bluuebunny/crossref_metadata_2025 huggingface dataset:
Useful approximations for converted‐wave AVO
Authors: Ramos Antonio C. B. , Castagna John P.
Published: October 2002

Converted‐wave amplitude versus offset (AVO) behavior may be fit with a cubic relationship between reflection coefficient and ray parameter. Attributes extracted using this form can be directly related to elastic parameters with low‐contrast or high‐contrast approximations to the Zoeppritz equations. The high‐contrast approximation has the advantage of greater accuracy; the low‐contrast approximation is analytically simpler. The two coefficients of the low‐contrast approximation are a function of the average ratio of compressional‐to‐shear‐wave velocity (α/β) and the fractional changes in S‐wave velocity and density (Δβ/β and Δρ/ρ). Because of its simplicity, the low‐contrast approximation is subject to errors, particularly for large positive contrasts in P‐wave velocity associated with negative contrasts in S‐wave velocity. However, for incidence angles up to 40° and models confined to |Δβ/β| < 0.25, the errors in both coefficients are relatively small. Converted‐wave AVO crossplotting of the coefficients of the low‐contrast approximation is a useful interpretation technique. The background trend in this case has a negative slope and an intercept proportional to the α/β ratio and the fractional change in S‐wave velocity. For constant α/β ratio, an attribute trace formed by the weighted sum of the coefficients of the low‐contrast approximation provides useful estimates of the fractional change in S‐wave velocity and density. Using synthetic examples, we investigate the sensitivity of these parameters to random noise. Integrated P‐wave and converted‐wave analysis may improve estimation of rock properties by combining extracted attributes to yield fractional contrasts in P‐wave and S‐wave velocities and density. Together, these parameters may provide improved direct hydrocarbon indication and can potentially be used to identify anomalies caused by low gas saturations.
Predictors for chemotherapy-related severe or febrile neutropenia: a review of the clinical literature
Authors: Wilson-Royalty Michele , Lawless Grant , Palmer Cynthia , Brown Ruth
Published: October 2002

Purpose. This paper summarizes a literature review of the risk factors and predictors for chemo-therapy-related severe or febrile neutropenia (grades 3 and 4). It explores the extent to which the literature supports the current ASCO guidelines, and assesses the feasibility of developing a predictive algorithm for patients who would benefit from rHuG-CSF (Neupogen).

Methods. An electronic literature search for English articles and abstracts identified 718 abstracts for review. From these, 121 articles were reviewed in depth. The review captured risk factors and predictors for grade 3-4 and/or febrile neutropenia, study design, patient characteristics, chemotherapy treatment, and the incidence of grade 3-4 and/or febrile neutropenia.

Results. Twenty-eight potential risk factors and predictors for severe or febrile neutropenia among cancer patients were identified and could be classified as patient-related, treatment-related, or disease-related characteristics. Some results were inconsistent across studies due to a lack of standardized methods of assessment and reporting. Approximately 1/3 of the factors were mentioned in more than one study and provided information on the statistical significance of findings. Several factors had cross-study support of their value and confirmed previous findings. Strong predictors of severe/febrile neutropenia included advanced age, performance status, myelosuppressive chemotherapy regimen, early low blood counts, the depth of the absolute neutrophil count (ANC) nadir, and a precipitous, early drop in blood counts of all hematopoietic cell types.

Conclusions. This literature review identified several key predictors and risk factors for development of grades 3 and 4 neutropenia in cancer patients. While additional confirmation is needed, there is sufficient consistency in the literature to support use of risk factors to identify patients who may need supportive care. Some of these risk factors were included in the ASCO CSF guidelines for the use of prophylactic support such as G-CSF; however, the ASCO publications have not included other important risk factors, such as age and early reduced ANC levels.
Alteration of p53 Pathway in Squamous Cell Carcinoma of the Head and Neck: Impact on Treatment Outcome in Patients Treated With Larynx Preservation Intent
Authors: Osman Iman , Sherman Eric , Singh Bhuvanesh , Venkatraman Ennapadam , Zelefsky Michael , Bosl George , Scher Howard , Shah Jatin , Shaha Ashok , Kraus Dennis , Cordon-Cardo Carlos , Pfister David G.
Published: October 2002

PURPOSE: To identify the role of p53 pathway alteration(s) as predictors of treatment outcome in patients with advanced, resectable, squamous cell carcinoma (SCC) of the larynx and pharynx treated with larynx preservation (LP) intent.

PATIENTS AND METHODS: Seventy-one patients treated on two consecutive LP protocols were studied based on availability of representative tissues. We analyzed the expression pattern of p53, its upstream regulator mdm2, and downstream transcriptional target p21/WAF1 by immunohistochemistry. Positive phenotype was defined as ≥ 20% of tumor cells showing nuclear immunoreactivity. Results were correlated with treatment outcomes.

