Publications

2005
McNamee CE, Nilsson M, von Corswant C, Söderman O. Physicochemical characterization of PEG1500-12-acyloxy-stearate micelles and liquid crystalline phases. Langmuir. 2005;21 (18) :8146-54.Abstract
PEG 12-acyloxy-stearates are used as drug delivery carriers that have low cell damage effects. The mechanical and physical properties surrounding these processes and surfactants are still however not known. In this study, the physicochemical micellar properties of PEG 12-acyloxy-stearates were characterized by optical microscopic, nuclear magnetic resonance, and small-angle X-ray scattering techniques. We determined the phase diagrams of the surfactants as a function of surfactant concentration and temperature, the micellar size and shape, and micellar dynamics. We found that each surfactant has a micellar, cubic Im3m, and hexagonal phase. The aggregation number in the discrete cubic phase, as determined by small-angle X-ray scattering, was approximately 150 for each surfactant, and showed no measurable chain-length dependence. The diffusion coefficients of the surfactant showed a discontinuity between the micellar and cubic phases, where the cubic phases gave very low values on the order of 10(-)(16) m(2) s(-)(1): this value indicates a non-bicontinuous cubic structure. In summary, these surfactants behave to a large extent as nonionic poly(ethylene glycol) surfactants with extended PEG headgroups.
Cabaleiro-Lago C, Nilsson M, Söderman O. Self-diffusion NMR studies of the host-guest interaction between beta-cyclodextrin and alkyltrimethylammonium bromide surfactants. Langmuir. 2005;21 (25) :11637-44.Abstract
Diffusion measurements by nuclear magnetic resonance (NMR) spectroscopy were used to investigate the host-guest association between beta-cyclodextrin (CD) and alkyltrimethylammonium bromide surfactants with different chain lengths, ranging from 6 up to 16 carbons. The scope and limitations of the method in the study of formation of inclusion complexes are discussed. The influences of the presence of CD in the micellization process have been studied, and the apparent critical micellar concentration and the self-diffusion coefficients of the species present in the systems have been calculated. The stoichiometries of the different complexes have been determined. Evidence for the formation of a 2:1 complex in the case of C(16)TAB has been found.
Goldstein JM, Jerram M, Poldrack R, Anagnoson R, Breiter HC, Makris N, Goodman JM, Tsuang MT, Seidman LJ. Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory. Neuropsychology. 2005;19 (4) :509-19.Abstract
Functional imaging studies of sex effects in working memory (WMEM) are few, despite significant normal sex differences in brain regions implicated in WMEM. This functional MRI (fMRI) study tested for sex effects in an auditory verbal WMEM task in prefrontal, parietal, cingulate, and insula regions. Fourteen healthy, right-handed community subjects were comparable between the sexes, including on WMEM performance. Per statistical parametric mapping, women exhibited greater signal intensity changes in middle, inferior, and orbital prefrontal cortices than men (corrected for multiple comparisons). A test of mixed-sex groups, comparable on performance, showed no significant differences in the hypothesized regions, providing evidence for discriminant validity for significant sex differences. The findings suggest that combining men and women in fMRI studies of cognition may obscure or bias results.
Frazier JA, Chiu S, Breeze JL, Makris N, Lange N, Kennedy DN, Herbert MR, Bent EK, Koneru VK, Dieterich ME, et al. Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. Am J Psychiatry. 2005;162 (7) :1256-65.Abstract
BACKGROUND: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. RESULTS: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. CONCLUSIONS: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.
Frazier JA, Breeze JL, Makris N, Giuliano AS, Herbert MR, Seidman L, Biederman J, Hodge SM, Dieterich ME, Gerstein ED, et al. Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder. Bipolar Disord. 2005;7 (6) :555-69.Abstract
OBJECTIVE: Few magnetic resonance imaging (MRI) studies of bipolar disorder (BPD) have investigated the entire cerebral cortex. Cortical gray matter (GM) volume deficits have been reported in some studies of adults with BPD; this study assessed the presence of such deficits in children with BPD. METHODS: Thirty-two youths with DSM-IV BPD (mean age 11.2 +/- 2.8 years) and 15 healthy controls (HC) (11.2 +/- 3.0 years) had structured and clinical interviews, neurological examinations, neurocognitive testing, and MRI scanning on a 1.5 T GE Scanner. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere, and these units were combined into frontal (FL), temporal (TL), parietal (PL), and occipital (OL) lobe volumes. Volumetric differences were examined using univariate linear regression models with alpha = 0.05. RESULTS: Relative to controls, the BPD youth had significantly smaller bilateral PL, and left TL. Analysis of PL and TL gyri showed significantly smaller volume in bilateral postcentral gyrus, and in left superior temporal and fusiform gyri, while the parahippocampal gyri were bilaterally increased in the BPD group. Although the FL overall did not differ between groups, an exploratory analysis showed that the right middle frontal gyrus was also significantly smaller in the BPD group. CONCLUSIONS: Children with BPD showed deficits in PL and TL cortical GM. Further analyses of the PL and TL found differences in areas involved in attentional control, facial recognition, and verbal and declarative memory. These cortical deficits may reflect early age of illness onset.
