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Tumor classification using phylogenetic methods on expression data.

Tumor classification is a well-studied problem in the field of bioinformatics. Developments in the field of DNA chip design have now made it possible to measure the expression levels of thousands of genes in sample tissue from healthy cell lines or tumors. A number of studies have examined the problems of tumor classification: class discovery, the problem of defining a number of classes of tumors using the data from a DNA chip, and class prediction, the problem of accurately classifying an unknown tumor, given expression data from the unknown tumor and from a learning set. The current work has applied phylogenetic methods to both problems. To solve the class discovery problem, we impose a metric on a set of tumors as a function of their gene expression levels, and impose a tree structure on this metric, using standard tree fitting methods borrowed from the field of phylogenetics. Phylogenetic methods provide a simple way of imposing a clear hierarchical relationship on the data, with branch lengths in the classification tree representing the degree of separation witnessed. We tested our method for class discovery on two data sets: a data set of 87 tissues, comprised mostly of small, round, blue-cell tumors (SRBCTs), and a data set of 22 breast tumors. We fit the 87 samples of the first set to a classification tree, which neatly separated into four major clusters corresponding exactly to the four groups of tumors, namely neuroblastomas, rhabdomyosarcomas, Burkitt's lymphomas, and the Ewing's family of tumors. The classification tree built using the breast cancer data separated tumors with BRCA1 mutations from those with BRCA2 mutations, with sporadic tumors separated from both groups and from each other. We also demonstrate the flexibility of the class discovery method with regard to standard resampling methodology such as jackknifing and noise perturbation. To solve the class prediction problem, we built a classification tree on the learning set, and then sought the optimal placement of each test sample within the classification tree. We tested this method on the SRBCT data set, and classified each tumor successfully.

Algorithms↗

fMRI pattern classification using neuroanatomically constrained boosting.

Pattern classification in functional MRI (fMRI) is a novel methodology to automatically identify differences in distributed neural substrates resulting from cognitive tasks. Reliable pattern classification is challenging due to the high dimensionality of fMRI data, the small number of available data sets, interindividual differences, and dependence on the acquisition methodology. Thus, most previous fMRI classification methods were applied in individual subjects. In this study, we developed a novel approach to improve multiclass classification across groups of subjects, field strengths, and fMRI methods. Spatially normalized activation maps were segmented into functional areas using a neuroanatomical atlas and each map was classified separately using local classifiers. A single multiclass output was applied using a weighted aggregation of the classifier's outputs. An Adaboost technique was applied, modified to find the optimal aggregation of a set of spatially distributed classifiers. This Adaboost combined the region-specific classifiers to achieve improved classification accuracy with respect to conventional techniques. Multiclass classification accuracy was assessed in an fMRI group study with interleaved motor, visual, auditory, and cognitive task design. Data were acquired across 18 subjects at different field strengths (1.5 T, 4 T), with different pulse sequence parameters (voxel size and readout bandwidth). Misclassification rates of the boosted classifier were between 3.5% and 10%, whereas for the single classifier, these were between 15% and 23%, suggesting that the boosted classifier provides a better generalization ability together with better robustness. The high computational speed of boosting classification makes it attractive for real-time fMRI to facilitate online interpretation of dynamically changing activation patterns.

Attention↗

A system for classifying mechanical injuries of the eye (globe). The Ocular Trauma Classification Group.

PURPOSE: To develop a classification system for mechanical injuries of the eye. METHODS: The Ocular Trauma Classification Group, a committee of 13 ophthalmologists from seven separate institutions, was organized to discuss the standardization of ocular trauma classification. To develop the classification system, the group reviewed trauma classification systems in ophthalmology and general medicine and, in detail, reports on the characteristics and outcomes of eye trauma, then established a classification system based on standard terminology and features of eye injuries at initial examination that have demonstrated prognostic significance. RESULTS: This system classifies both open-globe and closed-globe injuries according to four separate variables: type of injury, based on the mechanism of injury; grade of injury, defined by visual acuity in the injured eye at initial examination; pupil, defined as the presence or absence of a relative afferent pupillary defect in the injured eye; and zone of injury, based on the anteroposterior extent of the injury. This system is designed to be used by ophthalmologists and nonophthalmologists who care for patients or conduct research on ocular injuries. An ocular injury is classified during the initial examination or at the time of the primary surgical intervention and does not require extraordinary testing. CONCLUSIONS: This classification system will categorize ocular injuries at the time of initial examination. It is designed to promote the use of standard terminology and assessment, with applications to clinical management and research stud ies regarding eye injuries.

