bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending aromatase inhibitor sensitivity in hormone resistant breast cancer
Authors: Brodie Angela M.H. , Chumsri Saranya , Sukumar Sara , Sabnis Gauri J.
Published: March 2011

Aromatase inhibitors (AIs) are first-line treatment for ER+ breast cancer. However, despite responses initially, some patients can eventually acquire resistance. Moreover, 25% of all breast cancer patients do not express the estrogen receptor (ERα) and are innately resistance. In tumors of mouse models with acquired AI letrozole resistance, expression of ERα was reduced whereas HER2/growth factor signaling was enhanced. Treatment of mice with trastuzumab (HER2 antibody) reduced HER2/p-MAPK but restored ERα expression. The addition of trastuzumab to letrozole treatment when tumors progressed resulted in significantly longer tumor suppression than these drugs alone. Thus, inhibition of both HER2 and ERα signaling pathways was necessary to overcome resistance. In ERα-negative tumors, the receptor has been shown to be silenced by epigenetic modifications. Treatment of MDA-MB-231 ER-negative tumors with a histone deacetylase inhibitor, entinostat (ENT) increased expression of ERα and also aromatase. When ENT was combined with letrozole, tumor growth rate was markedly reduced compared with control tumors. ENT plus letrozole treatment also prevented the colonization and growth of MDA-MB-231 cells in the lung with significant reduction in visible and microscopic foci. These novel strategies could improve treatment for patients with acquired and innate resistance to AIs.
Benefits and risks during HRT: main safety issue breast cancer
Authors: Mueck Alfred O. , Ruan Xiangyan
Published: March 2011

To assess the benefits and risks during hormone replacement therapy (HRT) in postmenopausal women, the only placebo-controlled study testing clinical endpoints with high statistical power has been the Women's Health Initiative (WHI). Although this trial, conducted mainly in older high-risk women, might not reflect the practical conditions for the normal use of HRT, the WHI for the first time provides the main risks in relative as well as in absolute numbers, which are venous thromboembolism and breast cancer, and in older women also myocardial infarction and stroke. Proven benefits such as treatment of climacteric symptoms, reduction of osteoporotic fractures and decrease of colon cancer risk seem to be only important for younger women, because only with early start of HRT cardiovascular risks can be reduced. Reduction of cardiovascular risks can be achieved using transdermal HRT, which, however, was not tested in a placebo-controlled study design similar to that in the WHI. This review focuses on the results of the WHI, comparing different age groups, and in general especially on the main fear of women, risk of breast cancer, which has been defined as a special project between two universities, a close collaboration of a German and Chinese research group.
Correlates of identity statuses among Chinese adolescents in Hong Kong
Authors: Lam Rebecca S.Y. , Tam Vicky C.W.
Published: March 2011

This study investigates correlates of Hong Kong Chinese adolescents’ identity statuses with (i) parental and school contexts and (ii) major psychosocial developmental outcomes. Data were collected from 1260 Secondary 2–4 (equivalent to Grades 8–10 in the US school system) students through a questionnaire survey. Results of hierarchical regression analysis indicated that parental attributes of acceptance, values and goals, and psychological control, and school contextual factor of task orientations predicted identity achievement, whereas parents’ acceptance, psychological and firm control, and teacher's support predicted identity foreclosure. Regarding the impact on psychosocial development, another series of regression analyses revealed that (i) identity achievement predicted low depression, high self-esteem, and high self-efficacy; (ii) moratorium predicted low self-esteem; and (iii) foreclosure predicted high self-efficacy. Overall, the findings shed light on adolescent identity development in Hong Kong, facilitating discussions on identity-related issues.
Zur Bedeutung von λΟΓΟC im Prolog des Judasevangeliums
Authors: Förster Hans
Published: March 2011

The translation of the first lines of the Gospel of Judas has been the subject of scholarly debate. One of the major problems seems to be the meaning of the Greek word λΟΓΟC in Coptic context. This article, after presenting the debate, proposes a new translation of this passage, which takes into consideration the meaning of the word λΟΓΟC in other Coptic texts.
The Chronographiae of Julius Africanus and its Jewish Antecedents
Authors: Adler William
Published: March 2011

In der Forschung ist die Meinung verbreitet, dass Julius Africanus in seinen Chronographiae einfach geläufi ge Topoi der jüdischen (und christlichen) Tradition zu einer vollständigen Chronik ausgeweitet hat. Verf. analysiert die Art und Weise, wie Julius Africanus ältere jüdische Quellen und Traditionen benutzt hat, und berücksichtigt dabei die verschiedenen Bereiche des benutzten Quellenmaterials: mündliche Überlieferung palästinischer Provenienz, biblische Exegese, Historiographie, apokryphe Literatur (besonders das Jubiläenbuch und das äthiopische Henochbuch), Apologetik und apokalyptische Endzeitspekulation. Es zeigt sich, dass Julius Africanus dieses facettenreiche Quellenmaterial an die Erfordernisse der hellenistischen Universalchronik angepasst und so aus dem von ihm benutzten Material etwas ganz Eigenständiges geschaffen hat.
Susanna, the Fathers and the Passio Sereni (BHL 7595-6): Sexual Morals, Intertextuality and Early Christian Self-Definition
Authors: Praet Danny
Published: March 2011

