Laser Scanner Tests For Single-Event Upsets

NASA Technical Reports Server (NTRS)

Kim, Quiesup; Soli, George A.; Schwartz, Harvey R.

1992-01-01

Microelectronic advanced laser scanner (MEALS) is opto/electro/mechanical apparatus for nondestructive testing of integrated memory circuits, logic circuits, and other microelectronic devices. Multipurpose diagnostic system used to determine ultrafast time response, leakage, latchup, and electrical overstress. Used to simulate some of effects of heavy ions accelerated to high energies to determine susceptibility of digital device to single-event upsets.

Accuracy of a Rapid Diagnostic Test (Cypress Chagas Quick Test®) for the Diagnosis of Chronic Chagas Disease in a Nonendemic Area: A Retrospective Longitudinal Study.

PubMed

Angheben, Andrea; Staffolani, Silvia; Anselmi, Mariella; Tais, Stefano; Degani, Monica; Gobbi, Federico; Buonfrate, Dora; Gobbo, Maria; Bisoffi, Zeno

2017-11-01

We analyzed the accuracy of Chagas Quick Test ® , a rapid diagnostic test, for the diagnosis of chronic Chagas disease through a retrospective study on a cohort of 669 patients consecutively examined at a single reference center in Italy, during a 7-year period. We observed high concordance with serological reference standard but low accuracy for screening purposes (sensitivity/specificity: 82.8%/98.7%) at least in our nonendemic context.

Physical examination tests of the shoulder: a systematic review and meta-analysis of diagnostic test performance.

PubMed

Gismervik, Sigmund Ø; Drogset, Jon O; Granviken, Fredrik; Rø, Magne; Leivseth, Gunnar

2017-01-25

Physical examination tests of the shoulder (PETS) are clinical examination maneuvers designed to aid the assessment of shoulder complaints. Despite more than 180 PETS described in the literature, evidence of their validity and usefulness in diagnosing the shoulder is questioned. This meta-analysis aims to use diagnostic odds ratio (DOR) to evaluate how much PETS shift overall probability and to rank the test performance of single PETS in order to aid the clinician's choice of which tests to use. This study adheres to the principles outlined in the Cochrane guidelines and the PRISMA statement. A fixed effect model was used to assess the overall diagnostic validity of PETS by pooling DOR for different PETS with similar biomechanical rationale when possible. Single PETS were assessed and ranked by DOR. Clinical performance was assessed by sensitivity, specificity, accuracy and likelihood ratio. Six thousand nine-hundred abstracts and 202 full-text articles were assessed for eligibility; 20 articles were eligible and data from 11 articles could be included in the meta-analysis. All PETS for SLAP (superior labral anterior posterior) lesions pooled gave a DOR of 1.38 [1.13, 1.69]. The Supraspinatus test for any full thickness rotator cuff tear obtained the highest DOR of 9.24 (sensitivity was 0.74, specificity 0.77). Compression-Rotation test obtained the highest DOR (6.36) among single PETS for SLAP lesions (sensitivity 0.43, specificity 0.89) and Hawkins test obtained the highest DOR (2.86) for impingement syndrome (sensitivity 0.58, specificity 0.67). No single PETS showed superior clinical test performance. The clinical performance of single PETS is limited. However, when the different PETS for SLAP lesions were pooled, we found a statistical significant change in post-test probability indicating an overall statistical validity. We suggest that clinicians choose their PETS among those with the highest pooled DOR and to assess validity to their own specific clinical settings, review the inclusion criteria of the included primary studies. We further propose that future studies on the validity of PETS use randomized research designs rather than the accuracy design relying less on well-established gold standard reference tests and efficient treatment options.

Performance of Dengue Diagnostic Tests in a Single-Specimen Diagnostic Algorithm.

PubMed

Hunsperger, Elizabeth A; Muñoz-Jordán, Jorge; Beltran, Manuela; Colón, Candimar; Carrión, Jessica; Vazquez, Jesus; Acosta, Luz Nereida; Medina-Izquierdo, Juan F; Horiuchi, Kalanthe; Biggerstaff, Brad J; Margolis, Harold S

2016-09-15

Anti-dengue virus (DENV) immunoglobulin M (IgM) seroconversion has been the reference standard for dengue diagnosis. However, paired specimens are rarely obtained, and the interval for this testing negates its usefulness in guiding clinical case management. The presence of DENV viremia and appearance of IgM during the febrile phase of dengue provides the framework for dengue laboratory diagnosis by using a single serum specimen. Archived paired serum specimens (n = 1234) from patients with laboratory-confirmed dengue from 2005 through 2011 were used to determine the diagnostic performance of real-time reverse transcription polymerase chain reaction (RT-PCR), for detection of DENV serotypes 1-4, and enzyme-linked immunosorbent assays (ELISAs), for detection of DENV nonstructural protein 1 (NS1) antigen and anti-DENV IgM. During 1-3 days after illness onset, real-time RT-PCR and NS1 antigen testing detected 82%-69% and 90%-84% of cases, respectively, as viremia levels declined, while anti-DENV IgM ELISA detected 5%-41% of cases as antibody appeared. Over the 10-day period of the febrile phase of dengue, the cumulative effect of using these 3 types of tests in a diagnostic algorithm confirmed ≥90% of dengue cases. The use of molecular or NS1 antigen tests to detect DENV and one to detect anti-DENV IgM in a single serum specimen collected during the first 10 days of illness accurately identified ≥90% of dengue primary and secondary cases. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effects of disease severity distribution on the performance of quantitative diagnostic methods and proposal of a novel 'V-plot' methodology to display accuracy values.

PubMed

Petraco, Ricardo; Dehbi, Hakim-Moulay; Howard, James P; Shun-Shin, Matthew J; Sen, Sayan; Nijjer, Sukhjinder S; Mayet, Jamil; Davies, Justin E; Francis, Darrel P

2018-01-01

Diagnostic accuracy is widely accepted by researchers and clinicians as an optimal expression of a test's performance. The aim of this study was to evaluate the effects of disease severity distribution on values of diagnostic accuracy as well as propose a sample-independent methodology to calculate and display accuracy of diagnostic tests. We evaluated the diagnostic relationship between two hypothetical methods to measure serum cholesterol (Chol rapid and Chol gold ) by generating samples with statistical software and (1) keeping the numerical relationship between methods unchanged and (2) changing the distribution of cholesterol values. Metrics of categorical agreement were calculated (accuracy, sensitivity and specificity). Finally, a novel methodology to display and calculate accuracy values was presented (the V-plot of accuracies). No single value of diagnostic accuracy can be used to describe the relationship between tests, as accuracy is a metric heavily affected by the underlying sample distribution. Our novel proposed methodology, the V-plot of accuracies, can be used as a sample-independent measure of a test performance against a reference gold standard.

Panel-based Genetic Diagnostic Testing for Inherited Eye Diseases is Highly Accurate and Reproducible and More Sensitive for Variant Detection Than Exome Sequencing

PubMed Central

Bujakowska, Kinga M.; Sousa, Maria E.; Fonseca-Kelly, Zoë D.; Taub, Daniel G.; Janessian, Maria; Wang, Dan Yi; Au, Elizabeth D.; Sims, Katherine B.; Sweetser, David A.; Fulton, Anne B.; Liu, Qin; Wiggs, Janey L.; Gai, Xiaowu; Pierce, Eric A.

2015-01-01

Purpose Next-generation sequencing (NGS) based methods are being adopted broadly for genetic diagnostic testing, but the performance characteristics of these techniques have not been fully defined with regard to test accuracy and reproducibility. Methods We developed a targeted enrichment and NGS approach for genetic diagnostic testing of patients with inherited eye disorders, including inherited retinal degenerations, optic atrophy and glaucoma. In preparation for providing this Genetic Eye Disease (GEDi) test on a CLIA-certified basis, we performed experiments to measure the sensitivity, specificity, reproducibility as well as the clinical sensitivity of the test. Results The GEDi test is highly reproducible and accurate, with sensitivity and specificity for single nucleotide variant detection of 97.9% and 100%, respectively. The sensitivity for variant detection was notably better than the 88.3% achieved by whole exome sequencing (WES) using the same metrics, due to better coverage of targeted genes in the GEDi test compared to commercially available exome capture sets. Prospective testing of 192 patients with IRDs indicated that the clinical sensitivity of the GEDi test is high, with a diagnostic rate of 51%. Conclusion The data suggest that based on quantified performance metrics, selective targeted enrichment is preferable to WES for genetic diagnostic testing. PMID:25412400

Systematic review of patient history and physical examination to diagnose chronic low back pain originating from the facet joints.

PubMed

Maas, E T; Juch, J N S; Ostelo, R W J G; Groeneweg, J G; Kallewaard, J W; Koes, B W; Verhagen, A P; Huygen, F J P M; van Tulder, M W

2017-03-01

Patient history and physical examination are frequently used procedures to diagnose chronic low back pain (CLBP) originating from the facet joints, although the diagnostic accuracy is controversial. The aim of this systematic review is to determine the diagnostic accuracy of patient history and/or physical examination to identify CLBP originating from the facet joints using diagnostic blocks as reference standard. We searched MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Collaboration database from inception until June 2016. Two review authors independently selected studies for inclusion, extracted data and assessed the risk of bias. We calculated sensitivity and specificity values, with 95% confidence intervals (95% CI). Twelve studies were included, in which 129 combinations of index tests and reference standards were presented. Most of these index tests have only been evaluated in single studies with a high risk of bias. Four studies evaluated the diagnostic accuracy of the Revel's criteria combination. Because of the clinical heterogeneity, results were not pooled. The published sensitivities ranged from 0.11 (95% CI 0.02-0.29) to 1.00 (95% CI 0.75-1.00), and the specificities ranged from 0.66 (95% CI 0.46-0.82) to 0.91 (95% CI 0.83-0.96). Due to clinical heterogeneity, the evidence for the diagnostic accuracy of patient history and/or physical examination to identify facet joint pain is inconclusive. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. © 2016 European Pain Federation - EFIC®.

Chlorhexidine allergy in four specialist allergy centres in the United Kingdom, 2009–13: clinical features and diagnostic tests

PubMed Central

Helbert, M.; Sargur, R.; Swallow, K.; Harper, N.; Garcez, T.; Savic, S.; Savic, L.; Eren, E.

2017-01-01

Summary We describe an observational survey of diagnostic pathways in 104 patients attending four specialist allergy clinics in the United Kingdom following perioperative hypersensitivity reactions to chlorhexidine reactions. The majority were life‐threatening. Men undergoing urological or cardiothoracic surgery predominated. Skin prick testing and specific immunoglobulin (sIg)E testing were the most common tests used for diagnosis. Fifty‐three per cent of diagnoses were made on the basis of a single positive test. Where multiple tests were performed the sensitivity of intradermal, basophil activation and skin prick testing was 68% (50–86%), 50% (10–90%) and 35% (17–55%), respectively. Seven per cent were negative on screening tests initially, and 12 cases were only positive for a single test despite multiple testing. Intradermal tests appeared most sensitive in this context. Additional sensitization to other substances used perioperatively, particularly neuromuscular blocking agents (NMBA), was found in 28 patients, emphasizing the need to test for possible allergy to all drugs to which the patient was exposed even where chlorhexidine is positive. PMID:28194756

21 CFR 660.33 - Testing of source material.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660... incorporated into the Reagent Red Blood Cell product shall be individually tested, with no fewer than two donor... tests for each factor. The Reagent Red Blood Cell product may be tested with a single donor source of...

21 CFR 660.33 - Testing of source material.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660... incorporated into the Reagent Red Blood Cell product shall be individually tested, with no fewer than two donor... tests for each factor. The Reagent Red Blood Cell product may be tested with a single donor source of...

21 CFR 660.33 - Testing of source material.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660... incorporated into the Reagent Red Blood Cell product shall be individually tested, with no fewer than two donor... tests for each factor. The Reagent Red Blood Cell product may be tested with a single donor source of...

21 CFR 660.33 - Testing of source material.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660... incorporated into the Reagent Red Blood Cell product shall be individually tested, with no fewer than two donor... tests for each factor. The Reagent Red Blood Cell product may be tested with a single donor source of...

21 CFR 660.33 - Testing of source material.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660... incorporated into the Reagent Red Blood Cell product shall be individually tested, with no fewer than two donor... tests for each factor. The Reagent Red Blood Cell product may be tested with a single donor source of...

Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics

PubMed Central

Ardui, Simon; Ameur, Adam; Vermeesch, Joris R; Hestand, Matthew S

2018-01-01

Abstract Short read massive parallel sequencing has emerged as a standard diagnostic tool in the medical setting. However, short read technologies have inherent limitations such as GC bias, difficulties mapping to repetitive elements, trouble discriminating paralogous sequences, and difficulties in phasing alleles. Long read single molecule sequencers resolve these obstacles. Moreover, they offer higher consensus accuracies and can detect epigenetic modifications from native DNA. The first commercially available long read single molecule platform was the RS system based on PacBio's single molecule real-time (SMRT) sequencing technology, which has since evolved into their RSII and Sequel systems. Here we capsulize how SMRT sequencing is revolutionizing constitutional, reproductive, cancer, microbial and viral genetic testing. PMID:29401301

Molecular allergy diagnostics using multiplex assays: methodological and practical considerations for use in research and clinical routine: Part 21 of the Series Molecular Allergology.

PubMed

Jakob, Thilo; Forstenlechner, Peter; Matricardi, Paolo; Kleine-Tebbe, Jörg

The availability of single allergens and their use in microarray technology enables the simultaneous determination of specific IgE (sIgE) to a multitude of different allergens (> 100) in a multiplex procedure requiring only minute amounts of serum. This allows extensive individual sensitization profiles to be determined from a single analysis. Combined with a patient's medical history, these profiles simplify identification of cross-reactivity; permit a more accurate estimation of the risk of severe reactions; and enable the indication for specific immunotherapy to be more precisely established, particularly in cases of polysensitization. Strictly speaking, a multiplex assay is not a single test, but instead more than 100 simultaneous tests. This places considerable demands on the production, quality assurance, and interpretation of data. The following chapter describes the multiplex test systems currently available and discusses their characteristics. Performance data are presented and the sIgE values obtained from multiplex and singleplex assays are compared. Finally, the advantages and limitations of molecular allergy diagnostics using multiplex assays in clinical routine are discussed, and innovative possibilities for clinical research are described. The multiplex diagnostic tests available for clinical routine have now become well established. The interpretation of test results is demanding, particularly since all individual results need to be checked for their plausibility and clinical relevance on the basis of previous history (patient history, clinical symptoms, challenge test results). There is still room for improvement in certain areas, for example with respect to the overall test sensitivity of the method, as well as the availability and quality of particular allergens. The current test systems are just the beginning of a continuous development that will influence and most likely change clinical allergology in the coming years.

Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL.

PubMed

Deans, Zandra C; Costa, Jose Luis; Cree, Ian; Dequeker, Els; Edsjö, Anders; Henderson, Shirley; Hummel, Michael; Ligtenberg, Marjolijn Jl; Loddo, Marco; Machado, Jose Carlos; Marchetti, Antonio; Marquis, Katherine; Mason, Joanne; Normanno, Nicola; Rouleau, Etienne; Schuuring, Ed; Snelson, Keeda-Marie; Thunnissen, Erik; Tops, Bastiaan; Williams, Gareth; van Krieken, Han; Hall, Jacqueline A

2017-01-01

The clinical demand for mutation detection within multiple genes from a single tumour sample requires molecular diagnostic laboratories to develop rapid, high-throughput, highly sensitive, accurate and parallel testing within tight budget constraints. To meet this demand, many laboratories employ next-generation sequencing (NGS) based on small amplicons. Building on existing publications and general guidance for the clinical use of NGS and learnings from germline testing, the following guidelines establish consensus standards for somatic diagnostic testing, specifically for identifying and reporting mutations in solid tumours. These guidelines cover the testing strategy, implementation of testing within clinical service, sample requirements, data analysis and reporting of results. In conjunction with appropriate staff training and international standards for laboratory testing, these consensus standards for the use of NGS in molecular pathology of solid tumours will assist laboratories in implementing NGS in clinical services.

