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

The use of a standard time-sharing operating system to control a complex of real-time processes

When faced with the problem of providing software control for a complex of real-time processes it is fairly common to construct a purpose-built operating system. This paper presents our experience of taking the opposite approach and using a standard manufacturer- supplied operating system as the basis of the software system. (6 refs)

Physical Acoustics

Contains reports on three research projects.U. S. Navy (Office of Naval Research) under Contract N00014-67-A-0204-0019Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

Adaptive Method for the Experimental Detection of Instabilities

Motivated by numerical bifurcation detection, we present a methodology for the direct location of bifurcation points in nonlinear dynamic laboratory experiments. The procedure involves active, adaptive use of the bifurcation parameter(s) as control variable(s), coupled with the on-line identification of low-order nonlinear dynamic models from experimental time-series data. Application of the procedure to such “hard” transitions as saddle-node and subcritical Hopf bifurcations is demonstrated through simulated experiments of lumped as well as spatially distributed systems

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

Points, Walls and Loops in Resonant Oscillatory Media

In an experiment of oscillatory media, domains and walls are formed under the parametric resonance with a frequency double the natural one. In this bi-stable system, %phase jumps $\pi$ by crossing walls. a nonequilibrium transition from Ising wall to Bloch wall consistent with prediction is confirmed experimentally. The Bloch wall moves in the direction determined by its chirality with a constant speed. As a new type of moving structure in two-dimension, a traveling loop consisting of two walls and Neel points is observed.Comment: 9 pages (revtex format) and 6 figures (PostScript