Die Passio Sereni (BHL 7595-6) ist ein einzigartiger Fall von Intertextualität in der Hagiographie der Spätantike. Dieser Aufsatz will zeigen, dass die passio nicht historisch-authentisch ist, sondern eine reine literarische Konstruktion: ihre Erzählstruktur ist mit der alttestamentlichen Geschichte von Susanna und den zwei Ältesten fast identisch. Der frühchristliche Autor hat aber diese Daniel-Geschichte in einen Konflikt zwischen Heiden und Christen umgewandelt und auch die Rollen von Susanna und den Ältesten geschlechtlich und moralisch vertauscht. Eine heidnische Frau, die in einem Garten ein ehebrecherisches Rendezvous hatte, wird von einem alten christlichen Mann, Serenus, beobachtet. Die Pläne der Frau werden vereitelt, woraufhin die Frau ein falsches Zeugnis gegen Serenus ablegt. Eine Analyse des ursprünglichen Daniel-Apokryphons, ein Überblick über die Rezeption der passio in der Patristik und ein Vergleich mit dem alten römischen Ideal der pudicitia führen zu der Schlussfolgerung, dass die Passio Sereni (vermutlich etwa 400 n.Chr.) geschrieben wurde, um ein asketisches Christentum zu fördern als das einzig wahre Erbe der jüdischen und der römischen Tradition.
Sleep Deprivation Biases the Neural Mechanisms Underlying Economic Preferences
Authors: Venkatraman Vinod , Huettel Scott A. , Chuah Lisa Y. M. , Payne John W. , Chee Michael W. L.
Published: March 2011

A single night of sleep deprivation (SD) evoked a strategy shift during risky decision making such that healthy human volunteers moved from defending against losses to seeking increased gains. This change in economic preferences was correlated with the magnitude of an SD-driven increase in ventromedial prefrontal activation as well as by an SD-driven decrease in anterior insula activation during decision making. Analogous changes were observed during receipt of reward outcomes: elevated activation to gains in ventromedial prefrontal cortex and ventral striatum, but attenuated anterior insula activation following losses. Finally, the observed shift in economic preferences was not correlated with change in psychomotor vigilance. These results suggest that a night of total sleep deprivation affects the neural mechanisms underlying economic preferences independent of its effects on vigilant attention.
Temporal Uncertainty Separates Flashes from Their Background during Saccades
Authors: Maij Femke , Brenner Eli , Smeets Jeroen B. J.
Published: March 2011

It is known that spatial localization of flashed objects fails around the time of rapid eye movements (saccades). This mislocalization is often interpreted in terms of a combination of shifts and deformations of the brain's representation of space to account for the eye movement. Such temporary remapping of positions in space should affect all elements in a scene, leaving ordinal relationships between positions intact. We performed an experiment in which we presented flashes on a background with red and green regions to human subjects. We found that flashes that were presented on the green part of the background around the time of a saccade were readily reported to have been presented on the red part of the background and vice versa. This is inconsistent with the notion of a temporary shift and deformation of perceived space. To explain our results, we present a model that illustrates how temporal uncertainty could give rise to the observed spatial mislocalization. The model combines uncertainty about the time of the flash with a bias to localize targets where one is looking. It reproduced the pattern of mislocalization very accurately, showing that perisaccadic mislocalization can best be explained in terms of temporal uncertainty about the moment of the flash.
Functional Relationships between Agonist Binding Sites and Coupling Regions of Homomeric Cys-Loop Receptors
Authors: Andersen Natalia , Corradi Jeremías , Bartos Mariana , Sine Steven M. , Bouzat Cecilia
Published: March 2011

Each subunit in a homopentameric Cys-loop receptor contains a specialized coupling region positioned between the agonist binding domain and the ion conductive channel. To determine the contribution of each coupling region to the stability of the open channel, we constructed a receptor subunit (α7-5-HT3A) with both a disabled coupling region and a reporter mutation that alters unitary conductance, and coexpressed normal and mutant subunits. The resulting receptors show single-channel current amplitudes that are quantized according to the number of reporter mutations per receptor, allowing correlation of the number of intact coupling regions with mean open time. We find that each coupling region contributes an equal increment to the stability of the open channel. However, by altering the numbers and locations of active coupling regions and binding sites, we find that a coupling region in a subunit flanked by inactive binding sites can still stabilize the open channel. We also determine minimal requirements for channel opening regardless of stability and find that channel opening can occur in a receptor with one active coupling region flanked by functional binding sites or with one active binding site flanked by functional coupling regions. The overall findings show that, whereas the agonist binding sites contribute interdependently and asymmetrically to open-channel stability, the coupling regions contribute independently and symmetrically.
Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass
Authors: Roef Greet , Lapauw Bruno , Goemaere Stefan , Zmierczak Hans , Fiers Tom , Kaufman Jean-Marc , Taes Youri
Published: March 2011

Context

The hormonal factors involved in the regulation of peak bone mass (PBM) in men have not been fully investigated. Apart from gonadal steroids and somatotropic hormones, thyroid hormones are known to affect bone maturation and homeostasis and are additional candidate determinants of adult bone mass.

