bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Phase II Study of Two Irinotecan Schedules for Patients With Metastatic Breast Cancer Refractory to an Anthracycline, a Taxane, or Both
Authors: Perez Edith A. , Hillman David W. , Mailliard James A. , Ingle James N. , Ryan J. Michael , Fitch Tom R. , Rowland Kendrith M. , Kardinal Carl G. , Krook James E. , Kugler John W. , Dakhil Shaker R.
Published: July 2004

Purpose

A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules.

Patients and Methods

MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m2 weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m2 every 3 weeks.

Results

The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with ≥ 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm.

Conclusion

Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.
Incidence Proportions of Brain Metastases in Patients Diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System
Authors: Barnholtz-Sloan Jill S. , Sloan Andrew E. , Davis Faith G. , Vigneau Fawn D. , Lai Ping , Sawaya Raymond E.
Published: July 2004

Purpose

Population-based estimates of the incidence of brain metastases are not generally available. The purpose of this study was to calculate population-based incidence proportions (IPs) of brain metastases from single primary lung, melanoma, breast, renal, or colorectal cancer.

Patients and Methods

Patients diagnosed with single primary lung, melanoma, breast, renal, or colorectal cancer (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (MDCSS) were used for analysis. IP of brain metastases by primary site and variable of interest (race, sex, age at diagnosis of primary cancer, and Surveillance, Epidemiology, and End Results [SEER] stage of primary cancer) was calculated with 95% CIs.

Results

Total IP percentage (IP%) of brain metastases was 9.6% for all primary sites combined, and highest for lung (19.9%), followed by melanoma (6.9%), renal (6.5%), breast (5.1%), and colorectal (1.8%) cancers. Racial differences were seen with African Americans demonstrating higher IP% of brain metastases compared with other racial groups for most primary sites. IP% was significantly higher for female patients with lung cancer, and significantly higher for male patients with melanoma. The highest IP% of brain metastases occurred at different ages at diagnoses: age 40 to 49 years for primary lung cancer; age 50 to 59 years for primary melanoma, renal, or colorectal cancers; and age 20 to 39 for primary breast cancer. IP% significantly increased as SEER stage of primary cancer advanced for all primary sites.

Conclusion

Total IP% of brain metastases was lower than previously reported, and it varied by primary site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary cancer.
Repertory Grid as a Means to Compare and Contrast Developmental Theorists
Authors: Mayo Joseph A.
Published: July 2004

This article reports on the use of a repertory grid as a tool for studying conceptual systems in line with Kelly's (1955) personal construct theory. Using 7-point construct continua, students rated the positions of major developmental theorists on various bipolar constructs (e.g., nature–nurture, continuity–discontinuity) representing salient developmental issues. The results of objective testing, combined with the findings from a brief survey of students' attitudes toward repertory grid assignments, indicated that a repertory grid is a useful pedagogical strategy in terms of organizing course content, encouraging students' conceptual understanding, and challenging students intellectually. Moreover, when conjoined with the opportunity for classroom discussion, this technique stimulates active participation in the learning process.
Using Web-Based Quizzing to Improve Exam Performance: Lessons Learned
Authors: Daniel David B. , Broida John
Published: July 2004

This study examined the utility of Web-based quizzing. We assigned 3 classes to a no-quiz, in-class quiz, or Web-based quiz condition. Midsemester results demonstrated a positive effect for in-class quizzing but not Web-based quizzing. After several adjustments in quiz presentation and duration, the Web-based group increased exam performance to a level equivalent to the in-class quiz group for the second half of the semester. These results illustrate that online quizzing can be as effective as in-class quizzing, but only under specific conditions.
On Blue Tongues, Undergraduates, and Science: An Interview with Linda M. Bartoshuk
Authors: King Camille Tessitore
Published: July 2004

Camille Tessitore King is an Assistant Professor in the Department of Psychology at Stetson University in DeLand, Florida, where she teaches Introduction to Psychology, Great Experiments in Psychology, Biological Psychology, as well as other advanced topic courses such as Drugs and Behavior. She received her BA, MA, and PhD from the University of Virginia where her research career began as an undergraduate student. King's research focus is on identifying the neural circuits involved in taste-related behaviors.

