bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic and Pharmacodynamic Modeling of an Anti–Interleukin-6 Chimeric Monoclonal Antibody (Siltuximab) in Patients with Metastatic Renal Cell Carcinoma
Authors: Puchalski Thomas , Prabhakar Uma , Jiao Qun , Berns Birge , Davis Hugh M.
Published: February 2010

Purpose: Interleukin-6 (IL-6) induces tumor growth, invasion, metastasis, and angiogenesis. Siltuximab (CNTO 328) is a chimeric, murine-human monoclonal antibody that specifically binds human IL-6 with high affinity. C-reactive protein (CRP) can be a pharmacodynamic (PD) marker of IL-6 bioactivity. Reductions in CRP may correlate with clinical activity and IL-6 bioactivity.

Experimental Design: Starting-dose selection for this study was based on a previous siltuximab study in multiple myeloma patients. Pharmacokinetic (PK)/PD modeling explored the relationship between siltuximab PK and CRP suppression following i.v. siltuximab infusion in a three-part phase I/II study in 68 metastatic renal cell carcinoma patients. Modeling results were then used to simulate and determine which siltuximab dosage regimens would maintain CRP suppression below the lower limit of quantification (4 mg/L). Siltuximab was given at 1, 3, 6, or 12 mg/kg at weeks 1 and 4 and then every 2 weeks for 2 cycles in part 1; at 3 or 6 mg/kg every 3 weeks for 4 cycles in part 2; and at 6 mg/kg every 2 weeks for 6 cycles in part 3.

Results: A two-compartment PK model adequately described the serum siltuximab concentration-time data. An inhibitory indirect response PD model examined the relationship between siltuximab concentrations and CRP suppression. PD parameter estimates seemed reliable and physiologically relevant. Simulations showed that 6 mg/kg siltuximab every 2 weeks or 9 mg/kg every 3 weeks would reduce serum CRP to below 4 mg/L.

Conclusions: Using a stepwise design, PK/PD modeling was used to select the dose levels in this study. Furthermore, PK/PD modeling results were used to help select doses to be used in future siltuximab clinical development. Clin Cancer Res; 16(5); 1652–61
Accurate Outcome Prediction in Neuroblastoma across Independent Data Sets Using a Multigene Signature
Authors: De Preter Katleen , Vermeulen Joëlle , Brors Benedikt , Delattre Olivier , Eggert Angelika , Fischer Matthias , Janoueix-Lerosey Isabelle , Lavarino Cinzia , Maris John M. , Mora Jaume , Nakagawara Akira , Oberthuer André , Ohira Miki , Schleiermacher Gudrun , Schramm Alexander , Schulte Johannes H. , Wang Qun , Westermann Frank , Speleman Frank , Vandesompele Jo
Published: February 2010

Purpose: Reliable prognostic stratification remains a challenge for cancer patients, especially for diseases with variable clinical course such as neuroblastoma. Although numerous studies have shown that outcome might be predicted using gene expression signatures, independent cross-platform validation is often lacking.

Experimental Design: Using eight independent studies comprising 933 neuroblastoma patients, a prognostic gene expression classifier was developed, trained, tested, and validated. The classifier was established based on reanalysis of four published studies with updated clinical information, reannotation of the probe sequences, common risk definition for training cases, and a single method for gene selection (prediction analysis of microarray) and classification (correlation analysis).

Results: Based on 250 training samples from four published microarray data sets, a correlation signature was built using 42 robust prognostic genes. The resulting classifier was validated on 351 patients from four independent and unpublished data sets and on 129 remaining test samples from the published studies. Patients with divergent outcome in the total cohort, as well as in the different risk groups, were accurately classified (log-rank P < 0.001 for overall and progression-free survival in the four independent data sets). Moreover, the 42-gene classifier was shown to be an independent predictor for survival (odds ratio, >5).

Conclusion: The strength of this 42-gene classifier is its small number of genes and its cross-platform validity in which it outperforms other published prognostic signatures. The robustness and accuracy of the classifier enables prospective assessment of neuroblastoma patient outcome. Most importantly, this gene selection procedure might be an example for development and validation of robust gene expression signatures in other cancer entities. Clin Cancer Res; 16(5); 1532–41
Melanoma MicroRNA Signature Predicts Post-Recurrence Survival
Authors: Segura Miguel F. , Belitskaya-Lévy Ilana , Rose Amy E. , Zakrzewski Jan , Gaziel Avital , Hanniford Douglas , Darvishian Farbod , Berman Russell S. , Shapiro Richard L. , Pavlick Anna C. , Osman Iman , Hernando Eva
Published: February 2010

Purpose: To identify a melanoma microRNA (miRNA) expression signature that is predictive of outcome and then evaluate its potential to improve risk stratification when added to the standard-of-care staging criteria.

Experimental Design: Total RNA was extracted from 59 formalin-fixed paraffin-embedded melanoma metastases and hybridized to miRNA arrays containing 911 probes. We then correlated miRNA expression with post-recurrence survival and other clinicopathologic criteria.

