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At least 1,693 records · Page 94Linked to original sources
PubMed2003

Depressive mixed state: dimensional versus categorical definitions.

BACKGROUND: Recently, there has been a rebirth of studies on depressive mixed state (DMX), defined as a major depressive episode (MDE) plus few concurrent hypomanic symptoms. It is still unclear how to best define DMX. The study's aim was to test a categorical versus a dimensional definition of DMX. METHODS: Consecutive 260 bipolar II disorder and 173 unipolar MDE outpatients were interviewed with the Structured Clinical Interview for DSM-IV, when presenting for MDE treatment (drug-free). Hypomanic symptoms during index MDE were systematically assessed and graded by a hypomania rating scale (Hypomania Interview Guide, HIG). Different cutoffs of the HIG to define DMX were tested versus a categorical definition of DMX (requiring more than two concurrent hypomanic symptoms, DMX3). Sensitivity and specificity for predicting bipolar II diagnosis were compared. The best definition of DMX based on the HIG was also compared to DMX3 versus typical bipolar variables (early onset, many recurrences, atypical features, bipolar family history). RESULTS: An HIG cutoff of 8 had a specificity for predicting bipolar II diagnosis similar to that of DMX3. HIG>8 was strongly associated with bipolar family history (an important external diagnostic validator), and DMX3 was significantly associated with more bipolar variables (including bipolar family history). LIMITATION: The interview was done by a single interviewer. CONCLUSIONS: Similar specificity for predicting bipolar II disorder diagnosis and a similar strong association with bipolar family history suggest that a categorical and a dimensional definition of DMX could have similar validity. However, the dimensional definition (based on the scoring of a hypomania rating scale) could lead to a better assessment of hypomanic symptoms, resulting in more correct diagnoses of DMX.

Adult↗
PubMed1998

Evaluation of key sources of variability in the measurement of pharmaceutical drug products by near infrared reflectance spectroscopy.

Potential sources of variability in the measurement of solid oral drug products by near infrared reflectance spectroscopy were evaluated with statistical experimental design. Spectra were collected for two different tablet types according to the data collection and treatment parameters defined by the experimental design. Each tablet had three different dose-levels. Libraries were constructed using second-derivative spectra. Key figures-of-merit generated during internal and external library validation were used to calculate which parameters most strongly influence the library performance for dose-level discrimination. These responses and their corresponding experimental conditions were evaluated with the screening model in the JMP program. Segment value used for the second-derivative calculation was an an influential factor and had a complex effect. Orientation on the sampling platform also had an influential effect for embossed tablets. Collection of spectra over fewer days decreased variability within the library. More frequent reference spectrum collection improved the performance of libraries to a small degree. A larger sample population increased the range of spectral variability within a dose-level but apparently not the overall performance of the library. The number of scans averaged per spectrum was not an influential factor in this study. These results are summarized and used to recommend an approach to dose-level discrimination.

Evaluation Studies as Topic↗
PubMed1998

[In vivo study of kinematics of the elbow using electromagnetic goniometer].

We used an electromagnetic goniometer to study the angular and translations displacements between the humerus and the 2 bones of the forearm. The electromagnetic gionometer allows acquisition of the coordinates and analysis of the 6 degrees of motion. To validate our external fixation apparatus, we used a fresh body upper limb. At first, a series of measurements was conducted with the apparatus. We then performed a series of measurements, by fixing the transmitter and receiver with external fixation pins directly inserted into the bones of the arm and forearm. To assess the reproducibility of our method, we chose a healthy subject. We performed 20 measurements over his right and left elbows. In order to study normal elbow kinematics, we performed measurements on 10 healthy subjects. The study of rotation showed that the apparatus was adapted to measure flexion-extension. It limited pronation-supination movement to about 26.7 degrees. Abduction was increased by 19.7 degrees by our apparatus during flexion-extension, but abduction was reliable within a 2 degrees range for pronation-supination. The sliding movements recorded during flexion-extension were reliable within approximately 3 mm for frontal translations, 6 mm for fitting, and 1 mm for external translations. For the sliding movements recorded in pronation-supination, frontal translations were reliable within about 7 mm, fitting was reliable within 1.9 mm and external translations were reliable within about 2.9 mm. During flexion-extension of the elbow, flexion-extension, frontal translations and external translations were reproducible. The reproducibility test showed that only 6 measurements were reproducible. The kinematic elbow study of a healthy subject showed that the average amplitude of flexion-extension was close to the measurement observed with the manual goniometer. The results in the healthy subject showed that the elbow is more stable during pronation-supination than during flexion-extension. This preliminary study should allow us, in the near future, to study elbow prosthesis kinematics.