Linda M. Bartoshuk is a Professor in the Departments of Surgery and Psychology at Yale University School of Medicine, New Haven, Connecticut. She does psychophysical research on genetic variation in taste as well as with patients with taste disorders. She received her BA from Carleton College and her PhD from Brown University. She has been President of the Association for Chemoreception Sciences, the Eastern Psychological Association, and Divisions 1 (General Psychology) and 6 (Behavioral Neuroscience and Comparative Psychology) of the American Psychological Association.
The TOR pathway interacts with the insulin signaling pathway to regulateC. eleganslarval development, metabolism and life span
Authors: Jia Kailiang , Chen Di , Riddle Donald L.
Published: July 2004

The highly conserved target-of-rapamycin (TOR) protein kinases control cell growth in response to nutrients and growth factors. In mammals, TOR has been shown to interact with raptor to relay nutrient signals to downstream translation machinery. We report that in C. elegans, mutations in the genes encoding CeTOR and raptor result in dauer-like larval arrest, implying that CeTOR regulates dauer diapause. The daf-15 (raptor) and let-363 (CeTOR) mutants shift metabolism to accumulate fat, and raptor mutations extend adult life span. daf-15 transcription is regulated by DAF-16, a FOXO transcription factor that is in turn regulated by daf-2 insulin/IGF signaling. This is a new mechanism that regulates the TOR pathway. Thus, DAF-2 insulin/IGF signaling and nutrient signaling converge on DAF-15 (raptor) to regulate C. elegans larval development, metabolism and life span.
Localized Notch signal acts througheygandupdto promote global growth inDrosophilaeye
Authors: Chao Ju-Lan , Tsai Yu-Chen , Chiu Sue-Jean , Sun Y. Henry
Published: July 2004

Notch (N) signal is activated at the dorsoventral (DV) border of the Drosophila eye disc and is important for growth of the eye disc. In this study, we showed that the Pax protein Eyg is a major effector mediating the growth promotion function of N. eyg transcription is induced by N signaling occurring at the DV border. Like N, eyg controls growth of the eye disc. Loss of N signaling can be compensated by overexpressing eyg, whereas loss of the downstream eygblocked the function of N signaling. In addition, we showed that Nand eyg could induce expression of upd, which encodes the ligand for the Jak/STAT pathway and acts over long distance to promote cell proliferation. Loss of eyg or N can be compensated by overexpressing upd. These results suggest that upd is a major effector mediating the function of eyg and N. The functional link from N to eyg to upd explains how the localized Notch activation can achieve global growth control.
Coordinated regulation of gene expression by Brn3a in developing sensory ganglia
Authors: Eng S. Raisa , Lanier Jason , Fedtsova Natalia , Turner Eric E.
Published: July 2004

Mice lacking the POU-domain transcription factor Brn3a exhibit marked defects in sensory axon growth and abnormal sensory apoptosis. We have determined the regulatory targets of Brn3a in the developing trigeminal ganglion using microarray analysis of Brn3a mutant mice. These results show that Brn3 mediates the coordinated expression of neurotransmitter systems, ion channels, structural components of axons and inter- and intracellular signaling systems. Loss of Brn3a also results in the ectopic expression of transcription factors normally detected in earlier developmental stages and in other areas of the nervous system. Target gene expression is normal in heterozygous mice, consistent with prior work showing that autoregulation by Brn3a results in gene dosage compensation. Detailed examination of the expression of several of these downstream genes reveals that the regulatory role of Brn3a in the trigeminal ganglion appears to be conserved in more posterior sensory ganglia but not in the CNS neurons that express this factor.
The establishment of axial patterning in the maize leaf
Authors: Foster Toshi , Hay Angela , Johnston Robyn , Hake Sarah
Published: July 2004

The maize leaf consists of four distinct tissues along its proximodistal axis: sheath, ligule, auricle and blade. liguleless1 (lg1)functions cell autonomously to specify ligule and auricle, and may propagate a signal that correctly positions the blade-sheath boundary. The dominant Wavy auricle in blade (Wab1) mutation disrupts both the mediolateral and proximodistal axes of the maize leaf. Wab1 leaf blades are narrow and ectopic auricle and sheath extend into the blade. The recessive lg1-R mutation exacerbates the Wab1 phenotype; in the double mutants, most of the proximal blade is deleted and sheath tissue extends along the residual blade. We show that lg1 is misexpressed in Wab1 leaves. Our results suggest that the Wab1 defect is partially compensated for by lg1 expression. A mosaic analysis of Wab1 was conducted in Lg1+ and lg1-R backgrounds to determine if Wab1 affects leaf development in a cell-autonomous manner. Normal tissue identity was restored in all wab1+/–sectors in a lg1-R mutant background, and in three quarters of sectors in a Lg1+ background. These results suggest that lg1can influence the autonomy of Wab1. In both genotypes, leaf-halves with wab1+/– sectors were significantly wider than non-sectored leaf-halves, suggesting that Wab1 acts cell-autonomously to affect lateral growth. The mosaic analysis, lg1 expression data and comparison of mutant leaf shapes reveal previously unreported functions of lg1 in both normal leaf development and in the dominant Wab1mutant.
Functional divergence betweeneyelessandtwin of eyelessinDrosophila melanogaster
Authors: Punzo Claudio , Plaza Serge , Seimiya Makiko , Schnupf Pamela , Kurata Shoichiro , Jaeger Johannes , Gehring Walter J.
Published: July 2004

