Meta-analysis based SVM classification enables accurate detection of Alzheimer's disease across different clinical centers using FDG-PET and MRI.

The application of support vector machine classification (SVM) to combined information from magnetic resonance imaging (MRI) and [F18]fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to improve detection and differentiation of Alzheimer's disease dementia (AD) and frontotemporal lobar degeneration. To validate this approach for the most frequent dementia syndrome AD, and to test its applicability to multicenter data, we randomly extracted FDG-PET and MRI data of 28 AD patients and 28 healthy control subjects from the database provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and compared them to data of 21 patients with AD and 13 control subjects from our own Leipzig cohort. SVM classification using combined volume-of-interest information from FDG-PET and MRI based on comprehensive quantitative meta-analyses investigating dementia syndromes revealed a higher discrimination accuracy in comparison to single modality classification. For the ADNI dataset accuracy rates of up to 88% and for the Leipzig cohort of up to 100% were obtained. Classifiers trained on the ADNI data discriminated the Leipzig cohorts with an accuracy of 91%. In conclusion, our results suggest SVM classification based on quantitative meta-analyses of multicenter data as a valid method for individual AD diagnosis. Furthermore, combining imaging information from MRI and FDG-PET might substantially improve the accuracy of AD diagnosis.

A study of the cambial zone and conductive phloem of common beech (Fagus sylvatica L.) using an image analysis method. I. Influence of tree age on the structure

Quantification is a major problem when using histology to study the influence of ecological factors on tree structure. This paper presents a method to prepare and to analyse transverse sections of cambial zone and of conductive phloem in bark samples. The following paper (II) presents the automated measurement procedure. Part I here describes and discusses the preparation method, and the influence of tree age on the observed structure. Highly contrasted images of samples extracted at breast height during dormancy were analysed with an automatic image analyser. Between three young (38 years) and three old (147 years) trees, age-related differences were identified by size and shape parameters, at both cell and tissue levels. In the cambial zone, older trees had larger and more rectangular fusiform initials. In the phloem, sieve tubes were also larger, but their shape did not change and the area for sap conduction was similar in both categories. Nevertheless, alterations were limited, and demanded statistical analysis to be identified and ascertained. The physiological implications of the structural changes are discussed.

The IC3D classification of the corneal dystrophies.

BACKGROUND: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis. PURPOSE: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis. METHODS: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature. RESULTS: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available. CONCLUSIONS: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d.

IEF pattern classification-derived criteria for the identification of epoetin-delta in urine.

Epoetin-delta (Dynepo Shire Pharmaceuticals, Basing stoke, UK) is a synthetic form of erythropoietin (EPO) whose resemblance with endogenous EPO makes it hard to identify using the classical identification criteria. Urine samples collected from six healthy volunteers treated with epoetin-delta injections and from a control population were immuno-purified and analyzed with the usual IEF method. On the basis of the EPO profiles integration, a linear multivariate model was computed for discriminant analysis. For each sample, a pattern classification algorithm returned a bands distribution and intensity score (bands intensity score) saying how representative this sample is of one of the two classes, positive or negative. Effort profiles were also integrated in the model. The method yielded a good sensitivity versus specificity relation and was used to determine the detection window of the molecule following multiple injections. The bands intensity score, which can be generalized to epoetin-alpha and epoetin-beta, is proposed as an alternative criterion and a supplementary evidence for the identification of EPO abuse.

Binary classification of dyslipidemia from the waist-to-hip ratio and body mass index: a comparison of linear, logistic, and CART models.

BACKGROUND: We sought to improve upon previously published statistical modeling strategies for binary classification of dyslipidemia for general population screening purposes based on the waist-to-hip circumference ratio and body mass index anthropometric measurements. METHODS: Study subjects were participants in WHO-MONICA population-based surveys conducted in two Swiss regions. Outcome variables were based on the total serum cholesterol to high density lipoprotein cholesterol ratio. The other potential predictor variables were gender, age, current cigarette smoking, and hypertension. The models investigated were: (i) linear regression; (ii) logistic classification; (iii) regression trees; (iv) classification trees (iii and iv are collectively known as "CART"). Binary classification performance of the region-specific models was externally validated by classifying the subjects from the other region. RESULTS: Waist-to-hip circumference ratio and body mass index remained modest predictors of dyslipidemia. Correct classification rates for all models were 60-80%, with marked gender differences. Gender-specific models provided only small gains in classification. The external validations provided assurance about the stability of the models. CONCLUSIONS: There were no striking differences between either the algebraic (i, ii) vs. non-algebraic (iii, iv), or the regression (i, iii) vs. classification (ii, iv) modeling approaches. Anticipated advantages of the CART vs. simple additive linear and logistic models were less than expected in this particular application with a relatively small set of predictor variables. CART models may be more useful when considering main effects and interactions between larger sets of predictor variables.

