Inhibition of Tendon Cell Proliferation and Matrix Glycosaminoglycan Synthesis by Non-Steroidal Anti-Inflammatory Drugs in vitro

The purpose of this study was to investigate the effects of some commonly used non-steroidal anti-inflammatory drugs (NSAIDs) on human tendon. Explants of human digital flexor and patella tendons were cultured in medium containing pharmacological concentrations of NSAIDs. Cell proliferation was measured by incorporation of 3H-thymidine and glycosaminoglycan synthesis was measured by incorporation of 35S-Sulphate. Diclofenac and aceclofenac had no significant effect either on tendon cell proliferation or glycosaminoglycan synthesis. Indomethacin and naproxen inhibited cell proliferation in patella tendons and inhibited glycosaminoglycan synthesis in both digital flexor and patella tendons. If applicable to the in vivo situation, these NSAIDs should be used with caution in the treatment of pain after tendon injury and surgery

Transport of Cosmic Rays in Chaotic Magnetic Fields

The transport of charged particles in disorganised magnetic fields is an important issue which concerns the propagation of cosmic rays of all energies in a variety of astrophysical environments, such as the interplanetary, interstellar and even extra-galactic media, as well as the efficiency of Fermi acceleration processes. We have performed detailed numerical experiments using Monte-Carlo simulations of particle propagation in stochastic magnetic fields in order to measure the parallel and transverse spatial diffusion coefficients and the pitch angle scattering time as a function of rigidity and strength of the turbulent magnetic component. We confirm the extrapolation to high turbulence levels of the scaling predicted by the quasi-linear approximation for the scattering frequency and parallel diffusion coefficient at low rigidity. We show that the widely used Bohm diffusion coefficient does not provide a satisfactory approximation to diffusion even in the extreme case where the mean field vanishes. We find that diffusion also takes place for particles with Larmor radii larger than the coherence length of the turbulence. We argue that transverse diffusion is much more effective than predicted by the quasi-linear approximation, and appears compatible with chaotic magnetic diffusion of the field lines. We provide numerical estimates of the Kolmogorov length and magnetic line diffusion coefficient as a function of the level of turbulence. Finally we comment on applications of our results to astrophysical turbulence and the acceleration of high energy cosmic rays in supernovae remnants, in super-bubbles, and in jets and hot spots of powerful radio-galaxies.Comment: To be published in Physical Review D, 20 pages 9 figure

Synthesis of new chiral organosulfur donors with hydrogen bonding functionality and their first charge transfer salts

The syntheses of a range of enantiopure organosulfur donors with hydrogen bonding groups are described including TTF related materials with two, four, six and eight hydroxyl groups and multiple stereogenic centres and a pair of chiral N-substituted BEDT-TTF acetamides. Three charge transfer salts of enantiopure poly-hydroxy-substituted donors are reported, including a 4:1 salt with the meso stereoisomer of the dinuclear [Fe2(oxalate)5 ]4- anion in which both cation and anion have chiral components linked together by hydrogen bonding, and a semiconducting salt with triiodide

Pair Plasma Dominance in the Parsec-Scale Relativistic Jet of 3C345

We investigate whether a pc-scale jet of 3C345 is dominated by a normal plasma or an electron-positron plasma. We present a general condition that a jet component becomes optically thick for synchrotron self-absorption, by extending the method originally developed by Reynolds et al. The general condition gives a lower limit of the electron number density, with the aid of the surface brightness condition, which enables us to compute the magnetic field density. Comparing the lower limit with another independent constraint for the electron density that is deduced from the kinetic luminosity, we can distinguish the matter content. We apply the procedure to the five components of 3C345 (C2, C3, C4, C5, and C7) of which angular diameters and radio fluxes at the peak frequencies were obtainable from literature. Evaluating the representative values of Doppler beaming factors by their equipartition values, we find that all the five components are likely dominated by an electron-positron plasma. The conclusion does not depend on the lower cutoff energy of the power-law distribution of radiating particles.Comment: 17 page

Geo-additive models of Childhood Undernutrition in three Sub-Saharan African Countries

