Development of diagnostic and prognostic algorithms from vacuum circuit breaker restrike review and its validation proposal

The CIGRE WGs A3.20 and A3.24 identify the requirements of simulation tools to predict various stresses during the development and operational phases of medium voltage vacuum circuit breaker (VCB) testing. This paper reviews the modelling methodology [13], VCB models and tools to identify future research. It will include the application of the VCB model for the impending failure of a VCB using electro-magnetic-transient-program with diagnostic and prognostic algorithm development. The methodology developed for a VCB degradation model is to modify the dielectric equation to cover a restriking period of more than 1 millimetre.

Development of diagnostic and prognostic algorithms for SF6 puffer circuit breakers from transient waveforms : a validation proposal

- This paper presents a validation proposal for development of diagnostic and prognostic algorithms for SF6 puffer circuit-breakers reproduced from actual site waveforms. The re-ignition/restriking rates are duplicated in given circuits and the cumulative energy dissipated in interrupters by the restriking currents. The targeted objective is to provide a simulated database for diagnosis of re-ignition/restrikes relating to the phase to earth voltage and the number of re-ignition/restrikes as well as estimating the remaining life of SF6 circuit-breakers. The model-based diagnosis of a tool will be useful in monitoring re-ignition/restrikes as well as predicting a nozzle’s lifetime. This will help ATP users with practical study cases and component data compilation for shunt reactor switching and capacitor switching. This method can be easily applied with different data for the different dielectric curves of circuit breakers and networks. This paper presents modelling details and some of the available cases, required project support, the validation proposal, the specific plan for implementation and the propsed main contributions.

Individual patient data meta-analysis of diagnostic and prognostic studies in obstetrics, gynaecology and reproductive medicine

BACKGROUND: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine. METHODS/DESIGN: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians. DISCUSSION: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

Diagnostic and prognostic biomarker discovery strategies for autoimmune disorders.

Current clinical, laboratory or radiological parameters cannot accurately diagnose or predict disease outcomes in a range of autoimmune disorders. Biomarkers which can diagnose at an earlier time point, predict outcome or help guide therapeutic strategies in autoimmune diseases could improve clinical management of this broad group of debilitating disorders. Additionally, there is a growing need for a deeper understanding of multi-factorial autoimmune disorders. Proteomic platforms offering a multiplex approach are more likely to reflect the complexity of autoimmune disease processes. Findings from proteomic based studies of three distinct autoimmune diseases are presented and strategies compared. It is the authors' view that such approaches are likely to be fruitful in the movement of autoimmune disease treatment away from reactive decisions and towards a preventative stand point.

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

Ki-67 labeling in canine perianal glands neoplasms: A novel approach for immunohistological diagnostic and prognostic

Background: The antibody Ki-67 is a reliable and easy tool to accurately assess the growth fraction of neoplasms in humans and animals, and it has been used to predict the clinical outcome. Therefore, the aim of the present study was to investigate the immunohistochemical expression pattern of Ki-67 in normal and neoplastic perianal glands of dogs to evaluate the possible use of this proliferation marker as an ancillary method of perianal tumor diagnosis. We studied 42 cases of perianal gland neoplasms including adenomas (n = 15), epitheliomas (n = 15), and carcinomas (n = 12). As controls, 13 tissue samples from normal perianal glands were used. A Ki-67 index was established by a computer-assisted image analysis and compared with manual counting. Results: Out of the 42 cases of perianal gland neoplasms, 34 were from males and eight from females. Recurrence was reported in 14 cases, being higher (8/12) in carcinomas. Immunostaining for Ki-67 revealed that the carcinomas showed a higher proliferation rate (9.87%) compared to groups of epitheliomas (2.66%) and adenomas (0.36%). For adenomas and epitheliomas of the perianal glands the computer-assisted counting and the manual counting gave similar results; however, only the computer-assisted image analysis was efficient to predict the perianal gland carcinoma recurrence.Conclusion: Since there were significant differences in the number of Ki-67-positive nuclei, this marker proved to be effective in helping the classification of perianal gland neoplasms and to refine the diagnosis criteria, especially in those samples with high variation in morphology/area. Also, higher Ki-67 index is related to recurrence in cases of perianal gland carcinomas. Further, the computer-assisted image analysis proved to be a fast and reliable method to assess the Ki-67 index in perianal gland neoplasms. © 2013 Pereira et al.; licensee BioMed Central Ltd.