Objective

We aimed to investigate between-subject physiological variation in free and total thyroid hormone concentrations, TSH, and thyroid binding globulin (TBG) in relation to parameters of bone mass, geometry, and mineral density in healthy men at the age of PBM.

Design and setting

We recruited 677 healthy male siblings aged 25–45 years in a cross-sectional, population-based study. Areal and volumetric bone parameters were determined using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Total and free thyroid hormones, TBG, and TSH were determined using immunoassays.

Results

Free and total thyroid hormone concentrations were inversely associated with bone mineral density (BMD) and bone mineral content (BMC) at the hip and total body (free triiodothyronine (FT3), total T3 (TT3), and total T4 (TT4)) and at the spine (FT3). TBG was negatively associated with BMC and areal BMD at all sites. At the radius, cortical bone area was inversely associated with TT3, TT4, and TBG, and trabecular bone density was inversely associated with free thyroxine, TT4, and TBG. We observed inverse associations between cortical bone area at the mid-tibia and FT3, TT3, TT4, and TBG. No associations between TSH and DXA or pQCT measurements were found.

Conclusion

In healthy men at the age of PBM, between-subject variation in thyroid hormone concentrations affects bone density, with higher levels of FT3, TT3, TT4, and TBG being associated with less favorable bone density and content.
Bayesian Multiple Quantitative Trait Loci Mapping for Recombinant Inbred Intercrosses
Authors: Yuan Zhongshang , Zou Fei , Liu Yanyan
Published: March 2011

The Collaborative Cross (CC) is a renewable mouse resource that mimics the genetic diversity in humans. The recombinant inbred intercrosses (RIX) generated from CC recombinant inbred (RI) lines share similar genetic structures to those of F2 individuals. In contrast to F2 mice, genotypes of RIX can be inferred from the genotypes of their RI parents and can be produced repeatedly. Also, RIX mice do not typically share the same degree of relatedness. This unbalanced genetic relatedness requires careful statistical modeling to avoid a large number of false positive findings. For complex traits, mapping multiple genes simultaneously is arguably more powerful than mapping one gene at a time. In this article, we describe how we have developed a Bayesian quantitative trait locus (QTL) mapping method that simultaneously deals with the special genetic architecture of RIX and maps multiple genes. The performance of the proposed method is evaluated by extensive simulations. In addition, for a given set of RI lines, there are numerous ways to generate RIX samples. To provide a general guideline on future RIX studies, we compare several RIX designs through simulations.
Effect of Helicobacter pylori Eradication Therapy on Risk of Hospitalization for a Major Ulcer Event
Authors: Hsiao Fei‐Yuan , Tsai Yi‐Wen , Wen Yu‐Wen , Kuo Ken N. , Tsai Chia‐Rung , Huang Weng‐Foung
Published: March 2011

Study Objective. To compare Helicobacter pylori eradication therapy with antisecretory therapy aloneonthe riskofhospitalization for a major ulcer event.

Design. Retrospective, population‐based cohort study.

Data Source. The 2000–2006 National Health Insurance database in Taiwan.

Patients. A total of 838,176 patients diagnosed with a gastrointestinal ulcer and who filled at least one prescription for antiulcer therapy, either H. pylori eradication therapy (331,364 patients [39.53%])orantisecretory therapy alone (506,812 patients [60.47%]), between January1, 2001, and December 31, 2006.

Measurements and Main Results. The primary outcome was hospitalization for a major ulcer event, defined as a gastrointestinal ulcer with hemorrhage and/or perforation. Cox proportional hazards models, adjusted for demographic and clinical characteristics, were used to compare the risk of hospitalization for a major ulcer event between the group receiving H. pylori eradication therapy (triple or quadruple combination therapy that includes an antisecretory agent) and the group receiving antisecretory therapy alone (histamine2‐receptor blocker or proton pump inhibitor). The H. pylori eradication therapy group was divided into initial users (combination therapy received immediately after gastrointestinal ulcer diagnosis) and late users (combination therapy received after antisecretory therapy with time lag≤180 days, 181–365 days, or>365 days from ulcer diagnosis). A secondary analysis was conductedinthe three late H. pylorieradication therapy subgroups to determine if risk of hospitalization for major ulcer events differed by timing of receipt of therapy. Compared with the antisecretory therapy alone group, the H. pylori therapy group (initial users) had a significantly decreased risk of hospitalization for major ulcer events (adjusted hazard ratio [AHR] 0.57, 95% confidence interval [CI] 0.54–0.59, p<0.001). However, later use of H. pylori therapy was associated with a higher riskofhospitalization for major ulcer events (time lag 181–365 days, AHR 1.68, 95%CI1.51–1.86, p<0.001;>365 days, AHR 1.74, 95% CI1.67–1.80, p<0.001) compared with those who received H. pylori therapy within6months(≤180 days) after gastrointestinal ulcers were diagnosed.