Pax6 genes encode transcription factors with two DNA-binding domains that are highly conserved during evolution. In Drosophila,two Pax6 genes function in a pathway in which twin of eyeless (toy) directly regulates eyeless (ey),which is necessary for initiating the eye developmental pathway. To investigate the gene duplication of Pax6 that occurred in holometabolous insects like Drosophila and silkworm, we used different truncated forms of toy and small eyes(sey), and tested their capacity to induce ectopic eye development in an ey-independent manner. Even though the Paired domains of TOY and SEY have DNA-binding properties that differ from those of the Paired domain of EY, they all are capable of inducing ectopic eye development in an eymutant background. We also show that one of the main functional differences between toy and ey lies in the C-terminal region of their protein products, implying differences in their transactivation potential. Furthermore, we show that only the homeodomain (HD) of EY is able to downregulate the expression of Distal-less (Dll), a feature that is required during endogenous eye development. These results suggest distinct functions of the two DNA-binding domains of TOY and EY, and significant evolutionary divergence between the two Drosophila Pax6genes.
Phosphorylation of paxillin tyrosines 31 and 118 controls polarization and motility of lymphoid cells and is PMA-sensitive
Authors: Romanova Larisa Y. , Hashimoto Shigeru , Chay Kee-Oh , Blagosklonny Mikhail V. , Sabe Hisataka , Mushinski J. Frederic
Published: July 2004

Tyrosine phosphorylation of paxillin regulates actin cytoskeleton-dependent changes in cell morphology and motility in adherent cells. In this report we investigated the involvement of paxillin tyrosine phosphorylation in the regulation of actin cytoskeleton-dependent polarization and motility of a non-adherent IL-3-dependent murine pre-B lymphocytic cell line Baf3. We also assessed the effect of phorbol myristate acetate (PMA), a phorbol ester analogous to those currently in clinical trials for the treatment of leukemia, on paxillin phosphorylation. Using tyrosine-to-phenylalanine phosphorylation mutants of paxillin and phosphospecific antibody we demonstrated that IL-3 stimulated phosphorylation of paxillin tyrosine residues 31 and 118, whereas the tyrosines 40 and 181 were constitutively phosphorylated. Phosphorylation of paxillin residues 31 and 118 was required for cell polarization and motility. In the presence of IL-3, PMA dramatically reduced the phosphorylation of residues 31 and 118, which was accompanied by inhibition of cell polarization and motility. This PMA effect was partially recapitulated by expression of exogenous tyrosine 31 and 118 mutants of paxillin. We also demonstrated that PMA inhibited the IL-3-induced and activation-dependent tyrosine phosphorylation of focal adhesion kinase. Thus, our results indicate that phosphorylation of paxillin tyrosine residues 31 and 118 regulates actin-dependent polarization and motility of pre-B Baf3 cells, both of which could be inhibited by PMA. They also suggest that inhibition of upstream signaling by PMA contributes to the decrease of paxillin phosphorylation and subsequent changes in cell morphology.
Phospholipase C-γ1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis
Authors: Choi Jang Hyun , Park Jong Bae , Bae Sun Sik , Yun Sanguk , Kim Hyeon Soo , Hong Won-Pyo , Kim Il-Shin , Kim Jae Ho , Han Mi Young , Ryu Sung Ho , Patterson Randen L. , Snyder Solomon H. , Suh Pann-Ghill
Published: July 2004

Phospholipase C-γ1 (PLC-γ1), which interacts with a variety of signaling molecules through its two Src homology (SH) 2 domains and a single SH3 domain has been implicated in the regulation of many cellular functions. We demonstrate that PLC-γ1 acts as a guanine nucleotide exchange factor (GEF) of dynamin-1, a 100 kDa GTPase protein, which is involved in clathrin-mediated endocytosis of epidermal growth factor (EGF) receptor. Overexpression of PLC-γ1 increases endocytosis of the EGF receptor by increasing guanine nucleotide exchange activity of dynamin-1. The GEF activity of PLC-γ1 is mediated by the direct interaction of its SH3 domain with dynamin-1. EGF-dependent activation of ERK and serum response element (SRE) are both up-regulated in PC12 cells stably overexpressing PLC-γ1, but knockdown of PLC-γ1 by siRNA significantly reduces ERK activation. These results establish a new role for PLC-γ1 in the regulation of endocytosis and suggest that endocytosis of activated EGF receptors may mediate PLC-γ1-dependent proliferation.
Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX
Authors: Ishov Alexander M. , Vladimirova Olga V. , Maul Gerd G.
Published: July 2004