Cadaver↗
PubMed2003

Assessment of the accuracy of diagnostic tests: the cross-sectional study.

In diagnostic accuracy studies, the contrast of interest can be one of the following: one single test contrast; comparing two or more single tests; further testing in addition to previous diagnostics; and comparing alternative diagnostic strategies. The clinical diagnostic problem under study must be specified. Studies of "extreme contrasts" (as early phase evaluations) and studies in "clinical practice" settings (assessing clinical value) should be distinguished. Design options are (1) survey of the total study population, (2) case-referent approach, or (3) test-based enrollment. Data collection should generally be prospective, but ambispective and retrospective approaches are sometimes appropriate. In addition to determinants of primary interest [the test(s) under study] possible modifiers of test accuracy and confounding variables must be specified. The reference standard procedure should be independent from the test results. Applying a reference standard can be difficult in case of classification errors, lack of a clear pathophysiologic concept, incorporation bias, or invasive or complex investigations. Possible solutions are: an independent expert panel, and the delayed type cross-sectional study (clinical follow-up). Also, a prognostic criterion can be chosen. For studies to be relevant for practice, inclusion criteria must be based on "intention to diagnose" or "intention to screen." The recruitment procedure is preferably a consecutive series of presenting patients or a target population screening, respectively. Sample size estimation should be routine. Analysis has to be focused on the contrast of interest. Estimating test accuracy and prediction of outcome need different approaches. External (clinical) validation requires repeated studies in other, similar populations. Also, systematic reviews and meta-analysis have a role. To enable readers of diagnostic research reports to evaluate whether methodological key issues were addressed, authors are advised to follow the STARD guidelines.

Cross-Sectional Studies↗
PubMed1998

Predictive models of natural history in primary biliary cirrhosis.

Primary biliary cirrhosis is a slow, progressive disease. Although many years may elapse before asymptomatic primary biliary cirrhosis patients begin experiencing symptoms of liver disease, their overall survival is significantly lower than the normal population. The Mayo natural history model has been developed to depict patient survival in the absence of effective therapeutic intervention. Although there are a number of caveats in applying this model, it has been validated using external data sets and established as an accepted tool for clinical or research purposes. Furthermore, recent data suggest that the Mayo natural history model continues to provide useful, predictive information in the presence of ursodeoxycholic acid therapy, which has been shown to lower the serum bilirubin to the natural history model for patient survival. In addition to the natural history model for patient survival, mathematical models have been developed to describe histologic progression and development of esophageal varices.

Disease Progression↗
PubMedDate not supplied

Prediction of aqueous solubility of heteroatom-containing organic compounds from molecular structure.

The use of quantitative structure-property relationships (QSPRs) to predict aqueous solubilities (log S) of heteroatom-containing organic compounds from their molecular structure is presented. Three data sets are examined. Data set 1 contains 176 compounds having one or more nitrogen atoms with some oxygen (log S[mol/L] range is -7.41 to 0.96). Data set 2 contains 223 compounds having one or more oxygen atoms, with no nitrogen (log S[mol/L] range is -8.77 to 1.57). Data set 3 contains all 399 compounds from sets 1 and 2 (log S/mol/L] range is -8.77 to 1.57). After descriptor generation and feature selection, multiple linear regression (MLR) and computational neural network (CNN) models are developed for aqueous solubility prediction. The best results were obtained with nonlinear CNN models. Root-mean-square (rms) errors for training with the three data sets ranged from 0.3 to 0.6 log units. All models were validated with external prediction sets, with the rms errors ranging from 0.6 log units to 1.5 log units.

Journal Article↗
PubMedDate not supplied

Determination of Abraham solute parameters from molecular structure.