Tramo MJ, Cariani PA, Koh CK, Makris N, Braida LD. Neurophysiology and neuroanatomy of pitch perception: auditory cortex. Ann N Y Acad Sci. 2005;1060 :148-74.Abstract
We present original results and review literature from the past fifty years that address the role of primate auditory cortex in the following perceptual capacities: (1) the ability to perceive small differences between the pitches of two successive tones; (2) the ability to perceive the sign (i.e., direction) of the pitch difference [higher (+) vs. lower (-)]; and (3) the ability to abstract pitch constancy across changes in stimulus acoustics. Cortical mechanisms mediating pitch perception are discussed with respect to (1) gross and microanatomical distribution; and (2) candidate neural coding schemes. Observations by us and others suggest that (1) frequency-selective neurons in primary auditory cortex (A1) and surrounding fields play a critical role in fine-grained pitch discrimination at the perceptual level; (2) cortical mechanisms that detect pitch differences are neuroanatomically dissociable from those mediating pitch direction discrimination; (3) cortical mechanisms mediating perception of the "missing fundamental frequency (F0)" are neuroanatomically dissociable from those mediating pitch perception when F0 is present; (4) frequency-selective neurons in both right and left A1 contribute to pitch change detection and pitch direction discrimination; (5) frequency-selective neurons in right A1 are necessary for normal pitch direction discrimination; (6) simple codes for pitch that are based on single- and multiunit firing rates of frequency-selective neurons face both a "hyperacuity problem" and a "pitch constancy problem"-that is, frequency discrimination thresholds for pitch change direction and pitch direction discrimination are much smaller than neural tuning curves predict, and firing rate patterns change dramatically under conditions in which pitch percepts remain invariant; (7) cochleotopic organization of frequency-selective neurons bears little if any relevance to perceptual acuity and pitch constancy; and (8) simple temporal codes for pitch capable of accounting for pitches higher than a few hundred hertz have not been found in the auditory cortex. The cortical code for pitch is therefore not likely to be a function of simple rate profiles or synchronous temporal patterns. Studies motivated by interest in the neurophysiology and neuroanatomy of music perception have helped correct longstanding misconceptions about the functional role of auditory cortex in frequency discrimination and pitch perception. Advancing knowledge about the neural coding of pitch is of fundamental importance to the future design of neurobionic therapies for hearing loss.
Jansson J, Schillén K, Nilsson M, Söderman O, Fritz G, Bergmann A, Glatter O. Small-angle X-ray scattering, light scattering, and NMR study of PEO-PPO-PEO triblock copolymer/cationic surfactant complexes in aqueous solution. J Phys Chem B. 2005;109 (15) :7073-83.Abstract
The formation of triblock copolymer/surfactant complexes upon mixing a nonionic Pluronic polymer (PEO-PPO-PEO) with a cationic surfactant, hexadecyltrimethylammonium chloride (CTAC), has been studied in dilute aqueous solutions using small-angle X-ray scattering, static and dynamic light scattering, and self-diffusion NMR. The studied copolymer (denoted P123, EO(20)PO(68)EO(20)) forms micelles with a radius of 10 nm and a molecular weight of 7.5 x 10(5), composed of a hydrophobic PPO-rich core of radius 4 nm and a water swollen PEO corona. The P123/CTAC system has been investigated between 1 and 5 wt % P123 and with varying surfactant concentration up to approximately 170 mM CTAC (or a molar ratio n(CTAC)/n(P123) = 19.3). When CTAC is mixed with micellar P123 solutions, two different types of complexes are observed at various CTAC concentrations. At low molar ratios (>/=0.5) a "P123 micelle-CTAC" complex is obtained as the CTAC monomers associate noncooperatively with the P123 micelle, forming a spherical complex. Here, an increased interaction between the complexes with increasing CTAC concentration is observed. The interaction has been investigated by determining the structure factor obtained by using the generalized indirect Fourier transformation (GIFT) method. The interaction between the P123 micelle-CTAC complexes was modeled using the Percus-Yevick closure. For the low molar ratios a small decrease in the apparent molecular weight of the complex was obtained, whereas the major effect was the increase in electrostatic repulsion between the complexes. Between molar ratios 1.9 and 9 two coexisting complexes were found, one P123 micelle-CTAC complex and one "CTAC-P123" complex. The latter one consists of one or a few P123 unimers and a few CTAC monomers. As the CTAC concentration increases above a molar ratio of 9, the P123 micelles are broken up and only the CTAC-P123 complex that is slightly smaller than a CTAC micelle exists. The interaction between the P123/CTAC complexes was modeled with the hypernetted-chain closure using a Yukawa type potential in the GIFT analysis, due to the stronger electrostatic repulsion.
