bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates and correlates of employment in people with schizophrenia in the UK, France and Germany
Authors: Marwaha Steven , Johnson Sonia , Bebbington Paul , Stafford Mai , Angermeyer Matthias C. , Brugha Traolach , Azorin Jean-Michel , Kilian Reinhold , Hansen Karina , Toumi Mondher
Published: June 2007

Background

Little is known about international variations in employment rates among people with schizophrenia or about the factors associated with employment in this disorder.

Aims

To describe employment patterns and the variables associated with working in an international sample of people with schizophrenia.

Method

An analysis was made of baseline data from the European Schizophrenia Cohort study, a 2-year investigation of people with schizophrenia in contact with secondary services and living in France, Germany and the UK (n = 1208).

Results

Participants were working in all sections of the job market. People who had a degree, were living with their families or had experienced only a single episode of illness were more likely to be working. A continuous illness course, more severe non-psychotic symptoms and drug misuse reduced the odds of employment. There were large variations between centres in employment rates, which were highest in the three German study sites. These differences persisted after adjustment for individual characteristics.

Conclusions

Local social contexts may be as important as individual or illness-related factors in explaining employment status.
Determining when impairment constitutes incapacity for informed consent in schizophrenia research
Authors: Kim Scott Y. H. , Appelbaum Paul S. , Swan Jeffrey , Stroup T. Scott , McEvoy Joseph P. , Goff Donald C. , Jeste Dilip V. , Lamberti J. Steven , Leibovici Adrian , Caine Eric D.
Published: June 2007

Background

Although people with schizophrenia display impaired abilities for consent, it is not known how much impairment constitutes incapacity.

Aims

To assess a method for determining the categorical capacity status of potential participants in schizophrenia research.

Method

Expert-judgement validation of capacity thresholds on the sub-scales of the MacArthur Competence Assessment Tool – Clinical Research (MacCAT–CR) was evaluated using receiver operating characteristic (ROC) analysis in 91 people with severe mental illness and 40 controls.

Results

The ROC areas under the curve for the understanding, appreciation and reasoning sub-scales of the MacCAT–CR were 0.94 (95% CI 0.88–0.99), 0.85 (95% CI 0.76–0.94) and 0.80 (95% CI 0.70–0.90). These findings yielded negative and positive predictive values of incapacity that can guide the practice of investigators and research ethics committees.

Conclusions

By performing such validation studies for a few categories of research with varying risks and benefits, it might be possible to create evidence-based capacity determination guidelines for most schizophrenia research.
Consultant psychiatrists' working patterns
Authors: Mears Alex , Pajak Sarah , Kendall Tim , Katona Cornelius , Medina Jibby , Huxley Peter , Evans Sherrill , Gately Claire
Published: June 2007

Aims and Method

To explore relationships between different styles of working and measures of occupational pressure in consultant psychiatrists. A random sample of 500 consultant psychiatrists were sent a questionnaire about working patterns and lifestyle factors, with other sections using validated tools (such as the 12-item General Health Questionnaire; GHQ).

Results

There were 185 useable questionnaires returned (an adjusted response rate of 39%). Significant relationships were identified between job content and GHQ and burnout scores, indicating that occupational pressures are rendering some consultant posts ‘problem posts', leading to problematic levels of psychological distress among some consultants.

Clinical Implications

Although consultant psychiatrists are more satisfied than not with their jobs, steps need to be taken to address the causes of ‘problem posts', to reduce attrition in the most pressured individuals.
Acute in-patient psychiatry: service improvement – the time is now
Authors: McGeorge Maureen , Rae Malcolm
Published: June 2007

Psychiatric in-patient care is perhaps the component of mental health services that service users are most critical about. This, coupled with a growing awareness of the close association between quality and safety in this setting, has led to a recent flurry of national initiatives. These can be broadly grouped into those that have described the problems facing in-patient services and suggested some of the underlying causes, and those that are attempting to address these.
Residual Ductal Carcinoma In Situ in Patients With Complete Eradication of Invasive Breast Cancer After Neoadjuvant Chemotherapy Does Not Adversely Affect Patient Outcome
Authors: Mazouni Chafika , Peintinger Florentia , Wan-Kau Shu , Andre Fabrice , Gonzalez-Angulo Ana M. , Symmans W. Fraser , Meric-Bernstam Funda , Valero Vicente , Hortobagyi Gabriel N. , Pusztai Lajos
Published: June 2007

Purpose

To determine whether residual ductal carcinoma in situ (DCIS) after completion of preoperative chemotherapy affects the outcome of patients with histologically defined complete eradication of invasive cancer.

Patients and Methods

Retrospective analysis of a database including 2,302 breast cancer patients treated with neoadjuvant chemotherapy at The University of Texas M.D. Anderson Cancer Center between 1980 and 2004 was performed. The overall survival (OS), disease-free survival (DFS), and local recurrence-free survival were compared for patients with no residual invasive or in situ cancer (pathologic complete response [pCR]) and patients with no residual invasive cancer but persistent in situ disease (pCR+DCIS).

