bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete molecular responses are achieved after reduced intensity stem cell transplantation and donor lymphocyte infusion in chronic myeloid leukemia
Authors: Heaney Nicholas B. , Copland Mhairi , Stewart Karen , Godden Judith , Parker Anne N. , McQuaker I. Grant , Smith Graeme M. , Crawley Charles , Shepherd Pat , Holyoake Tessa L.
Published: April 2008

Patients with newly diagnosed chronic phase chronic myeloid leukemia were treated with imatinib mesylate (IM) for 6 to 12 months to establish disease control, before reduced intensity stem cell transplantation (RISCT). Escalating doses of donor lymphocyte infusions were given from 6 months after transplantation to eradicate residual disease. A total of 18 patients entered the study and 15 received RISCT (median follow-up, 31 months). RISCT was well tolerated with rapid engraftment, short inpatient stays, and few readmissions. Viral reactivation was common, although extensive graft-versus-host disease occurred infrequently. Donor lymphocyte infusions were given as part of the RISCT protocol in 13 of 15 patients. BCR-ABL transcripts continued to decrease after RISCT, and 8 (53%) patients achieved sustained undetectable levels. All patients are currently off IM. Although IM is now established as first-line therapy for chronic phase chronic myeloid leukemia, this protocol is a safe, well-tolerated, and effective strategy in these patients. This study is registered at http://www.controlled-trials.com as ISRCTN86187144.
High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study
Authors: Langer Christian , Radmacher Michael D. , Ruppert Amy S. , Whitman Susan P. , Paschka Peter , Mrózek Krzysztof , Baldus Claudia D. , Vukosavljevic Tamara , Liu Chang-Gong , Ross Mary E. , Powell Bayard L. , de la Chapelle Albert , Kolitz Jonathan E. , Larson Richard A. , Marcucci Guido , Bloomfield Clara D.
Published: April 2008

BAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile.
Capture of plasma membrane fragments from target cells by trogocytosis requires signaling in T cells but not in B cells
Authors: Aucher Anne , Magdeleine Eddy , Joly Etienne , Hudrisier Denis
Published: April 2008

Upon recognition of their respective cellular partners, T and B cells acquire their antigens by a process of membrane capture called trogocytosis. Here, we report that various inhibitors of actin polymerization or of kinases involved in intracellular signaling partially or fully inhibited trogocytosis by CD8+ and CD4+ T cells, whereas they had no effect on trogocytosis by B cells. Similarly, trogocytosis by T cells was inhibited at 4°C, whereas in B cells it was independent of temperature, indicating that trogocytosis by B cells does not rely on active processes. By contrast, most inhibitors we tested impaired both T-cell and B-cell activation. The differential effect of inhibitors on T-cell and B-cell trogocytosis was not due to the higher affinity of the B-cell receptor for its cognate antigen compared with the affinity of the T-cell receptor for its own antigen, but it correlated tightly with the abilities of T cells and B cells to form conjugates with their target cells in the presence of inhibitors. Trogocytosis thus has different requirements in different cell types. Moreover, the capture of membrane antigen by B cells is identified as a novel signaling-independent event of B-cell biology.
Comparative mapping of Brassica juncea and Arabidopsis thaliana using Intron Polymorphism (IP) markers: homoeologous relationships, diversification and evolution of the A, B and C Brassica genomes
Authors: Panjabi Priya , Jagannath Arun , Bisht Naveen C , Padmaja K Lakshmi , Sharma Sarita , Gupta Vibha , Pradhan Akshay K , Pental Deepak
Published: April 2008

Background

Extensive mapping efforts are currently underway for the establishment of comparative genomics between the model plant, Arabidopsis thaliana and various Brassica species. Most of these studies have deployed RFLP markers, the use of which is a laborious and time-consuming process. We therefore tested the efficacy of PCR-based Intron Polymorphism (IP) markers to analyze genome-wide synteny between the oilseed crop, Brassica juncea (AABB genome) and A. thaliana and analyzed the arrangement of 24 (previously described) genomic block segments in the A, B and C Brassica genomes to study the evolutionary events contributing to karyotype variations in the three diploid Brassica genomes.