Results: We identified a signature of 18 miRNAs whose overexpression was significantly correlated with longer survival, defined as more than 18 months post-recurrence survival. Subsequent cross-validation showed that a small subset of these miRNAs can predict post-recurrence survival in metastatic melanoma with an estimated accuracy of 80.2% (95% confidence interval, 79.8−80.6%). In contrast to standard-of-care staging criteria, a six-miRNA signature significantly stratified stage III patients into “better” and “worse” prognostic categories, and a multivariate Cox regression analysis revealed the signature to be an independent predictor of survival. Furthermore, we showed that most miRNAs from the signature also showed differential expression between patients with better and worse prognoses in the corresponding paired primary melanoma.

Conclusions: MiRNA signatures have potential as clinically relevant biomarkers of prognosis in metastatic melanoma. Our data suggest that molecularly based models of risk assessment can improve the standard staging criteria and support the incorporation of miRNAs into such models. Clin Cancer Res; 16(5); 1577–86
A Novel, Highly Sensitive Antibody Allows for the Routine Detection ofALK-Rearranged Lung Adenocarcinomas by Standard Immunohistochemistry
Authors: Mino-Kenudson Mari , Chirieac Lucian R. , Law Kenny , Hornick Jason L. , Lindeman Neal , Mark Eugene J. , Cohen David W. , Johnson Bruce E. , Jänne Pasi A. , Iafrate A. John , Rodig Scott J.
Published: February 2010

Purpose: Approximately 5% of lung adenocarcinomas harbor an EML4-ALK gene fusion and define a unique tumor group that may be responsive to targeted therapy. However ALK-rearranged lung adenocarcinomas are difficult to detect by either standard fluorescence in situ hybridization or immunohistochemistry (IHC) assays. In the present study, we used novel antibodies to compare ALK protein expression in genetically defined lung cancers and anaplastic large cell lymphomas.

Experimental Design: We analyzed 174 tumors with one standard and two novel monoclonal antibodies recognizing the ALK protein. Immunostained tissue sections were assessed for the level of tumor-specific ALK expression by objective quantitative image analysis and independently by three pathologists.

Results: ALK protein is invariably and exclusively expressed in ALK-rearranged lung adenocarcinomas but at much lower levels than in the prototypic ALK-rearranged tumor, anaplastic large cell lymphoma, and as a result, is often not detected by conventional IHC. We further validate a novel IHC that shows excellent sensitivity and specificity (100% and 99%, respectively) for the detection of ALK-rearranged lung adenocarcinomas in biopsy specimens, with excellent interobserver agreement between pathologists (κ statistic, 0.94).

Conclusions: Low levels of ALK protein expression is a characteristic feature of ALK-rearranged lung adenocarcinomas. However, a novel, highly sensitive IHC assay reliably detects lung adenocarcinomas with ALK rearrangements and obviates the need for fluorescence in situ hybridization analysis for the majority of cases, and therefore could be routinely applicable in clinical practice to detect lung cancers that may be responsive to ALK inhibitors. Clin Cancer Res; 16(5); 1561–71
Modulation of Lymphocyte Regulation for Cancer Therapy: A Phase II Trial of Tremelimumab in Advanced Gastric and Esophageal Adenocarcinoma
Authors: Ralph Christy , Elkord Eyad , Burt Deborah J. , O'Dwyer Jackie F. , Austin Eric B. , Stern Peter L. , Hawkins Robert E. , Thistlethwaite Fiona C.
Published: February 2010

Purpose: Cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T-cell activation, is targeted by the antibody tremelimumab to release potentially useful antitumor activity.

Experimental Design: This phase II trial investigated tremelimumab as a second-line treatment for patients with metastatic gastric and esophageal adenocarcinomas. Tremelimumab was given every 3 months until symptomatic disease progression. Safety, clinical efficacy, and immunologic activity were evaluated.

Results: Eighteen patients received tremelimumab. Most drug-related toxicity was mild; however, there was a single death due to bowel perforation that complicated colitis. Four patients had stable disease with clinical benefit; one patient achieved a partial response after eight cycles (25.4 months) and remains well on study at 32.7 months. Markers of regulatory phenotype, forkhead box protein 3 and CTLA4, doubled transiently in CD4+CD25high lymphocytes in the first month after tremelimumab before returning to baseline. In contrast, CTLA4 increased in CD4+CD25low/negative lymphocytes throughout the cycle of treatment. De novo proliferative responses to tumor-associated antigens 5T4 (8 of 18 patients) and carcinoembryonic antigen (5 of 13) were detected. Patients with a posttreatment carcinoembryonic antigen proliferative response had median survival of 17.1 months compared with 4.7 months for nonresponders (P = 0.004). Baseline interleukin-2 release after T-cell activation was higher in patients with clinical benefit and toxicity.

