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Automated segmentation of neuroanatomical structures in multispectral MR microscopy of the mouse brain.

We present the automated segmentation of magnetic resonance microscopy (MRM) images of the C57BL/6J mouse brain into 21 neuroanatomical structures, including the ventricular system, corpus callosum, hippocampus, caudate putamen, inferior colliculus, internal capsule, globus pallidus, and substantia nigra. The segmentation algorithm operates on multispectral, three-dimensional (3D) MR data acquired at 90-microm isotropic resolution. Probabilistic information used in the segmentation is extracted from training datasets of T2-weighted, proton density-weighted, and diffusion-weighted acquisitions. Spatial information is employed in the form of prior probabilities of occurrence of a structure at a location (location priors) and the pairwise probabilities between structures (contextual priors). Validation using standard morphometry indices shows good consistency between automatically segmented and manually traced data. Results achieved in the mouse brain are comparable with those achieved in human brain studies using similar techniques. The segmentation algorithm shows excellent potential for routine morphological phenotyping of mouse models.

Algorithms↗

Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis.

PURPOSE: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes. DESIGN: Cross-sectional study. PARTICIPANTS: Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes). METHODS: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness measured by OCT, and visual function test results. RESULTS: Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum. CONCLUSIONS: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.

Acute Disease↗

Developing a measure to assess attitudes toward epilepsy in the US population.

The aim of this study was to develop an instrument to measure the US public's attitudes toward people with epilepsy and to assess the initial reliability and validity of the instrument. A 46-item attitudinal instrument was developed and tested using a proportional, stratified, national, random-digit dial household telephone survey of adults aged > or = 18 (n=758). Exploratory factor analyses revealed four underlying constructs that accounted for 34.4% of the variance in the factor analysis: negative stereotypes (alpha=0.73); risk and safety concerns (alpha=0.85); work and role expectations (alpha=0.76); and personal fear and social avoidance (alpha=0.79). Knowledge was also assessed; participants with less knowledge about epilepsy had more negative attitudes. The results of these analyses provided evidence for reliability and construct validity of the instrument. Additional tests of the reliability, validity, and factor structure of the scales are necessary to refine the instrument.

Analysis of Variance↗

REPDOSE: A database on repeated dose toxicity studies of commercial chemicals--A multifunctional tool.

A database for repeated dose toxicity data has been developed. Studies were selected by data quality. Review documents or risk assessments were used to get a pre-screened selection of available valid data. The structure of the chemicals should be rather simple for well defined chemical categories. The database consists of three core data sets for each chemical: (1) structural features and physico-chemical data, (2) data on study design, (3) study results. To allow consistent queries, a high degree of standardization categories and glossaries were developed for relevant parameters. At present, the database consists of 364 chemicals investigated in 1018 studies which resulted in a total of 6002 specific effects. Standard queries have been developed, which allow analyzing the influence of structural features or PC data on LOELs, target organs and effects. Furthermore, it can be used as an expert system. First queries have shown that the database is a very valuable tool.

Animals↗

Comparative EPR and fluorescence conformational studies of fully active spin-labeled melanotropic peptides.

Similar to melanocyte stimulating hormone (alpha-MSH), its potent and long-acting analogue, [Nle(4), D-Phe(7)]alpha-MSH, when labeled with the paramagnetic amino acid probe 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (Toac), maintains its full biological potency, thus validating any comparative structural investigations between the two labeled peptides. Correlation times, calculated from the electron paramagnetic resonance signal of Toac bound to the peptides, and Toac-Trp distances, estimated from the Toac fluorescence quenching of the Trp residue present in the peptides, indicate a more rigid and folded structure for the potent analogue as compared to the hormone, in aqueous medium.

Animals↗

Problems and perspectives on the use of decision-analysis models for prostate cancer.

The use of modeling studies to illustrate the impact of decision choices in cancer treatment is becoming increasingly common. Decision makers should have some understanding of modeling terminology and issues to evaluate such studies. To be useful, prostate cancer treatment models must be based on acceptable structural assumptions, contain valid data and be understandable to clinical experts. Assumptions with regard to population age, clinical stage, tumor differentiation and combinations of treatment modalities used initially, and for later management of local relapse and distant metastases must all be considered. Difficulties abound because most data sources need some adjustment to avoid bias or to reflect current practice. Despite these difficulties, modeling studies may provide unique insights that are valuable for improving prostate cancer decision making.

Aged↗

Factor structure of trunk performance data for healthy subjects.

