The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): A review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals.

Progressive pseudorheumatoid dysplasia (PPRD) is a genetic, non-inflammatory arthropathy caused by recessive loss of function mutations in WISP3 (Wnt1-inducible signaling pathway protein 3; MIM 603400), encoding for a signaling protein. The disease is clinically silent at birth and in infancy. It manifests between the age of 3 and 6 years with joint pain and progressive joint stiffness. Affected children are referred to pediatric rheumatologists and orthopedic surgeons; however, signs of inflammation are absent and anti-inflammatory treatment is of little help. Bony enlargement at the interphalangeal joints progresses leading to camptodactyly. Spine involvement develops in late childhood and adolescence leading to short trunk with thoracolumbar kyphosis. Adult height is usually below the 3rd percentile. Radiographic signs are relatively mild. Platyspondyly develops in late childhood and can be the first clue to the diagnosis. Enlargement of the phalangeal metaphyses develops subtly and is usually recognizable by 10 years. The femoral heads are large and the acetabulum forms a distinct "lip" overriding the femoral head. There is a progressive narrowing of all articular spaces as articular cartilage is lost. Medical management of PPRD remains symptomatic and relies on pain medication. Hip joint replacement surgery in early adulthood is effective in reducing pain and maintaining mobility and can be recommended. Subsequent knee joint replacement is a further option. Mutation analysis of WISP3 allowed the confirmation of the diagnosis in 63 out of 64 typical cases in our series. Intronic mutations in WISP3 leading to splicing aberrations can be detected only in cDNA from fibroblasts and therefore a skin biopsy is indicated when genomic analysis fails to reveal mutations in individuals with otherwise typical signs and symptoms. In spite of the first symptoms appearing in early childhood, the diagnosis of PPRD is most often made only in the second decade and affected children often receive unnecessary anti-inflammatory and immunosuppressive treatments. Increasing awareness of PPRD appears to be essential to allow for a timely diagnosis. © 2012 Wiley Periodicals, Inc.

Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

BACKGROUND: Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. METHODS: We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. FINDINGS: We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). INTERPRETATION: Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. FUNDING: Swiss National Science Foundation.

Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe.

Meckel-Gruber Syndrome is a rare autosomal recessive lethal ciliopathy characterized by the triad of cystic renal dysplasia, occipital encephalocele and postaxial polydactyly. We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. The study population consisted of 191 cases of MKS identified between January 1990 and December 2011 in 34 European registries. The mean prevalence was 2.6 per 100 000 births in a subset of registries with good ascertainment. The prevalence was stable over time, but regional differences were observed. There were 145 (75.9%) terminations of pregnancy after prenatal diagnosis, 13 (6.8%) fetal deaths, 33 (17.3%) live births. In addition to cystic kidneys (97.7%), encephalocele (83.8%) and polydactyly (87.3%), frequent features include other central nervous system anomalies (51.4%), fibrotic/cystic changes of the liver (65.5% of cases with post mortem examination) and orofacial clefts (31.8%). Various other anomalies were present in 64 (37%) patients. As nowadays most patients are detected very early in pregnancy when liver or kidney changes may not yet be developed or may be difficult to assess, none of the anomalies should be considered obligatory for the diagnosis. Most cases (90.2%) are diagnosed prenatally at 14.3±2.6 (range 11-36) gestational weeks and pregnancies are mainly terminated, reducing the number of LB to one-fifth of the total prevalence rate. Early diagnosis is important for timely counseling of affected couples regarding the option of pregnancy termination and prenatal genetic testing in future pregnancies.

Contact Center Functionality - Collecting and Prioritizing Features of Modern Contact Center.

Tässä diplomityössä pohditaan call centereiden asemaa tämän päivän palveluympäristössä ja myöskin call centereiden tulevaisuutta contact centereinä. Tämä työ tutkii kuinka asiakastarpeita ja uusia toiminnallisuuksia voidaan etsiä olemassaolevaan, mutta vielä keskeneräiseen call center tuotteeseen. Tutkimus on tehty lukemalla artikkeleita ja kirjoja tulevaisuuden contact centereistä, haastattelemalla asiakkaita ja järjestämällä ideointisessio yrityksen asiantuntijoille. Näin saadut tulokset priorisoitiin tätä tarkoitusta varten kehitellyllä matriisilla. Lopullisena tuloksena on lista toiminnallisuuksista tärkeysjärjestyksessä ja tuote roadmap kaikkein tärkeimmistä toiminnallisuuksista. Tämä roadmap antaa tuotekehitykselle ehdotuksen mitä tulisi implementoida nykyiseen tuotteeseen ja mitkä ovat prioriteetit. Tässä työssä pohdiskellaan myös tuotteen modulaarista rakennetta.

Aberrant features of the Messinian coral reefs, Spain

Se describen someramente los principales arrecifes del Messiniense en España, haciendo hincapié en el conjunto de 'anomalias' presentan los arrecifes del Neógeno inferior en comparación con las asociaciones arrecifales actuales. Se discute la importancia y significado de Porites sp. como coral claramente dominante, y a menudo exclusivo, en la construcción de edificios arrecifales.

Investigating Neuroanatomical Features in Top Athletes at the Single Subject Level.

