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

312 MAX Phases: Elastic Properties and Lithiation

Interest in the Mn+1AXn phases (M = early transition metal; A = group 13–16 elements, and X = C or N) is driven by their ceramic and metallic properties, which make them attractive candidates for numerous applications. In the present study, we use the density functional theory to calculate the elastic properties and the incorporation of lithium atoms in the 312 MAX phases. It is shown that the energy to incorporate one Li atom in Mo3SiC2, Hf3AlC2, Zr3AlC2, and Zr3SiC2 is particularly low, and thus, theoretically, these materials should be considered for battery applications

A Clinical Trial of the Effects of Oral Beta-Carotene on the Responses of Human Skin to Solar Radiation

Beta-carotene (180 mg/day, p. o. ) or a placebo was administered to 30 normal male volunteers for 10 weeks, after which the volunteers were exposed to sunlight in the Arizona desert for up to 2 hours. Beta-carotene had a small but statistically significant effect in increasing the minimal erythema dose of sunburn radiation. The observed effects were too small to recommend the use of beta-carotene as a photoprotective agent for sunburn, but the methods developed provide a workable model for randomized controlled trials for evaluating the efficacy of systemic photoprotective agents

A Simple Explanation for DAMA with Moderate Channeling

We consider the possibility that the DAMA signal arises from channeled events in simple models where the dark matter interaction with nuclei is suppressed at small momenta. As with the standard WIMP, these models have two parameters (the dark matter mass and the size of the cross-section), without the need to introduce an additional energy threshold type of parameter. We find that they can be consistent with channeling fractions as low as about ~ 15%, so long as at least ~70% of the nuclear recoil energy for channeled events is deposited electronically. Given that there are reasons not to expect very large channeling fractions, these scenarios make the channeling explanation of DAMA much more compelling.Comment: 6 pages, 2 figure

Bumpy black holes from spontaneous Lorentz violation

We consider black holes in Lorentz violating theories of massive gravity. We argue that in these theories black hole solutions are no longer universal and exhibit a large number of hairs. If they exist, these hairs probe the singularity inside the black hole providing a window into quantum gravity. The existence of these hairs can be tested by future gravitational wave observatories. We generically expect that the effects we discuss will be larger for the more massive black holes. In the simplest models the strength of the hairs is controlled by the same parameter that sets the mass of the graviton (tensor modes). Then the upper limit on this mass coming from the inferred gravitational radiation emitted by binary pulsars implies that hairs are likely to be suppressed for almost the entire mass range of the super-massive black holes in the centers of galaxies.Comment: 40 pages, 4 figure

Beyond Hybridity to the Politics of Scale: International Intervention and 'Local' Politics

The evident failures of international peacebuilding and statebuilding interventions (PSBIs) have recently prompted a focus on the interaction between interventions and target societies and states. Especially popular has been the ‘hybridity’ approach, which understands forms of peace and governance emerging through the mixing of local and international agendas and institutions. This article argues that hybridity is a highly problematic optic. Despite contrary claims, hybridity scholarship falsely dichotomizes ‘local’ and ‘international’ ideal-typical assemblages, and incorrectly presents outcomes as stemming from conflict and accommodation between them. Scholarship in political geography and state theory provides better tools for explaining PSBIs’ outcomes as reflecting socio-political contestation over power and resources. We theorize PSBIs as involving a politics of scale, where different social forces promote and resist alternative scales and modes of governance, depending on their interests and agendas. Contestation between these forces, which may be located at different scales and involved in complex, tactical, multi-scalar alliances, explains the uneven outcomes of international intervention. We demonstrate this using a case study of East Timor, focusing on decentralization and land policy

KK Parity in Warped Extra Dimension

We construct models with a Kaluza-Klein (KK) parity in a five- dimensional warped geometry, in an attempt to address the little hierarchy problem present in setups with bulk Standard Model fields. The lightest KK particle (LKP) is stable and can play the role of dark matter. We consider the possibilities of gluing two identical slices of 5D AdS in either the UV (IR-UV-IR model) or the IR region (UV-IR-UV model) and discuss the model-building issues as well as phenomenological properties in both cases. In particular, we find that the UV-IR-UV model is not gravitationally stable and that additional mechanisms might be required in the IR-UV-IR model in order to address flavor issues. Collider signals of the warped KK parity are different from either the conventional warped extra dimension without KK parity, in which the new particles are not necessarily pair-produced, or the KK parity in flat universal extra dimensions, where each KK level is nearly degenerate in mass. Dark matter and collider properties of a TeV mass KK Z gauge boson as the LKP are discussed.Comment: 35 pages, 11 figure

Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher