bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenomic Prediction of Anthracycline-Induced Cardiotoxicity in Children
Authors: Visscher Henk , Ross Colin J.D. , Rassekh S. Rod , Barhdadi Amina , Dubé Marie-Pierre , Al-Saloos Hesham , Sandor George S. , Caron Huib N. , van Dalen Elvira C. , Kremer Leontien C. , van der Pal Helena J. , Brown Andrew M.K. , Rogers Paul C. , Phillips Michael S. , Rieder Michael J. , Carleton Bruce C. , Hayden Michael R. ,   Canadian Pharmacogenomics Network for Drug Safety Consortium
Published: September 2011

Purpose

Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity and mortality. Our aim was to identify genetic variants associated with ACT in patients treated for childhood cancer.

Patients and Methods

We carried out a study of 2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug biotransformation genes in a discovery cohort of 156 anthracycline-treated children from British Columbia, with replication in a second cohort of 188 children from across Canada and further replication of the top SNP in a third cohort of 96 patients from Amsterdam, the Netherlands.

Results

We identified a highly significant association of a synonymous coding variant rs7853758 (L461L) within the SLC28A3 gene with ACT (odds ratio, 0.35; P = 1.8 × 10−5 for all cohorts combined). Additional associations (P < .01) with risk and protective variants in other genes including SLC28A1 and several adenosine triphosphate–binding cassette transporters (ABCB1, ABCB4, and ABCC1) were present. We further explored combining multiple variants into a single-prediction model together with clinical risk factors and classification of patients into three risk groups. In the high-risk group, 75% of patients were accurately predicted to develop ACT, with 36% developing this within the first year alone, whereas in the low-risk group, 96% of patients were accurately predicted not to develop ACT.

Conclusion

We have identified multiple genetic variants in SLC28A3 and other genes associated with ACT. Combined with clinical risk factors, genetic risk profiling might be used to identify high-risk patients who can then be provided with safer treatment options.
Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epidermal Growth Factor Receptor, in Patients With Advanced Solid Tumors
Authors: Paz-Ares Luis G. , Gomez-Roca Carlos , Delord Jean-Pierre , Cervantes Andres , Markman Ben , Corral Jesus , Soria Jean-Charles , Bergé Yann , Roda Desamparados , Russell-Yarde Fiona , Hollingsworth Simon , Baselga José , Umana Pablo , Manenti Luigi , Tabernero Josep
Published: September 2011

Purpose

We conducted a phase I dose-escalation study to characterize the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), a humanized and glycoengineered immunoglobulin G1 anti–epidermal growth factor receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity.

Patients and Methods

Seventy-five patients with advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus-three trial design.

Results

No maximum-tolerated dose was reached for any dosing schedule. Common adverse events (AEs) included rash (80% of patients), infusion-related reactions (77%), and hypomagnesemia (56%). Grades 3 and 4 AEs were rash (grade 3, 25%), infusion-related reaction (grade 3, 7%; grade 4, 1%), paronychia (grade 3, 3%), and hypomagnesemia (grade 3, 1%; grade 4, 1%). RG7160 exposure increased greater than proportionally over the 50- to 400-mg dose range (with greater than proportional decline in clearance) and approximately dose proportionally above 400 mg (where clearance plateaued). A marked reduction in circulating natural killer cells and increased infiltration of immune effector cells into skin rash were seen. Clinical efficacy included one complete response and two partial responses in patients with colorectal cancer (including one with KRAS mutation) and disease stabilization in 27 patients.

Conclusion

RG7160 had an acceptable safety profile with manageable AEs and demonstrated promising efficacy in this heavily pretreated patient cohort. On the basis of modeling of available PK parameters, the RG7160 dose selected for part two of this study is 1,400 mg on days 1 and 8 followed by 1,400 mg every 2 weeks.
American Society of Clinical Oncology Endorsement of the Cancer Care Ontario Practice Guideline on Adjuvant Ovarian Ablation in the Treatment of Premenopausal Women With Early-Stage Invasive Breast Cancer
Authors: Griggs Jennifer J. , Somerfield Mark R. , Anderson Holly , Henry N. Lynn , Hudis Clifford A. , Khatcheressian James L. , Partridge Ann H. , Prestrud Ann Alexis , Davidson Nancy E.
Published: September 2011

Purpose

The American Society of Clinical Oncology (ASCO) has policies and procedures for endorsing practice guidelines that have been developed by other professional organizations.

Methods

The Cancer Care Ontario (CCO) Guideline on Adjuvant Ovarian Ablation (OA) in the Treatment of Premenopausal Women With Early-Stage Invasive Breast Cancer was reviewed for developmental rigor by methodologists. An ad hoc review panel of experts reviewed the content.