Conclusion. Helicobacter pyloritherapy given within 6 months of a diagnosis of gastrointestinal ulcer was associated with a reduced risk of hospitalization for major ulcer events. Our findings extend the evidence from clinical trials that report the value ofH. pylori eradication therapy in reducing ulcer recurrence by documenting the real‐world benefit of reducing the risk of hospitalization for major gastrointestinal ulcer events.
A Preclinical and Clinical Study of Lithium in Low-Grade Neuroendocrine Tumors
Authors: Lubner Sam J. , Kunnimalaiyaan Muthusamy , Holen Kyle D. , Ning Li , Ndiaye Mary , LoConte Noelle K. , Mulkerin Daniel L. , Schelman William R. , Chen Herbert
Published: March 2011

Background.

Low-grade neuroendocrine tumors (NETs) respond poorly to chemotherapy; effective, less toxic therapies are needed. Glycogen synthase kinase (GSK)-3β has been shown to regulate growth and hormone production in NETs. Use of lithium chloride in murine models suppressed carcinoid cell growth, reduced GSK-3β levels, and reduced expression of chromogranin A. This study assessed the efficacy of lithium chloride in patients with NETs.

Design.

Eligible patients had low-grade NETs. A single-arm, open-label phase II design was used. Lithium was dosed at 300 mg orally three times daily, titrated to serum levels of 0.8–1.0 mmol/L. The primary endpoint was objective tumor response by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included overall survival, progression-free survival, GSK-3β phosphorylation, and toxicity.

Results.

Fifteen patients were enrolled between October 3, 2007 and July 17, 2008, six men and nine women. The median age was 58 years. Patient diagnoses were carcinoid tumor for eight patients, islet cell tumor for five patients, and two unknown primary sites. Eastern Cooperative Oncology Group performance status scores were 0 or 1. Two patients came off study because of side effects. The median progression-free survival interval was 4.50 months. There were no radiographic responses. Because of an early stopping rule requiring at least one objective response in the first 13 evaluable patients, the study was closed to further accrual. Patients had pre- and post-therapy biopsies.

Conclusions.

Lithium chloride was ineffective at obtaining radiographic responses in our 13 patients who were treated as part of this study. Based on the pre- and post-treatment tumor biopsies, lithium did not potently inhibit GSK-3β at serum levels used to treat bipolar disorders.
Trastuzumab Beyond Progression in Retrospective Analyses: An Issue of Equal Opportunities
Authors: Montemurro Filippo , Redana Stefania , Geuna Elena , Milani Andrea , Rossi Valentina , Martinello Rossella , Valabrega Giorgio , Aglietta Massimo
Published: March 2011

Results of the Hermine study of trastuzumab beyond progression in breast cancer patients, published by Extra and colleagues in The Oncologist, are re-examined and an alternative explanation for the dismal postprogression survival time of patients stopping therapy is presented.
Climate determines upper, but not lower, altitudinal range limits of Pacific Northwest conifers
Authors: Ettinger A. K. , Ford K. R. , HilleRisLambers J.
Published: March 2011

Does climate determine species' ranges? Rapid rates of anthropogenic warming make this classic ecological question especially relevant. We ask whether climate controls range limits by quantifying relationships between climatic variables (precipitation, temperature) and tree growth across the altitudinal ranges of six Pacific Northwestern conifers on Mt. Rainier, Washington, USA. Results for three species (Abies amabilis, Callitropsis nootkatensis, Tsuga mertensiana) whose upper limits occur at treeline (>1600 m) imply climatic controls on upper range limits, with low growth in cold and high snowpack years. Annual growth was synchronized among individuals at upper limits for these high‐elevation species, further suggesting that stand‐level effects such as climate constrain growth more strongly than local processes. By contrast, at lower limits climatic effects on growth were weak for these high‐elevation species. Growth–climate relationships for three low‐elevation species (Pseudotsuga menziesii, Thuja plicata, Tsuga heterophylla) were not consistent with expectations of climatic controls on upper limits, which are located within closed‐canopy forest (<1200 m). Annual growth of these species was poorly synchronized among individuals. Our results suggest that climate controls altitudinal range limits at treeline, while local drivers (perhaps biotic interactions) influence growth in closed‐canopy forests. Climate‐change‐induced range shifts in closed‐canopy forests will therefore be difficult to predict accurately.
Potential Strategies to Eliminate Built Environment Disparities for Disadvantaged and Vulnerable Communities
Authors: Hutch Daniel J. , Bouye Karen E. , Skillen Elizabeth , Lee Charles , Whitehead LaToria , Rashid Jamila R.
Published: March 2011

In 2006, the Federal Collaboration on Health Disparities Research (FCHDR) identified the built environment as a priority for eliminating health disparities, and charged the Built Environment Workgroup with identifying ways to eliminate health disparities and improve health outcomes.

Despite extensive research and the development of a new conceptual health factors framework, gaps in knowledge exist in areas such as disproportionate environmental and community hazards, individual and cumulative risks, and other factors.

The FCHDR provides the structure and opportunity to mobilize and partner with built environment stakeholders, federal partners, and interest groups to develop tools, practices, and policies for translating and disseminating the best available science to reduce health disparities.
Factors Affecting Employment at Initiation of Dialysis
Authors: Muehrer Rebecca J. , Schatell Dori , Witten Beth , Gangnon Ronald , Becker Bryan N. , Hofmann R. Michael
Published: March 2011

Background and objectives

Half the individuals who reach ESRD are working age (<65 years old) and many are at risk for job loss. Factors that contribute to job retention among working-age patients with chronic kidney disease before ESRD are unknown. The purpose of the study is to understand factors associated with maintaining employment among working-age patients with advanced kidney failure.

Design, setting, participants, & measurements

In this retrospective study we reviewed the United States Renal Data System database (1992 through 2003) and selected all patients (n = 102,104) who were working age and employed 6 months before dialysis initiation. Factors that were examined for an association with maintaining employment status included demographics, comorbid conditions, ESRD cause, insurance, predialysis erythropoietin use, and dialysis modality.

Results

Maintaining employment at the same level during the final 6 months before dialysis was more likely among (1) white men ages 30 to 49 years; (2) patients with either glomerulonephritis, cystic, or urologic causes of renal failure; (3) patients choosing peritoneal dialysis for their first treatment; (4) those with employer group or other health plans; and (5) erythropoietin usage before ESRD. Maintaining employment status was less likely among patients with congestive heart failure, cardiovascular disease, cancer, and other chronic illnesses.

Conclusions

The rate of unemployment in working-age patients with chronic kidney disease and ESRD is high compared with that of the general population. Treating anemia with erythropoietin before kidney failure and educating patients about work-friendly home dialysis options might improve job retention.
Longitudinal Association of Depressive Symptoms with Rapid Kidney Function Decline and Adverse Clinical Renal Disease Outcomes
Authors: Kop Willem J. , Seliger Stephen L. , Fink Jeffrey C. , Katz Ronit , Odden Michelle C. , Fried Linda F. , Rifkin Dena E. , Sarnak Mark J. , Gottdiener John S.
Published: March 2011

Background and objectives

Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).

Design, setting, participants, & measurements

Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (≥8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m2. Outcomes were rapid decline in eGFR (>3 ml/min per m2 per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.

Results

Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.

Conclusions

Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.
Survival in Pediatric Dialysis and Transplant Patients
Authors: Samuel Susan M. , Tonelli Marcello A. , Foster Bethany J. , Alexander R. Todd , Nettel-Aguirre Alberto , Soo Andrea , Hemmelgarn Brenda R.
Published: March 2011

Background and objectives

Long-term follow-up data are few in children with ESRD. We sought to describe long-term survival, assess risk factors for death, and compare survival between two time periods in pediatric ESRD patients.

Design, setting, participants, & measurements

We used a population-based retrospective cohort utilizing data from a national organ failure registry and from Canada's universal healthcare system. We included 843 children (ages, 0 to 18) initiating renal replacement therapy from 1992 to 2007 and followed them until death or date of last contact (median follow-up, 6.8 years; interquartile range, 3.0 to 10.6). We assessed risk factors for death and examined cause-specific mortality.

Results

During 5991 patient-years of follow-up, 107 (12.7%) patients died. Unadjusted cumulative survival for the cohort was: 91.7% (95% CI, 89.8 to 93.7%) at 5 years and 85.8% (95% CI, 82.8 to 88.8%) at 10 years. Among patients commencing dialysis, overall adjusted survival was poorest among those who started dialysis at age <1 year. No secular trends in survival were noted for either dialysis or transplant patients. The proportion of incident patients receiving pre-emptive transplantation increased over time. Pre-emptively transplanted patients did not demonstrate superior adjusted survival compared with those who spent >2 years on dialysis before transplant (hazard ratio, 1.53; 95% CI, 0.63 to 3.67).

Conclusions

No significant improvements in survival were observed among ESRD patients over the study period. Time with transplant function had the strongest association with survival. Pre-emptive transplantation was not associated with improved survival in adjusted models.
Pharmacokinetics and Pharmacodynamics of Intravenous Daptomycin during Continuous Ambulatory Peritoneal Dialysis
Authors: Cardone Katie E. , Lodise Thomas P. , Patel Nimish , Hoy Christopher D. , Meola Shari , Manley Harold J. , Drusano George L. , Grabe Darren W.
Published: March 2011

Background and objectives

This study sought to (1) characterize the pharmacokinetic (PK) profile of intravenous (IV) daptomycin among patients receiving continuous ambulatory peritoneal dialysis (CAPD); (2) identify optimal IV CAPD dosing schemes; and (3) determine extent of daptomycin penetration into the peritoneal space after IV administration.

Design, setting, participants, & measurements

A PK study was conducted among eight CAPD patients. Population PK modeling and Monte Carlo simulation (MCS) were used to identify CAPD dosing schemes providing efficacy and toxicity plasma profiles comparable with those obtained from MCS using the daptomycin population PK model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. The primary efficacy exposure target was the area under the curve (AUC). For toxicity, the goal was to identify CAPD dosing schemes that minimized plasma trough concentrations in excess of 24.3 mg/L. Finally, peritoneal cavity penetration was determined.

Results

Administration of IV daptomycin 4 or 6 mg/kg, depending on indication, every 48 h was identified as the optimal CAPD dosing scheme. This regimen provided cumulative (AUC0–48) and daily partitioned (AUC0–24h and AUC24–48h) plasma AUC values similar to the SAB-IE or “typical patient” simulations. In addition, the proportion of patients likely to experience an elevated trough concentration in excess of 24.3 mg/L was similar between every 48 h CAPD dosing and the referent group. Penetration into the peritoneal cavity was 6% of plasma.

Conclusions

Daptomycin 4 or 6 mg/kg, on the basis of indication, IV every 48 h was found to be the optimal IV CAPD dosing scheme.
‘Youth’ Making Us Fit: On Europe as Operator of Political Technologies
Authors: Olsson Ulf , Petersson Kenneth , Krejsler John B.
Published: March 2011

This article problematizes the construction of youth as a ‘driving force’ in the contemporary configuration of the European Union (EU) as an educational and political space. The study draws empirical nourishment out of documents that are central to the ongoing formation of the Union, be it White Papers, scripts or memos concerning political arenas such as youth and education policies and the Bologna process. Theoretically the article draws on insights from post-Foucauldian traditions with a focus on mentalities, subject constructions, technologies and practices operating within the ongoing governmentalization of Europe. Central questions are ‘who’ and ‘what’ the problematization of youth as political technology is about. Drawing on homologies in the coding of citizen, independent of age, the authors claim that problematization of youth is directed to all of us. We are all, in the name of youth, expected to constantly ‘adapt’ ourselves in compliance with the aim of the Lisbon process. Furthermore, as the Union itself is coded in a similar way, we may even claim that the EU, literally speaking, appears as a youth project in itself. Thus, the notion that youth can be seen as political rationality that becomes a powerful driving force in the ongoing European project.
Dilemmas in the Implementation of Children's Right to Equity in Education in the Swedish Compulsory School
Authors: Francia Guadalupe
Published: March 2011

In order to illustrate and discuss the impacts of neo-liberal educational policies on equity, this article analyses the effects of different kinds of decentralisation strategies on the implementation of children's right to an equitable education in Sweden. It begins with a comprehensive overview of the changes implemented in the Swedish compulsory school system during the last two decades. It analyses the processes of transfer of authority and responsibility and discusses the complexity of interpreting these processes in terms of equity. This article examines the complex and contextual nature and consequences of decentralisation and centralisation strategies in order to better understand the implementation of children's right to equity in school practice. Although this analysis is based on the Swedish experience, it can contribute to a better understanding of the impacts of neo-liberal educational policies on equity in other European contexts.
The Bologna Process Policy Implementation in Russia and Ukraine: Similarities and Differences
Authors: Luchinskaya Daria , Ovchynnikova Olena
Published: March 2011

The recent establishment of the European Higher Education Area and the ongoing monitoring carried out by the Bologna Follow-up Group raises the question: to what extent have the objectives of the Bologna Process been implemented in the varied higher education systems of the 47 signatory states, including the former Soviet Union states? This article concentrates on the extent of the Bologna Process implementation in Russia and Ukraine at the national policy level, focusing on the European Credit Transfer System (ECTS), the dual-cycle degree organisation and the development of quality assurance. Based on official documentation, it appears that by 2009 Ukraine had achieved more than Russia in the implementation of Bologna aims and objectives. The theoretical approach suggested by Heinze and Krill is used to identify the national considerations of Russia and Ukraine relative to the Bologna Process, and Phillips and Ochs' model of policy transfer is employed to analyse the similarities and differences of the Bologna Process implementation in Russia and Ukraine. The findings suggest that while Ukraine may have implemented more of the Bologna Process objectives overall, including ECTS and the degree cycles, Russia has made progress in the diploma supplement, and both countries are at a similar level of quality assurance.
Student Training in Transversal Competences at the University of Cordoba
Authors: Serrano Rosario Mérida , Romero Julia Angulo , Bello Manuel Jurado , Pérez José Diz
Published: March 2011

This article describes a research project developed at the University of Cordoba during the academic year 2007–8, in which 2414 students took part, all studying courses included in a pilot scheme for the implementation of European Credit Transfer System credits. The aim was to ascertain the opinions of students in relation to their grasp and working level of the transversal competences encompassed in the Tuning Project. This article begins by clarifying the concept of competence as it is understood here, then contextualises the study within the research being carried out both within Spain and abroad, and finally presents the research results and identifies the most valued and least developed competences with a view to planning useful training activities.
A Challenge to Metrics as Evidence of Scholarity
Authors: Stelmach Bonnie L. , Von Wolff Stuart D.
Published: March 2011

Now that universities have shifted their priorities to those of the ‘cash nexus’, they increasingly articulate their accomplishments and validate their existence in business terms for a globally competitive academic market. But corporatizing trends and the use of bibliometric tools that rank publication and quantify scholarity impact a redefinition and reconceptualization of what it means to be a scholar as an instrument of the corporate regime. Judith Butler's notion of normalizing categories is the lens through which this article examines European and United Kingdom corporatizing strategies such as the Bologna Process and Research Assessment Exercise. Key to the discussion is a critique of bibliometric accountability mechanisms that privilege quantification and promote academic materialism. These devices become normative, and, thus, the definition of scholarity to which academics default.
Communicative Competences and the Use of ICT for Foreign Language Learning within the European Student Exchange Programme ERASMUS
Authors: Gómez José Ignacio Aguaded , Vicente Cristina Pozo
Published: March 2011

