Characterization of Lifestyle in Spinocerebellar Ataxia Type 3 and Association with Disease Severity

BACKGROUND: Lifestyle could influence the course of hereditary ataxias, but representative data are missing. OBJECTIVE: The objective of this study was to characterize lifestyle in spinocerebellar ataxia type 3 (SCA3) and investigate possible associations with disease parameters. METHODS: In a prospective cohort study, data on smoking, alcohol consumption, physical activity, physiotherapy, and body mass index (BMI) were collected from 243 patients with SCA3 and 119 controls and tested for associations with age of onset, disease severity, and progression. RESULTS: Compared with controls, patients with SCA3 were less active and consumed less alcohol. Less physical activity and alcohol abstinence were associated with more severe disease, but not with progression rates or age of onset. Smoking, BMI, or physiotherapy did not correlate with disease parameters. CONCLUSION: Differences in lifestyle factors of patients with SCA3 and controls as well as associations of lifestyle factors with disease severity are likely driven by the influence of symptoms on behavior. No association between lifestyle and disease progression was detected. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Theory of superconductor with kappa close to 1/sqrt{2}

As was firstly shown by E. Bogomolny, the critical Ginzburg-Landay (GL) parameter kappa =1/sqrt{2} at which a superconductor changes its behavior from type-I to type-II, is the special highly degenerate point where Abrikosov vortices do not interact and therefore all vortex states have the same energy. Developing a secular perturbation theory we studied how this degeneracy is lifted when kappa is slightly different from 1\sqrt{2} or when the GL theory is extended to the higher in T-Tc terms. We constructed a simple secular functional, that depends only on few experimentally measurable phenomenological parameters and therefore is quite efficient to study the vortex state of superconductor in this transitional region of kappa. Basing on this, we calculated such vortex state properties as: critical fields, energy of the normal-superconductor interface, energy of the vortex lattice, vortex interaction energy etc. and compared them with previous results that were based on bulky solutions of GL equations.Comment: Revtex, 14 pages, 4 postscript pictures embedded in the tex

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity-to-onset and, potentially, treatment-response markers in both human and preclinical SCA3 trials

Topological Color Codes and Two-Body Quantum Lattice Hamiltonians

Topological color codes are among the stabilizer codes with remarkable properties from quantum information perspective. In this paper we construct a four-valent lattice, the so called ruby lattice, governed by a 2-body Hamiltonian. In a particular regime of coupling constants, degenerate perturbation theory implies that the low energy spectrum of the model can be described by a many-body effective Hamiltonian, which encodes the color code as its ground state subspace. The gauge symmetry $\mathbf{Z}_{2}\times\mathbf{Z}_{2}$ of color code could already be realized by identifying three distinct plaquette operators on the lattice. Plaquettes are extended to closed strings or string-net structures. Non-contractible closed strings winding the space commute with Hamiltonian but not always with each other giving rise to exact topological degeneracy of the model. Connection to 2-colexes can be established at the non-perturbative level. The particular structure of the 2-body Hamiltonian provides a fruitful interpretation in terms of mapping to bosons coupled to effective spins. We show that high energy excitations of the model have fermionic statistics. They form three families of high energy excitations each of one color. Furthermore, we show that they belong to a particular family of topological charges. Also, we use Jordan-Wigner transformation in order to test the integrability of the model via introducing of Majorana fermions. The four-valent structure of the lattice prevents to reduce the fermionized Hamiltonian into a quadratic form due to interacting gauge fields. We also propose another construction for 2-body Hamiltonian based on the connection between color codes and cluster states. We discuss this latter approach along the construction based on the ruby lattice.Comment: 56 pages, 16 figures, published version

Separability criteria and entanglement witnesses for symmetric quantum states

We study the separability of symmetric bipartite quantum states and show that a single correlation measurement is sufficient to detect the entanglement of any bipartite symmetric state with a non-positive partial transpose. We also discuss entanglement conditions and entanglement witnesses for states with a positive partial transpose.Comment: 5 pages, no figures, LaTeX; v2: typos corrected, introduction extended; v3: small corrections, published version; for the proceedings of the DPG spring meeting, Hamburg, March 200

SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge

The variable link between PNA and NAO in observations and in multi-century CGCM simulations

The link between the Pacific/North American pattern (PNA) and the North Atlantic Oscillation (NAO) is investigated in reanalysis data (NCEP, ERA40) and multi-century CGCM runs for present day climate using three versions of the ECHAM model. PNA and NAO patterns and indices are determined via rotated principal component analysis on monthly mean 500 hPa geopotential height fields using the varimax criteria. On average, the multi-century CGCM simulations show a significant anti-correlation between PNA and NAO. Further, multi-decadal periods with significantly enhanced (high anti-correlation, active phase) or weakened (low correlations, inactive phase) coupling are found in all CGCMs. In the simulated active phases, the storm track activity near Newfoundland has a stronger link with the PNA variability than during the inactive phases. On average, the reanalysis datasets show no significant anti-correlation between PNA and NAO indices, but during the sub-period 1973–1994 a significant anti-correlation is detected, suggesting that the present climate could correspond to an inactive period as detected in the CGCMs. An analysis of possible physical mechanisms suggests that the link between the patterns is established by the baroclinic waves forming the North Atlantic storm track. The geopotential height anomalies associated with negative PNA phases induce an increased advection of warm and moist air from the Gulf of Mexico and cold air from Canada. Both types of advection contribute to increase baroclinicity over eastern North America and also to increase the low level latent heat content of the warm air masses. Thus, growth conditions for eddies at the entrance of the North Atlantic storm track are enhanced. Considering the average temporal development during winter for the CGCM, results show an enhanced Newfoundland storm track maximum in the early winter for negative PNA, followed by a downstream enhancement of the Atlantic storm track in the subsequent months. In active (passive) phases, this seasonal development is enhanced (suppressed). As the storm track over the central and eastern Atlantic is closely related to the NAO variability, this development can be explained by the shift of the NAO index to more positive values