpreted to form a theory about the effects of using load limits.

The major finding here is the proposition that system flow time, inventory, and order tardiness all deteriorate to the extent that load limits introduce idle time into the schedule. Based on the arguments presented here, a very cautious approach toward the use of input control schemes for anywhere but gateway work centers would be advised. The conclusions drawn here are to a great extent arrived at by interpreting the research results of others, so there is a clear need for further research which tests these assertions in a more direct and controlled way.
A risk/benefit analysis of sourcing strategies: Single vs. multiple sourcing
Authors: Treleven Mark , Bergman Schweikhart Sharon
Published: October 2002

As more companies recognize the importance of quality to their long‐term survival they are, among other actions, attempting to formulate sourcing strategies that are consistent with their quality strategies and policies. The two major sourcing strategy options available are multiple and single sourcing. Unfortunately, the literature has lagged behind the practitioner's needs for direction in this area and, therefore, provides little help to managers wrestling with this important and difficult issue.

This study uses a risk/benefit approach to carefully examine sourcing strategies from the perspective of the purchaser, or vendee. To ensure a complete and accurate identification and description of the various factors which influence sourcing decisions, intensive interviews were conducted with purchasing and quality personnel at the Manager and Director levels within a number of large, international organizations. Most of the interview data was collected at Control Data, General Mills, Honeywell, Pillsbury, and Unisys. This data was supplemented with information from managers at other companies and the literature which exists in this area.

The paper begins by describing the various definitions of single sourcing and the definition which is used for the purposes of this paper. Next, the factors which should influence managers' sourcing decisions are identified and classified into five risk/benefit categories. These categories are then incorporated into a conceptual risk/benefit assessment model for managers to use in the evaluation of their sourcing strategy. The conceptual model is an adaptation of the additive rating model used for facility location decisions [1].

It is suggested that the model would most appropriately be applied at the family of parts level. Application at this level would likely result in different sourcing strategies for different part families (and different organizations), depending on the characteristics of each family. This is consistent with the conclusions of Hahn, Kim and Kim [10].

This work contributes to the literature in several ways. The first of these contributions is the complete definition of the various levels of single sourcing. Compilation of the many factors associated with both single and multiple sourcing decisions is another contribution. Prior to this research, the identification of these factors had been incomplete, limited to single sourcing, fragmented across a number of articles, and disseminated largely by word of mouth. The construction of a framework within which these factors can be categorized is also new to the literature. The final contribution of this research is the development of a conceptual model to analyze the combined effects of these factors.
Multiplant manufacturing strategies among the fortune 500
Authors: Schmenner Roger W.
Published: October 2002

This paper identifies and examines four distinct multiplant strategies prevailing within the nation's largest manufacturing companies. These multiplant strategies govern the charters under which plants operate, thus helping to insure focused factory operations. Using detailed data drawn from over 300 plants, the paper reports on the apparent attractiveness of different strategies to different industry groups and singles out those specific plant characteristics which Fortune 500 plants attribute most often to each strategy. This information can aid in the assignment of plant charters, within company operating divisions.
Using decision modeling to examine management consensus: A study of a maintenance management control system
Authors: Stahl Michael J. , Zimmerer Thomas W.
Published: October 2002

Using a decision modeling approach, this research examined differences across levels of management in a large construction company concerning the criteria for a maintenance management control system. The six criteria were cost efficiency, productivity improvement, materials management, unification of work control, planning and scheduling, and information and retrieval. A decision‐making exercise was constructed that asked the respondent to make recommendations concerning the approval or disapproval of 32 hypothetical maintenance management systems. Among the 60 managers who completed the exercise, there was evidence of significant differences across levels of management concerning the criteria for a maintenance management control system. Additionally, distortions were observed between what the managers said was important and what their decisions indicated. These data demonstrate that the decision modeling approach presented can be effectively used to examine the degree of consensus within an organization.
A note on stopping rules for rolling production scheduling
Authors: Kropp Dean H. , Carlson Robert C. , Beckman Sara L.
Published: October 2002

Instead of solving fixed horizon production scheduling problems with specified terminal inventory conditions, we use forecasting to extend the problem horizon until stopping rule conditions are met. Major questions for this procedure relate to how to provide data for the extended problem and when to stop the process. We provide extensive computational results indicating that relatively simple methods perform quite well.