Results

The mean follow-up time was 250 months. Of the 2,302 treated patients, 78 (3.4%) had pCR, 199 (8.6%) had pCR+DCIS, and 2,025 (88%) had residual invasive cancer. For patients with pCR and pCR+DCIS, the 5-year DFS rates (87.1% in both groups) and 10-year DFS rates (81.3% v 81.7%, respectively) were similar; the 5-year OS rates (91.9% v 92.5%, respectively) and 10-year OS rates (91.8% v 92.5%, respectively) were also similar and significantly better than the rate of patients with residual invasive cancer (74.4%; P < .001). The 5-year locoregional recurrence-free survival rates were also not different between patients with pCR (92.8%; 95% CI, 86.1% to 96.4%) and patients with pCR+DCIS (90.9%; 95% CI, 77.3% to 96.5%; P = .63).

Conclusion

Residual DCIS in patients who experience complete eradication of the invasive cancer in the breast and lymph nodes does not adversely affect survival or local recurrence rate. Inclusion of patients with residual DCIS in the definition of pCR is justified when this outcome is used as an early surrogate for long-term survival.
Cell Cycle Regulators and Outcome of Adjuvant Cisplatin-Based Chemotherapy in Completely Resected Non–Small-Cell Lung Cancer: The International Adjuvant Lung Cancer Trial Biologic Program
Authors: Filipits Martin , Pirker Robert , Dunant Ariane , Lantuejoul Sylvie , Schmid Katharina , Huynh Anh , Haddad Vincent , André Fabrice , Stahel Rolf , Pignon Jean-Pierre , Soria Jean-Charles , Popper Helmut H. , Le Chevalier Thierry , Brambilla Elisabeth
Published: June 2007

Purpose

The International Adjuvant Lung Cancer Trial (IALT) demonstrated that adjuvant cisplatin-based chemotherapy improves the survival of patients with completely resected non–small-cell lung cancer (NSCLC). The purpose of our study was to determine whether cell cycle regulators are of prognostic and/or predictive value in patients who were enrolled onto the IALT.

Patients and Methods

Expression of p27Kip1, p16INK4A, cyclin D1, cyclin D3, cyclin E, and Ki-67 was immunohistochemically assessed in tumor specimens obtained from 778 IALT patients. Prognostic and predictive analyses were based on Cox models adjusted for clinical and pathologic parameters.

Results

There was a relationship between p27Kip1 status and benefit of cisplatin-based chemotherapy (test for interaction, P = .02). Among patients with p27Kip1-negative tumors, cisplatin-based chemotherapy resulted in longer overall survival compared with controls (adjusted hazard ratio [HR] for death = 0.66; 95% CI, 0.50 to 0.88; P = .006). In patients with p27Kip1-positive tumors, overall survival was not different between patients treated with cisplatin-based chemotherapy and controls (adjusted HR for death = 1.09; 95% CI, 0.82 to 1.45; P = .54). The other cell cycle regulators and Ki-67 did not predict benefit of adjuvant cisplatin-based chemotherapy. None of these biomarkers was significantly associated with overall survival of the patients in the total study population.

Conclusion

NSCLC patients with p27Kip1-negative tumors benefit from adjuvant cisplatin-based chemotherapy after complete tumor resection. Before establishing p27Kip1 as a routine marker for selection of patients for adjuvant chemotherapy, the predictive value of p27Kip1 has to be confirmed in patients from other trials.
Multicenter Phase II Study of Fertility-Sparing Treatment With Medroxyprogesterone Acetate for Endometrial Carcinoma and Atypical Hyperplasia in Young Women
Authors: Ushijima Kimio , Yahata Hideaki , Yoshikawa Hiroyuki , Konishi Ikuo , Yasugi Toshiharu , Saito Toshiaki , Nakanishi Toru , Sasaki Hiroshi , Saji Fumitaka , Iwasaka Tsuyoshi , Hatae Masayuki , Kodama Shoji , Saito Tsuyoshi , Terakawa Naoki , Yaegashi Nobuo , Hiura Masamichi , Sakamoto Atsuhiko , Tsuda Hitoshi , Fukunaga Masaharu , Kamura Toshiharu
Published: June 2007

Purpose

To assess the efficacy of fertility-sparing treatment using medroxyprogesterone acetate (MPA) for endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women.

Patients and Methods

This multicenter prospective study was carried out at 16 institutions in Japan. Twenty-eight patients having EC at presumed stage IA and 17 patients with AH at younger than 40 years of age were enrolled. All patients were given a daily oral dose of 600 mg of MPA with low-dose aspirin. This treatment continued for 26 weeks, as long as the patients responded. Histologic change of endometrial tissue was assessed at 8 and 16 weeks of treatment. Either estrogen-progestin therapy or fertility treatment was provided for the responders after MPA therapy. The primary end point was a pathologic complete response (CR) rate. Toxicity, pregnancy rate, and progression-free interval were secondary end points.

Results

CR was found in 55% of EC cases and 82% of AH cases. The overall CR rate was 67%. Neither therapeutic death nor irreversible toxicities were observed; however, two patients had grade 3 body weight gain, and one patient had grade 3 liver dysfunction. During the 3-year follow-up period, 12 pregnancies and seven normal deliveries were achieved after MPA therapy. Fourteen recurrences were found in 30 patients (47%) between 7 and 36 months.

