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- Ebrahimi-Fakhari, Darius, et al.
(författare)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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| 3. |
- Leonardi, M, et al.
(författare)
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20 Years of ICF-International Classification of Functioning, Disability and Health: Uses and Applications around the World
- 2022
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 19:18
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Tidskriftsartikel (refereegranskat)abstract
- The International Classification of Functioning Disability and Health (ICF) was approved in 2001 and, since then, several studies reported the increased interest about its use in different sectors. A recent overview that summarizes its applications is lacking. This study aims to provide an updated overview about 20 years of ICF application through an international online questionnaire, developed by the byline authors, and sent to each World Health Organization Collaborating Centers of the Family of International Classifications (WHO-FIC CCs). Data was collected during October 2020 and December 2021 and descriptive content analyses were used to report main results. Results show how, in most of the respondent countries represented by WHO-FIC CCs, ICF was mainly used in clinical practice, policy development and social policy, and in education areas. Despite its applications in different sectors, ICF use is not mandatory in most countries but, where used, it provides a biopsychosocial framework for policy development in health, functioning and disability. The study provides information about the needs related to ICF applications, that can be useful to organize targeted intervention plans. Furthermore, this survey methodology can be re-proposed periodically to monitor the use of the ICF in the future.
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| 5. |
- McHugo, S. A., et al.
(författare)
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Nanometer–scale metal precipitates in multicrystalline silicon solar cells
- 2001
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 89:8, s. 4282-4288
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we have utilized characterization methods to identify the nature of metal impurityprecipitates in low performance regions of multicrystalline silicon solar cells. Specifically, we haveutilized synchrotron-based x-ray fluorescence and x-ray absorption spectromicroscopy to study theelemental and chemical nature of these impurity precipitates, respectively. We have detectednanometer-scale precipitates of Fe, Cr, Ni, Cu, and Au in multicrystalline silicon materials from avariety of solar cell manufacturers. Additionally, we have obtained a direct correlation between theimpurity precipitates and regions of low light-induced current, providing direct proof that metalimpurities play a significant role in the performance of multicrystalline silicon solar cells.Furthermore, we have identified the chemical state of iron precipitates in the low-performanceregions. These results indicate that the iron precipitates are in the form of oxide or silicatecompound. These compounds are highly stable and cannot be removed with standard siliconprocessing, indicating remediation efforts via impurity removal need to be improved. Futureimprovements to multicrystalline silicon solar cell performance can be best obtained by inhibitingoxygen and metal impurity introduction as well as modifying thermal treatments during crystalgrowth to avoid oxide or silicate formation.
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| 6. |
- Ferrari, S., et al.
(författare)
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Visualizing Vortex Clusters in the Wake of a High-Speed Train
- 2017
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Ingår i: 2017 IEEE INTERNATIONAL CONFERENCE ON SYSTEMS, MAN, AND CYBERNETICS (SMC). - 1062-922X. - 9781538616451 ; 2017-January, s. 683-688
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Konferensbidrag (refereegranskat)abstract
- Visualization of fluid flows at a high-Reynolds number (Re similar to 10(5)) presents difficulties for user comprehension due to density and ambiguous interactions between vortices. Prior work has used cluster-based reduced-order modelling (CROM) to analyze the wake of a High-Speed Train (HST) with Re = 86,000. In this paper, we present a novel surface visualization to convey the spatiotemporal changes undergone by clustered vortices in the HST wake. This visualization is accomplished through dimensional reduction of 3D volumetric vortices into 1D ridges, and physics-based feature tracking. The result is 3D surfaces visualizing the behavior of the vortices in the HST wake. Compared to conventional still-image representations, these surfaces allow the user to quickly compare and analyze the two shedding cycles identified via CROM. The spatiotemporal differences of the primary vortices in these shedding cycles provide analytic insight to influence the aerodynamics of the HST.
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