Conclusion: Despite the disappointing response rate of tremelimumab, one patient had a remarkably durable benefit for this poor-prognosis disease. In vitro evidence of enhanced proliferative responses to relevant tumor-associated antigens suggests that combining CTLA4 blockade with antigen-targeted therapy may warrant further investigation. Clin Cancer Res; 16(5); 1662–72
Patient-Derived First Generation Xenografts of Non–Small Cell Lung Cancers: Promising Tools for Predicting Drug Responses for Personalized Chemotherapy
Authors: Dong Xin , Guan Jun , English John C. , Flint Julia , Yee John , Evans Kenneth , Murray Nevin , MacAulay Calum , Ng Raymond T. , Gout Peter W. , Lam Wan L. , Laskin Janessa , Ling Victor , Lam Stephen , Wang Yuzhuo
Published: February 2010

Purpose: Current chemotherapeutic regimens have only modest benefit for non–small cell lung cancer (NSCLC) patients. Cumulative toxicities/drug resistance limit chemotherapy given after the first-line regimen. For personalized chemotherapy, clinically relevant NSCLC models are needed for quickly predicting the most effective regimens for therapy with curative intent. In this study, first generation subrenal capsule xenografts of primary NSCLCs were examined for (a) determining responses to conventional chemotherapeutic regimens and (b) selecting regimens most effective for individual patients.

Experimental Design: Pieces (1×3×3 mm3) of 32 nontreated, completely resected patients' NSCLCs were grafted under renal capsules of nonobese diabetic/severe combined immunodeficient mice and treated with (A) cisplatin+vinorelbine, (B) cisplatin+docetaxel, (C) cisplatin+gemcitabine, and positive responses (treated tumor area ≤50% of control, P < 0.05) were determined. Clinical outcomes of treated patients were acquired.

Results: Xenografts from all NSCLCs were established (engraftment rate, 90%) with the retention of major biological characteristics of the original cancers. The entire process of drug assessment took 8 weeks. Response rates to regimens A, B, and C were 28% (9 of 32), 42% (8 of 19), and 44% (7 of 16), respectively. Certain cancers that were resistant to a particular regimen were sensitive to others. The majority of responsive tumors contained foci of nonresponding cancer cells, indicative of tumor heterogeneity and potential drug resistance. Xenografts from six of seven patients who developed recurrence/metastasis were nonresponsive.

Conclusions: Models based on first generation NSCLC subrenal capsule xenografts have been developed, which are suitable for quick assessment (6-8 weeks) of the chemosensitivity of patients' cancers and selection of the most effective regimens. They hold promise for application in personalized chemotherapy of NSCLC patients. Clin Cancer Res; 16(5); 1442–51
Does Lapatinib Work against HER2-negative Breast Cancers?
Authors: Mayer Ingrid A. , Arteaga Carlos L.
Published: February 2010

Aberrant growth factor receptor signaling can augment or suppress estrogen receptor (ER) function in hormone-dependent breast cancer cells and lead to escape from anti-estrogen therapy. Interruption of HER2/ER cross-talk with lapatinib can restore sensitivity to anti-estrogens and thus, should be investigated in combination with endocrine therapy in patients with ER+/HER2-negative breast cancers. Clin Cancer Res; 16(5); 1355–7
Chronic Cyclooxygenase-2 Inhibition Promotes Myofibroblast-Associated Intestinal Fibrosis
Authors: Davids Jennifer S. , Carothers Adelaide M. , Damas Beatrice C. , Bertagnolli Monica M.
Published: February 2010

Anti-inflammatory drugs prevent intestinal tumor formation, an activity related to their ability to inhibit inflammatory pathway signaling in the target tissue. We previously showed that treatment of Min/+ mice with the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib induced rapid tumor regression; however, drug-resistant tumors appeared with long-term treatment. In this study, we investigated whole-tissue changes in inflammatory signaling by studying constituents of the tissue stroma and extracellular matrix. We found that celecoxib resistance was associated with changes in factors regulating autocrine transforming growth factor-β (TGFβ) signaling. Chronic drug treatment expanded the population of bone marrow–derived CD34+ vimentin+ αSMA− myofibroblast precursors and αSMA+ vimentin+ F4/80− myofibroblasts in the lamina propria and submucosa, providing a source of increased TGFβ and COX-2 expression. Membrane constituents regulating TGFβ availability, including syndecan-1 and heparanase-1, were also modified by chronic treatment in a manner promoting increased TGFβ signaling. Finally, long-term celecoxib treatment induced tissue fibrosis, as indicated by increased expression of collagen, fibronectin, and laminin in the basement membrane. We conclude that chronic COX-2 inhibition alters TGFβ signaling in the intestinal mucosa, producing conditions consistent with chronic inflammation. Cancer Prev Res; 3(3); 348–58
Loss of Inhibitory Insulin Receptor Substrate-1 Phosphorylation Is an Early Event in Mammalian Target of Rapamycin–Dependent Endometrial Hyperplasia and Carcinoma
Authors: McCampbell Adrienne S. , Harris Heather A. , Crabtree Judy S. , Winneker Richard C. , Walker Cheryl L. , Broaddus Russell R.
Published: February 2010