Conclusion

The efficacy of fertility-sparing treatment with a high-dose of MPA for EC and AH was proven by this prospective trial. Even in responders, however, close follow-up is required because of the substantial rate of recurrence.
Customizing Cisplatin Based on Quantitative Excision Repair Cross-Complementing 1 mRNA Expression: A Phase III Trial in Non–Small-Cell Lung Cancer
Authors: Cobo Manuel , Isla Dolores , Massuti Bartomeu , Montes Ana , Sanchez Jose Miguel , Provencio Mariano , Viñolas Nuria , Paz-Ares Luis , Lopez-Vivanco Guillermo , Muñoz Miguel Angel , Felip Enriqueta , Alberola Vicente , Camps Carlos , Domine Manuel , Sanchez Jose Javier , Sanchez-Ronco Maria , Danenberg Kathleen , Taron Miquel , Gandara David , Rosell Rafael
Published: June 2007

Purpose

Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response.

Patients and Methods

From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate.

Results

Of 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02).

Conclusion

Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.
Vaccination of Patients With Advanced Non–Small-Cell Lung Cancer With an Optimized Cryptic Human Telomerase Reverse Transcriptase Peptide
Authors: Bolonaki Irini , Kotsakis Athanassios , Papadimitraki Elsa , Aggouraki Despoina , Konsolakis George , Vagia Aphrodite , Christophylakis Charalambos , Nikoloudi Irini , Magganas Elefterios , Galanis Athanassios , Cordopatis Paul , Kosmatopoulos Kostas , Georgoulias Vassilis , Mavroudis Dimitris
Published: June 2007

Purpose

To evaluate the immunological and clinical response as well as the safety of the optimized peptide telomerase reverse transcriptase p572Y (TERT572Y) presented by HLA-A*0201 in patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods

Twenty-two patients with advanced NSCLC and residual (n = 8) or progressive disease (PD; n = 14) following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide administered every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay and/or TERT572Y pentamer staining.

Results

Twelve (54.5%) of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT572-specific CD8+ cells were detected in 16 (76.2%) of 21 patients after the second vaccination, and 10 (90.9%) of 11 patients after the sixth vaccination. Stable disease (SD) occurred in eight (36.4%) of 22 vaccinated patients, with three (13.6%) having had PD before entering the study. The median duration of SD was 11.2 months. After a median follow-up of 10.0 months, patients with early developed immunological response (n = 16) had a significantly longer time to progression and overall survival (OS) than nonresponders (n = 5; log-rank tests P = .046 and P = .012, respectively). The estimated median OS was 30.0 months (range, 2.8 to 40.0 months) and 4.1 months (range, 2.4 to 10.9 months) for responders and nonresponders, respectively.

Conclusion

TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. Immunological response is associated with prolonged survival. These results are encouraging and warrant further evaluation in a randomized study.
Gill remodeling in fish – a new fashion or an ancient secret?
Authors: Nilsson Göran E.
Published: June 2007

While a large respiratory surface area is good for gas exchange, it also poses several problems, including energetically unfavorable fluxes of water and ions. As a result, fishes appear to have a respiratory surface area that is matched to their oxygen demands. When faced with changes in their need for oxygen uptake, e.g. through altered physical activity or altered ambient oxygen levels, fishes have long been known to make two different adjustments:(1) to change the water flow over the gills or (2) to change the blood flow inside the gills. It has recently become clear that at least some teleosts have a third option: to reversibly remodel the gill morphology. Studies have shown that the lamellae of crucian carp Carassius carassius gills are embedded in a cell mass during normoxic conditions or at low temperature,while much of this cell mass dies off in hypoxia and at higher temperatures,thereby exposing a much larger respiratory surface area. Gill remodeling has subsequently been seen in two more cyprinids and in the mangrove killifish Kryptolebias marmoratus. In the latter case it appears to be an adaptation to periods of air exposure. Gill remodeling in response to changing respiratory requirements could be an ancient mechanism, occurring in many more teleosts than presently known. It is tempting to suggest that gill remodeling has been overlooked in many fishes, either because it is relatively subtle in some species, or because fishes are often kept at the warmer end of their temperature range where they need fully protruding lamellae.
Acoustic feature recognition in the dogbane tiger moth,Cycnia tenera
Authors: Fullard James H. , Ratcliffe John M. , Christie Christopher G.
Published: June 2007

