bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurocognitive Function and Progression in Patients With Brain Metastases Treated With Whole-Brain Radiation and Motexafin Gadolinium: Results of a Randomized Phase III Trial
Authors: Meyers Christina A. , Smith Jennifer A. , Bezjak Andrea , Mehta Minesh P. , Liebmann James , Illidge Tim , Kunkler Ian , Caudrelier Jean-Michel , Eisenberg Peter D. , Meerwaldt Jacobus , Siemers Ross , Carrie Christian , Gaspar Laurie E. , Curran Walter , Phan See-Chun , Miller Richard A. , Renschler Markus F. 
Published: December 2003

Purpose To report the neurocognitive findings in a phase III randomized trial evaluating survival and neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd). Patients and Methods Patients were randomly assigned to receive WBRT 30 Gy in 10 fractions with or without MGd 5 mg/kg/d. Monthly neurocognitive testing for memory, executive function, and fine motor skill was performed. Results Four hundred one patients were enrolled (251 with non–small-cell lung cancer, 75 with breast cancer, and 75 with other cancers); 90.5% patients had impairment of one or more neurocognitive tests at baseline. Neurocognitive test scores of memory, fine motor speed, executive function, and global neurocognitive impairment at baseline were correlated with brain tumor volume and predictive of survival. There was no statistically significant difference between treatment arms in time to neurocognitive progression. Patients with lung cancer (but not other types of cancer) who were treated with MGd tended to have improved memory and executive function (P = .062) and improved neurologic function as assessed by a blinded events review committee (P = .048). Conclusion Neurocognitive tests are a relatively sensitive measure of brain functioning; a combination of tumor prognostic variables and brain function assessments seems to predict survival better than tumor variables alone. Although the addition of MGd to WBRT did not produce a significant overall improvement between treatment arms, MGd may improve memory and executive function and prolong time to neurocognitive and neurologic progression in patients with brain metastases from lung cancer.
Multicenter Phase II Study of Nordic Fluorouracil and Folinic Acid Bolus Schedule Combined With Oxaliplatin As First-Line Treatment of Metastatic Colorectal Cancer
Authors: Sørbye Halfdan , Glimelius Bengt , Berglund Åke , Fokstuen Tone , Tveit Kjell Magne , Brændengen Morten , Øgreid Dagfinn , Dahl Olav 
Published: December 2003

Purpose This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer. Patients and Methods Eighty-five patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m2 and, 30 minutes later, by a bolus injection with FA 60 mg/m2 every second week. The same doses of FU and FA were also given on day 2. Results Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients). Conclusion Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.
Multicenter Phase II Study of Erlotinib, an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
Authors: Soulieres Denis , Senzer Neil N. , Vokes Everett E. , Hidalgo Manuel , Agarwala Sanjiv S. , Siu Lillian L. 
Published: December 2003

Purpose To determine the efficacy and safety profiles of erlotinib in patients with advanced recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC). Patients and Methods Patients with locally recurrent and/or metastatic HNSCC, regardless of their HER1/EGFR status, were treated with erlotinib at an initial dose of 150 mg daily. Dose reductions or escalations were allowed based on tolerability of erlotinib. Results One-hundred fifteen patients were enrolled onto this study. Forty-seven percent of patients received erlotinib at 150 mg daily throughout the entire study, 6% had dose escalations, and 46% required dose reductions and/or interruptions. Five patients achieved partial responses on study, for an overall objective response rate of 4.3% (95% CI, 1.4% to 9.9%). Disease stabilization was maintained in 44 patients (38.3%) for a median duration of 16.1 weeks. The median progression-free survival was 9.6 weeks (95% CI, 8.1 to 12.1 weeks), and the median overall survival was 6.0 months (95% CI, 4.8 to 7.0 months). Subgroup analyses revealed a significant difference in overall survival favoring patients who developed at least grade 2 skin rashes versus those who did not (P = .045), whereas no difference was detected based on HER1/EGFR expression. Rash and diarrhea were the most common drug-related toxicities, encountered in 79% and 37% of patients, respectively, though the severity was mild to moderate in most cases. Conclusion Erlotinib was well tolerated in this heavily pretreated HNSCC population and produced prolonged disease stabilization; hence, further evaluation of its role in this tumor type is warranted.
Phase II Trial of PS-341 in Patients With Renal Cell Cancer: A University of Chicago Phase II Consortium Study
Authors: Davis Nancy B. , Taber David A. , Ansari Rafat H. , Ryan Christopher W. , George Christopher , Vokes Everett E. , Vogelzang Nicholas J. , Stadler Walter M. 
Published: December 2003

