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

Negative-coupling resonances in pump-coupled lasers

We consider coupled lasers, where the intensity deviations from the steady state, modulate the pump of the other lasers. Most of our results are for two lasers where the coupling constants are of opposite sign. This leads to a Hopf bifurcation to periodic output for weak coupling. As the magnitude of the coupling constants is increased (negatively) we observe novel amplitude effects such as a weak coupling resonance peak and, strong coupling subharmonic resonances and chaos. In the weak coupling regime the output is predicted by a set of slow evolution amplitude equations. Pulsating solutions in the strong coupling limit are described by discrete map derived from the original model.Comment: 29 pages with 8 figures Physica D, in pres

A sharp stability criterion for the Vlasov-Maxwell system

We consider the linear stability problem for a 3D cylindrically symmetric equilibrium of the relativistic Vlasov-Maxwell system that describes a collisionless plasma. For an equilibrium whose distribution function decreases monotonically with the particle energy, we obtained a linear stability criterion in our previous paper. Here we prove that this criterion is sharp; that is, there would otherwise be an exponentially growing solution to the linearized system. Therefore for the class of symmetric Vlasov-Maxwell equilibria, we establish an energy principle for linear stability. We also treat the considerably simpler periodic 1.5D case. The new formulation introduced here is applicable as well to the nonrelativistic case, to other symmetries, and to general equilibria

Hard-Loop Effective Action for Anisotropic Plasmas

We generalize the hard-thermal-loop effective action of the equilibrium quark-gluon plasma to a non-equilibrium system which is space-time homogeneous but for which the parton momentum distribution is anisotropic. We show that the manifestly gauge-invariant Braaten-Pisarski form of the effective action can be straightforwardly generalized and we verify that it then generates all n-point functions following from collisionless gauge-covariant transport theory for a homogeneous anisotropic plasma. On the other hand, the Taylor-Wong form of the hard-thermal-loop effective action has a more complicated generalization to the anisotropic case. Already in the simplest case of anisotropic distribution functions, it involves an additional term that is gauge invariant by itself, but nontrivial also in the static limit.Comment: 12 pages. Version 3: typo in (15) corrected, note added discussing metric conventions use

‘Care Co-ordinator In My Pocket’. A Feasibility study of Mobile-Assessment and Therapy for Psychosis (TechCare).

Objectives: The research aimed to examine the acceptability and feasibility of a mobile phone Application (App) based intervention ‘TechCare’, for individuals with psychosis in the North West of England. The main objectives were to determine whether appropriate individuals could be identified and recruited to the study and whether the TechCare App would be an acceptable intervention for individuals with psychosis. Methods: This was a mixed methods feasibility study, consisting of a test-run and feasibility evaluation of the TechCare App intervention. Setting: Early Intervention Services for psychosis, within an NHS Trusts in the North West of England. Participants: Sixteen participants (Test-run n=4, feasibility study n=12) aged between 18-65, recruited from the East, Central and North Lancashire Early Intervention Service (EIS). Intervention: A 6-week intervention, with the TechCare App assessing participants’ symptoms and responses in real-time and providing a personalised guided self-help based psychological intervention based on the principles of CBT. Results: A total of 83.33% (n=10) of participants completed the 6-week feasibility study, with 70% of completers achieving the set compliance threshold of ≥33% engagement with the TechCare App system. Analysis of the qualitative data suggested that participants held the view that the TechCare was both an acceptable and feasible means of delivering interventions in real-time. Conclusion: Innovative digital clinical technologies such as the TechCare App may have the potential to increase access to psychological interventions, reduce health inequality, and promote self-management with a real-time intervention, through enabling access to mental health resources in a stigma-free, evidence-based, and time-independent manner. Trial registration number: ClinicalTrials.gov Identifier: NCT0243961

Self-consistent stability analysis of spherical shocks.