Certain tiger moths (Arctiidae) defend themselves against bats by phonoresponding to their echolocation calls with trains of ultrasonic clicks. The dogbane tiger moth, Cycnia tenera, preferentially phonoresponds to the calls produced by attacking versus searching bats, suggesting that it either recognizes some acoustic feature of this phase of the bat's echolocation calls or that it simply reacts to their increased power as the bat closes. Here, we used a habituation/generalization paradigm to demonstrate that C. tenera responds neither to the shift in echolocation call frequencies nor to the change in pulse duration that is exhibited during the bat's attack phase unless these changes are accompanied by either an increase in duty cycle or a decrease in pulse period. To separate these features, we measured the moth's phonoresponse thresholds to pulsed stimuli with variable versus constant duty cycles and demonstrate that C. tenerais most sensitive to echolocation call periods expressed by an attacking bat. We suggest that, under natural conditions, C. tenera identifies an attacking bat by recognizing the pulse period of its echolocation calls but that this feature recognition is influenced by acoustic power and can be overridden by unnaturally intense sounds.
The vagus nerve mediates cardio-respiratory coupling that changes with metabolic demand in a temperate nototheniod fish
Authors: Campbell Hamish A. , Egginton Stuart
Published: June 2007

The extent and efficiency of cardio-respiratory coupling (CRC) in teleost fishes is unclear. We simultaneously monitored heart rate (fH) and ventilation rate (fV) in Paranotothenia angustata, and applied modern power spectral analysis (PSA) mathematics to examine the rate association under varying levels of oxygen consumption(ṀO2). At low ṀO2 (0.94 mmol O2 kg–1 h–1) there was a correspondingly low fH and fV(25.5±2.4 min–1 and 29.2±2.6 min–1, respectively). Heart rate variability (HRV) consisted of oscillatory components caused by periodic vagal inhibition of the heart beat. Cross-spectral analysis showed that fH and fV were coupled, with the response lag in heart beat being approximately one seventh of each ventilation cycle. Ingestion of food elevated ṀO2(1.99±0.02 mmol O2 kg–1h–1) and increased both fH and fV (45±2.3 min–1 and 52±2 min–1, respectively, P<0.05), but CRC was maintained despite a reduction in HRV. The elevated stress caused by handling and placement of fish into respirometry chambers raised fHand fV to a similar rate as observed after feeding,although high-frequency (>0.2 Hz) oscillations in fHwere lacking and ṀO2 was lower(1.82±0.03 mmol O2 kg–1h–1, P<0.05). Subsequent cardiac vagotomy elevated fH and fV (55.5±0.8 min–1 and 48.2±0.7 min–1,respectively; P<0.05) but abolished all HRV and CRC, although ṀO2 was significantly less for a given fH and fV compared to intact fish. Thus, P. angustataexhibits vagally mediated CRC, and the association between fH and fV varies according to oxygen demand.
Modulation of locomotor activity in larval zebrafish during light adaptation
Authors: Burgess Harold A. , Granato Michael
Published: June 2007

The neural basis of behavioral choice in vertebrates remains largely unknown. Zebrafish larvae have a defined locomotor repertoire as well as a simple nervous system and are therefore an attractive vertebrate system in which to study this process. Here we describe a high-throughput system for quantifying the kinematics of motor events in zebrafish larvae in order to measure the initiation frequency of different maneuvers. We use this system to analyze responses to photic stimuli and find that larvae respond to changes in illumination with both acute responses and extended behavioral programs. Reductions in illumination elicit large angle turns, distinct from startle responses, which orient larvae toward the source of light. In continuing darkness, larvae are transiently hyperactive before adopting a quiescent state. Indeed, locomotor activity is controlled by the state of light or dark adaptation similar to masking phenomena in higher vertebrates where light directly regulates motor activity. We propose that regulation of motor activity by photic stimuli in zebrafish larvae serves a behavioral goal of maximizing exposure to well lit environments optimal for feeding.
Effects of two bitter substances on olfactory conditioning in the moth Heliothis virescens
Authors: Jørgensen Kari , Stranden Marit , Sandoz Jean-Christophe , Menzel Randolf , Mustaparta Hanna
Published: June 2007

In nature, moths encounter nutritious and toxic substances in plants, and thus have to discriminate between a diversity of tastants. Whereas olfactory learning allowing memory of nutritious plants is well demonstrated, little is known about learning and memory of toxic items in adult lepidopterans. Moths may use bitter substances to detect and possibly learn to avoid noxious plants. We have studied the physiological and behavioural effects of two bitter substances, quinine and sinigrin, on the moth Heliothis virescens. Electrophysiological recordings showed responses to both compounds in gustatory receptor neurons on the antennae. The response patterns suggested a peripheral discrimination between quinine and sinigrin. We evaluated their putative aversive effect in an appetitive conditioning context where the moths learned to associate an odour with sucrose. We first aimed at enhancing olfactory conditioning of the proboscis extension response by testing the effect of the sucrose concentration on acquisition, retention and extinction. 2 mol l–1 and 3 mol l–1 sucrose concentration gave similar acquisition, retention and extinction performances. Experiments involving pre-exposure or facilitated extinction with an odour paired with quinine, sinigrin or no tastant showed a latent inhibitory effect,as well as an aversive effect of quinine and, to a lesser extent, of sinigrin. The results suggested that the two tastants may act as negative reinforcers in H. virescens.
Running in ostriches (Struthio camelus): three-dimensional joint axes alignment and joint kinematics
Authors: Rubenson Jonas , Lloyd David G. , Besier Thor F. , Heliams Denham B. , Fournier Paul A.
Published: June 2007