Predictive Accuracy of Sweep Frequency Impedance Technology in Identifying Conductive Conditions in Newborns.

PubMed

Aithal, Venkatesh; Kei, Joseph; Driscoll, Carlie; Murakoshi, Michio; Wada, Hiroshi

2018-02-01

Diagnosing conductive conditions in newborns is challenging for both audiologists and otolaryngologists. Although high-frequency tympanometry (HFT), acoustic stapedial reflex tests, and wideband absorbance measures are useful diagnostic tools, there is performance measure variability in their detection of middle ear conditions. Additional diagnostic sensitivity and specificity measures gained through new technology such as sweep frequency impedance (SFI) measures may assist in the diagnosis of middle ear dysfunction in newborns. The purpose of this study was to determine the test performance of SFI to predict the status of the outer and middle ear in newborns against commonly used reference standards. Automated auditory brainstem response (AABR), HFT (1000 Hz), transient evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission (DPOAE), and SFI tests were administered to the study sample. A total of 188 neonates (98 males and 90 females) with a mean gestational age of 39.4 weeks were included in the sample. Mean age at the time of testing was 44.4 hr. Diagnostic accuracy of SFI was assessed in terms of its ability to identify conductive conditions in neonates when compared with nine different reference standards (including four single tests [AABR, HFT, TEOAE, and DPOAE] and five test batteries [HFT + DPOAE, HFT + TEOAE, DPOAE + TEOAE, DPOAE + AABR, and TEOAE + AABR]), using receiver operating characteristic (ROC) analysis and traditional test performance measures such as sensitivity and specificity. The test performance of SFI against the test battery reference standard of HFT + DPOAE and single reference standard of HFT was high with an area under the ROC curve (AROC) of 0.87 and 0.82, respectively. Although the HFT + DPOAE test battery reference standard performed better than the HFT reference standard in predicting middle ear conductive conditions in neonates, the difference in AROC was not significant. Further analysis revealed that the highest sensitivity and specificity for SFI (86% and 88%, respectively) was obtained when compared with the reference standard of HFT + DPOAE. Among the four single reference standards, SFI had the highest sensitivity and specificity (76% and 88%, respectively) when compared against the HFT reference standard. The high test performance of SFI against the HFT and HFT + DPOAE reference standards indicates that the SFI measure has appropriate diagnostic accuracy in detection of conductive conditions in newborns. Hence, the SFI test could be used as adjunct tool to identify conductive conditions in universal newborn hearing screening programs, and can also be used in diagnostic follow-up assessments. American Academy of Audiology

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research.

PubMed

Waddell, Lisa A; Greig, Judy; Mascarenhas, Mariola; Harding, Shannon; Lindsay, Robbin; Ogden, Nicholas

2016-01-01

There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD. Included in the review are 48 studies on diagnostic tests used in North America published since 1995. Thirteen studies examined a two-tier serological test protocol vs. clinical diagnosis, 24 studies examined single assays vs. clinical diagnosis, 9 studies examined single immunoblot vs. clinical diagnosis, 7 studies compared culture or PCR direct detection methods vs. clinical diagnosis, 22 studies compared two or more tests with each other and 8 studies compared a two-tiered serological test protocol to another test. Recent studies examining the sensitivity and specificity of various test protocols noted that the Immunetics® C6 B. burgdorferi ELISA™ and the two tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms. There is a dramatic increase in test sensitivity with progression of B. burgdorferi infection from early to late LD. Direct detection methods, culture and PCR of tissue or blood samples were not as sensitive or timely compared to serological testing. It was also noted that there are a large number of both commercial (n = 42) and in-house developed tests used by private laboratories which have not been evaluated in the primary literature.

The Accuracy of Diagnostic Tests for Lyme Disease in Humans, A Systematic Review and Meta-Analysis of North American Research

PubMed Central

Lindsay, Robbin; Ogden, Nicholas

2016-01-01

There has been an increasing incidence of Lyme disease (LD) in Canada and the United States corresponding to the expanding range of the Ixodes tick vector and Lyme disease agent (Borrelia burgdorferi sensu stricto). There are many diagnostic tests for LD available in North America, all of which have some performance issues, and physicians are concerned about the appropriate use and interpretation of these tests. The objective of this systematic review is to summarize the North American evidence on the accuracy of diagnostic tests and test regimes at various stages of LD. Included in the review are 48 studies on diagnostic tests used in North America published since 1995. Thirteen studies examined a two-tier serological test protocol vs. clinical diagnosis, 24 studies examined single assays vs. clinical diagnosis, 9 studies examined single immunoblot vs. clinical diagnosis, 7 studies compared culture or PCR direct detection methods vs. clinical diagnosis, 22 studies compared two or more tests with each other and 8 studies compared a two-tiered serological test protocol to another test. Recent studies examining the sensitivity and specificity of various test protocols noted that the Immunetics® C6 B. burgdorferi ELISA™ and the two tier approach have superior specificity compared to proposed replacements, and the CDC recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms. There is a dramatic increase in test sensitivity with progression of B. burgdorferi infection from early to late LD. Direct detection methods, culture and PCR of tissue or blood samples were not as sensitive or timely compared to serological testing. It was also noted that there are a large number of both commercial (n = 42) and in-house developed tests used by private laboratories which have not been evaluated in the primary literature. PMID:28002488

Methods for the Joint Meta-Analysis of Multiple Tests

ERIC Educational Resources Information Center

Trikalinos, Thomas A.; Hoaglin, David C.; Small, Kevin M.; Terrin, Norma; Schmid, Christopher H.

2014-01-01

Existing methods for meta-analysis of diagnostic test accuracy focus primarily on a single index test. We propose models for the joint meta-analysis of studies comparing multiple index tests on the same participants in paired designs. These models respect the grouping of data by studies, account for the within-study correlation between the tests'…

Rocket engine diagnostics using qualitative modeling techniques

NASA Technical Reports Server (NTRS)

Binder, Michael; Maul, William; Meyer, Claudia; Sovie, Amy

1992-01-01

Researchers at NASA Lewis Research Center are presently developing qualitative modeling techniques for automated rocket engine diagnostics. A qualitative model of a turbopump interpropellant seal system has been created. The qualitative model describes the effects of seal failures on the system steady-state behavior. This model is able to diagnose the failure of particular seals in the system based on anomalous temperature and pressure values. The anomalous values input to the qualitative model are generated using numerical simulations. Diagnostic test cases include both single and multiple seal failures.

Rocket engine diagnostics using qualitative modeling techniques

NASA Technical Reports Server (NTRS)

Binder, Michael; Maul, William; Meyer, Claudia; Sovie, Amy

1992-01-01

Researchers at NASA Lewis Research Center are presently developing qualitative modeling techniques for automated rocket engine diagnostics. A qualitative model of a turbopump interpropellant seal system was created. The qualitative model describes the effects of seal failures on the system steady state behavior. This model is able to diagnose the failure of particular seals in the system based on anomalous temperature and pressure values. The anomalous values input to the qualitative model are generated using numerical simulations. Diagnostic test cases include both single and multiple seal failures.

How recent advances in molecular tests could impact the diagnosis of pneumonia.

PubMed

Murdoch, David R

2016-01-01

Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm.

[Diagnostic workup of fragrance allergy].

PubMed

Geier, J; Uter, W

2015-09-01

The diagnostic workup of contact allergy to fragrances must not be limited to patch testing with the two well-established fragrance mixes. False-positive reactions to these mixes occur in up to 50 % of the patch tested patients. For the diagnostic work-up of positive reactions, and in cases of suspected fragrance allergy, patch testing with the single mix components and additional fragrances is mandatory. Frequently sensitizing fragrance materials are the 14 components of the two fragrance mixes and tree moss (Evernia furfuracea), ylang ylang oil (I + II; Cananga odorata), lemongrass oil (Cymbopogon schoenanthus), sandalwood oil (Santalum album), jasmine absolute (Jasminum spp.), and, less frequently, clove oil (Eugenia caryophyllus), cedarwood oil (Cedrus atlantica/deodara, Juniperus virginiana), Neroli oil (Citrus aurantium amara flower oil), salicylaldehyde, narcissus absolute (Narcissus spp.), and patchouli oil (Pogostemon cablin).

Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya

PubMed Central

Kepha, Stella; Kihara, Jimmy H.; Njenga, Sammy M.; Pullan, Rachel L.; Brooker, Simon J.

2014-01-01

Objectives This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys. Methods Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates. Results Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected. Conclusions The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings. PMID:24810593

Diagnostic accuracy and cost-effectiveness of alternative methods for detection of soil-transmitted helminths in a post-treatment setting in western Kenya.

PubMed

Assefa, Liya M; Crellen, Thomas; Kepha, Stella; Kihara, Jimmy H; Njenga, Sammy M; Pullan, Rachel L; Brooker, Simon J

2014-05-01

This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to household surveys. Stool samples were collected from children (n = 652) attending 18 schools in Bungoma County and diagnosed by the Kato-Katz and Mini-FLOTAC coprological methods. Sensitivity and additional diagnostic performance measures were analyzed using Bayesian latent class modeling. Financial and economic costs were calculated for all survey and diagnostic activities, and cost per child tested, cost per case detected and cost per STH infection correctly classified were estimated. A sensitivity analysis was conducted to assess the impact of various survey parameters on cost estimates. Both diagnostic methods exhibited comparable sensitivity for detection of any STH species over single and consecutive day sampling: 52.0% for single day Kato-Katz; 49.1% for single-day Mini-FLOTAC; 76.9% for consecutive day Kato-Katz; and 74.1% for consecutive day Mini-FLOTAC. Diagnostic performance did not differ significantly between methods for the different STH species. Use of Kato-Katz with school-based sampling was the lowest cost scenario for cost per child tested ($10.14) and cost per case correctly classified ($12.84). Cost per case detected was lowest for Kato-Katz used in community-based sampling ($128.24). Sensitivity analysis revealed the cost of case detection for any STH decreased non-linearly as prevalence rates increased and was influenced by the number of samples collected. The Kato-Katz method was comparable in diagnostic sensitivity to the Mini-FLOTAC method, but afforded greater cost-effectiveness. Future work is required to evaluate the cost-effectiveness of STH surveillance in different settings.

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

PubMed

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

PAX1 Methylation Hallmarks Promising Accuracy for Cervical Cancer Screening in Asians: Results from a Meta-Analysis.

PubMed

Kong, Ling-Ying; Du, Wei; Wang, Li; Yang, Zhi; Zhang, Hong-Sheng

2015-01-01

DNA methylation has been proposed as a potential biomarker for cervical cancer detection. This study aimed to evaluate the diagnostic role of paired boxed gene 1 (PAX1) methylation for cervical cancer screening in Asians. Eligible studies were retrieved by searching the electronic databases, and the quality of the enrolled studies was assessed via the quality assessment for studies of diagnostic accuracy (QUADAS) tool. The bivariate meta-analysis model was employed to generate the summary receiver operator characteristic (SROC) curve using Stata 12.0 software. Cochran's Q test and I2 statistics were applied to assess heterogeneity among studies. Publication bias was evaluated by the Deeks' funnel plot asymmetry test. A total of 9 articles containing 15 individual studies were included. The SROC analysis showed that single PAX1 methylation allowed for the discrimination between cancer/high-grade squamous intraepithelial lesion (HSIL) patients and normal individuals with a sensitivity (95% confidence interval) of 0.80 (0.70 - 0.87) and specificity of 0.89 (0.86 - 0.92), corresponding to an area under curve (AUC) of 0.92. Notably, our subgroup analysis suggested that combing parallel testing of PAX1 methylation and HPV DNA (AUC, sensitivity, and specificity of 0.90, 0.82, and 0.84, respectively) seemed to harbor higher accuracy than single HPV DNA testing (AUC, sensitivity, and specificity of 0.81, 0.86, and 0.67, respectively). PAX1 methylation hallmarks a potential diagnostic value for cervical cancer screening in Asians, and parallel testing of PAX1 methylation and HPV in cervical scrapings confers an improved accuracy than single HPV DNA testing.

Diagnosis and therapy with CRISPR advanced CRISPR based tools for point of care diagnostics and early therapies.

PubMed

Uppada, Vanita; Gokara, Mahesh; Rasineni, Girish Kumar

2018-05-20

Molecular diagnostics is of critical importance to public health worldwide. It facilitates not only detection and characterization of diseases, but also monitors drug responses, assists in the identification of genetic modifiers and disease susceptibility. Based upon DNA variation, a wide range of molecular-based tests are available to assess/diagnose diseases. The CRISPR-Cas9 system has recently emerged as a versatile tool for biological and medical research. In this system, a single guide RNA (sgRNA) directs the endonuclease Cas9 to a targeted DNA sequence for site-specific manipulation. As designing CRISPR-guided nucleases can be done easily and relatively fast, the CRISPR/Cas9 system has evolved as widely used DNA editing tool. This technique led to a large number of gene editing studies in variety of organisms. CRISPR/Cas9-mediated diagnosis and therapy has picked up pace due to specificity and accuracy of CRISPR. The aim is not only to identify specific pathogens, especially virus but also to repair disease-causing alleles by changing the DNA sequence at the exact location on the chromosome. At present, PCR-based molecular diagnostic testing predominates; however, alternative technologies aimed at reducing genome complexity without PCR are anticipated to gain momentum in the coming years. Furthermore, development of integrated chip devices should allow point-of-care testing and facilitate genetic readouts from single cells and molecules. Together with molecular based therapy CRISPR based diagnostic testing will be a revolution in modern health care settings. In this review, we emphasize on current developing diagnostic techniques based upon CRISPR Cas approach along with short insights on its therapeutic usage. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of phenotypic detection methods for metallo-β-lactamases (MBLs) in clinical isolates of Pseudomonas aeruginosa.

PubMed

Peter, S; Lacher, A; Marschal, M; Hölzl, F; Buhl, M; Autenrieth, I; Kaase, M; Willmann, M

2014-07-01

Metallo-beta-lactamase (MBL) production in Pseudomonas aeruginosa is a growing issue across the globe. Fast and reliable diagnostic tools are needed for appropriate implementation of infection control measures. In this study we evaluated the performance of three commercial combined disk tests, two EDTA based in-house combined disk tests and the Carba NP test in comparison to molecular detection of MBL genes on 133 meropenem non-susceptible non-duplicate P. aeruginosa clinical isolates. The meropenem/DPA based commercial KPC + MBL-confirm ID kit (Rosco Diagnostica, Denmark) and the MASTDISCS™ ID carbapenemase (Enterobacteriaceae) detection disc set (MAST Diagnostics, UK) showed sensitivities of 31.1 % and 28.8 % and specificities of 69.3 % and 79.6 %, respectively. The total MBL confirm kit (Rosco Diagnostica, Denmark) contains imipenem/DPA and imipenem/EDTA combination disks. Evaluation of the single disk combinations revealed 84.4 % sensitivity and 81.8 % specificity for the imipenem/DPA assay and 86.7 % sensitivity and 51.1 % specificity for the imipenem/EDTA test. Applying both tests simultaneously resulted in a slightly higher sensitivity of 88.9 % but a lower specificity of 48.9 % when compared to the single tests alone. The Carba NP test showed 93.3 % sensitivity and 96.6 % specificity. All phenotypic combined disk tests lacked either sensitivity or specificity for the detection of MBL in P. aeruginosa. The Carba NP test showed excellent test properties, but suffers from drawbacks in handling and high costs. The optimal diagnostic approach needs to be chosen depending on the epidemiological situation, laboratory resources and availability of molecular confirmation tests.