Golland P, Grimson EWL, Shenton ME, Kikinis R. Detection and analysis of statistical differences in anatomical shape. Med Image Anal. 2005;9 (1) :69-86.Abstract
We present a computational framework for image-based analysis and interpretation of statistical differences in anatomical shape between populations. Applications of such analysis include understanding developmental and anatomical aspects of disorders when comparing patients versus normal controls, studying morphological changes caused by aging, or even differences in normal anatomy, for example, differences between genders. Once a quantitative description of organ shape is extracted from input images, the problem of identifying differences between the two groups can be reduced to one of the classical questions in machine learning of constructing a classifier function for assigning new examples to one of the two groups while making as few misclassifications as possible. The resulting classifier must be interpreted in terms of shape differences between the two groups back in the image domain. We demonstrate a novel approach to such interpretation that allows us to argue about the identified shape differences in anatomically meaningful terms of organ deformation. Given a classifier function in the feature space, we derive a deformation that corresponds to the differences between the two classes while ignoring shape variability within each class. Based on this approach, we present a system for statistical shape analysis using distance transforms for shape representation and the support vector machines learning algorithm for the optimal classifier estimation and demonstrate it on artificially generated data sets, as well as real medical studies.
Yeshwant K, Seldin EB, Gateno J, Everett P, White CL, Kikinis R, Kaban LB, Troulis MJ. Analysis of skeletal movements in mandibular distraction osteogenesis. J Oral Maxillofac Surg. 2005;63 (3) :335-40.Abstract
PURPOSE: The purpose of this study was to use geometric parameters of movement, calculated from 3-dimensional computed tomography (CT) data, to determine the curvilinear distractor dimensions required to correct mandibular deformities in a series of patients. MATERIALS AND METHODS: Preoperative CT scans from 15 patients with symmetric (n = 5) and asymmetric (n = 10) deformities were imported into a CT-based software program (Osteoplan; an open-source visualization application developed by Gering et al at the Surgical Planning Laboratory [SPL, Brigham and Womens Hospital, Boston, MA]). The software was used to reconstruct virtual 3-dimensional models from these scans. Two experienced surgeons, working with a computer scientist, then used Osteoplan to create an ideal treatment plan for each patient. In each case, the 3-dimensional curvilinear movement was quantified using 4 "parameters of movement" (POMs). These parameters were then used to prescribe a distraction device capable of executing the planned skeletal correction. Curvilinear distractor dimensions calculated by Osteoplan included the radius of curvature of the prescribed device, and the distractor elongation, pitch, and handedness. RESULTS: Treatment plans including POMs were developed for each patient. The radii of curvature for the prescribed distractors ranged from 2.3 to 14.1 cm, the distractor elongation dimensions ranged from 0.7 to 3.2 cm, and the pitch (horizontal plane) dimensions ranged from 0.005 to 0.8 cm. Handedness was either a left (n = 12) or right (n = 8) turning helix. CONCLUSION: The results of this study indicate that, using geometric parameters of movement calculated from 3-dimensional CT scans, curvilinear devices could be prescribed for correction of the range of skeletal deformities in this group of patients.
