Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis

<p>Objective: Anti–tumor necrosis factor (anti-TNF) therapies are highly effective in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but a significant number of patients exhibit only a partial or no therapeutic response. Inflammation alters local and systemic metabolism, and TNF plays a role in this. We undertook this study to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents.</p> <p>Methods: Urine was collected from 16 RA patients and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using nuclear magnetic resonance spectroscopy. Discriminating metabolites were identified, and the relationship between metabolic profiles and clinical outcomes was assessed.</p> <p>Results: Baseline urine metabolic profiles discriminated between RA patients who did or did not have a good response to anti-TNF therapy according to European League Against Rheumatism criteria, with a sensitivity of 88.9% and a specificity of 85.7%, with several metabolites contributing (in particular histamine, glutamine, xanthurenic acid, and ethanolamine). There was a correlation between baseline metabolic profiles and the magnitude of change in the Disease Activity Score in 28 joints from baseline to 12 months in RA patients (P = 0.04). In both RA and PsA, urinary metabolic profiles changed between baseline and 12 weeks of anti-TNF therapy. Within the responders, urinary metabolite changes distinguished between etanercept and infliximab treatment.</p> <p>Conclusion: The clear relationship between urine metabolic profiles of RA patients at baseline and their response to anti-TNF therapy may allow development of novel approaches to the optimization of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action.</p&gt

Heavy pseudoscalar mesons in a Schwinger-Dyson--Bethe-Salpeter approach

The mass spectrum of heavy pseudoscalar mesons, described as quark-antiquark bound systems, is considered within the Bethe-Salpeter formalism with momentum-dependent masses of the constituents. This dependence is found by solving the Schwinger-Dyson equation for quark propagators in rainbow-ladder approximation. Such an approximation is known to provide both a fast convergence of numerical methods and accurate results for lightest mesons. However, as the meson mass increases, the method becomes less stable and special attention must be devoted to details of numerical means of solving the corresponding equations. We focus on the pseudoscalar sector and show that our numerical scheme describes fairly accurately the $\pi$, $K$, $D$, $D_s$ and $\eta_c$ ground states. Excited states are considered as well. Our calculations are directly related to the future physics programme at FAIR.Comment: 9 pages, 3 figures; Based on materials of the contribution "Relativistic Description of Two- and Three-Body Systems in Nuclear Physics", ECT*, October 19-23, 200

Characterization of a Li-6 loaded liquid organic scintillator for fast neutron spectrometry and thermal neutron detection

The characterization of a liquid scintillator incorporating an aqueous solution of enriched lithium chloride to produce a scintillator with 0.40% Li-6 is presented, including the performance of the scintillator in terms of its optical properties and neutron response. The scintillator was incorporated into a fast neutron spectrometer, and the light output spectra from 2.5 MeV, 14.1 MeV, and Cf-252 neutrons were measured using capture-gated coincidence techniques. The spectrometer was operated without coincidence to perform thermal neutron measurements. Possible improvements in spectrometer performance are discussed.Comment: Submitted to Applied Radiation and Isotopes. 11 pages, 7 figures, 3 tables. Revision addresses reviewers' comment

True Superconductivity in a 2D "Superconducting-Insulating" System

We present results on disordered amorphous films which are expected to undergo a field-tuned Superconductor-Insulator Transition. Based on low-field data and I-V characteristics, we find evidence of a low temperature Metal-to-Superconductor transition. This transition is characterized by hysteretic magnetoresistance and discontinuities in the I-V curves. The metallic phase just above the transition is different from the "Fermi Metal" before superconductivity sets in.Comment: 3 pages, 4 figure

The therapeutic ratio in BNCT: Assessment using the Rat 9L gliosarcoma brain tumor and spinal cord models

During any radiation therapy, the therapeutic tumor dose is limited by the tolerance of the surrounding normal tissue within the treatment volume. The short ranges of the products of the {sup 10}B(n,{alpha}){sup 7}Li reaction produced during boron neutron capture therapy (BNCT) present an opportunity to increase the therapeutic ratio (tumor dose/normal tissue dose) to levels unprecedented in photon radiotherapy. The mixed radiation field produced during BNCT comprises radiations with different linear energy transfer (LET) and different relative biological effectiveness (RBE). The short ranges of the two high-LET products of the `B(n,a)`Li reaction make the microdistribution of the boron relative to target cell nuclei of particular importance. Due to the tissue specific distribution of different boron compounds, the term RBE is inappropriate in defining the biological effectiveness of the {sup 10}B(n,{alpha}){sup 7}Li reaction. To distinguish these differences from true RBEs we have used the term {open_quotes}compound biological effectiveness{close_quotes} (CBE) factor. The latter can be defined as the product of the true, geometry-independent, RBE for these particles times a {open_quotes}boron localization factor{close_quotes}, which will most likely be different for each particular boron compound. To express the total BNCT dose in a common unit, and to compare BNCT doses with the effects of conventional photon irradiation, multiplicative factors (RBEs and CBEs) are applied to the physical absorbed radiation doses from each high-LET component. The total effective BNCT dose is then expressed as the sum of RBE-corrected physical absorbed doses with the unit Gray-equivalent (Gy-Eq)