Insulin-like growth factor-I receptor signaling contributes to the development of endometrial hyperplasia, the precursor to endometrioid-type endometrial carcinoma, in humans and in rodent models. This pathway is under both positive and negative regulation, including S6 kinase (S6K) phosphorylation of insulin receptor substrate-1 (IRS-1) at S636/639, which occurs downstream of mammalian target of rapamycin (mTOR) activation to inhibit this adapter protein. We observed activation of mTOR with a high frequency in human endometrial hyperplasia and carcinoma, but an absence of IRS-1 phosphorylation, despite high levels of activated S6K. To explore when during disease progression mammalian target of rapamycin (mTOR) activation and loss of negative feedback to IRS-1 occurred, we used the Eker rat (Tsc2Ek/+) model, where endometrial hyperplasia develops as a result of loss of Tsc2, a “gatekeeper” for mTOR. We observed mTOR activation early in progression in hyperplasias and in some histologically normal epithelial cells, suggesting that event(s) in addition to loss of Tsc2 were required for progression to hyperplasia. In contrast, whereas IRS-1 S636/639 phosphorylation was observed in normal epithelium, it was absent from all hyperplasias, indicating loss of IRS-1 inhibition by S6K occurred during progression to hyperplasia. Treatment with a mTOR inhibitor (WAY-129327) significantly decreased hyperplasia incidence and proliferative indices. Because progression from normal epithelium to carcinoma proceeds through endometrial hyperplasia, these data suggest a progression sequence where activation of mTOR is followed by loss of negative feedback to IRS-1 during the initial stages of development of this disease. Cancer Prev Res; 3(3); 290–300
Metabolic Syndrome Is Not Associated With Increased Mortality or Cardiovascular Risk in Nondiabetic Patients With a New Diagnosis of Coronary Artery Disease
Authors: Petersen John L. , Yow Eric , AlJaroudi Wael , Shaw Linda K. , Goyal Abhinav , McGuire Darren K. , Peterson Eric D. , Harrington Robert A.
Published: February 2010

Background—

Metabolic syndrome (MetSyn) is associated with increased cardiovascular risk in the general population. Its prognostic implications are less well defined in patients with coronary artery disease.

Methods and Results—

We analyzed patients in the Duke Database for Cardiovascular Disease with a diagnosis of incident obstructive coronary artery disease. Diabetes mellitus (DM) was classified as a clinical history of DM, use of hypoglycemic drugs, or fasting glucose of ≥126 mg/dL. MetSyn was defined as having 3 of 5 characteristics: fasting glucose ≥100 and <126 mg/dL, low high-density lipoprotein cholesterol (men, <40 mg/dL; women, <50 mg/dL), triglycerides >150 mg/dL, blood pressure ≥130/85 mm Hg, or use of antihypertensive therapy, or body mass index ≥27. Death, myocardial infarction, or stroke was assessed at 6 months, 1 year, then annually. Cox proportional hazards models were generated to compare mortality and cardiovascular events between groups. The primary cohort consisted of 5744 patients; 1831 (31.9%) had DM, 2491 (43.4%) had MetSyn, and 1422 (24.7%) had no DM/MetSyn. Median follow-up was 5 years. Compared with no DM/MetSyn patients, DM patients had a higher adjusted risk for mortality (hazard ratio, 1.47; 95% CI, 1.28 to 1.69) but MetSyn patients did not (hazard ratio, 0.94; 95% CI, 0.81 to 1.08). Similar results were found for the combined end points of death or myocardial infarction, and death, myocardial infarction, or stroke.

Conclusions—

In a population of consecutive patients with a new diagnosis of coronary artery disease by angiography, MetSyn without DM was not an independent predictor of mortality or cardiovascular events.
Family Matters: Perceptions of Fairness Among Incarcerated Women
Authors: Faris Jeralyn , Miller JoAnn
Published: February 2010

Perceptions of fairness affect how social actors behave and think. Incarcerated women perceive varying degrees of fairness in terms of their prison experiences and with respect to legal institutions that address family and related matters. The authors analyze census survey data produced by women in prison and during small group interviews with mothers in prison to examine how the law is understood by them, focusing on perceptions of fairness. All told, women perceive that when it comes to family matters, they are treated fairly within prison, yet they perceive injustices by the legal system. The authors conclude the article by proposing that women, to be reasonable parents once they leave prison, require transition programs, such as Reentry Court programs, that are comprehensive and gender sensitive.
Does Urban Sprawl Increase the Costs of Providing Local Public Services? Evidence from Spanish Municipalities
Authors: Hortas-Rico Miriam , Solé-Ollé Albert
Published: February 2010

This paper examines the impact of urban sprawl, a phenomenon of particular interest in Spain, which is currently experiencing this process of rapid, low-density urban expansion. Many adverse consequences are attributed to urban sprawl (such as traffic congestion, air pollution and social segregation), although this paper is concerned primarily with the rising costs of providing local public services. The initial aim is to develop an accurate measure of urban sprawl so that its impact on municipal budgets can be tested empirically. Then, an empirical analysis is undertaken using a cross-sectional dataset of 2500 Spanish municipalities for the year 2003 and a piece-wise linear function to account for the potentially non-linear relationship between sprawl and local costs. The estimations derived from the expenditure equations for both aggregate and six disaggregated spending categories indicate that low-density development patterns lead to greater provision costs of local public services.
The Built Environment and Motor Vehicle Ownership and Use: Evidence from Santiago de Chile
Authors: Zegras Christopher
Published: February 2010

