bluuebunny/crossref_metadata_2025 huggingface dataset:
Time course of endothelial damage in septic shock: prediction of outcome
Authors: Hein Ortrud Vargas , Misterek Klaudia , Tessmann Jan-Peer , van Dossow Vera , Krimphove Michael , Spies Claudia
Published: May 2005

Introduction

Endothelial damage accounts greatly for the high mortality in septic shock. Higher expression of mediators (IL-6, IL-8, soluble intercellular adhesion molecule 1 [sICAM-1], soluble endothelial-linked adhesion molecule 1 [sELAM-1]) have been described for non-survivors in comparison with survivors. We investigated the predictive value of the mediators IL-6, IL-8, sELAM-1 and sICAM-1 and their time course in intensive care unit patients who developed septic shock with respect to outcome.

Materials and methods

We measured serum levels of IL-6, IL-8, sELAM-1 and sICAM-1 in 40 intensive care unit patients who developed septic shock. Measurements were performed until death or until resolution of septic shock. Clinical and laboratory data were also recorded.

Results

After 48 hours the levels of sELAM-1 and sICAM-1 increased in non-survivors and decreased in survivors. sELAM-1 was predictive for outcome on the third day (P = 0.02) and the fourth day (P = 0.02) after diagnosis of septic shock. This difference in the time course between survivors and non-survivors occurred 7 days before death of the patients (median, 10 days). sICAM-1 levels increased significantly in non-survivors over the study period (P < 0.001). sELAM-1 (P = 0.04), IL-6 (P = 0.04) and IL-8 (P = 0.008) were significantly higher in non-survivors over the whole study period. The age and norepinephrine dose >0.5 μg/kg/min were significantly different between the groups.

Conclusion

sELAM-1 showed a markedly opposing course after 48 hours of septic shock. This adhesion molecule may be a useful early predictor of disease severity in the course of septic shock after early initial treatment of the patients, and might suggest considering endothelial-restoring therapy.
The rarity of gene shuffling in conserved genes
Authors: Conant Gavin C , Wagner Andreas
Published: May 2005

Background

Among three sources of evolutionary innovation in gene function - point mutations, gene duplications, and gene shuffling (recombination between dissimilar genes) - gene shuffling is the most potent one. However, surprisingly little is known about its incidence on a genome-wide scale.

Results

We have studied shuffling in genes that are conserved between distantly related species. Specifically, we estimated the incidence of gene shuffling in ten organisms from the three domains of life: eukaryotes, eubacteria, and archaea, considering only genes showing significant sequence similarity in pairwise genome comparisons. We found that successful gene shuffling is very rare among such conserved genes. For example, we could detect only 48 successful gene-shuffling events in the genome of the fruit fly Drosophila melanogaster which have occurred since its common ancestor with the worm Caenorhabditis elegans more than half a billion years ago.

Conclusion

The incidence of gene shuffling is roughly an order of magnitude smaller than the incidence of single-gene duplication in eukaryotes, but it can approach or even exceed the gene-duplication rate in prokaryotes. If true in general, this pattern suggests that gene shuffling may not be a major force in reshaping the core genomes of eukaryotes. Our results also cast doubt on the notion that introns facilitate gene shuffling, both because prokaryotes show an appreciable incidence of gene shuffling despite their lack of introns and because we find no statistical association between exon-intron boundaries and recombined domains in the two multicellular genomes we studied.
Multimodality Therapy for Stage III Non–Small-Cell Lung Cancer
Authors: Farray Daniel , Mirkovic Nena , Albain Kathy S.
Published: May 2005

The treatment of stage III non–small-cell lung cancer has evolved over the last two decades, with combined-modality therapy the current standard of care. As a result, intermediate and long-term survival has improved for patients in this common stage category, compared to the poor outcomes achieved with the historical standard of once-daily radiation therapy alone. This review summarizes two decades of clinical research regarding bimodality and trimodality approaches for the heterogenous stage subsets within the stage III designation, discusses the rationale and status of prophylactic brain irradiation, and concludes with perspectives on progress and future directions. Chemotherapy plus radiotherapy given concurrently is the optimal treatment for the group of patients with advanced stage III disease. The potential role of a surgical resection following chemotherapy (with or without radiation) in this setting is still controversial. The only subsets for which trimodality treatments are clearly preferred include T4N0-1 disease and superior sulcus tumors. The other major stage III subgroup has a minimal disease burden with low tumor volume and/or microscopic N2 disease, thus technically could undergo a surgical resection upfront. Induction chemotherapy before surgery may yield a survival advantage, although the phase III trials in this area are not conclusive. Given the marked survival benefit from adjuvant chemotherapy after surgery in even earlier stages of non–small-cell lung cancer, the proper sequence of surgery and chemotherapy (before v after surgery) remains an important unresolved question in this subgroup. Furthermore, how to incorporate radiation therapy, as well as whether it should be given at all in this subset of patients, are other important issues actively under study in ongoing trials.
Extent of Damage and Repair in the p53 Tumor-Suppressor Gene After Treatment of Myeloma Patients With High-Dose Melphalan and Autologous Blood Stem-Cell Transplantation Is Individualized and May Predict Clinical Outcome
Authors: Dimopoulos Meletios A. , Souliotis Vassilis L. , Anagnostopoulos Athanasios , Papadimitriou Christos , Sfikakis Petros P.
Published: May 2005

Purpose

To quantitate the individual levels of melphalan-induced DNA damage formation and repair in vivo and to search for possible correlations with clinical outcome in patients with multiple myeloma (MM).

