Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects

"nBackground and the purpose of the study:The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated. "nMethods: The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC0-72, AUC0-∞, Cmax and Tmax. Similarity factor, dissolution efficiency (DE), and mean dissolution time (MDT) was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT) or fraction of the drug dissolved (FRD) vs fraction of the drug absorbed (FRA). "nResults: Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC0-∞, and Cmax of each two formulations in each bioequivalence studies were within the acceptable range of 80-125%. Differences were not observed between the untransformed Tmax values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50) did not reflect their in vivo properties. Major conclusions: Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in-process quality control of amiodarone tablet formulations

International Trade with Firm Heterogeneity in Factor Shares

This paper presents a trade model with capital and labor as factors of production. The main contribution of this paper is that it considers a new type of firm heterogeneity, which is empirically relevant: firms in this paper differ with respect to their factor shares in production. Therefore, this paper addresses the following four empirical facts on globalization, firms’ factor shares and factor prices: (i) firms within narrowly defined industries exhibit a large degree of heterogeneity in factor shares in production; (ii) exporters are, on average, more capital intensive than non—exporters; (iii) globalization decreases labor’s share in national income; (iv) the larger the share of exporters in the industry, the larger the increase in the industry’s wages due to globalization

Confinement interaction in nonlinear generalizations of the Wick-Cutkosky model

We consider nonlinear-mediating-field generalizations of the Wick-Cutkosky model. Using an iterative approach and eliminating the mediating field by means of the covariant Green function we arrive at a Lagrangian density containing many-point time-nonlocal interaction terms. In low-order approximations of $\phi^3{+}\phi^4$ theory we obtain the usual two-current interaction as well as a three-current interaction of a confining type. The same result is obtained without approximation for a version of the dipole model. The transition to the Hamiltonian formalism and subsequent canonical quantization is performed with time non-locality taken into account approximately. A relativistic three-particle wave equation is derived variationally by using a three-particle Fock space trial state. The non-relativistic limit of this equation is obtained and its properties are analyzed and discussed.Comment: 15 pages, 1 figure, LaTe

Horizontal Multinational Firms, Vertical Multinational Firms and Domestic Investment

We build a dynamic general equilibrium model with 2 countries, horizontal and vertical multinational activity and endogenous domestic and foreign investment. It is found that horizontal multinational activity always leads to a complementary relationship between domestic and foreign investment. Vertical multinational activity, in contrast, leads to either a substitutional or complementary relationship between domestic and foreign investment, depending on the firms' technologies. We test the theoretical implications with a panel of U.S. multinationals and find empirical support

A 6.0-mW 10.0-Gb/s Receiver With Switched-Capacitor Summation DFE

A low-power receiver with a one-tap decision feedback equalization (DFE) was fabricated in 90-nm CMOS technology. The speculative equalization is performed using switched-capacitor-based addition at the front-end sample-hold circuit. In order to further reduce the power consumption, an analog multiplexer is used in the speculation technique implementation. A quarter-rate-clocking scheme facilitates the use of low-power front-end circuitry and CMOS clock buffers. The receiver was tested over channels with different levels of ISI. The signaling rate with BER<10^-12 was significantly increased with the use of DFE for short- to medium-distance PCB traces. At 10-Gb/s data rate, the receiver consumes less than 6.0 mW from a 1.0-V supply. This includes the power consumed in all quarter-rate clock buffers, but not the power of a clock recovery loop. The input clock phase and the DFE taps are adjusted externally

Replicating the Family: The Biopolitics of Involvement Discourses Concerning Relatives in Nursing Home Institutions

The aim of this study was to describe the biopolitics of involvement discourses articulated by nursing staff concerning relatives in nursing home institutions, using a Foucault-inspired discourse analytical approach. Previous research has described how relatives have not been involved in nursing homes on their own terms. This is partly due to a lack of communication and knowledge, but it is also a consequence of an unclear organizational structure. Results from a discourse analysis of six focus group interviews with nursing staff show that the “involvement discourse” in nursing homes can be described as a “new” vs “old” family rhetoric. This rhetoric can be said to uphold, legitimize and provide different subject positions for both nursing staff and relatives concerning the conditions for involvement in nursing homes. As part of a “project of possibility” in elderly care, it may be possible to adopt a critical pedagogical approach among nursing staff in order to educate, strengthen and support them in reflecting on their professional norming and how it conditions the involvement of relatives