Placing regulatory proteins into different multiprotein complexes should modify key cellular processes. Here, we show that the transcription repressor Daxx and the SWI/SNF protein ATRX are both associated with two intranuclear domains: ND10/PML bodies and heterochromatin. The accumulation of ATRX at nuclear domain 10 (ND10) was mediated by its interaction with the N-terminus of Daxx. Binding of this complex to ND10 was facilitated by the interaction of the Daxx C-terminus with SUMOylated promyelocytic leukemia protein (PML). Although ATRX was present at heterochromatin during the entire cell cycle, Daxx was actively recruited to this domain at the end of S-phase. The FACT-complex member structure-specific recognition protein 1 (SSRP1) accumulated at heterochromatin simultaneously with Daxx and accumulation of both proteins depended on ATRX phosphorylation. Both Daxx and SSRP1 were released from heterochromatin early in G2 phase and Daxx was recruited back to ND10, indicating that both proteins localize to heterochromatin during a very short temporal window of the cell cycle. ATRX seems to assemble a repression multiprotein complex including Daxx and SSRP1 at heterochromatin during a specific stage of the cell cycle, whereas Daxx functions as an adapter for ATRX accumulation at ND10. A potential functional consequence of Daxx accumulation at heterochromatin was found in the S- to G2-phase transition. In Daxx–/– cells, S-phase was accelerated and the propensity to form double nuclei was increased, functional changes that could be rescued by Daxx reconstitution and that might be the basis for the developmental problems observed in Daxx knockout animals.
Genetic compensation for sarcoglycan loss by integrin α7β1 in muscle
Authors: Allikian Michael J. , Hack Andrew A. , Mewborn Stephanie , Mayer Ulrike , McNally Elizabeth M.
Published: July 2004

Disruption of the sarcoglycan complex leads to muscle membrane instability and muscular dystrophy in humans and mice. Through the dystrophin glycoprotein complex, sarcoglycan participates in connecting the internal cytoskeleton to the membrane and the extracellular matrix. Integrin α7β1 is also a transmembrane protein of skeletal and cardiac muscle that similarly links the cytoskeleton to the extracellular matrix. Mice lacking integrin α7 develop mild muscle degeneration, while sarcoglycan mutant mice display overt muscle degeneration and muscular dystrophy. In sarcoglycan-deficient muscle, integrin α7 protein was upregulated at the plasma membrane. To ascertain whether integrin α7 upregulation compensates for the loss of the transmembrane sarcoglycan linkage in sarcoglycan-deficient muscle, we generated mice lacking both integrin α7 and γ-sarcoglycan (gxi). These double-mutant gxi mice exhibit profound, rapid muscle degeneration leading to death before one month of age consistent with a weakened cellular attachment to the extracellular matrix. The regenerative capacity of gxi muscle was intact with increased embryonic myosin heavy chain expression, myofiber central nucleation and normal in vivo myoblast differentiation. Therefore, upregulation of integrin α7β1 compensates as a transmembrane muscle cell attachment for sarcoglycan consistent with overlapping roles for sarcoglycan and integrins in mediating cytoskeletal-membrane-extracellular matrix interaction.
The Plasmodium falciparum Vps4 homolog mediates multivesicular body formation
Authors: Yang Mei , Coppens Isabelle , Wormsley Steve , Baevova Pavlina , Hoppe Heinrich C. , Joiner Keith A.
Published: July 2004

Members of the apicomplexan family of parasites contain morphologically unique secretory organelles termed rhoptries that are essential for host cell invasion. Rhoptries contain internal membranes, and thus resemble multivesicular bodies. To determine whether multivesicular body endosomal intermediates are formed in Apicomplexa, we used the Plasmodium falciparum homolog of the class E gene, Vps4, as a probe. Endogenous P. falciparum Vps4 (PfVps4) localized to the cytoplasm of P. falciparum trophozoites, and transgenic PfVps4 localized to the cytosol in P. falciparum, in the related parasite Toxoplasma gondii and in COS cells. When mutated to block ATP hydrolysis, transiently expressed PfVps4 localized instead to large vesicular structures in P. falciparum. The same construct, and another mutant blocked in ATP binding, generated large cholesterol-enriched multivesicular bodies in both COS cells and T. gondii. Mutant PfVps4 structures in T. gondii co-localized with markers for early endosomes. These results demonstrate a conservation of Vps4 function across wide phylogenetic boundaries, and indicate that endosomal multivesicular bodies form in both P. falciparum and T. gondii.
Economic Insights from Internet Auctions
Authors: Bajari Patrick , Hortaçsu Ali
Published: July 2004

This paper surveys recent studies of internet auctions. Four main areas of research are summarized. First, we survey several studies that document and attempt to explain the frequently observed sniping, or last-second bidding behavior, in these auctions. Second, we summarize several methods proposed to quantify the distortions caused by asymmetric information in these markets, most notably due to the winner's curse. Third, we explore research about the role of reputation mechanisms installed to help combat these distortions. Finally, we discuss what internet auctions have to teach us about auction design.
What will the new genetic information do for us?
Authors: Watt Graham
Published: July 2004

The usefulness of new genetic information is frequently assumed, but depends crucially on asking the right research questions. Successful applications of the new knowledge will require effective integration with the ideas, concerns and expectations not only of patients and their families, but also health professionals in primary care. The answers to some of the most exciting questions, concerning new taxonomies of health and disease, are to be found not in teaching hospitals or academic centres, but in the population at large. New types of partnership are required between colleagues in biomedicine, epidemiology, social science and primary care. The greatest challenge, however, is to our social imagination. Can we develop the sustained relationships with families and communities, based on goodwill, mutuality and trust, on which the whole enterprise depends?
Evidence-based priority-setting: what do the decision-makers think?
Authors: Mitton Craig , Patten San
Published: July 2004

Objectives: Resource scarcity dictates the need for health organisations to set priorities. Although such activity should be based, at least in part, on evidence, there are limited examples in the literature of decision-makers reflecting on their use of evidence in priority-setting.