Patients and Methods

The formation and subsequent repair of DNA damage (monoadducts and interstrand cross-links) in the p53 tumor-suppressor gene, the proto-oncogene N-ras, and the housekeeping gene beta-actin during the first 24 hours after treatment with high-dose melphalan (HDM; 200 mg/m2) supported by autologous blood stem-cell transplantation (ABSCT) was measured in blood leukocytes of 26 patients with MM. The peak DNA adduct levels, the total amount of adducts over time, and the rate of adducts repair in each gene were correlated with response and time to progression after HDM.

Results

The levels of gene-specific DNA damage formation and the individual repairing capacity varied up to 16-fold among patients, indicating that the melphalan-induced biologic effect in vivo is highly individualized. A significantly greater DNA damage and a slower rate of repair in p53 for all end points under study were found in patients who achieved tumor reduction compared with nonresponding patients. Furthermore, longer progression-free survival correlated with increased peak monoadduct levels in the p53 gene (P = .032).

Conclusion

Increased DNA damage and slower repairing capacity in the p53 gene from blood leukocytes after HDM correlate with improved outcome of patients with MM who undergo ABSCT. These results suggest that quantitation of such biologic end points may identify patients who are more likely to benefit from this procedure.
Functional Imaging in Lung Cancer
Authors: Shankar Lalitha K. , Sullivan Daniel C.
Published: May 2005

Accurate detection of the presence and extent of disease is vital in the management of non–small-cell lung cancer. While computed tomography and magnetic resonance imaging tend to be the routine diagnostic modalities used in the management of lung cancer, there have been significant advances in the field of functional and molecular imaging. In this article, we review the performance of the functional imaging techniques that are currently available for the evaluation of non–small-cell lung cancer. The techniques range from evaluation of glucose metabolism in tumors with fluorodeoxyglucose, to evaluation of proliferation with fluorothymidine and evaluation of tumor hypoxia with agents such as fluoromisonidazole. Magnetic resonance imaging with an emphasis on dynamic contrast enhancement of tumors as well as detecting of malignant lymph nodes with targeted contrast agents is discussed. Emerging technologies such as lung imaging fluorescence endoscopy are considered. The role of functional imaging in planning, predicting response to, and evaluating effects of, various therapies is explored.
Epidemiology of Lung Cancer: Looking to the Future
Authors: Alberg Anthony J. , Brock Malcolm V. , Samet Jonathan M.
Published: May 2005

In the United States, the 20th century witnessed the emergence of a lung cancer epidemic that peaked and began to decline by the century's end, a decline that continues today. However, lung cancer continues to be an unabating pandemic. In research carried out over the last half of the 20th century, many factors were causally associated with lung cancer and studies were implemented to identify determinants of susceptibility to these factors. Cigarette smoking was identified as the single most predominant cause of the lung cancer epidemic, but other causes were found, including workplace agents (eg, asbestos, arsenic, chromium, nickel, and radon) and other environmental factors (passive smoking, indoor radon, and air pollution). Contemporary epidemiologic research on lung cancer now focuses on a new set of issues, primarily related to susceptibility to the well-identified causal factors, particularly smoking, and on the consequences of changes in tobacco products for risks to smokers. Diet and the possibility of reducing risk through chemoprevention remain a focus of research emphasis through experimental and observational approaches. Questions have also been raised about possible differences in susceptibility to lung cancer by sex and race.

Population patterns in smoking prevalence will continue to be the most powerful predictor of the future occurrence of lung cancer. Evaluation of recent US patterns in smoking prevalence indicates that for the next approximately 10 to 15 years, lung cancer rates will decrease, but will then level off starting in approximately 2030. Unless further reductions in the prevalence of cigarette smoking are achieved over the next decade, lung cancer will remain as an all too common, but avoidable, disease.
Adjuvant Chemotherapy in Completely Resected Non–Small-Cell Lung Cancer
Authors: Pisters Katherine M.W. , Le Chevalier Thierry
Published: May 2005