Onitsuka T, Nestor PG, Gurrera RJ, Shenton ME, Kasai K, Frumin M, Niznikiewicz MA, McCarley RW. Association between reduced extraversion and right posterior fusiform gyrus gray matter reduction in chronic schizophrenia. Am J Psychiatry. 2005;162 (3) :599-601.Abstract
OBJECTIVE: The authors examined the association between volume of the fusiform gyrus, a region involved in face processing, and the personality trait of extraversion in patients with schizophrenia. METHOD: Male patients (N=24) and age-matched male comparison subjects (N=26) completed NEO Five-Factor Inventory personality measures of extraversion and underwent high-spatial-resolution magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter. RESULTS: Low extraversion scores were significantly correlated with gray matter volume reductions in the right posterior fusiform gyrus for patients but not comparison subjects. CONCLUSIONS: Reduced right posterior fusiform gyrus volume may contribute to disease-related social disturbances, characterized by both low extraversion and reduced sensitivity to human faces.
Voglmaier MM, Seidman LJ, Niznikiewicz MA, Dickey CC, Shenton ME, McCarley RW. A comparative profile analysis of neuropsychological function in men and women with schizotypal personality disorder. Schizophr Res. 2005;74 (1) :43-9.Abstract
The purpose of this study was to compare the cognitive profiles of men and women with clinically defined schizotypal personality disorder (SPD). We examined the neuropsychological profile of SPD in 26 right-handed females and 31 right-handed males who met DSM-IV criteria for SPD, and matched comparison subjects. Cognitive performance was assessed on measures of abstraction, verbal and spatial intelligence, learning and memory, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of comparison groups matched for sex, age, handedness, ethnicity and parental SES. Overall, SPD subjects showed mild, general decrements in performance in most cognitive domains. However, unlike male SPD subjects, female SPDs did not show relative deficits in verbal learning and abstraction. The results suggest a less severe pattern of cognitive deficits in women with SPD compared to men, consistent with hypotheses of gender differences in cognitive function in schizophrenia.
Yeshwant KC, Seldin EB, Kikinis R, Kaban LB. A computer-assisted approach to planning multidimensional distraction osteogenesis. Atlas Oral Maxillofac Surg Clin North Am. 2005;13 (1) :1-12.
Topgaard D, Sakellariou D, Pines A. NMR spectroscopy in inhomogeneous B0 and B1 fields with non-linear correlation. J Magn Reson. 2005;175 (1) :1-10.Abstract
Resolved NMR spectra from samples in inhomogeneous B0 and B1 fields can be obtained with the so-called "ex situ" methodology, employing a train of composite or adiabatic z-rotation RF pulses to periodically refocus the inhomogeneous broadening during the detection of the time-domain signal. Earlier schemes relied on a linear correlation between the inhomogeneous B0 and B1 fields. Here the pulse length, bandwidth, and amplitude of the adiabatic pulses of the hyperbolic secant type are adjusted to improve the refocusing for a setup with non-linear correlation. The field correlation is measured using a two-dimensional nutation experiment augmented with a third dimension with varying RF carrier frequency accounting for off-resonance effects. The pulse optimization is performed with a computer algorithm using the experimentally determined field correlation and a standard adiabatic z-rotation pulse as a starting point for the iterative optimization procedure. The shape of the z-rotation RF pulse is manipulated to provide refocusing for the conditions given by the sample-, magnet-, and RF-coil geometry.
Verhey JF, Wisser J, Warfield SK, Rexilius J, Kikinis R. Non-rigid registration of a 3D ultrasound and a MR image data set of the female pelvic floor using a biomechanical model. Biomed Eng Online. 2005;4 :19.Abstract
BACKGROUND: The visual combination of different modalities is essential for many medical imaging applications in the field of Computer-Assisted medical Diagnosis (CAD) to enhance the clinical information content. Clinically, incontinence is a diagnosis with high clinical prevalence and morbidity rate. The search for a method to identify risk patients and to control the success of operations is still a challenging task. The conjunction of magnetic resonance (MR) and 3D ultrasound (US) image data sets could lead to a new clinical visual representation of the morphology as we show with corresponding data sets of the female anal canal with this paper. METHODS: We present a feasibility study for a non-rigid registration technique based on a biomechanical model for MR and US image data sets of the female anal canal as a base for a new innovative clinical visual representation. RESULTS: It is shown in this case study that the internal and external sphincter region could be registered elastically and the registration partially corrects the compression induced by the ultrasound transducer, so the MR data set showing the native anatomy is used as a frame for the US data set showing the same region with higher resolution but distorted by the transducer CONCLUSION: The morphology is of special interest in the assessment of anal incontinence and the non-rigid registration of normal clinical MR and US image data sets is a new field of the adaptation of this method incorporating the advantages of both technologies.