OBJECTIVE: To examine the factor structure of various measurements of trunk muscle performance for healthy subjects. DESIGN: A total of 22 performance scores were collected and their univariate and multi-variate relationships were examined. BACKGROUND: Extensive literature exists on the measurement of trunk performance data and the relationships between measurements but what needs to be collected to realize a true performance score remains unclear. METHODS: Trunk muscle performance scores of 150 subjects (71 males and 79 females) were obtained on an Isostation B-200 Dynamometer. Twenty-two parameters measuring range of motion, isometric strength, velocity, and endurance on all three planes of motion were collected. The factor structures were constructed using Principal Components Analysis. RESULTS: Clear-cut factor patterns (explained 96.3% of the total variance) suggests that the five-factor structure might be valid and appropriate for this population. The major loading on each factor indicated that: Factor 1 could be labeled as a static strength measure; Factor 2 as velocity; Factor 3 as flexibility; and Factors 4 and 5 as fatigue-resistance. CONCLUSIONS: No single mode of measurement can provide a good representation of a total trunk muscle performance. RelevanceFor the realization of trunk muscle performance, clinics have to measure all modes of isometric strength, velocity, range of motion, and endurance. Care must be taken in eliminating any parameter.

Adult↗

Pain catastrophizing and general health status in a large Dutch community sample.

The aim of the present study was to examine the association between pain catastrophizing and general health status in a Dutch adult community sample, including various subgroups of people with musculoskeletal pain in the analyses. For exploratory reasons this study partly replicated previous studies of the factor structure, reliability, and validity of the Pain Catastrophizing Scale (PCS). Results demonstrated that across different pain subgroups, catastrophizing uniquely contributed variance to the prediction of the various aspects of general health status beyond the variance explained by pain intensity, age, gender, and chronicity. Across subgroups strongest associations were found between catastrophizing and mental health, general health perception, social functioning, and vitality. Furthermore, the association between catastrophizing and the various aspects of general health status was not moderated by the chronicity of the pain. Results of the confirmatory factor analysis statistically confirmed a three-factor model of the PCS, which was invariant across different subgroups of people with musculoskeletal pain. Inter-factor correlations were high, and the incremental explanatory power of the three-factor model over that of a one-factor model was only marginal. This implies that a one-factor model might be justifiable as well, at least in the general community. Across various pain subgroups the reliability of the PCS total and subscales was adequate. Additional evidence for the concurrent validity of the PCS was found as well.

Adult↗

Psychometric analysis of the self-coherence survey.

Self-coherence, as measured by the Self-Coherence Survey, is an important determinant of psychosocial health in a variety of life circumstances. This report presents a psychometric analysis of the Self-Coherence Survey that resulted in three scales labelled Appraisal, Holism, and Introspection. The factorial structure, reliability, and validity of Self-Coherence was evaluated and replicated in two samples from the same community population (Phase I n = 433; Phase II n = 421). The three dimensions identified in the theoretical discussion of self-coherence published in this journal in 1993, were identified and replicated. Implications for further research and nursing practice are discussed.

Adolescent↗

Assessment of pain cognitions in cancer patients with chronic pain.

Although reports suggest that beliefs about pain play an important role in the adjustment and pain experience of non-cancer patients, the impact of cognitions on the pain experience is unknown in cancer patients. This study examined the factor structure, reliability, and validity of the Pain Cognition List-Experimental version, a measure developed to assess patients' self-statements about pain and the extent to which patients are effective in dealing with the pain. The Pain Cognition List-Experimental version was administered to 313 cancer patients during hospitalization. Confirmatory factor analysis was conducted to evaluate the adequacy of fit for the original five factors. Because of a failure to replicate the factors, exploratory factor analysis was conducted, finding the factors Pain Impact, Social Comparison, Acquiescence, and Outcome Efficacy. The internal consistency for the factor Pain Impact was high (r = 0.89), while the other three factors showed low reliability. The factor Catastrophizing, usually an important factor in non-cancer patients, did not emerge. No differences were found across sex. The factors Pain Impact and Acquiescence provided evidence for concurrent validity. Patients with district nursing showed higher scores on the factors Pain Impact and Acquiescence, and higher scores on Pain Impact and Acquiescence were associated with higher pain intensity scores. This study was an attempt to evaluate pain cognitions and beliefs in cancer patients. It is concluded that the Pain Cognition List for non-cancer patients cannot be easily used in cancer pain patients and that evaluation of pain cognitions in cancer patients is useful. Health care providers evaluating pain in cancer patients with chronic pain need to be aware of the impact pain cognitions have on patients' pain experience. Although more research is needed, measuring pain cognitions should be considered.

Chronic Disease↗

Latent variable models of alcohol-related constructs.

This study examines the improvement in validity coefficients and structural relationships derived from formally modeling latent variables of adverse alcohol-related constructs. Results of a confirmatory factor analysis of responses from 8,755 participants in the 1988 National Household Survey of Drug Abuse support a three-factor model of alcohol abuse, dependence, and adverse consequences. A comparison of construct intercorrelations shows latent variables to be superior to measurement approaches using unweighted sums, quantity x frequency calculation, and single-item measurement.