Methods: A participatory action-research project was conducted in a single health authority in Alberta. It included in-depth interviews and focus groups with senior decision-makers both before and after development and implementation of a macro-level priority-setting framework (programme budgeting and marginal analysis, PBMA). Data were thematically coded and information on the use of evidence in priority-setting is reported.

Results: Barriers to the use of evidence in priority-setting identified by decision-makers included crisis-orientated management, time constraints and a lack of skills. Decision-makers suggested using a mix of 'soft' and 'hard' forms of evidence in priority-setting. Following PBMA implementation, decision-makers wanted better information on capacity to benefit, but preferred to do this pragmatically from multiple sources of information rather than using a single metric.

Conclusion: In examining the perspectives of decision-makers in using evidence to support priority-setting, valuable information was derived which should provide insight for such processes in other jurisdictions. The main finding of a desire for pragmatic assessment of benefit is informative for those involved in both decision-making and research.
Are data on the uptake of disability benefits a useful addition to census data in describing population health care needs?
Authors: O'Reilly Dermot , Stevenson Mike
Published: July 2004

Objective: To determine if administrative data relating to the uptake of disability benefits held by government departments in Northern Ireland are fair and unbiased indicators of relative need for health care and therefore a useful addition to census data.

Method: This is an ecological study of the 566 electoral wards in Northern Ireland. The variation in uptake of a health-related benefit (Disability Living Allowance) was regressed against three other indicators of health (limiting long-term illness, mortality and the numbers of patients admitted to hospital). All the indicators had been indirectly standardised by age and sex. The unstandardised residuals from this model were regressed against the social and geographical factors, namely area deprivation score, religious denominational composition and urban/rural dwelling to see if they influenced benefit uptake above and beyond any association with ill health.

Results: The health factors alone explained 77.2% of the variation in benefit uptake, with limiting long-term illness being the major determinant; however, even after controlling for differences in health status, benefit uptake was shown to be higher in more urban areas and in areas that had a greater proportion of Catholics. Area deprivation was not associated with benefit uptake once health differences had been controlled for.

Conclusion: Administrative data on disability benefits can undoubtedly provide useful additional information for describing the levels of relative disadvantage or ill health of areas. However, because they also reflect variations in uptake, which appears to be confounded by social and geographical factors, we would urge caution when they are used to identify priority areas or to allocate resources.
'Questerviews': using questionnaires in qualitative interviews as a method of integrating qualitative and quantitative health services research
Authors: Adamson Joy , Gooberman-Hill Rachael , Woolhead Gillian , Donovan Jenny
Published: July 2004

Objectives: Multi-method approaches are increasingly advocated in health services research (HSR). This paper examines the use of standardised self-completion questionnaires and questions, during in-depth interviews, a technique termed 'questerviews'.

Methods: 'Questerview' techniques were used in four empirical studies of health perceptions conducted by the authors. The studies included both standardised self-completion questions or questionnaires and in-depth interviews. Respondents were tape-recorded while they completed the standardised questionnaires and were encouraged to discuss their definitions of terms and responses to items in-depth. In all studies, 'questerviews' were fully transcribed and data analysis involved the scrutinising of transcripts to identify emergent themes.

Results: Responses to the standardised items led to rich sources of qualitative data. They proved to be useful triggers as respondents discussed their understanding and definitions of terms, often explaining their responses with stories from their own experiences. The items triggered detailed exploration of the complex factors that comprise health, illness and healthcare seeking, and gave considerable insight into the ways in which people respond to standardised questions. Apparently simple questions and response categories conceal considerable complexity.

Conclusions: Inclusion of standardised survey questions in qualitative interviews can provide an easy and fruitful method to explore research issues and provide triggers to difficult or contested topics. Well designed and validated questionnaires produce data of immense value to HSR, and this value could be further enhanced by their use within a qualitative interview. We suggest that the technique of 'questerviews' is a tangible and pragmatic way of doing this.
Influencing prescribing in English primary care: the views of primary care organisations
Authors: Mason Anne , Drummond Michael , Towse Adrian , Cooke Jonathan
Published: July 2004

Objective: The rapid rise of prescribing expenditure is a concern in many industrialised countries and methods to manage medicines are widely employed. The purpose of this study was to identify the approaches to improve primary care prescribing by primary care organisations (PCOs) in the National Health Service (NHS) in England.

Methods: A questionnaire (Management of Medicines, MANMED) was mailed to prescribing advisers and prescribing leads in 332 PCOs.

Results: A response rate of 66% (220/332) was achieved. Most PCOs report the improvement of the quality of prescribing as their top priority, followed by budget adherence at both practice and PCO levels. Prescribing advisers typically offer several forms of support: practice visits, prescribing reviews, indicators of prescribing, prescribing newsletters, hands-on support, seminars and local formularies. PCOs are pursuing a wide range of prescribing initiatives, covering, on average, seven different therapeutic areas. National targets are the main driver for prescribing initiatives but other key influences include inappropriate prescribing and clinical governance. Although cost considerations are important, improving the quality of prescribing is perceived as the overriding principle on which PCO prescribing strategy is based. Multifaceted prescribing support is widespread and national targets are the largest single factor influencing choice of therapeutic area for prescribing initiatives.

Conclusions: Diversity in approaches presents the opportunity to improve the evidence base for medicines management. Not only could such research inform PCOs in their central aim of improving the quality of prescribing within the NHS, but it may also offer insights of relevance to other countries if the influence of process and context upon the effectiveness of medicines management is systematically explored.
False-Positive Urine Opiate Screening Associated with Fluoroquinolone Use
Authors: Zacher Jennifer L , Givone Donna M
Published: July 2004

OBJECTIVE:

To review the literature regarding false-positive urine opiate screens associated with the use of fluoroquinolones.

DATA SOURCES:

Literature was identified using MEDLINE (1966—February 2004), EMBASE, and all EBM Reviews with the terms quinolones, substance abuse detection, opiates, cross-reactions, false-positive reactions, and each fluoroquinolone. Article references were also reviewed.

DATA SYNTHESIS:

Various settings utilize the practice of screening for drugs of abuse, such as opiates. These screening procedures can impact aspects of one's life, such as employment; therefore, accuracy is of the utmost importance. Two clinical trials were evaluated which showed that certain fluoroquinolone antibiotics cross-react with some of the commonly used urine opiate screening immunoassays. This suggests the importance of verifying positive results in instances where one's livelihood can be affected.

CONCLUSIONS:

Fluoroquinolones can cause false-positive urine opiate screens. Clinicians should be aware of this potential interaction and may need to verify positive results.
The Effect of Clarithromycin on Inflammatory Markers in Chronic Obstructive Pulmonary Disease: Preliminary Data
Authors: Basyigit Ilknur , Yildiz Fusun , Ozkara Sevgiye Kacar , Yildirim Elif , Boyaci Hasim , Ilgazli Ahmet
Published: July 2004

BACKGROUND:

Clarithromycin is an antimicrobial agent that can be used for treatment of chronic obstructive pulmonary disease (COPD) exacerbations with bronchodilator therapy. However, it has also been shown that clarithromycin has antiinflammatory effects by the inhibition of cytokine production.

OBJECTIVE:

To evaluate the antiinflammatory effect of clarithromycin on serum and sputum interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and leukotriene B4 levels in patients with COPD.

METHODS:

Thirty men with mild to moderate COPD were enrolled in this prospective, single-center, double-blind, placebo-controlled study. None of the patients was receiving systemic or inhaled corticosteroids during the study. Subjects received either clarithromycin or placebo for 14 days. Before and after this treatment period, spirometric tests and arterial blood gas analysis were performed, blood was drawn for measurement of serum inflammatory markers, and sputum was induced.

RESULTS:

There were no statistically significant differences in baseline clinical or laboratory parameters between the groups. After the treatment, the induced sputum total cell counts, and IL-8 and TNF-α levels decreased significantly in the clarithromycin group compared with pretreatment levels (mean ± SD IL-8 1606 ± 367.3 vs 882 ± 143.6 pg/mL, p = 0.001; TNF-α 638.2 ± 287.5 vs 390 ± 235 pg/mL, p = 0.001). Similarly, decreases in serum inflammatory markers were found in the clarithromycin group while there was no significant change in the placebo group.

CONCLUSIONS:

This study demonstrated that the decrease in IL-8 and TNF-α levels might be related to the antiinflammatory effect of clarithromycin. Thus, we suggest that the use of clarithromycin in COPD exacerbations may either treat the infection or help control the inflammation. Future studies are needed to determine the clinical significance of these findings.
Clonazepam for Treatment of Sleep Disturbances Associated with Combat-Related Posttraumatic Stress Disorder
Authors: Cates Marshall E , Bishop Melanie H , Davis Lori L , Lowe Joette S , Woolley Thomas W
Published: July 2004

BACKGROUND:

Clonazepam is widely used for the treatment of posttraumatic stress disorder (PTSD)—related sleep disturbances despite very limited published data supporting its use for this indication.