RESULTS: Positive phenotype was observed in 35 (49%) of 71 cases for p53, in 52 (74%) of 70 for mdm2, and in 37 (54%) of 68 for p21. There was no correlation between p53 phenotype and p21 nuclear accumulation. The mdm2-negative phenotype was most predictive of major response at the primary tumor site (P = .088). p53-positive phenotype was associated with worse local control with LP (LCLP; 49% v 23%, P = .053) and inferior overall survival (OS; 51% v 29%, P = .017) at 5 years. On Cox regression analysis, p53-positive phenotype predicted inferior OS (P = .033) and showed a trend for worse LCLP (P = .102). When analyzed in a multivariate model as continuous variables, p53 showed a stronger correlation with inferior OS (P < .01), and mdm2 was associated with worse OS (P < .01).

CONCLUSION: Among the three markers studied, our data support p53 phenotype as the most informative predictor of unfavorable outcomes in the LP setting, and suggest a role for mdm2 phenotype that requires further exploration. Our analysis does not support a p53-dependent mechanism for p21 expression. Prospective and larger studies are necessary before integration of these molecular markers as part of molecular staging and predictors for organ preservation or other outcomes.
Age at Diagnosis and Outcome for Women With Ductal Carcinoma-In-Situ of the Breast: A Critical Review of the Literature
Authors: Vicini Frank A. , Recht Abram
Published: October 2002

PURPOSE: Patients younger than 35 to 45 years old at the time of diagnosis of invasive breast cancer have been found to have a worse prognosis than older patients in many studies. However, the impact of patient age at diagnosis on the outcome of treatment with either lumpectomy and radiation therapy (RT) or mastectomy for patients with ductal carcinoma-in-situ (DCIS) of the breast has not been extensively analyzed.

MATERIALS AND METHODS: Articles addressing the effect of patient age at diagnosis on the outcome of treatment of DCIS with lumpectomy and RT or mastectomy were identified through the MEDLINE and CancerLit databases and reference lists of relevant articles. Studies were reviewed to determine the impact of patient age at diagnosis on clinical and pathologic features of DCIS, the influence of age on outcome after lumpectomy and RT, and the impact of age on outcome after mastectomy.

RESULTS: DCIS in younger patients more frequently contains adverse prognostic pathologic factors and extends over a greater distance in the breast than in older patients. In series with adequate follow-up, younger patients treated with lumpectomy and RT had a significantly higher rate of local recurrence than older patients, especially for invasive local recurrences. Some studies have suggested that careful attention to margin status and excising larger volumes of tissue can reduce this difference substantially. No available data show that younger patients have better long-term cancer-free survival rates if treated by mastectomy rather than lumpectomy and RT.

CONCLUSION: Successful treatment of younger patients with DCIS with lumpectomy and RT requires careful attention to patient evaluation, selection, and surgical technique. When this is done, age at diagnosis should not be a contraindication to breast-conserving therapy.
Trimetrexate in Relapsed T-Cell Lymphoma With Skin Involvement
Authors: Sarris A. H. , Phan A. , Duvic M. , Romaguera J. , McLaughlin P. , Mesina O. , King K. , Medeiros L. J. , Rassidakis G. Z. , Samuels B. , Cabanillas F.
Published: October 2002

PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX) enters cells by passive diffusion and is not polyglutamylated, its activity in relapsed T-cell lymphoma was investigated.

PATIENTS AND METHODS: Eligible patients had histologically confirmed relapsed T-cell lymphoma involving the skin, had received more than one previous regimen, were older than 16 years, had normal organ function, and had no CNS disease or serious infections, including human immunodeficiency virus. TMTX (200 mg/m2) was given intravenously every 14 days without topical or systemic corticosteroids. Patients who responded received up to 12 doses.

RESULTS: Twenty patients were assessable for response. Median age was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sézary syndrome (14 with large-cell transformation), and two had peripheral T-cell lymphoma. Serum lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0 mg/L in 35% of patients. The median number of previous regimens was three (range, two to 15) and included MTX in five patients. Disease was refractory to the regimen immediately preceding TMTX in 85% of patients. Responses were complete in one and partial in eight patients (overall response rate, 45%). Two of five patients previously treated with MTX responded. Grade 3 or 4 mucositis was observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils less than 100/μL after 4%, and platelets less than 10,000/μL after 3% of TMTX doses.

CONCLUSION: TMTX is active with acceptable toxicity in this population and merits further investigation.
Incipient Angiogenesis in Barrett’s Epithelium and Lymphangiogenesis in Barrett’s Adenocarcinoma
Authors: Auvinen Merja I. , Sihvo Eero I.T. , Ruohtula Terhi , Salminen Jukka T. , Koivistoinen Aki , Siivola Päivi , Rönnholm Ragna , Rämö Juhani O. , Bergman Mathias , Salo Jarmo A.
Published: October 2002

PURPOSE: Barrett’s esophagus (BE), a precancerous condition for Barrett’s adenocarcinoma, is classically characterized by flames of salmon-colored mucosa extending into normal pale esophageal mucosa. This flaming is thought to be a consequence of continuous erosis of mucosa caused by chronic reflux. Another characteristic feature of Barrett’s adenocarcinoma patients is the frequent development of lymph node metastases. We addressed whether onset of angiogenesis occurs in BE and if the lymphatic system might provide a route for Barrett’s adenocarcinoma cells to infiltrate regular lymph nodes.