In this paper, we study self-similar solutions, and their linear stability as well, describing the flow within a spherical shell with finite thickness, expanding according to a power law of time, t q , where q>0. The shell propagates in a medium with initially uniform density and it is bounded by a strong shock wave at its outer border while the inner face is submitted to a time-dependent uniform pressure. For q=2/5, the well-known Sedov–Taylor solution is recovered. In addition, although both accelerated and decelerated shells can be unstable against dynamic perturbations, they exhibit highly different behaviors. Finally, the dispersion relation derived earlier by Vishniac (Vishniac, E.T. in Astrophys. J. 274:152, 1983) for an infinitely thin shell is obtained in the limit of an isothermal shock wave

Improving nitrogen cycling in a land surface model (CLM5) to quantify soil N2O, NO, and NH3 emissions from enhanced rock weathering with croplands

Surficial enhanced rock weathering (ERW) is a land-based carbon dioxide removal (CDR) strategy that involves applying crushed silicate rock (e.g., basalt) to agricultural soils. However, unintended biogeochemical interactions with the nitrogen cycle may arise through ERW increasing soil pH as basalt grains undergo dissolution that may reinforce, counteract, or even offset the climate benefits from carbon sequestration. Increases in soil pH could drive changes in the soil emissions of key non-CO2 greenhouse gases, e.g., nitrous oxide (N2O), and trace gases, e.g., nitric oxide (NO) and ammonia (NH3), that affect air quality and crop and human health. We present the development and implementation of a new improved nitrogen cycling scheme for the Community Land Model v5 (CLM5), the land component of the Community Earth System Model, allowing evaluation of ERW effects on soil gas emissions. We base the new parameterizations on datasets derived from soil pH responses of N2O, NO, and NH3 in ERW field trial and mesocosm experiments with crushed basalt. These new capabilities involve the direct implementation of routines within the CLM5 N cycle framework, along with asynchronous coupling of soil pH changes estimated through an ERW model. We successfully validated simulated “control” (i.e., no ERW) seasonal cycles of soil N2O, NO, and NH3 emissions against a wide range of global emission inventories. We benchmark simulated mitigation of soil N2O fluxes in response to ERW against a subset of data from ERW field trials in the US Corn Belt. Using the new scheme, we provide a specific example of the effect of large-scale ERW deployment with croplands on soil nitrogen fluxes across five key regions with high potential for CDR with ERW (North America, Brazil, Europe, India, and China). Across these regions, ERW implementation led to marked reductions in N2O and NO (both 18 %), with moderate increases in NH3 (2 %). While further developments are still required in our implementations when additional ERW data become available, our improved N cycle scheme within CLM5 has utility for investigating the potential of ERW point-source and regional effects of soil N2O, NO, and NH3 fluxes in response to current and future climates. This framework also provides the basis for assessing the implications of ERW for air quality given the role of NO in tropospheric ozone formation, as well as both NO and NH3 in inorganic aerosol formation

Effects of mineralogy, chemistry and physical properties of basalts on carbon capture potential and plant-nutrient element release via enhanced weathering

Mafic igneous rocks, such as basalt, are composed of abundant calcium- and magnesium-rich silicate minerals widely proposed to be suitable for scalable carbon dioxide removal (CDR) by enhanced rock weathering (ERW). Here, we report a detailed characterization of the mineralogy, chemistry, particle size and surface area of six mined basalts being used in large-scale ERW field trials. We use 1-D reactive transport modelling (RTM) of soil profile processes to simulate inorganic CDR potential via cation flux (Mg2+, Ca2+, K+ and Na+) and assess the release of the essential plant nutrients phosphorus (P) and potassium (K) for a typical clay-loam agricultural soil. The basalts are primarily composed of pyroxene and plagioclase feldspar (up to 71 wt%), with accessory olivine, quartz, glass and alkali feldspar. Mean crushed particle size varies by a factor of 10, owing to differences in the mining operations and grinding processes. RTM simulations, based on measured mineral composition and N2-gas BET specific surface area (SSA), yielded potential CDR values of between c. 1.3 and 8.5 t CO2 ha−1 after 15 years following a baseline application of 50 t ha−1 basalt. The RTM results are comparative for the range of inputs that are described and should be considered illustrative for an agricultural soil. Nevertheless, they indicate that increasing the surface area for slow-weathering basalts through energy intensive grinding prior to field application in an ERW context may not be warranted in terms of additional CDR gains. We developed a function to convert CDR based on widely available and easily measured rock chemistry measures to more realistic determinations based on mineralogy. When applied to a chemistry dataset for >1300 basalt analyses from 25 large igneous provinces, we simulated cumulative CDR potentials of up to c. 8.5 t CO2 ha−1 after 30 years of weathering, assuming a single application of basalt with a SSA of 1 m2 g−1. Our RTM simulations suggest that ERW with basalt releases sufficient phosphorus (P) to substitute for typical arable crop P-fertiliser usage in Europe and the USA offering potential to reduce demand for expensive rock-derived P

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium

Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleve