The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance:development of other autoantibodies and progression to type 1 diabetes

AIMS/HYPOTHESIS: Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention. METHODS: The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.2 years). Samples were screened for antibodies to GAD, insulinoma-associated antigen 2 (IA-2) and insulin, and all positive samples tested for antibodies to zinc transporter 8 and islet cell antibodies. RESULTS: Antibodies to at least one additional islet autoantigen appeared in 118 of 983 relatives (overall 5 year risk 22%, 95% CI [17.9, 26.1]). At baseline, antibodies to GAD alone (68%) were more frequent than antibodies to insulin (26%) or IA-2 (6%), but all were associated with a similar risk of developing additional autoantibodies. Risk was associated with younger age (p = 0.002) and HLA class II genotype, but was similar in high and intermediate genetic risk groups (p = 0.65). Relatives who became multiple autoantibody positive during the follow-up had increased risk of developing diabetes comparable with the risk in relatives with multiple autoantibodies at study entry. CONCLUSIONS/INTERPRETATION: Progression of islet autoimmunity in single autoantibody positive relatives in late childhood/adult life is associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. This heterogeneity in type 1 diabetes autoimmunity has potentially important implications for disease prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3830-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Instaseis: instant global seismograms based on a broadband waveform database

We present a new method and implementation (Instaseis) to store global Green's functions in a database which allows for near-instantaneous (on the order of milliseconds) extraction of arbitrary seismograms. Using the axisymmetric spectral element method (AxiSEM), the generation of these databases, based on reciprocity of the Green's functions, is very efficient and is approximately half as expensive as a single AxiSEM forward run. Thus, this enables the computation of full databases at half the cost of the computation of seismograms for a single source in the previous scheme and allows to compute databases at the highest frequencies globally observed. By storing the basis coefficients of the numerical scheme (Lagrange polynomials), the Green's functions are 4th order accurate in space and the spatial discretization respects discontinuities in the velocity model exactly. High-order temporal interpolation using Lanczos resampling allows to retrieve seismograms at any sampling rate. AxiSEM is easily adaptable to arbitrary spherically symmetric models of Earth as well as other planets. In this paper, we present the basic rationale and details of the method as well as benchmarks and illustrate a variety of applications. The code is open source and available with extensive documentation at www.instaseis.net

Instaseis: instant global seismograms based on a broadband waveform database

We present a new method and implementation (Instaseis) to store global Green's functions in a database which allows for near-instantaneous (on the order of milliseconds) extraction of arbitrary seismograms. Using the axisymmetric spectral element method (AxiSEM), the generation of these databases, based on reciprocity of the Green's functions, is very efficient and is approximately half as expensive as a single AxiSEM forward run. Thus, this enables the computation of full databases at half the cost of the computation of seismograms for a single source in the previous scheme and allows to compute databases at the highest frequencies globally observed. By storing the basis coefficients of the numerical scheme (Lagrange polynomials), the Green's functions are 4th order accurate in space and the spatial discretization respects discontinuities in the velocity model exactly. High-order temporal interpolation using Lanczos resampling allows to retrieve seismograms at any sampling rate. AxiSEM is easily adaptable to arbitrary spherically symmetric models of Earth as well as other planets. In this paper, we present the basic rationale and details of the method as well as benchmarks and illustrate a variety of applications. The code is open source and available with extensive documentation at www.instaseis.net

Controlling spatiotemporal chaos in oscillatory reaction-diffusion systems by time-delay autosynchronization

Diffusion-induced turbulence in spatially extended oscillatory media near a supercritical Hopf bifurcation can be controlled by applying global time-delay autosynchronization. We consider the complex Ginzburg-Landau equation in the Benjamin-Feir unstable regime and analytically investigate the stability of uniform oscillations depending on the feedback parameters. We show that a noninvasive stabilization of uniform oscillations is not possible in this type of systems. The synchronization diagram in the plane spanned by the feedback parameters is derived. Numerical simulations confirm the analytical results and give additional information on the spatiotemporal dynamics of the system close to complete synchronization.Comment: 19 pages, 10 figures submitted to Physica

Instaseis: instant global seismograms based on a broadband waveform database

Abstract. We present a new method and implementation (Instaseis) to store global Green's functions in a database which allows for near-instantaneous (on the order of milliseconds) extraction of arbitrary seismograms. Using the axisymmetric spectral element method (AxiSEM), the generation of these databases, based on reciprocity of the Green's functions, is very efficient and is approximately half as expensive as a single AxiSEM forward run. Thus, this enables the computation of full databases at half the cost of the computation of seismograms for a single source in the previous scheme and allows to compute databases at the highest frequencies globally observed. By storing the basis coefficients of the numerical scheme (Lagrange polynomials), the Green's functions are 4th order accurate in space and the spatial discretization respects discontinuities in the velocity model exactly. Highorder temporal interpolation using Lanczos resampling allows to retrieve seismograms at any sampling rate. AxiSEM is easily adaptable to arbitrary spherically symmetric models of Earth as well as other planets. In this paper, we present the basic rationale and details of the method as well as benchmarks and illustrate a variety of applications. The code is open source and available with extensive documentation at www.instaseis.net

Scenarios of domain pattern formation in a reaction-diffusion system

We performed an extensive numerical study of a two-dimensional reaction-diffusion system of the activator-inhibitor type in which domain patterns can form. We showed that both multidomain and labyrinthine patterns may form spontaneously as a result of Turing instability. In the stable homogeneous system with the fast inhibitor one can excite both localized and extended patterns by applying a localized stimulus. Depending on the parameters and the excitation level of the system stripes, spots, wriggled stripes, or labyrinthine patterns form. The labyrinthine patterns may be both connected and disconnected. In the the stable homogeneous system with the slow inhibitor one can excite self-replicating spots, breathing patterns, autowaves and turbulence. The parameter regions in which different types of patterns are realized are explained on the basis of the asymptotic theory of instabilities for patterns with sharp interfaces developed by us in Phys. Rev. E. 53, 3101 (1996). The dynamics of the patterns observed in our simulations is very similar to that of the patterns forming in the ferrocyanide-iodate-sulfite reaction.Comment: 15 pages (REVTeX), 15 figures (postscript and gif), submitted to Phys. Rev.

Breathing Current Domains in Globally Coupled Electrochemical Systems: A Comparison with a Semiconductor Model

Spatio-temporal bifurcations and complex dynamics in globally coupled intrinsically bistable electrochemical systems with an S-shaped current-voltage characteristic under galvanostatic control are studied theoretically on a one-dimensional domain. The results are compared with the dynamics and the bifurcation scenarios occurring in a closely related model which describes pattern formation in semiconductors. Under galvanostatic control both systems are unstable with respect to the formation of stationary large amplitude current domains. The current domains as well as the homogeneous steady state exhibit oscillatory instabilities for slow dynamics of the potential drop across the double layer, or across the semiconductor device, respectively. The interplay of the different instabilities leads to complex spatio-temporal behavior. We find breathing current domains and chaotic spatio-temporal dynamics in the electrochemical system. Comparing these findings with the results obtained earlier for the semiconductor system, we outline bifurcation scenarios leading to complex dynamics in globally coupled bistable systems with subcritical spatial bifurcations.Comment: 13 pages, 11 figures, 70 references, RevTex4 accepted by PRE http://pre.aps.or