Surgery alone has long been the standard treatment for patients with operable non–small-cell lung cancer (NSCLC). However, despite complete resection, 5-year survival rates have been disappointing, with about 50% of patients eventually suffering relapse and death from disease. Randomized trials conducted in the 1980s hinted at a survival benefit for postoperative cisplatin-based regimens, but they were underpowered. A meta-analysis published in 1995 found a nonsignificant 13% reduction in the risk of death associated with cisplatin-based chemotherapy, with an increase of survival of 5% at 5 years. This led to renewed interest in adjuvant chemotherapy in resected NSCLC. Thousands of patients have been included in a new generation of randomized trials in the last 10 years. Most of these recent studies have now been reported and several have demonstrated a clear survival advantage for patients treated with platin-based adjuvant therapy. These results also suggest a greater benefit with modern two-drug regimens. In view of the most recent data, postoperative platin-based chemotherapy can now be considered the standard of care for completely resected NSCLC patients with good performance status.
Lung Cancer in Women
Authors: Patel Jyoti D.
Published: May 2005

Lung cancer is the leading cause of cancer death in the United States and is responsible for 20,000 more deaths yearly in US women than breast cancer. Cigarette smoking is the major cause of lung cancer, and unfortunately, approximately 22 million US women smoke. Mounting evidence suggests that there are significant differences in lung cancer between the sexes. There is a difference in the histologic distribution of lung cancer, with glandular differentiation being more common in women. Genetic variation may account for differences in susceptibility, and hormonal and biologic factors may play a role in carcinogenesis. Lung cancer patients have few therapeutic options. A more thorough understanding of the heterogeneity of lung cancer across populations may lead to innovations in treatment and prevention strategies.
New Developments in Lung Cancer Screening
Authors: Mulshine James L.
Published: May 2005

Lung cancer is the most lethal cancer in our society. Late diagnosis of this disease is a major problem and so recent favorable reports with spiral computed tomography screening of high-risk populations have rekindled interest in improving early lung cancer detections. The process of lung cancer screening is a complicated process that involves many component activities. Interest to date has heavily focused on the initial case identification, but more recent reports have suggested that the issues with case work-up and surgical management also bear closer consideration. Given the dynamic nature of spiral computed tomography scan development and the remarkable improvements in imaging resolution over the last decade, there is an urgent need for research to establish optimal clinical management of early lung cancer detected in a screening setting.
Advances in the Biology of Lung Cancer Chemoprevention
Authors: Hirsch Fred R. , Lippman Scott M.
Published: May 2005

The heavy burden of lung cancer, which includes the highest worldwide mortality of any cancer, and its resistance to standard approaches (smoking cessation, screening, and therapy), have motivated an intense interest in chemoprevention of this disease. Randomized controlled trials of agents (including retinoids, beta-carotene, and vitamin E) to prevent lung cancer have produced only disappointing clinical results to date. New, molecular-targeted approaches are advancing rapidly, however, with many promising targets and interactive signaling pathways for developing novel agents and combinatorial approaches in this setting. This promise is illustrated by recent studies of 15-hydroxyprostaglandin dehydrogenase, which plays a critical role in polyunsaturated fatty acid metabolism and (like another important target, prostacyclin) is downstream of cyclooxygenase-2. 15-hydroxyprostaglandin dehydrogenase degrades prostaglandin E2, appears to have tumor suppressor activity, and can be induced both by peroxisome proliferator-activated receptor-gamma ligands and an epidermal growth factor receptor inhibitor. Other important targets/pathways include the insulin-like growth factor axis, phosphoinositide 3-kinase pathway, cyclin D and E family members, and epigenetic events. Defining highest lung cancer risk (eg, establishing molecular risk models through long-term analyses of high-risk cohorts) will facilitate the clinical development of molecular-targeted prevention that will potentially reduce the enormous burden of lung cancer.
Evolving Concepts in the Pathology and Computed Tomography Imaging of Lung Adenocarcinoma and Bronchioloalveolar Carcinoma
Authors: Travis William D. , Garg Kavita , Franklin Wilbur A. , Wistuba Ignacio I. , Sabloff Bradley , Noguchi Masayuki , Kakinuma Ryutaro , Zakowski Maureen , Ginsberg Michelle , Padera Robert , Jacobson Francine , Johnson Bruce E. , Hirsch Fred , Brambilla Elizabeth , Flieder Douglas B. , Geisinger Kim R. , Thunnisen Frederik , Kerr Keith , Yankelevitz David , Franks Teri J. , Galvin Jeffrey R. , Henderson Douglas W. , Nicholson Andrew G. , Hasleton Philip S. , Roggli Victor , Tsao Ming-Sound , Cappuzzo Federico , Vazquez Madeline
Published: May 2005

Purpose

To review recent advances in pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC).

Methods

A pathology/CT review panel of pathologists and radiologists met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The purpose was to determine if existing data was sufficient to propose modification of criteria for adenocarcinoma and BAC as newly published in the 2004 WHO Classification of Lung Tumors, and to address the pathologic/radiologic concept of diffuse/multicentric BAC.

