Hospital Service Plans: Their Contract Provisions and Administrative Procedures

We propose an FDI system for the wind turbine benchmark designed by the application of a generic automated method. No specific adaptation of the method for the wind turbine benchmark is needed, and the number of required human decisions, assumptions, as well as parameter choices is minimized. The method contains in essence three steps: generation of candidate residual generators, residual generator selection, and diagnostic test construction. The proposed FDI system performs well in spite of no specific adaptation or tuning to the benchmark. All faults in the predefined test sequence can be detected and all faults, except a double fault, can also be isolated shortly thereafter. In addition, there are no false or missed detections

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is < 30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay. We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings. In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions

An Efficient Implementation of Built in Self Diagnosis for Low Power Test Pattern Generator

A New architecture of Built-In Self-Diagnosis is presented in this project. The logic Built-In-Self-Test architecture method is extreme response compaction architecture. This architecture first time enables an autonomous on-chip evaluation of test responses with negligible hardware overhead. Architecture advantage is all data, which is relevant for a subsequent diagnosis, is gathered during just one test session. Due to some reasons, the existing method Built-In Self-Test is less often applied to random logic than to embedded memories.  The generation of deterministic test patterns can become prohibitively high due to hardware overhead. The diagnostic resolution of compacted test responses is in many cases poor and the overhead required for an acceptable resolution may become too high.  Modifications in Linear Feedback Shift Register to generate test pattern with security for modified Built-In-Self-Test applications with reduced power requirement. The modified Built-In-Self-Test circuit incorporates a fault syndrome compression scheme and improves the circuit speed with reduction of time

New challenges for BRCA testing:a view from the diagnostic laboratory

Increased demand for BRCA testing is placing pressures on diagnostic laboratories to raise their mutation screening capacity and handle the challenges associated with classifying BRCA sequence variants for clinical significance, for example interpretation of pathogenic mutations or variants of unknown significance, accurate determination of large genomic rearrangements and detection of somatic mutations in DNA extracted from formalin-fixed, paraffin-embedded tumour samples. Many diagnostic laboratories are adopting next-generation sequencing (NGS) technology to increase their screening capacity and reduce processing time and unit costs. However, migration to NGS introduces complexities arising from choice of components of the BRCA testing workflow, such as NGS platform, enrichment method and bioinformatics analysis process. An efficient, cost-effective accurate mutation detection strategy and a standardised, systematic approach to the reporting of BRCA test results is imperative for diagnostic laboratories. This review covers the challenges of BRCA testing from the perspective of a diagnostics laboratory

Molecular diagnostics of rare inherited SYNDROMES with a view on diagnostic test development

CHARGE syndrome, Sotos syndrome and 3p deletion syndrome are examples of rare inherited syndromes that have been recognized for decades but for which the molecular diagnostics only have been made possible by recent advances in genomic research. Despite these advances, development of diagnostic tests for rare syndromes has been hindered by diagnostic laboratories having limited funds for test development, and their prioritization of tests for which a (relatively) high demand can be expected. In this study, the molecular diagnostic tests for CHARGE syndrome and Sotos syndrome were developed, resulting in their successful translation into routine diagnostic testing in the laboratory of Medical Genetics (UTUlab). In the CHARGE syndrome group, mutation was identified in 40.5% of the patients and in the Sotos syndrome group, in 34%, reflecting the use of the tests in routine diagnostics in differential diagnostics. In CHARGE syndrome, the low prevalence of structural aberrations was also confirmed. In 3p deletion syndrome, it was shown that small terminal deletions are not causative for the syndrome, and that testing with arraybased analysis provides a reliable estimate of the deletion size but benign copy number variants complicate result interpretation. During the development of the tests, it was discovered that finding an optimal molecular diagnostic strategy for a given syndrome is always a compromise between the sensitivity, specificity and feasibility of applying a new method. In addition, the clinical utility of the test should be considered prior to test development: sometimes a test performing well in a laboratory has limited utility for the patient, whereas a test performing poorly in the laboratory may have a great impact on the patient and their family. At present, the development of next generation sequencing methods is changing the concept of molecular diagnostics of rare diseases from single tests towards whole-genome analysis.Siirretty Doriast