Sleep motor activity in parkinsonian syndromes at onset: a prospective study to determine potential diagnostic and prognostic markers

Aim of this study is to describe the possible diagnostic value of sleep disturbances in the differential diagnosis of neurodegenerative diseases characterized by parkinsonism at onset. 42 consecutive patients with parkinsonian features and disease duration up to 3 years were included in the BO-ProPark study. Each patient was evaluated twice, at baseline (T0) and 16 months later (T1). Patients were diagnosed as Parkinson disease (PD, 27 patients), PD plus (PD with cognitive impairment/dementia or dysautonomia, 4 patients) and parkinsonian syndrome (PS, 11 patients). All patients underwent a full night video-polysomnography scored by a neurologist blinded to the clinical diagnosis. Sleep efficiency and total sleep time were reduced in all patients; wake after sleep onset was higher in patients with atypical parkinsonisms than in PD patients. No significant differences between groups of patients were detected in other sleep parameters. The mean percentage of epochs with enhanced tonic muscle EMG activity during REM sleep was higher in PD plus and PS than in PD. No difference in phasic muscle EMG activity during REM sleep was seen between the two groups. REM behaviour disorder was more frequent in PD plus and PS than in PD patients. Our data suggest that REM sleep motor control is more frequently impaired at disease onset in patients with PS and PD plus compared to PD patients. The presence of RBD or an enhanced tonic muscle EMG activity in a patient with recent onset parkinsonian features should suggest a diagnosis of atypical parkinsonism, rather than PD. More data are needed to establish the diagnostic value of these features in the differential diagnosis of parkinsonisms. The evaluation of sleep disorders may be a useful tool in the differential diagnosis of parkinsonism at onset.

Diagnostic and prognostic implications of the PAX8-PPARγ translocation in thyroid carcinomas-a TMA-based study of 226 cases

AIMS Follicular thyroid carcinoma (FTC) has been a diagnostic challenge for decades. The PAX8-PPARγ rearrangement has been detected in FTC and classic papillary thyroid carcinomas (PTCs). The aims of this study were to assess the presence of PAX8-PPARγ by using tissue microarrays in a large cohort of different thyroid neoplasms, and to assess its diagnostic and prognostic implications. METHODS AND RESULTS Fluorescence in-situ hybridization (FISH) analysis for PAX8-PPARγ was performed on 226 thyroid tumours, comprising FTCs (n = 59), PTCs (n = 126), poorly differentiated thyroid carcinomas (PDs; n = 34), follicular thyroid adenomas (FTAs; n = 5), and follicular tumours of unknown malignant potential (FTUMPs; n = 2). PAX8-PPARγ was detected in 12% of FTCs, 1% of PTCs, 7% of PDs, and in both cases of FTUMP. There was no correlation between the extent of capsular or vascular invasion and PAX8-PPARγ, or between lymph node or haematogenous metastasis and PAX8-PPARγ. Overall survival (OS), tumour-specific survival (TSS) and relapse-free-survival (RFS) were not influenced by PAX8-PPARγ. CONCLUSIONS In this study, we demonstrate for the first time the presence of PAX8-PPARγ in PDs and FTUMPs, whereas in FTCs and PTCs the prevalence of PAX8-PPARγ is lower than previously reported. PAX8-PPARγ did not correlate with invasiveness or affect prognosis in any tumour type.

MicroRNA profile of poorly differentiated thyroid carcinomas: new diagnostic and prognostic insights.