Results

The ASCO ad hoc OA guideline review panel concurred that the recommendations are clear, thorough, based on the most relevant scientific evidence in this content area, and present options that will be acceptable to patients. According to the CCO guideline: one, OA should not be routinely added to systemic therapy with chemotherapy, tamoxifen, or the combination of tamoxifen and chemotherapy; two, OA alone is not recommended as an alternative to any other form of systemic therapy, except in the specific case of patients who are candidates for other forms of systemic therapy but who, for some reason, will not receive any other systemic therapy (eg, patients who cannot tolerate other forms of systemic therapy or patients who choose no other form of systemic therapy); and three, when chemical suppression using luteinizing hormone–releasing hormone agonists is the chosen method of OA, in the opinion of the Breast Cancer Disease Site Group, monthly injection is the recommended mode of administration. The mode of administration in nearly all of the available trials has been monthly administration.

Conclusion

The ASCO review panel agrees with the recommendations as stated in the CCO guideline, with the qualification that ongoing research studies may alter the recommendations of the panel.
The PACAP-Regulated Gene Selenoprotein T Is Highly Induced in Nervous, Endocrine, and Metabolic Tissues during Ontogenetic and Regenerative Processes
Authors: Tanguy Yannick , Falluel-Morel Anthony , Arthaud Sébastien , Boukhzar Loubna , Manecka Destiny-Love , Chagraoui Abdeslam , Prevost Gaetan , Elias Salah , Dorval-Coiffec Isabelle , Lesage Jean , Vieau Didier , Lihrmann Isabelle , Jégou Bernard , Anouar Youssef
Published: September 2011

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues.
Mutations associated with Charcot–Marie–Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome–autophagy pathways
Authors: Lee Samuel M. , Olzmann James A. , Chin Lih-Shen , Li Lian
Published: September 2011

Mutations in SIMPLE cause an autosomal dominant, demyelinating form of peripheral neuropathy termed Charcot–Marie–Tooth disease type 1C (CMT1C), but the pathogenic mechanisms of these mutations remain unknown. Here, we report that SIMPLE is an early endosomal membrane protein that is highly expressed in the peripheral nerves and Schwann cells. Our analysis has identified a transmembrane domain (TMD) embedded within the cysteine-rich (C-rich) region that anchors SIMPLE to the membrane, and suggests that SIMPLE is a post-translationally inserted, C-tail-anchored membrane protein. We found that CMT1C-linked pathogenic mutations are clustered within or around the TMD of SIMPLE and that these mutations cause mislocalization of SIMPLE from the early endosome membrane to the cytosol. The CMT1C-associated SIMPLE mutant proteins are unstable and prone to aggregation, and they are selectively degraded by both the proteasome and aggresome–autophagy pathways. Our findings suggest that SIMPLE mutations cause CMT1C peripheral neuropathy by a combination of loss-of-function and toxic gain-of-function mechanisms, and highlight the importance of both the proteasome and autophagy pathways in the clearance of CMT1C-associated mutant SIMPLE proteins.
Pulmonary compliance and lung volume varies with ecomorphology in anuran amphibians: implications for ventilatory-assisted lymph flux
Authors: Hedrick Michael S. , Hillman Stanley S. , Drewes Robert C. , Withers Philip C.
Published: September 2011

Vertical movement of lymph from ventral regions to the dorsally located lymph hearts in anurans is accomplished by specialized skeletal muscles working in concert with lung ventilation. We hypothesize that more terrestrial species with greater lymph mobilization capacities and higher lymph flux rates will have larger lung volumes and higher pulmonary compliance than more semi-aquatic or aquatic species. We measured in situ mean and maximal compliance (Δvolume/Δpressure), distensibility (%Δvolume/Δpressure) and lung volume over a range of physiological pressures (1.0 to 4.0 cmH2O) for nine species of anurans representing three families (Bufonide, Ranidae and Pipidae) that span a range of body masses and habitats from terrestrial to aquatic. We further examined the relationship between these pulmonary variables and lymph flux for a semi-terrestrial bufonid (Rhinella marina), a semi-aquatic ranid (Lithobates catesbeianus) and an aquatic pipid (Xenopus laevis). Allometric scaling of pulmonary compliance and lung volume with body mass showed significant differences at the family level, with scaling exponents ranging from ∼0.75 in Bufonidae to ∼1.3 in Pipidae. Consistent with our hypothesis, the terrestrial Bufonidae species had significantly greater pulmonary compliance and greater lung volumes compared with semi-aquatic Ranidae and aquatic Pipidae species. Pulmonary distensibility ranged from ∼20 to 35% cmH2O–1 for the three families but did not correlate with ecomorphology. For the three species for which lymph flux data are available, R. marina had a significantly higher (P<0.001) maximal compliance (84.9±2.7 ml cmH2O–1 kg–1) and lung volume (242.1±5.5 ml kg–1) compared with L. catesbeianus (54.5±0.12 ml cmH2O–1 kg–1 and 139.3±0.5 ml kg–1) and X. laevis (30.8±0.7 ml cmH2O–1 kg–1 and 61.3±2.5 ml kg–1). Lymph flux rates were also highest for R. marina, lowest for X. laevis and intermediate in L. catesbeianus. Thus, there is a strong correlation between pulmonary compliance, lung volume and lymph flux rates, which suggests that lymph mobilization capacity may explain some of the variation in pulmonary compliance and lung volume in anurans.
Social control of unreliable signals of strength in male but not female crayfish,Cherax destructor
Authors: Walter Gregory M. , van Uitregt Vincent O. , Wilson Robbie S.
Published: September 2011