Purpose Determine response rate, time to disease progression, and toxicity of the proteasome inhibitor PS-341 in patients with stage IV renal cell cancer. Patients and Methods PS-341 1.5 mg/m2 was administered intravenously twice weekly for 2 weeks every 21 days. Dose escalation to 1.7 mg/m2 ensued in the absence of grade 3 to 4 toxicities. Re-evaluation took place after three cycles. To assess proteasome inhibition, patients were randomly assigned to tumor core biopsy either before the first dose or after the third cycle of PS-341. Additionally, whole blood was collected at the same time intervals. Results Twenty-three patients were enrolled; 21 were assessable for response. Two patients were never treated (one patient refused treatment and one had insufficient tumor for biopsy). Eighteen patients completed at least three cycles of therapy; three patients experienced disease progression after two cycles. Grade 4 toxicities were arthralgia, diarrhea, and vomiting. Grade 3 toxicities included thrombocytopenia with one hemorrhage, anemia, febrile neutropenia, gastrointestinal toxicity, pain, fatigue, neuropathy (one sensory, one mixed sensorimotor), and electrolyte disturbances. Grade 1 to 2 neuropathy occurred in seven patients. One case of thrombosis and one case of pleural effusion occurred. Only one objective response was seen. Proteasome activity was measured by specific chymotryptic activity (SpA) and chymotryptic/tryptic activity (ChT:T). After PS-341, there was a decrease in mean whole blood SpA and ChT:T (P = .07 and .11, respectively). Conclusion Evidence is lacking for clinically significant activity of PS-341 in metastatic renal cell cancer. Insufficient biopsy and whole blood sample numbers preclude conclusions regarding proteasome inhibition within tumor. Further evaluation in this disease setting is not recommended.
The Combination of p53 Mutation and neu/erbB-2 Amplification Is Associated With Poor Survival in Node-Negative Breast Cancer
Authors: Bull Shelley B. , Ozcelik Hilmi , Pinnaduwage Dushanthi , Blackstein Martin E. , Sutherland Donald A.J. , Pritchard Kathleen I. , Tzontcheva Anjela T. , Sidlofsky Saul , Hanna Wedad M. , Qizilbash Ali H. , Tweeddale Mary E. , Fine Sheldon , McCready David R. , Andrulis Irene L. 
Published: December 2003

Purpose Increases in neu/erbB-2 have been implicated in breast cancer prognosis, but do not predict all recurrences. On the basis of evidence that p53 mutation is involved in the development of human neoplasia, we examined the prognostic value of p53 alterations in combination with neu/erbB-2 amplification. Patients and Methods A consecutive series of women were observed for recurrence and death (median follow-up of 85 months) and tumors from 543 individuals were analyzed for p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53 gene were analyzed by single-stranded conformational polymorphism and mutations were confirmed by DNA sequencing. The association of p53 mutation status and neu/erbB-2 amplification with risk of recurrence and death was examined in survival analyses with traditional and histologic markers as prognostic factors. Results p53 mutations occurred in 24.5% of the axillary node-negative breast carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2 amplification: 38.9% compared with only 20.9% in those without neu/erbB-2 amplification. We found elevated risks of disease recurrence and overall mortality in patients with both p53 mutation and neu/erbB-2 amplification in their tumor compared with patients with neither or only one of the alterations. This increase persisted with adjustment for other prognostic factors (relative risk, 2.32; P = .002 for recurrence; relative risk, 2.22; P = .004 for death). Conclusion Evaluation of tumors for p53 mutations may be beneficial to identify women at higher risk of disease recurrence and death when the tumor has neu/erbB-2 amplification, but in the absence of neu/erbB-2 amplification, the presence of p53 mutation may not provide additional independent prognostic information.
Menopausal Status Dependence of Early Mortality Reduction Due to Diagnosis of Smaller Breast Cancers (T1 v T2-T3): Relevance to Screening
Authors: Demicheli Romano , Bonadonna Gianni , Hrushesky William J.M. , Retsky Michael W. , Valagussa Pinuccia 
Published: December 2003