PATIENTS AND METHODS: Fifteen surgically resected Barrett’s dysplasia or adenocarcinoma patients were included. Immunohistochemistry and a modified whole mount analysis were used.

RESULTS: The incipient angiogenesis originates from the pre-existing vascular network in the lamina propria and infiltrates Barrett’s epithelium, giving its ominous salmon-red color. Barrett’s epithelium–specific goblet cells express vascular endothelial growth factor (VEGF)-A. The immature blood vessels show a relative absence of smooth muscle actin (SMA)-positive mural cells and express VEGF receptor (VEGFR)-2 and matrix metalloproteinase (MMP)-9 on their exterior. Coexpression of VEGF-C and its receptor VEGFR-3 on lymphatic vessels is demonstrated.

CONCLUSION: BE is strongly neovascularized not eroded. This novel concept of a molecular mechanism of the origin of BE might emphasize why precancerous BE can give rise to the more cancerous dysplasia and Barrett’s adenocarcinoma stages. In addition, adenocarcinoma cells induce lymphangiogenesis. The new lymphangiogenic vessels might provide a systemic route for adenocarcinoma cells to invade circulation and induce lymph node metastasis.
Chronic Arm Morbidity After Curative Breast Cancer Treatment: Prevalence and Impact on Quality of Life
Authors: Kwan Winkle , Jackson Jeremy , Weir Lorna M. , Dingee Carol , McGregor Greg , Olivotto Ivo A.
Published: October 2002

PURPOSE: To determine the prevalence of and contributing factors for chronic arm morbidity including lymphedema in breast cancer patients after treatment and to assess the impact of arm morbidity on quality of life (QOL).

PATIENTS AND METHODS: A four-question screening questionnaire was developed and mailed to a random sample of 744 breast cancer patients treated curatively in two cancer centers from 1993 to 1997. Patients were without recurrence and at least 2 years from diagnosis. Respondents were classified as with or without arm-related symptoms on the basis of the survey. Stratified random samples from each group were then invited for a detailed assessment of their symptoms and signs, including the presence of lymphedema. Their QOL was assessed by the European Organization for Research and Treatment of Cancer QOL Questionnaire C-30 and by a detailed arm problem questionnaire that assessed various aspects of daily arm functioning.

RESULTS: Approximately half of all screened patients were symptomatic and 12.5% of all assessed patients had lymphedema. Axillary dissection (AD) and axillary radiotherapy (RT) after dissection were statistically significantly related to the occurrence of arm symptoms (odds ratio for AD = 3.3, P < .001; odds ratio for RT = 3.1, P < .001). Symptomatic patients and patients with lymphedema both had impaired QOL compared with asymptomatic patients.

CONCLUSION: Treatment for breast cancer is associated with considerable arm morbidity, which has a negative impact on QOL. Arm morbidity should be carefully monitored in future studies involving local treatment modalities for breast cancer.
Vaccination of Metastatic Melanoma Patients With Autologous Tumor-Derived Heat Shock Protein gp96-Peptide Complexes: Clinical and Immunologic Findings
Authors: Belli Filiberto , Testori Alessandro , Rivoltini Licia , Maio Michele , Andreola Giovanna , Sertoli Mario Roberto , Gallino Gianfrancesco , Piris Adriano , Cattelan Alessandro , Lazzari Ivano , Carrabba Matteo , Scita Giorgio , Santantonio Cristina , Pilla Lorenzo , Tragni Gabrina , Lombardo Claudia , Arienti Flavio , Marchianò Alfonso , Queirolo Paola , Bertolini Francesco , Cova Agata , Lamaj Elda , Ascani Lucio , Camerini Roberto , Corsi Marco , Cascinelli Natale , Lewis Jonathan J. , Srivastava Pramod , Parmiani Giorgio
Published: October 2002

PURPOSE: To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, MA) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients.

PATIENTS AND METHODS: Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed.

RESULTS: No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders.

CONCLUSION: Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.
Cisplatin, Gemcitabine, and Ifosfamide As Weekly Therapy: A Feasibility and Phase II Study of Salvage Treatment for Advanced Transitional-Cell Carcinoma
Authors: Pagliaro Lance C. , Millikan Randall E. , Tu Shi-Ming , Williams Dallas , Daliani Danai , Papandreou Christos N. , Logothetis Christopher J.
Published: October 2002

PURPOSE: We investigated the feasibility, safety, and antitumor activity of weekly gemcitabine given in combination with low doses of cisplatin and ifosfamide in previously treated patients with advanced transitional-cell carcinoma (TCC) of the urothelium.

PATIENTS AND METHODS: Patients with measurable, metastatic or unresectable TCC who had received one or two prior chemotherapy regimens were eligible. On a 28-day course, doses of cisplatin 30 mg/m2, gemcitabine 800 mg/m2, and ifosfamide 1 g/m2 were given on day 1 and then repeated on day 8 and day 15 unless there was dose-limiting hematologic toxicity.