The maintenance of unreliable signals within animal populations remains a highly controversial subject in studies of animal communication. Crustaceans are an ideal group for studying unreliable signals of strength because their chela muscles are cryptically concealed beneath an exoskeleton, making it difficult for competitors to visually assess an opponent's strength. In this study, we examined the importance of social avenues for mediating the possible advantages gained by unreliable signals of strength in crustaceans. To do this, we investigated the factors that determine social dominance and the relative importance of signalling and fighting during aggressive encounters in male and female freshwater crayfish, Cherax destructor. Like other species of crayfish, we expected substantial variation in weapon force for a given weapon size, making the assessment of actual fighting ability of an opponent difficult from signalling alone. In addition, we expected fighting would be used to ensure that individuals that are weak for their signal (i.e. chela) size would not achieve higher than expected dominance. For both male and female C. destructor, we found large variation in the actual force of their chela for any given weapon size, indicating that it is difficult for competitors to accurately assess an opponent's force on signal size alone. For males, these unreliable signals of strength were controlled socially through increased levels of fighting and a decreased reliance on signalling, thus directly limiting the benefits accrued to individuals employing high-quality signals (large chelae) with only low resource holding potential. However, in contrast to our predictions, we found that females primarily relied on signalling to settle disputes, resulting in unreliable signals of strength being routinely used to establish dominance. The reliance by females on unreliable signals to determine dominance highlights our poor current understanding of the prevalence and distribution of dishonesty in animal communication.
Forelimb kinematics and motor patterns of swimming loggerhead sea turtles (Caretta caretta): are motor patterns conserved in the evolution of new locomotor strategies?
Authors: Rivera Angela R. V. , Wyneken Jeanette , Blob Richard W.
Published: September 2011

Novel functions in animals may evolve through changes in morphology, muscle activity or a combination of both. The idea that new functions or behavior can arise solely through changes in structure, without concurrent changes in the patterns of muscle activity that control movement of those structures, has been formalized as the neuromotor conservation hypothesis. In vertebrate locomotor systems, evidence for neuromotor conservation is found across evolutionary transitions in the behavior of terrestrial species, and in evolutionary transitions from terrestrial species to flying species. However, evolutionary transitions in the locomotion of aquatic species have received little comparable study to determine whether changes in morphology and muscle function were coordinated through the evolution of new locomotor behavior. To evaluate the potential for neuromotor conservation in an ancient aquatic system, we quantified forelimb kinematics and muscle activity during swimming in the loggerhead sea turtle, Caretta caretta. Loggerhead forelimbs are hypertrophied into wing-like flippers that produce thrust via dorsoventral forelimb flapping. We compared kinematic and motor patterns from loggerheads with previous data from the red-eared slider, Trachemys scripta, a generalized freshwater species exhibiting unspecialized forelimb morphology and anteroposterior rowing motions during swimming. For some forelimb muscles, comparisons between C. caretta and T. scripta support neuromotor conservation; for example, the coracobrachialis and the latissimus dorsi show similar activation patterns. However, other muscles (deltoideus, pectoralis and triceps) do not show neuromotor conservation; for example, the deltoideus changes dramatically from a limb protractor/elevator in sliders to a joint stabilizer in loggerheads. Thus, during the evolution of flapping in sea turtles, drastic restructuring of the forelimb was accompanied by both conservation and evolutionary novelty in limb motor patterns.
Long-term olfactory memories are stabilised via protein synthesis in Camponotus fellah ants
Authors: Guerrieri Fernando J. , d'Ettorre Patrizia , Devaud Jean-Marc , Giurfa Martin
Published: September 2011

Ants exhibit impressive olfactory learning abilities. Operant protocols in which ants freely choose between rewarded and non-rewarded odours have been used to characterise associative olfactory learning and memory. Yet, this approach precludes the use of invasive methods allowing the dissection of molecular bases of learning and memory. An open question is whether the memories formed upon olfactory learning that are retrievable several days after training are indeed based on de novo protein synthesis. Here, we addressed this question in the ant Camponotus fellah using a conditioning protocol in which individually harnessed ants learn an association between odour and reward. When the antennae of an ant are stimulated with sucrose solution, the insect extends its maxilla–labium to absorb the solution (maxilla–labium extension response). We differentially conditioned ants to discriminate between two long-chain hydrocarbons, one paired with sucrose and the other with quinine solution. Differential conditioning leads to the formation of a long-term memory retrievable at least 72 h after training. Long-term memory consolidation was impaired by the ingestion of cycloheximide, a protein synthesis blocker, prior to conditioning. Cycloheximide did not impair acquisition of either short-term memory (10 min) or early and late mid-term memories (1 or 12 h). These results show that, upon olfactory learning, ants form different memories with variable molecular bases. While short- and mid-term memories do not require protein synthesis, long-term memories are stabilised via protein synthesis. Our behavioural protocol opens interesting research avenues to explore the cellular and molecular bases of olfactory learning and memory in ants.
Deciphering a methylome: what can we read into patterns of DNA methylation?
Authors: Flores Kevin B. , Amdam Gro V.
Published: September 2011