Results

IP markers were highly efficient and generated easily discernable polymorphisms on agarose gels. Comparative analysis of the segmental organization of the A and B genomes of B. juncea (present study) with the A and B genomes of B. napus and B. nigra respectively (described earlier), revealed a high degree of colinearity suggesting minimal macro-level changes after polyploidization. The ancestral block arrangements that remained unaltered during evolution and the karyotype rearrangements that originated in the Oleracea lineage after its divergence from Rapa lineage were identified. Genomic rearrangements leading to the gain or loss of one chromosome each between the A-B and A-C lineages were deciphered. Complete homoeology in terms of block organization was found between three linkage groups (LG) each for the A-B and A-C genomes. Based on the homoeology shared between the A, B and C genomes, a new nomenclature for the B genome LGs was assigned to establish uniformity in the international Brassica LG nomenclature code.

Conclusion

IP markers were highly effective in generating comparative relationships between Arabidopsis and various Brassica species. Comparative genomics between the three Brassica lineages established the major rearrangements, translocations and fusions pivotal to karyotype diversification between the A, B and C genomes of Brassica species. The inter-relationships established between the Brassica lineages vis-à-vis Arabidopsis would facilitate the identification and isolation of candidate genes contributing to traits of agronomic value in crop Brassicas and the development of unified tools for Brassica genomics.
Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease
Authors: van Dellen Anton , Cordery Patricia M , Spires Tara L , Blakemore Colin , Hannan Anthony J
Published: April 2008

Background

Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit.

Results

We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running.

Conclusion

These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.
Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection
Authors: Goffinet Marine , Chinestra Patrick , Lajoie-Mazenc Isabelle , Medale-Giamarchi Claire , Favre Gilles , Faye Jean-Charles
Published: April 2008

Background

The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv) that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings.

Results

After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L), three scFvs (A8, C1 and D11) were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2), it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence.

Conclusion

We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated Rho in immunofluorescence studies implies that this new tool, in collaboration with currently used RhoA and B antibodies, has the potential to analyze Rho activation in cell function and tumor development.
HIV transfer between CD4 T cells does not require LFA-1 binding to ICAM-1 and is governed by the interaction of HIV envelope glycoprotein with CD4
Authors: Puigdomènech Isabel , Massanella Marta , Izquierdo-Useros Nuria , Ruiz-Hernandez Raul , Curriu Marta , Bofill Margarita , Martinez-Picado Javier , Juan Manel , Clotet Bonaventura , Blanco Julià
Published: April 2008

Background

Cell-to-cell HIV transmission requires cellular contacts that may be in part mediated by the integrin leukocyte function antigen (LFA)-1 and its ligands intercellular adhesion molecule (ICAM)-1, -2 and -3. The role of these molecules in free virus infection of CD4 T cells or in transinfection mediated by dendritic cells (DC) has been previously described. Here, we evaluate their role in viral transmission between different HIV producing cells and primary CD4 T cells.

Results

The formation of cellular conjugates and subsequent HIV transmission between productively infected MOLT cell lines and primary CD4 T cells was not inhibited by a panel of blocking antibodies against ICAM-1, ICAM-3 and α and β chains of LFA-1. Complete abrogation of HIV transmission and formation of cellular conjugates was only observed when gp120/CD4 interactions were blocked. The dispensable role of LFA-1 in HIV transmission was confirmed using non-lymphoid 293T cells, lacking the expression of adhesion molecules, as HIV producing cells. Moreover, HIV transmission between infected and uninfected primary CD4 T cells was abrogated by inhibitors of gp120 binding to CD4 but was not inhibited by blocking LFA-1 binding to ICAM-1 or ICAM-3. Rather, LFA-1 and ICAM-3 mAbs enhanced HIV transfer. All HIV producing cells (including 293T cells) transferred HIV particles more efficiently to memory than to naive CD4 T cells.

Conclusion

In contrast to other mechanisms of viral spread, HIV transmission between infected and uninfected T cells efficiently occurs in the absence of adhesion molecules. Thus, gp120/CD4 interactions are the main driving force of the formation of cellular contacts between infected and uninfected CD4 T cells whereby HIV transmission occurs.
Phase II Study of Dose-Adjusted EPOCH and Rituximab in Untreated Diffuse Large B-Cell Lymphoma With Analysis of Germinal Center and Post-Germinal Center Biomarkers
Authors: Wilson Wyndham H. , Dunleavy Kieron , Pittaluga Stefania , Hegde Upendra , Grant Nicole , Steinberg Seth M. , Raffeld Mark , Gutierrez Martin , Chabner Bruce A. , Staudt Louis , Jaffe Elaine S. , Janik John E.
Published: April 2008

Purpose

To assess the clinical outcome and the influence of biomarkers associated with apoptosis inhibition (Bcl-2), tumor proliferation (MIB-1), and cellular differentiation on the outcome with dose-adjusted (DA) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) plus rituximab (R) infusional therapy in diffuse large B-cell lymphoma (DLBCL) with analysis of germinal center B-cell (GCB) and post-GCB subtypes by immunohistochemistry.

Patients and Methods

Phase II study of 72 patients with untreated de novo DLBCL who were at least 18 years of age and stage II or higher. Radiation consolidation was not permitted.

Results

Patients had a median age of 50 years (range, 19 to 85) and 40% had a high-intermediate or high International Prognostic Index (IPI). At 5 years, progression-free survival (PFS) and overall survival (OS) were 79% and 80%, respectively, with a median potential follow-up of 54 months. PFS was 91%, 90%, 67%, and 47%, and OS was 100%, 90%, 74%, and 37%, for 0 to 1, 2, 3, and 4 to 5 IPI factors, respectively, at 5 years. The Bcl-2 and MIB-1 biomarkers were not associated with PFS or OS. Based on DA-EPOCH historical controls, rituximab only benefited Bcl-2 positive tumors. Bcl-6 expression was associated with higher PFS whereas GCB exhibited a marginally significant higher PFS compared with post-GCB DLBCL.

Conclusion

DA-EPOCH-R outcome was not affected by tumor proliferation and rituximab appeared to overcome the adverse effect of Bcl-2. Bcl-6 may identify a biologic program associated with a superior outcome. Overall, DA-EPOCH-R shows promising outcome in low and intermediate IPI groups. A molecular model of treatment outcome with rituximab and chemotherapy is presented.
Effects of morin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine in rats
Authors: Piao Yong-Ji , Choi Jun-Shik
Published: April 2008

This study investigated the effects of orally administered morin, an inhibitor of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), on the pharmacokinetics of orally and intravenously administered nicardipine in rats. Nicardipine is reportedly a substrate for CYP3A4 and P-gp. Nicardipine was administered orally (12 mgkg−1) with or without orally administered morin (1.5, 7.5 and 15 mgkg−1), and intravenously (4 mgkg−1) with or without orally administered morin (7.5 and 15 mgkg−1). In the presence of morin, the pharmacokinetic parameters of nicardipine were significantly altered in the oral group but not in the intravenous group, suggesting that CYP3A-mediated metabolism of nicardipine in the liver is not significantly inhibited by morin. The presence of 7.5 and 15 mgkg−1 of morin significantly increased (P< 0.01, 67.8–112%) the area under the plasma concentration-time curve and the peak plasma concentration (P< 0.01, 53.5–93.1%) of orally administered nicardipine. The presence of 7.5 and 15 mgkg−1 of morin significantly decreased (P < 0.01, 40.4–52.8%) the total body clearance of orally administered nicardipine compared with the control group. The enhanced oral bioavailability of nicardipine suggests that intestinal-mediated CYP3A4 metabolism and P-gp-mediated efflux of nicardipine are inhibited by morin. Based on these results, concomitant use of morin or morin-containing dietary supplements with nicardipine may require close monitoring for potential drug interactions.
ABCC2 haplotype is not associated with drug-resistant epilepsy
Authors: Seo Takayuki , Ishitsu Takateru , Oniki Kentaro , Abe Tomohide , Shuto Tsuyoshi , Nakagawa Kazuko
Published: April 2008

