Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers.

The objective of this work was to develop and validate a set of clinical criteria for the classification of patients affected by periodic fevers. Patients with inherited periodic fevers (familial Mediterranean fever (FMF); mevalonate kinase deficiency (MKD); tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS); cryopyrin-associated periodic syndromes (CAPS)) enrolled in the Eurofever Registry up until March 2013 were evaluated. Patients with periodic fever, aphthosis, pharyngitis and adenitis (PFAPA) syndrome were used as negative controls. For each genetic disease, patients were considered to be 'gold standard' on the basis of the presence of a confirmatory genetic analysis. Clinical criteria were formulated on the basis of univariate and multivariate analysis in an initial group of patients (training set) and validated in an independent set of patients (validation set). A total of 1215 consecutive patients with periodic fevers were identified, and 518 gold standard patients (291 FMF, 74 MKD, 86 TRAPS, 67 CAPS) and 199 patients with PFAPA as disease controls were evaluated. The univariate and multivariate analyses identified a number of clinical variables that correlated independently with each disease, and four provisional classification scores were created. Cut-off values of the classification scores were chosen using receiver operating characteristic curve analysis as those giving the highest sensitivity and specificity. The classification scores were then tested in an independent set of patients (validation set) with an area under the curve of 0.98 for FMF, 0.95 for TRAPS, 0.96 for MKD, and 0.99 for CAPS. In conclusion, evidence-based provisional clinical criteria with high sensitivity and specificity for the clinical classification of patients with inherited periodic fevers have been developed.

Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria. Resources are currently too limited to fund all the beneficial genetic testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit of information for important life decisions, benefit for other people apart from the person tested and the patient-specific likelihood of being affected by the condition tested for. It may be subject to a finite time window. Health need includes the severity of the condition tested for and its progression at the time of testing. Further discussion and better evidence is needed before clearly defined recommendations can be made or a prioritization algorithm proposed. To our knowledge, this is the first time a clinical society has initiated a decision process about health-care prioritization on a European level, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.

Object-oriented development of client / server application: case study of service control software

Tässä työssä on esitetty sen ohjelmiston kehittämisen prosessi, joka on tarkoitettu annettavien palveluiden valvottavaksi käyttäen prototyyppimallia. Raportti sisältää vaatimusten, kohteisiin suunnatun analyysin ja suunnittelun, realisointiprosessien kuvauksen ja prototyypin testauksen. Ohjelmiston käyttöala – antavien palveluiden valvonta. Vaatimukset sovellukselle analysoitiin ohjelmistomarkkinoiden perusteella sekä ohjelmiston engineeringin periaatteiden mukaisesti. Ohjelmiston prototyyppi on realisoitu käyttäen asiakas-/palvelinhybridimallia sekä ralaatiokantaa. Kehitetty ohjelmisto on tarkoitettu venäläisille tietokonekerhoille, jotka erikoistuvat pelipalvelinten antamiseen.

The Classification of Vitreous Seeds in Retinoblastoma and Response to Intravitreal Melphalan.

PURPOSE: To evaluate the clinical characteristics of the 3 classifications of vitreous seeds in retinoblastoma-dust (class 1), spheres (class 2), and clouds (class 3)-and their responses to intravitreal melphalan. DESIGN: Retrospective, bi-institutional cohort study. PARTICIPANTS: A total of 87 patient eyes received 475 intravitreal injections of melphalan (median dose, 30 μg) given weekly, a median of 5 times (range, 1-12 times). METHODS: At presentation, the vitreous seeds were classified into 3 groups: dust, spheres, and clouds. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response to weekly intravitreal melphalan injections and time to regression of vitreous seeds. Kaplan-Meier estimates of time to regression and ocular survival, patient survival, and event-free survival (EFS) were calculated and then compared using the Mantel-Cox test of curve. MAIN OUTCOME MEASURES: Time to regression of vitreous seeds, patient survival, ocular survival, and EFS. RESULTS: The difference in time to regression was significantly different for the 3 seed classes (P < 0.0001): the median time to regression was 0.6, 1.7, and 7.7 months for dust, spheres, and clouds, respectively. Eyes with dust received significantly fewer injections and a lower median and cumulative dose of melphalan, whereas eyes with clouds received significantly more injections and a higher median and cumulative dose of melphalan. Overall, the 2-year Kaplan-Meier estimates for ocular survival, patient survival, and EFS (related to target seeds) were 90.4% (95% confidence interval [CI], 79.7-95.6), 100%, and 98.5% (95% CI, 90-99.7), respectively. CONCLUSIONS: The regression and response of vitreous seeds to intravitreal melphalan are different for each seed classification. The vitreous seed classification can be predictive of time to regression, number, median dose, and cumulative dose of intravitreal melphalan injections required.