Although locomotor kinematics in walking and running birds have been examined in studies exploring many biological aspects of bipedalism, these studies have been largely limited to two-dimensional analyses. Incorporating a five-segment, 17 degree-of-freedom (d.f.) kinematic model of the ostrich hind limb developed from anatomical specimens, we quantified the three-dimensional(3-D) joint axis alignment and joint kinematics during running (at ∼3.3 m s–1) in the largest avian biped, the ostrich. Our analysis revealed that the majority of the segment motion during running in the ostrich occurs in flexion/extension. Importantly, however, the alignment of the average flexion/extension helical axes of the knee and ankle are rotated externally to the direction of travel (37° and 21°, respectively) so that pure flexion and extension at the knee will act to adduct and adbuct the tibiotarsus relative to the plane of movement, and pure flexion and extension at the ankle will act to abduct and adduct the tarsometatarsus relative to the plane of movement. This feature of the limb anatomy appears to provide the major lateral (non-sagittal) displacement of the lower limb necessary for steering the swinging limb clear of the stance limb and replaces what would otherwise require greater adduction/abduction and/or internal/external rotation, allowing for less complex joints, musculoskeletal geometry and neuromuscular control. Significant rotation about the joints'non-flexion/extension axes nevertheless occurs over the running stride. In particular, hip abduction and knee internal/external and varus/valgus motion may further facilitate limb clearance during the swing phase, and substantial non-flexion/extension movement at the knee is also observed during stance. Measurement of 3-D segment and joint motion in birds will be aided by the use of functionally determined axes of rotation rather than assumed axes, proving important when interpreting the biomechanics and motor control of avian bipedalism.
New Product Diffusion with Influentials and Imitators
Authors: Van den Bulte Christophe , Joshi Yogesh V.
Published: June 2007

We model the diffusion of innovations in markets with two segments: influentials who are more in touch with new developments and who affect another segment of imitators whose own adoptions do not affect the influentials. This two-segment structure with asymmetric influence is consistent with several theories in sociology and diffusion research, as well as many “viral” or “network” marketing strategies. We have four main results. (1) Diffusion in a mixture of influentials and imitators can exhibit a dip or “chasm” between the early and later parts of the diffusion curve. (2) The proportion of adoptions stemming from influentials need not decrease monotonically, but may first decrease and then increase. (3) Erroneously specifying a mixed-influence model to a mixture process where influentials act independently from each other can generate systematic changes in the parameter values reported in earlier research. (4) Empirical analysis of 33 different data series indicates that the two-segment model fits better than the standard mixed-influence, the Gamma/Shifted Gompertz, and the Weibull-Gamma models, especially in cases where a two-segment structure is likely to exist. Also, the two-segment model fits about as well as the Karmeshu-Goswami mixed-influence model, in which the coefficients of innovation and imitation vary across potential adopters in a continuous fashion.
Modeling Page Views Across Multiple Websites with an Application to Internet Reach and Frequency Prediction
Authors: Danaher Peter J.
Published: June 2007

In this study, we develop a multivariate generalization of the negative binomial distribution (NBD). This new model has potential application to situations where separate NBDs are correlated, such as for page views across multiple websites. In turn, our page view model is used to predict the audience for Internet advertising campaigns. For very large Internet advertising schedules, a simple approximation to the multivariate model is also derived. In a test of nearly 3,000 Internet advertising schedules, the two new models are compared with some proprietary and nonproprietary models previously used for Internet advertising and are shown to be significantly more accurate.
Deconstructing Each Item’s Category Contribution
Authors: Kalyanam Kirthi , Borle Sharad , Boatwright Peter
Published: June 2007

Retailers and manufacturers believe that the mere presence of certain items in a retail assortment increases the sales volume of the whole assortment. This paper provides an empirical study of the role of every item in an assortment. Our results show that many items affect category sales over and above their own sales volume. After deconstructing the role of a stockout of individual items into three effects—lost own sales, substitution to other items, and the category sales impact—we find that the category impact has the largest magnitude. Interestingly, the disproportionate impact of individual items on category sales is not restricted to top-selling items, for almost every single individual item affects category sales. It seems that variety is indeed the price of entry in retailing. Our results support recent findings that more frequently purchased categories are less adversely affected by reductions in assortment. We also find that the assortment appears to gain attractiveness when certain items are out of stock, a result that is consistent with the discussion in the literature concerning category clutter.
Magnetic Resonance-Based Tracking and Quantification of Intravenously Injected Neural Stem Cell Accumulation in the Brains of Mice with Experimental Multiple Sclerosis
Authors: Politi Letterio S. , Bacigaluppi Marco , Brambilla Elena , Cadioli Marcello , Falini Andrea , Comi Giancarlo , Scotti Giuseppe , Martino Gianvito , Pluchino Stefano
Published: June 2007