Nosology and classification of genetic skeletal disorders: 2010 revision.

Genetic disorders involving the skeletal system arise through disturbances in the complex processes of skeletal development, growth and homeostasis and remain a diagnostic challenge because of their variety. The Nosology and Classification of Genetic Skeletal Disorders provides an overview of recognized diagnostic entities and groups them by clinical and radiographic features and molecular pathogenesis. The aim is to provide the Genetics, Pediatrics and Radiology community with a list of recognized genetic skeletal disorders that can be of help in the diagnosis of individual cases, in the delineation of novel disorders, and in building bridges between clinicians and scientists interested in skeletal biology. In the 2010 revision, 456 conditions were included and placed in 40 groups defined by molecular, biochemical, and/or radiographic criteria. Of these conditions, 316 were associated with mutations in one or more of 226 different genes, ranging from common, recurrent mutations to "private" found in single families or individuals. Thus, the Nosology is a hybrid between a list of clinically defined disorders, waiting for molecular clarification, and an annotated database documenting the phenotypic spectrum produced by mutations in a given gene. The Nosology should be useful for the diagnosis of patients with genetic skeletal diseases, particularly in view of the information flood expected with the novel sequencing technologies; in the delineation of clinical entities and novel disorders, by providing an overview of established nosologic entities; and for scientists looking for the clinical correlates of genes, proteins and pathways involved in skeletal biology. © 2011 Wiley-Liss, Inc.

Proposal of a new classification for optimising outcome assessment following partial cricotracheal resections in severe pediatric subglottic stenosis.

OBJECTIVE: Creation of a patent subglottic airway after partial cricotracheal resection (PCTR) may not always result in successful decannulation due to associated parameters such as co-morbidity and/or glottic involvement. We classified patients after incorporating these additional parameters into the original Myer-Cotton classification to assess whether this could better predict the outcome measures after PCTR. METHODS: One hundred children with Myer-Cotton grade III or IV subglottic stenosis who underwent PCTR between 1978 and 2008 were identified from a prospectively collected database. The patients were classified into four groups based on the association of co-morbidity and/or glottic involvement. Delay in decannulation, revision open surgery and rates of decannulation were the outcome measures compared between the groups. RESULTS: There were 68 children with Myer-Cotton grade III and 32 children with grade IV stenosis. Based on the new classification, there were 36 children with isolated SGS, 31 with associated co-morbidity, 19 with associated glottic involvement and 14 children with both co-morbidity and glottic involvement. A trend towards less optimal results was noticed with the association of co-morbidity and/or glottic involvement. Statistical significance was reached for maximum decannulation failure in the group with both co-morbidity and glottic involvement. Delayed decannulation significantly correlated in the group with associated glottic involvement. CONCLUSION: This new classification is relatively simple and aimed at providing more accurate and uniform prognostic information to both patients and surgeons when dealing with the whole spectrum of severe SGS.

Documentation of fracture severity with the AO classification of pediatric long-bone fractures.

BACKGROUND: The AO comprehensive pediatric longbone fracture classification system describes the localization and morphology of fractures, and considers severity in 3 categories: (1) simple, (2) wedge, and (3) complex. We evaluated the reliability and accuracy of surgeons in using this rating system. MATERIAL AND METHODS: In a first validation phase, 5 experienced pediatric (orthopedic) surgeons reviewed radiographs of 267 prospectively collected pediatric fractures (agreement study A). In a second study (B), 70 surgeons of various levels of experience in 15 clinics classified 275 fractures via internet. Simple fractures comprised about 90%, 99% and 100% of diaphyseal (D), metaphyseal (M), and epiphyseal (E) fractures, respectively. RESULTS: Kappa coefficients for severity coding in D fractures were 0.82 and 0.51 in studies A and B, respectively. The median accuracy of surgeons in classifying simple fractures was above 97% in both studies but was lower, 85% (46-100), for wedge or complex D fractures. INTERPRETATION: While reliability and accuracy estimates were satisfactory as a whole, the ratings of some individual surgeons were inadequate. Our findings suggest that the classification of fracture severity in children should be done in only two categories that distinguish between simple and wedge/complex fractures.

