bluuebunny/crossref_metadata_2025_split huggingface dataset:
A French multicenter randomised trial comparing two dose-regimens of prothrombin complex concentrates in urgent anticoagulation reversal
Authors: Kerebel Delphine , Joly Luc-Marie , Honnart Didier , Schmidt Jeannot , Galanaud Damien , Negrier Claude , Kursten Friedrich , Coriat Pierre ,   Lex206 Investigator Group
Published: January 2013

Abstract
Introduction
Prothrombin complex concentrates (PCC) are haemostatic blood preparations indicated for urgent anticoagulation reversal, though the optimal dose for effective reversal is still under debate. The latest generation of PCCs include four coagulation factors, the so-called 4-factor PCC. The aim of this study was to compare the efficacy and safety of two doses, 25 and 40 IU/kg, of 4-factor PCC in vitamin K antagonist (VKA) associated intracranial haemorrhage.

Methods
We performed a phase III, prospective, randomised, open-label study including patients with objectively diagnosed VKA-associated intracranial haemorrhage between November 2008 and April 2011 in 22 centres in France. Patients were randomised to receive 25 or 40 IU/kg of 4-factor PCC. The primary endpoint was the international normalised ratio (INR) 10 minutes after the end of 4-factor PCC infusion. Secondary endpoints were changes in coagulation factors, global clinical outcomes and incidence of adverse events (AEs).

Results
A total of 59 patients were randomised: 29 in the 25 IU/kg and 30 in the 40 IU/kg group. Baseline demographics and clinical characteristics were comparable between the groups. The mean INR was significantly reduced to 1.2 - and ≤1.5 in all patients of both groups - 10 minutes after 4-factor PCC infusion. The INR in the 40 IU/kg group was significantly lower than in the 25 IU/kg group 10 minutes (P = 0.001), 1 hour (P = 0.001) and 3 hours (P = 0.02) after infusion. The 40 IU/kg dose was also effective in replacing coagulation factors such as PT (P = 0.038), FII (P = 0.001), FX (P <0.001), protein C (P = 0.002) and protein S (0.043), 10 minutes after infusion. However, no differences were found in haematoma volume or global clinical outcomes between the groups. Incidence of death and thrombotic events was similar between the groups.

Conclusions
Rapid infusion of both doses of 4-factor PCC achieved an INR of 1.5 or less in all patients with a lower INR observed in the 40 IU/kg group. No safety concerns were raised by the 40 IU/kg dose. Further trials are needed to evaluate the impact of the high dose of 4-factor PCC on functional outcomes and mortality.

Trial registration
Eudra CT number 2007-000602-73.
Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1
Authors: Nies Anne T , Niemi Mikko , Burk Oliver , Winter Stefan , Zanger Ulrich M , Stieger Bruno , Schwab Matthias , Schaeffeler Elke 
Published: January 2013

Abstract
Background
Organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and OATP2B1 (encoded by SLCO1B1, SLCO1B3, SLCO2B1) mediate the hepatic uptake of endogenous compounds like bile acids and of drugs, for example, the lipid-lowering atorvastatin, thereby influencing hepatobiliary elimination. Here we systematically elucidated the contribution of SLCO variants on expression of the three hepatic OATPs under consideration of additional important covariates.

Methods
Expression was quantified by RT-PCR and immunoblotting in 143 Caucasian liver samples. A total of 109 rare and common variants in the SLCO1B3-SLCO1B1 genomic region and the SLCO2B1 gene were genotyped by MALDI-TOF mass spectrometry and genome-wide SNP microarray technology. SLCO1B1 haplotypes affecting hepatic OATP1B1 expression were associated with pharmacokinetic data of the OATP1B1 substrate atorvastatin (n = 82).

Results
Expression of OATP1B1, OATP1B3, and OATP2B1 at the mRNA and protein levels showed marked interindividual variability. All three OATPs were expressed in a coordinated fashion. By a multivariate regression analysis adjusted for non-genetic and transcription covariates, increased OATP1B1 expression was associated with the coding SLCO1B1 variant c.388A > G (rs2306283) even after correction for multiple testing (P = 0.00034). This held true for haplotypes harboring c.388A > G but not the functional variant c.521T > C (rs4149056) associated with statin-related myopathy. c.388A > G also significantly affected atorvastatin pharmacokinetics. SLCO variants and non-genetic and regulatory covariates together accounted for 59% of variability of OATP1B1 expression.