RESULTS: Fifty-one patients were registered; 10 patients participated in a pilot study, after which 41 patients were registered onto the phase II protocol. Forty-eight patients (94.1%) had dose-limiting hematologic toxicity on day 8 or day 15. Nonhematologic toxicity of grade 3 or greater consisted mainly of nausea and vomiting (seven patients, 13.7%) and infection (seven patients, 13.7%). Responses could be assessed in 49 of 51 eligible patients; two complete responses (4.1%) and 18 partial responses (36.7%) were observed for an overall response rate of 40.8% (exact 95% confidence interval, 27% to 56%).

CONCLUSION: This regimen of cisplatin, gemcitabine, and ifosfamide is not feasible for weekly administration because of hematologic toxicity. Nevertheless, there was promising activity with only two doses per 28-day cycle. On the basis of these results, we have initiated a phase II trial of this combination given as a single dose every 14 days in patients with untreated, metastatic urothelial carcinoma.
Further approaches to computing fundamental characteristics of birth-death processes
Authors: Ball Frank , Stefanov Valeri T.
Published: October 2002

General and unifying approaches are discussed for computing fundamental characteristics of both continuous-time and discrete-time birth-death processes. In particular, an exponential family framework is used to derive explicit expressions, in terms of continued fractions, for joint generating functions of first-passage times and a whole collection of associated random quantities, and a random sum representation is used to obtain formulae for means, variances and covariances of stopped reward functions defined on a birth-death process.
The distributions of cluster functionals of extreme events in a dth-order Markov chain
Authors: Yun Seokhoon
Published: October 2002

The paper concerns the asymptotic distributions of cluster functionals of extreme events in a dth-order stationary Markov chain {Xn, n = 1,2,…} for which the joint distribution of (X1,…,Xd+1) is absolutely continuous. Under some distributional assumptions for {Xn}, we establish weak convergence for a class of cluster functionals and obtain representations for the asymptotic distributions which are well suited for simulation. A number of examples important in applications are presented to demonstrate the usefulness of the results.
Optimal control of a dam using Pλ,τM policies and penalty cost when the input process is a compound Poisson process with positive drift
Authors: Abdel-Hameed Mohamed
Published: October 2002

In this paper we consider the optimal control of an infinite dam using policies assuming that the input process is a compound Poisson process with a non-negative drift term, and using the total discounted cost and long-run average cost criteria. The results of Lee and Ahn (1998) as well as other well-known results are shown to follow from our results.
An insensitivity property of Lundberg's estimate for delayed claims
Authors: Brémaud Pierre
Published: October 2002

This short note shows that the Lundberg exponential upper bound in the ruin problem of non-life insurance with compound Poisson claims is also valid for the Poisson shot noise delayed-claims model, and that the optimal exponent depends only on the distribution of the total claim per accident, not on the time it takes to honour the claim. This result holds under Cramer's condition.
Martingales versus PDEs in finance: an equivalence result with examples
Authors: Heath David , Schweizer Martin
Published: October 2002

We provide a set of verifiable sufficient conditions for proving in a number of practical examples the equivalence of the martingale and the PDE approaches to the valuation of derivatives. The key idea is to use a combination of analytic and probabilistic assumptions that covers typical models in finance falling outside the range of standard results from the literature. Applications include Heston's stochastic volatility model and the Black-Karasinski term structure model.
Simple ratio prophet inequalities for a mortal with multiple choices
Authors: Assaf David , Samuel-Cahn Ester
Published: October 2002

Let Xi ≥ 0 be independent, i = 1,…, n, with known distributions and let Xn*= max(X1,…,Xn). The classical ‘ratio prophet inequality’ compares the return to a prophet, which is EXn*, to that of a mortal, who observes the Xis sequentially, and must resort to a stopping rule t. The mortal's return is V(X1,…,Xn) = max EXt, where the maximum is over all stopping rules. The classical inequality states that EXn* < 2V(X1,…,Xn). In the present paper the mortal is given k ≥ 1 chances to choose. If he uses stopping rules t1,…,tk his return is E(max(Xt1,…,Xtk)). Let t(b) be the ‘simple threshold stopping rule’ defined to be the smallest i for which Xi ≥ b, or n if there is no such i. We show that there always exists a proper choice of k thresholds, such that EXn* ≤ ((k+1)/k)Emax(Xt1,…,Xtk)), where ti is of the form t(bi) with some added randomization. Actually the thresholds can be taken to be thej/(k+1) percentile points of the distribution of Xn*, j = 1,…,k, and hence only knowledge of the distribution of Xn* is needed.
On probability generating functions for waiting time distributions of compound patterns in a sequence of multistate trials
Authors: Fu James C. , Chang Y. M.
Published: October 2002

Probability generation functions of waiting time distributions of runs and patterns have been used successfully in various areas of statistics and applied probability. In this paper, we provide a simple way to obtain the probability generating functions for waiting time distributions of compound patterns by using the finite Markov chain imbedding method. We also study the characters of waiting time distributions for compound patterns. A computer algorithm based on Markov chain imbedding technique has been developed for automatically computing the distribution, probability generating function, and mean of waiting time for a compound pattern.
Selecting the last success in Markov-dependent trials
Authors: Hsiau Shoou-Ren , Yang Jiing-Ru
Published: October 2002