Bartling SH, Peldschus K, Rodt T, Kral F, Matthies H, Kikinis R, Becker H. Registration and fusion of CT and MRI of the temporal bone. J Comput Assist Tomogr. 2005;29 (3) :305-10.Abstract
OBJECTIVE: To present and evaluate a registration method to fuse complementary information of CT and MRI of the temporal bone. METHODS: CT and MRI of the temporal bone of 26 patients were independently registered 4 times. A manual, iterative, intrinsic, rigid, and retrospective registration method was used. Mean CREm (consistency registration error) was calculated as a reproducibility measurement. RESULTS: CREm was 0.6 mm (95% CI = 0.52-0.68 mm). T-test revealed no difference between pathologic and normal cases (t[102] = -1.71; P = 0.09). Time needed: 13 minutes. In the registered and fused datasets, important bony surgical landmarks (eg, facial nerve canal, inner ear) could be assessed in 3 dimensions relatively to tumor tissue (eg, acoustic schwannoma). Fluid distribution within partially obliterated cochleae could be assigned to either scalae. CONCLUSION: An accurate, reproducible registration and fusion method that improves tumor surgery and cochlea implantation planning with only minor changes to the clinical workflow was presented and described. We suggest this method in selected cases.
Lange A, Kubicki MM, Wachter J, Zabel M. Chemistry of transition-metal clusters with mixed Sb/S ligands: evidence for a terminal Sb=S double bond in Cp*3Rh3Sb2S5 (Cp* = C5Me5). Inorg Chem. 2005;44 (21) :7328-32.Abstract
The reaction of [Cp2*Rh2Cl4] (Cp* = C5Me5) with a slight excess of K(3)SbS(3) in boiling THF gave the neutral clusters [Cp*4Rh4S5] (1), [Cp*3Rh3Sb2S5] (2), and after salt metathesis [Cp*3Rh3SbSn]PF6 (3; n = 5 and 6). The structures of 1-3 are heterocubane clusters with CpRh, S, and Sb vertices but with sulfur inserted into one (1 and 2) or two (3) edges. X-ray diffraction analysis of 2 additionally reveals a very short Sb-S distance of 2.297(1) A within the novel mu3-Sb2S4 ligand. Density functional theory calculation of the model compounds [SSbS]3-, [HSSbS]2-, and [HSSbH2S]0 provided strong evidence for the existence of a stable terminal Sb=S double bond in 2.
Dickey CC, McCarley RW, Niznikiewicz MA, Voglmaier MM, Seidman LJ, Kim S, Shenton ME. Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive persons with schizotypal personality disorder. Schizophr Res. 2005;78 (2-3) :297-308.Abstract
INTRODUCTION: Schizotypal personality disorder (SPD) shares with schizophrenia many biological features, yet little is known about the clinical characteristics of persons diagnosed with this disorder. This report describes the clinical, cognitive and socio-occupational characteristics of a community sample of subjects diagnosed with SPD. METHOD: Sixty-four male and 40 female neuroleptic-naive DSM-IV SPD subjects and 59 male and 51 female comparison subjects were recruited from the community for a total sample of 214 subjects. Demographic and cognitive differences between groups and, within the SPD group, the effect of gender on clinical features, such as the SPD criteria, SAPS, SANS, Schizotypal Personality Questionnaire, and co-morbidity, were examined using ANOVA and Chi-square distributions. RESULTS: SPD subjects, in contrast to comparison subjects, had significantly lower socio-economic status, poorer social relationships and skills, and lower vocabulary scores. Furthermore, SPD subjects demonstrated more impairment on Vocabulary scores than on Block Design, as measured by the WAIS-R, a pattern not seen in comparison subjects. In the SPD cohort, positive symptoms predominated and nearly half were co-morbid for major depression. With respect to gender, male SPD subjects, compared with female SPD subjects, evinced significantly more negative symptoms, fewer friends, had more odd speech, and were more likely to also suffer from paranoid and narcissistic personality disorders. In contrast to male SPD subjects, female SPD subjects perceived themselves to be more disorganized. CONCLUSIONS: SPD subjects, similar to schizophrenics, are impaired socially, occupationally, and cognitively, particularly in the area of verbal measures. Moreover, male SPD subjects may be more severely affected than female SPD subjects across multiple domains of functioning.