Time dependent mean field theory of the superfluid-insulator phase transition

We develop a time-dependent mean field approach, within the time-dependent variational principle, to describe the Superfluid-Insulator quantum phase transition. We construct the zero temperature phase diagram both of the Bose-Hubbard model (BHM), and of a spin-S Heisenberg model (SHM) with the XXZ anisotropy. The phase diagram of the BHM indicates a phase transition from a Mott insulator to a compressibile superfluid phase, and shows the expected lobe-like structure. The SHM phase diagram displays a quantum phase transition between a paramagnetic and a canted phases showing as well a lobe-like structure. We show how the BHM and Quantum Phase model (QPM) can be rigorously derived from the SHM. Based on such results, the phase boundaries of the SHM are mapped to the BHM ones, while the phase diagram of the QPM is related to that of the SHM. The QPM's phase diagram obtained through the application of our approach to the SHM, describes the known onset of the macroscopic phase coherence from the Coulomb blockade regime for increasing Josephson coupling constant. The BHM and the QPM phase diagrams are in good agreement with Quantum Monte Carlo results, and with the third order strong coupling perturbative expansion.Comment: 15 pages, 8 figures. To be published in Phys. Rev.

BPA uptake in rat tissues after partial hepatectomy

In boron neutron capture therapy (BNCT), boron given as boronophenylalanine (BPA) accumulates transiently not only in tumors but also in normal tissues. Average boron concentrations in transplanted 9L gliosarcoma tumors of 20 rats were 2.5 to 3.7 times concentrations found in blood. Although boron levels in a variety of tissues were also higher than blood the concentrations were less than the lowest found in the tumor. Further note than although BPA is a structural analogue of phenylalanine (Phe), the pathway of BPA uptake into regenerating liver may not be linked to Phe uptake mechanisms

Vortex Lattice Melting into Disentangled Liquid Followed by the 3D-2D Decoupling Transition in YBa_2Cu_4O_8 Single Crystals

A sharp resistance drop associated with vortex lattice melting was observed in high quality YBa_2Cu_4O_8 single crystals. The melting line is well described well by the anisotropic GL theory. Two thermally activated flux flow regions, which were separated by a crossover line B_cr=1406.5(1-T/T_c)/T (T_c=79.0 K, B_cr in T), were observed in the vortex liquid phase. Activation energy for each region was obtained and the corresponding dissipation mechanism was discussed. Our results suggest that the vortex lattice in YBa_2Cu_4O_8 single crystal melts into disentangled liquid, which then undergoes a 3D-2D decoupling transition.Comment: 5 pages, 4 eps figures, RevTex (Latex2.09

The Role of Human-Automation Consensus in Multiple Unmanned Vehicle Scheduling

Objective: This study examined the impact of increasing automation replanning rates on operator performance and workload when supervising a decentralized network of heterogeneous unmanned vehicles. Background: Futuristic unmanned vehicles systems will invert the operator-to-vehicle ratio so that one operator can control multiple dissimilar vehicles connected through a decentralized network. Significant human-automation collaboration will be needed because of automation brittleness, but such collaboration could cause high workload. Method: Three increasing levels of replanning were tested on an existing multiple unmanned vehicle simulation environment that leverages decentralized algorithms for vehicle routing and task allocation in conjunction with human supervision. Results: Rapid replanning can cause high operator workload, ultimately resulting in poorer overall system performance. Poor performance was associated with a lack of operator consensus for when to accept the automation’s suggested prompts for new plan consideration as well as negative attitudes toward unmanned aerial vehicles in general. Participants with video game experience tended to collaborate more with the automation, which resulted in better performance. Conclusion: In decentralized unmanned vehicle networks, operators who ignore the automation’s requests for new plan consideration and impose rapid replans both increase their own workload and reduce the ability of the vehicle network to operate at its maximum capacity. Application: These findings have implications for personnel selection and training for futuristic systems involving human collaboration with decentralized algorithms embedded in networks of autonomous systems.Aurora Flight Sciences Corp.United States. Office of Naval Researc

Two-dimensional SIR epidemics with long range infection

We extend a recent study of susceptible-infected-removed epidemic processes with long range infection (referred to as I in the following) from 1-dimensional lattices to lattices in two dimensions. As in I we use hashing to simulate very large lattices for which finite size effects can be neglected, in spite of the assumed power law $p({\bf x})\sim |{\bf x}|^{-\sigma-2}$ for the probability that a site can infect another site a distance vector ${\bf x}$ apart. As in I we present detailed results for the critical case, for the supercritical case with $\sigma = 2$, and for the supercritical case with $0< \sigma < 2$. For the latter we verify the stretched exponential growth of the infected cluster with time predicted by M. Biskup. For $\sigma=2$ we find generic power laws with $\sigma-$dependent exponents in the supercritical phase, but no Kosterlitz-Thouless (KT) like critical point as in 1-d. Instead of diverging exponentially with the distance from the critical point, the correlation length increases with an inverse power, as in an ordinary critical point. Finally we study the dependence of the critical exponents on $\sigma$ in the regime $0<\sigma <2$, and compare with field theoretic predictions. In particular we discuss in detail whether the critical behavior for $\sigma$ slightly less than 2 is in the short range universality class, as conjectured recently by F. Linder {\it et al.}. As in I we also consider a modified version of the model where only some of the contacts are long range, the others being between nearest neighbors. If the number of the latter reaches the percolation threshold, the critical behavior is changed but the supercritical behavior stays qualitatively the same.Comment: 14 pages, including 29 figure