This article presents the results from a mainly statistical and comparative analysis regarding the communicative competences and the use of information and communication technologies (ICTs) of German exchange students. The data was extracted from two exhaustive, rigorous and methodical questionnaires related to communicative and ICT competences, which were completed by 20 exchange students from the Romanisches Seminar at the University of Bonn, Germany, their native language being German, whilst learning Spanish as a foreign language. Generally, the results confirm that a six-month stay in a foreign country increases the use of ICT and widely improves language skills, which can also be referred to as communicative competences in Spanish for native speakers of German.
p38 Mitogen-Activated Protein Kinase-Dependent Transactivation of ErbB Receptor Family
Authors: Hemi Rina , Yochananov Yafit , Barhod Ehud , Kasher-Meron Michal , Karasik Avraham , Tirosh Amir , Kanety Hannah
Published: March 2011

OBJECTIVE

Stress stimuli such as tumor necrosis factor (TNF) have been shown to induce insulin receptor substrate (IRS)-1 serine phosphorylation and insulin resistance by transactivation of ErbB receptors. We aimed at elucidating the potential role of p38 mitogen-activated protein kinase (p38MAPK) in mediating stress-induced ErbB receptors activation.

RESEARCH DESIGN AND METHODS

p38MAPK effect on ErbBs transactivation and insulin signaling was assessed in Fao or HepG2 cells, exposed to stress stimuli, and on metabolic parameters in ob/ob and C57/BL6 mice.

RESULTS

High-fat diet–fed mice and ob/ob mice exhibited elevated hepatic p38MAPK activation associated with glucose intolerance and hyperinsulinemia. Liver expression of dominant-negative (DN)-p38MAPKα in ob/ob mice reduced fasting insulin levels and improved glucose tolerance, whereas C57/BL6 mice overexpressing wild-type p38MAPKα exhibited enhanced IRS-1 serine phosphorylation and reduced insulin-stimulated IRS-1 tyrosine phosphorylation. Fao or HepG2 cells exposed to TNF, anisomycin, or sphingomyelinase demonstrated rapid transactivation of ErbB receptors leading to PI3-kinase/Akt activation and IRS-1 serine phosphorylation. p38MAPK inhibition either by SB203580, by small interfering RNA, or by DN-p38MAPKα decreased ErbB receptors transactivation and IRS-1 serine phosphorylation and partially restored insulin-stimulated IRS-1 tyrosine phosphorylation. When cells were incubated with specific ErbB receptors antagonists or in cells lacking ErbB receptors, anisomycin- and TNF-induced IRS-1 serine phosphorylation was attenuated, despite intact p38MAPK activation. The stress-induced p38MAPK activation leading to ErbB receptors transactivation was associated with intracellular reactive oxygen species generation and was attenuated by treatment with antioxidants.

CONCLUSIONS

Hepatic p38MAPK is activated following various stress stimuli. This event is upstream to ErbB receptors transactivation and plays an important role in stress-induced IRS-1 serine phosphorylation and insulin resistance.
Threefolds with big and nef anticanonical bundles II
Authors: Jahnke Priska , Peternell Thomas , Radloff Ivo
Published: March 2011

In a follow-up to our paper [Threefolds with big and nef anticanonical bundles I, Math. Ann., 2005, 333(3), 569–631], we classify smooth complex projective threefolds Xwith −K
X big and nef but not ample, Picard number γ(X) = 2, and whose anticanonical map is small. We assume also that the Mori contraction of X and of its flop X
+ are not both birational.
Synthesis and Properties of Partially Hydrogenated Ethyl ([3,4']Bipyridin-6'-ylsulfanyl) Acetates
Authors: Krauze A. , Andžāns Z. , Duburs G.
Published: March 2011

Synthesis and Properties of Partially Hydrogenated Ethyl ([3,4']Bipyridin-6'-ylsulfanyl) Acetates

Ethyl 2'-hydroxy-1',2',3',4'-tetrahydro[3,4']bipyridine-3'-carboxylate 3 and the corresponding ethyl 1',4'-dihydro[3,4']bipyridine-3'-carboxylate 4 as potential cardiovascular agents have been prepared by alkylation of 2'-hydroxy-1',2',3',4'-tetrahydro[3,4']bipyridine-6'-thiolate 1 or betaine 2 with ethyl bromoacetate. The treatment of [3,4']bipyridine 4 with KOH/H2O gave diethyl 3-amino-4-(pyridin-3-yl)-4,7-dihydrothieno[2,3-b]-pyridine-2,5-dicarboxylate 5, but subsequent treatment of the remaining reaction mixture with acetic acid excess gave ethyl 3-oxo-7-(pyridin-3-yl)-2,3-dihydro-7H-thiazolo[3,2-a]pyridine-6-carboxylate 7 - the product of intramolecular acylation. Compounds 4, 5 and 7 have been prepared using the one-pot synthesis method. Alkylation of [3,4']bipyridine 4 with iodomethane gave 1',4'-dihydro[3,4'] bipyridin-1-ium iodide 8.
Trapped mode resonances in metalo-dielectric structures with electric asymmetry materials
Authors: Rotaru Mihai , Sykulski Jan
Published: March 2011