The Abraham solute parameters are well-known factors for the quantitative description of solute/solvent interactions. A quantitative structure-property relationship (QSPR) is reported for the E, S, A, and B parameters of a large set of 457 solutes, of very different chemical nature. The proposed models, derived from multilinear regression analysis (MLRA) and computational neural networks (CNN), contain five descriptors calculated solely from the molecular structure of compounds. Good correlations were obtained for the four parameters studied, and the corresponding values of R(2) and standard deviations are better or similar than those derived from other theoretical bases. All models were validated by external prediction sets. The proposed QSPR models, both by MLRA and CNN, contain analogous descriptors encoding similar information, that agree with the accepted physicochemical meaning of the Abraham parameters; however, some descriptors which encode information that is not associated with this physicochemical meaning are also included in the QSPR models.

Journal Article↗
PubMed2005

Exploring the role of different drug transport routes in permeability screening.

The influence of different drug transport routes in intestinal drug permeability screening assays was studied. Three experimental models were compared: the small-intestine-like 2/4/A1 cell model, which has a leaky paracellular pathway, the Caco-2 cell model, which has a tighter paracellular pathway, and artificial hexadecane membranes (HDMs), which exclusively model the passive transcellular pathway. The models were investigated regarding their ability to divide passively and actively transported compounds into two permeability classes and to rank compounds according to human intestinal absorption. In silico permeability models based on two-dimensional (2D) and three-dimensional (3D) molecular descriptors were also developed and validated using external test sets. The cell-based models classified 80% of the acceptably absorbed compounds (FA >/= 30%) correctly, compared to 60% correct classifications using the HDM model. The best compound ranking was obtained with 2/4/A1 (r(s) = 0.74; r(s) = 0.95 after removing actively transported outliers). The in silico model based on 2/4/A1 permeability gave results of similar quality to those obtained when using experimental permeability, and it was also better than the experimental HDM model at compound ranking (r(s) = 0.85 and 0.47, respectively). We conclude that the paracellular transport pathway present in the cell models plays a significant role in models used for intestinal permeability screening and that 2/4/A1 in vitro and in silico models are promising alternatives for drug discovery permeability screening.

Administration, Oral↗
PubMed2005

Improved approach for proteochemometrics modeling: application to organic compound--amine G protein-coupled receptor interactions.

MOTIVATION: Proteochemometrics is a novel technology for the analysis of interactions of series of proteins with series of ligands. We have here customized it for analysis of large datasets and evaluated it for the modeling of the interaction of psychoactive organic amines with all the five known families of amine G protein-coupled receptors (GPCRs). RESULTS: The model exploited data for the binding of 22 compounds to 31 amine GPCRs, correlating chemical descriptions and cross-descriptions of compounds and receptors to binding affinity using a novel strategy. A highly valid model (q2 = 0.76) was obtained which was further validated by external predictions using data for 10 other entirely independent compounds, yielding the high q2ext = 0.67. Interpretation of the model reveals molecular interactions that govern psychoactive organic amines overall affinity for amine GPCRs, as well as their selectivity for particular amine GPCRs. The new modeling procedure allows us to obtain fully interpretable proteochemometrics models using essentially unlimited number of ligand and protein descriptors.

Amines↗
PubMed2007

Development and validation of a food frequency questionnaire for the assessment of dietary total antioxidant capacity.

The total antioxidant capacity (TAC) of the diet may be an important tool to monitor the protective effect of plant foods in epidemiological studies. We developed a semi-quantitative FFQ for the assessment of dietary TAC by 3 different assays, i.e., Trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). The FFQ consists of 53 questions about the major sources of dietary TAC in Northern Italy and was validated against a 3-d weighed food record (3D-WR) in 285 individuals (159 males and 126 females) aged 35-88 y and living in the province of Parma (Italy). Plasma TAC was also evaluated in a subgroup of subjects using the TEAC and FRAP assays. The FFQ was associated with 3D-WR (quadratic-weighted kappa = 0.49 for TEAC, 0.53 for TRAP, and 0.49 for FRAP; P < 0.0001) and proved reasonably accurate to classify individuals into quartiles of TAC intake. The FFQ had a good repeatability when readministered after 1 y in 55 subjects (quadratic-weighted kappa for intertertile agreement = 0.66 for TEAC, 0.70 for TRAP and 0.68 for FRAP; P < 0.0001). With both dietary instruments, the main contributors to TAC intake were coffee and tea in women and alcoholic beverages in men, followed by fruits and vegetables in both sexes. Plasma TAC and dietary TAC were not associated. In conclusion, our FFQ has the potential for being used to rank subjects on the basis of their antioxidant intake as determined by dietary TAC in large epidemiological studies. The FFQ should be validated in external populations before being used for research purposes.