In a sequence of Markov-dependent trials, the optimal strategy which maximizes the probability of stopping on the last success is considered. Both homogeneous Markov chains and nonhomogeneous Markov chains are studied. For the homogeneous case, the analysis is divided into two parts and both parts are realized completely. For the nonhomogeneous case, we prove a result which contains the result of Bruss (2000) under an independence structure.
Markov-modulated linear fluid networks with Markov additive input
Authors: Kella Offer , Stadje Wolfgang
Published: October 2002

We consider a network of dams to which the external input is a multivariate Markov additive process. For each state of the Markov chain modulating the Markov additive process, the release rates are linear (constant multiple of the content level). Each unit of material processed by a given station is then divided into fixed proportions each of which is routed to another station or leaves the system. For each state of the modulating process, this routeing is determined by some substochastic matrix. We identify simple conditions for stability and show how to compute transient and stationary characteristics of such networks.
An asymptotic expansion for the optimal stopping boundary in problems with non-linear costs of observation
Authors: Irle A. , Kubillus O. , Paulsen V.
Published: October 2002

The assumption of linear costs of observation usually leads to optimal stopping boundaries which are straight lines. For non-linear costs of observation, the question arises of how the shape of cost functions influences the shape of optimal stopping boundaries. In Irle (1987), (1988) it was shown that, under suitable assumptions on c, for the problem of optimal stopping (Wt + x)+ - c(s + t), t ∊ [0,∞), the optimal stopping boundary h(t) can be enscribed between k1/c'(t) and k2/c'(t) for some constants k1, k2. In this paper we find the exact asymptotic expansion h(t) = 1/(4c'(t))(1 + o(1)).
The annihilating process
Authors: O'Hely Martin , Sudbury Aidan
Published: October 2002

An annihilating process is an interacting particle system in which the only interaction is that a particle may kill a neighbouring particle. Since there is no birth and no movement, once a particle has no neighbours its site remains occupied for ever. It is shown that with initial configuration ℤ the distribution of particles at all times is a renewal process and that the probability that a site remains occupied for all time tends to 1/e. Time-dependent behaviour is also calculated for the tree 𝕋r.
A weak derivative approach to optimization of threshold parameters in a multicomponent maintenance system
Authors: Heidergott Bernd
Published: October 2002

We consider a multicomponent maintenance system controlled by an age replacement policy: when one of the components fails, it is immediately replaced; all components older than a threshold age θ are preventively replaced. Costs are associated with each maintenance action, such as replacement after failure or preventive replacement. We derive a weak derivative estimator for the derivative of the cost performance with respect to θ. The technique is quite general and can be applied to many other threshold optimization problems in maintenance. The estimator is easy to implement and considerably increases the efficiency of a Robbins-Monro type of stochastic approximation algorithm. The paper is self-contained in the sense that it includes a proof of the correctness of the weak derivative estimation algorithm.
Moment convergence in conditional limit theorems
Authors: Janson Svante
Published: October 2002

Consider a sum ∑1NYi of random variables conditioned on a given value of the sum ∑1NXi of some other variables, where Xi and Yi are dependent but the pairs (Xi,Yi) form an i.i.d. sequence. We consider here the case when each Xi is discrete. We prove, for a triangular array ((Xni,Yni)) of such pairs satisfying certain conditions, both convergence of the distribution of the conditioned sum (after suitable normalization) to a normal distribution, and convergence of its moments. The results are motivated by an application to hashing with linear probing; we give also some other applications to occupancy problems, random forests, and branching processes.
On the convergence and limits of certain matrix sequences arising in quasi-birth-and-death Markov chains
Authors: He Qi-Ming , Neuts Marcel F.
Published: October 2002

We study the convergence of certain matrix sequences that arise in quasi-birth-and-death (QBD) Markov chains and we identify their limits. In particular, we focus on a sequence of matrices whose elements are absorption probabilities into some boundary states of the QBD. We prove that, under certain technical conditions, that sequence converges. Its limit is either the minimal nonnegative solution G of the standard nonlinear matrix equation, or it is a stochastic solution that can be explicitly expressed in terms of G. Similar results are obtained relative to the standard matrix R that arises in the matrix-geometric solution of the QBD. We present numerical examples that clarify some of the technical issues of interest.
Supernumerary digital flexion creases: An additional clinical manifestation of Alagille syndrome
Authors: Kamath Binita M. , Loomes Kathleen M. , Oakey Rebecca J. , Krantz Ian D.
Published: October 2002