The methylation of cytosines within cytosine–guanine (CG) dinucleotides is an epigenetic mark that can modify gene transcription. With the advent of high-throughput sequencing, it is possible to map methylomes, i.e. detect methylated CGs on a genome-wide scale. The methylomes sequenced to date reveal a divergence in prevalence and targeting of CG methylation between taxa, despite the conservation of the DNA methyltransferase enzymes that cause DNA methylation. Therefore, interspecific methylation usage is predicted to diverge. In various taxa, this tenet gains support from patterns of CG depletion that can be traced in DNA before methylomes are explicitly mapped. Depletion of CGs in methylated genomic regions is expected because methylated cytosines are subject to increased mutability caused by nucleotide deamination. However, the basis of diverging interspecific methylation usage is less clear. We use insights from the methylome of honeybees (Apis mellifera) to emphasize the possible importance of organismal life histories in explaining methylation usage and the accuracy of methylation prediction based on CG depletion. Interestingly, methylated genes in honeybees are more conserved across taxa than non-methylated genes despite the divergence in utilization of methylation and the increased mutability caused by deamination.
Atorvastatin: Extended-Interval Dosing
Authors: Generali Joyce A. , Cada Dennis J.
Published: September 2011

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
Comparison of Intravenous Immunoglobulin Formulations: Product Formulary, and Cost Considerations
Authors: Mark Scott M.
Published: September 2011

Purpose

A review of the different formulations of intravenous immunoglobulin (IVIG) replacement therapy for primary immunodeficiency and other severe diseases, focusing on the comparative efficacy, safety, and tolerability of these formulations. This review discusses the manufacturing processes, physicochemical properties, and other attributes of IVIG therapy that affect its clinical utility.

IVIG therapy is a preferred treatment for patients with certain types of primary immunodeficiency, neuroimmunologic, and autoimmune hematologic disorders, as well as for immunomodulation in bone marrow and some solid organ transplants. The IVIG products available in the United States include lyophilized, 5% liquid, and 10% ready-to-use liquid formulations. Differences among these formulations in their manufacturing processes, excipients, pH, and physicochemical properties may be reflected as differences in clinical efficacy, safety, and tolerability. For example, compared with lyophilized and 5% liquid IVIG formulations, 10% ready-to-use IVIG liquid formulations may be associated with better tolerability because of lower IgA concentrations, optimal pH, use of glycine or proline stabilizers, low sodium content, and less osmolality. Liquid formulations (both 5% and 10%) may provide greater convenience than lyophilized formulations for both patients and health care providers, because they do not require further dilution before administration and have shorter infusion times.

Conclusion

Before selecting an IVIG product for a hospital formulary, pharmacists should be knowledgeable about the product's concentration to ensure delivery of the proper dosage, the staff training needed for proper administration, the potential benefits and problems of brand substitution, the safety and efficacy of each formulation, the hospital's policies on off-label use of IVIG, and the impact of reimbursement.
Cost Savings Associated with a Dedicated Drug Information Service in an Academic Medical Center
Authors: Brown Jamie N.
Published: September 2011

Objectives

Document interventions made by a drug information center affiliated with a single academic medical center and calculate the cost avoidance associated with the identified interventions.

Methods

All drug information requests received by the drug information center from January 1, 2008 through December 31, 2008 were reviewed. Responses were put into an economic model for cost avoidance, and avoidance of research time was calculated for each profession.

Results

The drug information center documented 270 drug information requests during the study period. Pharmacists were the heaviest users of the drug information center, and the most common classification of drug information questions asked were therapeutic evaluations. There were 186 drug information responses that met the economic model definition for a patient-specific intervention, totaling an estimated cost avoidance of $130,200. In regard to research time savings, the drug information center invested a total of 554.4 research hours into question responses, associated with a total workload savings of $27,283 in research time avoided.

Conclusion

A beneficial effect of having a dedicated drug information center was demonstrated at an academic tertiary care teaching medical center. Cost avoidance calculations for all interventions and research time avoided totaled $157,483 for the 1-year study period.
Heavy Drinking and Use of Sedative or Anxiolytic Drugs Among Aging Men: An II-Year Follow-Up of the FinDrink Study
Authors: Ilomäki Jenni , Bell J Simon , Kauhanen Jussi , Enlund Hannes
Published: September 2011

Background:

Most studies on heavy drinking and sedative/anxiolytic drug use have been cross-sectional, and evidence for a possible temporal association is lacking.