This paper examines the relationships between the built environment—both ‘neighborhood’ design characteristics and relative location—and motor vehicle ownership and use in a rapidly motorising, developing city context, that of Santiago de Chile. A vehicle choice model suggests that income dominates the household vehicle ownership decision, but also detects a relationship between several built environment characteristics and a household’s likelihood of car ownership. A second model, directly linked to the ownership model to correct for selection bias and endogeneity, suggests a strong relationship with locational characteristics like distance to the central business district and Metro stations. Elasticities of vehicle kilometres travelled (VKT), calculated via the combined models, suggest that income plays the overall largest single role in determining VKT. In combination, however, a range of different design and relative location characteristics also display a relatively strong association with VKT.
The Influence of Frequency and Semantic Similarity on How Children Learn Grammar
Authors: Abbot-Smith Kirsten , Tomasello Michael
Published: February 2010

Lexically based learning and semantic analogy may both play a role in the learning of grammar. To investigate this, 5-year-old German children were trained on a miniature language (nominally English) involving two grammatical constructions, each of which was associated with a different semantic verb class.Training was followed by elicited production and grammaticality judgement tests with ‘trained verbs’ and a ‘generalization’ test, involving untrained verbs. In the ‘trained verbs’ judgement test the children were above chance at associating particular verbs with the constructions in which they had heard them. They did this significantly more often with verbs which they had heard especially frequently in particular constructions, indicating lexically based learning. There was also an interaction between frequency and semantic class (or the particular verbs). In the generalization judgement test the children were at chance overall. In the elicited production generalization test 75% of the children used the same construction for all items.
Translation Equivalents and the Emergence of Multiple Lexicons in Early Trilingual Development
Authors: Montanari Simona
Published: February 2010

This study examines lexical differentiation in early trilingual development through an analysis of the translation equivalents (TEs) produced by a Tagalog—Spanish—English trilingual child. The child’s cumulative vocabulary between 1;4 and 2;0 was reconstructed through diary records and audio-recordings, and the extent to which phonetically distinct equivalent doublets and triplets were represented in her cumulative lexicon was examined. The results indicate that TEs were produced from early on, similarly to bilingual children. However, the amount of input heard in each language determined the number and types of equivalents acquired. Also, learning a second TE took less time than learning a first, suggesting that the initial differentiation of the lexicon as evidenced by doublets might facilitate the emergence of multiple lexical systems.
Developing Noun Phrase Complexity at School Age: A Text-Embedded Cross-Linguistic Analysis
Authors: Ravid Dorit , Berman Ruth A.
Published: February 2010

Development of noun phrase structure and use is analyzed as an important facet of syntactic acquisition from middle childhood to adolescence. Noun phrases occurring in narrative and expository texts produced in both speech and writing by 96 native speakers of English and Hebrew were identified and examined by a set of specially devised criteria including length in words, syntactic depth, abstractness of head nouns, and nature of modifiers. Results reveal a clear and consistent developmental increment in NP complexity from age 9 to 12, and particularly from age 16 years; written expository texts emerge as a favored site for use of syntactically complex constructions; and nominal elements play a more central role in the discursive syntax of Hebrew than English. Findings are discussed in terms of the interplay between psycholinguistic factors of cognitive processing constraints and the impact of increased literacy in later language development.
Role of Motivation in the Relationship Between Depression, Self-care, and Glycemic Control in Adults With Type 2 Diabetes
Authors: Egede Leonard E. , Osborn Chandra Y.
Published: February 2010

Purpose

The mechanism by which depression influences health outcomes in persons with diabetes is uncertain. The purpose of this study was to test whether depression is related to self-care behavior via social motivation and indirectly related to glycemic control via self-care behavior.

Methods

Patients with diabetes were recruited from an outpatient clinic. Information gathered pertained to demographics, depression, and diabetes knowledge (information); diabetes fatalism (personal motivation); social support (social motivation); and diabetes self-care (behavior). Hemoglobin A1C values were extracted from the patient medical record. Structural equation models tested the predicted pathways.

Results

Higher levels of depressive symptoms were significantly related to having less social support and decreased performance of diabetes self-care behavior. In addition, when depressive symptoms were included in the model, fatalistic attitudes were no longer associated with behavioral performance.