Adult↗

A comparison between analysis time and inter-analyst reliability using spectral analysis of kinematic data and posture classification.

This study compares the time needed to analyze data and the inter-analyst variability using observational posture classification vs. spectral analysis of upper limb kinematic measurements made using an electrogoniometer for selected industrial jobs. Eight trained analysts studied four jobs using both methods. An incomplete fixed block experimental design was used, whereby each analyst used one method for each job. The four jobs included (1) punch press operation, (2) packaging, (3) parts hanging, and (4) construction vehicle operation. The posture classification analysis method involved visually classifying tipper extremity joint angles into specific zones relative to the range of motion for every one-third second (10 frames) of videotape. Spectral analysis required the analysts to identify cycle break points. The electrogoniometer signals were synchronized with each cycle, and power spectra for each joint were computed. The average difference in RMS joint deviation among analysts was 0.9 (SD = 0.61 degrees) for spectral analysis and 7.1 (SD = 2.53 degrees) for posture classification. The average difference in mean joint angle was 0.8 (SD = 0.59 degrees) for spectral analysis and 11.4 (SD = 1.58 degrees) for posture classification. Repetition frequency differed an average of 0.05 Hz (SD = 0.054 Hz) for spectral analysis and 0.07 Hz (SD = 0.058 Hz) for posture classification. Posture classification took a factor of 6.3 more time than cycle break point assignment for spectral analysis. Even considering the additional time needed for sensor attachment for direct measurement, posture classification took an average factor of 1.29 more time than spectral analysis using electrogoniometer data.

Biomechanical Phenomena↗

Classification of trochanteric fracture of the proximal femur: a study of the reliability of current systems.

Five observers using the Jensen modification of the Evans classification and the AO classification (with and without subgroups) classified the radiographs of 88 trochanteric hip fractures. Each observer classified the radiographs independently on two occasions 3 months apart. Kappa statistical analysis was used for determination of intra- and inter-observer variation. For the Jensen classification, the mean kappa value was 0.52 (range: 0.44-0.60) for intra-observer variation and 0.34 (range: 0.17-0.38) for inter-observer variation. For the AO system with subgroups, the mean kappa value was 0.42 (range: 0.20-0.65) for intra-observer variation and 0.33 (range: 0.14-0.48) for inter-observer variation. For the AO classification system without subgroups, the mean kappa value was 0.71 (range: 0.60-0.81) for intra-observer variation and 0.62 (range: 0.50-0.71) for inter-observer variation. We recommend classifying trochanteric fractures into three groups as that of the AO system without the subgroups. For ease of use, these three groups may be termed stable trochanteric, unstable trochanteric and trans-trochanteric. Neither the Jensen classification nor the AO classification with subgroups is an acceptable classification system for trochanteric hip fractures.

Femur Head↗

Risk classification after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Prediction of patient outcome is an important aspect of the management and study of aneurysmal subarachnoid hemorrhage (SAH). In the present study, we evaluated the prognostic value of two multivariate approaches to risk classification, Classification and Regression Trees (CART) and multiple logistic regression, and compared them with the best single predictor of outcome, level of consciousness. METHODS: Data prospectively collected in the first Cooperative Aneurysm Study of intravenous nicardipine after aneurysmal SAH (NICSAH I, n = 885) were used to develop the prediction models. Low-, medium-, and high-risk groups for unfavorable outcome were devised using CART and a stepwise logistic regression analysis. Admission factors incorporated into both classification schemes were: level of consciousness, age, location of aneurysm (basilar versus other), and the Glasgow Coma Score. The CART prediction tree also branched on a dichotomy of admission glucose level. The two multivariate classifications were then compared with a prediction scheme based on the single best performing prognostic factor, level of consciousness in an independent series, NICSAH II (n = 353), and also in the original training dataset. RESULTS: A similar discrimination of risk was achieved by the three classification systems in the testing sample (NICSAH II). The 8%, 19%, and 52% rates of unfavorable outcome obtained from low-, medium-, and high-risk groups defined by LOC approximated those obtained using the more complex multivariate systems. CONCLUSION: Although multivariate classification systems are useful to characterize the relationship of multiple risk factors to outcome, the simple clinical measure LOC is favored as a concise and practical classification for predicting the probability of unfavorable outcome after aneurysmal SAH.

