121,825 research outputs found
Chemical Derivatization of Sulfated Glycosaminoglycans
No full textSulfated glycosaminoglycans (GAGs) are a family of complex polysaccharides ubiquitously distributed in extracellular matrices and at cell surfaces and playing key roles in a myriad of biological processes. Their structures are based on disaccharide building blocks, usually containing an amino sugar and an uronic acid, decorated with one or more sulfate groups. Many efforts to gain access to a large number of sulfated GAG polysaccharides with potential tailored biomedical applications, usually based on suitable chemical (and chemo-enzymatic) derivatization procedures that modified the native polysaccharide structures, have been reported in the last two decades. In this review we survey such reactions on the basis of (i) the sulfated GAG substrate [(fucosylated) chondroitin sulfate, dermatan sulfate, heparin, and heparan sulfate], and (ii) the sort of structural modification (sulfation pattern modification, oxidation, carboxy group derivatization, N- and O-acylation, reducing-end functionalization)
Pharmacokinetics of oral anticoagulants in patients with atrial fibrillation and extreme obesity
No full textPurpose: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. Methods: We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs’ peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs’ plasma concentration out of the expected range. Findings: A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9 patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. Implications: Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
The vanishing author in computer-generated works: a critical analysis of recent Australian case law
No full textAbstract
The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals
Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi-synthetic chondroitin sulfate
No full texttMicrobial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccha-ride by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for itsregioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfationpatterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possess-ing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc)units could be obtained through the two-pots route, whereas the one-pot pathway allowed an additionalsulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabi-lization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA andGalNAc, respectively, when the benzylidene-acetylation reactions were conducted in a one-pot fashion.Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moietieswas accomplished
The clinical presentation of syncope influences the head-up tilt test responses
No full textIntroduction: Little is still known about the positivity rate of nitroglycerin (NTG) potentiated head-up tilt test (HUTT) according to the history-based clinical features of syncope. The study aimed to compare the HUTT positivity rate and type of responses in patients with classical and non-classical vasovagal syncope (VVS). Materials and Methods: We retrospectively evaluated all consecutive patients who underwent NTG-potentiated HUTT for VVS. The study population was dichotomized into classical and non-classical VVS. Results: A total of 1285 VVS patients (45± 19.1 years; 49.6% male) were enrolled: 627 (48.8%) had a history of classical VVS and 658 (51.2%) of non-classical VVS. HUTT was positive in 866 (67.4%) patients. The positivity rate was significantly higher in patients with classical compared to those with non-classical VVS (81.5% vs 54%; P< 0.0001). Cardioinhibitory response showed similar total positivity rate (27.6% vs 31%; P= 0.17), but higher relative prevalence among positive tests (57.7% vs 33.9%, P< 0.0001) in patients with non-classical VVS. At multivariable analysis, classical reflex syncope, male sex, history of traumatic syncope and use of diuretics were independent predictors of HUTT positivity. Conclusion: The clinical presentation of syncope influences the overall HUTT positivity rate and the type of responses. Cardioinhibitory response and traumatic syncope are more likely in patients with non-classical VVS
- …