Results

Solitary small, peripheral BACs have an excellent prognosis. Most lung adenocarcinomas with a BAC pattern are not pure BAC, but rather adenocarcinoma, mixed subtype with invasive patterns. This applies to tumors presenting with a diffuse/multinodular as well as solitary nodule pattern. The percent of BAC versus invasive components in lung adenocarcinomas appears to be prognostically important. However, a consensus definition of “minimally invasive” BAC with a favorable prognosis could not be achieved. While recognition of a BAC component is possible, the diagnosis of BAC with exclusion of invasive adenocarcinoma cannot be made by small biopsy or cytology specimens.

Conclusion

There is a need to work toward a mutual understanding and consensus between pathologists, clinicians, and researchers with the use of the term BAC versus adenocarcinoma. Future studies should make some attempt to quantitate these components and/or other features such as size of scar, size of invasive component, or pattern of invasion. Hopefully, this work will allow definition of a category of adenocarcinoma, mixed subtype with predominant BAC/minimal invasion and a favorable prognosis.
Angiogenesis and Lung Cancer: Prognostic and Therapeutic Implications
Authors: Herbst Roy S. , Onn Amir , Sandler Alan
Published: May 2005

Lung cancer is the most common cause of cancer death worldwide, with most patients dying with metastatic disease. The prognosis for the majority of patients remains poor. It is evident that advances in the treatment of this and other tumor types will require new approaches, and recent research has focused on molecular-targeted therapies. A key therapeutic strategy is inhibition of specific processes essential for tumor vascular development (a concept known to be beneficial in colorectal cancer) and a range of such antiangiogenic agents are currently in development. The most promising of these target the proangiogenic vascular endothelial growth factor (VEGF), either by preventing VEGF-receptor binding or inhibiting downstream receptor signaling. However, other more direct approaches against tumor vasculature are also in development. Since antiangiogenic agents often exert an indirect, cytostatic effect, many are being evaluated in combination with conventional chemotherapies in order to optimize the anticancer effects of both strategies. Additionally, the combination of several antiangiogenic agents is also being explored. This has become possible given the large number of agents currently available. As part of this evaluation process, the assessment of surrogate markers of target inhibition and treatment effect is ongoing in the hope of identifying reliable surrogate markers to aid the development of this new generation of anticancer agents.
Systemic Therapy of Advanced Bronchioloalveolar Cell Carcinoma: Challenges and Opportunities
Authors: Miller Vincent A. , Hirsch Fred R. , Johnson David H.
Published: May 2005

Bronchioloalveolar cell carcinoma (BAC) has fascinated physicians with its unique epidemiology, pathology, clinical manifestations, and natural history when compared with other non–small-cell lung cancer (NSCLC) subtypes. However, the relative rarity of pure BAC as defined by the WHO, and the inconsistent definitions used in various series, has limited systematic study of this entity. Retrospective and prospective studies suggest that patients with BAC treated with cytotoxic chemotherapy have a longer median survival than those with other subtypes of NSCLC. However, the widely accepted view that BAC is less chemosensitive than other NSCLCs is not clearly supported by the small body of available literature. Antitumor activity of cytotoxic agents and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been documented in phase II trials but no phase III trials have been conducted in this disease. The observation that profound responses to gefitinib and erlotinib often occurred in NSCLC patients with BAC, and that EGFR tyrosine kinase domain mutations were identified in large part by careful study of such patients, serves as a paradigm for translational research in this disease. The recognition that pure BAC and adenocarcinoma with BAC features behave similarly and as such represent a relatively common entity will facilitate accrual to BAC specific studies. Alternatively, stratification of these histologic subtypes in broader clinical trials in NSCLC is warranted. However, for either strategy to succeed in advancing our understanding of the molecular biology of BAC, it must be accompanied by central pathologic review with detailed classification of such, and of adequate tissue for measurement of known or putative targets of action of the agent under study.
Cost-effectiveness of a community-based screening programme for chronic atrial fibrillation in Japan
Authors: Maeda K , Shimbo T , Fukui T
Published: May 2005

Objectives: To examine the cost-effectiveness of a community-based screening programme for chronic atrial fibrillation (AF) in Japan.

Methods: Using a computer model of a Markov process, the cost-effectiveness of an annual ECG screening programme and an annual pulse palpation screening programme for arrhythmia were compared with no screening. A hypothetical Japanese population of 65 year old individuals was followed until 85 years of age. We assumed that individuals with irregular beats on palpation were worked up by ECG and that ECG was perfect in detecting AF, whereas palpation was not. It was also assumed that patients diagnosed with AF received anticoagulant therapy, that some AF patients developed ischaemic stroke, and that some on anticoagulant therapy developed intracranial or gastrointestinal haemorrhage. Costs, efficacy of anticoagulation, utility of health status, and clinical variables were estimated from the literature. Outcomes were expressed as US dollars per quality-adjusted life-year (QALY).

Results: Both annual ECG screening programme and annual palpation screening programme were more costly and at the same time more effective compared with no screening, with their incremental cost-effectiveness ratios approximately US$8000 per QALY in males and US$10,000 per QALY in females. Sensitivity analyses showed high sensitivity of cost-effectiveness ratios to the incidence of ischaemic stroke and anticoagulants prescription rate. Two annual screening programmes were similar in effectiveness and costs.

Conclusion: To prevent ischaemic stroke associated with AF, both annual ECG screening and annual palpation screening were favourable in the context of conventional criteria for cost-effectiveness.
A Choice Model for Packaged Goods: Dealing with Discrete Quantities and Quantity Discounts
Authors: Allenby Greg M. , Shively Thomas S. , Yang Sha , Garratt Mark J.
Published: May 2005

Utility maximizing solutions to economic models of choice for goods with either discrete quantities or non-linear prices cannot always be obtained using standard first-order conditions such as Kuhn-Tucker and Roy's identity. When quantities are discrete, there is no guarantee that derivatives of the utility function are equal to derivatives of the budget constraint. Moreover, when prices are nonlinear, as in the case of quantity discounts, first-order conditions can be associated with the minimum rather than the maximum value of utility. In these cases, the utility function must be directly evaluated to determine its maximum. This evaluation can be computationally challenging when there exist many offerings and when stochastic elements are introduced into the utility function. In this paper, we provide an economic model of demand for substitute brands that is flexible, parsimonious, and easy to implement. The methodology is demonstrated with a scanner panel data set of light-beer purchases. The model is used to explore the effects of price promotions on primary and secondary demand, and the utility of product assortment.
Consumer Learning and Brand Valuation: An Application on Over-the-Counter Drugs
Authors: Akçura M. Tolga , Gönül Füsun F. , Petrova Elina
Published: May 2005

We develop a brand choice model with learning based on the Kalman filter methodology. The model enables us to separate the effects of contemporaneous marketing promotions from the impact of the perceived quality valuation accrued through product usage over time. We also account for idiosyncratic consumer learning and preferences. The results point to the presence of heterogeneity in the valuation carryover coefficients across consumers and brands. In contrast to our expectations, a higher price is not important for most of the consumers in the sample. The model enables us to compare brands in terms of their memorability, which determines brand salience on the next purchase occasion. Our findings suggest that price promotions may be deficient as a tool to increase market share in the studied product category. The proposed model is applicable to other consumer goods contingent on consumers' being sufficiently motivated to learn their own preferences via personal experience. Brand managers can use the model for comparative diagnostics and market performance simulation under different price and promotion scenarios. This paper is instructive to the application of a relatively new methodology; we illustrate the analytical potential of the model by demonstrating its inferential power in a specific marketing context.
Contingent Pricing to Reduce Price Risks
Authors: Biyalogorsky Eyal , Gerstner Eitan
Published: May 2005

The price for a product may be set too low, causing the seller to leave money on the table, or too high, driving away potential buyers. Contingent pricing can be useful in mitigating these problems. In contingent pricing arrangements, price is contingent on whether the seller succeeds in obtaining a higher price within a specified period. We show that if the probability of obtaining the high price is not too high, sellers profit from using contingent pricing while economic efficiency increases. The optimal contingent pricing structure depends on the buyer's risk attitude—a deep discount is most profitable if buyers are risk prone. A consolation reward is most profitable if buyers are risk averse. To motivate buyers to participate in a contingent pricing arrangement, the seller must provide sufficient incentives. Consequently, buyers also benefit from contingent pricing. In addition, because the buyers with the highest willingness-to-pay get the product, contingent pricing increases the efficiency of resource allocation.
Reactance to Recommendations: When Unsolicited Advice Yields Contrary Responses
Authors: Fitzsimons Gavan J. , Lehmann Donald R.
Published: May 2005

Recommendations often play a positive role in the decision process by reducing the difficulty associated with choosing between options. However, in certain circumstances recommendations play a less positive and more undesirable role from the perspectives of both the recommending agent or agency and the person receiving the recommendation. Across a series of four studies, we explore consumer response when recommendations by experts and intelligent agents contradict the consumer's initial impressions of choice options. We find that unsolicited advice that contradicts initial impressions leads to the activation of a reactant state on the part of the decision maker. This reactance, in turn, leads to a behavioral backlash that results not only in consumers ignoring the agents' recommendations but in intentionally contradicting them.
An Empirical Analysis of Determinants of Retailer Pricing Strategy
Authors: Shankar Venkatesh , Bolton Ruth N.
Published: May 2005

This paper empirically investigates the determinants of retailers' pricing decisions. It finds that competitor factors explain the most variance in retailer pricing strategy. Only in the cases of price-promotion coordination and relative brand price do category and chain factors explain much variance in retailer pricing. These findings are derived from a simultaneous equation model of how underlying dimensions of retailers' pricing strategies are influenced by variables representing the market, chain, store, category, brand, customer, and competition. The optical scanner data base describes 1,364 brand-store combinations from six categories of consumer packaged goods in five U.S. markets over a two-year time period. Our study classifies retailers' pricing strategies based on four underlying dimensions: price consistency, price-promotion intensity, price-promotion coordination, and relative brand price. These four pricing dimensions are statistically related to: (1) competitor price and deal frequency (competitor factors), (2) storability and necessity (category factors), (3) chain positioning and size (chain factors), (4) store size and assortment (store factors), (5) brand preference and advertising (brand factors), and (6) own-price and deal elasticities (customer factors). These findings are useful to retailers profiling alternative pricing strategies, and to manufacturers customizing the levels of marketing support spending for different retailers.
The Shape of Advertising Response Functions Revisited: A Model of Dynamic Probabilistic Thresholds
Authors: Vakratsas Demetrios , Feinberg Fred M. , Bass Frank M. , Kalyanaram Gurumurthy
Published: May 2005

