Disease progression of spinocerebellar ataxia types 1, 2, 3 and 6 before and after ataxia onset

OBJECTIVE: Our aim was to study the evolution of ataxia and neurological symptoms before and after ataxia onset in the most common spinocerebellar ataxias (SCAs), SCA1, SCA2, SCA3 and SCA6. We therefore jointly analysed the data of the EUROSCA and RISCA studies, which recruited ataxic and non-ataxic mutation carriers. METHODS: We used mixed effect models to analyse the evolution of Scale for the Rating and Assessment of Ataxia (SARA) scores, SCA Functional Index (SCAFI) and Inventory of Non-Ataxia Signs (INAS) counts. We applied multivariable modelling to identify factors associated with SARA progression. In the time interval 5 years prior to and after ataxia onset, we calculated sensitivity to change ratios (SCS) of SARA, SCAFI and INAS. RESULTS: 2740 visits of 677 participants were analysed. All measures showed non-linear progression that was best fitted by linear mixed models with linear, quadratic and cubic time effects. R(2) values indicating quality of the fit ranged from 0.70 to 0.97. CAG repeat was associated with faster progression in SCA1, SCA2 and SCA3, but not SCA6. 5 years prior to and after ataxia onset, SARA had the highest SCS of all measures with a mean of 1.21 (95% CI: 1.20, 1.21) in SCA1, 0.94 (0.93, 0.94) in SCA2 and 1.23 (1.22, 1.23) in SCA3. INTERPRETATION: Our data have important implications for the understanding of disease progression in SCA1, SCA2, SCA3 and SCA6 across the lifespan. Furthermore, our study provides information for the design of interventional trials, especially in pre-ataxic mutation carriers close to ataxia onset and patients in early disease stages

Development of SARA(home), a new video-based tool for the assessment of ataxia at home

BACKGROUND: Clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA) cannot be used to study ataxia at home or to assess daily fluctuations. The objective of the current study was to develop a video-based instrument, SARA(home), for measuring ataxia severity easily and independently at home. METHODS: Based on feasibility of self-application, we selected 5 SARA items (gait, stance, speech, nose-finger test, fast alternating hand movements) for SARA(home) (range, 0-28). We compared SARA(home) items with total SARA scores in 526 patients with spinocerebellar ataxia types 1, 2, 3, and 6 from the EUROSCA natural history study. To prospectively validate the SARA(home), we directly compared the self-applied SARA(home) and the conventional SARA in 50 ataxia patients. To demonstrate feasibility of independent home recordings in a pilot study, 12 ataxia patients were instructed to obtain a video each morning and evening over a period of 14 days. All videos were rated offline by a trained rater. RESULTS: SARA(home) extracted from the EUROSCA baseline data was highly correlated with conventional SARA (r = 0.9854, P < 0.0001). In the prospective validation study, the SARA(home) was highly correlated with the conventional SARA (r = 0.9254, P < 0.0001). Five of 12 participants of the pilot study obtained a complete set of 28 evaluable videos. Seven participants obtained 13-27 videos. The intraindividual differences between the lowest and highest SARA(home) scores ranged from 1 to 5.5. CONCLUSION: The SARA(home) and the conventional SARA are highly correlated. Application at home is feasible. There was a considerable degree of intraindividual variability of the SARA(home) scores

Numerical design of a new forging press drive incorporating non-circular gears

Manufacturing processes as well as products have to be improved continually to meet all the requirements of international competition. Along with economic demands, changing consumer and environmental legislation lead to increased pressure for new and advanced products and processes. Consequently, the forging industry continually tries to improve hot forging processes. Precision hot forging technology, used for the production of connecting rods, bevel gears, straight planet gears, helical gears, clutch gearing or constant velocity joints, has been improved constantly [1-3]. Precision forging is carried out with closed dies in order to guarantee the continuous quality of the workpiece and to avoid possible damage to the forged parts by clipping or piercing operations. Many variables influence the quality of the final product and the economics of the process, especially the workpiece temperature, the die temperature and the pressure dwell time. High workpiece temperatures lead to high temperatures on the surface of the dies. Therefore, the temperature load depends directly on the pressure dwell time. Excessive temperature loads inevitably lead to damage of the dies [4]. This article presents a numerical study of a new press concept using non-circular gears in the drive mechanism. The new press kinematics result in a reduced pressure dwell time in comparison with a conventional press kinematic. © IMechE 2001

Automatische Einstellung des Schneidspaltes Abschlussbericht

SIGLEAvailable from TIB Hannover: RO 146(122) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekArbeitsgemeinschaft Industrieller Forschungsvereinigungen 'Otto von Guericke' e.V. (AIF), Koeln (Germany); Bundesministerium fuer Wirtschaft, Bonn (Germany)DEGerman

Stage-dependent biomarker changes in spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies, knowledge of early biomarker changes is needed. We analyzed cross-sectional data of 292 SCA3 mutation carriers. Blood concentrations of mutant ATXN3 were high before and after ataxia onset, while neurofilament light deviated from normal 13.3 years before onset. Pons and cerebellar white matter volumes decreased and deviated from normal 2.2 years and 0.6 years before ataxia onset. We propose a staging model of SCA3 that includes a biomarker stage characterized by objective indicators of neurodegeneration before ataxia onset