1,721,006 research outputs found
Utjecaj različitih soli visoko permeabilne slabe baze doksazosina na oralnu apsorpciju
Get PDFIn this study, the usefulness of biorelevant in vitro data and of canine data in forecasting early exposure after the
administration of two phases of a BCS Class II compound, i.e., doxazosin base (DB) and its mesylate salt (DM)
was evaluated. DB, DM, and doxazosin hydrochloride (DH) were prepared and extensively characterized.
The solubility of prepared substances was tested in vitro in various media, including human aspirates, using the
shake flask method. Dissolution experiments were performed in simple buffer media and biorelevant media
simulating gastric and intestinal fluids in the fasted and fed state. Pharmacokinetic (PK) studies were performed
in dogs with DB and DM tablets in the fasting and fed state, while the results form human PK study on DM
tablets in the fasted state were available from previous Pliva´s study. Analytical method for determination of
doxazosin in canine plasma was developed and validated using canine samples collected in the fed state in order
to assure the suitability of the method for measurement of low concentrations of doxazosin in plasma and high
specificity of the method despite the number of interfering compounds in the fed state plasma samples.
Solubilities of DB and DM in human gastric fluid were forecasted by data in fasted state simulating gastric fluid
containing physiological components (FaSSGF-V2) but not by data in HClpH 1.8. Unlike data in FaSSGF-V2,
dissolution of DB and DM tablets in HClpH 1.6 is rapid. Dissolution of DB tablet in FaSSGF-V2 is incomplete and
conversion to DH seems to occur. Differences between DB and DM in dissolution in the small intestine are
overestimated in the absence of physiological solubilizers. Using the in vitro data and previously described
modelling procedures, the cumulative doxazosin profile in plasma was simulated and the 0–2 h profile was used
for evaluating early exposure. Individual cumulative doxazosin profiles in plasma, after single DM tablet
administrations to 24 adults in fasting state, were constructed from corresponding actual plasma profiles.
Compared with in vitro DM data in aqueous buffers, DM data in biorelevant media led to better prediction of
early exposure. Based on intersubject variability in early exposure after DM administration and simulated
profiles, the administered phase, DB or DM, does not have a significant impact on early exposure in fasting
state. Early exposure in dogs (evaluated based on partial AUCs) was significantly higher after administration of
DM to dogs. Therefore, dog is not a good model for predicting differences between DB or DM in the fasted
state, but it may be a good model for predicting food effects and differences between DB and DM in the fed
state.Glavni ciljevi ovog rada bili su istražiti da li postoje razlike u apsorpciji između lipofilne slabe baze doksazosina
(DB) i njegove mesilatne soli (DM), procijeniti sposobnost predviđanja tih razlika kod ljudi temljem in vitro
podataka, te in vivo podataka dobivenih farmakokinetskom studijom na psima. Obzirom da baze i nehidrokloridne
soli mogu prelaziti u hidrokloridne soli u kiselom mediju želuca, pored DB i DM pripremljena je,
karakterizirana i in vitro ispitana i hidrokloridna sol doksazosina (DH). Topljivost pripremljenih supstancija
ispitana je in vitro u različitim medijima metodom zasićene otopine. Brzina oslobađanja ispitana je u
jednostavnim vodenim puferima kao i biorelevantnim medijima koji simuliraju želučane i crijevne tekućine sa i
bez hrane.
Farmakokinetičke studije na psima napravljene su sa DB i DM 2 mg tabletama, sa i bez hrane, dok su rezultati
studije na zdravim dobrovoljcima nakon primjene 2 mg DM tableta bez hrane bile raspoložive iz prijašnje
Plivine studije. Analitička metoda za određivanje doksazosina u psećoj plazmi razvijena je i validirana koristeći
pseću plazmu prikupljenu u studiji s hranom, s obzirom da se u tom slučaju očekuju niže koncentracije lijeka te
veći broj interferirajućih spojeva u plazmi koji bi mogli narušavati specifičnost bioanalitičke metode.
Rezultati in vitro ispitivanja pokazuju da je topljivost DB i DM u humanom želučanom soku moguće bolje
predvidjeti koristeći biorelevantni medij (FaSSGF-V2) nego razrijeđenu kiselinu HClpH1.8. Također je pokazano
da je brzina oslobađanja doksazosina iz DB i DM tableta puno brža u HClpH1.6 nego u FaSSGF-V2. Nepotpuno
oslobađanje aktivne supstancije iz DB tableta u FaSSGF-V2 ukazuje na prelazak DB u DH. Rezultati također
pokazuju da su u odsustvu fizioloških solubilizatora, razlike u brzini oslobađanja doksazosina iz DB i DM
tableta u tankom crijevu precijenjene.
Moguće razlike u apsorpciji između DB i DM procijenjene su mjerenjem rane izloženosti, tj. brzine apsorpcije
0–2 h nakon primjene lijeka. Koristeći in vitro podatke, prosječnu bioraspoloživost nakon oralne primjene,
enterohepatičku cirkulaciju doksazosina kod ljudi, te prethodno objavljene parametre in silico modeliranja,
simuliran je kumulativni profil doksazosina u plazmi za DB i DM. Pojedinačni kumulativni profili doksazosina u
plazmi nakon primjene jediničnih 2 mg doza DM tableta u 24 zdrava dobrovoljca, konstruirani su iz
pripadajućih profila u plazmi. Rezultati pokazuju da u slučaju DM tableta, in vitro podaci u biorelevantnim
medijima bolje predviđaju ranu izloženost nego podaci u jednostavnim puferima.
Uzevši u obzir varijabilnost u ranoj izloženosti među pojedincima nakon primjene DM tableta te simulirane
profile za DB i DM, dolazi se do zaključka da vrsta administrirane supstancije (DB ili DM) nema značajnog
utjecaja na ranu izloženost kod ljudi. U studiji s psima se pokazalo da je rana izloženost kod DM bila značajno
viša nego kod DB što upućuje na zaključak da psi nisu prikladan model za procjenu razlika u brzini apsorpcije
između DB i DM kod primjene lijeka bez hrane, no mogli bi biti koristan model za predviđanje utjecaja hrane
kao i razlika između DB i DM nakon primjene lijeka s hranom
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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