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

Mission Concept for the Single Aperture Far-Infrared (SAFIR) Observatory

The Single Aperture Far-InfraRed (SAFIR) Observatory's science goals are driven by the fact that the earliest stages of almost all phenomena in the universe are shrouded in absorption by and emission from cool dust and gas that emits strongly in the far-infrared and submillimeter. Over the past several years, there has been an increasing recognition of the critical importance of this spectral region to addressing fundamental astrophysical problems, ranging from cosmological questions to understanding how our own Solar System came into being. The development of large, far-infrared telescopes in space has become more feasible with the combination of developments for the James Webb Space Telescope and of enabling breakthroughs in detector technology. We have developed a preliminary but comprehensive mission concept for SAFIR, as a 10 m-class far-infrared and submillimeter observatory that would begin development later in this decade to meet the needs outlined above. Its operating temperature (<4K) and instrument complement would be optimized to reach the natural sky confusion limit in the far-infrared with diffraction-limited peformance down to at least 40 microns. This would provide a point source sensitivity improvement of several orders of magnitude over that of Spitzer or Herschel, with finer angular resolution, enabling imaging and spectroscopic studies of individual galaxies in the early universe. We have considered many aspects of the SAFIR mission, including the telescope technology, detector needs and technologies, cooling method and required technology developments, attitude and pointing, power systems, launch vehicle, and mission operations. The most challenging requirements for this mission are operating temperature and aperture size of the telescope, and the development of detector arrays.Comment: 36 page

Masses of ground and excited-state hadrons

We present the first Dyson-Schwinger equation calculation of the light hadron spectrum that simultaneously correlates the masses of meson and baryon ground- and excited-states within a single framework. At the core of our analysis is a symmetry-preserving treatment of a vector-vector contact interaction. In comparison with relevant quantities the root-mean-square-relative-error/degree-of freedom is 13%. Notable amongst our results is agreement between the computed baryon masses and the bare masses employed in modern dynamical coupled-channels models of pion-nucleon reactions. Our analysis provides insight into numerous aspects of baryon structure; e.g., relationships between the nucleon and Delta masses and those of the dressed-quark and diquark correlations they contain.Comment: 25 pages, 7 figures, 4 table

Comment on: “Peatland carbon stocks and burn history: Blanket bog peat core evidence highlights charcoal impacts on peat physical properties and long-term carbon storage”, by A. Heinemeyer, Q. Asena, W.L. Burn and A.L. Jones (Geo: Geography and Environment. 2018; e00063)

A recent paper by Heinemeyer et al. (2018) in this journal has suggested that the use of prescribed fire may enhance carbon accumulation in UK upland blanket bogs. We challenge this finding based on a number of concerns with the original manuscript including the lack of an unburned control, insufficient replication, unrecognised potential confounding factors, and potentially large inaccuracies in the core dating approach used to calculate carbon accumulation rates. We argue that burn‐management of peatlands is more likely to lead to carbon loss than carbon gain

Survey of nucleon electromagnetic form factors

A dressed-quark core contribution to nucleon electromagnetic form factors is calculated. It is defined by the solution of a Poincare' covariant Faddeev equation in which dressed-quarks provide the elementary degree of freedom and correlations between them are expressed via diquarks. The nucleon-photon vertex involves a single parameter; i.e., a diquark charge radius. It is argued to be commensurate with the pion's charge radius. A comprehensive analysis and explanation of the form factors is built upon this foundation. A particular feature of the study is a separation of form factor contributions into those from different diagram types and correlation sectors, and subsequently a flavour separation for each of these. Amongst the extensive body of results that one could highlight are: r_1^{n,u}>r_1^{n,d}, owing to the presence of axial-vector quark-quark correlations; and for both the neutron and proton the ratio of Sachs electric and magnetic form factors possesses a zero.Comment: 43 pages, 17 figures, 12 tables, 5 appendice

Oral contraceptive use and anterior cruciate ligament injury: comparison of active comparator new user cohort and case-control study designs

Background: This study further investigates a protective association between oral contraceptive (OC) use and anterior cruciate ligament (ACL) injury noted in prior case-control studies. Methods: Active comparator new user cohort analysis of women aged 13–45 years in the United States from the IBM MarketScan Commercial Claims and Encounters database who newly-initiated low-dose OCs (exposed) or underwent intrauterine device (IUD) insertion (comparison group) from 2000 to 2014. Women were followed for ACL injury starting 90 days after OC initiation or IUD insertion until OC or IUD discontinuation or end of continuous enrollment. Adjusted hazard ratios (adjHR) and 95% confidence intervals (CI) were estimated controlling for age. Secondary analysis replicated previously-published case-control studies assessing “ever” versus “never” OC use over 1- and 5-year periods among women who underwent ACL reconstruction compared to age-matched controls. Results: In the cohort analysis, 2,370,286 women initiated OCs and 621,798 underwent IUD insertion. There were 3571 (0.15%) ACL injuries during an average 370.6 days of continuous OC use and 1620 (0.26%) during an average 590.5 days of IUD use. No difference in risk of ACL injury was observed between OC initiators and IUD users (adjHR = 0.95; 95%CI 0.89, 1.01). The case-control analysis replicated the slight protective association observed in prior studies over a 5-year period (OR = 0.90; 95%CI 0.85, 0.94). Conclusions: This cohort study suggests no association between OC use and ACL injury, while the case-control study suggested bias from uncontrolled confounding and selection factors may have influenced previous findings that suggested a protective association between OC use and ACL injury

Percolation on two- and three-dimensional lattices

In this work we apply a highly efficient Monte Carlo algorithm recently proposed by Newman and Ziff to treat percolation problems. The site and bond percolation are studied on a number of lattices in two and three dimensions. Quite good results for the wrapping probabilities, correlation length critical exponent and critical concentration are obtained for the square, simple cubic, HCP and hexagonal lattices by using relatively small systems. We also confirm the universal aspect of the wrapping probabilities regarding site and bond dilution.Comment: 15 pages, 6 figures, 3 table