Towards Modernizing the Characterization of Shock and Detonation Physics Performance via Novel Diagnostics and Tests

NASA Astrophysics Data System (ADS)

Salyer, Terry

2017-06-01

For the bulk of detonation performance experiments, a fairly basic set of diagnostic techniques has evolved as the standard for acquiring the necessary measurements. Gold standard techniques such as pin switches and streak cameras still produce the high-quality data required, yet much room remains for improvement with regard to ease of use, cost of fielding, breadth of data, and diagnostic versatility. Over the past several years, an alternate set of diagnostics has been under development to replace many of these traditional techniques. Pulse Correlation Reflectometry (PCR) is a capable substitute for pin switches with the advantage of obtaining orders of magnitude more data at a small fraction of the cost and fielding time. Spectrally Encoded Imaging (SEI) can replace most applications of streak camera with the advantage of imaging surfaces through a single optical fiber that are otherwise optically inaccessible. Such diagnostics advance the measurement state of the art, but even further improvements may come through revamping the standardized tests themselves such as the copper cylinder expansion test. At the core of this modernization, the aforementioned diagnostics play a significant role in revamping and improving the standard test suite for the present era. This research was performed under the auspices of the United States Department of Energy.

Bias-corrected diagnostic performance of the naked-eye single-tube red-cell osmotic fragility test (NESTROFT): an effective screening tool for beta-thalassemia.

PubMed

Mamtani, Manju; Jawahirani, Anil; Das, Kishor; Rughwani, Vinky; Kulkarni, Hemant

2006-08-01

It is being increasingly recognized that a majority of the countries in the thalassemia-belt need a cost-effective screening program as the first step towards control of thalassemia. Although the naked eye single tube red cell osmotic fragility test (NESTROFT) has been considered to be a very effective screening tool for beta-thalassemia trait, assessment of its diagnostic performance has been affected with the reference test- and verification-bias. Here, we set out to provide estimates of sensitivity and specificity of NESTROFT corrected for these potential biases. We conducted a cross-sectional diagnostic test evaluation study using data from 1563 subjects from Central India with a high prevalence of beta-thalassemia. We used latent class modelling after ensuring its validity to account for the reference test bias and global sensitivity analysis to control the verification bias. We also compared the results of latent class modelling with those of five discriminant indexes. We observed that across a range of cut-offs for the mean corpuscular volume (MCV) and the hemoglobin A2 (HbA2) concentration the average sensitivity and specificity of NESTROFT obtained from latent class modelling was 99.8 and 83.7%, respectively. These estimates were comparable to those characterizing the diagnostic performance of HbA2, which is considered by many as the reference test to detect beta-thalassemia. After correction for the verification bias these estimates were 93.4 and 97.2%, respectively. Combined with the inexpensive and quick disposition of NESTROFT, these results strongly support its candidature as a screening tool-especially in the resource-poor and high-prevalence settings.

Molecular diagnostics for hereditary hearing loss in children.

PubMed

Sommen, Manou; Wuyts, Wim; Van Camp, Guy

2017-08-01

Hearing loss (HL) is the most common birth defect in industrialized countries with far-reaching social, psychological and cognitive implications. It is an extremely heterogeneous disease, complicating molecular testing. The introduction of next-generation sequencing (NGS) has resulted in great progress in diagnostics allowing to study all known HL genes in a single assay. The diagnostic yield is currently still limited, but has the potential to increase substantially. Areas covered: In this review the utility of NGS and the problems for comprehensive molecular testing for HL are evaluated and discussed. Expert commentary: Different publications have proven the appropriateness of NGS for molecular testing of heterogeneous diseases such as HL. However, several problems still exist, such as pseudogenic background of some genes and problematic copy number variant analysis on targeted NGS data. Another main challenge for the future will be the establishment of population specific mutation-spectra to achieve accurate personalized comprehensive molecular testing for HL.

Aerospike Engine Post-Test Diagnostic System Delivered to Rocketdyne

NASA Technical Reports Server (NTRS)

Meyer, Claudia M.

2000-01-01

The NASA Glenn Research Center at Lewis Field, in cooperation with Rocketdyne, has designed, developed, and implemented an automated Post-Test Diagnostic System (PTDS) for the X-33 linear aerospike engine. The PTDS was developed to reduce analysis time and to increase the accuracy and repeatability of rocket engine ground test fire and flight data analysis. This diagnostic system provides a fast, consistent, first-pass data analysis, thereby aiding engineers who are responsible for detecting and diagnosing engine anomalies from sensor data. It uses analytical methods modeled after the analysis strategies used by engineers. Glenn delivered the first version of PTDS in September of 1998 to support testing of the engine s power pack assembly. The system was used to analyze all 17 power pack tests and assisted Rocketdyne engineers in troubleshooting both data acquisition and test article anomalies. The engine version of PTDS, which was delivered in June of 1999, will support all single-engine, dual-engine, and flight firings of the aerospike engine.

Effects of disease severity distribution on the performance of quantitative diagnostic methods and proposal of a novel ‘V-plot’ methodology to display accuracy values

PubMed Central

Dehbi, Hakim-Moulay; Howard, James P; Shun-Shin, Matthew J; Sen, Sayan; Nijjer, Sukhjinder S; Mayet, Jamil; Davies, Justin E; Francis, Darrel P

2018-01-01

Background Diagnostic accuracy is widely accepted by researchers and clinicians as an optimal expression of a test’s performance. The aim of this study was to evaluate the effects of disease severity distribution on values of diagnostic accuracy as well as propose a sample-independent methodology to calculate and display accuracy of diagnostic tests. Methods and findings We evaluated the diagnostic relationship between two hypothetical methods to measure serum cholesterol (Cholrapid and Cholgold) by generating samples with statistical software and (1) keeping the numerical relationship between methods unchanged and (2) changing the distribution of cholesterol values. Metrics of categorical agreement were calculated (accuracy, sensitivity and specificity). Finally, a novel methodology to display and calculate accuracy values was presented (the V-plot of accuracies). Conclusion No single value of diagnostic accuracy can be used to describe the relationship between tests, as accuracy is a metric heavily affected by the underlying sample distribution. Our novel proposed methodology, the V-plot of accuracies, can be used as a sample-independent measure of a test performance against a reference gold standard. PMID:29387424

21 CFR 870.1435 - Single-function, preprogrammed diagnostic computer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Single-function, preprogrammed diagnostic computer... Single-function, preprogrammed diagnostic computer. (a) Identification. A single-function, preprogrammed diagnostic computer is a hard-wired computer that calculates a specific physiological or blood-flow parameter...

21 CFR 870.1435 - Single-function, preprogrammed diagnostic computer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Single-function, preprogrammed diagnostic computer... Single-function, preprogrammed diagnostic computer. (a) Identification. A single-function, preprogrammed diagnostic computer is a hard-wired computer that calculates a specific physiological or blood-flow parameter...

21 CFR 870.1435 - Single-function, preprogrammed diagnostic computer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Single-function, preprogrammed diagnostic computer... Single-function, preprogrammed diagnostic computer. (a) Identification. A single-function, preprogrammed diagnostic computer is a hard-wired computer that calculates a specific physiological or blood-flow parameter...

21 CFR 870.1435 - Single-function, preprogrammed diagnostic computer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Single-function, preprogrammed diagnostic computer... Single-function, preprogrammed diagnostic computer. (a) Identification. A single-function, preprogrammed diagnostic computer is a hard-wired computer that calculates a specific physiological or blood-flow parameter...

Shifting from glucose diagnostic criteria to the new HbA(1c) criteria would have a profound impact on prevalence of diabetes among a high-risk Spanish population.

PubMed

Costa, B; Barrio, F; Cabré, J-J; Piñol, J-L; Cos, F-X; Solé, C; Bolibar, B; Castell, C; Lindström, J; Barengo, N; Tuomilehto, J

2011-10-01

To investigate changes in the prevalence of diabetes and pre-diabetes by shifting from 2-h plasma glucose and/or fasting plasma glucose diagnostic criteria to the proposed new HbA(1c) -based criteria when applied to a Mediterranean population detected to have a high risk of Type 2 diabetes. Individuals without diabetes aged 45-75 years (n = 2287) were screened using the Finnish Diabetes Risk Score questionnaire, a 2-h oral glucose tolerance test plus HbA(1c) test. Prevalence and degree of diagnostic overlap between three sets of criteria (2-h plasma glucose, fasting plasma glucose and HbA(1c) ) and three diagnostic categories (normal, pre-diabetes and diabetes) were calculated. Defining diabetes by a single HbA(1c) measurement resulted in a dramatic decrease in prevalence (1.3%), particularly in comparison with diabetes defined by 2-h plasma glucose (8.6%), but was also significant with regard to fasting plasma glucose (2.8%). A total of 201 screened subjects (8.8%) were classified as having diabetes and 1023 (44.7%) as having pre-diabetes based on at least one of these criteria; among these, the presence of all three criteria simultaneously classified only 21 and 110 individuals respectively, about ten percent of each group. The single overlap index between subjects diagnosed as having diabetes by 2-h plasma glucose/fasting plasma glucose vs. HbA(1c) was 13.9/28%. Similarly, the single overlap index regarding pre-diabetes was 19.2/27.1%. A shift from the glucose-based diagnosis to the HbA(1c) -based diagnosis for diabetes will reduce diabetes prevalence with a low overall or single degree of overlap between diagnostic categories in this high-risk Spanish population. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

A comparative analysis of costs of single and dual rapid HIV and syphilis diagnostics: results from a randomised controlled trial in Colombia

PubMed Central

Obure, Carol Dayo; Gaitan-Duarte, Hernando; Losada Saenz, Ricardo; Gonzalez, Lina; Angel-Muller, Edith; Laverty, Maura; Perez, Freddy

2017-01-01

Background HIV and congenital syphilis are major public health burdens contributing to substantial perinatal morbidity and mortality globally. Although studies have reported on the costs and cost-effectiveness of rapid diagnostic tests (RDTs) for syphilis screening within antenatal care in a number of resource-constrained settings, empirical evidence on country-specific cost and estimates of single RDTs compared with dual RDTs for HIV and syphilis are limited. Methods A cluster randomised controlled study design was used to compare the incremental costs of two testing algorithms: (1) single RDTs for HIV and syphilis and (2) dual RDTs for HIV and syphilis, in 12 health facilities in Bogota and Cali, Colombia. The costs of single HIV and syphilis RDTs and dual HIV and syphilis RDTs were collected from each of the health facilities. The economic costs per woman tested for HIV and syphilis and costs per woman treated for syphilis defined as the total costs required to test and treat one woman for syphilis were estimated. Results A total of 2214 women were tested in the study facilities. Cost per pregnant woman tested and cost per woman treated for syphilis were US$10.26 and US$607.99, respectively in the single RDT arm. For the dual RDTs, the cost per pregnant woman tested for HIV and syphilis and cost per woman treated for syphilis were US$15.89 and US$1859.26, respectively. Overall costs per woman tested for HIV and syphilis and cost per woman treated for syphilis were lower in Cali compared with Bogota across both intervention arms. Staff costs accounted for the largest proportion of costs while treatment costs comprised <1% of the preventive programme. Conclusions Findings show lower average costs for single RDTs compared with dual RDTs with costs sensitive to personnel costs and the scale of output at the health facilities. Trial registration number NCT02454816; results. PMID:28495681

Molecular allergy diagnostics using IgE singleplex determinations: methodological and practical considerations for use in clinical routine: Part 18 of the Series Molecular Allergology.

PubMed

Kleine-Tebbe, Jörg; Jakob, Thilo

Allergen molecules (synonyms: single allergens, allergen components) open up new horizons for the targeted allergen-specific diagnostics of immunoglobulin E (IgE) in singleplex determination. The following rationales support the targeted use of allergen molecules and, more importantly, improve test properties: (1) increased test sensitivity ("analytical sensitivity"), particularly when important allergens are under-represented or lacking in the extract; (2) improved test selectivity (analytical specificity), particularly when the selected IgE repertoire against an allergen yields additional information on: (a) potential risk, (b) possible cross-reactivity, or (c) primary (species-specific) sensitization. However, the appropriate indication for the use of single allergens can only be established on a case-by-case basis (depending on the clinical context and previous history) and in an allergen-specific manner (depending on the allergen source and the single allergens available), rather than in a standardized way. Numerous investigations on suspected food allergy, insect venom allergy, or sensitization to respiratory allergens have meanwhile demonstrated the successful use of defined molecules for allergen-specific singleplex IgE diagnosis. Specific IgE to single allergens is limited in its suitability to predict the clinical relevance of sensitivity on an individual basis. In food allergies, one can at best identify the relative risk of a clinical reaction on the basis of an IgE profile, but no absolutely reliable prediction on (future) tolerance can be made. Ultimately, the clinical relevance of all IgE findings depends on the presence of corresponding symptoms and can only be assessed on an individual basis (previous history, symptom log, and provocation testing with the relevant allergen source where appropriate). Thus, also in molecular allergology, the treating physician and not the test result should determine the clinical relevance of diagnostic findings. Supplementary material is available for this article at 10.1007/s40629-015-0067-z and is accessible for authorized users.

Does the patient with chest pain have a coronary heart disease? Diagnostic value of single symptoms and signs--a meta-analysis.

PubMed

Haasenritter, Jorg; Stanze, Damaris; Widera, Grit; Wilimzig, Christian; Abu Hani, Maren; Sonnichsen, Andreas C; Bosner, Stefan; Rochon, Justine; Donner-Banzhoff, Norbert

2012-10-01

To determine the diagnostic value of single symptoms and signs for coronary heart disease (CHD) in patients with chest pain. Searches of two electronic databases (EMBASE 1980 to March 2008, PubMed 1966 to May 2009) and hand searching in seven journals were conducted. Eligible studies recruited patients presenting with acute or chronic chest pain. The target disease was CHD, with no restrictions regarding case definitions, eg, stable CHD, acute coronary syndrome (ACS), acute myocardial infarction (MI), or major cardiac event (MCE). Diagnostic tests of interest were items of medical history and physical examination. Bivariate random effects model was used to derive summary estimates of positive (pLR) and negative likelihood ratios (nLR). We included 172 studies providing data on the diagnostic value of 42 symptoms and signs. With respect to case definition of CHD, diagnostically most useful tests were history of CHD (pLR=3.59), known MI (pLR=3.21), typical angina (pLR=2.35), history of diabetes mellitus (pLR=2.16), exertional pain (pLR=2.13), history of angina pectoris (nLR=0.42), and male sex (nLR=0.49) for diagnosing stable CHD; pain radiation to right arm/shoulder (pLR=4.43) and palpitation (pLR=0.47) for diagnosing MI; visceral pain (pLR=2.05) for diagnosing ACS; and typical angina (pLR=2.60) and pain reproducible by palpation (pLR=0.13) for predicting MCE. We comprehensively reported the accuracy of a broad spectrum of single symptoms and signs for diagnosing myocardial ischemia. Our results suggested that the accuracy of several symptoms and signs varied in the published studies according to the case definition of CHD.