Several studies have investigated the association between the ABCB1 polymorphism and drug-resistant epilepsy. However, the effect of ABCC2 polymorphisms on anti-epileptic drug (AED) responsiveness remains unknown. The ABCC2 polymorphisms have been genotyped in 279 Japanese epileptic patients treated with AEDs. The association between the AED responsiveness and the polymorphisms was estimated by a haplotype-based analysis. No genotype or haplotype was associated with drug-resistant epilepsy. On the other hand, the delGCGC haplotype at G-1774delG, C-24T, G1249A and C3972T was over represented among the epileptic patients with a complication of mental retardation in comparison with those without (32.4% vs 22.0%; P = 0.009); and the G-1774delG allele was also associated with mental retardation (P = 0.03). No association between the ABCC2 genotypes or haplotypes, and the responsiveness of AEDs was observed, although this finding was inconclusive because of the small sample size.
The ability of selected pyridinium salts to increase the cytotoxic activity of vincristine but not doxorubicin towards sensitive and multidrug resistant promyelocytic leukaemia HL60 cells
Authors: Maruszewska Agnieszka , Kostrzewa-Nowak Dorota , Adamus Jan , Czupryńska Katarzyna , Maryniak Dominika , Gebicki Jerzy , Tarasiuk Jolanta
Published: April 2008

The aim of this study was to examine the effect of selected pyridinium salts, 1-methyl-3-nitropyridine chloride (MNP+Cl−) and 3,3,6,6,10-pentamethyl-3,4,6,7-tetrahydro-[1,8(2H,5H)-dion]acridine chloride (MDION+Cl−), on the activity of doxorubicin (DOX) and vincristine (VINC) towards human promyelocytic leukaemia HL60 cells as well as its multidrug resistant (MDR) sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). MNP and MDION salts were much less cytotoxic themselves (about 100-fold and 2000-fold compared with DOX and VINC, respectively) against HL60 cells but, in contrast to DOX and VINC, they conserved an important cytotoxic activity towards resistant HL60/VINC and HL60/DOX cells (resistance factor, RF = 2–4.5). It was shown that MNP+Cl− and MDION+Cl− increased the cytotoxicity of non-bioreductive antitumour agent VINC towards human promyelocytic leukaemia HL60 cells and its resistant sublines HL60/VINC and HL60/DOX. However, in the case of DOX the decrease in its cytotoxic activity towards all studied cell lines was observed in the presence of MNP+Cl− and MDION+Cl−. Presented data suggest that the bioreductive drug DOX, in contrast to VINC, could compete with pyridinium salts (MNP+Cl− and MDION+Cl−) for NADPH-dependent oxidoreductases and for undergoing cellular reductive activation. This could explain the inefficiency of these salts to increase the cytotoxic activity of DOX against examined leukaemic HL60 cell line and its MDR sublines, HL60/VINC and HL60/DOX.
Misphasing of Ion Motion in Quadratic Potential Induced by Space-Periodic Disturbance
Authors: Boldin Ivan A. , Nikolaev Eugene N.
Published: April 2008

An ideally quadratic potential used in different types of ion mass analyzer such as Paul trap, Kingdon trap and quadratic field reflectron may be space-periodically disturbed due to inaccuracy of fabrication and design features. If ion motion in such devices is computer-simulated, disturbances of potential may be caused by the peculiarity of the computation method. The problem investigated in this work is the effect that weak space-periodic disturbance of a quadratic potential takes on the ion motion in such a potential. The effect of the disturbance we considered is the misphasing of an ion cloud oscillating in a disturbed quadratic potential. A method to evaluate the characteristic misphasing time is presented. For the case of disturbance amplitude being constant along ion trajectories, the designated problem may be considered analytically. If the disturbance amplitude depends on oscillation co-ordinate, the result can be obtained by use of numerical integration. An example of numerical calculation is presented.
Ion Optical Evaluation of a Miniature Double-Focusing Mass Spectrograph
Authors: Nishiguchi Masaru , Ishihara Morio , Katakuse Itsuo , Toyoda Michisato
Published: April 2008

A new miniature double-focusing mass spectrograph has been designed and constructed. The ion optical system was designed based on Mattauch–Herzog geometry. The mass spectrograph employs a focal plane detector consisting of a microchannel plate, a phosphor layer, a fiber-optic plate and a charge-coupled device. For the evaluation of the ion optics of the instrument, the energy and angular focal planes were investigated both experimentally and by simulation. Double focusing was satisfactorily achieved along a straight line over a wide mass range, and the experimental and simulated results were mutually consistent. A second-order element of the transfer matrix was also measured experimentally and proved to be in good agreement with the simulated result.
How Complex Do Movie Channel Contracts Need to Be?
Authors: Raut Sumit , Swami Sanjeev , Lee Eunkyu , Weinberg Charles B.
Published: April 2008