Eliciting the in situ accumulation and persistence patterns of stem cells following transplantation would provide critical insight toward human translation of stem cell-based therapies. To this end, we have developed a strategy to track neural stem/precursor cells (NPCs) in vivo using magnetic resonance (MR) imaging. Initially, we evaluated three different human-grade superparamagnetic iron oxide particles for labeling NPCs and found the optimal labeling to be achieved with Resovist. Next, we carried out in vivo experiments to monitor the accumulation of Resovist-labeled NPCs following i.v. injection in mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. With a human MR scanner, we were able to visualize transplanted cells as early as 24 hours post-transplantation in up to 80% of the brain demyelinating lesions. Interestingly, continued monitoring of transplanted mice indicated that labeled NPCs were still present 20 days postinjection. Neuropathological analysis confirmed the presence of transplanted NPCs exclusively in inflammatory demyelinating lesions and not in normal-appearing brain areas. Quantification of transplanted cells by means of MR-based ex vivo relaxometry (R2*) showed significantly higher R2* values in focal inflammatory brain lesions from EAE mice transplanted with labeled NPCs as compared with controls. Indeed, sensitive quantification of low numbers of NPCs accumulating into brain inflammatory lesions (33.3–164.4 cells per lesion; r2 = .998) was also obtained. These studies provide evidence that clinical-grade human MR can be used for noninvasive monitoring and quantification of NPC accumulation in the central nervous system upon systemic cell injection.

Disclosure of potential conflicts of interest is found at the end of this article.
Concise Review: Prospects of Stem Cell Therapy for Temporal Lobe Epilepsy
Authors: Shetty Ashok K. , Hattiangady Bharathi
Published: June 2007

Certain regions of the adult brain have the ability for partial self-repair after injury through production of new neurons via activation of neural stem/progenitor cells (NSCs). Nonetheless, there is no evidence yet for pervasive spontaneous replacement of dead neurons by newly formed neurons leading to functional recovery in the injured brain. Consequently, there is enormous interest for stimulating endogenous NSCs in the brain to produce new neurons or for grafting of NSCs isolated and expanded from different brain regions or embryonic stem cells into the injured brain. Temporal lobe epilepsy (TLE), characterized by hyperexcitability in the hippocampus and spontaneous seizures, is a possible clinical target for stem cell-based therapies. This is because these approaches have the potential to curb epileptogenesis and prevent chronic epilepsy development and learning and memory dysfunction after hippocampal damage related to status epilepticus or head injury. Grafting of NSCs may also be useful for restraining seizures during chronic epilepsy. The aim of this review is to evaluate current knowledge and outlook pertaining to stem cell-based therapies for TLE. The first section discusses the behavior of endogenous hippocampal NSCs in human TLE and animal models of TLE and evaluates the role of hippocampal neurogenesis in the pathophysiology and treatment of TLE. The second segment considers the prospects for preventing or suppressing seizures in TLE using exogenously applied stem cells. The final part analyzes problems that remain to be resolved before initiating clinical application of stem cell-based therapies for TLE.

Disclosure of potential conflicts of interest is found at the end of this article.
Changes in and Prognostic Value of Hormone Receptor Status in a Series of Operable Breast Cancer Patients Treated with Neoadjuvant Chemotherapy
Authors: Tacca Olivier , Penault-Llorca Frédérique , Abrial Catherine , Mouret-Reynier Marie-Ange , Raoelfils Inès , Durando Xavier , Achard Jean-Louis , Gimbergues Pierre , Curé Hervé , Chollet Philippe
Published: June 2007

The aim of this study was to detect and analyze changes in hormone receptor (HR) status after treatment of operable breast cancer with neoadjuvant chemotherapy (NCT). Patients were treated from 1982 to 2004 with different NCT combinations, mainly in successive prospective phase II trials. HR status before and after NCT was retested and reviewed in a blinded fashion by two pathologists, for 420 patients from a database of 710 patients. Among these 420 tumors, 145 (35%) were HR negative and 275 (65%) were HR positive before NCT. The HR status had changed after treatment in 98 patients (23%): 61 patients (42%) initially HR negative became HR positive. This HR-positive switch was significantly correlated with better overall survival (OS), compared with patients with unchanged HR-negative tumors. Moreover, this HR-positive switch also had an effect on disease-free survival (DFS). Conversely, 37 patients (13%) initially HR positive became HR negative after NCT. However, this group of previously positive patients still had a survival advantage for OS, but not for DFS. The Allred score was evaluated before and after chemotherapy. An increase in Allred score after NCT was significantly correlated with better DFS but not OS. It was previously shown, for other tumor parameters, that residual disease after NCT, rather than parameters evaluated on the initial biopsy, must be considered for patient prognosis. In this work, NCT induced variations in HR status in 23% of patients. A positive switch in HR status after NCT could be an indicator of better prognosis for patient outcome.
FDA Drug Approval Summary: Bevacizumab (Avastin®) Plus Carboplatin and Paclitaxel as First-Line Treatment of Advanced/Metastatic Recurrent Nonsquamous Non-Small Cell Lung Cancer
Authors: Cohen Martin H. , Gootenberg Joe , Keegan Patricia , Pazdur Richard
Published: June 2007