Reading Out Single-Molecule Digital RNA and DNA Isothermal Amplification in Nanoliter Volumes with Unmodified Camera Phones

PubMed Central

2016-01-01

Digital single-molecule technologies are expanding diagnostic capabilities, enabling the ultrasensitive quantification of targets, such as viral load in HIV and hepatitis C infections, by directly counting single molecules. Replacing fluorescent readout with a robust visual readout that can be captured by any unmodified cell phone camera will facilitate the global distribution of diagnostic tests, including in limited-resource settings where the need is greatest. This paper describes a methodology for developing a visual readout system for digital single-molecule amplification of RNA and DNA by (i) selecting colorimetric amplification-indicator dyes that are compatible with the spectral sensitivity of standard mobile phones, and (ii) identifying an optimal ratiometric image-process for a selected dye to achieve a readout that is robust to lighting conditions and camera hardware and provides unambiguous quantitative results, even for colorblind users. We also include an analysis of the limitations of this methodology, and provide a microfluidic approach that can be applied to expand dynamic range and improve reaction performance, allowing ultrasensitive, quantitative measurements at volumes as low as 5 nL. We validate this methodology using SlipChip-based digital single-molecule isothermal amplification with λDNA as a model and hepatitis C viral RNA as a clinically relevant target. The innovative combination of isothermal amplification chemistry in the presence of a judiciously chosen indicator dye and ratiometric image processing with SlipChip technology allowed the sequence-specific visual readout of single nucleic acid molecules in nanoliter volumes with an unmodified cell phone camera. When paired with devices that integrate sample preparation and nucleic acid amplification, this hardware-agnostic approach will increase the affordability and the distribution of quantitative diagnostic and environmental tests. PMID:26900709

A review of current and future molecular diagnostic tests for use in the microbiology laboratory.

PubMed

Jannes, Geert; De Vos, Daniel

2006-01-01

Nucleic acid-based diagnostics gradually are replacing or complementing culture-based, biochemical, and immunological assays in routine microbiology laboratories. Similar to conventional tests, the first-generation deoxyribonucleic acid assays determined only a single analyte. Recent improvements in detection technologies have paved the way for the development of multiparameter assays using macroarrays or micro-arrays, while the introduction of closed-tube real-time polymerase chain reaction systems has resulted in the development of rapid microbial diagnostics with a reduced contamination risk. The use of these new molecular technologies is not restricted to detection and identification of microbial pathogens but also can be used for genotyping, allowing one to determine antibiotic resistance or to perform microbial fingerprinting.

Advanced Neuropsychological Diagnostics Infrastructure (ANDI): A Normative Database Created from Control Datasets

PubMed Central

de Vent, Nathalie R.; Agelink van Rentergem, Joost A.; Schmand, Ben A.; Murre, Jaap M. J.; Huizenga, Hilde M.

2016-01-01

In the Advanced Neuropsychological Diagnostics Infrastructure (ANDI), datasets of several research groups are combined into a single database, containing scores on neuropsychological tests from healthy participants. For most popular neuropsychological tests the quantity, and range of these data surpasses that of traditional normative data, thereby enabling more accurate neuropsychological assessment. Because of the unique structure of the database, it facilitates normative comparison methods that were not feasible before, in particular those in which entire profiles of scores are evaluated. In this article, we describe the steps that were necessary to combine the separate datasets into a single database. These steps involve matching variables from multiple datasets, removing outlying values, determining the influence of demographic variables, and finding appropriate transformations to normality. Also, a brief description of the current contents of the ANDI database is given. PMID:27812340

Advanced Neuropsychological Diagnostics Infrastructure (ANDI): A Normative Database Created from Control Datasets.

PubMed

de Vent, Nathalie R; Agelink van Rentergem, Joost A; Schmand, Ben A; Murre, Jaap M J; Huizenga, Hilde M

2016-01-01

In the Advanced Neuropsychological Diagnostics Infrastructure (ANDI), datasets of several research groups are combined into a single database, containing scores on neuropsychological tests from healthy participants. For most popular neuropsychological tests the quantity, and range of these data surpasses that of traditional normative data, thereby enabling more accurate neuropsychological assessment. Because of the unique structure of the database, it facilitates normative comparison methods that were not feasible before, in particular those in which entire profiles of scores are evaluated. In this article, we describe the steps that were necessary to combine the separate datasets into a single database. These steps involve matching variables from multiple datasets, removing outlying values, determining the influence of demographic variables, and finding appropriate transformations to normality. Also, a brief description of the current contents of the ANDI database is given.

Single-shot high-resolution characterization of optical pulses by spectral phase diversity

DOE PAGES

Dorrer, C.; Waxer, L. J.; Kalb, A.; ...

2015-12-15

The concept of spectral phase diversity is proposed and applied to the temporal characterization of optical pulses. The experimental trace is composed of the measured power of a plurality of ancillary optical pulses derived from the pulse under test by adding known amounts of chromatic dispersion. The spectral phase of the pulse under test is retrieved by minimizing the error between the experimental trace and a trace calculated from the optical spectrum using the known diagnostic parameters. An assembly composed of splitters and dispersive delay fibers has been used to generate 64 ancillary pulses whose instantaneous power can be detectedmore » in a single shot with a high-bandwidth photodiode and oscilloscope. Pulse-shape reconstruction for pulses shorter than the photodetection impulse response has been demonstrated.The diagnostic is experimentally shown to accurately characterize pulses from a chirped-pulse–amplification system when its stretcher is detuned from the position for optimal recompression. As a result, various investigations of the performance with respect to the number of ancillary pulses and the range of chromatic dispersion generated in the diagnostic are presented.« less

Single-shot high-resolution characterization of optical pulses by spectral phase diversity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorrer, C.; Waxer, L. J.; Kalb, A.

The concept of spectral phase diversity is proposed and applied to the temporal characterization of optical pulses. The experimental trace is composed of the measured power of a plurality of ancillary optical pulses derived from the pulse under test by adding known amounts of chromatic dispersion. The spectral phase of the pulse under test is retrieved by minimizing the error between the experimental trace and a trace calculated from the optical spectrum using the known diagnostic parameters. An assembly composed of splitters and dispersive delay fibers has been used to generate 64 ancillary pulses whose instantaneous power can be detectedmore » in a single shot with a high-bandwidth photodiode and oscilloscope. Pulse-shape reconstruction for pulses shorter than the photodetection impulse response has been demonstrated.The diagnostic is experimentally shown to accurately characterize pulses from a chirped-pulse–amplification system when its stretcher is detuned from the position for optimal recompression. As a result, various investigations of the performance with respect to the number of ancillary pulses and the range of chromatic dispersion generated in the diagnostic are presented.« less

A stochastic model to determine the economic value of changing diagnostic test characteristics for identification of cattle for treatment of bovine respiratory disease.

PubMed

Theurer, M E; White, B J; Larson, R L; Schroeder, T C

2015-03-01

Bovine respiratory disease is an economically important syndrome in the beef industry, and diagnostic accuracy is important for optimal disease management. The objective of this study was to determine whether improving diagnostic sensitivity or specificity was of greater economic value at varied levels of respiratory disease prevalence by using Monte Carlo simulation. Existing literature was used to populate model distributions of published sensitivity, specificity, and performance (ADG, carcass weight, yield grade, quality grade, and mortality risk) differences among calves based on clinical respiratory disease status. Data from multiple cattle feeding operations were used to generate true ranges of respiratory disease prevalence and associated mortality. Input variables were combined into a single model that calculated estimated net returns for animals by diagnostic category (true positive, false positive, false negative, and true negative) based on the prevalence, sensitivity, and specificity for each iteration. Net returns for each diagnostic category were multiplied by the proportion of animals in each diagnostic category to determine group profitability. Apparent prevalence was categorized into low (<15%) and high (≥15%) groups. For both apparent prevalence categories, increasing specificity created more rapid, positive change in net returns than increasing sensitivity. Improvement of diagnostic specificity, perhaps through a confirmatory test interpreted in series or pen-level diagnostics, can increase diagnostic value more than improving sensitivity. Mortality risk was the primary driver for net returns. The results from this study are important for determining future research priorities to analyze diagnostic techniques for bovine respiratory disease and provide a novel way for modeling diagnostic tests.

Selection of Atypia/Follicular Lesion of Unknown Significance Patients for Surgery Versus Active Surveillance, Without Using Genetic Testing: A Single Institute Experience, Prospective Analysis, and Recommendations.

PubMed

Cohen, Oded; Tzelnick, Sharon; Lahav, Yonatan; Schindel, Doron; Halperin, Doron; Yehuda, Moshe

2017-07-01

Atypia/follicular lesion of unknown significance (AUS/FLUS) has variable rates of malignancy. The recommended management includes active surveillance (AS), repeated fine-needle aspiration (RFNA), diagnostic surgery, or genetic testing for malignancy. The objective of this study was to assess the management of AUS/FLUS patients in a dedicated thyroid clinic without implementing genetic testing. This was a single institute cohort study of all patients aged ≥18 years who underwent ultrasound-guided FNA thyroid biopsies between January 2009 and January 2013 and were followed until January 2016. The median follow-up time was 4.6 years (range 3.2-6.8 years). Forty-eight (57%) patients were referred to AS, and 36 (43%) patients were referred for diagnostic surgery. Thirty-six (75%) patients from the AS group underwent RFNA. An additional eight patients from the AS group subsequently underwent diagnostic surgery. Malignancies were found in 15/44 (34%) diagnostic surgical samples, and benign cytologies were found in 61.1% of the RFNAs. Analysis of adherence to follow-up in the 36 AS patients showed an adherence rate of only 53%, with males tending to comply better than females did (31.6% vs. 5.8%, respectively; p = 0.052), especially males in their sixth decade of life. Genetic tests for AUS/FLUS patients are accepted today as complementary evaluations in many well-developed health systems. Yet, when these tests are not feasible due to financial or availability issues, careful management of AUS/FLUS patients may still offer good results in the selection of patients for surgery or AS. The present results also indicate that compliance to follow-up schedules is a major consideration when selecting patients for AS.

Cost-effectiveness of alternative test strategies for the diagnosis of coronary artery disease.

PubMed

Garber, A M; Solomon, N A

1999-05-04

The appropriate roles for several diagnostic tests for coronary disease are uncertain. To evaluate the cost-effectiveness of alternative approaches to diagnosis of coronary disease. Meta-analysis of the accuracy of alternative diagnostic tests plus decision analysis to assess the health outcomes and costs of alternative diagnostic strategies for patients at intermediate pretest risk for coronary disease. Studies of test accuracy that met inclusion criteria; published information on treatment effectiveness and disease prevalence. Men and women 45, 55, and 65 years of age with a 25% to 75% pretest risk for coronary disease. 30 years. Societal. Diagnostic strategies were initial angiography and initial testing with one of five noninvasive tests--exercise treadmill testing, planar thallium imaging, single-photon emission computed tomography (SPECT), stress echocardiography, and positron emission tomography (PET)--followed by coronary angiography if noninvasive test results were positive. Testing was followed by observation, medical treatment, or revascularization. Life-years, quality-adjusted life-years (QALYs), costs, and costs per QALY. Life expectancy varied little with the initial diagnostic test; for a 55-year-old man, the best-performing test increased life expectancy by 7 more days than the worst-performing test. More sensitive tests increased QALYs more. Echocardiography improved health outcomes and reduced costs relative to stress testing and planar thallium imaging. The incremental cost-effectiveness ratio was $75,000/QALY for SPECT relative to echocardiography and was greater than $640,000 for PET relative to SPECT. Compared with SPECT, immediate angiography had an incremental cost-effectiveness ratio of $94,000/QALY. Qualitative findings varied little with age, sex, pretest probability of disease, or the test indeterminancy rate. Results varied most with sensitivity to severe coronary disease. Echocardiography, SPECT, and immediate angiography are cost-effective alternatives to PET and other diagnostic approaches. Test selection should reflect local variation in test accuracy.

Demise of Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry as an Infectious Diseases Diagnostic Tool.

PubMed

Özenci, Volkan; Patel, Robin; Ullberg, Måns; Strålin, Kristoffer

2018-01-18

Although there are several US Food and Drug Administration (FDA)-approved/cleared molecular microbiology diagnostics for direct analysis of patient samples, all are single target or panel-based tests. There is no FDA-approved/cleared diagnostic for broad microbial detection. Polymerase chain reaction (PCR)/electrospray ionization-mass spectrometry (PCR/ESI-MS), commercialized as the IRIDICA system (Abbott) and formerly PLEX-ID, had been under development for over a decade and had become CE-marked and commercially available in Europe in 2014. Capable of detecting a large number of microorganisms, it was under review at the FDA when, in April 2017, Abbott discontinued it. This turn of events represents not only the loss of a potential diagnostic tool for infectious diseases but may be a harbinger of similar situations with other emerging and expensive microbial diagnostics, especially genomic tests. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Recurrent Pneumonia in Children: A Reasoned Diagnostic Approach and a Single Centre Experience.

PubMed

Montella, Silvia; Corcione, Adele; Santamaria, Francesca

2017-01-29

Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%-9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician.

Single DNA imaging and length quantification through a mobile phone microscope

NASA Astrophysics Data System (ADS)

Wei, Qingshan; Luo, Wei; Chiang, Samuel; Kappel, Tara; Mejia, Crystal; Tseng, Derek; Chan, Raymond Yan L.; Yan, Eddie; Qi, Hangfei; Shabbir, Faizan; Ozkan, Haydar; Feng, Steve; Ozcan, Aydogan

2016-03-01

The development of sensitive optical microscopy methods for the detection of single DNA molecules has become an active research area which cultivates various promising applications including point-of-care (POC) genetic testing and diagnostics. Direct visualization of individual DNA molecules usually relies on sophisticated optical microscopes that are mostly available in well-equipped laboratories. For POC DNA testing/detection, there is an increasing need for the development of new single DNA imaging and sensing methods that are field-portable, cost-effective, and accessible for diagnostic applications in resource-limited or field-settings. For this aim, we developed a mobile-phone integrated fluorescence microscopy platform that allows imaging and sizing of single DNA molecules that are stretched on a chip. This handheld device contains an opto-mechanical attachment integrated onto a smartphone camera module, which creates a high signal-to-noise ratio dark-field imaging condition by using an oblique illumination/excitation configuration. Using this device, we demonstrated imaging of individual linearly stretched λ DNA molecules (48 kilobase-pair, kbp) over 2 mm2 field-of-view. We further developed a robust computational algorithm and a smartphone app that allowed the users to quickly quantify the length of each DNA fragment imaged using this mobile interface. The cellphone based device was tested by five different DNA samples (5, 10, 20, 40, and 48 kbp), and a sizing accuracy of <1 kbp was demonstrated for DNA strands longer than 10 kbp. This mobile DNA imaging and sizing platform can be very useful for various diagnostic applications including the detection of disease-specific genes and quantification of copy-number-variations at POC settings.

Naked-eye fingerprinting of single nucleotide polymorphisms on psoriasis patients

NASA Astrophysics Data System (ADS)

Valentini, Paola; Marsella, Alessandra; Tarantino, Paolo; Mauro, Salvatore; Baglietto, Silvia; Congedo, Maurizio; Paolo Pompa, Pier

2016-05-01

We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics.We report a low-cost test, based on gold nanoparticles, for the colorimetric (naked-eye) fingerprinting of a panel of single nucleotide polymorphisms (SNPs), relevant for the personalized therapy of psoriasis. Such pharmacogenomic tests are not routinely performed on psoriasis patients, due to the high cost of standard technologies. We demonstrated high sensitivity and specificity of our colorimetric test by validating it on a cohort of 30 patients, through a double-blind comparison with two state-of-the-art instrumental techniques, namely reverse dot blotting and sequencing, finding 100% agreement. This test offers high parallelization capabilities and can be easily generalized to other SNPs of clinical relevance, finding broad utility in diagnostics and pharmacogenomics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr02200f

Diagnostic Accuracy of History and Physical Examination of Superior Labrum Anterior-Posterior Lesions

PubMed Central

Michener, Lori A.; Doukas, William C.; Murphy, Kevin P.; Walsworth, Matthew K.