The motion picture industry is characterized by a dynamic market environment, limited shelf space and product category management, and consequently, complex channel contracts specifying the split of box office revenue between distributors and exhibitors. Although such a contracting practice creates a considerable administrative effort and channel conflict, it is not clear whether such complexity is necessary for superior channel performance. This study investigates this question by analyzing the impact of movie contract structure on movie scheduling and channel member profitability. We develop and analyze a game-theoretic model using the genetic algorithm approach and a decision support system, SilverScreener, to capture strategic behaviors of channel members in a complex market environment. We find that simpler two-part tariff or 50/50 split contracts perform as well as the current contracts. Thus, the complexity of the market environment need not be reflected in the complexity of the channel contracts. Channel contract structure has significant impact on channel member profitability and the exhibitor's movie-scheduling behavior. In particular, our results indicate that the flat rate contract structure represents an attractive alternative to the current practice for distributors.
Research Note—Does Demand Fall When Customers Perceive That Prices Are Unfair? The Case of Premium Pricing for Large Sizes
Authors: Anderson Eric T. , Simester Duncan I.
Published: April 2008

We analyze a large-scale field test conducted with a mail-order catalog firm to investigate how customers react to premium prices for larger sizes of women's apparel. We find that customers who demand large sizes react unfavorably to paying a higher price than customers for small sizes. Further investigation suggests that these consumers perceive that the price premium is unfair. Overall, premium pricing led to a 6% to 8% decrease in gross profits.
Old and New Methods for Lost-Sales Inventory Systems
Authors: Zipkin Paul
Published: April 2008

We consider the notoriously difficult discrete-time inventory model with stochastic demands, a constant lead time, and lost sales. We show that the effective state space is a relatively manageable compact set. Then, we test various plausible heuristics. We find that several perform reasonably well, although none is perfect. However, the standard base-stock policy (a direct analogue of the optimal policy for a backlog system) performs badly. We also show that the optimal cost is increasing in the lead time.
An Effective Multirestart Deterministic Annealing Metaheuristic for the Fleet Size and Mix Vehicle-Routing Problem with Time Windows
Authors: Bräysy Olli , Dullaert Wout , Hasle Geir , Mester David , Gendreau Michel
Published: April 2008

This paper presents a new deterministic annealing metaheuristic for the fleet size and mix vehicle-routing problem with time windows. The objective is to service, at minimal total cost, a set of customers within their time windows by a heterogeneous capacitated vehicle fleet. First, we motivate and define the problem. We then give a mathematical formulation of the most studied variant in the literature in the form of a mixed-integer linear program. We also suggest an industrially relevant, alternative definition that leads to a linear mixed-integer formulation. The suggested metaheuristic solution method solves both problem variants and comprises three phases. In Phase 1, high-quality initial solutions are generated by means of a savings-based heuristic that combines diversification strategies with learning mechanisms. In Phase 2, an attempt is made to reduce the number of routes in the initial solution with a new local search procedure. In Phase 3, the solution from Phase 2 is further improved by a set of four local search operators that are embedded in a deterministic annealing framework to guide the improvement process. Some new implementation strategies are also suggested for efficient time window feasibility checks. Extensive computational experiments on the 168 benchmark instances have shown that the suggested method outperforms the previously published results and found 167 best-known solutions. Experimental results are also given for the new problem variant.
Choice Construction versus Preference Construction: The Instability of Preferences Learned in Context
Authors: Amir On , Levav Jonathan
Published: April 2008

Preference consistency implies that people have learned their willingness to trade off attributes. The authors argue that this is not necessarily the case. Instead, they show that when people learn preferences in context (e.g., through repeated choices made from a trinary choice set that includes an asymmetrically dominated decoy), they learn a context-specific choice heuristic (e.g., they always choose the asymmetrically dominating option), which leads to less consistent preferences across contexts. In contrast, repeated choices from sets containing only two options impel people to learn their subjective attribute weights, yielding preferences that are consistent across contexts. The difference between choice construction and preference construction is of importance to marketing managers because repeat purchase is typically interpreted as a signal of customer preference. The authors show that this “preference” might just be a learned solution to the choice problem and that as soon as the competitive context changes (even in a normatively meaningless way), so will consumers' preferences.
The Temporal and Spatial Dimensions of Price Search: Insights from Matching Household Survey and Purchase Data
Authors: Gauri Dinesh K. , Sudhir K. , Talukdar Debabrata
Published: April 2008

