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A comprehensive multiattribute system for classifying the health status of survivors of childhood cancer.

PURPOSE: A multiattribute health status classification system was devised to describe comprehensively the health status of survivors of childhood cancer. METHODS: The system consists of seven attributes: sensation, mobility, emotion, cognition, self-care, pain, and fertility. Three to five levels of functioning are defined for each attribute. Any specific combination of seven attribute levels constitutes a health state. In the first survey, the system was used to classify the health status of 20 children currently undergoing therapy for high-risk acute lymphoblastic leukemia (ALL), Wilms' tumor, or neuroblastoma, and eight who had completed treatment. A second survey consisted of 13 children with brain tumors on active treatment. RESULTS: In general, independent ratings by clinicians were in agreement, and consensus was readily achieved in 1 to 2 minutes per patient. Children on therapy experienced a higher burden of morbidity than those off treatment. Brain tumor patients experienced more morbidity than patients in the first survey. CONCLUSION: The multiattribute system provides a compact but comprehensive tool for long-term follow-up of survivors of childhood cancer. It captures both multiple sequelae and varying levels of severity. By using a mathematical utility function, a single summary score of health-related quality of life may be assigned to each health state. Additional studies to establish reproducibility, validity, responsiveness, and generalizability are indicated.

Activities of Daily Living↗

Roadmap for developing and validating therapeutically relevant genomic classifiers.

Oncologists need improved tools for selecting treatments for individual patients. The development of therapeutically relevant prognostic markers has traditionally been slowed by poor study design, inconsistent findings, and lack of proper validation studies. Microarray expression profiling provides an exciting new technology for relating tumor gene expression to patient outcome, but it also provides increased challenges for translating initial research findings into robust diagnostics that benefit patients and physicians in therapeutic decision making. This article attempts to clarify some of the misconceptions about the development and validation of multigene expression signature classifiers and highlights the steps needed to move genomic signatures into clinical application as therapeutically relevant and robust diagnostics.

Biomarkers, Tumor↗

Afirma genomic sequencing classifier performance in young patients with cytologically indeterminate thyroid nodules.

CONTEXT: The Afirma Genomic Sequencing Classifier (GSC) is validated in patients &#x2265; 21 years with a 96% negative predictive value for malignancy when GSC-(B)enign. Afirma GSC has not been formally studied in patients <21 years of age with indeterminate thyroid nodules (ITNs). OBJECTIVE: To evaluate Afirma GSC in young patients with ITNs. DESIGN: Retrospective analysis of Afirma GSC testing. SETTING: ITNs referred for molecular testing in a real-world setting. PARTICIPANTS: Forty-nine ITNs from 49 patients < 21 years of age who had histopathology or 2 years' clinical follow-up data ascertained. INTERVENTION: None. MAIN OUTCOME MEASURE: Afirma GSC test performance. RESULTS: In 49 ITNs from patients aged 9 to 20 years (median 18.5 [interquartile range, 17.3-19.8]), 30 were GSC-B and 19 GSC-(S)uspicious, among which 14 (73.7%) were malignant (ie, true positive) and 5 (26.3%) were benign (ie, false positive). All 30 Afirma GSC-B cases were either histologically (n = 9) or clinically benign (n = 21) (ie, true negative). All 14 malignancies were GSC-S (sensitivity 100% [95% CI, 77-100]); 30/35 clinically or histologically benign cases were GSC-B (specificity 86% [95% CI, 70-95]). Negative predictive value for an Afirma GSC-B result was 100% [95% CI, 88-100]. Genomic alterations were not detected in the 30 GSC-B samples. Among the 14 malignant samples, there were 9 papillary thyroid carcinomas, 1 oncocytic carcinoma, 1 noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and 3 follicular thyroid carcinomas. CONCLUSION: In young patients with ITNs, the Afirma GSC demonstrated an excellent negative predictive value when defining a thyroid nodule result by histology or clinical follow-up.

Thyroid Nodule↗

Clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing.