In sport events like Olympic Games or World Championships competitive athletes keep pushing the boundaries of human performance. Compared to team sports, high achievements in many athletic disciplines depend solely on the individual's performance. Contrasting previous research looking for expertise-related differences in brain anatomy at the group level, we aim to demonstrate changes in individual top athlete's brain, which would be averaged out in a group analysis. We compared structural magnetic resonance images (MRI) of three professional track-and-field athletes to age-, gender- and education-matched control subjects. To determine brain features specific to these top athletes, we tested for significant deviations in structural grey matter density between each of the three top athletes and a carefully matched control sample. While total brain volumes were comparable between athletes and controls, we show regional grey matter differences in striatum and thalamus. The demonstrated brain anatomy patterns remained stable and were detected after 2 years with Olympic Games in between. We also found differences in the fusiform gyrus in two top long jumpers. We interpret our findings in reward-related areas as correlates of top athletes' persistency to reach top-level skill performance over years.

The relative salience of facial features when differentiating faces based on an interference paradigm

Research on face recognition and social judgment usually addresses the manipulation of facial features (eyes, nose, mouth, etc.). Using a procedure based on a Stroop-like task, Montepare and Opeyo (J Nonverbal Behav 26(1):43-59, 2002) established a hierarchy of the relative salience of cues based on facial attributes when differentiating faces. Using the same perceptual interference task, we established a hierarchy of facial features. Twenty-three participants (13 men and 10 women) volunteered for the experiment to compare pairs of frontal faces. The participants had to judge if the eyes, nose, mouth and chin in the pair of images were the same or different. The factors manipulated were the target-distractive factor (4 face components 9 3 distractive factors), interference (absent vs. present) and correct answer (the same vs. different). The analysis of reaction times and errors showed that the eyes and mouth were processed before the chin and nose, thus highlighting the critical importance of the eyes and mouth, as shown by previous research.

Identification of Methylated Genes Associated with Aggressive Clinicopathological Features in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. Methodology/Principal Findings: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n=38). After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n=25) in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9,HOXA9,AHR,NR2F2 ,and ROBO1) frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. Conclusions: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP) that may influence the behaviour of the tumours.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

The Key Features of Knowledge and Knowledge Management in Product Development Process

Tutkimusongelmana oli kuinka tiedon johtamisella voidaan edesauttaa tuotekehitysprosessia. Mitkä ovat ne avaintekijät tietoympäristössä kuin myös itse tiedossa, joilla on merkitystä erityisesti tuotekehitysprosessin arvon muodostumiseen ja prosessien kehittämiseen? Tutkimus on laadullinen Case-tutkimus. Tutkimusongelmat on ensin selvitetty kirjallisuuden avulla, jonka jälkeen teoreettinen viitekehys on rakennettu tutkimaan rajattua ongelma-aluetta case-yrityksestä. Empiirisen tutkimuksen materiaali koostuu pääasiallisesti henkilökohtaisten teemahaastattelujen aineistosta. Tulokset merkittävimmistä tiedon hyväksikäytön haittatekijöistä, kuten myös parannusehdotukset on lajiteltu teoreettisessa viitekehyksessä esitettyjen oletustekijöiden mukaan. Haastatteluissa saadut vastaukset tukevat kirjallisuudesta ja alan ammattilaiselta saatua käsitystä tärkeimmistä vaikuttavista tekijöistä. Tärkeimmät toimenpiteet ja aloitteet joilla parannettaisiin tiedon muodostumista, koskivat ennnen kaikkea työnteon ulkoisia olosuhteita, eikä niinkään tiedon muodostumisen prosessia itseään. Merkittävimpiä haittatekijöitä olivat kultturiin, fyysiseen ja henkiseen tilaan ja henkilöstöresursseihin liittyvät ongelmat. Ratkaisuja ongelmiin odotettiin saatavan lähinnä tietotekniikan, henkilöstöresurssien ja itse tiedon muokkaamisen avulla. Tuotekehitysprosessin ydin tietovirtojen ja –pääomien luokittelu ja tulkitseminen tiedon muodostusta kuvaavan Learning Spiralin avulla antoi lähinnä teoreettisia viitteitä siitä millaisia keinoja on olemassa tiedon lisäämiseen ja jakamiseen eri tietotyypeittäin. Tulosten perusteella caseyrityksessä pitäisi kiinnittää erityistä huomiota tiedon dokumentointiin ja jakamiseen erityisesti sen tiedon osalta, joka on organisaatiossa vain harvalla ja/tai luonteeltaan hyvin tacitia.

Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients.

PURPOSE: The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type. METHODS: The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients' clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis. RESULTS: The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679±0.068, Akaike's information criterion 566.7, P<0.001). CONCLUSION: A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM.

Neotectonic features in the Catalan Coastal Ranges, Northeastern Spain

The Catalan Coastal Ranges constitute the northwestem emerged sector of the Catalan-Valencian domain of the Valencia trough. Since late Oligocene this domain of the Valencia trough was subjected to extension wich gradually attenuated during later periods. The Miocene tectonic evolution of the Catalan Coastal Ranges is relativelly well known while the Pliocene to-Quaternary stages have not been studied in detail. The recorded seismicity of the area is moderate and constant but not sufficiently intense to cliaracterize and locate recent tectonics. However, geological analysis provides further information. A morphotectonic and deformational analysis of the Catalan Coastal Ranges is presented in this paper.