A new targeted CFTR mutation panel based on next-generation sequencing technology

Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0% and 95.6% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling

An Infrastructural IP for Interactive MPEG-4 SoC Functional Verification

This paper introduces a specific architecture including an infrastructural IP for functional verification and diagnostics, which is suitable for functional core-based testing of an MPEG4 SoC. Our advanced MPEG4 SoC results in a high complexity SoC with limited physical access to many different functional cores. The proposed test method provides direct monitoring and control for each core, which enables core verification at actual speed. It significantly decreases the verification time due to the large number of required test vectors in typical MPEG4 verification. Furthermore, it also makes the system scalable for functional core expansion due to upgrading of standards. The proposed infrastructural IP is also linked to PC-based interactive tools to simplify the verification of individual and integrated cores. It also provides detailed diagnostic data that enables simple system debugging. The debugging tools also feature test-pattern generation and simulation of expected values. Actual system implementation has shown full functionality of our proposed method

Model-Independent Diagnostics of Highly Reddened Milky Way Star Clusters: Age Calibration

The next generation near- and mid-infrared Galactic surveys will yield a large number of new highly obscured star clusters. Detailed characterization of these new objects with spectroscopy is time-consuming. Diagnostic tools that will be able to characterize clusters based only on the available photometry will be needed to study large samples of the newly found objects. The brightness difference between the red clump and the main-sequence turn-off point have been used as a model-independent age calibrator for clusters with ages from a few 10$^8$ to 10$^{10}$ yr in the optical. Here we apply for the first time the method in the near-infrared. We calibrated this difference in $K$-band, which is likely to be available for obscured clusters, and we apply it to a number of test clusters with photometry comparable to the one that will be yielded by the current or near-future surveys. The new calibration yields reliable ages over the range of ages for which the red clump is present in clusters. The slope of the relation is smoother than that of the corresponding $V$-band relation, reducing the uncertainty in the age determinations with respect to the optical ones.Comment: 5 pages, 5 eps figure, accepted for publication in Astronomy and Astrophysic

Rapid detection of copy number variations and point mutations in BRCA1/2 genes using a single workflow by ion semiconductor sequencing pipeline

Molecular analysis of BRCA1 (MIM# 604370) and BRCA2 (MIM #600185) genes is essential for familial breast and ovarian cancer prevention and treatment. An efficient, rapid, cost-effective accurate strategy for the detection of pathogenic variants is crucial. Mutations detection of BRCA1/2 genes includes screening for single nucleotide variants (SNVs), small insertions or deletions (indels), and Copy Number Variations (CNVs). Sanger sequencing is unable to identify CNVs and therefore Multiplex Ligation Probe amplification (MLPA) or Multiplex Amplicon Quantification (MAQ) is used to complete the BRCA1/2 genes analysis. The rapid evolution of Next Generation Sequencing (NGS) technologies allows the search for point mutations and CNVs with a single platform and workflow. In this study we test the possibilities of NGS technology to simultaneously detect point mutations and CNVs in BRCA1/2 genes, using the OncomineTM BRCA Research Assay on Personal Genome Machine (PGM) Platform with Ion Reporter Software for sequencing data analysis (Thermo Fisher Scientific). Comparison between the NGS-CNVs, MLPA and MAQ results shows how the NGS approach is the most complete and fast method for the simultaneous detection of all BRCA mutations, avoiding the usual time consuming multistep approach in the routine diagnostic testing of hereditary breast and ovarian cancers

Fault isolation schemes for a class of continuous-time stochastic dynamical systems

In this paper a new method for fault isolation in a class of continuous-time stochastic dynamical systems is proposed. The method is framed in the context of model-based analytical redundancy, consisting in the generation of a residual signal by means of a diagnostic observer, for its posterior analysis. Once a fault has been detected, and assuming some basic a priori knowledge about the set of possible failures in the plant, the isolation task is then formulated as a type of on-line statistical classification problem. The proposed isolation scheme employs in parallel different hypotheses tests on a statistic of the residual signal, one test for each possible fault. This isolation method is characterized by deriving for the unidimensional case, a sufficient isolability condition as well as an upperbound of the probability of missed isolation. Simulation examples illustrate the applicability of the proposed scheme