We investigate the geographical and socioeconomic determinants of childhood undernutrition in Malawi, Tanzania and Zambia, three neighboring countries in Southern Africa using the 1992 Demographic and Health Surveys. We estimate models of undernutrition jointly for the three countries to explore regional patterns of undernutrition that transcend boundaries, while allowing for country-specific interactions. We use semiparametric models to flexibly model the effects of selected so-cioeconomic covariates and spatial effects. Our spatial analysis is based on a flexible geo-additive model using the district as the geographic unit of anal-ysis, which allows to separate smooth structured spatial effects from random effect. Inference is fully Bayesian and uses recent Markov chain Monte Carlo techniques. While the socioeconomic determinants generally confirm what is known in the literature, we find distinct residual spatial patterns that are not explained by the socioeconomic determinants. In particular, there appears to be a belt run-ning from Southern Tanzania to Northeastern Zambia which exhibits much worse undernutrition, even after controlling for socioeconomic effects. These effects do transcend borders between the countries, but to a varying degree. These findings have important implications for targeting policy as well as the search for left-out variables that might account for these residual spatial patterns

Setting the stage: social-environmental and motivational predictors of optimal training engagement

In this paper, we will firstly explore the central tenets of SDT. Research that has examined the social-environmental and motivation-related correlates of optimal training, performance and health-related engagement through the theoretical lens of SDT will be reviewed. Drawing from SDT-driven work undertaken in educational, sport and dance settings, we will draw conclusions and suggest future directions from a research and applied perspective

Conditional Reverse Tet-Transactivator Mouse Strains for the Efficient Induction of TRE-Regulated Transgenes in Mice

Tetracycline or doxycycline (dox)-regulated control of genetic elements allows inducible, reversible and tissue specific regulation of gene expression in mice. This approach provides a means to investigate protein function in specific cell lineages and at defined periods of development and disease. Efficient and stable regulation of cDNAs or non-coding elements (e.g. shRNAs) downstream of the tetracycline-regulated element (TRE) requires the robust expression of a tet-transactivator protein, commonly the reverse tet-transactivator, rtTA. Most rtTA strains rely on tissue specific promoters that often do not provide sufficient rtTA levels for optimal inducible expression. Here we describe the generation of two mouse strains that enable Cre-dependent, robust expression of rtTA3, providing tissue-restricted and consistent induction of TRE-controlled transgenes. We show that these transgenic strains can be effectively combined with established mouse models of disease, including both Cre/LoxP-based approaches and non Cre-dependent disease models. The integration of these new tools with established mouse models promises the development of more flexible genetic systems to uncover the mechanisms of development and disease pathogenesis

A Phase II Trial of Lutikizumab, an Anti–Interleukin‐1α/β Dual Variable Domain Immunoglobulin, in Knee Osteoarthritis Patients With Synovitis

Objective: To assess the efficacy and safety of the anti–interleukin‐1α/β (anti–IL‐1α/β) dual variable domain immunoglobulin lutikizumab (ABT‐981) in patients with knee osteoarthritis (OA) and evidence of synovitis. Methods: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2–3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI‐assessed synovitis at week 26. Results: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab‐treated and placebo‐treated patients. Changes from baseline in MRI‐assessed synovitis at week 26 and other key symptom‐ and most structure‐related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high‐sensitivity C‐reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations. Conclusion: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL‐1 inhibitors, suggest that IL‐1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis

The effects of an experimental programme to support students’ autonomy on the overt behaviours of physical education teachers

Although the benefits of autonomy supportive behaviours are now well established in the literature, very few studies have attempted to train teachers to offer a greater autonomy support to their students. In fact, none of these studies has been carried out in physical education (PE). The purpose of this study is to test the effects of an autonomy-supportive training on overt behaviours of teaching among PE teachers. The experimental group included two PE teachers who were first educated on the benefits of an autonomy supportive style and then followed an individualised guidance programme during the 8 lessons of a teaching cycle. Their behaviours were observed and rated along 3 categories (i.e., autonomy supportive, neutral and controlling) and were subsequently compared to those of three teachers who formed the control condition. The results showed that teachers in the experimental group used more autonomy supportive and neutral behaviours than those in the control group, but no difference emerged in relation to controlling behaviours. We discuss the implications for schools of our findings

Landau levels in the case of two degenerate coupled bands: kagome lattice tight-binding spectrum

The spectrum of charged particles hopping on a kagome lattice in a uniform transverse magnetic field shows an unusual set of Landau levels at low field. They are unusual in two respects: the lowest Landau levels are paramagnetic so their energies decrease linearly with increasing field magnitude, and the spacings between the levels are not equal. These features are shown to follow from the degeneracy of the energy bands in zero magnetic field. We give a general discussion of Landau levels in the case of two degenerate bands, and show how the kagome lattice tight-binding model includes one special case of this more general problem. We also discuss the consequences of this for the behavior of the critical temperature of a kagome grid superconducting wire network, which is the experimental system that originally motivated this work.Comment: 18 pages, 8 figure