No abstract

Summary. A mixed model is a flexible tool for joint modeling purposes, especially when the gathered data are unbalanced. However, computational problems due to the dimension of the joint covariance matrix of the random effects arise as soon as the number of outcomes and/or the number of used random effects per outcome increases. We propose a pairwise approach in which all possible bivariate models are fitted, and where inference follows from pseudo-likelihood arguments. The approach is applicable for linear, generalized linear, and nonlinear mixed models, or for combinations of these. The methodology will be illustrated for linear mixed models in the analysis of 22-dimensional, highly unbalanced, longitudinal profiles of hearing thresholds.

Abstract:We investigated the spatiotemporal variables of gait leading up to freezing. Gait analysis was carried out on 14 patients with Parkinson's disease in the off phase of the medication cycle. A computerised, three-dimensional gait analysis system was used to measure the walking pattern. After several trials of normal walking with voluntary stopping, distracting manoeuvres and obstacles on the walkway were used to provoke freezing or festination. The gait variables of normal (off phase), festinating, prestop, and prefreezing strides were analysed using analysis of variance for repeated-measures. Cadence was excessively increased (68%) and stride length decreased (69%) during festination compared with normal off walking; a pattern which remained pronounced when comparing prefreezing strides with normal stopping. Analysing in more detail the three steps before a freeze, we found a progressive decrease of stride length and stable cadence rates and proportions of double support phases. The relationship between cadence and stride length exhibited an exponential increase of cadence with a decreasing stride length during festination and freezing. Results suggest that freezing is caused by a combination of an increasing inability to generate stride length superimposed on a dyscontrol of the cadence of walking.

Expression of EGFR ligands in primary tumors significantly predicts outcome in KRAS WT cmCRC treated with cetuximab and irinotecan.