Prior work in marketing has suggested that advertising threshold effects—levels beneath which there is essentially no sales response—are rarely encountered in practice. Because advertising policies settle into effective ranges through early trial and error, thresholds cannot be observed directly, and arguments for their existence must be based primarily on a "statistical footprint," that is, on relative fits of a range of model types. To detect possible threshold effects, we formulate a switching regression model with two "regimes," in only one of which advertising is effective. Mediating the switch between the two regimes is a logistic function of category-specific dynamic variables (e.g., order of entry, time in market, number of competitors) and advertising levels, nesting a variety of alternative formulations, among them both standard concave and S-shaped responses. A sequence of comparisons among parametrically related models strongly suggests: that threshold effects exist; that market share response to advertising is not necessarily globally concave; that superior fit cannot be attributed to model flexibility alone; and that dynamic, environmental, competitive, and brand-specific factors can influence advertising effectiveness. These effects are evident in two evolving durables categories (SUVs and minivans), although not in the one mature, nondurable category (liquid detergent) studied.
Long-Run Effects of Promotion Depth on New Versus Established Customers: Three Field Studies
Authors: Anderson Eric T. , Simester Duncan I.
Published: May 2005

We use the results of three large-scale field experiments to investigate how the depth of a current price promotion affects future purchasing of first-time and established customers. While most previous studies have focused on packaged goods sold in grocery stores, we consider durable goods sold through a direct mail catalog. The findings reveal different effects for first-time and established customers. Deeper price discounts in the current period increased future purchases by first-time customers (a positive long-run effect) but reduced future purchases by established customers (a negative long-run effect). Overall, the results show evidence of several long-run effects: forward buying, selection, customer learning, and increased deal sensitivity. Short-run metrics that ignore these effects overstate the overall change in demand for established customers. The implication is that if prices are set based on short-run elasticity, then they will be too low. Among first-time customers, the short-run metrics underestimate the total increase in demand. If prices are set based on short-run elasticity, then they will be too high.
Multiple Discreteness and Product Differentiation: Demand for Carbonated Soft Drinks
Authors: Dubé Jean-Pierre
Published: May 2005

For several of the largest supermarket product categories, such as carbonated soft drinks, canned soups, ready-to-eat cereals, and cookies, consumers regularly purchase assortments of products. Within the category, consumers often purchase multiple products and multiple units of each alternative selected on a given trip. This multiple discreteness violates the single-unit purchase assumption of multinomial logit and probit models. The misspecification of such demand models in categories exhibiting multiple discreteness would produce incorrect measures of consumer response to marketing mix variables. In studying product strategy, these models would lead to misleading managerial conclusions.

We use an alternative microeconomic model of demand for categories that exhibit the multiple discreteness problem. Recognizing the separation between the time of purchase and the time of consumption, we model consumers purchasing bundles of goods in anticipation of a stream of consumption occasions before the next trip. We apply the model to a panel of household purchases for carbonated soft drinks.
Is Having More Channels Really Better? A Model of Competition Among Commercial Television Broadcasters
Authors: Liu Yong , Putler Daniel S. , Weinberg Charles B.
Published: May 2005

Competitive behavior in commercial television broadcasting is modeled to examine program choice and the effects of more channels being available on firm strategy. Specifically, broadcasters compete by selecting both the "type" and quality level of a program to offer, but do not compete on price. We obtain five major results. First, a comparison of monopoly and duopoly markets indicates that broadcasters in an industry with a larger number of competitors may provide programs of lower quality compared to broadcasters in an industry with a smaller number. Second, in terms of viewer welfare, having more channels available is not necessarily "better." Third, broadcasters tend to choose an intermediate level of differentiation in terms of the types of programs they provide, resulting in a "counterprogramming" strategy. In other words, avoidance of price competition is not required for competitors to differentiate themselves from each other. Fourth, if one broadcaster starts the evening with a higher-quality (higher-rated) program than its competitor, its second program should also be of higher quality. Finally, a broadcaster's first program should be of equal or higher quality than its second program. Put another way, it always behooves a broadcaster to "lead with its best."
Endogeneity in Marketing Decision Models
Authors: Shugan Steven M.
Published: May 2005

