Objective To review patterns of publication of clinical trials funded by US National Institutes of Health (NIH) in peer reviewed biomedical journals indexed by Medline.Design Cross sectional analysis. Conclusions Despite recent improvement in timely publication, fewer than half of trials funded by NIH are published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. Moreover, after a median of 51 months after trial completion, a third of trials remained unpublished.

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The well accepted "free drug hypothesis" for small-molecule drugs assumes that only the free (unbound) drug concentration at the therapeutic target can elicit a pharmacologic effect. Unbound (free) drug concentrations in plasma are readily measurable and are often used as surrogates for the drug concentrations at the site of pharmacologic action in pharmacokinetic-pharmacodynamic analysis and clinical dose projection in drug discovery. Furthermore, for permeable compounds at pharmacokinetic steady state, the free drug concentration in tissue is likely a close approximation of that in plasma; however, several factors can create and maintain disequilibrium between the free drug concentration in plasma and tissue, leading to free drug concentration asymmetry. These factors include drug uptake and extrusion mechanisms involving the uptake and efflux drug transporters, intracellular biotransformation of prodrugs, membrane receptor-mediated uptake of antibody-drug conjugates, pH gradients, unique distribution properties (covalent binders, nanoparticles), and local drug delivery (e.g., inhalation). The impact of these factors on the free drug concentrations in tissues can be represented by K p,uu , the ratio of free drug concentration between tissue and plasma at steady state. This review focuses on situations in which free drug concentrations in tissues may differ from those in plasma (e.g., K p,uu > or <1) and discusses the limitations of the surrogate approach of using plasmafree drug concentration to predict free drug concentrations in tissue. This is an important consideration for novel therapeutic modalities since systemic exposure as a driver of pharmacologic effects may provide limited value in guiding compound optimization, selection, and advancement. Ultimately, a deeper understanding of the relationship between free drug concentrations in plasma and tissues is needed.

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We present the superconducting properties and phase compositions of Mg 1Ϫx Zr x B 2 bulk samples fabricated by a solid-state reaction at ambient pressure. It is found that a small amount of Zr atoms may be introduced into the lattice of MgB 2 , while the majority of them forms ZrB 2 phase. The Mg 0.9 Zr 0.1 B 2 sample shows the highest J C of 2.1ϫ10 6 A/cm 2 in 0.56 T at 5 K and 1.83ϫ10 6 A/cm 2 in self-field at 20 K, higher irreversibility field and larger upper critical field in MgB 2 bulk samples. The combination of good grain connection, the reduction of grain size and small ZrB 2 particles in the sample may be responsible for the significant enhancement of J C in Zr-doped samples. This technique has a great potential to prepare high performance MgB 2 bulk samples and wires on an industrial scale.

Due to the inconvenience of application, risk of extra damage to fragile soft tissues, and the high incidence of latestage complications, significant research endeavors have been focused on developing safe and effective bioadhesives to replace or assist the traditional suture techniques for wound closure. Here, we describe a fast and high strength bioadhesive based on polysaccharides and peptide dendrimers (OCMC/G3KP) with inherent hemostatic ability and antibacterial properties. Compared with the commercial bioadhesive Coseal, the OCMC/G3KP hydrogel shows a remarkable 5-fold increase in adhesion strength. The in vivo studies further confirm the superior wound healing performance of the OCMC/G3KP hydrogel in contrast with Coseal and conventional sutures. The OCMC/G3KP hydrogels are efficient and biocompatible bioadhesives with precise controllability that could be flexibly modulated to meet diverse clinical demands.