"Voxel-based morphometry" should not be used with imperfectly registered images.

John Ashburner and Karl Friston (2000) introduced a standardized method of "voxel-based morphometry" (VBM) for comparisons of local concentrations of gray matter between two groups of subjects. Segmented images of gray matter from grossly normalized high-resolution images are smoothed and their group differences analyzed by the now-conventional voxelwise Worsley approach to Gaussian random fields of differences. This comment concerns an unfortunate interaction between the algorithm's spatial normalization and voxelwise comparison steps, whereby several obvious quantitative confounds are injected at the core of the inference engine the authors put forward. Specifically, the statistics of the resulting voxelwise comparisons are uninformative about group differences wherever the spatial normalization algorithm has failed to register on any robustly appearing image gradient. The method of Ashburner and Friston is defensible only far from all image gradients.     

Pain in U.S. nursing homes: validating a pain scale for the minimum data set

PURPOSE: The aim of this study was to validate a pain scale for the Minimum Data Set (MDS) assessment instrument and examine prevalence of pain in major nursing home subpopulations, including type of admission and cognitive status. DESIGN AND METHODS: This study considered validation of the MDS pain items and derivation of scale performed against the Visual Analogue Scale (VAS), using Automatic Interaction Detection. The derivation data describe 95 postacute care nursing home patients who are able to communicate. The scale is then used in retrospective analysis of 34,675 Michigan nursing home residents. RESULTS: A four-group scale was highly predictive of VAS pain scores (variance explanation 56%) and therefore quite valid in detecting pain. In the prevalence sample, only 47% of postacute patients compared to 63% of postadmission patients reported no pain, and these percentages rose with increasing cognitive impairment. IMPLICATIONS: Pain is prevalent in nursing home residents, especially in those with cognitive dysfunction, and often untreated.     

Plasminogen-enriched pulse-spray thrombolysis with tPA: further developments

PURPOSE: To further improve methods for pulsed plasminogen-enriched thrombolysis and to compare results with the best obtainable with use of tissue plasminogen activator (tPA) alone. MATERIALS AND METHODS: Parameters of plasminogen-enriched pulse-spray thrombolysis were manipulated in groups of rabbits with inferior vena cava thrombosis, and weights of 1-hour residual thrombus were compared. Variables evaluated were (i) tPA pulse frequency, (ii) amount of plasminogen used for enrichment, (iii) tPA concentration and amount, (iv) pulsed versus infused tPA, and (v) admixture versus separation of plasminogen and tPA. RESULTS: With use of 3 mg of tPA and approximately 0.9 mg plasminogen enrichment, efficacy varied directly with pulse frequency over a pulse range of every 15 minutes to every 30 seconds. With use of 30-second pulses of tPA at a concentration 0.125 mg/mL, efficacy also correlated directly with increasing plasminogen enrichment up to, but not beyond, approximately 1.8 mg per 1.24 g of clot. Optimized methodology yielded 89% lysis in 1 hour, as compared to 74% lysis previously reported with use of optimized low-concentration (0.01 mg/ mL) tPA alone. Plasminogen enrichment in conjunction with low concentrations of tPA, admixture of tPA and plasminogen, and fractionation of the plasminogen enrichment all proved to be nonproductive or counterproductive. CONCLUSION: Optimized in vivo postthrombotic plasminogen enrichment significantly accelerated thrombolysis of experimental clots compared to use of optimized tPA alone.     

Functional morphology of the first cervical vertebra in humans and nonhuman primates

The cervical vertebral column bears or balances the weight of the head supported by the nuchal muscles that partly originate from the cervical vertebrae. The position of the head relative to the vertebral column, and consequently locomotion and posture behavior, could thus be associated with the form of the cervical vertebrae. In spite of this assumption and some empirical indications along these lines, primate vertebral morphologies have been reported to be very similar and not clearly related to locomotion. We therefore study the relationship between the morphology of the first cervical vertebra, the atlas, and the locomotion pattern within primates using a geometric morphometric approach. Our analysis is based on a total of 116 vertebrae of adult Homo sapiens, Gorilla gorilla, Pan troglodytes, Pongo pygmaeus, Hylobates lar, Macaca mulatta, Papio hamadryas, Ateles geoffroyi, and Alouatta palliata. On each atlas, 56 landmarks were digitized and superimposed by Procrustes registration. The resulting shape variables were analyzed by principal component analysis, multivariate regression, and partial least-squares analysis. We found that the nine primate species differ clearly in their atlas morphology and that allometric shape change is distinct between the nonhuman primates and Homo sapiens. We could further identify morphological features that relate to the species' locomotion pattern. Human atlas shape, however, cannot be predicted by an extrapolation of the nonhuman primate model. This implies that either the primate atlas is generalized enough to allow bipedal locomotion or else the human atlas morphology is a unique adaptation different from that in the more orthograde nonhuman primates.