Alagille syndrome (AGS; OMIM 118450) is a complex dominantly inherited multisystem disorder involving the liver, heart, eyes, facies, skeleton, and other systems. Criteria for the clinical diagnosis have been established as the presence of bile duct paucity on liver biopsy in association with three of five major clinical findings (cholestasis, butterfly vertebrae, posterior embryotoxon, congenital heart disease, and facial features). Jagged1 has been identified as the AGS disease gene. Jagged1 is a large gene, with no mutational hot spots, making molecular testing difficult at this time. Other clinical features would prove helpful in establishing the diagnosis in the absence of molecular confirmation. Supernumerary digital flexion creases have been identified in 16/46 (35%) of AGS probands examined through the Alagille Syndrome Diagnostic Center at the Children's Hospital of Philadelphia. Although digital abnormalities have been noted in AGS in the past, including short distal phalanges and fifth finger clinodactyly, digital crease abnormalities have never before been reported. Supernumerary digital creases have been reported in less than 1% of the general population. The presence of extra and missing digital creases in individuals with normal joint anatomy, their occurrence in several syndromes, and mouse in situ expression studies indicate that genetic factors contribute to digital crease formation. However, these factors are poorly understood. Hypotheses regarding the origin of flexion creases are discussed. The identification of supernumerary digital creases in one‐third of AGS probands provides another diagnostic aid and allows for speculation of the role of Jagged1 in the molecular development of digital crease patterns. © 2002 Wiley‐Liss, Inc.
Analysis of craniofacial development in children with hypohidrotic ectodermal dysplasia
Authors: Johnson Euphemia LaRee , Roberts Michael W. , Guckes Albert D. , Bailey L'Tanya J. , Phillips Ceib L. , Wright J. Timothy
Published: October 2002

Ectodermal dysplasias (ED) are a heterogeneous group of inheritable disorders characterized by abnormal development of embryologic ectoderm derivatives. The purposes of this study were to: 1) create baseline cephalometric norms for male children with ED; 2) assess craniofacial growth and development in hypohidrotic ED male children with severe hypodontia, compared with non‐ED children with class I dental relationships; 3) compare the craniofacial morphology of titanium dental implant‐treated ED males with non‐implant‐treated ED males; and 4) correlate the severity of hypodontia to craniofacial dysmorphology. Cephalometric radiographs of class I individuals and implant‐treated and nontreated ED groups were used to evaluate craniofacial morphology. Traditional cephalometric landmarks and measurements were used to compare groups using the generalized estimate equation analysis. Age, gender, and the number of permanent maxillary teeth present had a significant (P = .01) explanatory relationship with the craniofacial measures when comparing untreated ED children to norms. Mean craniofacial differences between ED and non‐ED children still existed when the explanatory effects of these variables were controlled, indicating dysmorphology in several craniofacial structures (e.g., cranial base, mandibular length). The number of missing maxillary permanent teeth was significantly related with craniofacial dysmorphology in the ED population. Craniofacial morphology did not differ significantly between implant‐treated and nontreated ED children, suggesting that treatment with intraosseous dental implants, as applied in this population, did not rescue normal craniofacial growth and development. © 2002 Wiley‐Liss, Inc.
Association of hypoxia‐inducible factors 1α and 2α with activated angiogenic pathways and prognosis in patients with endometrial carcinoma
Authors: Sivridis Efthimios , Giatromanolaki Alexandra , Gatter Kevin C. , Harris Adrian L. , Koukourakis Michael I. ,   for the Tumor and Angiogenesis Research Group
Published: October 2002

BACKGROUND

Hypoxia‐inducible factor 1α (HIF‐1α) and HIF‐2α are essential regulatory proteins for the adaptation of tumor cells to hypoxia, and they stimulate angiogenesis through activation of the vascular endothelial growth factor (VEGF) gene.

METHODS

HIF‐1α and HIF‐2α proteins were studied immunohistochemically in a group of 81 patients with Stage I endometrial adenocarcinoma of the endometrioid cell type. The results were correlated with intratumoral angiogenesis, the expression of the angiogenic factors VEGF and thymidine phosphorylase (TP), and the VEGF/receptor (VEGF/KDR) complex. Relations also were sought with estrogen receptor (ER) and progesterone receptor (PR), with the apoptosis‐related proteins bcl‐2 and p53, with several histopathologic parameters, and with patient prognosis. In addition, a sample of 25 normal endometria at various phases of the menstrual cycle was studied for the presence of HIF‐1α and HIF‐2α.

RESULTS

HIF‐1α expression was detected in 49% of endometrial carcinomas. The expression was cytoplasmic or mixed nuclear/cytoplasmic. HIF‐1α expression was associated with up‐regulation of the VEGF pathway and with increased standard microvessel density (sMVD) and activated VEGF/KDR microvessel density (aMVD). It also was associated with a poor prognosis in both univariate and multivariate analyses. HIF‐2α protein showed a pattern of expression similar to the pattern seen in HIF‐1α, but expression of HIF‐2α protein occurred in only 17% of endometrial carcinomas, and it was associated with increased TP reactivity. There also was a relation of HIF‐1α expression with well‐differentiated endometrial neoplasms, and there was a marginal association of HIF‐1α and HIF‐2α with ER expression. With reference to normally cycling tissues, HIF‐1α nuclear/cytoplasmic expression was particularly strong in the samples of early proliferative phase endometrium compared with HIF‐2α protein expression, which showed a constant reaction throughout the menstrual cycle.

CONCLUSIONS

The up‐regulation of HIF‐1α and, to a lesser extent, of HIF‐2α is a common event in Stage I endometrial adenocarcinomas. In these tumors, HIF‐1α expression is related to increased angiogenesis, through activation of the VEGF angiogenic pathway, and to an unfavorable prognosis. HIF‐2α accumulation is associated with increased expression of the angiogenic factor TP. Cancer 2002;95:1055–63. © 2002 American Cancer Society.