Conclusions

Among adults with diabetes, depression impedes the adoption of effective self-management behaviors (including physical activity, appropriate dietary behavior, foot care, and appropriate self-monitoring of blood glucose behavior) through a decrease in social motivation.
Accuracy and Perceived Expert Status in Group Decisions: When Minority Members Make Majority Members More Accurate Privately
Authors: Sinaceur Marwan , Thomas-Hunt Melissa C. , Neale Margaret A. , O'Neill Olivia A. , Haag Christophe
Published: February 2010

We examined how the minority’s perceived (i.e., not real) expertise affects group discussion and performance. In two experiments, participants were randomly assigned to interacting groups in which the minority faction was perceived as either expert or not. Groups performed a decision task that involved solving a murder mystery. Both experiments showed that minorities perceived as expert (vs. not perceived as expert) made majority individuals acquire more accurate private judgments after group discussion, although the public group decision was not more accurate. In parallel, perceived expertise made minority members change their own judgments less. Experiment 1 also showed that minorities’ questioning behaviors mediated the effect of minorities’ perceived expertise on majority members’ private accuracy. Experiment 2 further showed that majority members’ deeper processing was also a mediator. Thus, minorities with perceived expertise serve as a catalyst, increasing the quality of majority members’ cognitions, but not their own.
Causal Uncertainty and Psychological Well-Being: The Moderating Role of Accommodation (Secondary Control)
Authors: Tobin Stephanie J. , Raymundo Melissa M.
Published: February 2010

Causal uncertainty about one’s own outcomes (CU-Own) is associated with negative affect, depression, and a lack of perceived primary control. We predicted that accommodation, or secondary control, would act as a psychological buffer for high—CU-Own individuals, reducing negative affect and depression.We tested this hypothesis in two studies: one cross-sectional (Study 1) and one longitudinal (Study 2). Participants completed measures of CU-Own, harmony control, and depression in Study 1 and measures of CU-Own, harmony control, flexible goal adjustment, and negative affect in Study 2. Analyses reveal that the CU-Own-depression and CU-Own—negative affect associations were weaker when harmony control or flexible goal adjustment was high. Additional analyses in Studies 1 and 2 examined the roles played by primary control, locus of control, optimism, pessimism, and causal importance. Implications for the CU and accommodation literatures are discussed.
Power Differences in the Construal of a Crisis: The Immediate Aftermath of September 11, 2001
Authors: Magee Joe C. , Milliken Frances J. , Lurie Adam R.
Published: February 2010

In this research, we examine the relationship between power and three characteristics of construal—abstraction, valence, and certainty—in individuals’ verbatim reactions to the events of September 11, 2001, and during the immediate aftermath of the terrorist attacks. We conceptualize power as a form of social distance and find that position power (but not expert power) was positively associated with the use of language that was more abstract (vs. concrete), positive (vs. negative), and certain (vs. uncertain). These effects persist after controlling for temporal distance, geographic distance, and impression management motivation. Our results support central and corollary predictions of Construal Level Theory (Liberman, Trope, & Stephan, 2007; Trope & Liberman, 2003) in a high-consequence, real-world context, and our method provides a template for future research in this area outside of the laboratory.
E-textbook use, information seeking behaviour and its impact: Case study business and management
Authors: Nicholas David , Rowlands Ian , Jamali Hamid R.
Published: February 2010

This paper evaluates the e-book usage and information seeking and reading behaviour of thousands of business and management students. Comparisons are made with students in other subjects. The data largely come from the Joint Information Systems Committee (JISC)-funded National e-Books Observatory (NeBO) project as well as the JISC User Behaviour Observational Study. The main sources of data were: a) transactional logs obtained from the MyiLibrary platform regarding 127 UK universities; b) questionnaire data for more than 5000 students and staff at these universities; c) hard-copy library circulation and retail sales data; and d) focus groups held with 50 staff and students from selected universities. The main findings were that e-textbooks can prove to be extremely popular and widely used, mainly for obtaining snippets of information and for fact finding. The main reason for using e-textbooks was ease of access and convenience.
Integrating Sustainability Into the Marketing Curriculum: Learning Activities That Facilitate Sustainable Marketing Practices
Authors: Borin Norm , Metcalf Lynn
Published: February 2010

In response to political, social, and competitive forces, many firms are developing sustainable marketing strategies. Marketing educators can play an important role in assisting these firms by developing curricula that build the knowledge and skills required to enable marketing graduates to contribute to sustainable marketing efforts. Marketing graduates must not only understand but also be equipped to apply a sustainable marketing thought process to the challenges businesses face today. The authors assist in this goal by (a) presenting key learning objectives in the area of sustainable marketing, (b) describing learning activities that will help students achieve the learning objectives identified, and (c) providing resources that not only support the learning objectives but also connect them to traditional marketing concepts, as well as to concepts from other disciplines.
Health-related Quality of Life in Boys With Duchenne Muscular Dystrophy: Agreement Between Parents and Their Sons
Authors: Bray Paula , Bundy Anita C. , Ryan Monique M. , North Kathryn N. , Everett Anna
Published: February 2010

