1,721,463 research outputs found

    Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid Stem Cells from Myelomeningocele

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    Myelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the backbone and spinal canal do not close completely during early embryonic development. This condition results in serious morbidity and increased mortality after birth. Folic acid significantly reduces, and conversely, folate antagonist methotrexate (MTX) and valproic acid (VPA) increase the occurrence of NTDs, including MMC. How these pharmacological agents exactly influence the early neurulation process is still largely unclear. Here, we characterized human amniotic fluid-derived stem cells (AFSCs) from prenatally diagnosed MMC and observed an effect of MTX and VPA administration on the early neural differentiation process. We found that MMC-derived AFSCs highly expressed early neural and radial glial genes that were negatively affected by MTX and VPA exposure. In conclusion, we setup a human cell model of MMC to study early neurogenesis and for drug screening purposes. We also proposed the detection of early neural gene expression in AFSCs as an additional MMC diagnostic tool

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Concerning the timing of antibiotic administration in women undergoing caesarean section: a systematic review and meta-analysis

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    Objective To assess the effects on maternal infectious morbidity and neonatal outcomes of the timing of antibiotic prophylaxis in women undergoing caesarean section. A recent National Institute for Health and Clinical Excellence (NICE) guideline reported that antibiotic administration before skin incision reduces the risk of maternal infection; this recommendation was based on a meta-analysis, however one including trials that were not double blind and not including a trial published recently. Design Systematic review and meta-analysis. Data sources Searches of PubMed and EMBASE and reference lists of the retrieved articles. Inclusion criteria Randomised double-blind controlled trials comparing the administration of antibiotics before skin incision with administration after cord clamping. Data extraction and analysis Data on maternal total infectious morbidity, endometritis and wound infection, as well as neonatal intensive care unit admission, neonatal infection and neonatal sepsis were extracted and combined using random effects meta-analysis. Results Five studies reporting on 1777 parturients were included in our systematic review. The relative risk (RR) for maternal total infectious morbidity for antibiotic administration before incision compared with antibiotic administration after cord clamping was 0.64 (95% CI 0.36 to 1.15). Likewise, there was no difference in the risk of wound infection (RR 0.72, 95% CI 0.41 to 1.27). Parturients receiving the antibiotic preoperatively had a significantly reduced risk of endometritis (RR 0.48, 95% CI 0.27 to 0.87; number needed to treat 41, 95% CI 23 to 165). Analyses of the neonatal outcome parameters revealed no differences between the regimens of antibiotic administration, but were based on few studies. Conclusions In contrast to a recent NICE guideline, we did not find a reduction in total infectious morbidity with antibiotic administration before skin incision; we confirmed a reduction in the risk of endometritis and a lack of effect on the risk for wound infection

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    Het verminderen van invasiviteit van herstel van foetale spina bifida - naar nieuwe technieken

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    Though not a lethal condition, the prenatal correction of open spina bifida aperta (SBA) was proposed, because it could halt its in utero progressive nature hence prevent severe postnatal morbidity. In 1995, fetal surgery was proven safe and effective in the fetal lamb model. After initial exploratory clinical trials demonstrating feasibility and safety, in 2011 the randomized clinical trial (Management Of Myelomeningocele Study, MOMS) demonstrated the efficacy of midgestational anatomical SBA fetal repair. Prenatal, rather than postnatal repair, reduces the brain shunt rate at 12 months, increases the likelihood of walking at 30 months and reduces intermittent catheterization rates at school age. This comes at the expense of an increased risk for prematurity and maternal morbidity, both in the index and subsequent pregnancies. The hysterotomy, through which the procedure is done, is responsible in subsequent pregnancies for a 10% risk of rupture with concomitant fetal death in nearly one in two cases. To reduce these side effects, the concept of fetoscopic SBA repair was reintroduced. Though theoretically attractive, we thought we could not embrace it clinically without proper preclinical validation. We first conducted a systematic review in chapter 4 showing that in fetal lambs, a two-layer SBA repair through hysterotomy is safe and effective. However, functional assessment methods were lacking in this model, and the lesion was induced in different ways and used to study either the effects on the spinal cord or the brain. In chapter 5, we showed that motor evoked potentials recording and analysis in neonatal lambs is feasible and can reliably assess neuromotor function. Furthermore in chapter 6 we demonstrated that prenatal myelotomy replicates the full phenotype of a lumbar myeloschisis. We eventually reported in chapter 7 that a layered watertight compared to non-watertight fetal repair achieves in this model more neuroprotection and better brain and spinal cord neuromorphology. In preparation for clinical implementation, we investigated whether such watertight repair could be done by fetoscopy. In chapter 8 a systematic review of the clinical literature indicated that, in its early experience, fetoscopy was not safe yet neuroprotective. One factor explaining lack of safety was the use of CO2 for amnio-insufflation, which in lambs induces fetal acidosis and hypercapnia. We therefore assessed the feasibility and safety of fetoscopic repair using humidified and heated CO2. In chapter 9, we showed this was feasible and safe using an anesthetic technique that maintains maternal physiological homeostasis. In parallel, we performed in chapter 10 a meta-analysis to determine the learning curve of open and fetoscopic approaches and assess the need for training. Surgeons reach competency after 35 cases for standard hysterotomy. For percutaneous fetoscopy, competency is not reached prior to 56 cases. We then designed a five-step training program for fetoscopic SBA repair on a pelvic trainer, rabbit cadavers, a high-fidelity model in rabbits, fetal lambs and finally human fetuses. We trained three fetal surgeons and showed in chapter 11 that ≥33 procedures may be necessary to reach competency. Eventually, our fetal team successfully performed three human fetoscopic SBA repair and propose to implement this training program more broadly.status: Publishe
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