1,722,049 research outputs found
If inhibition: breaking new ground in the treatment of stable coronary artery disease
No full textoronary artery disease (CAD) is today the leading cause of mortality
worldwide, and it continues to be a major burden upon public health.1
Despite falling CAD mortality rates in Western European countries, the
number of CAD patients may actually be increasing as a result of aging
populations and the improving prognosis for coronary patients, the latter due to
more effective treatments for acute coronary syndrome and revascularization,
and improved prevention.2 CAD is expected to remain the world's leading cause of
disease burden (which represents aggregate mortality and morbidity) in 2020, despite
considerable progress in prevention and treatment over the past 20 years.3
Despite marked advances in primary and secondary prevention, several unmet
needs remain in CAD management. Current guidelines recommend a two-pronged
management strategy for patients with stable CAD, who require one treatment to
relieve symptoms alongside another to reduce long-term morbidity and mortality.4
Despite the progress in the field, for various reasons that include inappropriate drug
dosage and patient nonadherence to treatment schedules, many patients in clinical
practice do not reach therapeutic goals. In addition, the optimization of treatment
can be hindered by insufficient efficacy in patients with refractory angina and
by a long list of medication contraindications. Another factor is poor tolerability,
which may lead to treatment discontinuation and a reduction in the efficacy of even
the most rigorous management strategy.
The results of the Clinical Outcomes Utilizing Revascularization and Aggressive
druG Evaluation (COURAGE) trial show no extra benefit in terms of all-cause mortality,
myocardial infarction, or other major cardiovascular events, with addition of
percutaneous coronary intervention (PCI) in stable CAD patients receiving optimized
medical therapy.5 Furthermore, interventions are not always possible, and most
revascularized patients still require anti-ischemic/antianginal treatment after the
procedure.
Clearly, these factors indicate the importance of developing novel therapeutic
approaches that can improve CAD management. Heart rate is one of the clinical
parameters that is most frequently assessed in daily practice. As it is the main determinant
of ischemia, heart rate reduction is an established important therapeutic
strategy in the prevention of ischemia. A strong association between elevated heart
rate and increased risk of total and cardiovascular mortality has been shown in the
general population, as well as in patients with hypertension, diabetes, and CAD.6
Experimental data have demonstrated the involvement of heart rate in the development and progression of atherosclerosis.7 Consistent
with this understanding of the important role of heart rate,
ivabradine (Procoralan), the first selective and specific If inhibitor,
opens up promising opportunities in the management
of CAD
Alternate-strand DNA triple-helix formation using short acridine-linked oligonucleotides
Full text linkWe have used DNAase I footprinting to examine the formation of intermolecular DNA triple helices at sequences containing adjacent blocks of purines and pyrimidines. The target sites G6T6·A6C6 and T6G6·C6A6 were cloned into longer DNA fragments and used as substrates for DNAase I footprinting, which examined the binding of the acridine (Acr)-linked oligonucleotides Acr-T5G5 and Acr-G5T5 respectively. These third strands were designed to incorporate both G·GC triplets, with antiparallel G(n) strands held together by reverse Hoogsteen base pairs, and T·AT triplets, with the two T-containing strands arranged antiparallel to each other. We find that Acr-T5G5 binds to the target sequence G6T6·A6C6, in the presence of magnesium at pH 7.0, generating clear DNAase I footprints. In this structure the central guanine is not recognized by the third strand and is accessible to modification by dimethyl sulphate. Under these conditions no footprint was observed with Acr-G5T5 and T6G6·C6A6, though this triplex was evident in the presence of manganese chloride. Manganese also facilitated the binding of Acr-T5G5to a second site in the fragment containing the sequence T6G6·C6A6. This represents interaction with the sequence G4ATCT6, located at the boundary between the synthetic insert and the remainder of the fragment, and suggests that this bivalent metal ion may stabilize triplexes that contain one or two mismatches. Manganese did not affect the interaction of either oligonucleotide with G6T6·A6C6.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
Full text linkWe 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
Interaction of bleomycin with a bent DNA fragment
No full textThe interaction of bleomycin with a kinetoplast DNA fragment has been examined using various footprinting techniques. This DNA adopts a bent structure and displays an unusually low gel mobility on account of its phased runs of adenines. The bleomycin-cobalt complex increases the mobility of this DNA fragment, in contrast with other DNAs which show a decreased rate of gel migration, suggesting that the antibiotic removes DNA bending, possibly via an unwinding mechanism. Removal of the bending is confirmed by hydroxy-radical footprinting which produces a more even ladder of bands in the presence of the ligand. Cleavage by bleomycin is at the sequence G-pyrimidine, though not all such sites are affected to the same extent and some cutting is found at GA and GG. DNAase I footprinting confirms the antibiotic-binding sites but reveals that some strong cleavage sites do not yield footprints. Bleomycin renders adenines on the 3' side of its cleavage sites (GT, GC and GA) hyper-reactive to diethyl pyrocarbonate.</p
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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