Proteomic identification of heterogeneous nuclear ribonucleoprotein L as a novel component of SLM/Sam68 nuclear bodies

Background: Active pre-mRNA splicing occurs co-transcriptionally, and takes place throughout the nucleoplasm of eukaryotic cells. Splicing decisions are controlled by networks of nuclear RNA-binding proteins and their target sequences, sometimes in response to signalling pathways. Sam68 (Src-associated in mitosis 68 kDa) is the prototypic member of the STAR (Signal Transduction and Activation of RNA) family of RNA-binding proteins, which regulate splicing in response to signalling cascades. Nuclear Sam68 protein is concentrated within subnuclear organelles called SLM/Sam68 Nuclear Bodies (SNBs), which also contain some other splicing regulators, signalling components and nucleic acids. Results: We used proteomics to search for the major interacting protein partners of nuclear Sam68. In addition to Sam68 itself and known Sam68-associated proteins (heterogeneous nuclear ribonucleoproteins hnRNP A1, A2/B1 and G), we identified hnRNP L as a novel Sam68-interacting protein partner. hnRNP L protein was predominantly present within small nuclear protein complexes approximating to the expected size of monomers and dimers, and was quantitatively associated with nucleic acids. hnRNP L spatially co-localised with Sam68 as a novel component of SNBs and was also observed within the general nucleoplasm. Localisation within SNBs was highly specific to hnRNP L and was not shared by the closely-related hnRNP LL protein, nor any of the other Sam68-interacting proteins we identified by proteomics. The interaction between Sam68 and hnRNP L proteins was observed in a cell line which exhibits low frequency of SNBs suggesting that this association also takes place outside SNBs. Although ectopic expression of hnRNP L and Sam68 proteins independently affected splicing of CD44 variable exon v5 and TJP1 exon 20 minigenes, these proteins did not, however, co-operate with each other in splicing regulation of these target exons. Conclusion: Here we identify hnRNP L as a novel SNB component. We show that, compared with other identified Sam68-associated hnRNP proteins and hnRNP LL, this co-localisation within SNBs is specific to hnRNP L. Our data suggest that the novel Sam68-hnRNP L protein interaction may have a distinct role within SNBs

Export Growth and Factor Market Competition: Theory and Some Evidence

Empirical evidence suggests that sectoral export growth decreases exporters' survival probability, whereas this is not true for non-exporters. Models with firm heterogeneity in total factor productivity (TFP) predict the opposite. To solve this puzzle, we develop a two{factor framework where firms differ in factor intensities. Thus, export growth increases competition for the factor used intensively by exporters, eliminating some of them, while non-exporters benefit. Interacting heterogeneity in factor shares with heterogeneity in TFP we show that factor market competition reduces the growth in average TFP brought about by trade liberalization..

Antioxidant Activity of Leaves and Fruits of Iranian Conifers

Cupressus semipervirens var. horizontalis, Cupressus semipervirens var. semipervirens, Cupressus semipervirens cv. Cereifeormis, Juniperus communis subsp. hemisphaerica, Juniperus excelsa subsp. excelsa, Juniperus excelsa subsp. polycarpos, Juniperus foetidissima, Juniperus oblonga, Juniperus sabina, Platycladus orientalis and Taxus baccata are Iranian conifers. The antioxidant activity of leaves and fruits of these 11 different taxons were evaluated. The leaves of both male and female, and fruits of these plants were collected from different areas of the country. Methanol extract of leaves and fruits of these taxons were prepared. Antioxidant activity of each extracts was measured using two different tests of the ferric thiocyanate method and thiobarbituric acid. Results indicated that the methanol extracts of leaves, of male and female, and fruits of all these species (27 samples) possessed antioxidant activity when tested with both methods. The antioxidant activity was then compared with those of α-tocopherol (a natural antioxidant) and butylated hydroxytoluene (a synthetic antioxidant). Methanol extract of fruits of C. semipervirens cv. Cereifeormis showed the highest antioxidant activity while the methanol extract of leaves of C. semipervirens var. semipervirens possessed the lowest antioxidant activity. However, our finding showed that most of the tested extracts were showing strong antioxidant activity even higher than α-tocopherol