Vaina LM, Cowey A, Jakab M, Kikinis R. Deficits of motion integration and segregation in patients with unilateral extrastriate lesions. Brain. 2005;128 (Pt 9) :2134-45.Abstract
Functional neuroimaging in human subjects and single cell recordings in monkeys show that several extra-striate visual areas are activated by visual motion. However, the extent to which different types of motion are processed in different regions remains unclear, although neuropsychological studies of patients with circumscribed lesions hint at regional specialization. We, therefore, studied four patients with unilateral damage to different regions of extrastriate visual cortex on a series of visual discrimination tasks that required them, to a different extent, to integrate local motion signals in order to correctly perceive the direction of global motion. Performance was assessed psychophysically and compared with that of control subjects and with the patients' performance with stimuli presented in the visual field ipsilateral to the lesion. The results indicate considerable regional specialization in extra-striate regions for different aspects of motion processing, namely the largest displacement from frame to frame (D-max) that can sustain perception of coherent motion; perception of relative speed; the amount of coherent motion needed to sustain a percept of global motion in a particular direction; the detection of discontinuities within a moving display; the extraction of form from motion. It was also clear that a defect in local motion, i.e. D-max, can be overcome by integrating local motion signals over a longer period of time. Although no patient suffered from only one defect, the overall pattern of results strongly supports the notion of regional specialization for different aspects of motion processing.
Gurrera RJ, Dickey CC, Niznikiewicz MA, Voglmaier MM, Shenton ME, McCarley RW. The five-factor model in schizotypal personality disorder. Schizophr Res. 2005;80 (2-3) :243-51.Abstract
Studies of the five-factor model of personality in schizotypal personality disorder (SPD) have produced inconsistent results, particularly with respect to openness. In the present study, the NEO-FFI was used to measure five-factor personality dimensions in 28 community volunteers with SPD and 24 psychiatrically healthy individuals. Standard multivariate statistical analyses were used to evaluate personality differences as a function of diagnosis and gender. Individuals with SPD had significantly higher levels of neuroticism and significantly lower levels of extraversion, agreeableness and conscientiousness than those without SPD. Female, but not male, SPD subjects had significantly higher openness levels than their healthy counterparts, and this gender-specific group difference persisted when SPD symptom severity was statistically controlled. These findings suggest that gender-associated differences in openness may account for prior inconsistent findings regarding this dimension, and they further underscore the importance of examining gender effects in future studies of SPD.
Zou KH, Resnic FS, Talos I-F, Goldberg-Zimring D, Bhagwat JG, Haker SJ, Kikinis R, Jolesz FA, Ohno-Machado L. A global goodness-of-fit test for receiver operating characteristic curve analysis via the bootstrap method. J Biomed Inform. 2005;38 (5) :395-403.Abstract
OBJECTIVE: Medical classification accuracy studies often yield continuous data based on predictive models for treatment outcomes. A popular method for evaluating the performance of diagnostic tests is the receiver operating characteristic (ROC) curve analysis. The main objective was to develop a global statistical hypothesis test for assessing the goodness-of-fit (GOF) for parametric ROC curves via the bootstrap. DESIGN: A simple log (or logit) and a more flexible Box-Cox normality transformations were applied to untransformed or transformed data from two clinical studies to predict complications following percutaneous coronary interventions (PCIs) and for image-guided neurosurgical resection results predicted by tumor volume, respectively. We compared a non-parametric with a parametric binormal estimate of the underlying ROC curve. To construct such a GOF test, we used the non-parametric and parametric areas under the curve (AUCs) as the metrics, with a resulting p value reported. RESULTS: In the interventional cardiology example, logit and Box-Cox transformations of the predictive probabilities led to satisfactory AUCs (AUC=0.888; p=0.78, and AUC=0.888; p=0.73, respectively), while in the brain tumor resection example, log and Box-Cox transformations of the tumor size also led to satisfactory AUCs (AUC=0.898; p=0.61, and AUC=0.899; p=0.42, respectively). In contrast, significant departures from GOF were observed without applying any transformation prior to assuming a binormal model (AUC=0.766; p=0.004, and AUC=0.831; p=0.03), respectively. CONCLUSIONS: In both studies the p values suggested that transformations were important to consider before applying any binormal model to estimate the AUC. Our analyses also demonstrated and confirmed the predictive values of different classifiers for determining the interventional complications following PCIs and resection outcomes in image-guided neurosurgery.

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