Adolescent↗

The unhealthy lifestyle of people with schizophrenia.

BACKGROUND: Schizophrenia has a high natural mortality of a largely environmental aetiology. There is, however, little research about possible risk factors. This study measured the diet, cigarette and alcohol use, exercise and obesity of a cohort of people with schizophrenia and compared results to general population rates. METHODS: Semi-structured interview using validated research instruments on 102 middle-aged subjects with a diagnosis of schizophrenia, living in the community. Results were compared to general population norms using standard statistical tests. RESULTS: The subjects ate a diet higher in fat and lower in fibre than the general population. They look little exercise but were not significantly more obese. They smoked heavily but drank less alcohol. Most differences remained significant after controlling for social class. CONCLUSIONS: People with schizophrenia have an unhealthy lifestyle, which probably contributes to the excess mortality of the disease. They are therefore an appropriate target group for health promotion interventions.

Energy Intake↗

Clinical global impressions in Alzheimer's clinical trials.

This article reviews the history of Clinical Global Impressions of Change (CGIC) instruments, their use and limitations in clinical trials of Alzheimer's disease, and the development of the National Institute on Aging's Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC). Originally, CGICs were simple and unstructured instruments that asked a clinician to rate change over the duration of a clinical trial. The method, however, failed to consistently detect treatment effects, leading to the development of more structured and subsequently validated approaches, such as the Clinician Interview-Based Impression Scale (CIBI) and the ADCS-CGIC. Both are currently used in clinical trials. The implications and importance of choosing an appropriate global rating are discussed.

Aged↗

Mesoporous silica composites containing multiple regions with distinct pore size and complex pore organization.

Porous ceramics are of great interest for filtration, catalysis, and reactive separation processes. Performance in these applications is highly dependent on features such as pore size distribution and connectivity and wall composition. Here, we describe a method allowing the rational design and synthesis of mesoporous silica composites with controlled heterogeneous pore architectures and demonstrate its validity by producing structures with predetermined placement of regions having different pore size and pore organization.

Journal Article↗

Total synthesis, structure revision, and absolute configuration of (-)-brevenal.

Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(I) thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (-)-2, which also unambiguously established the absolute configuration of the natural product.

Magnetic Resonance Spectroscopy↗

Psychometric properties and clinical utility of the scale for suicide ideation with inpatient children.

The purpose of the current study was to examine the psychometric properties and clinical utility of the Scale for Suicide Ideation (SSI) for children. The SSI was administered to 100 children who were hospitalized. Data were not used from 13 subjects due to the presence of a psychotic disorder or IQ less than 70, leaving 87 participants. The SSI was examined regarding its internal consistency, concurrent validity, construct validity, and factor structure when used with children. Based on the findings, the SSI appears to have adequate psychometric properties and can be used by clinicians and researchers examining children in an inpatient setting. Recommendations for clinicians are included to help make the SSI more functional in use for children.

Child↗

Testing factorial validity and gender invariance of the pain catastrophizing scale.

Recent research has indicated that the Pain Catastrophizing Scale (PCS) is a reliable measure that taps three dimensions of a singular construct. Gender differences have been found consistently in catastrophizing, with women reporting significantly higher scores than men on the PCS. This study was designed to cross-validate the factor structure of the PCS, independently for men and women, through second-order confirmatory factor analysis. Results indicate that the second-order models provide a good fit to the data. The conceptualization of catastrophizing as a singular latent construct, within a hierarchical factorial structure that consists of three first-order factors--rumination, magnification, and helplessness, was supported for both men and women. The second research objective was to test the two models for gender equivalence. Results indicate that all constraints held across gender. Together, these findings support the psychometric soundness of the PCS and indicate that the gender differences found are not due to an inadequate fit of the measurement or structural model.

Adolescent↗

Psychological and behavioral consequences of job loss: a covariance structure analysis using Weiner's (1985) attribution model.

B. Weiner's (1985) attribution model of achievement motivation and emotion was used as a theoretical foundation to examine the mediating processes between involuntary job loss and employment status. Seventy-nine manufacturing employees were surveyed 1 month prior to permanent displacement, and finding another job was assessed 18 months later. Covariance structure analysis was used to evaluate goodness of fit and to compare the model to alternative measurement and structural representations. Discriminant validity analyses indicated that the causal dimensions underlying the model were not independent. Model predictions were supported in that internal and stable attributions for job loss negatively influenced finding another job through expectations for re-employment. These predictions held up even after controlling for influential unmeasured variables. Practical and theoretical implications are discussed.

Adaptation, Psychological↗