Confirmatory factor analysis of the Wechsler Memory Scale-Revised in a sample of clients with alcohol dependency

Previous analyses of the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) have reported one-, two-, and three-factor solutions and raised questions about the validity of the visual memory subtests. These various findings may stem in part from different methods of analysis, and from the study of different participant samples. To address these issues, we analysed data from the WMS-R and a spatial maze test administered to 154 participants with a history of alcohol dependence. Results from confirmatory factor analysis supported the interpretation of three factors underlying the WMS-R subtests and the spatial maze score in this sample, namely, attention-concentration, immediate memory, and delayed recall. This result held despite the inclusion of the maze score which is a well-validated measure of visuo-spatial memory.     

Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface

Recognition by integrin proteins on the cell surface regulates the adhesive interactions between cells and their surroundings. The structure of the 'I' domain that is found in some but not all integrins, has been determined. However, the only integrin ligands for which structures are known, namely fibronectin and VCAM-1, are recognized by integrins that lack I domains. The intercellular adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the immunoglobulin superfamily (IgSF), but they are recognized by an I domain-containing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or CD11a/CD18). Here we present the crystal structure of the extracellular region of ICAM-2. The glutamic acid residue at position 37 is critical for LFA-1 binding and is proposed to coordinate the Mg2+ ion in the I domain; this Glu 37 is surrounded by a relatively flat recognition surface and lies in a beta-strand, whereas the critical aspartic acid residue in VCAM-1 and fibronectin lie in protruding loops. This finding suggests that there are differences in the architecture of recognition sites between integrins that contain or lack I domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement of N-linked glycans in the membrane-proximal region of domain 2 may be important for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens.     

Impairments of movement kinematics in patients with Huntington's disease: a comparison with and without a concurrent task

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movements profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially, with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand is its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.     

p53 expression in neurofibroma and malignant peripheral nerve sheath tumor. An immunohistochemical study of sporadic and NF1-associated tumors

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.     

Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition

Regenerative axon growth in peripheral neurons is accompanied by increased expression of the growth-associated protein GAP-43. We examined the increase of GAP-43 immunoreactivity in DRG neurons following lesions at different distances along the sciatic nerve, using immunocytochemistry. To control for the variable involvement of DRG axons following injury at different sites, injured neurons were identified by retrograde labeling with Fluoro-Gold. GAP-43 labeling was similar for proximal, distal, and far-distal injuries when only injured neurons are considered. Our results stand in contrast to studies which show that GAP-43 upregulation in neurons of the central nervous system occurs only when lesions are made close to the cell body. This suggests that the mechanisms which control GAP-43 expression following injury differ between central and peripheral neurons.     

Design and simulation of waveguide electrooptic beam deflectors

Numerical simulation based on the scalar beam propagation method, was used to investigate the performance of waveguide electrooptic beam deflectors. The deflectors under investigation consist of a stack of electrooptically controlled prisms in a waveguide. The results were compared to earlier simplified analysis. It was found that for given overall device dimensions, the number of interfaces between prisms in a prism-type electrooptic deflector has significant influence on the device performance when it is small. To avoid wavefront distortion, unwanted reflection from the interfaces, and asymmetry in the deflection angles caused by small number of interfaces, one should use more than about ten interfaces in a typical deflector. Additional insights of device operation and design issues are discussed     

Estimating confidence intervals for cost-effectiveness ratios: an example from a randomized trial

Cost-effectiveness ratios usually appear as point estimates without confidence intervals, since the numerator and denominator are both stochastic and one cannot estimate the variance of the estimator exactly. The recent literature, however, stresses the importance of presenting confidence intervals for cost-effectiveness ratios in the analysis of health care programmes. This paper compares the use of several methods to obtain confidence intervals for the cost-effectiveness of a randomized intervention to increase the use of Medicaid's Early and Periodic Screening, Diagnosis and Treatment (EPSDT) programme. Comparisons of the intervals show that methods that account for skewness in the distribution of the ratio estimator may be substantially preferable in practice to methods that assume the cost-effectiveness ratio estimator is normally distributed. We show that non-parametric bootstrap methods that are mathematically less complex but computationally more rigorous result in confidence intervals that are similar to the intervals from a parametric method that adjusts for skewness in the distribution of the ratio. The analyses also show that the modest sample sizes needed to detect statistically significant effects in a randomized trial may result in confidence intervals for estimates of cost-effectiveness that are much wider than the boundaries obtained from deterministic sensitivity analyses.     

New energy transfer dyes for DNA sequencing

We have synthesized a set of four energy transfer dyes and demonstrated their use in automated DNA sequencing. The donor dyes are the 5- or 6-carboxy isomers of 4'-aminomethylfluorescein and the acceptor dyes are a novel set of four 4,7-dichloro-substituted rhodamine dyes which have narrower emission spectra than the standard, unsubstituted rhodamines. A rigid amino acid linker, 4-aminomethylbenzoic acid, was used to separate the dyes. The brightness of each dye in an automated sequencing instrument equipped with a dual line argon ion laser (488 and 514 nm excitation) was 2-2.5 times greater than the standard dye-primers with a 2 times reduction in multicomponent noise. The overall improvement in signal-to-noise was 4- to 5-fold. The utility of the new dye set was demonstrated by sequencing of a BAC DNA with an 80 kb insert. Measurement of the extinction coefficients and the relative quantum yields of the dichlororhodamine components of the energy transfer dyes showed their values were reduced by 20-25% compared with the dichlororhodamine dyes alone.