Purpose To provide data relevant to the paradoxical mortality excess for women age 40 to 49 years observed during the first 6 to 8 years in the invited group in all mammography screening studies. Patients and Methods In 1,173 patients undergoing mastectomy alone as primary treatment, allocated to subsets according to menopausal status and tumor size, hazard rates for death were calculated. The ratios between the hazard rate for T2-T3 patients and the corresponding value for T1 patients were assessed over time. Results For postmenopausal patients, the ratio appeared to be time-dependent, dropping from the maximum value of approximately 5 at the first year after surgery to a near constant value of approximately 2 after 5 to 6 years. Premenopausal patients, on the contrary, showed a nearly constant ratio of approximately 3. Therefore, although in each T-category the 10-year survival of premenopausal and postmenopausal patients was similar, its time distribution was menopause-dependent. In particular, the difference between cumulative survival of premenopausal and postmenopausal T2-T3 patients attained statistical significance after 3 years. Conclusion The mortality reduction due to the diagnosis of smaller tumors is significantly higher for postmenopausal women than for premenopausal women during early postsurgery time. According to the hypothesis that primary tumor surgical removal, occurring sooner in the invited group than in the control arm of screening trials, results in some acceleration of metastasis development, a greater number of unfavorable events (recurrence and death) should occur in the invited group. We suggest that for younger women, the early balance between benefit from tumor downsizing and harm from surgery-induced metastasis acceleration results in harm. This disadvantage does not occur in postmenopausal women.
Stocking Decisions for Low-Usage Items in a Multilocation Inventory System
Authors: Kukreja Anil , Schmidt Charles P. , Miller David M. 
Published: December 2003

This research shows that organizations with a number of “sister” plants, warehouses, or other stocking points can profit from the concept of proactive use of transshipments as an element of their inventory control policy. For certain types of parts, employing transshipments can significantly reduce the total inventory needed throughout the entire collection of stocking points. The study is motivated by a real-life situation involving a large utility company having 29 power-generating plants in five Southeastern states where there are thousands of parts that are commonly used at multiple plants. At present, each plant operates independently and maintains enough stock to meet its own requirements. Transshipments take place between plants whenever there is an emergency requirement for a part, but no explicit consideration is given to this effect while deciding on stocking levels at different plants. In the case we examined, by setting stocking levels to explicitly take account of transshipments, total system cost could be reduced by about 70% over the company's decentralized policy. In general, this work considers a single-echelon, N-location, continuous-review inventory system in which complete pooling of stock is permitted among the locations. A model is developed for slow-moving, expensive, and consumable parts that are common to two or more locations. A one-for-one ordering policy and queueing theory allow development and solution of a system of equations for the probability distribution of net inventory at each location. A heuristic procedure is also developed to determine cost-effective stocking levels. Actual data from the utility company are used to demonstrate the applicability of the model. Savings achieved as a result of pooling are reported.
The Effects of Worker Learning, Forgetting, and Heterogeneity on Assembly Line Productivity
Authors: Shafer Scott M. , Nembhard David A. , Uzumeri Mustafa V. 
Published: December 2003

The authors investigate through several simulations how patterns of learning and forgetting affect the operating performance of an assembly line. A unique aspect of this study is that a distribution of learning/forgetting behavior based on an empirical population of workers is used rather than assuming the same learning pattern for all employees. The paper demonstrates that modeling only central tendency and not the variations across workers tends to systematically underestimate overall productivity. The data used to estimate the parameters for the distribution of learning curves were collected from an assembly line that produces car radios. Analysis of the models fit to a population of workers reveals that higher levels of previous experience are positively correlated with higher steady-state productivity levels and negatively correlated with the learning rate. To further motivate the study, a conceptual model with several factors hypothesized to influence assembly line productivity is presented. Among key factors included in the model are the rate of worker learning, the size of the worker pool, task tenure, and the magnitude of worker forgetting. In controlled computer simulation experiments, each of these factors was found to be statistically significant, as were a number of the two-way interaction terms.
Optimal Investment in Knowledge Within a Firm Using a Market Mechanism
Authors: Ba Sulin , Stallaert Jan , Whinston Andrew B. 
Published: December 2003