Trapped mode resonances in metalo-dielectric structures with electric asymmetry materials

This paper investigates the possibility of exciting high quality trapped resonant modes on frequency selective surfaces consisting of identical sub-wavelength metallic inclusions (symmetrically split rings) with no structural asymmetry but exhibitting electrical asymmetry. The electrical symmetry is broken by using different dielectric substrates. The existence of such anti-symmetric trapped mode on geometrical symmetric structure is demonstrated through numerical simulation. Numerical results suggest that the high quality factor observed for these resonant modes is achieved via weak coupling between the "trapped modes" and free space which enables the excitation of these modes.
Shoreline dynamics of Calypsostranda (NW Wedel Jarlsberg Land, Svalbard) during the last century
Authors: Zagórski Piotr
Published: March 2011

Shoreline dynamics of Calypsostranda (NW Wedel Jarlsberg Land, Svalbard) during the last century

A 6 km long stretch of the coast of Calypsostranda between Skilvika and Joseph-bukta, situated on the western side of Recherchefjorden, was investigated. It is made of an accumulative marine terrace at a height of 2-8 m a.s.l. (terrace 1) and width of 40-180 m, divided by a cliffed section in the frontal moraines of Renardbreen. From the character and intensity of changes, the area was divided into 6 zones. The aim was to analyse the dynamics of changes within coastal zone from 1936 to 2007 and to characterise the influence of various morphogenetic factors (marine, fluvial, cryospheric). The important element of this study has been to determine sources and directions of sediment transport. The dynamics of changes of coastal zone in the Calypsostranda region was established from archival maps and precise GPS measurements for the periods: 1936-1960, 1960-1990, 1990-2000, 2000-2005, 2005-2006, 2006-2007. Comparing the extension of shoreline between 1936 and 2007 showed that there was more erosion than accumulation. Nearly 110 000 m2 of the area of terrace 1 decreased, whereas about 77 000 m2 appeared. The net balance for 1936-2007 was about -32 700 m2, on average over the whole length of the shoreline, it retreated by 5.7 m (0.08 m a-1). The cease of sediment delivery in the extramarginal sandur fans area of Renardbreen caused intensification of marine processes, that made the shoreline retreat by over 100 m. Continuing sediment delivery from the Scottelva catchment, with contribution of material from erosion of the north end of the shoreline studies, caused the aggradation of coastal zone by over 60 m near its mouth.
The first recorded occurrence of Hirudo verbana Carena, 1820 (Hirudinea: Arhynchobdellida: Hirudinidae) in Romania
Authors: Gagiu Adrian
Published: March 2011

The first recorded occurrence of Hirudo verbana Carena, 1820 (Hirudinea: Arhynchobdellida: Hirudinidae) in Romania

In 2005, a Hirudo verbana specimen was observed in Stracoş Valley, within the Tăşad Reserve (Bihor county, north-western Romania). Since the coloration pattern of this once forgotten species matches its genetic differentiation, the identification of the specimen as belonging to the southeastern European H. verbana appears plausible. The species was previously cited in southern, central and eastern Europe, but not in Romania. Therefore, the present observation might be its first recognized occurrence in the country. As recently pointed out, H. verbana is one of the three species commonly known as the European medicinal leech and the most abundant as such. Most international and national conservation legislation containing only H. medicinalis (including IUCN, CITES, Berne Convention) needs completion, according to the new taxonomy.
Phenology and biometrics of Moustached Warbler Acrocephalus melanopogon (Passeriformes: Sylviidae) in Romania
Authors: Chişamera Gabriel , Pocora Viorel , Gogu-Bogdan Mircea , Adam Costică
Published: March 2011

Phenology and biometrics of Moustached Warbler Acrocephalus melanopogon (Passeriformes: Sylviidae) in Romania

A complete list of all records on the Moustached Warbler (Acrocephalus melanopogon) available in Romania was compiled from literature and completed with new records based on field studies, examination of museum collections and data gathered from ringing campaigns of Romanian Ornithological Ringing Centre during 1990 - 2010. The record review is complemented by distribution map. Biometric data of caught specimens are presented and supplemented by data from the literature of other specimens from Romania.
Factors influencing the breeding habitat use by amphibians in the alpine area of the Retezat National Park (Romania)
Authors: Plăiaşu Rodica , Băncilă Raluca , Samoilă Ciprian , Cogălniceanu Dan
Published: March 2011

Factors influencing the breeding habitat use by amphibians in the alpine area of the Retezat National Park (Romania)

We analyzed the distribution of amphibians according to the characteristics of breeding ponds in the alpine areas of the Retezat National Park. We inventoried 50 aquatic habitats between 1920 and 2260 m a.s.l. Three amphibian species are present at high altitudes:Rana temporaria, Bufo bufoandMesotriton alpestris. They were found in 70% of the aquatic habitats, but only 48% were used as spawning sites. Human impacts and predators were the most influential variables explaining the occurrence ofR. temporaria, whereas location and pond adjacent terrain were important forM. alpestris. Moderate grazing had a positive effect by maintaining low vegetation or providing nutrients input in the oligotrophic aquatic habitats.