Learning Objectives

After completing this course, the reader will be able to: Describe the bevacizumab mechanism of action.List the current bevacizumab indications.Discuss the role of bevacizumab in the treatment of specific non-small cell lung cancer histologies.Describe the clinical trial design leading to bevacizumab approval by the FDA.Identify the major adverse events associated with bevacizumab treatment.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Efficacy and Safety of Every-2-Week Darbepoetin Alfa in Patients with Anemia of Cancer: A Controlled, Randomized, Open-Label Phase II Trial
Authors: Charu Veena , Belani Chandra P. , Gill Ahmad N. , Bhatt Mukesh , Tomita Dianne , Rossi Greg , Ben-Jacob Ali
Published: June 2007

This randomized, controlled trial evaluated the effect of darbepoetin alfa on hospitalization days, transfusion requirements, hemoglobin levels, and fatigue in patients with anemia of cancer (AOC). Eligible patients were anemic (hemoglobin ≤11 g/dl) due to cancer, ≥18 years old, and had not received chemotherapy or radiotherapy within 4 weeks of study screening. Patients were randomized 4:1 to receive darbepoetin alfa, 3.0 μg/kg every 2 weeks (Q2W) (n = 226), or observation only for 12 weeks (n = 59), followed by an optional 9 weeks of darbepoetin alfa, 3.0 μg/kg Q2W. Endpoints were compared between the two treatment arms at week 13. A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect, so the study was terminated early. Therefore, results for the primary endpoint should be interpreted cautiously. The hospitalization rate was similar (0.5 days) for both the darbepoetin alfa and observation groups (p = .73). Transfusion incidence (weeks 5–12) was significantly lower for darbepoetin alfa patients (8%) than for observation patients (22%) (p = .0092). By week 13, hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa, compared with 0.1 g/dl in the observation group p < .0001. Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy–Fatigue score (mean change in score at week 13: darbepoetin alfa, 6.0; observation, 2.2; p < .05). Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC, resulting in significant improvements in health-related quality of life.
Factors Associated With Successful Smoking Cessation in the United States, 2000
Authors: Lee Chung-won , Kahende Jennifer
Published: June 2007

Objectives. Each year, nearly 2 in 5 cigarette smokers try to quit, but fewer than 10% succeed. Taking a multifaceted approach to examine the predictors of successfully quitting smoking, we identified factors associated with successful quitting so that cessation programs could be tailored to those at highest risk for relapse.

Methods. Using data from the 2000 National Health Interview Survey, we employed multiple regression analysis to compare demographic, behavioral, and environmental characteristics of current smokers who tried unsuccessfully to quit in the previous 12 months with characteristics of those able to quit for at least 7 to 24 months before the survey.

Results. Successful quitters were more likely than those unable to quit to have rules against smoking in their homes, less likely to have switched to light cigarettes for health concerns, and more likely to be aged 35 years or older, married or living with a partner, and non-Hispanic White, and to have at least a college education.

Conclusions. Programs promoting smoking cessation might benefit by involving family or other household members to encourage smoke-free homes.
Predictors of Sustained Smoking Cessation: A Prospective Analysis of Chronic Smokers From the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study
Authors: Augustson Erik M. , Wanke Kay L. , Rogers Scott , Bergen Andrew W. , Chatterjee Nilanjan , Synder Kirk , Albanes Demetrius , Taylor Phil R. , Caporaso Neil E.
Published: June 2007

Objectives. Because US smoking rates have not declined during the past decade, there is a renewed need to identify factors associated with smoking cessation. Using a nested case–control design, we explored the association between ability to sustain cessation over an extended period and demographic, smoking, medical, and behavioral variables.

Methods. We selected a sample of 1379 sustained quitters (abstinent from smoking for at least 40 months) and 1388 relapsers (abstinent for more than 8 months before relapse) from participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, a nutritional intervention study involving Finnish men aged 50 to 69 years at baseline. Contingency table and multiple regression analyses were used to evaluate potential differences between the 2 groups on baseline variables.

Results. Compared with sustained quitters, relapsers were more likely to report symptoms of emotional distress and higher levels of nicotine dependence, to drink more alcohol, and to report more medical conditions.

Conclusions. Factors associated with both tobacco use and comorbid conditions impact an individual’s ability to maintain long-term smoking cessation. Understanding the underlying mechanisms of action and potential common pathways among these factors may help to improve smoking cessation therapies.
The Effects of Changes in Smoking Prevalence on Obesity Prevalence in the United States
Authors: Flegal Katherine M.
Published: June 2007

Objectives. Reduction of cigarette smoking is an important public health goal. However, lower smoking prevalence may be associated with increased obesity prevalence. I sought to estimate the effect of decreases in smoking prevalence on obesity prevalence in the United States population.

Methods. I combined current weight data by smoking status from the 1999–2002 National Health and Nutrition Examination Survey (NHANES) with smoking prevalence data from past NHANES surveys to estimate weight status had smoking prevalence not changed.

Results. Even relatively large changes in the prevalence of smoking were estimated to have little effect on obesity prevalence. For example, if smoking prevalence in 1999–2002 were at the higher 1971–1975 smoking level, the estimated 1999–2002 obesity prevalence would be 22.5% rather than the actual value of 23.9%, a difference of only 1.4 percentage points. Estimates for other weight categories were similarly small.