OBJECTIVE:

We conducted a pilot-controlled trial to provide more data on this clinical practice and lay the foundation for more definitive studies.

METHODS:

The study was designed as a randomized, single-blind (ie, patient only), placebo-controlled, crossover clinical trial involving administration of clonazepam 1 mg at bedtime for one week followed by 2 mg at bedtime for one week. The following week served as a washout period before the alternate treatment was begun. Patients completed sleep diaries each morning upon awakening throughout the study. Parameters included quantity of sleep, quality of sleep, frequency and intensity of difficulty falling or staying asleep, and frequency and intensity of recurrent distressing dreams.

RESULTS:

Six patients with combat-related PTSD participated in the study. There were no statistically significant differences between clonazepam and placebo for any measure, although clonazepam therapy resulted in mild to moderate numeric improvements in difficulty falling or staying asleep. Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to receive further treatment with clonazepam at the conclusion of the trial.

CONCLUSIONS:

Clonazepam therapy was largely ineffective in improving sleep disturbances, particularly nightmares, associated with combat-related PTSD. The small sample size was a significant limitation of this study, but the prospective design and single-blind, placebo-control parameters were strengths. Further studies are needed to further define the role of this widespread clinical practice.
Toward Extending the Compromise Effect to Complex Buying Contexts
Authors: Dhar Ravi , Menon Anil , Maach Bryan
Published: July 2004

Kivetz, Netzer, and Srinivasan (2004) make an important contribution to the theory of choice models by demonstrating through a rigorous analysis of four alternative models that the compromise effect systematically affects choice in a wide range of conditions. The value and impact of their work can be enhanced by extensions that examine key underlying institutional variables that may shape the nature and scope of compromise effects. The authors provide a set of issues that further research can effectively pursue in the context of institutional buying processes and the purchase of complex solutions rather than individual products.
Extending Compromise Effect Models to Complex Buying Situations and Other Context Effects
Authors: Kivetz Ran , Netzer Oded , Srinivasan V.
Published: July 2004

Building on the work of Dhar, Menon, and Maach (2004) , this commentary describes how the compromise effect models developed in the work of Kivetz, Netzer, and Srinivasan (2004) can be extended to predict complex (business-to-business) purchase decisions and additional behavioral context effects. The authors clarify their general modeling approach and outline how it applies to choices among solutions (augmented products) and group decision making. They then hypothesize about the influence of business-to-business and technology markets on various context effects (e.g., compromise and asymmetric dominance). They show how the models incorporate various context effects and discuss ideas for further research.
The Influence of Loyalty Programs and Short-Term Promotions on Customer Retention
Authors: Lewis Michael
Published: July 2004

Despite the proliferation of loyalty programs in a wide range of categories, there is little empirical research that focuses on the measurement of such programs. The key to measuring the influence of loyalty programs is that they operate as dynamic incentive schemes by providing benefits based on cumulative purchasing over time. As such, loyalty programs encourage consumers to shift from myopic or single-period decision making to dynamic or multiple-period decision making. In this study the author models customers' response to a loyalty program under the assumption that purchases represent the sequential choices of customers who are solving a dynamic optimization problem. The author estimates the theoretical model using a discrete-choice dynamic programming formulation. The author evaluates a specific loyalty program with data from an online merchant that specializes in grocery and drugstore items. Through simulation and policy experiments, it is possible to evaluate and compare the long-term effects of the loyalty program and other marketing instruments (e.g., e-mail coupons, fulfillment rates, shipping fees) on customer retention. Empirical results and policy experiments suggest that the loyalty program under study is successful in increasing annual purchasing for a substantial proportion of customers.
The Customer Relationship Management Process: Its Measurement and Impact on Performance
Authors: Reinartz Werner , Krafft Manfred , Hoyer Wayne D.
Published: July 2004

An understanding of how to manage relationships with customers effectively has become an important topic for both academicians and practitioners in recent years. However, the existing academic literature and the practical applications of customer relationship management (CRM) strategies do not provide a clear indication of what specifically constitutes CRM processes. In this study, the authors (1) conceptualize a construct of the CRM process and its dimensions, (2) operationalize and validate the construct, and (3) empirically investigate the organizational performance consequences of implementing CRM processes. Their research questions are addressed in two cross-sectional studies across four different industries and three countries. The first key outcome is a theoretically sound CRM process measure that outlines three key stages: initiation, maintenance, and termination. The second key result is that the implementation of CRM processes has a moderately positive association with both perceptual and objective company performance.
Determinants of Product-Use Compliance Behavior
Authors: Bowman Douglas , Heilman Carrie M. , Seetharaman P.B.
Published: July 2004

