Sample size re-estimation for clinical trials with longitudinal negative binomial counts including time trends

In some diseases, such as multiple sclerosis, lesion counts obtained from magnetic resonance imaging (MRI) are used as markers of disease progression. This leads to longitudinal, and typically overdispersed, count data outcomes in clinical trials. Models for such data invariably include a number of nuisance parameters, which can be difficult to specify at the planning stage, leading to considerable uncertainty in sample size specification. Consequently, blinded sample size re-estimation procedures are used, allowing for an adjustment of the sample size within an ongoing trial by estimating relevant nuisance parameters at an interim point, without compromising trial integrity. To date, the methods available for re-estimation have required an assumption that the mean count is time-constant within patients. We propose a new modeling approach that maintains the advantages of established procedures but allows for general underlying and treatment-specific time trends in the mean response. A simulation study is conducted to assess the effectiveness of blinded sample size re-estimation methods over fixed designs. Sample sizes attained through blinded sample size re-estimation procedures are shown to maintain the desired study power without inflating the Type I error rate and the procedure is demonstrated on MRI data from a recent study in multiple sclerosis.     

The Multimedia activity recall for children and adolescents (MARCA): development and evaluation

Background  

Self-report recall questionnaires are commonly used to measure physical activity, energy expenditure and time use in children and adolescents. However, self-report questionnaires show low to moderate validity, mainly due to inaccuracies in recalling activity in terms of duration and intensity. Aside from recall errors, inaccuracies in estimating energy expenditure from self-report questionnaires are compounded by a lack of data on the energy cost of everyday activities in children and adolescents. This article describes the development of the Multimedia Activity Recall for Children and Adolescents (MARCA), a computer-delivered use-of-time instrument designed to address both the limitations of self-report recall questionnaires in children, and the lack of energy cost data in children.     

Biophysical foundations underlying TMS: Setting the stage for an effective use of neurostimulation in the cognitive neurosciences

Transcranial Magnetic Stimulation (TMS) induces electrical currents in the brain to stimulate neural tissue. This article reviews our present understanding of TMS methodology, focusing on its biophysical foundations. We concentrate on how the laws of electromagnetic induction apply to TMS; addressing issues such as the location, area (i.e., focality), depth, and mechanism of TMS. We also present a review of the present limitations and future potential of the technique.     

Three-dimensional spinal curvature in idiopathic scoliosis

Scoliosis is usually considered as a deformity of the spine in the frontal plane, without reference to curvatures in other planes. In this study, the three-dimensional shape of the spine of 104 patients with untreated idiopathic scoliosis (5-55 degrees Cobb) was studied by means of stereo radiographs to determine relationships between curvature of the spine in the frontal plane view, in the lateral view, and in the intermediate views. There was a weak but statistically significant correlation (r = 0.2) relating greater scoliosis with lesser kyphosis or greater lordosis. In the thoracic region, the sagittal plane spinal curvature was less than that measured in a population without scoliosis (mean difference, 7.72 +/- 9.9 degrees). Seventy-four of 76 scolioses in the upper region of the spine with lateral curvature greater than 5 degrees Cobb were kyphotic. Sixty-four of 84 curves greater than 5 degrees Cobb in the lower region were lordotic. Measuring curvatures in the plane of symmetry of the rotated apical vertebra altered these ratios to 69 of 76 kyphotic in the upper region and 68 of 84 lordotic in the lower region. The plane of maximum curvature of sections of the spine with scoliosis was not related to the plane of symmetry of the rotated apical vertebra, for in kyphotic regions of the spine the rotations of these two planes were in opposite directions. In all cases, the magnitudes of the rotations were quite different, i.e., by a factor of -0.22 for curves in thoracic region and by a factor of 0.24 for curves in the lumbar region. This implies that mechanical measures to correct this spinal deformity or to prevent progression should apply different rotations to the apex from those applied to the curve as a whole and, in opposite senses, in curves in kyphotic regions. There was no evidence of an abnormality of sagittal curvature of a magnitude to implicate it in the etiology or in the treatment.