We investigated human leukocyte antigen (HLA) class I and class II antigens in 56 Japanese patients with subacute thyroiditis (SAT) who visited our out-patient clinic between 1988 and 1990. We found SAT to be associated with not only HLA-B35 (40 patients; P < 0.000001; relative risk, 18.02), but also with HLA-B67 antigens (9 patients; P < 0.00001; relative risk, 11.20). No heterozygotes of HLA-B35 or HLA-B67 were found in any of the 56 patients with SAT. Either HLA-B35 or HLA-B67 antigen is found in 87% of patients with SAT. When season of onset and clinical course of SAT were compared in the 49 patients with HLA-B35-positive SAT (B35-SAT) and HLA-B67-positive SAT (B67-SAT), we were able to identify certain characteristics: 1) B67-SAT often followed the course from transient thyrotoxicosis to a hypothyroid phase to a euthyroid phase [6 of 9 B67-SAT (67%) vs. 10 of 40 B35-SAT (25%); P < 0.05]; and 2) B67-SAT occurred mostly during the summer or autumn and at a higher rate than did B35-SAR [8 of 9 B67-SAT (89%) vs. 17 of 40 B35-SAT (43%)], whereas B35-SAT occurred throughout the year. We conclude that there are at least two types of SAT that can be classified by association with either HLA-B35 or HLA-B67 antigens.

Acute Disease↗

Development of novel techniques to classify physical activity mode using accelerometers.

PURPOSE: Use of accelerometers to assess physical activity (PA) is widespread in public health research, but their utility is often limited by the accuracy of data-processing techniques. We hypothesized that more sophisticated approaches to data processing could distinguish between activity types based on accelerometer data, providing a more accurate picture of PA. METHODS: Using data from MTI Actigraphs worn by six subjects during four activities (walking, walking uphill, vacuuming, working at a computer), quadratic discriminant analysis (QDA) was performed, and a hidden Markov model (HMM) was trained to recognize the activities. The ability of the new analytic techniques to accurately classify PA was assessed. RESULTS: The mean (SE) percentage of time points for which the QDA correctly identified activity mode was 70.9% (1.2%). Computer work was correctly recognized most frequently (mean (SE) percent correct = 100% (0.01%)), followed by vacuuming (67.5% (1.5%)), uphill walking (58.2% (3.5%)), and walking (53.6% (3.3%)). The mean (SE) percentage of time points for which the HMM correctly identified activity mode was 80.8% (0.9%). Vacuuming was correctly recognized most frequently (mean (SE) percent correct = 98.8% (0.05%)), followed by computer work (97.3% (0.7%)), walking (62.6% (2.3%)), and uphill walking (62.5% (2.3%)). In contrast to a traditional method of data processing that misidentified the intensity level of 100% of the time spent vacuuming and walking uphill, the QDA and HMM approaches correctly estimated the intensity of activity 99% of the time. CONCLUSION: The novel approach of estimating activity mode, rather than activity level, may allow for more accurate field-based estimates of physical activity using accelerometer data, and this approach warrants more study in a larger and more diverse population of subjects and activities.

Acceleration↗

Clinical characteristics, diagnosis and management of patients with pulmonary thromboembolism who are not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension.

BACKGROUND: There have been many cases of pulmonary thromboembolism (PTE) that were not diagnosed in the acute phase and not classified as chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was clarify the clinical characteristics of chronic PTE. METHODS AND RESULTS: The study subjects were 601 patients (chronic PTE = 92, acute PTE = 456, CTEPH = 53) who were clinically diagnosed before their death. Dyspnea and chest pain, which are frequently found in acute PTE, were found less frequently in chronic PTE. The diagnosis of chronic PTE is often delayed in cases of mild to moderate severity with atypical onset. Chronic heart failure and chronic respiratory failure were most frequent in chronic PTE, and cerebrovascular disease was present in approximately 15% of the cases of chronic PTE. Pulmonary angiography and ventilation lung scan were used least frequently in acute PTE. Heparin and thrombolysis were used most frequently in acute PTE. CONCLUSIONS: Besides the atypical onset and reduced severity, the presence of preexisting diseases may be one of the reasons why the diagnosis for chronic PTE is delayed. The diagnostic and management techniques differ according to the type of PTE.

Adult↗

RNA secondary structure prediction from sequence alignments using a network of k-nearest neighbor classifiers.

We present a machine learning method (a hierarchical network of k-nearest neighbor classifiers) that uses an RNA sequence alignment in order to predict a consensus RNA secondary structure. The input to the network is the mutual information, the fraction of complementary nucleotides, and a novel consensus RNAfold secondary structure prediction of a pair of alignment columns and its nearest neighbors. Given this input, the network computes a prediction as to whether a particular pair of alignment columns corresponds to a base pair. By using a comprehensive test set of 49 RFAM alignments, the program KNetFold achieves an average Matthews correlation coefficient of 0.81. This is a significant improvement compared with the secondary structure prediction methods PFOLD and RNAalifold. By using the example of archaeal RNase P, we show that the program can also predict pseudoknot interactions.

