1,091 research outputs found

    Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab

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    <p>Objective To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA).</p> <p>Methods GO–REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14.</p> <p>Results Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone.</p> <p>Conclusions This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.</p&gt

    Associations between neighborhood characteristics: well-being and health vary over the life course

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    Background: Neighborhood characteristics are important determinants of individual health and well-being. For example, characteristics such as noise and pollution affect health directly, while other characteristics affect health and well-being by either providing resources (e.g. social capital in the neighborhood), which individuals can use to cope with health problems, or limiting the use thereof (e.g. crime). This also suggests that there might be age differentials in the impact of these characteristics, since individuals at different stages of life might need different resources. However, there is a lack of empirical evidence on age differentials in associations between well-being, health, and neighborhood characteristics. Objective: This paper studies associations between a wide range of neighborhood characteristics with the health and well-being of residents of the greater Berlin area. In particular, we focus on differences in the effects between younger (aged 20-35) and older (aged 60+) residents. Methods: We used data from the Berlin Aging Study II (312 younger and 993 older residents of the Berlin metropolitan area in Germany). We used survey data on health and well-being, combined these with subjective perceptions of the neighborhood, and geo-referenced indicators on the neighborhood, e.g. amenities (public transport, physicians, and hospitals). Results: The results show that access to public transportation is associated with better outcomes on all measures of health and well-being, and social support is associated with higher life satisfaction and better mental health. There are considerable differences between both age groups: while the associations between access to public transport and health and well-being are similar for both age groups, neighborhood social capital shows stronger associations for older residents. However, the difference is not always statistically significant. Conclusion: Having access to services is associated with better health and well-being regardless of age. Local policy makers should focus on lowering barriers to mobility in order to improve the health and well-being of the population. Since the social capital of a neighborhood is associated with better health and well-being among older residents, investments that increase social capital (e.g. community centers) might be warranted in neighborhoods with higher shares of older residents

    Baryon Charge Radii and Quadrupole Moments in the 1/N_c Expansion: The 3-Flavor Case

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    We develop a straightforward method to compute charge radii and quadrupole moments for baryons both with and without strangeness, when the number of QCD color charges is N_c. The minimal assumption of the single-photon exchange ansatz implies that only two operators are required to describe these baryon observables. Our results are presented so that SU(3) flavor and isospin symmetry breaking can be introduced according to any desired specification, although we also present results obtained from two patterns suggested by the quark model with gluon exchange interactions. The method also permits to extract a number of model-independent relations; a sample is r^2_Lambda / r_n^2 = 3/(N_c+3), independent of SU(3) symmetry breaking.Comment: 30 pages, no figures, REVTeX

    Rings and rigidity transitions in network glasses

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    Three elastic phases of covalent networks, (I) floppy, (II) isostatically rigid and (III) stressed-rigid have now been identified in glasses at specific degrees of cross-linking (or chemical composition) both in theory and experiments. Here we use size-increasing cluster combinatorics and constraint counting algorithms to study analytically possible consequences of self-organization. In the presence of small rings that can be locally I, II or III, we obtain two transitions instead of the previously reported single percolative transition at the mean coordination number rˉ=2.4\bar r=2.4, one from a floppy to an isostatic rigid phase, and a second one from an isostatic to a stressed rigid phase. The width of the intermediate phase  rˉ~ \bar r and the order of the phase transitions depend on the nature of medium range order (relative ring fractions). We compare the results to the Group IV chalcogenides, such as Ge-Se and Si-Se, for which evidence of an intermediate phase has been obtained, and for which estimates of ring fractions can be made from structures of high T crystalline phases.Comment: 29 pages, revtex, 7 eps figure

    Critical point network for drainage between rough surfaces

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    In this paper, we present a network method for computing two-phase flows between two rough surfaces with significant contact areas. Low-capillary number drainage is investigated here since one-phase flows have been previously investigated in other contributions. An invasion percolation algorithm is presented for modeling slow displacement of a wetting fluid by a non wetting one between two rough surfaces. Short-correlated Gaussian process is used to model random rough surfaces.The algorithm is based on a network description of the fracture aperture field. The network is constructed from the identification of critical points (saddles and maxima) of the aperture field. The invasion potential is determined from examining drainage process in a flat mini-channel. A direct comparison between numerical prediction and experimental visualizations on an identical geometry has been performed for one realization of an artificial fracture with a moderate fractional contact area of about 0.3. A good agreement is found between predictions and observations

    Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.

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    The vasculature is a key regulator of leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases including multiple sclerosis (MS). However, the impact of endothelial-derived factors on CNS immune responses remains unknown. Bioactive lipids, in particular oxysterols downstream of Cholesterol-25-hydroxylase (Ch25h), promote neuroinflammation but their functions in the CNS are not well-understood. Using floxed-reporter Ch25h knock-in mice, we trace Ch25h expression to CNS endothelial cells (ECs) and myeloid cells and demonstrate that Ch25h ablation specifically from ECs attenuates experimental autoimmune encephalomyelitis (EAE). Mechanistically, inflamed Ch25h-deficient CNS ECs display altered lipid metabolism favoring polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) expansion, which suppresses encephalitogenic T lymphocyte proliferation. Additionally, endothelial Ch25h-deficiency combined with immature neutrophil mobilization into the blood circulation nearly completely protects mice from EAE. Our findings reveal a central role for CNS endothelial Ch25h in promoting neuroinflammation by inhibiting the expansion of immunosuppressive myeloid cell populations

    Spin fluctuations in nearly magnetic metals from ab-initio dynamical spin susceptibility calculations:application to Pd and Cr95V5

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    We describe our theoretical formalism and computational scheme for making ab-initio calculations of the dynamic paramagnetic spin susceptibilities of metals and alloys at finite temperatures. Its basis is Time-Dependent Density Functional Theory within an electronic multiple scattering, imaginary time Green function formalism. Results receive a natural interpretation in terms of overdamped oscillator systems making them suitable for incorporation into spin fluctuation theories. For illustration we apply our method to the nearly ferromagnetic metal Pd and the nearly antiferromagnetic chromium alloy Cr95V5. We compare and contrast the spin dynamics of these two metals and in each case identify those fluctuations with relaxation times much longer than typical electronic `hopping times'Comment: 21 pages, 9 figures. To appear in Physical Review B (July 2000

    Very-high energy gamma-ray astronomy: A 23-year success story in high-energy astroparticle physics

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    Very-high energy (VHE) gamma quanta contribute only a minuscule fraction - below one per million - to the flux of cosmic rays. Nevertheless, being neutral particles they are currently the best "messengers" of processes from the relativistic/ultra-relativistic Universe because they can be extrapolated back to their origin. The window of VHE gamma rays was opened only in 1989 by the Whipple collaboration, reporting the observation of TeV gamma rays from the Crab nebula. After a slow start, this new field of research is now rapidly expanding with the discovery of more than 150 VHE gamma-ray emitting sources. Progress is intimately related with the steady improvement of detectors and rapidly increasing computing power. We give an overview of the early attempts before and around 1989 and the progress after the pioneering work of the Whipple collaboration. The main focus of this article is on the development of experimental techniques for Earth-bound gamma-ray detectors; consequently, more emphasis is given to those experiments that made an initial breakthrough rather than to the successors which often had and have a similar (sometimes even higher) scientific output as the pioneering experiments. The considered energy threshold is about 30 GeV. At lower energies, observations can presently only be performed with balloon or satellite-borne detectors. Irrespective of the stormy experimental progress, the success story could not have been called a success story without a broad scientific output. Therefore we conclude this article with a summary of the scientific rationales and main results achieved over the last two decades.Comment: 45 pages, 38 figures, review prepared for EPJ-H special issue "Cosmic rays, gamma rays and neutrinos: A survey of 100 years of research
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