The authors examine factors that affect product-usage compliance, or the act of using a product as it is intended to be used. They develop a conceptual model of compliant behavior as a function of four main constructs: (1) salience/mindfulness, (2) the consumer's costs and benefits of compliant behavior, (3) advertising and distribution cues to action, and (4) the perceived threats associated with noncompliant behavior. They test the model using a regression mixture model of compliant behavior calibrated on unique panel data from four categories of pharmaceutical drugs that are used to treat chronic (i.e., lifelong) ailments. The findings include insights into the dynamics of product compliance: The data support the proposed four-stage evolution of compliant behavior between consecutive service provider (e.g., doctor) interventions. For marketers, the authors find substantial heterogeneity across consumers for the effects of cues from advertising and distribution. For example, in some segments, advertising has a positive impact on compliance (directly and/or by heightening responsiveness to product-efficacy evaluations), whereas in other segments, its effect is negative. Thus, the authors shed new light on the effects of advertising, which has both strong advocates and opponents in the pharmaceutical industry.
The Determinants of Pre- and Postpromotion Dips in Sales of Frequently Purchased Goods
Authors: Macé Sandrine , Neslin Scott A.
Published: July 2004

The authors empirically study the relationships between pre- and post-promotion dips in weekly store data and Universal Product Code (UPC), category, and store trading-area customer characteristics. Drawing on recent advances in econometric modeling, they estimate 39,441 pre- and postpromotion dip elasticities in 83 stores in ten product categories. They relate these elasticities to 24 characteristics, such as UPC price and market share, category budget share and storability, and store trading-area demographics. The authors find that UPC, category, and store trading-area customer characteristics all explain significant variation in the elasticities. For example, both pre- and postpromotion dips are stronger for high-priced, frequently promoted, mature, high-market-share UPCs. They find that postpromotion dips are not significantly different for private labels but are more prominent for UPCs with less predictable promotion patterns. They also find that stores with trading areas that consist of older customers who live in larger households and own cars are particularly prone to postpromotion dips. The findings potentially deepen the understanding of stockpiling and deceleration and blend two trends in promotion response research: an increased focus on pre- and postpromotion effects and a greater emphasis on examination of cross-sectional differences in promotion response.
The Recoverability of Segmentation Structure from Store-Level Aggregate Data
Authors: Bodapati Anand V. , Gupta Sachin
Published: July 2004

The authors focus on estimating a latent-class choice model with consumer response segments when only store-level aggregate data are available. Most of the proposed methodologies in the marketing literature require household panel data, which can be difficult to obtain. There is a growing stream of work in marketing and in empirical industrial organization that estimates segmentation structure with aggregate data. This article is a careful attempt to understand the extent to which disaggregate structure in the form of a latent-class model can be recovered from aggregate data. The authors show that under specific assumptions and when the household-level model is correctly specified, most of a latent-class segmentation structure is identifiable even if only store-level aggregate data are available. Therefore, the store data-based estimates for the latent-class model are consistent. In other words, the mean absolute deviation (MAD) of the estimates goes to zero with infinite sample size. To assess how well latent-class structure can be estimated from store data sets of sample sizes that are comparable to those in real life, the authors simulate more than 60,000 store data sets and compute the consequent model estimates and their estimation errors. The results show that the MAD of the latent-class estimates diminishes much more slowly with store data than with household data. Moreover, the rate is so slow that obtaining estimates with reasonably small MADs often requires unreasonably large sample sizes. The authors' simulations offer guidance on conditions that favor obtaining more accurate estimates from store-level data.
Behavioral State Instability in Orexin Knock-Out Mice
Authors: Mochizuki Takatoshi , Crocker Amanda , McCormack Sarah , Yanagisawa Masashi , Sakurai Takeshi , Scammell Thomas E.
Published: July 2004

Narcolepsy is caused by a lack of orexin (hypocretin), but the physiologic process that underlies the sleepiness of narcolepsy is unknown. Using orexin knock-out (KO) mice as a model of narcolepsy, we critically tested the three leading hypotheses: poor circadian control of sleep and wakefulness, inadequate activation of arousal regions, or abnormal sleep homeostasis. Compared with wild-type (WT) littermates, orexin KO mice had essentially normal amounts of sleep and wake, but wake and non-rapid eye movement (NREM) bouts were very brief, with many more transitions between all behavioral states. In constant darkness, orexin KO mice had normal amplitude and timing of sleep-wake rhythms, providing no evidence for disordered circadian control. When placed in a new, clean cage, both groups of mice remained awake for ∼45 min, demonstrating that, even in the absence of orexin, fundamental arousal regions can be engaged to produce sustained wakefulness. After depriving mice of sleep for 2-8 hr, orexin KO mice recovered their NREM and rapid eye movement sleep deficits at comparable rates and to the same extent as WT mice, with similar increases in EEG delta power, suggesting that their homeostatic control of sleep is normal. These experiments demonstrate that the fragmented wakefulness of orexin deficiency is not a consequence of abnormal sleep homeostasis, poor circadian control, or defective fundamental arousal systems. Instead, the fragmented behavior of orexin KO mice may be best described as behavioral state instability, with apparently low thresholds to transition between states.