Algorithms↗

Prediction of peptide binding to major histocompatibility complex class II molecules through use of boosted fuzzy classifier with SWEEP operator method.

To treat autoimmune diseases, it is important to identify which peptides bind to major histocompatibility complex (MHC) class II molecules (HLA-DRs). Predicting the peptides that bind to MHC class II molecules can effectively reduce the number of experiments required for identifying helper T cell epitopes. In our previous study, we applied fuzzy neural networks (FNNs) to solve this problem. However, an FNN requires a long calculation time and a large number of peptides; this means performing several experiments. In this study, we applied a boosted fuzzy classifier with the SWEEP operator method (BFCS) to solve this problem. For comparison, two other conventional modeling methods, namely, support vector machine and FNN combined with the SWEEP operator method (FNN-SWEEP) instead of using solely an FNN, were employed. Compared with FNN, FNN-SWEEP is extremely fast and has an almost identical prediction accuracy. The model constructed by BFCS showed an accuracy approximately 5%-10% higher than that constructed by FNN-SWEEP. In addition, BFCS was 30,000-120,000 times faster than FNN-SWEEP. This result suggests that BFCS has the potential to function as a new method of predicting peptides that bind to various protein receptors.

Fuzzy Logic↗

[Particle numbers in classified sizes of roadside dust caused by studded tires in the air at different heights from the pavement surface].

Increased use of motor vehicles has produced various risks to human health due to air pollution by noxious gases, heavy metals and roadside dust. Since the late 1970s, the wide spread use of studded tires for cars has caused pavement wear, resulting in not only economic losses, but also roadside air pollution in cold and snowy regions in Japan. The most serious environmental problem in Sapporo, a city with heavy snowfall, in the 1980s, was roadside dust derived from studded tires. The inhabitants suffered from this dust in the early winter and in the early spring when the streets were not covered with snow. To investigate the influence of such roadside dust upon human health, particle numbers in classified sizes of roadside dust were counted after the roadside dust in the air was collected with a device we constructed at 30, 60, 90, 120, 150, and 180 cm above the pavement surface. The results indicated that the concentration of roadside dust in the air did not greatly vary according to the height from the pavement surface. The results also suggested that xenogranuloma, reported in lungs of stray dogs, under roadside dust-pollution conditions such as those examined here, may occur in humans in the future.

Air Pollutants↗

A high resolution chromosome image processor for study purposes, NIRS-1000:CHROMO STUDY, and algorithm developing to classify radiation induced aberrations.

Since 1989 we have promoted a project to develop an automated scoring system of radiation induced chromosome aberrations. As a first step, a high resolution image processing system for study purposes, NIRS-1000:CHROMO STUDY, has been developed. It is composed of: (1) CHROMO MARKER whose main purpose is to mark on images to make image data base, (2) CHROMO ALGO whose purpose is algorithm development, and (3) METAPHASE RANKER whose purposes are metaphase finding and ranking with a high power objective lens. However, METAPHASE RANKER is presently under development. The system utilizes a high definition video system so as to realize the best spatial resolution that is achievable with an optical microscope using an objective lens (x 100, numerical aperture 1.4). The video camera has 1024 effective scan lines to realize 0.1 microns sampling on a specimen. The system resolution achieved on the hard copy is less than 0.3 microns on a specimen. A preliminary algorithm has been developed to classify the aberrations on the system using projection information of gray level. The preliminary test results on excellent 10 metaphases show that the correct classification ratio is 92.7%, that the detection rate of the aberrations is 83.3% and that the false positive rate is 6.1%.

Algorithms↗

The phylogenetic relationships of the hat-shaped ascospore-forming, nitrate-assimilating Pichia species, formerly classified in the genus Hansenula Sydow et Sydow, based on the partial sequences of 18S and 26S ribosomal RNAs (Saccharomycetaceae): the proposals of three new genera, Ogataea, Kuraishia, and Nakazawaea.