Objective:

To prospectively investigate whether heavy drinking predicts initiation, continuation, or discontinuation of sedative/anxiolytic drugs at 4 arid 11 years and, conversely, whether sedative/anxiolytic drug use predicts heavy drinking.

Method:

This was a longitudinal population-based study conducted in Kuopio, Finland, An age-stratified random sample of 1516 men aged 42, 48, 54, and 60 years received a structured clinical examination at baseline (August 1986-December 1989). Follow-up clinical examinations were conducted at 4 (n − 1038) and 11 (n = 854) years. Multinomial logistic regression was used to compute odds ratios and 95% confidence intervals for the association between sedative/anxiolytic drug use and initiation, continuation, and discontinuation of heavy drinking (≥14 drinks/wk). The reverse association between heavy drinking and sedative/anxiolytic drug use was also investigated. Regression models were adjusted for age, working status, smoking, and depressive symptoms.

Results:

At baseline 12.9% (134/1038) of participants were heavy drinkers and 4.0% (41/1030) used sedative/anxiolytic drugs. In multivariate analyses, baseline heavy drinking predicted initiation of sedative/anxiolytic drug use at 4 years (OR 2.96; 95% CI 1.23 to 7.15). Conversely, baseline sedative/anxiolytic drug use predicted continuation of heavy drinking at 11 years in unadjusted analysis (OR 3.30; 95% CI 1.19 to 8.44). However, the association was not statistically significant in adjusted analyses (OR 2.69; 95% CI 0.86 to 8.44).

Conclusions:

The main finding of this study was the association between heavy drinking and subsequent initiation of sedative/anxiolytic drugs that was not fully explained by baseline depressive symptoms. This may inform strategies to optimize the use of sedative/anxiolytic drugs, and assist in the early identification of patients at risk of heavy drinking. Clinicians should consider a patent's alcohol consumption prior to prescribing or dispensing sedative/anxiolytic drugs. Clinicians should also monitor patients prescribed sedative/anxiolytic drugs for subsequent heavy drinking.
Extension of ThermoML: The IUPAC standard for thermodynamic data communications (IUPAC Recommendations 2011)
Authors: Frenkel Michael , Chirico Robert D. , Diky Vladimir , Brown Paul L. , Dymond John H. , Goldberg Robert N. , Goodwin Anthony R. H. , Heerklotz Heiko , Königsberger Erich , Ladbury John E. , Marsh Kenneth N. , Remeta David P. , Stein Stephen E. , Wakeham William A. , Williams Peter A.
Published: September 2011

ThermoML is an XML-based approach for storage and exchange of experimental, predicted, and critically evaluated thermophysical and thermochemical property data. Extensions to the ThermoML schema for the representation of speciation, complex equilibria, and properties of biomaterials are described. The texts of 14 data files illustrating the new extensions are provided as Supplementary Information together with the complete text of the updated ThermoML schema.
Rejectable Choice Sets: How Seemingly Irrelevant No-Choice Options Affect Consumer Decision Processes
Authors: Parker Jeffrey R. , Schrift Rom Y.
Published: September 2011

To date, research on no-choice options has primarily examined the conditions that foster choice deferral, thus focusing on the frequency with which consumers select the no-choice option. In this article, the authors argue that even if the no-choice option is not selected, its mere presence in the choice set may alter consumers' choices. More specifically, they investigate how decision processes and preferences change when consumers have a no-choice option versus when they are forced to choose from a given choice set. They propose that the inclusion of a no-choice option in a choice set affects preferences by leading consumers to determine not only which alternative is best, but which, if any, are acceptable (i.e., meet the consumer's minimum needs). Accordingly, the authors demonstrate that the inclusion of a no-choice option in the choice set (1) leads to more alternative- (rather than attribute-) based information processing, (2) increases the importance of attributes that are more meaningful when alternatives are evaluated one by one (i.e., enriched attributes), and (3) increases the importance of attributes with levels that are closer to the consumer's minimum needs (thresholds). They demonstrate that such changes influence consumers' preference structures and ultimate choices. They conclude with a discussion of the theoretical, methodological, and managerial implications of these findings.
What Drives Immediate and Ongoing Word of Mouth?
Authors: Berger Jonah , Schwartz Eric M.
Published: September 2011

Word of mouth (WOM) affects diffusion and sales, but why are certain products talked about more than others, both right after consumers first experience them and in the months that follow? This article examines psychological drivers of immediate and ongoing WOM. The authors analyze a unique data set of everyday conversations for more than 300 products and conduct both a large field experiment across various cities and a controlled laboratory experiment with real conversations. The results indicate that more interesting products get more immediate WOM but, contrary to intuition, do not receive more ongoing WOM over multiple months or overall. In contrast, products that are cued more by the environment or are more publicly visible receive more WOM both right away and over time. Additional analyses demonstrate which promotional giveaways in WOM marketing campaigns are associated with increased WOM. overall, the findings shed light on psychological drivers of WOM and provide insight into designing more effective WOM campaigns.
Price Presentation Effects in Purchases Involving Trade-Ins
Authors: Srivastava Joydeep , Chakravarti Dipankar
Published: September 2011