Calcium Channel Blockers↗

Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients.

In 1982, the French-American-British (FAB) cooperative group proposed a classification of myelodysplastic syndromes (MDS) based on morphological features in blood and bone marrow, namely on medullary and peripheral blast count, Auer rods, ring sideroblasts and the number of monocytes in the peripheral blood. This classification has been used for numerous studies regarding morphology, prognosis and treatment of MDS. Some details of this morphological classification remained unclear, and some patients were unclassifiable. A working group of the World Health Organization (WHO) recently proposed a new classification of MDS, based on a significant modification of the original FAB proposals. CMML and RAEB-T were removed from the MDS classification and RAEB was split into two groups with medullary blast counts below and above 10%. In addition, a group of patients with less than 5% medullary blasts but evidence of multilineage dysplasia was defined. MDS patients with 5q- as the sole chromosomal anomaly were also considered a separate group. The aim of the present study was to validate the new classification with respect to prognostic importance, and to correlate it with cytogenetic and hematological features in a large series of patients (n=1600) with a long-term follow up. We were able to confirm a significant difference in prognosis between RAEB I and RAEB II, as well as a difference between refractory anemia and multilineage dysplasia. Furthermore, patients with 5q- anomaly had a much better prognosis than other WHO subtypes, but this was only true for patients with a medullary blast count below 5%. In summary, the WHO classification appears to define morphological subgroups that are more homogeneous with respect to prognosis than the FAB subtypes.

Adolescent↗

[Patient classification systems in intermediate and long-term stay institutions: evolution and future perspectives].

The importance of long term care sector is increasingly growing. Actually, the use of patient classification systems is a useful tool for the planning and management of health services for chronic and geriatric patients. Despite being much less known, patient classification systems have had a richer and earlier development in the long term care sector than in the acute care sector. Thus, one could could see the evolution from classifications based on the assessment of functional dependency to classifications progressively including variables corresponding to clinical complexity, and finally to complex systems such as RUG-III. Patient classification systems were first utilised as tools for the financing of long term centres, based on the patients' characteristics. Later, their applications have spread out to objectives related to the management of centres, assessment of quality of care, staff allocation level, control of access and national policies. In Spain, the only experience in the use of a patient classification system is the one used by the Catalan Health Care Administration which uses a classification for the financing of their centres.

Activities of Daily Living↗

Classification of distal radius fractures: an analysis of interobserver reliability and intraobserver reproducibility.

The Frykman, Melone, Mayo, and AO classification systems for distal radius fractures were evaluated for interobserver reliability and intraobserver reproducibility in a clinical setting using initial plain radiographs. Two attending orthopedic hand surgeons and two attending radiologists classified 55 sets of distal radius fractures. kappa-statistics were used to establish a relative level of agreement between observers for the two readings and between separate readings by the same observer. Interobserver agreement was rated as moderate for the Mayo classification and fair for the Frykman, Melone, and AO classifications. Intraobserver agreement was substantial for only one of four observers for each of the Frykman, Melone, and Mayo, while the remaining three observers achieved only fair to moderate reproducibility. Intraobserver agreement for the AO classification was fair for all four of the observers. Neither interobserver or intraobserver agreement was affected by combining similar subclasses in the Melone classification or by reducing the number of categories in the AO system from 27 to 9. However, further reducing the AO system to its three main types brought agreement to the "substantial" level. No difference was found in interobserver agreement between the first and second readings or in interobserver or intraobserver agreement between orthopedic hand surgeons and radiologists. Understanding the limitations of fracture classifications based solely on plain radiographs can help avoid undue reliance on them. Given the low degree of interobserver and intraobserver agreement for each of the distal radius fracture classifications in this study, their use as the sole means for determining the direction of treatment or for the direct comparison of results among different studies is not warranted.