DOI 10.1002/cncr.10774
Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas
Authors: Meric Funda , Hess Kenneth R. , Varma Datla G. K. , Hunt Kelly K. , Pisters Peter W. T. , Milas Kresimira M. , Patel Shreyaskumar R. , Benjamin Robert S. , Plager Carl , Papadopoulos Nicholas E. J. , Burgess Michael A. , Pollock Raphael E. , Feig Barry W.
Published: October 2002

BACKGROUND

Downstaging of large soft tissue sarcomas can be accomplished by the use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that radiographic response to NeoCT predicts improved local control and survival.

METHODS

The authors reviewed the medical records of 65 patients with Stage II or III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with doxorubicin or ifosfamide‐based NeoCT from January 1991 to December 1996. Radiographic response and impact on surgical therapy were determined retrospectively by comparing imaging studies obtained before and after chemotherapy.

RESULTS

The radiographic responses observed were partial response (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20 patients [31%]); and progressive disease (17 patients [26%]). Downstaging sufficient to decrease the scope of the operation occurred in 13% of the patients, 78% had no change, and 9% had disease progression sufficient to increase the scope of the operation. Patients having any radiographic response (PR or MR) had a higher margin‐negative resection rate, a better local recurrence‐free survival rate, and a better overall survival rate than did nonresponders.

CONCLUSIONS

The NeoCT regimens used in this study resulted in tumor shrinkage sufficient to impact surgical therapy in a few patients. However, radiographic response predicted improved local control and overall survival rate. Cancer 2002;95:1120–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10794
Detection of human herpes virus type 6 DNA in precancerous lesions of the uterine cervix
Authors: Tran‐Thanh Danh , Koushik Anita , Provencher Diane , Drouin Pierre , Dubuc‐Lissoir Josée , Gauthier Philippe , Allaire Guy , Kornegay Janet , Franco Eduardo , Coutlée François
Published: October 2002

Human herpes virus type 6 (HHV‐6) DNA has been suggested to be a cofactor to human papillomavirus (HPV) in cervical cancer. In a cross‐sectional study, we investigated the association between HHV‐6 DNA detected in cervical brushings and high‐grade squamous intraepithelial lesions (HSIL), while controlling for genital infection with 27 genotypes of HPV. Of the 320 women recruited from an oncologic gynecology clinic, 50 had invasive cervical cancer, 65 had HSIL, 80 had low‐grade squamous intraepithelial lesions (LSIL), and 125 were normal. Four of the seven HHV‐6‐positive women had HSIL. HHV‐6 was associated with HSIL after adjusting for age and socioeconomic status (odds ratio [OR] of 10.9, 95% confidence interval [CI]: 1.1–107.1). This association was no longer significant after controlling for HPV (OR = 6.4, 95% CI = 0.3–128.5). HHV‐6 was detected in cervical samples from women with precancerous and cancerous lesions of the cervix, but not significantly more frequently than in normal women. J. Med. Virol. 68:606–610, 2002. © 2002 Wiley‐Liss, Inc.
Rodent host specificity of European hantaviruses: Evidence of Puumala virus interspecific spillover
Authors: Klingström J. , Heyman P. , Escutenaire S. , Sjölander K. Brus , Jaegere F. De , Henttonen H. , Lundkvist Å.
Published: October 2002

In order to investigate rodent host specificity of European hantaviruses, experimental infection of colonized and wild‐trapped rodents was performed. In addition to the natural rodent reservoir, Clethrionomys glareolus, Puumala hantavirus (PUUV) could infect colonized Microtus agrestis and Lemmus sibiricus, but not Syrian hamsters or Balb/C mice. Neither C. glareolus, nor M. agrestis, could be readily infected by Tula hantavirus (TULV). Wild‐trapped Apodemus flavicollis and A. agrarius, the natural reservoirs of Dobrava (DOBV) and Saaremaa (SAAV) hantaviruses, respectively, could both be infected by SAAV. NMRI mice could also be infected by SAAV, but with lower efficiency as compared to Apodemus mice. Balb/C and NMRI laboratory mice, but not C. glareolus, could be infected by DOBV. To our knowledge, this is the first time DOBV and SAAV have been shown to infect adult laboratory mice. Moreover, potential hantavirus spillover infections were investigated in wild‐trapped rodents. In addition to the natural host C. glareolus, we also found M. arvalis and A. sylvaticus with a history of PUUV infection. We did not find any C. glareolus or A. sylvaticus infected with TULV, a hantavirus which is known to circulate in the same geographical regions of Belgium, J. Med. Virol. 68:581–588, 2002. © 2002 Wiley‐Liss, Inc.
Persistence of earlier HIV‐1 drug resistance mutations at new treatment failure
Authors: Svedhem Veronica , Lindkvist Annica , Lidman Knut , Sönnerborg Anders
Published: October 2002