Price promotions are pervasive in grocery markets. A household can respond to price promotions by effectively cherry-picking through (1) spatial price search across stores and (2) temporal price search across time. However, extant research has analyzed these two dimensions of price search only separately and therefore underestimates both the consumer response to price promotions and the impact of promotions on retail profit. In this article, the authors introduce an integrated analysis of spatial and temporal price search. They seek answers to three questions: First, what are the predictors of household decisions to perform either spatial or temporal price search? Second, how effective are the temporal, spatial, and spatiotemporal price search strategies in obtaining lower prices? and Third, what is the impact of alternative price search strategies on retailer profit? The authors use a unique data collection approach that combines household surveys with observed purchase data to address these questions. Their key results are as follows: Geography (the spatial configuration of store and household locations) and opportunity costs are useful predictors of a household's price search pattern. Households that claim to search spatiotemporally avail approximately three-quarters of the available savings on average. Households that search only temporally save about the same as those that search only spatially. The negative effect of cherry-picking on retailer profits is not as high as is typically believed.
Is Firm Trust Essential in a Trusted Environment? how Trust in the Business Context Influences Customers
Authors: Grayson Kent , Johnson Devon , Chen Der-Fa Robert
Published: April 2008

Customers are influenced not only by how much they trust a company and its representatives but also by how much they trust the broader context in which the market exchange is taking place. In this article, the authors test two rival sociological perspectives regarding the influence of customer trust in the broader context. One perspective proposes that trust in the context replaces trust in individual firms and their representatives. This view suggests that firm/representative trust is not always critical, especially for customers with high trust in the context. An alternative perspective is that trust in the context fosters and legitimates trust in firms and their representatives. This view implies that firm/representative trust is a necessary mediator of the influence of trust in the context. The authors test predictions based on both perspectives, using empirical results from two studies implemented in two countries. The results from both studies support the proposition that trust in firms and their representatives is a necessary mediator of trust in the broader context.
Importance of Early Neglect for Childhood Aggression
Authors: Kotch Jonathan B. , Lewis Terri , Hussey Jon M. , English Diana , Thompson Richard , Litrownik Alan J. , Runyan Desmond K. , Bangdiwala Shrikant I. , Margolis Benyamin , Dubowitz Howard
Published: April 2008

OBJECTIVE. The goal was to examine the association between early childhood neglect (birth to age 2 years) and later childhood aggression at ages 4, 6, and 8 years, compared with aggression's associations with early childhood abuse and later abuse and neglect.

METHODS. A prospective cohort of 1318 predominantly at-risk children, recruited from 4 US cities and 1 southern state, were monitored from birth to 8 years of age. Maltreatment was determined through review of local child protective services records. A hierarchical, linear model approach, a special case of general, linear, mixed modeling, was used to predict aggressive behavior scores, as reported by the child's primary caregiver at ages 4, 6, and 8 years.

RESULTS. Only early neglect significantly predicted aggression scores. Early abuse, later abuse, and later neglect were not significantly predictive in a controlled model with all 4 predictors.

CONCLUSION. This longitudinal study suggests that child neglect in the first 2 years of life may be a more-important precursor of childhood aggression than later neglect or physical abuse at any age.
Growth and Nutrient Intakes of Human Milk–Fed Preterm Infants Provided With Extra Energy and Nutrients After Hospital Discharge
Authors: O'Connor Deborah L. , Khan Sobia , Weishuhn Karen , Vaughan Jennifer , Jefferies Ann , Campbell Douglas M. , Asztalos Elizabeth , Feldman Mark , Rovet Joanne , Westall Carol , Whyte Hilary ,   on behalf of the Postdischarge Feeding Study Group
Published: April 2008

OBJECTIVES. The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk–fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding.

METHODS. Human milk–fed (≥80% feeding per day) low birth weight (750–1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain ∼80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups.

RESULTS. Infants in the intervention group were longer during the study period, and those born ≤1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group.