Conclusions
Our results show that expression of OATP1B1, but not of OATP1B3 and OATP2B1, is significantly affected by genetic variants. The SLCO1B1 variant c.388A > G is the major determinant with additional consequences on atorvastatin plasma levels.
Development of the γ-amino butyric acid (GABA)-ergic signaling system and its role in larval swimming in sea urchin
Authors: Katow Hideki , Abe Kouki , Katow Tomoko , Zamani Alemeh , Abe Hirokazu 
Published: January 2013

Summary
The present study aimed to elucidate the development and γ-amino butyric acid (GABA)-ergic regulation of larval swimming in the sea urchin Hemicentrotus pulcherrimus by cloning, namely, glutamate decarboxylase (Hp-gad), the GABAA receptor (Hp-gabrA), and GABAA receptor-associated protein (Hp-gabarap), and by performing immunohistochemistry. The regulation of larval swimming was increasingly dependent on the GABAergic system, which was active from the 2-day-post-fertilization (dpf) pluteus stage onwards. GABA-immunoreactive cells were detected as a subpopulation of secondary mesenchyme cells during gastrulation and eventually constituted the ciliary band and a subpopulation of blastocoelar cells during the pluteus stage. Hp-gad transcription was detected by reverse transcription-polymerase chain reaction during the period when Hp-Gad-positive cells were seen as a subpopulation of blastocoelar cells and on the apical side of the ciliary band from the 2-dpf pluteus stage. Consistent with these observations, inhibition of GAD with 3-mercaptopropioninc acid inhibited GABA-immunoreactivity and larval swimming dose dependently. Hp-gabrA amplimers were detected weakly in unfertilized eggs and 4-dpf plutei, but strongly from fertilized eggs to 2-dpf plutei, and Hp-GabrA, together with GABA, was localized at the ciliary band in association with dopamine receptor D1 from the 2-arm pluteus stage. Hp-gabarap transcription and protein expression were detected from the swimming blastula stage. GABAA receptor inhibition by bicuculline inhibited larval swimming dose dependently. Inhibition of larval swimming by either 3-mercaptopropionic acid or bicuculline was more severe in older larvae (17-dpf and 34-dpf plutei) than in younger ones (1-dpf prism larvae).
The invisible cues that guide king penguin chicks home. The use of magnetic and acoustic cues during orientation and short-range navigation
Authors: Nesterova Anna P. , Chiffard Jules , Couchoux Charline , Bonadonna Francesco 
Published: January 2013

SummaryKing penguins (Aptenodytes patagonicus) live in large and densely populated colonies, where navigation can be challenging due to the presence of many conspecifics that could obstruct locally available cues. Our previous experiments demonstrated that visual cues were important but not essential for king penguin chicks' homing. The main objective of this study was to investigate the importance of non-visual cues, such as magnetic and acoustic cues, for chicks' orientation and short-range navigation. In a series of experiments, the chicks were individually displaced from the colony to an experimental arena where they were released under different conditions. In the magnetic experiments, a strong magnet was attached to the chicks' heads. Trials were conducted in daylight and at night to test the relative importance of visual and magnetic cues. Our results showed that when the geomagnetic field around chicks was modified, their orientation in the arena and the overall ability to home was not affected. In the low sound experiment we limited the acoustic cues available to the chicks by putting ear pads over their ears, and in the loud sound experiment we provided additional acoustic cues by broadcasting colony sounds on the opposite side of the arena to the real colony. In the low sound experiment, the behavior of the chicks was not affected by the limited sound input. In the loud sound experiment, the chicks reacted strongly to the colony sound. These results suggest that king penguin chicks may use the sound of the colony while orienting towards their home.
Negative gravitactic behavior ofCaenorhabditis japonicadauer larvae
Authors: Okumura Etsuko , Tanaka Ryusei , Yoshiga Toyoshi 
Published: January 2013

