bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Phase II Study of Erlotinib in Combination With Placebo or R1507, a Monoclonal Antibody to Insulin-Like Growth Factor-1 Receptor, for Advanced-Stage Non–Small-Cell Lung Cancer
Authors: Ramalingam Suresh S. , Spigel David R. , Chen David , Steins Martin B. , Engelman Jeffrey A. , Schneider Claus-Peter , Novello Silvia , Eberhardt Wilfried E.E. , Crino Lucio , Habben Kai , Liu Lian , Jänne Pasi A. , Brownstein Carrie M. , Reck Martin 
Published: October 2011

PurposeR1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study.Patients and MethodsPatients with advanced-stage non–small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate.ResultsIn all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo.ConclusionThe combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR.
Grammatische Illusionen – Lokal wohlgeformt – global deviant
Authors: Haider Hubert 
Published: October 2011

Abstract
Grammatical illusions are linguistic equivalents of optical illusions in visual processing. A grammatical illusion amounts to an expression that is judged acceptable in spite of its grammatical deviance. It is the hitherto insufficiently appreciated fourth “aggregate state”, that completes the set of four logical pairings of the properties “(un-)grammatical” and “(un-)acceptable”.
A typical source of syntactic illusions is the mental processor's attempt to repair grammatical inconsistencies resulting from contradicting requirements of syntactic regularities. The resulting pseudo-solutions tend to be appraised as acceptable, although they remain patently ungrammatical.
The consequences of this phenomenon, when acknowledged, are evident: Acceptability turns out to be neither a necessary nor a sufficient property of a grammatical construction. The attempt of modeling any construction that is (introspectively) judged acceptable as grammatically well-formed is tantamount to the attempt of devising a grammatical derivation for constructions of arbitrary (un)grammaticality. Informant consultation results are contaminated and of limited value. Syntactic investigations (and semantic ones as well) deserve more reliable standards of data assessment than mere sampling of self-perception testimonies and corpus search.
Aspekt, Temporalität und Argumentstruktur bei attributiven Partizipien des Deutschen
Authors: Lübbe Anja , Rapp Irene 
Published: October 2011

Abstract
German has two participles, both of which occur in prenominal position. Traditionally, both participles are considered to be associated with particular semantic and syntactic features. The present participle (malend ‘painting’) is subject-oriented; it has imperfective aspect and indicates simultaneity of the participle event and the matrix clause event. The past participle (gemalt ‘painted’) is object-oriented; it has perfective aspect and indicates that the participle event precedes the event of the matrix clause. In this paper, we will first argue that aspect is indeed an inherent – hence invariant – feature of the participle morphology: The present participle always presents an event as ongoing, whereas the past participle presents it as completed. Secondly, we will show that participles – as non-finite verb forms – lack tense. Hence, their temporal properties vary according to lexical, syntactic and pragmatic factors. It will be demonstrated that the unmarked temporal readings of the participles are due to the maxim of relation. Finally, we will argue that the argument selection properties of both participles are grammatically determined; however, these properties can be altered if certain conditions are met.
Rietveld refinement of energy-dispersive synchrotron measurements
Authors: Apel Daniel , Klaus Manuela , Genzel Christoph , Balzar Davor 
Published: October 2011

Abstract
In the past two decades the energy-dispersive diffraction (EDD) method has become a powerful tool in many fields of materials research such as residual stress, texture, and crystal structure analysis, because of its favorable ratio of a comparatively low experimental effort in form of a simple and fixed instrumental setup to a high information content included in the measured diffraction patterns. However, mainly due to the rather poor instrumental resolution only little work has been done so far to apply the well-established methods of diffraction line profile analysis to the EDD data. In the paper, a Rietveld program is introduced that allows for particle size and strain broadening analysis by refining the whole EDD äpattern. With the examples of synchrotron measurements performed on the materials science beamline EDDI at BESSY II on instrumental standard as well as samples exhibiting size and/or strain broadened diffraction lines, it is demonstrated that the generalized Thompson, Cox & Hastings approach (TCH) using pseudo-Voigt functions for describing the diffraction line profiles yields sound and reliable results on the materials microstructure. For a first proof of the theoretical assumptions this Rietveld program is based on, the Pawley approach was used to extract the peak intensities obtained from powder samples affected by microstructural broadening. An excellent agreement with the results of the size-strain round robin was obtained. Future enhancements of the program code which aim at its application to full residual stress and microstructure analysis in the near surface zone and also in the material voläume of polycrystalline materials are discussed.
Treatment and screening of hypothyroidism in pregnancy: results of a European survey
Authors: Vaidya Bijay , Hubalewska-Dydejczyk Alicja , Laurberg Peter , Negro Roberto , Vermiglio Francesco , Poppe Kris 
Published: October 2011