There are many critical concerns (including the accounting for endogeneity) when one is properly estimating response functions. However, it is sometimes (certainly not always) better to leave some variables exogenous when building mathematical models intended to help decision makers. The exogenous variables allow the decision maker to better adapt the mathematical model to different situations and to incorporate myriad variables and constraints outside of the model.
Optimal Allocation of Proposals to Reviewers to Facilitate Effective Ranking
Authors: Cook Wade D. , Golany Boaz , Kress Moshe , Penn Michal , Raviv Tal
Published: May 2005

Peer review of research proposals and articles is an essential element in research and development processes worldwide. Here we consider a problem that, to the best of our knowledge, has not been addressed until now: how to assign subsets of proposals to reviewers in scenarios where the reviewers supply their evaluations through ordinal ranking. The solution approach we propose for this assignment problem maximizes the number of proposal pairs that will be evaluated by one or more reviewers. This new approach should facilitate meaningful aggregation of partial rankings of subsets of proposals by multiple reviewers into a consensus ranking. We offer two ways to implement the approach: an integer-programming set-covering model and a heuristic procedure. The effectiveness and efficiency of the two models are tested through an extensive simulation experiment.
On the Benefits of Pooling in Production-Inventory Systems
Authors: Benjaafar Saif , Cooper William L. , Kim Joon-Seok
Published: May 2005

We study inventory pooling in systems with symmetric costs where supply lead times are endogenously generated by a finite-capacity production system. We investigate the sensitivity of the cost advantage of inventory pooling to various system parameters, including loading, service levels, demand and production time variability, and structure of the production system. The analysis reveals differences in how various parameters affect the cost reduction from pooling and suggests that these differences stem from the manner in which the parameters influence the induced correlation between lead-time demands of the demand streams. We compare these results with those obtained for pure inventory systems, where lead times are exogenous. We also compare inventory pooling with several forms of capacity pooling.
Bertrand Supertraps
Authors: Cabral Luís M. B. , Villas-Boas Miguel
Published: May 2005

We study oligopoly price competition between multiproduct firms—firms whose products interact in the profit function. Specifically, we focus on the impact of intrafirm product interactions on the level of equilibrium profits. This impact may be decomposed in two different ways: (a) a direct effect (keeping the competitors’ actions fixed) plus a strategic effect (i.e., through the competitors’ actions); or, alternatively, (b) a competitive advantage effect (change in firm i only) plus an imitation effect (change in all other firms). We derive conditions such that (a) the strategic effect more than outweighs the direct effect, and conditions such that (b) the imitation effect more than outweighs the competitive advantage effect: Bertrand supertraps. For example, an increase in the degree of economies of scope would increase profits if prices were fixed or if the change were limited to firm i’s cost function. However, if all firms increase the degree of economies of scope then all firms receive lower profits. A variety of other applications is considered, including learning curves, core competencies, demand synergies, systems competition, compatibility, bundling, network effects, switching costs, durable goods, long-term contracts.
Diversification and the Optimal Construction of Basis Portfolios
Authors: Lehmann Bruce N. , Modest David M.
Published: May 2005

Nontrivial diversification possibilities arise when a factor model describes security returns. This paper catalogs the merits of alternative strategies for constructing basis portfolios to mimic the common factors. We show how to use the 𝜒2 statistic for the joint significance of mean basis portfolio returns to rank alternative procedures and the bootstrap to perform inferences on the disparity between 𝜒2 statistics across portfolio formation procedure, estimation method, cross-section size, and number of factors. Our main conclusion is that maximum likelihood factor analysis coupled with minimum idiosyncratic risk portfolio formation yields economically and statistically superior basis portfolios compared with those derived from asymptotic principal components.
The Impact of Contractor Behavior on the Client’s Payment-Scheduling Problem
Authors: Szmerekovsky Joseph G.
Published: May 2005

Recent approaches to modeling the client’s payment-scheduling problem allow the client to control both the timing of payments and the completion times of activities. In practice, the activity schedule is typically determined by the contractor rather than the client. This paper addresses this drawback by considering a model in which the client selects the payment activities and the contractor selects the activity schedule, each to maximize his own net present value (NPV). In addition, the contractor has the option to reject the project if it does not provide a minimum NPV. The new model is shown to be NP-hard in the strong sense and a branch-and-bound procedure is provided for its solution. Results are obtained for the new model that contradict those of the older models. The benefits to the client are no longer increasing with retention and no longer decreasing with the number of payments. Furthermore, it is no longer ideal for the client to focus payments at the beginning and end of the project. Empirical evidence based on a randomly generated data set suggests that the market for the contractor’s services, the timing of benefits received by the client, and the project duration drive these new results.
Inventory Sharing and Rationing in Decentralized Dealer Networks
Authors: Zhao Hui , Deshpande Vinayak , Ryan Jennifer K.
Published: May 2005