Object-Oriented Modelling of Multilayer Networks

Tämä diplomityökuuluu tietoliikenneverkkojen suunnittelun tutkimukseen ja pohjimmiltaan kohdistuu verkon mallintamiseen. Tietoliikenneverkkojen suunnittelu on monimutkainen ja vaativa ongelma, joka sisältää mutkikkaita ja aikaa vieviä tehtäviä. Tämä diplomityö esittelee ”monikerroksisen verkkomallin”, jonka tarkoitus on auttaa verkon suunnittelijoita selviytymään ongelmien monimutkaisuudesta ja vähentää verkkojen suunnitteluun kuluvaa aikaa. Monikerroksinen verkkomalli perustuu yleisille objekteille, jotka ovat yhteisiä kaikille tietoliikenneverkoille. Tämä tekee mallista soveltuvan mielivaltaisille verkoille, välittämättä verkkokohtaisista ominaisuuksista tai verkon toteutuksessa käytetyistä teknologioista. Malli määrittelee tarkan terminologian ja käyttää kolmea käsitettä: verkon jakaminen tasoihin (plane separation), kerrosten muodostaminen (layering) ja osittaminen (partitioning). Nämä käsitteet kuvataan yksityiskohtaisesti tässä työssä. Monikerroksisen verkkomallin sisäinen rakenne ja toiminnallisuus ovat määritelty käyttäen Unified Modelling Language (UML) -notaatiota. Tämä työ esittelee mallin use case- , paketti- ja luokkakaaviot. Diplomityö esittelee myös tulokset, jotka on saatu vertailemalla monikerroksista verkkomallia muihin verkkomalleihin. Tulokset osoittavat, että monikerroksisella verkkomallilla on etuja muihin malleihin verrattuna.

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome.

Classification-Based compression of Multispectral Images

The purpose of this thesis is to present a new approach to the lossy compression of multispectral images. Proposed algorithm is based on combination of quantization and clustering. Clustering was investigated for compression of the spatial dimension and the vector quantization was applied for spectral dimension compression. Presenting algo¬rithms proposes to compress multispectral images in two stages. During the first stage we define the classes' etalons, another words to each uniform areas are located inside the image the number of class is given. And if there are the pixels are not yet assigned to some of the clusters then it doing during the second; pass and assign to the closest eta¬lons. Finally a compressed image is represented with a flat index image pointing to a codebook with etalons. The decompression stage is instant too. The proposed method described in this paper has been tested on different satellite multispectral images from different resources. The numerical results and illustrative examples of the method are represented too.

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE).

Product information management system design framework for production oriented company

Diplomityössä luodaan viitekehys tuotetiedonhallintajärjestelmän esisuunnittelua varten. Siinä on kolme ulottuvuutta: lisäarvontuotto-, toiminnallisuus- ja ohjelmistoulottuvuus. Viitekehys auttaa- tunnistamaan lisäarvontuottokomponentit, joihin voidaan vaikuttaa tiettyjen ohjelmistoluokkien tarjoamilla tuotetiedonhallintatoiminnallisuuksilla. Viitekehyksen järjestelmäsuunnittelullista näkökulmaa hyödynnetään tutkittavissa yritystapauksissa perustuen laskentamatriisin muotoon mallinnettuihin ulottuvuuksien välisiin suhteisiin. Matriisiin syötetään lisäarvontuotto- ja toiminnallisuuskomponenttien saamat tärkeydet kohdeyrityksessä suoritetussa haastattelututkimuksessa. Matriisin tuotos on tietyn ohjelmiston soveltuvuus kyseisen yrityksen tapauksessa. Soveltuvuus on joukko tunnuslukuja, jotka analysoidaan tulostenkäsittelyvaiheessa. Soveltuvuustulokset avustavat kohdeyritystä sen valitessa lähestymistapaansa tuotetiedonhallintaan - ja kuvaavat esisuunnitellun tuotetiedonhallintajärjestelmän. Viitekehyksen rakentaminen vaatii perinpohjaisen lähestymistavan merkityksellisten lisäarvontuotto- ja toiminnallisuuskomponenttien sekä ohjelmistoluokkien määrittämiseen. Määritystyö perustuu työssä yksityiskohtaisesti laadittujen menetelmien ja komponenttiryhmitysten hyödyntämiselle. Kunkin alueen analysointi mahdollistaa viitekehyksen ja laskentamatriisin rakentamisen yhdenmukaisten määritysten perusteella. Viitekehykselle on ominaista sen muunneltavuus. Nykymuodossaan se soveltuu elektroniikka- ja high-tech yrityksille. Viitekehystä voidaan hyödyntää myös muilla toimialoilla muokkaamalla lisäarvontuottokomponentteja kunkin toimialan intressien mukaisesti. Vastaavasti analysoitava ohjelmisto voidaan valita tapauskohtaisesti. Laskentamatriisi on kuitenkin ensin päivitettävä valitun ohjelmiston kyvykkyyksillä, minkä jälkeen viitekehys voi tuottaa soveltuvuustuloksia kyseiseen yritystapaukseen perustuen