BackgroundMaternal hypothyroidism in pregnancy is associated with several adverse outcomes. The Endocrine Society Guidelines for the management of thyroid diseases in pregnancy were published in 2007; however, impact of the guidelines in routine clinical practice is unknown. Therefore, we have carried out a survey of members of the European Thyroid Association (ETA) to study current practices relating to the management of hypothyroidism in pregnancy.Subjects and methodsIn December 2010, we emailed an electronic questionnaire survey based on clinical case scenarios to 605 members of the ETA. Responses from 190 clinician members (from 28 European countries) were analyzed.ResultsFor a pregnant woman with newly diagnosed overt hypothyroidism, most responders initiated a full dose of l-thyroxine (l-T4). For a woman with hypothyroidism planning pregnancy, 50% recommended increasing the dose of l-T4 as soon as pregnancy is confirmed, whilst 43% favored testing thyroid function before adjusting the dose. Responders used diverse combinations of tests to monitor the dose of l-T4. The target of thyroid function tests that responders aimed to achieve with l-T4 was also inconsistent. Forty-two percent responders or their institutions screened all pregnant women for thyroid dysfunction, 43% performed targeted screening of only the high-risk group, whilst 17% did not carry out systemic screening. Timing of the screening, tests used, and criteria for starting treatment and monitoring were variable.ConclusionsThere is wide variation in the clinical practice relating to the treatment and screening of hypothyroidism during pregnancy in Europe.
Extrapolation of Adult Data and Other Data in Pediatric Drug-Development Programs
Authors: Dunne Julia , Rodriguez William J. , Murphy M. Dianne , Beasley B. Nhi , Burckart Gilbert J. , Filie Jane D. , Lewis Linda L. , Sachs Hari C. , Sheridan Philip H. , Starke Peter , Yao Lynne P. 
Published: October 2011

OBJECTIVES:
In 1994, the US Food and Drug Administration (FDA) proposed an approach, based on extrapolation of efficacy findings from adults to the pediatric population, to maximize the use of adult data and other data when designing pediatric drug-development programs. We examined the experience of the FDA in using extrapolation to evaluate how and when it was used and any changes in scientific assumptions over time.

METHODS:
We reviewed 370 pediatric studies submitted to the FDA between 1998 and 2008 in response to 159 written requests (166 products) issued under the Pediatric Exclusivity Provision. We identified cases in which efficacy was extrapolated from adult data or other data, we categorized the type of pediatric data required to support extrapolation, and we determined whether the data resulted in new pediatric labeling.

RESULTS:
Extrapolation of efficacy from adult data occurred for 82.5% of the drug products (137 of 166). Extrapolation was defined as complete for 14.5% of the products (24 of 166) and partial for 68% of them (113 of 166). Approaches to extrapolation changed over time for 19% of the therapeutic indications studied (13 of 67). When extrapolation was used, 61% of the drug products (84 of 137) obtained a new pediatric indication or extension into a new age group; this number decreased to 34% (10 of 29) when there was no extrapolation.

CONCLUSIONS:
Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals for pediatric use.
Disability 3, 12, and 24 Months After Traumatic Brain Injury Among Children and Adolescents
Authors: Rivara Frederick P. , Koepsell Thomas D. , Wang Jin , Temkin Nancy , Dorsch Andrea , Vavilala Monica S. , Durbin Dennis , Jaffe Kenneth M. 
Published: October 2011

OBJECTIVE:
To examine disability in children and adolescents after traumatic brain injury (TBI) across the spectrum of injury severity.

METHODS:
This was a prospective cohort study of children younger than 18 years treated for a TBI (n = 729) or an arm injury (n = 197) between March 1, 2007, and September 30, 2008. The main outcome measures were disability in health-related quality of life, adaptive skills, and participation in social and community activities 3, 12, and 24 months after injury compared with preinjury functioning.

RESULTS:
The health-related quality of life for children with moderate or severe TBI was lower at all follow-up times compared with baseline, but there was some improvement during the first 2 years after injury. Three months after injury, there was a substantial decrease in the level of activities in which children with moderate and severe TBI were able to participate; these activities improved at 12 and 24 months but were still significantly impaired. Communication and self-care abilities in children with moderate and severe TBI were lower at 3 months than at baseline and did not improve by 24 months. Children who met the definition of mild TBI but had an intracranial hemorrhage had lower quality-of-life scores at 3 months.