An increasing number of manufacturers have started to pursue a strategy that promotes inventory sharing among the dealers in their distribution network. In this paper we analyze a decentralized dealer network in which each independent dealer is given the flexibility to share his inventory. We model inventory sharing as a multiple demand classes problem in which each dealer faces his own customer demand with high priority, and inventory-sharing requests from other dealers with low priority. Assuming that each dealer uses a base-stock and threshold-rationing policy for his inventory-stocking and inventory-sharing decisions, we explicitly model the interactions between the dealers through inventory sharing and obtain a closed-form cost function for each dealer based on the steady-state distribution of the inventory levels at the two dealers. We then provide a detailed supermodularity analysis of the inventory-sharing and inventory-rationing game in which each dealer has a two-dimensional strategy set (stocking level and rationing level). We show that the full-sharing game (in which dealers precommit to sharing all of their on-hand inventory) and the fixed-sharing-level game (in which dealers precommit to sharing a portion of their on-hand inventory) are supermodular, and thus a pure-strategy Nash equilibrium is guaranteed to exist. For the rationing game (in which dealers precommit to their stocking levels), we show that there exists a dominant strategy equilibrium on the dealers’ sharing (rationing) levels. Finally, a comprehensive computational study is conducted to highlight the impact of the manufacturer’s incentives, subsidies, and/or transshipment fees on the dealers’ sharing behavior.
Integrated Scheduling of Production and Distribution Operations
Authors: Chen Zhi-Long , Vairaktarakis George L.
Published: May 2005

Motivated by applications in the computer and food catering service industries, we study an integrated scheduling model of production and distribution operations. In this model, a set of jobs (i.e., customer orders) are first processed in a processing facility (e.g., manufacturing plant or service center) and then delivered to the customers directly without intermediate inventory. The problem is to find a joint schedule of production and distribution such that an objective function that takes into account both customer service level and total distribution cost is optimized. Customer service level is measured by a function of the times when the jobs are delivered to the customers. The distribution cost of a delivery shipment consists of a fixed charge and a variable cost proportional to the total distance of the route taken by the shipment. We study two classes of problems under this integrated scheduling model. In the first class of problems, customer service is measured by the average time when the jobs are delivered to the customers; in the second class, customer service is measured by the maximum time when the jobs are delivered to the customers. Two machine configurations in the processing facility—single machine and parallel machine—are considered. For each of the problems studied, we provide an efficient exact algorithm, or a proof of intractability accompanied by a heuristic algorithm with worst-case and asymptotic performance analysis. Computational experiments demonstrate that the heuristics developed are capable of generating near-optimal solutions. We also investigate the possible benefit of using the proposed integrated model relative to a sequential model where production and distribution operations are scheduled sequentially and separately. Computational tests show that in many cases a significant benefit can be achieved by integration.
Option Pricing with Downward-Sloping Demand Curves: The Case of Supply Chain Options
Authors: Burnetas Apostolos , Ritchken Peter
Published: May 2005

This article investigates the role of option contracts in a supply chain when the demand curve is downward sloping. We consider call (put) options that provide the retailer with the right to reorder (return) goods at a fixed price. We show that the introduction of option contracts causes the wholesale price to increase and the volatility of the retail price to decrease. In general, options are not zero-sum games. Conditions are derived under which the manufacturer prefers to use options. When this happens the retailer is also better off, if the uncertainty in the demand curve is low. However, if the uncertainty is sufficiently high, then the introduction of option contracts alters the equilibrium prices in a way that hurts the retailer.
Bundling Information Goods of Decreasing Value
Authors: Geng Xianjun , Stinchcombe Maxwell B. , Whinston Andrew B.
Published: May 2005

Consumers’ average value for information goods, websites, weather forecasts, music, and news declines with the number consumed. This paper provides simple guidelines to optimal bundling marketing strategies in this case. If consumers’ values do not decrease too quickly, we show that bundling is approximately optimal. If consumers’ values to subsequent goods decrease quickly, we show by example that one should expect bundling to be suboptimal.
Trust Building Among Strangers
Authors: Ho Teck-Hua , Weigelt Keith
Published: May 2005

The trust-building process is basic to social science. We investigate it in a laboratory setting using a novel multistage trust game where social gains are achieved if players trust each other in each stage. In each stage, also, players have an opportunity to appropriate these gains or be trustworthy by sharing them. Players are strangers because they do not know the identity of others and they will not play them again. Thus, there is no prospect of future interaction to induce trusting behavior, and we study the trust-building process where there is little scope for social relations and networks.

Standard game theory, which assumes all players are opportunistic and untrustworthy and thus should have zero trust for others, is used to construct a null hypothesis. We test whether people are trusting or trustworthy and examine how inferring the intentions of those who trust affects trustworthiness. We also investigate the effect of stake on trust, and study the evolution of trust.

Results show subjects exhibit some degree of trusting behavior, although a majority of them are not trustworthy and claim the entire social gain. Players are more reluctant to trust in later stages than in earlier ones and are more trustworthy if they are certain of the trustee’s intention. Surprisingly, subjects are more trusting and trustworthy when the stake size increases. Finally, we find the subpopulation that invests in initiating the trust-building process modifies its trusting behavior based on the relative fitness of trust.