Conclusions. Decreases in the prevalence of cigarette smoking probably had only a small effect, often less than 1 percentage point, on increasing the prevalence of obesity and decreasing the prevalence of healthy weight in the population.
Under the Radar: Smokeless Tobacco Advertising in Magazines With Substantial Youth Readership
Authors: Morrison Margaret A. , Krugman Dean M. , Park Pumsoon
Published: June 2007

Objectives. In light of the Smokeless Tobacco Master Settlement Agreement (STMSA) and the fact that smokeless tobacco advertising has received little attention, we examined industry data to assess smokeless tobacco advertising in popular magazines. Of particular interest was the level of advertising in magazines with high youth readership and the amount of reach and frequency that was generated among readers aged 12 to 17 years.

Methods. We used readership data from Mediamark Research Inc, advertising expenditure data from TNS Media Intelligence, and Adplus, a media planning program from Telmar to document the composition of adult and youth readership of magazines in which smokeless tobacco products were advertised, industry expenditures on advertising, and adolescents’ exposure to smokeless tobacco advertising.

Results. The STMSA appears to have had a limited effect on the advertising of smokeless tobacco products to youth; both before and after the agreement, smokeless tobacco companies advertised in magazines with high adolescent readership.

Conclusions. Popular magazines with smokeless tobacco advertising reach a large number of adolescents through a combination of both youth-oriented and adult magazines. These exposure levels have generally increased since the STMSA.
High School Seniors’ Smoking Initiation and Progression 1 Year After Graduation
Authors: Tercyak Kenneth P. , Rodriguez Daniel , Audrain-McGovern Janet
Published: June 2007

We explored cigarette smoking prevalence rates in former high school seniors 1 year after graduation and found that among 12th grade never smokers, 25% initiated smoking, and among 12th grade ever smokers, 39% increased their cigarette use. Alcohol use in 12th grade, along with not attending college, were both positively related to smoking progression. Risk for smoking initiation does not end at adolescence, and the public health community must continue tobacco control initiatives throughout adolescence and young adulthood.
Smoking and Cessation Behaviors Among Young Adults of Various Educational Backgrounds
Authors: Solberg Leif I. , Asche Stephen E. , Boyle Raymond , McCarty Maribet C. , Thoele Merry Jo
Published: June 2007

Objectives. We sought to determine whether the educational backgrounds of young adult smokers (aged 18 to 24 years) affect their cessation attitudes or behaviors in ways that could be used to improve smoking interventions.

Methods. We surveyed 5580 members of the HealthPartners health plan and conducted a follow-up survey 12 months later of current and former smokers. Respondents were divided into subgroups according to educational level.

Results. Higher levels of education were associated with lower smoking rates (16% among students in 4-year colleges, 31% among those in technical or 2-year colleges, and 48% among those with a high school education or less) as well as less frequent or heavy smoking. However, number of quit attempts in the past year, level of interest in quitting, and smoking relapse rates did not vary according to educational level. Seventy-three percent of those who had attempted to quit had not used some form of assistance.

Conclusions. Rates of smoking among young adults, especially those at low educational levels, are relatively high. However, most members of this age group are interested in quitting, regardless of educational background.
“A Whole ’Nother Smoke” or a Cigarette in Disguise: How RJ Reynolds Reframed the Image of Little Cigars
Authors: Delnevo Cristine D. , Hrywna Mary
Published: June 2007

Present-day consumption of little cigars rivals that of the early 1970s when sales of little cigars boomed. This boom was largely attributed to RJ Reynolds, and documents reveal how and why they became a powerful force in little cigar sales. RJ Reynolds designed a little cigar, Winchesters, for cigarette smokers and produced one as close to a cigarette as legally possible.

Initially, RJ Reynolds intended to capitalize on the cigarette advertising broadcast ban, but the price and tax structure was more critical to Winchester’s success. Today, the tobacco industry is fighting again to sustain its unique application of federal definitions for little cigars. Regulatory efforts are needed to close taxation loopholes for the little cigar.
Treating Tobacco Dependence in Clinically Depressed Smokers: Effect of Smoking Cessation on Mental Health Functioning
Authors: Prochaska Judith J. , Hall Sharon M. , Tsoh Janice Y. , Eisendrath Stuart , Rossi Joseph S. , Redding Colleen A. , Rosen Amy B. , Meisner Marc , Humfleet Gary L. , Gorecki Julie A.
Published: June 2007

We analyzed data from a randomized trial of 322 actively depressed smokers and examined the effect of smoking cessation on their mental health functioning. Only 1 of 10 measures at 4 follow-up time points was significant: participants who successfully stopped smoking reported less alcohol use than did participants who continued smoking. Depressive symptoms declined significantly over time for participants who stopped smoking and those who continued smoking; there were no group differences. Individuals in treatment for clinical depression can be helped to stop smoking without adversely affecting their mental health functioning.
Future time perspective, possible selves, and academic achievement
Authors: Leondari Angeliki
Published: June 2007

Possible selves and education are oriented toward future goals. This chapter surveys the literature that links possible selves achievement with motivation toward academic achievement.