This study investigated agreement between boys and their parents when reporting on health-related quality of life and the effects of steroid use, age, and physical functioning on self-reported health-related quality of life in boys with Duchenne muscular dystrophy. The Pediatric Quality of Life Inventory™ and brief functional measures were administered to 35 parent-son dyads. We found that agreement between parents and their sons was moderate (intraclass correlation coefficient [ICC]2,1 = 0.66; 95% confidence interval [CI], 0.40-0.80) to poor (ICC2,1 = 0.64; 95% CI, 0.43-0.64). The boys’ self-reports revealed a relationship between disease progression and physical functioning (r = —.75; P = .01); however, disease stage was not related to psychosocial functioning (r = —.27; NS). Parents and boys affected by Duchenne muscular dystrophy have a moderate to poor agreement on health-related quality of life measures, with parents reporting lower overall health-related quality of life when compared with their sons.
A Diffusion Tensor Imaging Study of the Cerebellar Pathways in Children With Autism Spectrum Disorder
Authors: Sivaswamy Lalitha , Kumar Ajay , Rajan Deepa , Behen Michael , Muzik Otto , Chugani Diane , Chugani Harry
Published: February 2010

Children with autistic spectrum disorder are known to have histopathological abnormalities in the cerebellum. Diffusion tensor imaging has been utilized to study abnormalities in connectivity and microintegrity in brains of such children. A region of interest approach was adopted to study cerebellar outflow and inflow pathways in 27 children (24 males; mean age, 5.0 years) with autism, and comparison was made with 16 normally developing controls. An increase in the mean diffusivity of bilateral superior cerebellar peduncles in those with autistic spectrum disorder was noted, as was a reversal of the asymmetry pattern in fractional anisotropy of the middle cerebellar peduncle and the inferior cerebellar peduncle in the autistic spectrum disorder group, compared with controls. This study reiterates the underconnectivity between the cerebellum and neocortex, using diffusion tensor imaging.
Pediatric Epilepsy and First Afebrile Seizure in Singapore: Epidemiology and Investigation Yield at Presentation
Authors: Chan Derrick , Phuah Huan-Kee , Ng Yen-Ling , Choong Chew-Thye , Lim Kim-Whee , Goh Winnie H. S.
Published: February 2010

The authors studied pediatric epilepsy and first afebrile seizure at presentation in Singapore. A total of 211 participants aged 1 month to 15 years with first presentation for afebrile seizures were recruited from November 2002 to May 2004; 108 with ≥2 prior afebrile seizures (newly diagnosed epilepsy) and 103 with first afebrile seizures. A χ2 analysis of demographics, risk factors, examination, and investigation findings showed significant differences in development (normal in 87% [newly diagnosed epilepsy] and 93% [first afebrile seizure], P = .046), neurological examination (normal in 92% [newly diagnosed epilepsy] and 98% [first afebrile seizure], P = .016), and electroencephalogram findings (abnormal in 75% [newly diagnosed epilepsy] and 36.9% [first afebrile seizure], P < .005). Pediatric epilepsy incidence at our institution is 24 per 100 000 person-years and is highest in early childhood. Focal epilepsy is more common than generalized epilepsy. Patients with first afebrile seizure and abnormal development, neurological examination, and electroencephalogram findings should be monitored for future development of epilepsy. Population-based studies are recommended.
Divine Command/Divine Law: A Biblical Perspective
Authors: Miller Patrick D.
Published: February 2010

The starting point for thinking about divine command is the reality of God, the initiating and effecting word of God and the character of God, reflected in Scripture especially in regard to goodness and justice.The necessity of social interaction as context for divine command is reflected in several ways; among those mentioned here are the divine council, the covenant, and the incarnation, the word made flesh and living among us. The covenant is central to thinking about divine commands as they are reflected in Scripture. It presumes a relationship between God and those commanded and is a voluntary association. Obedience to the divine commands results from the goodness of God and is only to the Lord. As such the ethic of command becomes also an ethic of response. Rather than being commands to be obeyed without reason or thought and only because they are commanded by God, the divine commands of Scripture and the law generally involve rationality and persuasion, teaching and interpretation. They chart a way of freedom.
Divine Law/Divine Command: The Ground of Ethics in the Western Tradition — Muslim Perspectives
Authors: Nanji Azim
Published: February 2010

The article examines the ideas of divine command and divine law in their Quranic and Muslim legal contexts. It suggests a strong connection between western and Muslim values based on linkages developed in medieval times through Latin appropriation of Arabic studies of Classical philosophy. It also traces the need to address common, contemporary concerns such as poverty, through a shared ethical stance.
The Undoing of Sex: The Proper Enjoyment of Divine Command
Authors: Hemming Laurence Paul
Published: February 2010

This paper examines the way in which divine law and divine command have in cases been commandeered for the purposes of demonstrating fidelity to religious orthodoxy. It takes the example of one theologian’s investigation into the tradition and asks whether, in the very name of producing an orthodox theology of sexual difference, the debate does not end up being cast in contemporary, sexualised terms. It then takes the example of how contemporary understandings of sexual difference can be read back into ancient texts by examining a reading of Parmenides, and by comparison with Aristotle’s reading of sexual difference shows how that reading can be questioned. It concludes with an examination of a reading of a text of St. Augustine to show (1) how the traditions of celibacy and marriage have not been commensurate in the Christian tradition and (2) what goes wrong when they are asserted to be commensurate.
Is MARS system enough for A.phalloides-induced liver failure treatment?
Authors: Sorodoc Laurentiu , Lionte Catalina , Sorodoc Victorita , Petris Ovidiu , Jaba Irina
Published: February 2010