Adult↗

The Tabár classification of mammographic parenchymal patterns.

The purpose of this study was to describe one method of classification, based on anatomic-mammographic correlations, developed by Tabár. We also wanted to examine how the mammograms categorized as low- and high-risk according to Tabár and Wolfe criteria related to each other and to three selected risk factors for breast cancer. The study materials are based on questionnaires and mammograms from 3,640 Norwegian women, aged 40-56 years, participating in the third Tromsö study. The mammograms were categorized into five groups. Line drawings and their pathologic correlates of the five patterns are described in detail. The Tabár classification is based on anatomic-mammographic correlations, following three-dimensional (thick slice technique) histopathologic-mammographic comparisons, rather than simple pattern reading (Wolfe classification). For analysis patterns I-III (Tabár) and N1 and P1 (Wolfe) were grouped into low-risk groups and patterns IV and V (Tabár) and P2 and DY Wolfe) into high-risk groups. The overall agreement on high-risk versus low risk for the two classifications was 54% with a kappa-value of 0.22. The study displays that the strength of association between high-risk mammographic patterns and the three selected risk factors parity, number of children and age at first birth is of greater magnitude when the Tabár instead of the Wolfe classification is applied. More patients are needed to compare the classification directly with the risk of cancer. This study indicates that further development of the classification of mammograms may increase the usefulness of mammographic patterns in research and clinical practice.

Adult↗

[Definition and classification of basal joint osteoarthritis. A critical analysis and proposals. Treatment options].

Several definitions and classifications of basal joint osteoarthritis exist. Each of them can be criticized. The authors propose to define basal thumb osteoarthritis as osteoarthritis of the trapezometacarpal joint associated or not with lesions of scapho-trapezio-trapezoid and/or metacarpophalangeal joints. The proposed classification is derived from the Eaton-Littler classification. Stage O is identical to stage I of the Eaton-Littler classification: trapeziometacarpal instability without cartilage lesions. Stage I is osteoarthritis of the trapeziometacarpal joint only, without metacarpophalangeal deformity. Stage II is trapeziometacarpal osteoarthrites combined with reductible hyperextension deformity of the metacarpophalangeal joint. Stage III is trapeziometacarpal osteoarthrites combined with irreductible metacarpophalangeal deformity. Stage IV is identical to stage IV of the Eaton-Littler classification: combined trapeziometacarpal and scapho-trapezio-trapezoid osteoarthritis. The advantage of the proposed classification is that basal joint osteoarthritis is not only defined as real or potential (stage O) osteoarthritis of the trapeziometacarpal joint, but also includes precise evaluation of two other joints at the base of the thumb. This classification can be a guide for treatment options.

Carpal Bones↗

A new system of classification for spinal injuries.

BACKGROUND CONTEXT: A comprehensive classification for spinal trauma has proved difficult to achieve as attested to by the number of systems in use today. In addition, few systems can be applied to all levels of the spine, and the first two cervical vertebrae are usually treated as altogether separate from the remainder of the spine. Consequently, outcome data and comparison of published data are difficult, at best. PURPOSE: The purpose of this presentation is to introduce a new system for classification of spine trauma applicable to all levels of the spine. STUDY DESIGN/SETTING: A different way of viewing the vertebrae is proposed. It allows the inclusion of all levels of the spinal column in a unified classification system based on the morphology of the injury. Each vertebra is viewed as a bony ring, and the rings are linked, above and below, by three osseoligamentous structures. These are the end plate-disc-end plate anteriorly and the facet joints posteriorly. Equivalent structures for the links are defined for the atlas and axis. PATIENT SAMPLE: The x-rays and computed tomographic or magnetic resonance imaging of patients with spine trauma were used to apply this classification to acute injuries. The sample used was all patients with spine trauma admitted, during a 1-year period, to a level 1 trauma center. Not all the patients were treated by the author, and no attempt was made to determine indications for treatment or treatment outcomes on the basis of this new classification system. METHODS: A new classification retrospectively applied to a defined patient population, which appeared to be representative of known trauma patterns. RESULTS: All patients with spinal trauma in this patient population were classifiable by this new system. All fracture types proposed in this system were represented in the patient sample. CONCLUSION: This new classification system appears to warrant further study.