CONCLUSIONS:
Children with moderate or severe TBI and children with mild TBI who had intracranial hemorrhage had substantial long-term reduction in their quality of life, participation in activities with others, and ability to communicate and care for themselves.
Biomimetic Polymer Nanoparticles Embedding Quantum Dots
Authors: Ishihara Kazuhiko , Goto Yusuke , Matsuno Ryosuke 
Published: October 2011

ABSTRACTTo develop new functional fluorescence probe based on semiconductor nanoparticles, such as quantum dots (QD)s, we investigated polymer particle embedding QDs and covered with artificial cell membrane-biointerface. These nanoparticles were prepared by assembling 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer as a platform and biomolecules immobilized on the surface of the nanoparticles. The fluorescence property of QDs remained after embedding in the polymer nanoparticles. The MPC polymer surface showed high resistance to non-specific cellular uptake due to the phosphorylcholine groups in the side chain. On the other hand, when cell-penetration oligopeptide, octaarginine was immobilized on the surface, they could permeate the membrane of cells effectively and good fluorescence based on QDs could be observed. Cytotoxicity and inflammation reaction was not produced by these nanoparticles even after immobilization of octapeptide. In conclusion, we could obtain stable fluorescence polymer nanoparticles covered with artificial cell membrane, which are useful as an excellent bioimaging probe and as a novel evaluation tool for biomolecular function in the target cells.
Statin Therapy for the Prevention of Atrial Fibrillation: A Meta‐analysis of Randomized Controlled Trials
Authors: Wang Zhongsu , Zhang Yong , Gao Mei , Wang Jiangrong , Wang Qing , Wang Xiaojun , Su Lequn , Hou Yinglong 
Published: October 2011

Study Objectives. To assess the efficacy of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) for primary and secondary prevention of atrial fibrillation, and to evaluate the efficacy of individual statins and their dosages.Design. Meta‐analysis of 20 randomized controlled trials.Patients. A total of 32,311 patients who received either a statin (16,203 patients) or a placebo or active control regimen (16,108 patients) for either primary or secondary prevention of atrial fibrillation as part of a research study.Measurements and Main Results. A systemic literature search of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register was performed to identify randomized controlled trials involving the prevention of atrial fibrillation with statin therapy. Effect size was expressed as odds ratio (OR) with 95% confidence interval (CI). Subgroup analysis was performed to explore the reasons for heterogeneity. Of the 20 trials, atorvastatin was studied in 11, pravastatin in five, rosuvastatin in three, and simvastatin in one. Overall, among the 32,311 patients in these trials, the risk of atrial fibrillation was significantly reduced by statins (OR 0.59, 95% CI 0.45‐0.76), and the drugs were effective for both primary prevention (OR 0.67, 95% CI 0.51‐0.88) and secondary prevention (OR 0.40, 95% CI 0.20‐0.83). Secondary prevention was not superior to primary prevention, however. A significant benefit was observed in the atorvastatin‐treated subgroup (OR 0.43, 95% CI 0.27‐0.66), especially in the dose range of 10–40 mg/day (OR 0.29, 95% CI 0.19‐0.45). No protective effect was observed in the pravastatin subgroup (OR 1.03, 95% CI 0.77‐1.37).Conclusion. This meta‐analysis suggests that statin therapy is useful for the prevention of atrial fibrillation. The benefit of statins in secondary prevention was significant but not superior to primary prevention. Atorvastatin was more effective than pravastatin, and its effects were dose related, with lower doses being more effective. The number of trials focusing on individual drugs is still insufficient, and more randomized controlled trials are necessary to further support these conclusions.
Blood Pressure Level Attainment Among Patients with Coronary Artery Disease and Uncontrolled Blood Pressure
Authors: McConnell Karen J. , Morris Jessica L. , Delate Thomas , Cymbala Alicia A. , Hornak Roseanne , Kauffman Amy B. , McGinnis Brandy D. ,   Clinical Pharmacy Cardiac Risk Service Study Group
Published: October 2011