The twenty-seven strains of the hat-shaped ascospore-forming, nitrate-assimilating species, formerly classified in the genus Hansenula, of the genus Pichia were examined for their 18S and 26S rRNA partial base sequencings. All the strains examined were separate phylogenetically from the type strain of P. membranaefaciens (type species of genus Pichia). Based on the sequence data obtained [by number of base differences (five or more) with P. anomala and base sequences on fingerprint segment] in the 18S rRNA partial base sequences, these species were divided into seven groups. Group I, including P. anomala (identical to H. anomala, type species of genus Hansenula), P. canadensis, P. muscicola, P. silvicola, P. subpelliculosa, P. americana, P. bimundalis, P. ciferrii, P. syndowiorum, P. bispora, and P. fabianii, corresponded to the genus Hansenula Sydow et Sydow. Groups II and III were comprised of P. capsulata and P. holstii, respectively. Group IV included P. angusta, P. minuta var. minuta, P. minuta var. nonfermentans, P. philodendra, P. glucozyma, and P. henricii. Groups V, VI, and VII included P. jadinii, P. petersonii, and P. dryadoides, respectively. The nitrate assimilation-negative species, P. wickerhamii was phylogenetically distant from P. membranaefaciens. The seven groupings are discussed phylogenetically and taxonomically. For Groups IV, II, and III, the three new genera were proposed as Ogataea, Kuraishia, and Nakazawaea, respectively, with the type species, O. minuta (identical to P. minuta), K. capsulata (identical to P. capsulata), and N. holstii (identical to P. holstii).

Base Sequence↗

High survival rate of 6 cases of pulmonary large cell neuroendocrine carcinoma formerly classified as small cell carcinoma.

UNLABELLED: In the revised WHO classification of lung cancer, published in 1999, large cell neuroendocrine carcinoma (LCNEC) was employed as a new histological entity. LCNEC is generally considered a high-grade malignant lung cancer, and appropriate treatment remains to be determined. Before its new classification, LCNEC had long been classified into several entities. Advancing the review of previous cases in Nippon Medical School Hospital, we noticed that some LCNEC patients were formally diagnosed as having small cell lung cancer (SCLC), and they showed long-term survival. MATERIAL AND METHODS: All histological specimens of surgically resected SCLC in Nippon Medical School Hospital were reclassified according to the 1999 WHO classification manual. Their neuroendocrine differentiations were confirmed by the use of immunostainings with chromogranin A and synaptophysin. RESULTS: Fourteen cases satisfied the qualifications for both histological and clinical reevaluation. Among them, 6 patients were reclassified as LCNEC, and their stage distribution was as follow: IA; 1, IB; 2, IIIA; 2, and IIIB; 1. Their survival term ranged from 33.8 to 78.0 months; 5 were still alive, and 1 (IIIB) died 57.6 months after surgery. DISCUSSION: According to this study, all the LCNEC patients who were treated as SCLC patients showed more favorable prognoses than patients described in published studies, even overall lung cancer. Therefore, it is suggested that multimodality therapy for SCLC may improve the prognoses of patients with LCNEC.

Aged↗

Cleavage capability of water buffalo follicular oocytes classified by cumulus cells and fertilized in vitro.

Water buffalo (Murrah) oocytes were collected from ovaries obtained from the slaughter house. They were classified according to the character of the cumulus cells under a stereomicroscope, and cultured in 25 mM Hepes buffered Tissue Culture Medium-199 (TCM-199) supplemented with 5% estrous water buffalo serum in an atmosphere containing 5% CO2 in air at 39 degrees C. After 20-24 hr of in vitro maturation, the oocytes were fertilized using capacitated sperm obtained from 4 different bulls. For cleavage the oocytes were cultured at 39 degrees C in TCM-199 supplemented with 1% estrous water buffalo serum and in an atmosphere containing 5% CO2 in air. The good oocytes, with compact and dense cumulus cells cleaved significantly higher (p less than 0.01, 67.3%), than those of fair. partially naked oocytes with thin cumulus layers (27.5%, 25/91) or small remnants of cumulus cells and poor naked oocytes (3/100). A substantial variation cumulus layers (27.5% 25/91) or small remnants of cumulus cells and poor naked oocytes (3/100). A substantial variation in fertilization and developmental rates (16.0% to 43.8%) was observed among 4 different bulls. Late non-surgically into 14 buffalo recipients on day 6 or 7 of their estrous cycle. One recipient was diagnosed to be pregnant by rectal palpation on day 60 and confirmed to be so on day 90 post-estrus.

Animals↗

Characteristics of the 16S-23S rRNA intergenic spacer region of Mycoplasma haemomuris, previously classified as 'Haemobartonella muris'.