The diagnosis of conventional and oncocytic poorly differentiated (oPD) thyroid carcinomas is difficult. The aim of this study is to characterise their largely unknown miRNA expression profile and to compare it with well-differentiated thyroid tumours, as well as to identify miRNAs which could potentially serve as diagnostic and prognostic markers. A total of 14 poorly differentiated (PD), 13 oPD, 72 well-differentiated thyroid carcinomas and eight normal thyroid specimens were studied for the expression of 768 miRNAs using PCR-Microarrays. MiRNA expression was different between PD and oPD thyroid carcinomas, demonstrating individual clusters on the clustering analysis. Both tumour types showed upregulation of miR-125a-5p, -15a-3p, -182, -183-3p, -222, -222-5p, and downregulation of miR-130b, -139-5p, -150, -193a-5p, -219-5p, -23b, -451, -455-3p and of miR-886-3p as compared with normal thyroid tissue. In addition, the oPD thyroid carcinomas demonstrated upregulation of miR-221 and miR-885-5p. The difference in expression was also observed between miRNA expression in PD and well-differentiated tumours. The CHAID algorithm allowed the separation of PD from well-differentiated thyroid carcinomas with 73-79% accuracy using miR-23b and miR-150 as a separator. Kaplan-Meier and multivariate analysis showed a significant association with tumour relapses (for miR-23b) and with tumour-specific death (for miR-150) in PD and oPD thyroid carcinomas. MiRNA expression is different in conventional and oPD thyroid carcinomas in comparison with well-differentiated thyroid cancers and can be used for discrimination between these tumour types. The newly identified deregulated miRNAs (miR-150, miR-23b) bear the potential to be used in a clinical setting, delivering prognostic and diagnostic informations.

Noninvasive Urinary Metabolomic Profiling Identifies Diagnostic and Prognostic Markers in Lung Cancer

Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1,500 Da) were measured in urine collected from 469 patients with lung cancer and 536 population controls using unbiased liquid chromatography/mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further confirmed in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared with the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA) were each significantly (P < 0.00001) elevated in non-small cell lung cancer and associated with worse prognosis [HR = 1.81 (P = 0.0002), and 1.54 (P = 0.025), respectively]. Creatine riboside was the strongest classifier of lung cancer status in all and stage I-II cases, important for early detection, and also associated with worse prognosis in stage I-II lung cancer (HR = 1.71, P = 0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 to 0.99. Both metabolites were significantly (P < 0.03) enriched in tumor tissue compared with adjacent nontumor tissue (N = 48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis.

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study

BACKGROUND AND PURPOSE The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

Zoologia medicinalis hibernica or, A treatise of birds, beasts, fishes, reptiles, or insects in this kingdom : giving an account of their medicinal virtues, and their names in English, Irish, and Latin : to which is added, a short treatise of the diagnostic and prognostic parts of medicine .../

Mode of access: Internet.

The adoption and use of diagnostic and prognostic technology within UK-based manufacturers

Manufacturers are seeking increasingly innovative ways to achieve competitive advantage. An emerging trend is to exploit diagnostic and prognostic technology to support service-led competitive strategies where the emphasis is put on the 'sale of use' rather than the 'sale of product'. However, little is known about the extent to which this technology is being exploited, the drivers and inhibitors, and the sectors where adoption is most prolific. This paper introduces the results of a survey conducted across the UK manufacturing sector to explore the extent, motivations, benefits, and challenges of deploying diagnostic and prognostic technology as an element of competitive strategy.

A database ATP simulated waveforms of shunt reactor switching cases with vacuum breakers on motor circuits

This paper presents a database ATP (Alternative Transient Program) simulated waveforms for shunt reactor switching cases with vacuum breakers in motor circuits following interruption of the starting current. The targeted objective is to provide multiple reignition simulated data for diagnostic and prognostic algorithms development, but also to help ATP users with practical study cases and component data compilation for shunt reactor switching. This method can be easily applied with different data for the different dielectric curves of circuit-breakers and networks. This paper presents design details, discusses some of the available cases and the advantages of such simulated data.