Study Objectives. To determine the proportion of patients with coronary artery disease (CAD) and uncontrolled blood pressure who attained a blood pressure of less than 130/80 mm Hg, and to compare patient‐ and health system—specific characteristics and identify factors independently associated with attaining this blood pressure level.Design. Retrospective, longitudinal, cohort study.Setting. Health maintenance organization.Patients. A cohort of 1380 patients (14%) who had uncontrolled blood pressure out of 9785 adults with established CAD enrolled in the Clinical Pharmacy Cardiac Risk Service.Measurements and Main Results. Uncontrolled hypertension was defined as a mean of two consecutive blood pressure readings of 140/90 mm Hg or higher in 2006 or 2007, most proximal to December 31, 2007 (baseline). The cohort was followed from January 1, 2008–June 30, 2009 (follow‐up). The follow‐up blood pressure level was the mean of the last two consecutive blood pressure readings most proximal to June 30, 2009. Of the 1380 patients, 34.9% (482 patients), 34.0% (469), and 31.1% (429) attained a blood pressure below 130/80, 130/80–139/89, and 140/90 mm Hg or higher, respectively, at follow‐up. Significantly more patients in the less than 130/80 mm Hg group were male, had Medicare insurance, had lower baseline systolic and/or diastolic blood pressures, and had a higher Chronic Disease Score compared with the other groups. For every additional clinic visit, there was a 3% increased likelihood of attaining a blood pressure below 130/80 mm Hg (adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01‐1.04). Patients experiencing a cardiac event during the follow‐up period were approximately twice as likely to attain a blood pressure below 130/80mm Hg (OR 1.97, 95% CI 1.04‐3.77) compared with those who did not have a subsequent event.Conclusion. Despite systematic and aggressive treatment of blood pressure in patients with CAD and uncontrolled blood pressure, a minority of patients attained a blood pressure of less than 130/80 mm Hg. Considering that higher utilization of the health care system was associated with reaching this blood pressure level and that a similar number of therapeutic interventions in the groups resulted in variable success for blood pressure lowering, attaining a blood pressure level of less than 130/80 mm Hg may be difficult for some patients with CAD.
Oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes exposed to clomazone (in vitro)
Authors: Santi Adriana , Menezes Charlene , Duarte Marta , Leitemperger Jossiele , Lópes Thais , Loro Vania 
Published: October 2011

Oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes exposed to clomazone (in vitro)The aim of this study was to investigate the effect of clomazone herbicide on oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes inin vitroconditions. The activity of catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE), as well as the levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were measured in human erythrocytes exposed (in vitro) to clomazone at varying concentrations in the range of 0, 100, 250 and 500 μg/L for 1 h at 37°C. TBARS levels were significantly higher in erythrocytes incubated with clomazone at 100, 250 and 500 μg/L. However, erythrocyte CAT and AChE activities were decreased at all concentrations tested. SOD activity was increased only at 100 μg/L of clomazone. GSH levels did not change with clomazone exposure. These results clearly showed clomazone to induce oxidative stress and AChE inhibition in human erythrocytes (in vitro). We, thus, suggest a possible role of ROS on toxicity mechanism induced by clomazone in humans.
Evaluation of selenium status and its distribution in organs of free living foxes (Vulpes vulpes) from an Se deficient area
Authors: Pilarczyk B. , Pilarczyk R. , Tomza-Marciniak A. , Hendzel D. , Bąkowska M. , Stankiewicz T. 
Published: October 2011

Evaluation of selenium status and its distribution in organs of free living foxes (Vulpes vulpes) from an Se deficient area
The objective of the study was to determine selenium status and its distribution in the organs of free living foxes from selenium deficient areas of north-western Poland. Samples of organs harvested from 40 foxes shot during the 2008-2009 hunting seasons served as experimental material. Selenium concentration in the organs was determined spectrofluorometrically. Selenium distribution in tissues depends largely on its dietary content. Our study indicated that concentrations of selenium in the examined organs followed the order: kidney>liver>spleen>lung>heart and kidneys were the organ with the highest retention of this element. Mean selenium concentration in fox kidneys was 0.60 ± 0.15 μg/g wet weight. Several times less selenium on average was found in the liver (0.27 plusmn; 0.09 μg/g w.w.), lungs (0.17 ± 0.06 μg/g w.w.), spleen (0.19 ± 0.06 μg/g w.w.) and heart (0.13 ± 0.05 μg/g w.w.). All the animals studied were deficient in selenium.
Paleolimnology of Lake Yamanaka as reflected on particle-size distribution
Authors: Adhikari Danda Pani 
Published: October 2011

A 17.63 m long bore-hole core extracted from the deepest part of Lake Yamanaka, one of the Fuji-five Lakes at the northeasternfoot of Mount Fuji, central Japan, composed of sediment with intercalations of scoria fallout deposits. The sediment of the upper11.4 m was investigated for grain-size distribution by using a laser diffraction particle size analyser. The mean grain-size profileshowed various degrees of fluctuations, both short-and long-terms, and the size-frequency distribution revealed unimodal-trimodalmixing of sediments. Changes in lake size and water depth appear to be the main factors affecting the variability in the grain-sizedistribution and properties. The lake level appears low during 7000–5000 cal BP and 2800–1150 cal BP and relatively high during5000–2800 cal BP and 1150 cal BP– present.DOI: http://dx.doi.org/10.3126/bdg.v14i0.5437Bulletin of the Department of Geology Vol.14 2011, pp.35-42