CONCLUSIONS. Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk–fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided.
Vaccination Coverage by Special Health Care Needs Status in Young Children
Authors: O'Connor Kathleen S. , Bramlett Matthew D.
Published: April 2008

OBJECTIVE. The purpose of this study was to compare vaccination coverage among children 19 to 35 months of age with and without special health care needs overall and among demographic subgroups.

METHODS. Data are from the National Survey of Children With Special Health Care Needs, a module of the State and Local Area Integrated Telephone Survey, which was sponsored by the Health Resources and Services Administration Maternal and Child Health Bureau and conducted in 2000–2002 by the Centers for Disease Control and Prevention National Center for Health Statistics. We used data from the National Immunization Survey and the National Survey of Children With Special Health Care Needs to examine immunization coverage rates for individual vaccines and an array of combined series vaccinations. The relationship between special needs and immunization status was analyzed by age, gender, and race or ethnicity of the child; the child's health insurance type; the mother's educational attainment and presence in the household; and household income relative to the federal poverty level.

RESULTS. Overall, there were no significant differences between children with and without special needs for any of the individual antigens or combined immunization series. Some significant differences by special needs status were found within certain demographic subgroups.

CONCLUSIONS. Our results suggest that, generally children with special health care needs have immunization rates that are very similar to typically developing children. There is some evidence that children with special health care needs are at risk for underimmunization if they are non-Hispanic white or live in an affluent household and are more likely to be immunized if they are Hispanic, poor, publicly insured, or if their mothers did not complete high school. These findings may be due to outreach or support programs that target disadvantaged children. However, it is important to note that the majority of comparisons within demographic subgroups show no significant differences between children with special health care needs and children without special health care needs.
Choreoathetosis After Herpes Simplex Encephalitis With Basal Ganglia Involvement on MRI
Authors: Kullnat Megan Wills , Morse Richard P.
Published: April 2008

Children with herpes simplex virus encephalitis have a relapse in ∼25% of cases, which rarely may present as a movement disorder, most often choreoathetosis. The anatomic basis for herpes simplex virus encephalitis-associated movement disorders has been poorly understood, because neuroimaging, to date, has not been able to show the direct involvement of the areas of the brain that typically govern such movements. We present a patient with abnormal involuntary movements after herpes simplex virus encephalitis, with new lesions on MRI between the time of initial presentation and the development of choreoathetosis. To our knowledge, this is the first patient with a post-herpes simplex virus encephalitis movement disorder with neuroradiographic evidence of thalamic involvement correlating with the onset of abnormal involuntary movements. We describe this patient and review the literature on movement disorders and herpes simplex virus encephalitis. Current understanding of the pathophysiology of post-herpes simplex virus encephalitis movement disorders proposes 2 possible mechanisms that may be responsible: reinfection with the resumption of viral replication, or a postinfectious, immune-mediated process.
Inattention, Hyperactivity, and School Performance in a Population of School-Age Children With Complex Congenital Heart Disease
Authors: Shillingford Amanda J. , Glanzman Marianne M. , Ittenbach Richard F. , Clancy Robert R. , Gaynor J. William , Wernovsky Gil
Published: April 2008

INTRODUCTION. There is a growing interest in characterizing the neurodevelopmental outcomes of school-age survivors of cardiac surgery. The purpose of this study was to examine a population of 5- to 10-year-old children who underwent newborn cardiac surgery for complex congenital heart disease to characterize and assess risk factors for problems with inattention and hyperactivity, as well as the use of remedial school services.

PATIENTS AND METHODS. This study was a cross-sectional analysis of patients who underwent newborn cardiac surgery and were enrolled in a neuroprotection trial conducted at our institution between 1992 and 1997. Parents and teachers completed questionnaires for the school-age child to elicit information pertaining to the child's general health and academic performance. The severity of hyperactivity and inattention were assessed by using 2 standardized questionnaires (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV and Behavior Assessment System for Children). In addition to calculating descriptive estimates of their occurrence, single-covariate logistic regression models were specified and tested by using 3 different outcomes (inattention, hyperactivity, and use of remedial school services) and 14 different covariates representing preoperative, intraoperative, and postoperative factors.