When a new purchase involves trading in an old item, the prices of component transactions may be presented in different ways. The authors report three studies that examine how different price presentations influence evaluations and choice in an otherwise equivalent overall exchange. Although consumers play both buyer and seller roles in purchases involving trade-ins, the authors find that consumers' evaluation of the overall exchange typically places more weight on the price of the new purchase than the trade-in. However, they also show that the weights can be shifted systematically by (1) directly manipulating the importance of the trade-in and (2) indirectly priming a seller (vs. buyer) mind-set. In these instances, consumers place more weight on the trade-in price than the price of the new purchase.
Der Gebrauch der typographischen Zeichen und der Interpunktionszeichen im Französischen, Deutschen und Rumänischen
Authors: Sinner Carsten
Published: September 2011

Punctuation marks have special importance in bringing out the meaning of a text. Nonetheless, they are not normally taken into consideration in text production in foreign languages and therefore constitute a strong source of interference. This article analyses the use of a series of punctuation marks (hyphen, quotation marks, etc.) in French, German and Romanian, highlighting the differences and trying to give explanations for the abuse of several signs in texts in the different languages written by non-native and native authors. Evidence is given that the use of the punctuation marks in a foreign language following the norms of the mother tongue may produce misunderstandings on behalf of native readers. Furthermore, it can be shown that the prescriptive and descriptive grammars of the implied languages do not represent current tendencies of use.
Gesten im interkulturellen Vergleich – eine kontrastive Analyse der Bedeutungen von zwei Emblemen in Kolumbien und Deutschland
Authors: Merz Andreas
Published: September 2011

The following paper aims at highlighting intercultural misunderstandings that can occur due to different semantic values of emblems, a gesture type generally defined as having an accepted verbal translation in a certain culture or community. To illustrate such problems, the semantic meanings of two emblems in Colombia and Germany are described. Misunderstandings caused by the use of these emblems are then explained from a communicative point of view, using Austin's speech-act theory. Additionally, the article offers a short review on the history of emblem research.
Die Syntax beim Übersetzen von Rechtstexten
Authors: Vlachopoulos Stefanos
Published: September 2011

The goal of this paper is to establish the interplay of functionality and syntactic adaptations in the translation of legal texts. We will attempt to gain insight into the choices the translators of legal texts make and how these can be justified by the function of the target text in the legal target culture. The comparison of the syntactic means used by the text producer to achieve a particular aim and the syntactic structures the translators chose in order to transfer the source text meaning functionally into the target culture is expected to yield insight into if, how and why the translators employed (or not) the stylistic inventory of the target system.
Lokalisierung von digitalen Spielen – Evaluierung der deutschen Version von Tropico 3
Authors: Friedrich Gunnar
Published: September 2011

Digital games are playing an ever growing role in today's society and economy due to technological and social developments. This trend is accompanied by an increasing need for professional translators and linguistic QA testers. But what are the stance and the chances of Translation Studies in the face of this trend? The following article tries to answer this question by analyzing the current situation and developing a QA model for the evaluation of translation and linguistic testing of digital games.
E-Learning – Enhancing the Curriculum
Authors: Cragie Stella
Published: September 2011

Universities are constantly looking for ways to enhance teaching and learning. Using online delivery is an excellent way to achieve an innovative, customized mode of teaching that benefits students in many ways, for example: flexibility, independence, engagement, motivation and participation. Institutions also benefit owing to lower costs of delivery, wider audiences, variety of technical and social features, flexiblity of management and access. The better designed the course is, the more effective it will be, while issues such as funding and support are crucial to success.
Unheimliche Heimat. Kafka, Freud und die Frage der Rückkehr in W. G. Sebalds Schwindel. Gefühle
Authors: Laufer Almut
Published: September 2011

Druck der Zensur, nicht Aufhebung der Zielvorstellungen ist die richtige Begründung für das Vorherrschen der ober-flächlichen Assoziationen. Die oberflächlichen Assoziationen ersetzen in der Darstellung die tiefen, wenn die Zensur diese normalen Verbindungswege ungangbar macht. Es ist, wie wenn ein allgemeines Verkehrshindernis, z.B. eine Überschwemmung, im Gebirge die großen und breiten Straßen unwegsam werden läßt; der Verkehr wird dann auf unbequemen und steilen Fußpfaden aufrechterhalten, die sonst nur der Jäger begangen hat.
Attentional Modulation of fMRI Responses in Human V1 Is Consistent with Distinct Spatial Maps for Chromatically Defined Orientation and Contrast
Authors: Song Joo-Hyun , Rowland Jess , McPeek Robert M. , Wade Alex R.
Published: September 2011