SummaryGravity on Earth is a constant stimulus and many organisms are able to perceive and respond to it. However, there is no clear evidence that nematodes respond to gravity. In this study, we demonstrated negative gravitaxis in a nematode using dauer larvae (DL) of Caenorhabditis japonica and form an association with their carrier insect. C. japonica DL demonstrating nictation, a typical host-finding behavior, had a negative gravitactic behavior, whereas non-nictating C. japonica and C. elegans DL did not. The negative gravitactic index of nictating DL collected from younger nematode cultures was higher than that from older cultures. A 24-h incubation of nictating DL in M9 buffer did not alter their negative gravitactic behavior but a longer incubation resulted in less pronounced negative gravitaxis. These results are indicative of negative gravitaxis in nictating C. japonica DL, which is maintained once initiated, seems to be affected by the age of DL, and does not appear to be a simple passive mechanism.
Rapid mitochondrial adjustments in response to short-term hypoxia and re-oxygenation in the Pacific oysterCrassostrea gigas
Authors: Sussarellu Rossana , Dudognon Tony , Fabioux Caroline , Soudant Philippe , Moraga Dario , Kraffe Edouard 
Published: January 2013

SummaryAs oxygen concentrations in marine coastal habitats can fluctuate rapidly and drastically, sessile marine organisms like the oyster Crassostrea gigas can experience marked and rapid oxygen variations. In this study, we investigated the responses of oyster gill mitochondria to short-term hypoxia (3 h and 12 h, at 1.7 mg O2 L-1) and subsequent re-oxygenation. Mitochondrial respiratory rates (state 3 and 4 stimulated by glutamate), phosphorylation efficiency (RCR ratio and ADP/O) were measured. Cytochrome c oxidase activity (CCO) and cytochrome concentrations (a, b, c1, c) were measured to investigate the rearrangements of respiratory chain subunits. The potential implication of an alternative oxidase (AOX) was investigated using an inhibitor of the respiratory chain (antimycin A) and through gene expression analysis in gills and digestive gland. Results indicate a down regulation of mitochondrial capacity, with 60% inhibition of respiratory rates after 12 h of hypoxia. RCR ratio remained stable, while ADP/O increased after 12 h of hypoxia and 1 h of re-oxygenation, suggesting increased phosphorylation efficiency. CCO showed a fast and remarkable increase of its catalytic activity only after 3 h of hypoxia. AOX mRNA levels showed similar patterns in gill and digestive gland, and were up regulated after 12 and 24 h of hypoxia and during re-oxygenation. Results suggest a set of controls in regulating mitochondrial functions in response to oxygen fluctuations and demonstrate the fast and extreme plasticity of oyster mitochondria in response to oxygen variations.
Konstanz und Dynamik
Authors: Klauser Hella 
Published: January 2013

Zusammenfassung:
Vom 12.–15. September 2012 fand in Konstanz der Schweizer Bibliothekskongress BIS (Bibliothek Information Schweiz) 2012 statt. ‚Konstanz und Dynamik – Konstanz versus Dynamik?‘ lautete das Thema, und Bibliotheken und Politik, Informationskompetenz, Vernetzung und Elending wurden in diesem Spannungsfeld diskutiert. Auch um die Zukunft der Bibliotheken ging es. Die Notwendigkeit einer nationalen Gesamtstrategie für die Bibliotheken in der Schweiz wurde bestätigt, verschiedene Sprachräume und die Autonomie der 26 Kantone und Gemeinden bieten keine einfachen Voraussetzungen dazu.
Wie schreibt man Digital Humanities richtig?
Authors: Stäcker Thomas 
Published: January 2013

Zusammenfassung:
Die Digital Humanities sind in aller Munde. Die Beschäftigung mit den digitalen Geisteswissenschaften eröffnet aber nicht nur neue Forschungsgebiete, sondern bringt auch eine neue Art zu schreiben mit sich, weil wissenschaftliche Publikationen selbst Gegenstände der digital humanities sind. Elektronische Publikationen, die im Internet erscheinen, müssen, anders als ihre gedruckten Vorgänger dem Umstand Rechnung tragen, dass man sie nicht nur lesen, sondern maschinell bearbeiten kann. Das hat beträchtliche Auswirkungen auf die Texte, mit denen sich auf diese Weise neue Funktionen verbinden, aber auch auf das akademische Publikationswesen, das sich auf gewandelte Produktions- und Distributionsbedingungen einstellen muss. Der erste Teil des Beitrages widmet sich dieser neuen Art zu schreiben, indem er die technischen und formalen Voraussetzungen für elektronische Publikationen analysiert. Der zweite Teil versucht unter der Überschrift „Open Access – Open Source“ die Anforderungen und Auswirkungen elektronischen Publizierens auf das akademische Publizieren im Ganzen auszuloten.
Bündnisse für Bildung: Große
Verantwortung und Herausforderung
Authors: Zimmermann Olaf 
Published: January 2013

Zusammenfassung:
Unter der gemeinsamen Überschrift „Kultur macht stark“ wurden 35 „Gewinner“, darunter auch der Deutsche Bibliotheksverband e. V. (dbv), gekürt, die in den nächsten fünf Jahren lokale Bündnisse für Bildung verwirklichen werden. Ziel des vom Bundesbildungsministerium ins Leben gerufenen Förderprogramms ist es unter anderem, den in Deutschland ausgeprägten Zusammenhang zwischen Herkunft und Bildungserfolg abzuschwächen. Es gilt, die Stärken der verschiedenen Partner zu erkennen und zu nutzen und so die kulturelle Bildung immer weiter zu entwickeln und zu begleiten. Dazu gehört auch ein Blick auf gescheiterte Vorhaben.
Unwanted sexual experiences among adolescents: shedding light on the gray zone between consensual and non-consensual sex
Authors: Akre Christina , Chabloz Jeanne-Marie , Belanger Richard E. , Michaud Pierre-André , Suris Joan-Carles 
Published: January 2013

Abstract
This study aimed at exploring adolescents’ perceptions of unwanted sexual experiences (USE) in order to set up definitions, categories, and boundaries on the continuum between consensual and non-consensual sex.
Methods: We conducted a qualitative thematic analysis of four focus group discussions gathering a total of 29 male and female adolescents aged 16–20 years.
Results: Analysis of participants’ discourse revealed three main characteristics that define USE, namely, regret, as most situations discussed were said to be acceptable or not in terms of whether there were regrets after the fact; misperception of sexual intent; and lack of communication between partners.
Conclusions: Our findings revealed that health professionals should be aware of the subtle aspects identifying USE when screening for situations that can have adverse psychological consequences. Where prevention is concerned, it appears important to address these aspects of USE in sex education classes.
Detached, distraught or discerning? Fathers of adolescents with chronic illness: a review of the literature
Authors: Goldstein Henry , Akré Christina , Bélanger Richard E. , Suris Joan-Carles 
Published: January 2013

AbstractParenting a child with chronic disease provides a unique set of challenges for both mothers and fathers throughout all phases of the illness. However, fathers of these children are under-represented in existing research. This review focuses on the fathers of children with chronic disease included in 44 original articles. We address the challenges to the father’s role as breadwinner, leader and strength-giver in the family. Three time-periods describe the obstacles fathers tackle when parenting children with chronic disease: a) diagnosis and short-term, characterized by distress, isolation and uncertainty; b) the mastery period, characterized by the struggle to establish routine and by support and spirituality; and c) the long-term, characterized by relationship and personality change, worries and bereavement. Overall, whilst current research has revealed some key themes pertaining to fathers of children with chronic disease, further studies are required to foster the development of support mechanisms for the specific needs of these fathers.
Smaller pelvic size in pregnant adolescents contributes to lower birth weight
Authors: Alves João G. , Siqueira Lídia C. , Melo Luiza M. , Figueiroa José N. 
Published: January 2013