The intergenic spacer region between the 16S and 23S rRNA genes of Mycoplasma haemomuris, previously classified as 'Haemobartonella muris', was amplified by PCR and sequenced for analysis of the primary and secondary structures of the RNA transcript. The spacer region consisted of 219 base-pairs and lacked the spacer tRNA gene. A hypothetical secondary structure predicted in the RNA transcript of the spacer region was tentatively assigned box A and box B loci peculiar to the members of the Mycoplasma. Mycoplasma haemomuris and the other species of the genus Mycoplasma are consistent with these characteristics of the spacer region.

Base Sequence↗

Reliability and validity of DESIGN, a tool that classifies pressure ulcer severity and monitors healing.

OBJECTIVE: This study reviews the validity and reliability of DESIGN, a tool for classifying pressure ulcer severity and monitoring progression towards healing. Only the tool's healing progression component was evaluated. METHOD: Inter-rater reliability was evaluated by calculating the agreement rate of scores, based on eight photos of pressure ulcers and six actual ulcers, made by a panel of seven nurses. Validity was assessed, using the same eight photos, by comparing DESIGN scores with those made using the validated Pressure Sore Status Tool (PSST). RESULTS: The DESIGN inter-rater reliability results showed a high correlation of r = 0.98 for the photos and r = 0.91 for the real-life patients with pressure ulcers, respectively, for all seven raters based on total scores. For validity, a correlation greater than 0.91 was found between the DESIGN and PSST scores. CONCLUSION: Based on our results, DESIGN was found to have both high inter-rater reliability and high validity among the seven nurses who quantitatively evaluated the wound-healing progress of the pressure ulcers in this study.

Humans↗

Toward complete and accurate reporting of studies of diagnostic accuracy. The STARD initiative.

Our objective was to improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in the study, and to evaluate its generalizability. The Standards for Reporting of Diagnostic Accuracy Steering Committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organizations shortened this list during a 2-day consensus meeting with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy. The search for published guidelines regarding diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25-item checklist, using evidence whenever available. A prototypical flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation, the reference standard, or both. Evaluation of research depends on complete and accurate reporting. If medical journals adopt the checklist and the flow diagram, the quality of reporting of studies of diagnostic accuracy should improve, to the advantage of clinicians, researchers, reviewers, journals, and the public.

Algorithms↗

Classifying the illumination condition from two light sources by color histogram assessment.

We investigate and propose a method for assessment of the illumination condition covering two light sources. The method may be of some support for color vision and multispectral analysis methods that rely on a specific illumination condition. It is constrained to classifying the illumination condition for dielectric objects illuminated by two light sources. The reflected light is modeled by the dichromatic reflection model, which describes the light as the sum of its body reflections and surface reflections. Further, reflected light from an object illuminated by two light sources may give from one to four primary reflections depending on the condition, and it may be expressed as an additive mixture of these reflections. An additive mixture of two reflections expressed in chromaticities is limited to falling within the area enclosed by the chromaticities of the primary reflections of the light sources. So after finding the set of primary chromaticities enclosing the pixel points' chromaticities, it is possible for one to assess the current illumination condition. Since the method operates on pixel points globally, it is independent of illumination geometry and hence may be used on irregular objects. Two experiments are performed. One uses regular objects in a well-controlled laboratory environment and demonstrates that the pixel-point distribution is as expected. The second experiment demonstrates the method's potential use in support of spectroscopic analysis of vegetation through assessing the illumination condition of barley plants in an outdoor illumination condition.

Color↗

Classifying asthma.

The most widely known method of asthma classification is the severity classification recommended in the National Asthma Education and Prevention Program 1997 guidelines, which also formed the basis of the Global Initiative for Asthma guidelines. This method was developed to direct a hierarchy of asthma therapy based on the patient's severity of disease. However, this severity classification has not been validated and has a number of limitations; in particular, it is challenging for physicians to apply reliably. Moreover, it does not allow asthma control to be assessed after the initiation of treatment, even though symptom control is a key objective of the treatment guidelines. A number of tools have been evaluated to provide longitudinal information on asthma control, and some of these have been validated. Clinically relevant measures of inflammation, such as eosinophilic airway inflammation, may also be helpful in classifying asthma and in guiding the use of antiinflammatory therapy. This may be a particularly useful approach in patients who are asymptomatic but have poor lung function, by permitting physicians to determine whether inflammatory processes are active, thus requiring ICS therapy. In the clinical setting, easy-to-use tools are needed to enable longitudinal assessments of symptom control and (ideally) disease progression.

Asthma↗