Cervical Vertebrae↗

Classification of some active HIV-1 protease inhibitors and their inactive analogues using some uncorrelated three-dimensional molecular descriptors and a fuzzy c-means algorithm.

A fuzzy c-means algorithm was used to classify some 3D convex hull descriptors computed for 345 active HIV-1 protease inhibitors collected from literature and 437 inactive analogues searched from the MDL/ISIS database. The number of descriptors used to represent each compound was from 4 to 8, and they were uncorrelated using the principal component analysis. These uncorrelated descriptors were then divided into two groups and classified by the fuzzy c-means algorithm. The classification produced a clear-cut switch in membership functions computed for each uncorrelated descriptor at the group boundary. Compounds with nonswitching membership functions computed were treated as outliers, and they were counted for estimating the accuracy of the classification. The averaged accuracy of classification for the active inhibitor set was about 80% which was better than that directly classified by a linear discriminant function on the original 3D convex hull descriptors. The whole classification scheme was also applied to several sets of some conventional descriptors computed for each compound, but the averaged accuracy was around 58%. Further classification using some 3D convex hull descriptors searched from comparing the distribution of these descriptors was performed on a new data set composed of 289 outliers-deducted active inhibitors and 63 outliers identified from the inactive analogues through previous classification. This final classification identified 19 inactive analogues which were similar in structural and topological features to those of some highly active inhibitors classified together with them.

Algorithms↗

A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan.

Orally administered, immediate-release (IR) drug products in the top 200 drug product lists from the United States (US), Great Britain (GB), Spain (ES), and Japan (JP) were provisionally classified based on the Biopharmaceutics Classification System (BCS). The provisional classification is based on the aqueous solubility of the drugs reported in readily available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. Oral IR drug products constituted more that 50% of the top 200 drug products on all four lists, and ranged from 102 to 113 in number. Drugs with dose numbers less than or equal to unity are defined as high-solubility drugs. More than 50% of the oral IR drug products on each list were determined to be high-solubility drugs (55-59%). The provisional classification of permeability is based on correlations of the human intestinal permeabilities of 29 reference drugs with the calculated Log P or CLogP lipophilicity values for the uncharged chemical form. The Log P and CLogP estimates were linearly correlated (r2 = 0.79) for 187 drugs. Metoprolol was chosen as the reference compound for permeability and Log P or CLogP. A total of 62-69.0% and 56-60% of the drugs on the four lists exhibited CLogP and Log P estimates, respectively, greater than or equal to the corresponding metoprolol value and are provisionally classified as high-permeability drugs. We have compared the BCS classification in this study with the recently proposed BDDCS classification based on fraction dose metabolism. Although the two approaches are based on different in vivo processes, fraction dose metabolized and fraction dose absorbed are highly correlated and, while depending on the choice of reference drug for permeability classification, e.g., metoprolol vs cimetidine or atenolol, show excellent agreement in drug classification. In summary, more than 55% of the drug products were classified as high-solubility (Class 1 and Class 3) drugs in the four lists, suggesting that in vivo bioequivalence (BE) may be assured with a less expensive and more easily implemented in vitro dissolution test.

Administration, Oral↗

Metaphorical analysis of psychiatric classification as a psychological test.

In this taxonomic article we explore the metaphor of comparing a psychiatric classification to a psychological test. Structurally, diagnostic criteria are like test items; diagnostic categories are like scales; and classification are like tests. Analytically, the ideas of reliability and validity are the primary concepts invoked in the empirical evaluation of both classifications and tests. However, when the metaphor is explored in more detail, the differences between classifications and tests become clear. These differences are discussed in terms of the structural and analytical relations between tests and classifications. This metaphorical analysis of classifications as tests suggests that certain issues that have been discussed in regard to psychological tests, particularly reliability and validity, may require modification when applied to psychiatric classification.

Humans↗

pT classification, grade, and vascular invasion as prognostic indicators in urothelial carcinoma of the upper urinary tract.

