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

Direct amplification of nodD from community DNA reveals the genetic diversity of Rhizobium leguminosarum in soil

Sequences of nodD, a gene found only in rhizobia, were amplified from total community DNA isolated from a pasture soil. The polymerase chain reaction (PCR) primers used, Y5 and Y6, match nodD from Rhizobium leguminosarum biovar trifolii, R. leguminosarum biovar viciae and Sinorhizobium meliloti. The PCR product was cloned and yielded 68 clones that were identified by restriction pattern as derived from biovar trifolii [11 restriction fragment length polymorphism (RFLP) types] and 15 clones identified as viciae (seven RFLP types). These identifications were confirmed by sequencing. There were no clones related to S. meliloti nodD. For comparison, 122 strains were isolated from nodules of white clover (Trifolium repens) growing at the field site, and 134 from nodules on trap plants of T. repens inoculated with the soil. The nodule isolates were of four nodD RFLP types, with 77% being of a single type. All four of these patterns were also found among the clones from soil DNA, and the same type was the most abundant, although it made up only 34% of the trifolii-like clones. We conclude that clover selects specific genotypes from the available soil population, and that R. leguminosarum biovar trifolii was approximately five times more abundant than biovar viciae in this pasture soil, whereas S. meliloti was rare

LHC Signature of Mirage Mediation

We study LHC phenomenology of mirage mediation scenario in which anomaly and modulus contributions to soft SUSY breaking terms are comparable to each other. A Monte Carlo study of mirage mediation, with model parameters $\alpha=1$,$M_0=500$ GeV, $n_M=1/2$, $n_H=1$ and $\rm{tan}\beta=10$, is presented. It is shown that masses of supersymmetric particles can be measured in a model independent way, providing information on SUSY breaking sector. In particular, the mass ratio of gluino to the lightest neutralino for the benchmark scenario is determined to be 1.9 \lesssim m_{\tildeg}/m_{\tilde\chi_1^0} \lesssim 3.1, well reproducing theoretical input value of $m_{\tilde g}/m_{\tilde\chi_1^0} \simeq 2.5$ which is quite distinctive from the predictions $m_{\tilde g}/m_{\tilde\chi_1^0} \gtrsim 6$ of other SUSY scenarios in which gaugino masses are unified at the GUT scale. The model parameters of mirage mediation can be also determined from various kinematic distributions

On the spherical-axial transition in supernova remnants

A new law of motion for supernova remnant (SNR) which introduces the quantity of swept matter in the thin layer approximation is introduced. This new law of motion is tested on 10 years observations of SN1993J. The introduction of an exponential gradient in the surrounding medium allows to model an aspherical expansion. A weakly asymmetric SNR, SN1006, and a strongly asymmetric SNR, SN1987a, are modeled. In the case of SN1987a the three observed rings are simulated.Comment: 19 figures and 14 pages Accepted for publication in Astrophysics & Space Science in the year 201

Some parasitic and other natural diseases of the African elephant in the Kruger National Park

Detailed descriptions are given of the lesions encountered at autopsy on a random selection of 32 free-living African elephants [Loxodonta africana (Blumenbach, 1797)]. Lymphoid nodules with inclusion bearing syncytia caused by a herpes virus were found in many lungs and similar lesions occurred in the pancreas. Suspected viral lesions somewhat resembling bovine granular vaginitis were encountered in the genitalia. Dipetalonema gossi Baylis, 1923, which was originally recorded from the abdominal cavity, was recovered from the portal veins of several animals. They proved to be responsible for severe intrahepatic vasculitis and eosinophilic hepatitis in 50% of the elephants. Grammocephalus clathratus (Baird, 1868) Railliet & Henry 1910 was constantly present in the bile ducts where fairly marked cholangitis was produced. Even mild localized pancreatitis was sometimes caused by these parasites. Parabronema africanum Baylis, 1921 was found in large numbers in gastric ulcers. A new mite, Loxanoetus bassoni Fain, 1970 was obtained from the ears. The livers of two elephants contained a few suspected schistosome ova. Siderotic and haemangiomatoid splenic lesions occurred in several adult animals. Many of the cows had multiple periuterine papillomata. Arteriosclerosis of the aorta was occasionally encountered. Skin lesions resembling porcine lesions of zinc deficiency were observed. Mycotic lesions were seen once in the lungs and lymph nodes. The aetiology of focal disseminated cystitis in 39% of the cows was not established.The journals have been scanned in colour with a HP 5590 scanner; 600 dpi. Adobe Acrobat v.11 was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Oscillation of the tunnel splitting in nanospin systems within the particle mapping formalism

The oscillation of tunnel splitting in the biaxial spin system within magnetic field along the anisotropy axis is analyzed within the particle mapping approach, rather than in the (\theta-\phi) spin coherent-state representation. In our mapping procedure, the spin system is transformed into a particle moving in the restricted $S^1$ geometry whose wave function subjects to the boundary condition involving additional phase shift. We obtain the new topological phase that plays the same role as the Wess-Zumino action in spin coherent-state representation. Considering the interference of two possible trajectories, instanton and anti-instanton, we get the identical condition for the field at which tunneling is quenched, with the previous result within spin coherent-state representation.Comment: 11 pages, 1 figure; Some typographical errors have been correcte

Measurement of the Cross Sections and Analyzing Powers for Transitions in 58-Ni Using 200 MeV Proton Scattering

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Multi-Channel Kondo Necklace

A multi--channel generalization of Doniach's Kondo necklace model is formulated, and its phase diagram studied in the mean--field approximation. Our intention is to introduce the possible simplest model which displays some of the features expected from the overscreened Kondo lattice. The $N$ conduction electron channels are represented by $N$ sets of pseudospins \vt_{j}, $j=1, ... , N$, which are all antiferromagnetically coupled to a periodic array of |\vs|=1/2 spins. Exploiting permutation symmetry in the channel index $j$ allows us to write down the self--consistency equation for general $N$. For $N>2$, we find that the critical temperature is rising with increasing Kondo interaction; we interpret this effect by pointing out that the Kondo coupling creates the composite pseudospin objects which undergo an ordering transition. The relevance of our findings to the underlying fermionic multi--channel problem is discussed.Comment: 29 pages (2 figures upon request from [email protected]), LATEX, submitted for publicatio