Attending to different stimulus features such as contrast or orientation can change the pattern of neural responses in human V1 measured with fMRI. We show that these pattern changes are much more distinct for colored stimuli than for achromatic stimuli. This is evidence for a classic model of V1 functional architecture in which chromatic contrast and orientation are coded in spatially distinct neural domains, while achromatic contrast and orientation are not.
Pitx3 Is a Critical Mediator of GDNF-Induced BDNF Expression in Nigrostriatal Dopaminergic Neurons
Authors: Peng Changgeng , Aron Liviu , Klein Rüdiger , Li Meng , Wurst Wolfgang , Prakash Nilima , Le Weidong
Published: September 2011

Pitx3 is a critical homeodomain transcription factor for the proper development and survival of mesodiencephalic dopaminergic (mdDA) neurons in mammals. Several variants of this gene have been associated with human Parkinson's disease (PD), and lack ofPitx3in mice causes the preferential loss of substantia nigra pars compacta (SNc) mdDA neurons that are most affected in PD. It is currently unclear how Pitx3 activity promotes the survival of SNc mdDA neurons and which factors act upstream and downstream of Pitx3 in this context. Here we show that a transient expression of glial cell line-derived neurotrophic factor (GDNF) in the murine ventral midbrain (VM) induces transcription ofPitx3via NF-κB-mediated signaling, and that Pitx3 is in turn required for activating the expression of brain-derived neurotrophic factor (BDNF) in a rostrolateral (SNc) mdDA neuron subpopulation during embryogenesis. The loss ofBDNFexpression correlates with the increased apoptotic cell death of this mdDA neuronal subpopulation inPitx3−/−mice, whereas treatment of VM cell cultures with BDNF augments the survival of thePitx3−/−mdDA neurons. Most importantly, only BDNF but not GDNF protects mdDA neurons against 6-hydroxydopamine-induced cell death in the absence ofPitx3. As the feedforward regulation of GDNF, Pitx3, and BDNF expression also persists in the adult rodent brain, our data suggest that the disruption of the regulatory interaction between these three factors contributes to the loss of mdDA neurons inPitx3−/−mutant mice and perhaps also in human PD.
Vulnerability to Depression: From Brain Neuroplasticity to Identification of Biomarkers
Authors: Blugeot Aurélie , Rivat Cyril , Bouvier Elodie , Molet Jenny , Mouchard Amandine , Zeau Brigitte , Bernard Christophe , Benoliel Jean-Jacques , Becker Chrystel
Published: September 2011

A stressful event increases the risk of developing depression later in life, but the possible predisposing factors remain unknown. Our study aims to characterize latent vulnerability traits underlying the development of depressive disorders in adult animals. Four weeks after a priming stressful event, serum corticosterone concentration returned to control values in all animals, whereas the other biological parameters returned to basal level in only 58% of animals (called nonvulnerable). In contrast, 42% of animals displayed persistent decreased serum and hippocampus BDNF concentrations, reduced hippocampal volume and neurogenesis, CA3 dendritic retraction and decrease in spine density, as well as amygdala neuron hypertrophy, constituting latent vulnerability traits to depression. In this group, called vulnerable, a subsequent mild stress evoked a rise of serum corticosterone levels and a “depressive” phenotype, in contrast to nonvulnerable animals. Intracerebroventricular administration of 7,8-dihydroxyflavone, a selective TrkB receptor agonist, dampened the development of the “depressive” phenotype. Our results thus characterize the presence of latent vulnerability traits that underlie the emergence of depression and identify the association of low BDNF with normal corticosterone serum concentrations as a predictive biomarker of vulnerability to depression.
Carbon Nanotube Scaffolds Tune Synaptic Strength in Cultured Neural Circuits: Novel Frontiers in Nanomaterial–Tissue Interactions
Authors: Cellot Giada , Toma Francesca Maria , Kasap Varley Zeynep , Laishram Jummi , Villari Ambra , Quintana Mildred , Cipollone Sara , Prato Maurizio , Ballerini Laura
Published: September 2011

A long-term goal of tissue engineering is to exploit the ability of supporting materials to govern cell-specific behaviors. Instructive scaffolds code such information by modulating (via their physical and chemical features) the interface between cells and materials at the nanoscale. In modern neuroscience, therapeutic regenerative strategies (i.e., brain repair after damage) aim to guide and enhance the intrinsic capacity of the brain to reorganize by promoting plasticity mechanisms in a controlled fashion. Direct and specific interactions between synthetic materials and biological cell membranes may play a central role in this process. Here, we investigate the role of the material's properties alone, in carbon nanotube scaffolds, in constructing the functional building blocks of neural circuits: the synapses. Using electrophysiological recordings and rat cultured neural networks, we describe the ability of a nanoscaled material to promote the formation of synaptic contacts and to modulate their plasticity.
The Neural and Cognitive Time Course of Theory of Mind
Authors: McCleery Joseph P. , Surtees Andrew D. R. , Graham Katharine A. , Richards John E. , Apperly Ian A.
Published: September 2011