Clinicopathologic features predictive of patient outcome in upper urinary tract urothelial carcinoma are not well defined. The aim of this study was to assess the role of pT classification, tumor grade, and vascular invasion in predicting metastasis-free survival. A total of 190 consecutive invasive upper urinary tract urothelial cancers operated between 01/1984 and 12/2004 were re-evaluated with respect to pT classification, tumor grade (according to the three-tiered WHO 1973 and the recent two-tiered grading system following the WHO/ISUP consensus classification), as well as presence of lymph and/or blood vessel invasion. Prognostic impact was analyzed using the Kaplan-Meier method and the Log-Rank test. For multivariate testing, a Cox's proportional hazards regression model was used. pT1 was present in 81 (43%), pT2 in 29 (15%), pT3 in 73 (38%), and pT4 in seven (4%) cases. There were 12 (6%) G1, 96 (51%) G2, and 82 (43%) G3 tumors or 84 (44%) low-grade and 106 (56%) high-grade tumors according to the two-tiered system. The presence of vascular invasion in 72/190 (38%) tumors was associated with high pT classification (P<0.001) and high tumor grade (P<0.001). Disease progression occurred in 39% of patients, with 5- and 10-year metastasis-free survival rates of 56 and 45%, respectively. On univariate analysis, all investigated parameters showed prognostic significance. The negative influence of vascular invasion on patient outcome was strikingly strong in high pT classification and high-grade cancers. On multivariate analysis, pT classification (P<0.001) and vascular invasion (P<0.001) proved to be independent prognostic factors, whereas tumor grade according to the two-tiered system missed statistical significance (P=0.06). In conclusion, pT classification and vascular invasion are independent prognostic factors with respect to metastasis-free survival and should be used to guide adjuvant therapy strategies in affected patients. Presence (or absence) of vascular invasion should be commented upon separately in the pathology report.

Adult↗

Classification of pain following spinal cord injury.

Pain continues to be a significant management problem in people with spinal cord injuries. Despite this there is little consensus regarding the nature, terminology and definitions of the various types of pain that occur following spinal cord injury. This has led to large variations in the reported incidence and prevalence of pain following spinal cord injury. Treatment studies have been hampered by inconsistent and inaccurate identification of pain types. We believe that both research and management would benefit from an agreed upon classification system which accurately and reliably identifies the types of pain that occur following spinal cord injury. We have reviewed the literature on the classification of pain following spinal cord injury and have developed a classification system which adopts the strengths of previous systems and attempts to avoid the weakness inherent in others. Our proposed classification system of pain following spinal cord injury includes four major divisions: musculoskeletal, visceral, neuropathic and other types of pain. We have divided neuropathic pain on the basis of region into two subdivisions: neuropathic at level and neuropathic below level pain. We have further divided neuropathic at level pain into two categories: radicular and central, to indicate the presumed site of the lesion responsible for pain generation. We believe that our proposed classification system is comprehensive, simple and readily applicable in the clinical and research situation. It is our hope that this proposed classification will contribute to the eventual development of a universal system for the classification of pain following spinal cord injury.

Humans↗

Test-retest reliability of the Donovan spinal cord injury pain classification scheme.

STUDY DESIGN: Videotape rating by independent viewers. OBJECTIVE: To determine the test-retest reliability of the Donovan spinal cord injury (SCI) pain classification scheme. SETTING: Rehabilitation Centre, Alabama, USA. METHODS: A total of 28 individuals with SCI reported 60 pain sites. A structured interview and physical exam were used to illicit information to classify each pain site according to the Donovan criteria. All structured interviews and exams were videotaped. Three independent raters viewed the videotapes on two occasions, separated by a 3-month interval, and classified each pain site using the Donovan pain classification scheme. RESULTS: Considering all three raters together, 78% of the pain sites were consistently classified from one period to the next. Within each rater, consistent classification ranged from 67 to 83%. However, inter-rater agreement for the classification of each pain site into the various types of pain was low for both periods (about 50-60%). CONCLUSIONS: Pain classification within each rater generally showed adequate test-retest reliability when using the Donovan SCI pain classification scheme. However, reliability estimates of agreement across raters highlight the ongoing need to exam and improve the psychometric characteristics of the various pain classification schemes.

Adult↗