A key transcription cofactor on the nascent sex chromosomes of European tree frogs (Hyla arborea)

We show that MED15, a key component of the transcription complex Mediator, lies within the nonrecombining segment of nascent sex chromosomes in the male-heterogametic Hyla arborea. Both X and Y alleles are expressed during embryonic development and differ by three frame-preserving indels (eight amino acids in total) within their glutamine-rich central part. These changes have the potential to affect the conformation of the Mediator complex and to activate genes in a sex-specific way and might thus represent the first steps toward the acquisition of a male-specific function. Alternatively, they might result from an ancestral neutral polymorphism, with different alleles picked by chance on the X and Y chromosomes when MED15 was trapped in the nonrecombining segment.

Classification and management of seeds in retinoblastoma. Ellsworth Lecture Ghent August 24th 2013.

Retinoblastoma has the unique capacity to accelerate its own intra-ocular propagation by adopting semi-solid or even liquid growth properties through seeding. Until recently, the presence of any degree of seeding was mostly incompatible with successful conservative management, due to the multiresistant nature of the seeds. Surprisingly, this well-recognized retinoblastoma behavior has not undergone any detailed description of seeding patterns and anatomic sites. In this paper, we describe the phenotypic variability of seeds across the four possible intraocular seeding compartments and classify them into three fundamental types: namely dust, spheres, and clouds. We also provide an overview of the different therapeutic strategies developed for seeding, with special attention to intravitreal chemotherapy as the treatment of choice for vitreous and retro-hyaloid seeding. Finally, we propose criteria to enable assessment of the response to treatment by reporting seed regression patterns, as well as a clinical grading system for the retinal toxicity observed following intravitreal melphalan.

Evolution of C(4) phosphoenolpyruvate carboxykinase in grasses, from genotype to phenotype.

C(4) photosynthesis is an adaptation over the classical C(3) pathway that has evolved multiple times independently. These convergences are accompanied by strong variations among the independent C(4) lineages. The decarboxylating enzyme used to release CO(2) around Rubisco particularly differs between C(4) species, a criterion used to distinguish three distinct biochemical C(4) subtypes. The phosphoenolpyruvate carboxykinase (PCK) serves as a primary decarboxylase in a minority of C(4) species. This enzyme is also present in C(3) plants, where it is responsible for nonphotosynthetic functions. The genetic changes responsible for the evolution of C(4)-specific PCK are still unidentified. Using phylogenetic analyses on PCK sequences isolated from C(3) and C(4) grasses, this study aimed at resolving the evolutionary history of C(4)-specific PCK enzymes. Four independent evolutions of C(4)-PCK were shown to be driven by positive selection, and nine C(4)-adaptive sites underwent parallel genetic changes in different C(4) lineages. C(4)-adaptive residues were also observed in C(4) species from the nicotinamide adenine dinucleotide phosphate-malic enzyme (NADP-ME) subtype and particularly in all taxa where a PCK shuttle was previously suggested to complement the NADP-ME pathway. Acquisitions of C(4)-specific PCKs were mapped on a species tree, which revealed that the PCK subtype probably appeared at the base of the Chloridoideae subfamily and was then recurrently lost and secondarily reacquired at least three times. Linking the genotype to subtype phenotype shed new lights on the evolutionary transitions between the different C(4) subtypes.

Health problems among detainees in Switzerland: a study using the ICPC-2 classification.

BACKGROUND: Little is known about the health status of prisoners in Switzerland. The aim of this study was to provide a detailed description of the health problems presented by detainees in Switzerland's largest remand prison. METHODS: In this retrospective cross-sectional study we reviewed the health records of all detainees leaving Switzerland's largest remand prison in 2007. The health problems were coded using the International Classification for Primary Care (ICPC-2). Analyses were descriptive, stratified by gender. RESULTS: A total of 2195 health records were reviewed. Mean age was 29.5 years (SD 9.5); 95% were male; 87.8% were migrants. Mean length of stay was 80 days (SD 160). Illicit drug use (40.2%) and mental health problems (32.6%) were frequent, but most of these detainees (57.6%) had more generic primary care problems, such as skin (27.0%), infectious diseases (23.5%), musculoskeletal (19.2%), injury related (18.3%), digestive (15.0%) or respiratory problems (14.0%). Furthermore, 7.9% reported exposure to violence during arrest by the police. CONCLUSION: Morbidity is high in this young, predominantly male population of detainees, in particular in relation to substance abuse. Other health problems more commonly seen in general practice are also frequent. These findings support the further development of coordinated primary care and mental health services within detention centers.