Neuroimaging and neuropsychological studies implicate both frontal and temporoparietal cortices when humans reason about the mental states of others. Here, we report an event-related potentials study of the time course of one such “theory of mind” ability: visual perspective taking. The findings suggest that posterior cortex, perhaps the temporoparietal cortex, calculates and represents the perspective of self versus other, and then, later, the right frontal cortex resolves conflict between perspectives during response selection.
Synaptic Properties of Thalamic Input to the Subgranular Layers of Primary Somatosensory and Auditory Cortices in the Mouse
Authors: Viaene Angela N. , Petrof Iraklis , Sherman S. Murray
Published: September 2011

The classification of synaptic inputs is an essential part of understanding brain circuitry. In the present study, we examined the synaptic properties of thalamic inputs to pyramidal neurons in layers 5a, 5b, and 6 of primary somatosensory (S1) and auditory (A1) cortices in mouse thalamocortical slices. Stimulation of the ventral posterior medial nucleus and the ventral division of the medial geniculate body resulted in three distinct response classes, two of which have never been described before in thalamocortical projections. Class 1A responses included synaptic depression and all-or-none responses, while Class 1B responses exhibited synaptic depression and graded responses. Class 1C responses are characterized by mixed facilitation and depression as well as graded responses. Activation of metabotropic glutamate receptors was not observed in any of the response classes. We conclude that Class 1 responses can be broken up into three distinct subclasses, and that thalamic inputs to the subgranular layers of cortex may combine with other, intracortical inputs to drive their postsynaptic target cells. We also integrate these results with our recent, analogous study of thalamocortical inputs to granular and supragranular layers (Viaene et al., 2011).
Direct Structural Connections between Voice- and Face-Recognition Areas
Authors: Blank Helen , Anwander Alfred , von Kriegstein Katharina
Published: September 2011

Currently, there are two opposing models for how voice and face information is integrated in the human brain to recognize person identity. The conventional model assumes that voice and face information is only combined at a supramodal stage (Bruce and Young, 1986; Burton et al., 1990; Ellis et al., 1997). An alternative model posits that areas encoding voice and face information also interact directly and that this direct interaction is behaviorally relevant for optimizing person recognition (von Kriegstein et al., 2005; von Kriegstein and Giraud, 2006). To disambiguate between the two different models, we tested for evidence of direct structural connections between voice- and face-processing cortical areas by combining functional and diffusion magnetic resonance imaging. We localized, at the individual subject level, three voice-sensitive areas in anterior, middle, and posterior superior temporal sulcus (STS) and face-sensitive areas in the fusiform gyrus [fusiform face area (FFA)]. Using probabilistic tractography, we show evidence that the FFA is structurally connected with voice-sensitive areas in STS. In particular, our results suggest that the FFA is more strongly connected to middle and anterior than to posterior areas of the voice-sensitive STS. This specific structural connectivity pattern indicates that direct links between face- and voice-recognition areas could be used to optimize human person recognition.
Microglial Cells Contribute to Endogenous Brain Defenses after Acute Neonatal Focal Stroke
Authors: Faustino Joel V. , Wang Xia , Johnson Cali E. , Klibanov Alexander , Derugin Nikita , Wendland Michael F. , Vexler Zinaida S.
Published: September 2011

Macrophages are viewed as amplifiers of ischemic brain injury, but the origin of injury-producing macrophages is poorly defined. The role of resident brain macrophages—microglial cells—in stroke remains controversial. To determine whether microglial cells exert injurious effects after neonatal focal stroke, we selectively depleted these cells with intracerebral injection of liposome-encapsulated clodronate before transient middle cerebral artery occlusion in postnatal day 7 rats. Phagocytosis of apoptotic neurons by activated microglia was poor in animals with unmanipulated microglia, and depletion of these cells did not increase the number of apoptotic neurons. Lack of microglia increased the brain levels of several cytokines and chemokines already elevated by ischemia–reperfusion, and also increased the severity and volume of injury, suggesting that microglial cells contribute to endogenous protection during the subacute injury phase. Then, to determine whether accumulation of reactive oxygen species in microglia adversely affects phagocytosis of dying neurons and contributes to injury, we delivered reduced glutathione (GSH) into microglia, again using liposomes. Remarkably, pharmacologically increased intracellular GSH concentrations in microglia induced superoxide accumulation in lipid rafts in these cells, further increased the brain levels of macrophage chemoattractants, and exacerbated injury. Together, these data show that microglia are part of the endogenous defense mechanisms and that, while antioxidants can protect the injured neonatal brain, high levels of reducing equivalents in activated microglia, GSH, trigger superoxide production, favor the reorganization of lipids, amplify local inflammation and exacerbate injury.