RESULTS. Data were obtained from parents and/or teachers for 109 children. Fifty-three (49%) were receiving some form of remedial academic services, and 15% were assigned to a special-education classroom. The number of children receiving clinically significant scores for inattention and hyperactivity on the Behavior Assessment System for Children was 3 to 4 times higher than observed in the general population. On the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, 30% of the parents reported high-risk scores for inattention and 29% reported high-risk scores for hyperactivity. No perioperative factors were statistically associated with adverse outcomes.

CONCLUSION. In this cohort of children with complex congenital heart disease, a significant proportion of the children were at risk for inattention and hyperactivity, and nearly half were using remedial school services. We did not identify any perioperative risk factors, which correlated with high-risk scores or the use of remedial school services. Ongoing neurodevelopmental follow-up and screening are recommended in this vulnerable population.
Readmission for Neonatal Jaundice in California, 1991–2000: Trends and Implications
Authors: Burgos Anthony E. , Schmitt Susan K. , Stevenson David K. , Phibbs Ciaran S.
Published: April 2008

OBJECTIVE. We sought to describe population-based trends, potential risk factors, and hospital costs of readmission for jaundice for term and late preterm infants.

METHODS. Birth-cohort data were obtained from the California Office of Statewide Health Planning and Development and contained infant vital statistics data linked to infant and maternal hospital discharge summaries. The study population was limited to healthy, routinely discharged infants through the use of multiple exclusion criteria. All linked readmissions occurred within 14 days of birth. International Classification of Diseases, Ninth Revision, codes were used to further limit the sample to readmission for jaundice. Hospital discharge records were the source of diagnoses, hospital charges, and length-of-stay information. Hospital costs were estimated using hospital-specific ratios of costs to charges and adjusted to 1991.

RESULTS. Readmission rates for jaundice generally rose after 1994 and peaked in 1998 at 11.34 per 1000. The readmission rate for late preterm infants (as a share of all infants) over the study period remained at <2 per 1000. Factors associated with increased likelihood of hospital readmission for jaundice included gestational age 34 to 39 weeks, birth weight of <2500 g, male gender, Medicaid or private insurance, and Asian race. Factors associated with a decreased likelihood of readmission for jaundice were cesarean section delivery and black race. The mean cost of readmission for all infants was $2764, with a median cost of $1594.

CONCLUSIONS. Risk-adjusted readmission rates for jaundice rose following the 1994 hyperbilirubinemia guidelines and declined after postpartum length-of-stay legislation in 1998. In 2000, the readmission rate remained 6% higher than in 1991. These findings highlight the complex relationship among newborn physiology, socioeconomics, race or ethnicity, public policy, clinical guidelines, and physician practice. These trend data provide the necessary baseline to study whether revised guidelines will change practice patterns or improve outcomes. Cost data also provide a break-even point for prevention strategies.
A Policy-Based School Intervention to Prevent Overweight and Obesity
Authors: Foster Gary D. , Sherman Sandy , Borradaile Kelley E. , Grundy Karen M. , Vander Veur Stephanie S. , Nachmani Joan , Karpyn Allison , Kumanyika Shiriki , Shults Justine
Published: April 2008

BACKGROUND. The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic settings. Schools are ideal settings for population-based interventions to address obesity.

OBJECTIVE. The purpose of this work was to examine the effects of a multicomponent, School Nutrition Policy Initiative on the prevention of overweight (85.0th to 94.9th percentile) and obesity (>95.0th percentile) among children in grades 4 through 6 over a 2-year period.

METHODS. Participants were 1349 students in grades 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50% of students eligible for free or reduced-price meals. Schools were matched on school size and type of food service and randomly assigned to intervention or control. Students were assessed at baseline and again after 2 years. The School Nutrition Policy Initiative included the following components: school self-assessment, nutrition education, nutrition policy, social marketing, and parent outreach.

RESULTS. The incidences of overweight and obesity after 2 years were primary outcomes. The prevalence and remission of overweight and obesity, BMI z score, total energy and fat intake, fruit and vegetable consumption, body dissatisfaction, and hours of activity and inactivity were secondary outcomes. The intervention resulted in a 50% reduction in the incidence of overweight. Significantly fewer children in the intervention schools (7.5%) than in the control schools (14.9%) became overweight after 2 years. The prevalence of overweight was lower in the intervention schools. No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years.

CONCLUSION. A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grades 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals.