Roger Weber

For similarity search in high-dimensional vector spaces (or ‘HDVSs’), researchers have proposed a number of new methods (or adaptations of existing methods) based, in the main, on data-space partitioning. However, the performance of these methods generally degrades as dimensionality increases. Although this phenomenon-known as the ‘dimensional curse’-is well known, little or no quantitative a.nalysis of the phenomenon is available. In this paper, we provide a detailed analysis of partitioning and clustering techniques for similarity search in HDVSs. We show formally that these methods exhibit linear complexity at high dimensionality, and that existing methods are outperformed on average by a simple sequential scan if the number of dimensions exceeds around 10. Consequently, we come up with an alternative organization based on approximations to make the unavoidable sequential scan as fast as possible. We describe a simple vector approximation scheme, called VA-file, and report on an experimental evaluation of this and of two tree-based index methods (an R*-tree and an X-tree).

This article reviews several tools we have developed to improve the understanding of locomotor training following spinal cord injury (SCI), with a view toward implementing locomotor training with robotic devices. We have developed (1) a small-scale robotic device that allows testing of locomotor training techniques in rodent models, (2) an instrumentation system that measures the forces and motions used by experienced human therapists as they manually assist leg movement during locomotor training, (3) a powerful, lightweight leg robot that allows investigation of motor adaptation during stepping in response to force-field perturbations, and (4) computational models for locomotor training. Results from the initial use of these tools suggest that an optimal gait-training robot will minimize disruptive sensory input, facilitate appropriate sensory input and gait mechanics, and intelligently grade and time its assistance. Currently, we are developing a pneumatic robot designed to meet these specifications as it assists leg and pelvic motion of people with SCI.

BACKGROUND: A growing number of case reports have described tenofovir (TDF)-related proximal renal tubulopathy and impaired calculated glomerular filtration rates (cGFR). We assessed TDF-associated changes in cGFR in a large observational HIV cohort. METHODS: We compared treatment-naive patients or patients with treatment interruptions > or = 12 months starting either a TDF-based combination antiretroviral therapy (cART) (n = 363) or a TDF-sparing regime (n = 715). The predefined primary endpoint was the time to a 10 ml/min reduction in cGFR, based on the Cockcroft-Gault equation, confirmed by a follow-up measurement at least 1 month later. In sensitivity analyses, secondary endpoints including calculations based on the modified diet in renal disease (MDRD) formula were considered. Endpoints were modelled using pre-specified covariates in a multiple Cox proportional hazards model. RESULTS: Two-year event-free probabilities were 0.65 (95% confidence interval [CI] 0.58-0.72) and 0.80 (95% CI 0.76-0.83) for patients starting TDF-containing or TDF-sparing cART, respectively. In the multiple Cox model, diabetes mellitus (hazard ratio [HR] = 2.34 [95% CI 1.24-4.42]), higher baseline cGFR (HR = 1.03 [95% CI 1.02-1.04] by 10 ml/min), TDF use (HR = 1.84 [95% CI 1.35-2.51]) and boosted protease inhibitor use (HR = 1.71 [95% CI 1.30-2.24]) significantly increased the risk for reaching the primary endpoint. Sensitivity analyses showed high consistency. CONCLUSION: There is consistent evidence for a significant reduction in cGFR associated with TDF use in HIV-infected patients. Our findings call for a strict monitoring of renal function in long-term TDF users with tests that distinguish between glomerular dysfunction and proximal renal tubulopathy, a known adverse effect of TDF.

To determine whether skin blood flow is local or takes part in general regulatory mechanisms, we recorded laser-Doppler flowmetry (LDF; left and right index fingers), blood pressure, muscle sympathetic nerve activity (MSNA), R-R interval, and respiration in 10 healthy volunteers and 3 subjects after sympathectomy. We evaluated 1) the synchronism of LDF fluctuations in two index fingers, 2) the relationship with autonomically mediated fluctuations in other signals, and 3) the LDF ability to respond to arterial baroreflex stimulation (by neck suction at frequencies from 0.02 to 0.20 Hz), using spectral analysis (autoregressive uni- and bivariate, time-variant algorithms). Synchronous LDF fluctuations were observed in the index fingers of healthy subjects but not in sympathectomized patients. LDF fluctuations were coherent with those obtained for blood pressure, MSNA, and R-R interval. LDF fluctuations were leading blood pressure in the low-frequency (LF; 0.1 Hz) band and lagging in the respiratory, high-frequency (HF; approximately 0.25 Hz) band, suggesting passive "downstream" transmission only for HF and "upstream" transmission for LF from the microvessels. LDF fluctuations were responsive to sinusoidal neck suction up to 0.1 Hz, indicating response to sympathetic modulation. Skin blood flow thus reflects modifications determined by autonomic activity, detectable by frequency analysis of spontaneous fluctuations.