Adult↗
PubMed2025

Augmented kurtosis-based projection pursuit: a novel, advanced machine learning approach for multi-omics data analysis and integration.

Due to the heterogeneity of multi-omics data, exacting their maximum information potential remains a challenge. Whereas some solutions have been offered, most cannot overcome the large linear dynamic range associated with such data, while others require large biological effect sizes to produce meaningful models. Here, we (i)&#xa0;perform a comprehensive benchmarking of multi-omics data analysis tools, and (ii)&#xa0;introduce kurtosis-based projection pursuit analysis, augmented with classification and regression trees (kPPA-CART) as a robust, easy-to-implement alternative. Using ground truth data, we demonstrate that kPPA-CART exhibits superiority in inferring biological significance from low-intensity (low-count) features and studies with small biological effect sizes. Applying it to experimental breast cancer data from The Cancer Genome Atlas, we identify novel genes that cluster the samples into subtypes that mimic the canonical PAM50 classes with notable improvements. Validating with external metastatic breast cancer data from the AURORA US consortium, kPPA-CART identifies genes that are associated with poor event-free survival and additional clustering associated with increased tumor mutational burden. Finally, we provide an R package and an online implementation of kPPA-CART.

Humans↗
PubMed2002

Proteo-chemometrics analysis of MSH peptide binding to melanocortin receptors.

The published data for six melanocortin peptides binding to wild-type and chimeric melanocortin MC(1)/MC(3) receptors were analysed using the novel proteo-chemometrics modelling approach. The chimeric receptors and the peptides were coded using binary descriptors and used to correlate with the experimental data for affinity or selectivity for peptides binding to receptors. Correlations were achieved using partial least squares projection to latent structures (PLS) and statistically valid models were obtained. The models were further improved by adding cross-terms and applying orthogonal signal correction. The models were validated using external prediction, with half of the data being excluded from the modelling. Interpretation of the results using PLS coefficient plots revealed that the binding pocket for the melanocortins is located between the first, second, third, sixth and seventh transmembrane regions of the melanocortin receptors, in good agreement with previous three-dimensional models for the interactions of melanocortins with melanocortin receptors. Further, analysis of cross-terms between peptide descriptors indicated that the proteo-chemometrics modelling is able to distinguish between differences in the conformational space of the peptides that affect binding affinity and selectivity.

Humans↗
PubMedDate not supplied

Activity-based diary for Parkinson's disease.

The objective of this study was to develop a Parkinson's disease diary that evaluates a patient's difficulties in performing activities as a substitute for the amount of "on"- and "off"-time and to assess its clinimetric qualities. In this study, 84 patients with Parkinson's disease kept a diary for 2 or 3 periods of 5 days. Daily, five items were recorded across 11 time periods. Patients simultaneously recorded "on-off" in the traditional way. The diary was easily understood, and median recording time was 5-10 minutes a day. Clinimetric analysis showed that the diary could be reduced successfully to 3 days, in which five items (walking, transfers, manual activities, dyskinesias, and sleep) with four response options (no, slight, moderate, and severe difficulty) were assessed seven times daily. Sumscores of the first three items accurately predicted being "on" or "off" in 93% of the cases, making separate scoring of "on" and "off" unnecessary. The diary was internally consistent and showed good reproducibility. Construct validity with external measures was adequate, and comparisons between patients grouped by disease severity and by degree of fluctuations revealed significant differences in the expected directions. Taken together, this Parkinson's disease diary has a sound clinimetric basis, provides information on the extent of perceived disability, and thereby accurately reflects the severity of "off"-periods and the variability of motor fluctuations.

Activities of Daily Living↗
PubMed2001

Complications of epilepsy surgery after 654 procedures in Sweden, September 1990-1995: a multicenter study based on the Swedish National Epilepsy Surgery Register.

