Sampling Patients Within and Across Health Care Providers: Multi-Stage Non-Nested Samples in Health Services Research

In order to better inform study design decisions when sampling patients within and across health care providers we develop a simulation-based approach for designing complex multi-stage samples. The approach explores the tradeoff between competing design goals such as precision of estimates, coverage of the target population and cost.We elicit a number of sensible candidate designs, evaluate these designs with respect to multiple sampling goals, investigate their tradeoffs, and identify the design that is the best compromise among all goals. This approach recognizes that, in the practice of sampling, precision of the estimates is not the only important goal, and that there are tradeoffs with coverage and cost that should be explicitly considered. One can easily add other goals. We construct a sample frame with all phase III clinical cancer treatment trials that are conducted by cooperative oncology groups of the National Cancer Institute from October 1, 1998 through December 31, 1999. Simulation results for our study suggest sampling a different number of trials and institutions than initially considered.Simulations of different study designs can uncover efficiency gains both in terms of improved precision of the estimates and in terms of improved coverage of the target population. Simulations enable us to explore the tradeoffs between competing sampling goals and to quantify these efficiency gains. This is true even for complex designs where the stages are not strictly nested in one another.     

Grasp synthesis for upper-extremity FNS

Functional neuromuscular stimulation (FNS) has been used in upper extremity neuroprostheses to provide grasp and release for quadriplegic individuals. The goal of this project was to determine the electrode/muscle input/output characteristics with the greatest influence on the grasp output. This was evaluated by simulating the grasp synthesis procedure, using a model of the electrode/muscle output as a function of stimulus level and joint angle. The parameters of this model were determined from experimental data from 112 electrodes. The grasp output for 500 different modelled pairs of electrodes were analysed, with each pair consisting of a thumb flexor and a thumb extensor. The simulation results indicate that the most influential electrode input/output characteristics are the output stiffness, defined as the change in force output for a unit change in joint angle at a constant level of stimulation, and the length dependency mean-squared error. Recruitment gain was found to be of secondary influence on the grasp output, and the threshold, force direction and non-linearity of the stimulus level to force relationship were found to have little influence on the grasp output. These results establish criteria for electrode selection and implantation for use in upper extremity FNS.     

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.