The objective was to study the persistence of drug resistance mutations detected earlier at virological failure during second or third line antiretroviral therapy. Therefore, in HIV‐1 infected patients, with a virological treatment failure, genotypic resistance testing was carried out before change of therapy and at the next treatment failure. The majority of primary and secondary resistance mutations persisted in both the reverse transcriptase (RT) and the protease genes. After changing from zidovudine‐ to stavudine‐containing regimens, the thymidine analogue mutations (especially M41L and T215Y/F) were found at new treatment failure in almost all patients. The M184V mutation disappeared in most (64%) non‐3TC treated patients, although it persisted in a few didanosine‐ and abacavir‐treated subjects. The primary protease inhibitor (PI) mutations reverted back to wild type in most patients who did not receive a new PI. In contrast, after changing from indinavir to saquinavir or nelfinavir, the M46I/L and/or V82A/F/ST disappeared in only 9 of 21 occasions at the new treatment failure. Most secondary mutations persisted with the exception of N88D. In patients with multiple treatment failures, most NRTI mutations thus persist frequently at new failures with modified treatment. A similar pattern is seen for protease inhibitors. The data suggest that clinical cross‐resistance may develop via common pathways within all categories of drugs in heavily treated patients. J. Med. Virol. 68:473–478, 2002. © 2002 Wiley‐Liss, Inc.
Rigid‐plastic hybrid element analyses of the plane strain upsetting
Authors: Guo Yong‐Ming , Nakanishi Kenji , Yokouchi Yasuto
Published: October 2002

A rigid‐plastic hybrid element method (HEM) for simulation of metal forming is developed. This method is a mixed approach of the rigid‐plastic domain‐BEM and the rigid‐plastic FEM based on the theory of compressible plasticity. Because the compatibilities of not only velocity but also velocity's derivative between the adjoining boundary elements and finite elements can be met, the velocities and the derivatives of the velocity can be calculated with the same precision for the rigid‐plastic HEM. Then, it is considered that the rigid‐plastic HEM is a more precise method in formulation than the conventional rigid‐plastic FEMs for which the compatibilities of velocity's derivative cannot be met. The plane strain upsetting processes with two friction factors are analyzed by the rigid‐plastic HEM in this article. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 726–737, 2002; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/num.10031.
A formal set of algorithms for project scheduling with critical path scheduling/material requirements planning
Authors: Aquilano Nicholas J. , Smith Dwight E.
Published: October 2002

A hybrid model combining the critical path method (CPM) with material requirements planning (MRP) has been suggested (Aquilano) as a more robust method for scheduling projects and resources. The primary advantage of this technique is that resource acquisition lead times as well as inventory records are integrated into the process of computing the project schedule. This paper presents a set of formal CPM/MRP algorithms that may be used to compute the early and late start schedules as well as the critical sequence. A number of modifications have been incorporated into the CPM/MRP technique to improve the viability of CPM/MRP as a tool for application to actual project scheduling problems. A simple example project is used to demonstrate the CPM/MRP model.

The CPM/MRP technique is designed to overcome a basic shortcoming of previously suggested project scheduling methodologies. CPM was initially designed to schedule projects subject to technological constraints only. Later, additional techniques were introduced to consider constraints upon various aspects of resource availability (Davis). None of the suggested techniques attempted to integrate resource acquisition lead time with the generation of requirements for resources. Obviously such a technique would require the integration of inventory records into the scheduling technique.

The combination of CPM and MRP provides a possible vehicle for overcoming this drawback in CPM. Both CPM and MRP are linear models that generate schedules based upon precedence relationships. An integrated approach is useful since activities could be scheduled subject to information about the inventory position. An activity may be scheduled as soon as all resources are on hand. It is only delayed by those resources which must be acquired and activities which proceed it in the project network.

CPM/MRP also shows promise as an aid to constrained resource scheduling since computations regarding resource availability are an integrated part of the technique. The effect of resource allocation decisions is immediately evident in the MRP‐type time phased records.

Results of the tests run on short projects of up to 300 activities and resources have shown that the program does work satisfactorily. Execution time for a 300 item network tested was approximately ten seconds on a CYBER 175.
A simulation study of smoothing constant limits for an adaptive forecasting system
Authors: Flowers A.Dale
Published: October 2002

A set of computer simulation experiments were designed to investigate the use of Winters' forecasting models with the adaptive system of Trigg and Leach for short term forecasting. These two methods are popular and effective methods used for short term forecasting, but no systematic study of their joint usage has been reported. The results provide a set of smoothing constant limits which yielded accurate forecasts for the experimental conditions investigated. The experimental conditions were designed to cover as wide a range of situations as possible to maximize potential usefulness to practitioners.
Estimating and auditing aggregate inventory levels at multiple stocking points
Authors: Ballou Ronald H.
Published: October 2002

Relatively little attention has been given to methods for estimating and auditing distribution network inventories in the aggregate. This article shows that a simple polynomial equation whose coefficients can be determined by means of regression analysis techniques is a good, basic tool for estimating overall inventory levels and can be used to provide insight into the effectiveness of inventory control policies at different stocking points. It also serves as the basis for auditing and controlling current inventory policies on an ongoing basis. Tests of the model in a number of actual cases revealed a predictable association between the inventory policy being used and the coefficient values in the polynomial equation.