OBJECTIVE: To present the first national multicenter study on complications after epilepsy surgery procedures to include all epilepsy surgery centers in Sweden: Göteborg, Linköping, Lund, Stockholm, Umeå, and Uppsala. METHODS: Every epilepsy surgery procedure in Sweden is reported to the Swedish National Epilepsy Surgery Register. The report includes relevant social and medical items and complications. A complication is defined as minor if it resolves within 3 months and major if it affects activities of daily living and lasts longer than 3 months. Follow-up data are recorded for 2 years after the operation. Intrinsic checkpoints and external revision validate the register data. RESULTS: During the inclusion period (September 1990-December 1995), 654 surgical procedures were performed (age range, 6 mo-67 yr). Of these, 205 were invasive electrode procedures (182 first investigations and 23 reinvestigations), and 449 were therapeutic procedures (375 first operations and 74 reoperations). After invasive electrode procedures, only minor complications were reported (6.3%). For all 449 therapeutic procedures (including reoperations), minor complications were reported in 8.9% and major complications in 3.1 %. Only one major complication was reported in a patient under the age of 35 years. CONCLUSION: This is the first national multicenter study on complications after epilepsy surgery. It demonstrates that these procedures as performed at six different centers in Sweden are safe, but also that risk is related to age. In patients younger than age 35 years, the risk for a major complication after invasive subdural strip electrode investigation and epilepsy surgery is low.

Adolescent↗
PubMed2003

Validity of a gambling scale for the addiction severity index.

This study assessed the validity of an adaptation of the Addiction Severity Index (ASI) for evaluating severity of gambling problems. Participants (N = 597) from four different populations (pathological gamblers enrolled in a treatment study, pathological gamblers initiating outpatient treatment at a community-based program, frequent gamblers recruited from advertisement, and substance abusers) completed the ASI, along with a supplemental gambling subscale (ASI-G). Internal consistency of the ASI-G was good (alpha =.90), and a principal components analysis indicated a single factor explained 73% of the variance in responses. ASI-G scores demonstrated excellent convergent validity with other measures of gambling and convergent validity with external sources, including collateral informant and clinician-rated reports. ASI-G scores discriminated among the samples tested. Temporal stability of ASI-G scores was high during a 1-month period for patients with substance abuse disorder who were not seeking gambling treatment. For treatment-seeking gamblers, the number of treatment sessions attended was significantly associated with reductions in ASI-G scores. Together, these data suggest that the ASI-G subscale may be a useful tool for assessing severity of gambling problems in a variety of populations.

Adult↗
PubMed2002

Classification of G-protein coupled receptors by alignment-independent extraction of principal chemical properties of primary amino acid sequences.

We have developed an alignment-independent method for classification of G-protein coupled receptors (GPCRs) according to the principal chemical properties of their amino acid sequences. The method relies on a multivariate approach where the primary amino acid sequences are translated into vectors based on the principal physicochemical properties of the amino acids and transformation of the data into a uniform matrix by applying a modified autocross-covariance transform. The application of principal component analysis to a data set of 929 class A GPCRs showed a clear separation of the major classes of GPCRs. The application of partial least squares projection to latent structures created a highly valid model (cross-validated correlation coefficient, Q(2) = 0.895) that gave unambiguous classification of the GPCRs in the training set according to their ligand binding class. The model was further validated by external prediction of 535 novel GPCRs not included in the training set. Of the latter, only 14 sequences, confined in rapidly expanding GPCR classes, were mispredicted. Moreover, 90 orphan GPCRs out of 165 were tentatively identified to GPCR ligand binding class. The alignment-independent method could be used to assess the importance of the principal chemical properties of every single amino acid in the protein sequences for their contributions in explaining GPCR family membership. It was then revealed that all amino acids in the unaligned sequences contributed to the classifications, albeit to varying extent; the most important amino acids being those that could also be determined to be conserved by using traditional alignment-based methods.

Amino Acids↗
PubMed1996

A descriptive study of the work of community psychiatric nurses with elderly demented people.

This study examines the work of community psychiatric nurses (CPNs) with elderly demented people. A total of 14 cases, taken from the caseloads of four CPNs, were examined by direct observation of CPNs' practice and in-depth interviews. The data were analysed using a method suggested by Dey (1993). The validity of the findings was checked internally by means of respondent validation and externally by CPNs from other teams working with elderly demented people. It was found that the CPNs operated two strategies: one directed towards the client and the other towards the family. The process underlying these strategies consisted of five overlapping phases: assessment, planning, intervention, evaluation, and termination. The CPNs' working process was set within a framework containing their understanding of what they understood as 'community', the management style within the team and the quality and availability of clinical supervision. This process is integrated with existing literature on community psychiatric nursing and suggestions are made regarding possible developments within the speciality.

Aged↗