Abstract
Adolescent pregnancy is associated with low birth weight. This has been explained by socioeconomic or emotional factors. However, an adolescent’s pelvis may not be completely developed and this can contribute to impairing fetal growth. Our aim was to compare the relationship between pelvic size and birth weight among adolescents and adult mothers. A cross-sectional study was carried out at Instituto de Medicina Infantil Professor Fernando Figueira (IMIP), Brazil. We studied 125 healthy adolescents and 207 healthy adult women, all of whom were primiparous with a singleton term and low-risk pregnancy. The conjugate, intercristal and interspinous diameters were assessed by the Collins pelvimeter. The effect of pelvic size on the birth weight was evaluated using principal component analysis and multiple linear regression model. The mean pelvic size was smaller in adolescent mothers compared to adult ones (35.1 cm vs. 37.5 cm; p<0.001; t-test). After adjusting for other confounding variables, the predicted birth weights corresponding to these mean values of pelvic size were: 3020±27 g for adolescent mothers and 3145±26 g for adult mothers and showed a significant difference (p<0.001). We concluded that a pelvis that is less than fully developed in adolescents, as assessed by pelvic size, may contribute to lower birth weight in adolescent mothers.
Structure-property relationship of biodegradable poly(butylene succinate)/polycaprolactone coated inorganic particle composites
Authors: Liu Yiming , Liu Qing , Meng Bing , Wu Zhihua 
Published: January 2013

Abstract
Polycaprolactone (PCL)-coated micro kaolin and nano-titania were prepared by high-speed hybrid mechanical coating. Poly(butylene succinate) (PBS)-coated inorganic particle composites were prepared by the melt-blending process. The influence of coated kaolin microparticles on the dynamic rheological behavior, non-isothermal crystallization behavior, micromorphology, and mechanical behavior were investigated. The effect of coated nano-titania on the mechanical properties of PBS-coated kaolin composites was also studied. A dynamic rheological property indicates that the complex viscosity of PBS-coated kaolin microcomposites is higher than neat PBS. Differential scanning calorimetry (DSC) implies that the micrometric size of kaolin particles restrains the crystallization of PBS. Scanning electronic microscopy (SEM) reveals a well dispersed state of coated kaolin in the polymer matrix. The impact strength of PBS-coated kaolin microcomposites is improved, while the tensile strength and elongation at break is decreased, but still appreciable. The introduction of coated nano-titania improves the impact strength dramatically, and the elongation at break of composites is considerable.
Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study
Authors: Schmidt Ulla , Nygaard Birte , Jensen Ebbe Winther , Kvetny Jan , Jarløv Anne , Faber Jens 
Published: January 2013

BackgroundA recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.HypothesisPeripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy.MethodsSerum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication.ResultsTSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups.ConclusionsT4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.
Gene Copy-Number Variation in Haploid and Diploid Strains of the Yeast Saccharomyces cerevisiae
Authors: Zhang Hengshan , Zeidler Ane F B , Song Wei , Puccia Christopher M , Malc Ewa , Greenwell Patricia W , Mieczkowski Piotr A , Petes Thomas D , Argueso Juan Lucas 
Published: January 2013

Abstract
The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rates orders of magnitude higher than base substitutions, yet our understanding of the mechanisms leading to CNVs has been lagging. We examined CNV in a region of chromosome 5 (chr5) in haploid and diploid strains of Saccharomyces cerevisiae. We optimized a CNV detection assay based on a reporter cassette containing the SFA1 and CUP1 genes that confer gene dosage-dependent tolerance to formaldehyde and copper, respectively. This optimized reporter allowed the selection of low-order gene amplification events, going from one copy to two copies in haploids and from two to three copies in diploids. In haploid strains, most events involved tandem segmental duplications mediated by nonallelic homologous recombination between flanking direct repeats, primarily Ty1 elements. In diploids, most events involved the formation of a recurrent nonreciprocal translocation between a chr5 Ty1 element and another Ty1 repeat on chr13. In addition to amplification events, a subset of clones displaying elevated resistance to formaldehyde had point mutations within the SFA1 coding sequence. These mutations were all dominant and are proposed to result in hyperactive forms of the formaldehyde dehydrogenase enzyme.