There has been an extensive research literature on auctions, but recent developments in technology have resulted in new interest in auction mechanisms as a practical way of allocating resources. This paper presents a new double-auction mechanism to handle resource allocation for public goods when complementarity exists. The mechanism is placed in the context of an organization's internal knowledge investment. Knowledge goods have two distinct characteristics. First, knowledge within an organization can be considered a public good, so it is subject to the free-rider problem. Second, knowledge is interrelated and interdependent; that is, there is complementarity among knowledge components. The value of knowledge often derives from a bundle of knowledge components, rather than from its individual pieces. These two characteristics present a serious challenge to allocating organizational resources for knowledge goods. We introduce an internal market in which knowledge providers offer knowledge projects and knowledge consumers place bids to acquire them. The mechanism is a Groves-Clarke-type double auction that allows bundled knowledge goods to be traded so as to recognize complementarities between knowledge projects. The market mechanism we propose is incentive compatible; i.e., it induces people to reveal their true valuation. In addition, it allows trades of knowledge bundles to determine which knowledge components are most valuable from the organization's viewpoint. Under mild assumptions, the mechanism is a computationally tractable solution to operating a market of bundled public goods. We further show how “imputed prices” can be calculated for subsets of knowledge components and prove that a market mechanism that does not allow bundle orders or does not address the free-rider problem yields a systematic underinvestment in knowledge.
Process and Product Improvement in Manufacturing Systems with Correlated Stages
Authors: Zantek Paul F. , Wright Gordon P. , Plante Robert D. 
Published: December 2003

Manufacturing systems typically contain processing and assembly stages whose output quality is significantly affected by the output quality of preceding stages in the system. This study offers and empirically validates a procedure for (1) measuring the effect of each stage's performance on the output quality of subsequent stages including the quality of the signal product, and (2) identifying stages in a manufacturing system where management should concentrate investments in process quality improvement. Our proposed procedure builds on the precedence ordering of the stages in the system and uses the information provided by correlations between the product quality measurements across stages. The starting point of our procedure is a computer executable network representation of the statistical relationships between the product quality measurements; execution automatically converts the network to a simultaneous-equations model and estimates the model parameters by the method of least squares. The parameter estimates are used to measure and rank the impact of each stage's performance on variability in intermediate stage and final product quality. We extend our work by presenting an economic model, which uses these results, to guide management in deciding on the amount of investment in process quality improvement for each stage. We report some of the findings from an extensive empirical validation of our procedure using circuit board production line data from a major electronics manufacturer. The empirical evidence presented here highlights the importance of accounting for quality linkages across stages in (a) identifying the sources of variation in product quality and (b) allocating investments in process quality improvement.
Consumer Surplus in the Digital Economy: Estimating the Value of Increased Product Variety at Online Booksellers
Authors: Brynjolfsson Erik , Hu Yu (Jeffrey) , Smith Michael D. 
Published: December 2003

We present a framework and empirical estimates that quantify the economic impact of increased product variety made available through electronic markets. While efficiency gains from increased competition significantly enhance consumer surplus, for instance, by leading to lower average selling prices, our present research shows that increased product variety made available through electronic markets can be a significantly larger source of consumer surplus gains. One reason for increased product variety on the Internet is the ability of online retailers to catalog, recommend, and provide a large number of products for sale. For example, the number of book titles available at Amazon.com is more than 23 times larger than the number of books on the shelves of a typical Barnes & Noble superstore, and 57 times greater than the number of books stocked in a typical large independent bookstore. Our analysis indicates that the increased product variety of online bookstores enhanced consumer welfare by $731 million to $1.03 billion in the year 2000, which is between 7 and 10 times as large as the consumer welfare gain from increased competition and lower prices in this market. There may also be large welfare gains in other SKU-intensive consumer goods such as music, movies, consumer electronics, and computer software and hardware.
The Quickest Transshipment Problem
Authors: Hoppe Bruce , Tardos Éva 
Published: December 2003

A dynamic network consists of a graph with capacities and transit times on its edges. The quickest transshipment problem is defined by a dynamic network with several sources and sinks; each source has a specified supply and each sink has a specified demand. The problem is to send exactly the right amount of flow out of each source and into each sink in the minimum overall time. Variations of the quickest transshipment problem have been studied extensively; the special case of the problem with a single sink is commonly used to model building evacuation. Similar dynamic network flow problems have numerous other applications; in some of these, the capacities are small integers and it is important to find integral flows. There are no polynomial-time algorithms known for most of these problems. In this paper we give the first polynomial-time algorithm for the quickest transshipment problem. Our algorithm provides an integral optimum flow. Previously, the quickest transshipment problem could only be solved efficiently in the special case of a single source and single sink.