1,720,965 research outputs found
Extra-renal adverse effects of mTOR inhibitors: know them to optimize their use in renal transplantation
The mammalian target of rapamycin inhibitors (mTOR-I) sirolimus and everolimus represents a class of immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2 and PI3K confers the anti-neoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are a valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft damage. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects (e.g., pulmonary toxicity, hematological disorders, dismetabolism, lymphedema) that need to be early diagnosed and treated to avoid severe illness in renal transplant patients. All these side effects are most of the time reversible and dose related. Therefore, it is unquestionable that these particular drugs should be administered at the lowest dose able to maintain relatively low trough levels, in order to increase their importance and specific therapeutic effects minimizing or avoiding drug toxicities. Utilization of low dosages of mTOR-I should be encouraged not only in CNI-combined schemas, but also when administered alone in CNI-free immunosuppressive protocol
Extra-renal adverse effects of mTOR inhibitors: know them to optimize their use in renal transplantation.
The mammalian target of rapamycin inhibitors (mTOR-I) sirolimus and everolimus represents a class of immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR), a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2 and PI3K confers the anti-neoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are a valid option to calcineurine inhibitors (CNIs) for maintenance immunosuppression in renal transplant recipients with chronic allograft damage. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects (e.g., pulmonary toxicity, hematological disorders, dismetabolism, lymphedema) that need to be early diagnosed and treated to avoid severe illness in renal transplant patients. All these side effects are most of the time reversible and dose related. Therefore, it is unquestionable that these particular drugs should be administered at the lowest dose able to maintain relatively low trough levels, in order to increase their importance and specific therapeutic effects minimizing or avoiding drug toxicities. Utilization of low dosages of mTOR-I should be encouraged not only in CNI-combined schemas, but also when administered alone in CNI-free immunosuppressive protocol
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Variations on the Author
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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
Everolimus-associated interstitial pneumonia in a renal transplant patient: a case report
The mTOR inhibitors (mTORi, mammalian target of rapamycin; sirolimus and everolimus) have been recently introduced in clinical practice to improve the therapeutic strategies for maintenance of organ transplant and to slow down the progression of chronic renal failure, thanks to their good immunosuppressive properties and absence of renal toxicity. Additionally, mTORi have some antineoplastic and cardioprotective effects.
At the same time, mTORi have several collateral effects, often dose dependent and generally reversible after cessation or minimization of the drug dosage. In particular, in the last years, sirolimus-associated pulmonary toxicity has been reported.
We describe a clinical case of a young woman with a renal transplant, followed at our Renal Transplant Center, hospitalized for fever and cough unresponsive to antibiotic therapy that, at the time of admission in our renal unit, showed a chest CT scan diagnosis compatible with a drug-related organizing pneumonia or interstitial infiltrates (BOOP).
Based on the above diagnosis, we decided to significantly reduce the mTORi dosage reaching stable trough level of 2.5-3 ug/L.
After few days, we assisted at an improvement of the clinical status, defervescence and reduction of the pulmonary symptoms. Besides, the microbiological and neoplastic laboratory tests performed on bronchial washing were negative.
At day 15, a new chest CT showed a significant reduction of multiple parenchyma areas of thickening. After 3 months, the medical conditions have improved with stable renal function.
Our case report describes an everolimus-related “lung syndrome” successfully treated with a significant minimization of mTORi dosage. Our experience may be useful to help clinicians treating mTORi-related pulmonary complications
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