Patients with Amanita phalloides-induced liver failure (LF) have a high mortality, despite significant advances in intensive care managemet. Our study evaluated the effect of Molecular Absorbents Recirculating System (MARS) comparative with optimal intensive care (OIC) in adults with this condition, in the absence of liver transplantation (LT). Six consecutive patients (women, range 16—61 years) affected by A.phalloides-induced LF were treated with OIC (3 patients) and MARS (3 patients). Laboratory parameters and hepeatic encephalopaty were evaluated 15 min before and 24 hours following each MARS treatment. Three 6-hour sessions per patient were performed in MARS group, with a statistically significant decrease in ammonia (p value 0.011), alaninaminotransferase (ALT) and prothrombin time (PT) (p value 0.004). Two patients had a significant rebound in bilirubin (+116%; p value 0. 04) 24 hours following MARS. Mortality in MARS group was 66.7%. Survival rate in OIC was 0%. Negative prognostic markers: lack of PT and hepatic encephalopaty improvement, rebound in bilirubin, and delay of MARS therapy initiation. No significant adverse reactions occurred during MARS. MARS is an effective depurative therapy in adults with A.phalloides-induced LF, but alone is not enough. Survival is predicted by the results of the initial MARS, amount of mushroom consumed, and time from toxin exposure.
Intrathecal cytokine and chemokine profiling in neuropsychiatric lupus or lupus complicated with central nervous system infection
Authors: Lu XY , Zhu CQ , Qian J. , Chen XX , Ye S. , Gu YY
Published: February 2010

The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFα, IFNγ, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus. Lupus (2010) 19, 689—695.
Decivilizing, civilizing or informalizing? The international development of Mixed Martial Arts
Authors: Sánchez García Raúl , Malcolm Dominic
Published: February 2010

This article contributes to ongoing debates about trends in violence in sport through an examination of the emergence of Mixed Martial Arts (MMA). The article counters suggestions that the rise of MMA is indicative of a decivilizing and/or de-sportizing process, arguing instead that the development of MMA can best be explained with reference to the concepts of informalization and the ‘quest for excitement’. More particularly, the article argues that MMA emerged as a global sport as a consequence of the ascendancy of professionalism over amateurism, through a hybridization of Eastern and Western combat styles, and due to participants’ desires to generate increased levels of excitement. The article argues that despite academic and public portrayals to the contrary, considerable self-restraint characterizes the violence in MMA. The sport has, however, oscillated between more and less violent forms as relatively ‘de-sensitized’ participants and wider public lobbies have contested the definition of socially tolerable violence. In order to maintain spectator appeal under increasingly stringent regulation promoters have sought to make ‘cosmetic’ changes to MMA to increase the appearance of de-controlled violence. The article concludes by arguing that combat sports are inherently contentious as they necessarily exist close to the boundary between ‘real’ and ‘mock’ fighting and thus on the margins of modern sport.
Fine-Grained Multithreading Support for Hybrid Threaded MPI Programming
Authors: Balaji Pavan , Buntinas Darius , Goodell David , Gropp William , Thakur Rajeev
Published: February 2010

As high-end computing systems continue to grow in scale, recent advances in multi- and many-core architectures have pushed such growth toward more dense architectures, that is, more processing elements per physical node, rather than more physical nodes themselves. Although a large number of scientific applications have relied so far on an MPI-everywhere model for programming high-end parallel systems; this model may not be sufficient for future machines, given their physical constraints such as decreasing amounts of memory per processing element and shared caches. As a result, application and computer scientists are exploring alternative programming models that involve using MPI between address spaces and some other threaded model, such as OpenMP, Pthreads, or Intel TBB, within an address space. Such hybrid models require efficient support from an MPI implementation for MPI messages sent from multiple threads simultaneously. In this paper, we explore the issues involved in designing such an implementation. We present four approaches to building a fully thread-safe MPI implementation, with decreasing levels of critical-section granularity (from coarse-grain locks to fine-grain locks to lock-free operations) and correspondingly increasing levels of complexity. We present performance results that demonstrate the performance implications of the different approaches.
A qualitative exploration of adolescents’ experiences of chronic fatigue syndrome
Authors: Jelbert Rebecca , Stedmon Jacqui , Stephens Alison
Published: February 2010

The aim of this study is to provide a qualitative perspective of adolescents’ experiences of Chronic Fatigue Syndrome (CFS). Five adolescents who were considered to have recovered from CFS participated in semistructured interviews regarding their experience. The transcripts were then analysed using interpretative phenomenological analysis. Five main themes were identified to represent common shared experiences across participants.These related to seeking understanding around the illness, experiences of loss, perceived influences on the illness, difficult emotional experiences, and adolescents’ status post recovery. While significant efforts are being made to increase knowledge and understanding of CFS within the child and adolescent population there is still much to be learned, as is evident from this direct account of adolescents’ experiences. We identify implications for clinical practice and suggestions for future research in light of listening to the adolescents’ stories.