Detailed Clinical, Ophthalmic, and Genetic Characterization of ADGRV1-Associated Usher Syndrome

Purpose: To present the clinical characteristics, retinal features, natural history, and genetics of ADGRV1-Usher syndrome (USH). Design: Multicenter international retrospective cohort study. Methods: Clinical notes, hearing loss history, multimodal retinal imaging, and molecular diagnosis were reviewed. Thirty patients (28 families) with USH type 2 and disease-causing variants in ADGRV1 were identified. Visual function, retinal imaging, and genetics were evaluated and correlated, with retinal features also compared with those of the commonest cause of USH type 2, USH2A-USH. Results: The mean age at the first visit was 38.6 ± 12.0 years (range: 19-74 years), and the mean follow-up time was 9.0 ± 7.7 years. Hearing loss was reported in the first decade of life by all patients, 3 (10%) described progressive loss, and 93% had moderate-severe impairment. Visual symptom onset was at 17.0 ± 7.7 years of age (range: 6-32 years), with 13 patients noticing problems before the age of 16. At baseline, 90% of patients had no or mild visual impairment. The most frequent retinal features were a hyperautofluorescent ring at the posterior pole (70%), perimacular patches of decreased autofluorescence (59%), and mild-moderate peripheral bone-spicule–like deposits (63%). Twenty-six (53%) variants were previously unreported, 19 families (68%) had double-null genotypes, and 9 were not-double-null. Longitudinal analysis showed significant differences between baseline and follow-up central macular thickness (−1.25 µm/y), outer nuclear layer thickness (−1.19 µm/y), and ellipsoid zone width (−40.9 µm/y). The rate of visual acuity decline was 0.02 LogMAR (1 letter)/y, and the rate of constriction of the hyperautofluorescent ring was 0.23 mm2/y. Conclusions: ADGRV1-USH is characterized by early-onset, usually non-progressive, mild-to-severe hearing loss and generally good central vision until late adulthood. Perimacular atrophic patches and relatively retained ellipsoid zone and central macular thickness in later adulthood are more often seen in ADGRV1-USH than in USH2A-USH

Magnetic polaron and Fermi surface effects in the spin-flip scattering of EuB6

The spin-flip scattering (SFS) between conduction and 4f(7) Eu2+ (S-8(7/2)) electrons in the paramagnetic phase of EuB6 (Tgreater than or equal to2T(c)similar or equal to30 K) is studied by means of electron spin resonance (ESR) at three frequencies. The single Dysonian resonance observed in all cases suggests a metallic environment for the Eu2+ ions. The ESR at high field, Hsimilar or equal to12.05 kG (nusimilar or equal to33.9 GHz), has an anisotropic linewidth with cubic symmetry. The low-field, 1.46 kG (4.1 Ghz) and 3.35 kG (9.5 GHz), ESR linewidths are unexpectedly broader and have a smaller anisotropy than at the higher field. The unconventional narrowing and anisotropy of the linewidth at higher fields are indicative of a homogeneous resonance and microscopic evidence for a strong reduction in spin-flip scattering between the spins of Eu2+ and the states in the electron and hole pockets at the X points of the Brillouin zone by magnetic polarons.701

Coexisting on-center and off-center Yb3+ sites in Ce1-xYbxFe4P12 skutterudites

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Electron-spin-resonance (ESR) measurements performed on the filled skutterudite system Ce1-xYbxFe4P12 (x less than or similar to 0.003) unequivocally reveal the coexistence of two Yb3+ resonances associated with sites of considerably different occupations and temperature behaviors. Detailed analysis of the ESR data suggests a scenario where the fraction of oversized (Fe2P3)(4) cages that host Yb ions are filled with a low occupation of on-center Yb3+ sites and a highly occupied T-dependent distribution of off-center Yb3+ sites. Analysis of the Yb-171(3+)(I=1/2) isotope hyperfine splittings reveal that these two sites are associated with a low (similar to 1 GHz) and a high (greater than or similar to 15 GHz) rattling frequency, respectively. Our findings introduce Yb3+ in T-h symmetry systems and use the Yb3+ ESR as a sensitive microscopic probe to investigate the Yb3+ ions dynamics.805Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)DOE [DE-FG02-98ER45707]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)DOE [DE-FG02-98ER45707

Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis

<p>Abstract</p> <p>Background</p> <p>The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma diagnosis by combining imaging and visual field data, using the anatomical organization of retinal ganglion cells.</p> <p>Methods</p> <p>Data from 1499 eyes of glaucoma suspects and 895 eyes with glaucoma were identified at a single glaucoma center. Each underwent Heidelberg Retinal Tomograph (HRT) imaging and standard automated perimetry. A new measure combining these two tests, the structure function index (SFI), was defined in 3 steps: 1) calculate the probability that each visual field point is abnormal, 2) calculate the probability of abnormality for each of the six HRT optic disc sectors, and 3) combine those probabilities with the probability that a field point and disc sector are linked by ganglion cell anatomy. The SFI was compared to the HRT and visual field using receiver operating characteristic (ROC) analysis.</p> <p>Results</p> <p>The SFI produced an area under the ROC curve (0.78) that was similar to that for both visual field mean deviation (0.78) and pattern standard deviation (0.80) and larger than that for a normalized measure of HRT rim area (0.66). The cases classified as glaucoma by the various tests were significantly non-overlapping. Based on the distribution of test values in the population with mild disease, the SFI may be better able to stratify this group while still clearly identifying those with severe disease.</p> <p>Conclusions</p> <p>The SFI reflects the traditional clinical diagnosis of glaucoma by combining optic nerve structure and function. In doing so, it identifies a different subset of patients than either visual field testing or optic nerve head imaging alone. Analysis of prospective data will allow us to determine whether the combined index of structure and function can provide an improved standard for glaucoma diagnosis.</p

Noncubic symmetry in Ca 1-xEu xB 6 (0.15≲x≤1.00): An electron-spin-resonance study

The Eu2+ (4 f7, S=72) g value in Ca1-x Eux B6 (0.15≲x≤1.00) was measured by means of electron spin resonance at two frequencies (fields), 9.4 (≈3.4 kOe) and 34.4 GHz (≈12.1 kOe). The g value was found to be anisotropic and magnetic-field dependent. The amplitude of the anisotropy increases at low temperatures. The observed angular and temperature dependences of the g value suggest tetragonal symmetry caused, presumably, by a distortion along a direction perpendicular to the largest crystal face, the [001] direction. Due to the platelet shape of the samples, part of the anisotropy of the g value can also be attributed to demagnetization effects. The g values decrease at higher fields, which is interpreted in terms of a two-band model involving an exchange interaction between the localized Eu2+ 4 f7 electrons with conduction Eu2+ 5d -like electrons and B 2p -like holes. © 2006 American Institute of Physics

Noncubic symmetry in Ca 1-xEu xB 6 (0.15≲x≤1.00): An electron-spin-resonance study

The Eu2+ (4 f7, S=72) g value in Ca1-x Eux B6 (0.15≲x≤1.00) was measured by means of electron spin resonance at two frequencies (fields), 9.4 (≈3.4 kOe) and 34.4 GHz (≈12.1 kOe). The g value was found to be anisotropic and magnetic-field dependent. The amplitude of the anisotropy increases at low temperatures. The observed angular and temperature dependences of the g value suggest tetragonal symmetry caused, presumably, by a distortion along a direction perpendicular to the largest crystal face, the [001] direction. Due to the platelet shape of the samples, part of the anisotropy of the g value can also be attributed to demagnetization effects. The g values decrease at higher fields, which is interpreted in terms of a two-band model involving an exchange interaction between the localized Eu2+ 4 f7 electrons with conduction Eu2+ 5d -like electrons and B 2p -like holes. © 2006 American Institute of Physics

Noncubic symmetry in Ca1-xEuxB6 (0.15 less than or similar to x <= 1.00): An electron-spin-resonance study

The Eu2+ (4f(7), S=7/2) g value in Ca1-xEuxB6 (0.15 less than or similar to x <= 1.00) was measured by means of electron spin resonance at two frequencies (fields), 9.4 (approximate to 3.4 kOe) and 34.4 GHz (approximate to 12.1 kOe). The g value was found to be anisotropic and magnetic-field dependent. The amplitude of the anisotropy increases at low temperatures. The observed angular and temperature dependences of the g value suggest tetragonal symmetry caused, presumably, by a distortion along a direction perpendicular to the largest crystal face, the [001] direction. Due to the platelet shape of the samples, part of the anisotropy of the g value can also be attributed to demagnetization effects. The g values decrease at higher fields, which is interpreted in terms of a two-band model involving an exchange interaction between the localized Eu2+ 4f(7) electrons with conduction Eu2+ 5d-like electrons and B 2p-like holes. (C) 2006 American Institute of Physics.99

Thermally activated exchange narrowing of the Gd3+ ESR fine structure in a single crystal of Ce1-xGdxFe 4P12 (x-0.001) skutterudite

We report electron spin resonance (ESR) measurements in the Gd3+ doped semiconducting filled skutterudite compound Ce1-xGd xFe4P12 (x-0.001). As the temperature T varies from T- 150 K to T- 165 K, the Gd3+ ESR fine and hyperfine structures coalesce into a broad inhomogeneous single resonance. At T- 200 K the line narrows and as T increases further, the resonance becomes homogeneous with a thermal broadening of 1.1(2) Oe/K. These results suggest that the origin of these features may be associated with a subtle interdependence of thermally activated mechanisms that combine: (i) an increase with T of the density of activated conduction carriers across the T-dependent semiconducting pseudogap; (ii) the Gd3+ Korringa relaxation process due to an exchange interaction JfdS.s between the Gd3+ localized magnetic moments and the thermally activated conduction carriers; and (iii) a relatively weak confining potential of the rare earth ions inside the oversized (Fe 2P3)4 cage, which allows the rare earths to become rattler Einstein oscillators above T- 148 K. We argue that the rattling of the Gd3+ ions, via a motional narrowing mechanism, also contributes to the coalescence of the ESR fine and hyperfine structure. © 2011 American Physical Society

Gd 3+ and Eu 2+ local environment in Ca 1-xEu xB 6 (0.0001 ≤ x ≤ 0.30) and Ca 1-xGd xB 6 (0.0001 ≤ x ≤ 0.01)

Local environment of Gd 3+ and Eu 2+ 4f 7 ions, S =7/2, in Ca 1-xEu xB 6 (0.0001 ≤ x ≤ 0.30) and Ca xGd xB 6 (0.0001 ≤ x ≤ 0.01) is investigated by means of electron spin resonance (ESR). For x ≤ 0.001 the spectra show resolved fine structures due to the cubic crystal electric field and, in the case of Eu, the hyperfine structure due to the nuclear hyperfine field is also observed. The resonances have Lorentzian line shape, indicating insulating host for the Gd 3+ and Eu 2+ ions. As x increases, the ESR lines broaden due to local distortions caused by the Ca/Gd,Eu ions substitution. For Gd (x ≈ 0.001) and Eu (x ≈ 0.02), the spectra present superposition of Lorentzian and Dysonian resonances, suggesting a coexistence of insulating and metallic hosts for the Gd 3+ and Eu 2+ ions. The Gd 3+ and Eu 2+ fine structures are still observable up to x ≈ 0.003 for Gd and x ≈ 0.15 for Eu. For larger values of x the fine and hyperfine structures are no longer observed, the line width increases, and the line shape becomes pure Dysonian anticipating the metallic and semimetallic character of GdB 6 and EuB 6, respectively. These results clearly show that in the low concentration regime the Ca 1-xR xB 6 = Gd, Eu) systems are intrinsically inhomogeneous. No evidence of weak ferromagnetism (WF) was found in the ESR spectra of either metallic or insulating phases of these compounds, suggesting that, if WF is present in these materials, the Gd 3+ and Eu 2+ 4f 7 -electrons are shielded from the WF field. © 2006 WILEY-VCH Verlag GmbH &amp; Co. KGaA