2011-01-01

Context: Type I superior labrum anterior-posterior (SLAP) lesions involve degenerative fraying and probably are not the cause of shoulder pain. Type II to IV SLAP lesions are tears of the labrum. Objective: To determine the diagnostic accuracy of patient history and the active compression, anterior slide, and crank tests for type I and type II to IV SLAP lesions. Design: Cohort study. Setting: Clinic. Patients or Other Participants: Fifty-five patients (47 men, 8 women; age = 40.6 ± 15.1 years) presenting with shoulder pain. Intervention(s): For each patient, an orthopaedic surgeon conducted a clinical examination of history of trauma; sudden onset of symptoms; history of popping, clicking, or catching; age; and active compression, crank, and anterior slide tests. The reference standard was the intraoperative diagnosis. The operating surgeon was blinded to the results of the clinical examination. Main Outcome Measure(s): Diagnostic utility was calculated using the receiver operating characteristic curve and area under the curve (AUC), sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR). Forward stepwise binary regression was used to determine a combination of tests for diagnosis. Results: No history item or physical examination test had diagnostic accuracy for type I SLAP lesions (n = 13). The anterior slide test had utility (AUC = 0.70, +LR = 2.25, −LR = 0.44) to confirm and exclude type II to IV SLAP lesions (n = 10). The combination of a history of popping, clicking, or catching and the anterior slide test demonstrated diagnostic utility for confirming type II to IV SLAP lesions (+LR = 6.00). Conclusions: The anterior slide test had limited diagnostic utility for confirming and excluding type II to IV SLAP lesions; diagnostic values indicated only small shifts in probability. However, the combination of the anterior slide test with a history of popping, clicking, or catching had moderate diagnostic utility for confirming type II to IV SLAP lesions. No single item or combination of history items and physical examination tests had diagnostic utility for type I SLAP lesions. PMID:21944065

A New Single-Step PCR Assay for the Detection of the Zoonotic Malaria Parasite Plasmodium knowlesi

PubMed Central

Lucchi, Naomi W.; Poorak, Mitra; Oberstaller, Jenna; DeBarry, Jeremy; Srinivasamoorthy, Ganesh; Goldman, Ira; Xayavong, Maniphet; da Silva, Alexandre J.; Peterson, David S.; Barnwell, John W.; Kissinger, Jessica; Udhayakumar, Venkatachalam

2012-01-01

Background Recent studies in Southeast Asia have demonstrated substantial zoonotic transmission of Plasmodium knowlesi to humans. Microscopically, P. knowlesi exhibits several stage-dependent morphological similarities to P. malariae and P. falciparum. These similarities often lead to misdiagnosis of P. knowlesi as either P. malariae or P. falciparum and PCR-based molecular diagnostic tests are required to accurately detect P. knowlesi in humans. The most commonly used PCR test has been found to give false positive results, especially with a proportion of P. vivax isolates. To address the need for more sensitive and specific diagnostic tests for the accurate diagnosis of P. knowlesi, we report development of a new single-step PCR assay that uses novel genomic targets to accurately detect this infection. Methodology and Significant Findings We have developed a bioinformatics approach to search the available malaria parasite genome database for the identification of suitable DNA sequences relevant for molecular diagnostic tests. Using this approach, we have identified multi-copy DNA sequences distributed in the P. knowlesi genome. We designed and tested several novel primers specific to new target sequences in a single-tube, non-nested PCR assay and identified one set of primers that accurately detects P. knowlesi. We show that this primer set has 100% specificity for the detection of P. knowlesi using three different strains (Nuri, H, and Hackeri), and one human case of malaria caused by P. knowlesi. This test did not show cross reactivity with any of the four human malaria parasite species including 11 different strains of P. vivax as well as 5 additional species of simian malaria parasites. Conclusions The new PCR assay based on novel P. knowlesi genomic sequence targets was able to accurately detect P. knowlesi. Additional laboratory and field-based testing of this assay will be necessary to further validate its utility for clinical diagnosis of P. knowlesi. PMID:22363751

A manifesto for cardiovascular imaging: addressing the human factor†

PubMed Central

Fraser, Alan G

2017-01-01

Abstract Our use of modern cardiovascular imaging tools has not kept pace with their technological development. Diagnostic errors are common but seldom investigated systematically. Rather than more impressive pictures, our main goal should be more precise tests of function which we select because their appropriate use has therapeutic implications which in turn have a beneficial impact on morbidity or mortality. We should practise analytical thinking, use checklists to avoid diagnostic pitfalls, and apply strategies that will reduce biases and avoid overdiagnosis. We should develop normative databases, so that we can apply diagnostic algorithms that take account of variations with age and risk factors and that allow us to calculate pre-test probability and report the post-test probability of disease. We should report the imprecision of a test, or its confidence limits, so that reference change values can be considered in daily clinical practice. We should develop decision support tools to improve the quality and interpretation of diagnostic imaging, so that we choose the single best test irrespective of modality. New imaging tools should be evaluated rigorously, so that their diagnostic performance is established before they are widely disseminated; this should be a shared responsibility of manufacturers with clinicians, leading to cost-effective implementation. Trials should evaluate diagnostic strategies against independent reference criteria. We should exploit advances in machine learning to analyse digital data sets and identify those features that best predict prognosis or responses to treatment. Addressing these human factors will reap benefit for patients, while technological advances continue unpredictably. PMID:29029029

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

PubMed

Punetha, Jaya; Kesari, Akanchha; Uapinyoying, Prech; Giri, Mamta; Clarke, Nigel F; Waddell, Leigh B; North, Kathryn N; Ghaoui, Roula; O'Grady, Gina L; Oates, Emily C; Sandaradura, Sarah A; Bönnemann, Carsten G; Donkervoort, Sandra; Plotz, Paul H; Smith, Edward C; Tesi-Rocha, Carolina; Bertorini, Tulio E; Tarnopolsky, Mark A; Reitter, Bernd; Hausmanowa-Petrusewicz, Irena; Hoffman, Eric P

2016-05-27

Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies. To evaluate efficiency of next-generation sequencing technologies to provide molecular diagnostics for patients with previously undiagnosed myopathies. We tested a targeted re-sequencing approach, using a 45 gene emulsion PCR myopathy panel, with subsequent sequencing on the Illumina platform in 94 undiagnosed patients. We compared the targeted re-sequencing approach to exome sequencing for 10 of these patients studied. We detected likely pathogenic mutations in 33 out of 94 patients with a molecular diagnostic rate of approximately 35%. The remaining patients showed variants of unknown significance (35/94 patients) or no mutations detected in the 45 genes tested (26/94 patients). Mutation detection rates for targeted re-sequencing vs. whole exome were similar in both methods; however exome sequencing showed better distribution of reads and fewer exon dropouts. Given that costs of highly parallel re-sequencing and whole exome sequencing are similar, and that exome sequencing now takes considerably less laboratory processing time than targeted re-sequencing, we recommend exome sequencing as the standard approach for molecular diagnostics of myopathies.

[The clinical economic analysis of the methods of ischemic heart disease diagnostics].

PubMed

Kalashnikov, V Iu; Mitriagina, S N; Syrkin, A L; Poltavskaia, M G; Sorokina, E G

2007-01-01

The clinical economical analysis was applied to assess the application of different techniques of ischemic heart disease diagnostics - the electro-cardiographic monitoring, the treadmill-testing, the stress-echo cardiographic with dobutamine, the single-photon computerized axial tomography with load, the multi-spiral computerized axial tomography with coronary arteries staining in patients with different initial probability of disease occurrence. In all groups, the best value of "cost-effectiveness" had the treadmill-test. The patients with low risk needed 17.4 rubles to precise the probability of ischemic heart disease occurrence at 1%. In the group with medium and high risk this indicator was 9.4 and 24.7 rubles correspondingly. It is concluded that to precise the probability of ischemic heart disease occurrence after tredmil-test in the patients with high probability it is appropriate to use the single-photon computerized axial tomography with load and in the case of patients with low probability the multi-spiral computerized axial tomography with coronary arteries staining.

Rapid and sensitive multiplex single-tube nested PCR for the identification of five human Plasmodium species.

PubMed

Saito, Takahiro; Kikuchi, Aoi; Kaneko, Akira; Isozumi, Rie; Teramoto, Isao; Kimura, Masatsugu; Hirasawa, Noriyasu; Hiratsuka, Masahiro

2018-06-01

Malaria is caused by five species of Plasmodium in humans. Microscopy is currently used for pathogen detection, requiring considerable training and technical expertise as the parasites are often difficult to differentiate morphologically. Rapid diagnostic tests are as reliable as microscopy and offer faster diagnoses but possess lower detection limits and are incapable of distinguishing among the parasitic species. To improve global health efforts towards malaria control, a rapid, sensitive, species-specific, and economically viable diagnostic method is needed. In this study, we designed a malaria diagnostic method involving a multiplex single-tube nested PCR targeting Plasmodium mitochondrial cytochrome c oxidase III and single-stranded tag hybridization chromatographic printed-array strip. The detection sensitivity was found to be at least 40 times higher than that of agarose gel electrophoresis with ethidium bromide. This system also enables the identification of both single- and mixed-species malaria infections. The assay was validated with 152 Kenyan samples; using nested PCR as the standard, the assay's sensitivity and specificity were 88.7% and 100.0%, respectively. The turnaround time required, from PCR preparation to signal detection, is 90min. Our method should improve the diagnostic speed, treatment efficacy, and control of malaria, in addition to facilitating surveillance within global malaria eradication programs. Copyright © 2018 Elsevier B.V. All rights reserved.

[Educating health workers is key in congenital syphilis elimination in Colombia].

PubMed

Garcés, Juan Pablo; Rubiano, Luisa Consuelo; Orobio, Yenifer; Castaño, Martha; Benavides, Elizabeth; Cruz, Adriana

2017-09-01

Colombia promotes the diagnosis and treatment of gestational syphilis in a single visit using rapid diagnostic tests to prevent mother-to-child transmission. Additionally, integrated health programs pursue the coordinated prevention of mother-to-child transmission of syphilis/HIV. To identify knowledge gaps among health workers in the prevention of mother-to-child transmission of syphilis/HIV and to provide recommendations to support these programs. We conducted a descriptive study based on 306 surveys of health workers in 39 health institutions in the city of Cali. Surveys inquired about planning, management and implementation of services for pregnant women, clinical knowledge of HIV/syphilis rapid diagnostic tests, and prior training. Knowledge deficits in the management of gestational syphilis were detected among the surveyed health workers, including physicians. Rapid tests for syphilis are currently used in clinical laboratories in Cali, however, procedural deficiencies were observed in their use, including quality control assurance. During the two years prior to the survey, training of health workers in the prevention of mother-to-child transmission of syphilis/HIV had been limited. Health workers are interested in identifying and treating gestational syphilis in a single event, in using rapid diagnostic tests and in receiving training. Intensive training targeting health workers, policy/decision makers and academic groups is needed to ensure adequate implementation of new strategies for the prevention of mother-to-child transmission of syphilis/HIV.

Analysis and modification of a single-mesh gear fatigue rig for use in diagnostic studies

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.; Townsend, Dennis P.; Oswald, Fred B.; Decker, Harry J.

1992-01-01

A single-mesh gear fatigue rig was analyzed and modified for use in gear mesh diagnostic research. The fatigue rig allowed unwanted vibration to mask the test-gear vibration signal, making it difficult to perform diagnostic studies. Several possible sources and factors contributing to the unwanted components of the vibration signal were investigated. Sensor mounting location was found to have a major effect on the content of the vibration signal. In the presence of unwanted vibration sources, modal amplification made unwanted components strong. A sensor location was found that provided a flatter frequency response. This resulted in a more useful vibration signal. A major network was performed on the fatigue rig to reduce the influence of the most probable sources of the noise in the vibration signal. The slave gears were machined to reduce weight and increase tooth loading. The housing and the shafts were modified to reduce imbalance, looseness, and misalignment in the rotating components. These changes resulted in an improved vibration signal, with the test-gear mesh frequency now the dominant component in the signal. Also, with the unwanted sources eliminated, the sensor mounting location giving the most robust representation of the test-gear meshing energy was found to be at a point close to the test gears in the load zone of the bearings.

Bench-top validation testing of selected immunological and molecular Renibacterium salmoninarum diagnostic assays by comparison with quantitative bacteriological culture

USGS Publications Warehouse

Elliott, D.G.; Applegate, L.J.; Murray, A.L.; Purcell, M.K.; McKibben, C.L.

2013-01-01

No gold standard assay exhibiting error-free classification of results has been identified for detection of Renibacterium salmoninarum, the causative agent of salmonid bacterial kidney disease. Validation of diagnostic assays for R. salmoninarum has been hindered by its unique characteristics and biology, and difficulties in locating suitable populations of reference test animals. Infection status of fish in test populations is often unknown, and it is commonly assumed that the assay yielding the most positive results has the highest diagnostic accuracy, without consideration of misclassification of results. In this research, quantification of R. salmoninarum in samples by bacteriological culture provided a standardized measure of viable bacteria to evaluate analytical performance characteristics (sensitivity, specificity and repeatability) of non-culture assays in three matrices (phosphate-buffered saline, ovarian fluid and kidney tissue). Non-culture assays included polyclonal enzyme-linked immunosorbent assay (ELISA), direct smear fluorescent antibody technique (FAT), membrane-filtration FAT, nested polymerase chain reaction (nested PCR) and three real-time quantitative PCR assays. Injection challenge of specific pathogen-free Chinook salmon, Oncorhynchus tshawytscha (Walbaum), with R. salmoninarum was used to estimate diagnostic sensitivity and specificity. Results did not identify a single assay demonstrating the highest analytical and diagnostic performance characteristics, but revealed strengths and weaknesses of each test.

A New Conceptual Approach to Teaching the Interpretation of Clinical Tests

ERIC Educational Resources Information Center

Linn, Shai

2004-01-01

Courses in clinical epidemiology usually include acquainting students with a single 2X2 table. All diagnostic test characteristics are explained using this table. This pedagogic approach may be misleading. A new didactic approach is hereby proposed, using two tables, each with specific analogous notations (uppercase and lowercase) and derived…

Lyssaviruses: special emphasis on rabies virus and other members of the lyssavirus genus.

PubMed

Harkess, Graeme; Fooks, Anthony R

2011-01-01

Rabies is routinely diagnosed based on the clinical description and history of exposure in a rabies-endemic country. A negative diagnostic test for rabies virus or a related lyssavirus does not exclude the clinical diagnosis. Diagnostic tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. Often, only a sample from a single time point is investigated reducing the overall sensitivity of any diagnosis. With the advent of molecular biology, tests have been developed that are rapid, robust, and sensitive in support of the rapid detection and strain identification of rabies virus from clinical specimens. These molecular tests complement conventional tests in rabies diagnosis, particularly for human cases, for which an early laboratory diagnosis is critical and may decrease the number of unnecessary contacts with the patient, reduce the requirement for invasive and costly interventions, and enable the appropriate medical treatment regimen to be administered for the patient. The barrier to success is in transferring the technology for the latest techniques in rabies diagnosis to rabies-endemic countries. These barriers are not insurmountable and in liaison with international organisations, especially OIE, FAO, and WHO, these diagnostic tests will be validated for rabies diagnosis and surveillance, and implemented in modern and well-equipped diagnostic laboratories throughout the world.

Neurocysticercosis: Diagnostic problems & current therapeutic strategies

PubMed Central

Rajshekhar, Vedantam

2016-01-01

Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530

Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.

PubMed

Harrington, Jennifer; Palmert, Mark R

2012-09-01

Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications. The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH. A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH. Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups. Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.

Sequential Test Strategies for Multiple Fault Isolation

NASA Technical Reports Server (NTRS)

Shakeri, M.; Pattipati, Krishna R.; Raghavan, V.; Patterson-Hine, Ann; Kell, T.

1997-01-01

In this paper, we consider the problem of constructing near optimal test sequencing algorithms for diagnosing multiple faults in redundant (fault-tolerant) systems. The computational complexity of solving the optimal multiple-fault isolation problem is super-exponential, that is, it is much more difficult than the single-fault isolation problem, which, by itself, is NP-hard. By employing concepts from information theory and Lagrangian relaxation, we present several static and dynamic (on-line or interactive) test sequencing algorithms for the multiple fault isolation problem that provide a trade-off between the degree of suboptimality and computational complexity. Furthermore, we present novel diagnostic strategies that generate a static diagnostic directed graph (digraph), instead of a static diagnostic tree, for multiple fault diagnosis. Using this approach, the storage complexity of the overall diagnostic strategy reduces substantially. Computational results based on real-world systems indicate that the size of a static multiple fault strategy is strictly related to the structure of the system, and that the use of an on-line multiple fault strategy can diagnose faults in systems with as many as 10,000 failure sources.

Verifying Diagnostic Software

NASA Technical Reports Server (NTRS)

Lindsey, Tony; Pecheur, Charles

2004-01-01

Livingstone PathFinder (LPF) is a simulation-based computer program for verifying autonomous diagnostic software. LPF is designed especially to be applied to NASA s Livingstone computer program, which implements a qualitative-model-based algorithm that diagnoses faults in a complex automated system (e.g., an exploratory robot, spacecraft, or aircraft). LPF forms a software test bed containing a Livingstone diagnosis engine, embedded in a simulated operating environment consisting of a simulator of the system to be diagnosed by Livingstone and a driver program that issues commands and faults according to a nondeterministic scenario provided by the user. LPF runs the test bed through all executions allowed by the scenario, checking for various selectable error conditions after each step. All components of the test bed are instrumented, so that execution can be single-stepped both backward and forward. The architecture of LPF is modular and includes generic interfaces to facilitate substitution of alternative versions of its different parts. Altogether, LPF provides a flexible, extensible framework for simulation-based analysis of diagnostic software; these characteristics also render it amenable to application to diagnostic programs other than Livingstone.

Utility of quantitative sensory testing and screening tools in identifying HIV-associated peripheral neuropathy in Western Kenya: pilot testing.

PubMed

Cettomai, Deanna; Kwasa, Judith; Kendi, Caroline; Birbeck, Gretchen L; Price, Richard W; Bukusi, Elizabeth A; Cohen, Craig R; Meyer, Ana-Claire

2010-12-08

Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings. We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy. The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS--83% sensitivity, 71% specificity; Subjective-PNS-total--83% sensitivity, 83% specificity; Subjective-PNS-max and NSS--67% sensitivity, 92% specificity; Brief-PNS--0% sensitivity, 92% specificity; monofilament--100% sensitivity, 88% specificity; graduated tuning fork--83% sensitivity, 88% specificity; two-point discrimination--75% sensitivity, 58% specificity. Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

Technological Innovations for High-Throughput Approaches to In Vitro Allergy Diagnosis.

PubMed

Chapman, Martin D; Wuenschmann, Sabina; King, Eva; Pomés, Anna

2015-07-01

Allergy diagnostics is being transformed by the advent of in vitro IgE testing using purified allergen molecules, combined with multiplex technology and biosensors, to deliver discriminating, sensitive, and high-throughput molecular diagnostics at the point of care. Essential elements of IgE molecular diagnostics are purified natural or recombinant allergens with defined purity and IgE reactivity, planar or bead-based multiplex systems to enable IgE to multiple allergens to be measured simultaneously, and, most recently, nanotechnology-based biosensors that facilitate rapid reaction rates and delivery of test results via mobile devices. Molecular diagnostics relies on measurement of IgE to purified allergens, the "active ingredients" of allergenic extracts. Typically, this involves measuring IgE to multiple allergens which is facilitated by multiplex technology and biosensors. The technology differentiates between clinically significant cross-reactive allergens (which could not be deduced by conventional IgE assays using allergenic extracts) and provides better diagnostic outcomes. Purified allergens are manufactured under good laboratory practice and validated using protein chemistry, mass spectrometry, and IgE antibody binding. Recently, multiple allergens (from dog) were expressed as a single molecule with high diagnostic efficacy. Challenges faced by molecular allergy diagnostic companies include generation of large panels of purified allergens with known diagnostic efficacy, access to flexible and robust array or sensor technology, and, importantly, access to well-defined serum panels form allergic patients for product development and validation. Innovations in IgE molecular diagnostics are rapidly being brought to market and will strengthen allergy testing at the point of care.

Single-centre study of the diagnostic performance of plasma metanephrines with seated sampling for the diagnosis of phaeochromocytoma/paraganglioma.

PubMed

Boot, Christopher; Toole, Barry; Johnson, Sarah J; Ball, Stephen; Neely, Dermot

2017-01-01

Background Measurement of plasma metanephrines is regarded as one of the best screening tests for phaeochromocytoma/paraganglioma. Current guidelines recommend that samples are ideally collected in the supine position after 30 min rest and interpreted using supine reference ranges, in order to optimize the diagnostic performance of the test. Current practice in our centre is to collect samples for plasma metanephrines from seated patients. The aim of the study was to determine, if seated sampling for plasma metanephrines provides acceptable diagnostic performance in our centre. Methods Clinical and laboratory data of 113 patients, gathered over a four-year period 2010-2014, were reviewed. All had undergone preoperative plasma metanephrines measurement and had postoperative histopathology confirmation or exclusion of phaeochromocytoma/paraganglioma. Results Of 113 patients included in the study, 40 had a histological diagnosis of phaeochromocytoma/paraganglioma. The remaining 73 patients had an alternative adrenal pathology. The diagnostic sensitivity of normetanephrine or metanephrine above the upper limit of our in-house seated reference range was 93%. However, excluding three cases of paraganglioma determined clinically and biochemically to be non-functional raised the sensitivity to 100%. Diagnostic specificity was 90%. Applying published supine reference ranges made no difference to diagnostic sensitivity in this group of patients but decreased diagnostic specificity to 75%. Conclusions While these data are derived from a relatively small study population, they demonstrate acceptable diagnostic performance for seated plasma metanephrines as a screening test for phaeochromocytoma/paraganglioma. These data highlight a high diagnostic sensitivity for plasma metanephrines with seated sampling in our centre.

Arrhythmia discrimination by physician and defibrillator: importance of atrial channel.

PubMed

Diemberger, Igor; Martignani, Cristian; Biffi, Mauro; Frabetti, Lorenzo; Valzania, Cinzia; Cooke, Robin M T; Rapezzi, Claudio; Branzi, Angelo; Boriani, Giuseppe

2012-01-26

Many ICD carriers experience inappropriate shocks, but the relative merits of dual- /single-chamber devices for arrhythmia discrimination still remain unclear. We explored possible advantages of the atrial data provided by dual-chamber implantable defibrillators (ICD) for discrimination of real-life supraventricular/ventricular tachyarrhythmias (SVT/VT). 100 dual-chamber traces from 24 ICD were blindly reviewed in dual-chamber and simulated single-chamber (with/without discriminator data) reading modes by five electrophysiologists who determined chamber of origin and provided Likert-scale "confidence" ratings. We assessed 1) intra/interobserver concordance; 2) diagnostic accuracy, using expert diagnoses as a reference standard; 3) ROC curves of sensitivity/specificity of "likelihood perception" scores, generated by combining chamber-of-origin diagnostic judgments with Likert-scale "confidence" ratings. We also assessed diagnostic accuracy of automated discrimination by all possible dual-/single-chamber algorithm configurations. Interobserver concordance was "substantial" (modified Cohen kappa-test values for dual-/single-chamber, 0.79/0.68); intraobserver concordance "almost complete" (kappa ≥ 0.89). Dual-chamber mode provided best diagnostic sensitivity/specificity (99%/92%) and highest reader confidence (p<0.001). Area under ROC curves of sensitivity/specificity values for the "likelihood perception" score (representing electrophysiologists' perceptions of the likelihood that an episode was of ventricular origin) was highest in dual-chamber mode (0.98 vs. 0.93 for both single-chamber modes; p<0.001). Regarding automated discrimination, all four dual-chamber configurations conferred 100% sensitivity (specificity values ranged 39%-88%), whereas single-chamber configurations appeared inferior (best sensitivity/specificity combination, 89%/64%). Availability of the atrial channel helps in reducing inappropriate ICD therapies by providing relevant advantages in terms of both appropriate cardiologist's post-hoc discrimination of SVT/VT (improving program tailoring) and automated arrhythmia discrimination. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Single-shot, high-resolution, fiber-based phase-diversity photodetection of optical pulses

NASA Astrophysics Data System (ADS)

Dorrer, C.; Waxer, L. J.; Kalb, A.; Hill, E. M.; Bromage, J.

2016-03-01

Temporally characterizing optical pulses is an important task when building, optimizing, and using optical sources. Direct photodetection with high-bandwidth photodiodes and real-time oscilloscopes is only adequate for optical pulses longer than ~10 ps; diagnostics based on indirect strategies are required to characterize femtosecond and sub-10-ps coherent sources. Most of these diagnostics are based on nonlinear optics and can be difficult to implement for the single-shot characterization of nonrepetitive events. A temporal diagnostic based on phase diversity is demonstrated in the context of picosecond high-energy laser systems, where single-shot pulse measurements are required for system safety and interpretation of experimental results. A plurality of ancillary optical pulses obtained by adding known amounts of chromatic dispersion to the pulse under test are directly measured by photodetection and processed to reconstruct the input pulse shape. This high-sensitivity (~50-pJ) diagnostic is based on a pulse replicator composed of fiber splitters and delay fibers, making it possible to operate with fiber sources and free-space sources after fiber coupling. Experimental data obtained with a high-bandwidth real-time oscilloscope demonstrate accurate characterization of pulses from a high-energy chirped-pulse amplification system, even for pulses shorter than the photodetection impulse response.

Diagnostic evaluation of rapid tests for scrub typhus in the Indian population is needed.

PubMed

Shivalli, Siddharudha

2016-05-12

Owing to frequent outbreaks witnessed in different parts of the country in the recent past, scrub typhus is being described as a re-emerging infectious disease in India. Differentiating scrub typhus from other endemic diseases like malaria, leptospirosis, dengue fever, typhoid, etc. is difficult due to overlapping clinical features and a lower positivity for eschars in Asian populations. Hence, the diagnosis heavily relies on laboratory tests. Costs and the need of technical expertise limit the wide use of indirect immunoperoxidase or immunofluorescence assays, ELISA and PCR. The Weil-Felix test is the most commonly used and least expensive serological test, but lacks both sensitivity and specificity. Hence, the diagnosis of scrub typhus is often delayed or overlooked. With due consideration of the cost, rapidity, single test result and simplicity of interpretation, rapid diagnostic tests have come into vogue. However, evaluation of rapid diagnostic tests for scrub typhus in the Indian population is needed to justify or discourage their use. Research studies are needed to find the most suitable test in terms of the rapidity of the result, simplicity of the procedure, ease of interpretation and cost to be used in the Indian populace.

A comparative analysis of costs of single and dual rapid HIV and syphilis diagnostics: results from a randomised controlled trial in Colombia.

PubMed

Obure, Carol Dayo; Gaitan-Duarte, Hernando; Losada Saenz, Ricardo; Gonzalez, Lina; Angel-Muller, Edith; Laverty, Maura; Perez, Freddy

2017-11-01

HIV and congenital syphilis are major public health burdens contributing to substantial perinatal morbidity and mortality globally. Although studies have reported on the costs and cost-effectiveness of rapid diagnostic tests (RDTs) for syphilis screening within antenatal care in a number of resource-constrained settings, empirical evidence on country-specific cost and estimates of single RDTs compared with dual RDTs for HIV and syphilis are limited. A cluster randomised controlled study design was used to compare the incremental costs of two testing algorithms: (1) single RDTs for HIV and syphilis and (2) dual RDTs for HIV and syphilis, in 12 health facilities in Bogota and Cali, Colombia. The costs of single HIV and syphilis RDTs and dual HIV and syphilis RDTs were collected from each of the health facilities. The economic costs per woman tested for HIV and syphilis and costs per woman treated for syphilis defined as the total costs required to test and treat one woman for syphilis were estimated. A total of 2214 women were tested in the study facilities. Cost per pregnant woman tested and cost per woman treated for syphilis were US$10.26 and US$607.99, respectively in the single RDT arm. For the dual RDTs, the cost per pregnant woman tested for HIV and syphilis and cost per woman treated for syphilis were US$15.89 and US$1859.26, respectively. Overall costs per woman tested for HIV and syphilis and cost per woman treated for syphilis were lower in Cali compared with Bogota across both intervention arms. Staff costs accounted for the largest proportion of costs while treatment costs comprised <1% of the preventive programme. Findings show lower average costs for single RDTs compared with dual RDTs with costs sensitive to personnel costs and the scale of output at the health facilities. NCT02454816; results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis.

PubMed

Enabulele, Osahon; Awunor, Simeon Nyemike

2016-01-01

Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co-infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test.

Typhoid fever in a Tertiary Hospital in Nigeria: Another look at the Widal agglutination test as a preferred option for diagnosis

PubMed Central

Enabulele, Osahon; Awunor, Simeon Nyemike

2016-01-01

Background: Single Widal agglutination test rather than blood culture, is commonly employed to diagnose typhoid fever in Nigeria. We took another look at the Widal agglutination test as a preferred option for diagnosis of typhoid fever by determining the specificity and sensitivity of Widal agglutination test in febrile adult patients. Materials and Methods: Two hundred and seventy-one blood samples from consecutive adults (>18 years) with febrile illness attending the General Practice Clinic of the University of Benin Teaching Hospital were tested using the Widal agglutination test, blood culture, and malaria parasite test on each sample to establish the diagnosis of typhoid fever. Results: Of the 271 blood samples 124 (45.76%) were positive following a Widal agglutination test, 60 (22.10%) blood samples grew Salmonella organisms on blood culture while 55 (20.29%) blood samples showed a co-infection of typhoid fever and malaria. A sensitivity of 35%, specificity of 51%, positive predictive value of 17%, and a negative predictive value of 73% were observed for Widal agglutination test as a diagnostic modality for typhoid fever infection. Conclusion: A single Widal agglutination test is not a valid diagnostic option for typhoid fever while co-infection with malaria parasite is the preponderant microbiological finding in typhoid fever infections. The severity of malaria parasitemia is associated with positive titers on Widal test. PMID:27397952

Single Assay for Simultaneous Detection and Differential Identification of Human and Avian Influenza Virus Types, Subtypes, and Emergent Variants

PubMed Central

Metzgar, David; Myers, Christopher A.; Russell, Kevin L.; Faix, Dennis; Blair, Patrick J.; Brown, Jason; Vo, Scott; Swayne, David E.; Thomas, Colleen; Stenger, David A.; Lin, Baochuan; Malanoski, Anthony P.; Wang, Zheng; Blaney, Kate M.; Long, Nina C.; Schnur, Joel M.; Saad, Magdi D.; Borsuk, Lisa A.; Lichanska, Agnieszka M.; Lorence, Matthew C.; Weslowski, Brian; Schafer, Klaus O.; Tibbetts, Clark

2010-01-01

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents. PMID:20140251

Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants.

PubMed

Metzgar, David; Myers, Christopher A; Russell, Kevin L; Faix, Dennis; Blair, Patrick J; Brown, Jason; Vo, Scott; Swayne, David E; Thomas, Colleen; Stenger, David A; Lin, Baochuan; Malanoski, Anthony P; Wang, Zheng; Blaney, Kate M; Long, Nina C; Schnur, Joel M; Saad, Magdi D; Borsuk, Lisa A; Lichanska, Agnieszka M; Lorence, Matthew C; Weslowski, Brian; Schafer, Klaus O; Tibbetts, Clark

2010-02-03

For more than four decades the cause of most type A influenza virus infections of humans has been attributed to only two viral subtypes, A/H1N1 or A/H3N2. In contrast, avian and other vertebrate species are a reservoir of type A influenza virus genome diversity, hosting strains representing at least 120 of 144 combinations of 16 viral hemagglutinin and 9 viral neuraminidase subtypes. Viral genome segment reassortments and mutations emerging within this reservoir may spawn new influenza virus strains as imminent epidemic or pandemic threats to human health and poultry production. Traditional methods to detect and differentiate influenza virus subtypes are either time-consuming and labor-intensive (culture-based) or remarkably insensitive (antibody-based). Molecular diagnostic assays based upon reverse transcriptase-polymerase chain reaction (RT-PCR) have short assay cycle time, and high analytical sensitivity and specificity. However, none of these diagnostic tests determine viral gene nucleotide sequences to distinguish strains and variants of a detected pathogen from one specimen to the next. Decision-quality, strain- and variant-specific pathogen gene sequence information may be critical for public health, infection control, surveillance, epidemiology, or medical/veterinary treatment planning. The Resequencing Pathogen Microarray (RPM-Flu) is a robust, highly multiplexed and target gene sequencing-based alternative to both traditional culture- or biomarker-based diagnostic tests. RPM-Flu is a single, simultaneous differential diagnostic assay for all subtype combinations of type A influenza viruses and for 30 other viral and bacterial pathogens that may cause influenza-like illness. These other pathogen targets of RPM-Flu may co-infect and compound the morbidity and/or mortality of patients with influenza. The informative specificity of a single RPM-Flu test represents specimen-specific viral gene sequences as determinants of virus type, A/HN subtype, virulence, host-range, and resistance to antiviral agents.

[What is hidden behind the Baking Tray Task? Study of sensibility and specificity in right-hemispheric stroke patients].

PubMed

Garcia-Fernandez, Juan; Garcia-Molina, Alberto; Aparicio-Lopez, Celeste; Sanchez-Carrion, Rocío; Ensenat, Antònia; Pena-Casanova, Jordi; Roig-Rovira, Teresa

2015-12-16

Tham and Tegner proposed the Baking Tray Task (BTT) as a fast simple assessment test for detecting spatial negligence. However, very few studies have examined its validity as a diagnostic test. To analyse the diagnostic validity of the BTT by measuring its specificity and sensitivity in a sample of subjects with right hemisphere strokes. Forty-eight patients with right hemisphere vascular lesions were distributed in two groups (negligence group, n = 35; non-negligence group, n = 13) according to the scores obtained in a battery of visuospatial examination tests. The participants' performance on the BTT was compared with that of a healthy control group (n = 12). The results showed a high level of sensitivity of the BTT, but low specificity. The performance on the BTT of eight of the 13 members of the non-negligence group was suggestive of negligence. The BTT has proved to be a sensitive test for the detection of spatial negligence. Yet, based on its low specificity, its use alone as a single diagnostic test is not recommended.

Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials

PubMed Central

Siontis, George CM; Mavridis, Dimitris; Greenwood, John P; Coles, Bernadette; Nikolakopoulou, Adriani; Jüni, Peter; Salanti, Georgia

2018-01-01

Abstract Objective To evaluate differences in downstream testing, coronary revascularisation, and clinical outcomes following non-invasive diagnostic modalities used to detect coronary artery disease. Design Systematic review and network meta-analysis. Data sources Medline, Medline in process, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO International Clinical Trials Registry Platform, and Clinicaltrials.gov. Eligibility criteria for selecting studies Diagnostic randomised controlled trials comparing non-invasive diagnostic modalities in patients presenting with symptoms suggestive of low risk acute coronary syndrome or stable coronary artery disease. Data synthesis A random effects network meta-analysis synthesised available evidence from trials evaluating the effect of non-invasive diagnostic modalities on downstream testing and patient oriented outcomes in patients with suspected coronary artery disease. Modalities included exercise electrocardiograms, stress echocardiography, single photon emission computed tomography-myocardial perfusion imaging, real time myocardial contrast echocardiography, coronary computed tomographic angiography, and cardiovascular magnetic resonance. Unpublished outcome data were obtained from 11 trials. Results 18 trials of patients with low risk acute coronary syndrome (n=11 329) and 12 trials of those with suspected stable coronary artery disease (n=22 062) were included. Among patients with low risk acute coronary syndrome, stress echocardiography, cardiovascular magnetic resonance, and exercise electrocardiograms resulted in fewer invasive referrals for coronary angiography than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00), respectively). There was no effect on the subsequent risk of myocardial infarction, but estimates were imprecise. Heterogeneity and inconsistency were low. In patients with suspected stable coronary artery disease, an initial diagnostic strategy of stress echocardiography or single photon emission computed tomography-myocardial perfusion imaging resulted in fewer downstream tests than coronary computed tomographic angiography (0.24 (0.08 to 0.74) and 0.57 (0.37 to 0.87), respectively). However, exercise electrocardiograms yielded the highest downstream testing rate. Estimates for death and myocardial infarction were imprecise without clear discrimination between strategies. Conclusions For patients with low risk acute coronary syndrome, an initial diagnostic strategy of stress echocardiography or cardiovascular magnetic resonance is associated with fewer referrals for invasive coronary angiography and revascularisation procedures than non-invasive anatomical testing, without apparent impact on the future risk of myocardial infarction. For suspected stable coronary artery disease, there was no clear discrimination between diagnostic strategies regarding the subsequent need for invasive coronary angiography, and differences in the risk of myocardial infarction cannot be ruled out. Systematic review registration PROSPERO registry no CRD42016049442. PMID:29467161

Novel PCRs for differential diagnosis of cestodes.

PubMed

Roelfsema, Jeroen H; Nozari, Nahid; Pinelli, Elena; Kortbeek, Laetitia M

2016-02-01

Cestodes or tapeworms belong to a diverse group of helminths. The adult Taenia saginata and Taenia solium tapeworm can infest the human gut and the larval stage of Echinococcus spp. and T. solium can infect tissues of the human body, causing serious disease. Molecular diagnostics can be performed on proglottids, eggs and on cyst fluids taken by biopsy. Detection of cestodes when a helminthic infection is suspected is of vital importance and species determination is required for appropriate patient care. For routine diagnostics a single test that is able to detect and type a range of cestodes is preferable. We sought to improve our diagnostic procedure that used to rely on PCR and subsequent sequencing of the Cox1 and Nad1 genes. We have compared these PCRs with novel PCRs on the 12S rRNA and Nad5 gene and established the sensitivity and specificity. A single PCR on the 12S gene proved to be very suitable for detection and specification of Taenia sp. and Echinococcus sp. Both targets harbour enough polymorphic sites to determine the various Echinococcus species. The 12S PCR was most sensitive of all tested. Copyright © 2015 Elsevier Inc. All rights reserved.

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

PubMed

Taylor, Rachel L; Parry, Neil R A; Barton, Stephanie J; Campbell, Christopher; Delaney, Claire M; Ellingford, Jamie M; Hall, Georgina; Hardcastle, Claire; Morarji, Jiten; Nichol, Elisabeth J; Williams, Lindsi C; Douzgou, Sofia; Clayton-Smith, Jill; Ramsden, Simon C; Sharma, Vinod; Biswas, Susmito; Lloyd, I Chris; Ashworth, Jane L; Black, Graeme C; Sergouniotis, Panagiotis I

2017-07-01

To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD). Single-center retrospective case series. Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016. Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation. Diagnostic yield and clinical usefulness of genetic testing. Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion. Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Evaluation of Rib Fractures on a Single-in-plane Image Reformation of the Rib Cage in CT Examinations.

PubMed

Dankerl, Peter; Seuss, Hannes; Ellmann, Stephan; Cavallaro, Alexander; Uder, Michael; Hammon, Matthias

2017-02-01

This study aimed to evaluate the diagnostic performance of using a reformatted single-in-plane image reformation of the rib cage for the detection of rib fractures in computed tomography (CT) examinations, employing different levels of radiological experience. We retrospectively evaluated 10 consecutive patients with and 10 patients without rib fractures, whose CT scans were reformatted to a single-in-plane image reformation of the rib cage. Eight readers (two radiologists, two residents in radiology, and four interns) independently evaluated the images for the presence of rib fractures using a reformatted single-in-plane image and a multi-planar image reformation. The time limit was 30 seconds for each read. A consensus of two radiologist readings was considered as the reference standard. Diagnostic performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) was assessed and evaluated per rib and per location (anterior, lateral, posterior). To determine the time limit, we prospectively analyzed the average time it took radiologists to assess the rib cage, in a bone window setting, in 50 routine CT examinations. McNemar test was used to compare the diagnostic performances. Single image reformation was successful in all 20 patients. The sensitivity, specificity, PPV, and NPV for the detection of rib fractures using the conventional multi-planar read were 77.5%, 99.2%, 89.9%, and 98.0% for radiologists; 46.3%, 99.7%, 92.5%, and 95.3% for residents; and 29.4%, 99.4%, 82.5%, and 93.9% for interns, respectively. Sensitivity, PPV, and NPV increased across all three groups of experience, using the reformatted single-in-plane image of the rib cage (radiologists: 85.0%, 98.6%, and 98.7%; residents: 80.0%, 92.8%, and 98.2%; interns: 66.9%, 89.9%, and 97.1%), whereas specificity did not change significantly (99.9%, 99.4%, and 99.3%). The diagnostic performance of the interns and residents was significantly better when evaluating the single-in-plane image reformations (P < .01). The diagnostic performance of the radiologists was better when evaluating the single-in-plane image reformations; however, there was no significant difference (statistical power: 0.32). The diagnostic performance for the detection of rib fractures, using CT images that have been reformatted to a single-in-plane image, improves for readers from different educational levels when the evaluation time is restricted to 30 seconds or less. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics.

PubMed

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-07-21

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics

PubMed Central

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-01-01

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format. PMID:23685876

[The prevalence of yaws among the Aka in the Congo].

PubMed

Coldiron, M; Obvala, D; Mouniaman-Nara, I; Pena, J; Blondel, C; Porten, K

2013-05-01

This study, conducted in 2012 in two districts of the Congo (Bétou and Enyellé), screened for yaws (endemic treponemiasis) that could be treated by a single dose of azithromycin. The screening involved a clinical history, followed by a clinical examination of the children reporting dermatological problems. A rapid diagnostic test for treponema was performed on the children with suspicious lesions. Of 6215 children screened, 485 (7.8%) had such lesions; 480 (99.0%) of them had a rapid diagnostic test, and it was positive for 183 (38.1%). This so-called Morges strategy is aimed at eradicating yaws in endemic areas.

Evaluation performance of diagnostic methods of intestinal parasitosis in school age children in Ethiopia.

PubMed

Yimer, Mulat; Hailu, Tadesse; Mulu, Wondemagegn; Abera, Bayeh

2015-12-26

Although the sensitivity of Wet mount technique is questionable, it is the major diagnostic technique for routine diagnosis of intestinal parasitosis in Ethiopia. Therefore, the aim of this study was the evaluation performance of diagnostic methods of intestinal parasitosis in school age children in Ethiopia. A cross sectional study was conducted from May to June 2013. Single stool sample was processed for direct, Formol ether concentration (FEC) and Kato Katz methods. The sensitivity and negative predictive value (NPV) of diagnostic tests were calculated in terms of the "Gold" standard method (the combined result of the three methods altogether). A total of 422 school age children were participated in this study. The prevalence of intestinal parasites was high (74.6%) with Kato Katz technique. The sensitivity of Wet mount, FEC and Kato Katz tests against the Gold standard test was 48.9, 63.1 and 93.7%, respectively. Kato Katz technique revealed a better NPV 80.4 (80.1-80.6) as compared to the Wet mount (33.7%) and FEC techniques (41.3%). In this study, the Kato Katz technique outperformed the other two methods but the true values for sensitivity, specificity and diagnostic values are not known. Moreover, it is labor intensive and not easily accessible. Hence, it is preferable to use FEC technique to complement the Wet mount test.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets.

PubMed

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 10 2 -10 5 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing.

A Paper-Based Device for Performing Loop-Mediated Isothermal Amplification with Real-Time Simultaneous Detection of Multiple DNA Targets

PubMed Central

Seok, Youngung; Joung, Hyou-Arm; Byun, Ju-Young; Jeon, Hyo-Sung; Shin, Su Jeong; Kim, Sanghyo; Shin, Young-Beom; Han, Hyung Soo; Kim, Min-Gon

2017-01-01

Paper-based diagnostic devices have many advantages as a one of the multiple diagnostic test platforms for point-of-care (POC) testing because they have simplicity, portability, and cost-effectiveness. However, despite high sensitivity and specificity of nucleic acid testing (NAT), the development of NAT based on a paper platform has not progressed as much as the others because various specific conditions for nucleic acid amplification reactions such as pH, buffer components, and temperature, inhibitions from technical differences of paper-based device. Here, we propose a paper-based device for performing loop-mediated isothermal amplification (LAMP) with real-time simultaneous detection of multiple DNA targets. We determined the optimal chemical components to enable dry conditions for the LAMP reaction without lyophilization or other techniques. We also devised the simple paper device structure by sequentially stacking functional layers, and employed a newly discovered property of hydroxynaphthol blue fluorescence to analyze real-time LAMP signals in the paper device. This proposed platform allowed analysis of three different meningitis DNA samples in a single device with single-step operation. This LAMP-based multiple diagnostic device has potential for real-time analysis with quantitative detection of 102-105 copies of genomic DNA. Furthermore, we propose the transformation of DNA amplification devices to a simple and affordable paper system approach with great potential for realizing a paper-based NAT system for POC testing. PMID:28740546

Tuberculous otitis media: a significant diagnostic challenge.

PubMed

Vaamonde, Pedro; Castro, Crisanto; García-Soto, Nicolas; Labella, Torcuato; Lozano, Ascensión

2004-06-01

This study was undertaken to revise the diagnostic characteristics of tuberculous otitis media (TOM), a disorder that is often diagnosed late, leading to delay in specific treatment. Retrospective study of a longitudinal series of 10 TOM patients over a 7-year period at an institutional referral center. Most patients showed intractable otorrhea, moderately severe hearing loss, and necrotic eardrums with granulation tissue and single perforations. Multiple perforations, facial palsy, and cervical adenopathies were rare (<10% of patients). CT generally showed soft tissue involvement of the middle ear without bone erosion. The most effective laboratory test microbiological culture of exudate (diagnostic efficacy 71%). Specific antibiotic treatment was effective in all cases. The diagnosis of TOM remains a significant challenge for otorhinolaryngologists. If there are strong clinical grounds for suspicion, standard laboratory tests for tuberculosis should be repeated even if initially negative.

Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland.

PubMed

Nuñez-Garcia, Javier; Downs, Sara H; Parry, Jessica E; Abernethy, Darrell A; Broughan, Jennifer M; Cameron, Angus R; Cook, Alasdair J; de la Rua-Domenech, Ricardo; Goodchild, Anthony V; Gunn, Jane; More, Simon J; Rhodes, Shelley; Rolfe, Simon; Sharp, Michael; Upton, Paul A; Vordermeier, H Martin; Watson, Eamon; Welsh, Michael; Whelan, Adam O; Woolliams, John A; Clifton-Hadley, Richard S; Greiner, Matthias

2018-05-01

Bovine Tuberculosis (bTB) in cattle is a global health problem and eradication of the disease requires accurate estimates of diagnostic test performance to optimize their efficiency. The objective of this study was, through statistical meta-analyses, to obtain estimates of sensitivity (Se) and specificity (Sp), for 14 different ante-mortem and post-mortem diagnostic tests for bTB in cattle. Using data from a systematic review of the scientific literature (published 1934-2009) diagnostic Se and Sp were estimated using Bayesian logistic regression models adjusting for confounding factors. Random effect terms were used to account for unexplained heterogeneity. Parameters in the models were implemented using Markov Chain Monte Carlo (MCMC), and posterior distributions for the diagnostic parameters with adjustment for covariates (confounding factors) were obtained using the inverse logit function. Estimates for Se and/or Sp of the tuberculin skin tests and the IFN-γ blood test were compared with estimates published 2010-2015. Median Se for the single intradermal comparative cervical tuberculin skin (SICCT) test (standard interpretation) was 0.50 and Bayesian credible intervals (CrI) were wide (95% CrI 0.26, 0.78). Median Sp for the SICCT test was 1.00 (95% CrI 0.99, 1.00). Estimates for the IFN-γ blood test Bovine Purified Protein Derivative (PPD)-Avian PPD and Early Secreted Antigen target 6 and Culture Filtrate Protein 10 (ESAT-6/CFP10) ESAT6/CFP10 were 0.67 (95% CrI 0.49, 0.82) and 0.78 (95% CrI 0.60, 0.90) respectively for Se, and 0.98 (95% CrI 0.96, 0.99) and 0.99 (95% CrI 0.99, 1.00) for Sp. The study provides an overview of the accuracy of a range of contemporary diagnostic tests for bTB in cattle. Better understanding of diagnostic test performance is essential for the design of effective control strategies and their evaluation. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Biotechnology Conference: Diagnostics 󈨛 Held in Cambridge, England on 10 and 11 December 1987.

DTIC Science & Technology

1988-05-25

settings. 1 -hour culture confirmation test for herpes (ColorGene DNA hybridization test for HSV confirmation). This test NEW AMPEROMETRIC BIOSENSORS...I Thin Layer Technology: Monolayers to Multi Thin Films ................. 1 Single-Step Immunoassay Systems...if this thin-layer pr•ccss~is probe technolh,,y. and biosensors. The aim of the con- demonstrated in Figure 1 . which shows the disposition of ference

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing. PMID:23226057

Intelligent Engine Systems

NASA Technical Reports Server (NTRS)

Xie, Ming

2008-01-01

A high bypass jet engine fan case represents one of the largest, heaviest single components in an engine. In addition to supporting the inlet and providing the fan flowpath, the most critical function is the containment of a failed fan blade. In this development program, a lightweight, low-cost composite containment case with diagnostic capabilities was developed, fabricated, and tested. The fan case design, containment methods, and diagnostic concepts evaluated in the initial Propulsion 21 program were improved and scaled up to a full case design.

Gear Damage Detection Integrating Oil Debris and Vibration Measurement Technologies Developed

NASA Technical Reports Server (NTRS)

Gyekeyeski, Andrew L.; Sawicki, Jerzy T.

2001-01-01

The development of highly reliable health-monitoring systems is one technology area recommended for reducing the number of helicopter accidents. Helicopter transmission diagnostics are an important part of a helicopter health-monitoring system because helicopters depend on the power train for propulsion, lift, and flight maneuvering. One technique currently being tested for increasing the reliability and decreasing the false alarm rate of current transmission diagnostic tools is the replacement of simple single-sensor limits with multisensor systems integrating different measurement technologies.

Ethical principles and pitfalls of genetic testing for dementia.

PubMed

Hedera, P

2001-01-01

Progress in the genetics of dementing disorders and the availability of clinical tests for practicing physicians increase the need for a better understanding of multifaceted issues associated with genetic testing. The genetics of dementia is complex, and genetic testing is fraught with many ethical concerns. Genetic testing can be considered for patients with a family history suggestive of a single gene disorder as a cause of dementia. Testing of affected patients should be accompanied by competent genetic counseling that focuses on probabilistic implications for at-risk first-degree relatives. Predictive testing of at-risk asymptomatic patients should be modeled after presymptomatic testing for Huntington's disease. Testing using susceptibility genes has only a limited diagnostic value at present because potential improvement in diagnostic accuracy does not justify potentially negative consequences for first-degree relatives. Predictive testing of unaffected subjects using susceptibility genes is currently not recommended because individual risk cannot be quantified and there are no therapeutic interventions for dementia in presymptomatic patients.

Paper-based sample-to-answer molecular diagnostic platform for point-of-care diagnostics.

PubMed

Choi, Jane Ru; Tang, Ruihua; Wang, ShuQi; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

2015-12-15

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

Value of transmission electron microscopy for primary ciliary dyskinesia diagnosis in the era of molecular medicine: Genetic defects with normal and non-diagnostic ciliary ultrastructure.

PubMed

Shapiro, Adam J; Leigh, Margaret W

2017-01-01

Primary ciliary dyskinesia (PCD) is a genetic disorder causing chronic oto-sino-pulmonary disease. No single diagnostic test will detect all PCD cases. Transmission electron microscopy (TEM) of respiratory cilia was previously considered the gold standard diagnostic test for PCD, but 30% of all PCD cases have either normal ciliary ultrastructure or subtle changes which are non-diagnostic. These cases are identified through alternate diagnostic tests, including nasal nitric oxide measurement, high-speed videomicroscopy analysis, immunofluorescent staining of axonemal proteins, and/or mutation analysis of various PCD causing genes. Autosomal recessive mutations in DNAH11 and HYDIN produce normal TEM ciliary ultrastructure, while mutations in genes encoding for radial spoke head proteins result in some cross-sections with non-diagnostic alterations in the central apparatus interspersed with normal ciliary cross-sections. Mutations in nexin link and dynein regulatory complex genes lead to a collection of different ciliary ultrastructures; mutations in CCDC65, CCDC164, and GAS8 produce normal ciliary ultrastructure, while mutations in CCDC39 and CCDC40 cause absent inner dynein arms and microtubule disorganization in some ciliary cross-sections. Mutations in CCNO and MCIDAS cause near complete absence of respiratory cilia due to defects in generation of multiple cellular basal bodies; however, the scant cilia generated may have normal ultrastructure. Lastly, a syndromic form of PCD with retinal degeneration results in normal ciliary ultrastructure through mutations in the RPGR gene. Clinicians must be aware of these genetic causes of PCD resulting in non-diagnostic TEM ciliary ultrastructure and refrain from using TEM of respiratory cilia as a test to rule out PCD.

No added diagnostic value of non-phosphorylated tau fraction (p-taurel) in CSF as a biomarker for differential dementia diagnosis.

PubMed

Goossens, Joery; Bjerke, Maria; Struyfs, Hanne; Niemantsverdriet, Ellis; Somers, Charisse; Van den Bossche, Tobi; Van Mossevelde, Sara; De Vil, Bart; Sieben, Anne; Martin, Jean-Jacques; Cras, Patrick; Goeman, Johan; De Deyn, Peter Paul; Van Broeckhoven, Christine; van der Zee, Julie; Engelborghs, Sebastiaan

2017-07-14

The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls. The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

A general diagnostic model applied to language testing data.

PubMed

von Davier, Matthias

2008-11-01

Probabilistic models with one or more latent variables are designed to report on a corresponding number of skills or cognitive attributes. Multidimensional skill profiles offer additional information beyond what a single test score can provide, if the reported skills can be identified and distinguished reliably. Many recent approaches to skill profile models are limited to dichotomous data and have made use of computationally intensive estimation methods such as Markov chain Monte Carlo, since standard maximum likelihood (ML) estimation techniques were deemed infeasible. This paper presents a general diagnostic model (GDM) that can be estimated with standard ML techniques and applies to polytomous response variables as well as to skills with two or more proficiency levels. The paper uses one member of a larger class of diagnostic models, a compensatory diagnostic model for dichotomous and partial credit data. Many well-known models, such as univariate and multivariate versions of the Rasch model and the two-parameter logistic item response theory model, the generalized partial credit model, as well as a variety of skill profile models, are special cases of this GDM. In addition to an introduction to this model, the paper presents a parameter recovery study using simulated data and an application to real data from the field test for TOEFL Internet-based testing.

Determining the Optimal Number of Core Needle Biopsy Passes for Molecular Diagnostics.

PubMed

Hoang, Nam S; Ge, Benjamin H; Pan, Lorraine Y; Ozawa, Michael G; Kong, Christina S; Louie, John D; Shah, Rajesh P

2018-03-01

The number of core biopsy passes required for adequate next-generation sequencing is impacted by needle cut, needle gauge, and the type of tissue involved. This study evaluates diagnostic adequacy of core needle lung biopsies based on number of passes and provides guidelines for other tissues based on simulated biopsies in ex vivo porcine organ tissues. The rate of diagnostic adequacy for pathology and molecular testing from lung biopsy procedures was measured for eight operators pre-implementation (September 2012-October 2013) and post-implementation (December 2013-April 2014) of a standard protocol using 20-gauge side-cut needles for ten core biopsy passes at a single academic hospital. Biopsy pass volume was then estimated in ex vivo porcine muscle, liver, and kidney using side-cut devices at 16, 18, and 20 gauge and end-cut devices at 16 and 18 gauge to estimate minimum number of passes required for adequate molecular testing. Molecular diagnostic adequacy increased from 69% (pre-implementation period) to 92% (post-implementation period) (p < 0.001) for lung biopsies. In porcine models, both 16-gauge end-cut and side-cut devices require one pass to reach the validated volume threshold to ensure 99% adequacy for molecular characterization, while 18- and 20-gauge devices require 2-5 passes depending on needle cut and tissue type. Use of 20-gauge side-cut core biopsy needles requires a significant number of passes to ensure diagnostic adequacy for molecular testing across all tissue types. To ensure diagnostic adequacy for molecular testing, 16- and 18-gauge needles require markedly fewer passes.

Whole-genome sequencing expands diagnostic utility and improves clinical management in paediatric medicine

PubMed Central

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond H; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-01

The standard of care for first-tier clinical investigation of the aetiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy-number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion–deletions (indels) and single-nucleotide variant (SNV) mutations. Whole-genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilised WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a fourfold increase in diagnostic rate over CMA (8%; P value=1.42E−05) alone and more than twofold increase in CMA plus targeted gene sequencing (13%; P value=0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harbouring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counselling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis. PMID:28567303

Whole Genome Sequencing Expands Diagnostic Utility and Improves Clinical Management in Pediatric Medicine.

PubMed

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-13

The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. Whole genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilized WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counseling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis.

True versus Apparent Malaria Infection Prevalence: The Contribution of a Bayesian Approach

PubMed Central

Claes, Filip; Van Hong, Nguyen; Torres, Kathy; Mao, Sokny; Van den Eede, Peter; Thi Thinh, Ta; Gamboa, Dioni; Sochantha, Tho; Thang, Ngo Duc; Coosemans, Marc; Büscher, Philippe; D'Alessandro, Umberto; Berkvens, Dirk; Erhart, Annette

2011-01-01

Aims To present a new approach for estimating the “true prevalence” of malaria and apply it to datasets from Peru, Vietnam, and Cambodia. Methods Bayesian models were developed for estimating both the malaria prevalence using different diagnostic tests (microscopy, PCR & ELISA), without the need of a gold standard, and the tests' characteristics. Several sources of information, i.e. data, expert opinions and other sources of knowledge can be integrated into the model. This approach resulting in an optimal and harmonized estimate of malaria infection prevalence, with no conflict between the different sources of information, was tested on data from Peru, Vietnam and Cambodia. Results Malaria sero-prevalence was relatively low in all sites, with ELISA showing the highest estimates. The sensitivity of microscopy and ELISA were statistically lower in Vietnam than in the other sites. Similarly, the specificities of microscopy, ELISA and PCR were significantly lower in Vietnam than in the other sites. In Vietnam and Peru, microscopy was closer to the “true” estimate than the other 2 tests while as expected ELISA, with its lower specificity, usually overestimated the prevalence. Conclusions Bayesian methods are useful for analyzing prevalence results when no gold standard diagnostic test is available. Though some results are expected, e.g. PCR more sensitive than microscopy, a standardized and context-independent quantification of the diagnostic tests' characteristics (sensitivity and specificity) and the underlying malaria prevalence may be useful for comparing different sites. Indeed, the use of a single diagnostic technique could strongly bias the prevalence estimation. This limitation can be circumvented by using a Bayesian framework taking into account the imperfect characteristics of the currently available diagnostic tests. As discussed in the paper, this approach may further support global malaria burden estimation initiatives. PMID:21364745

Bayesian Correction for Misclassification in Multilevel Count Data Models.

PubMed

Nelson, Tyler; Song, Joon Jin; Chin, Yoo-Mi; Stamey, James D

2018-01-01

Covariate misclassification is well known to yield biased estimates in single level regression models. The impact on hierarchical count models has been less studied. A fully Bayesian approach to modeling both the misclassified covariate and the hierarchical response is proposed. Models with a single diagnostic test and with multiple diagnostic tests are considered. Simulation studies show the ability of the proposed model to appropriately account for the misclassification by reducing bias and improving performance of interval estimators. A real data example further demonstrated the consequences of ignoring the misclassification. Ignoring misclassification yielded a model that indicated there was a significant, positive impact on the number of children of females who observed spousal abuse between their parents. When the misclassification was accounted for, the relationship switched to negative, but not significant. Ignoring misclassification in standard linear and generalized linear models is well known to lead to biased results. We provide an approach to extend misclassification modeling to the important area of hierarchical generalized linear models.

Effect of Background Pressure on the Performance and Plume of the HiVHAc Hall Thruster

NASA Technical Reports Server (NTRS)

Huang, Wensheng; Kamhawi, Hani; Haag, Thomas

2013-01-01

During the Single String Integration Test of the NASA HiVHAc Hall thruster, a number of plasma diagnostics were implemented to study the effect of varying facility background pressure on thruster operation. These diagnostics include thrust stand, Faraday probe, ExB probe, and retarding potential analyzer. The test results indicated a rise in thrust and discharge current with background pressure. There was also a decrease in ion energy per charge, an increase in multiply-charged species production, a decrease in plume divergence, and a decrease in ion beam current with increasing background pressure. A simplified ingestion model was applied to determine the maximum acceptable background pressure for thrust measurement. The maximum acceptable ingestion percentage was found to be around 1%. Examination of the diagnostics results suggest the ionization and acceleration zones of the thruster were shifting upstream with increasing background pressure.

An enhancement to the NA4 gear vibration diagnostic parameter

NASA Technical Reports Server (NTRS)

Decker, Harry J.; Handschuh, Robert F.; Zakrajsek, James J.

1994-01-01

A new vibration diagnostic parameter for health monitoring of gears, NA4*, is proposed and tested. A recently developed gear vibration diagnostic parameter NA4 outperformed other fault detection methods at indicating the start and initial progression of damage. However, in some cases, as the damage progressed, the sensitivity of the NA4 and FM4 parameters tended to decrease and no longer indicated damage. A new parameter, NA4* was developed by enhancing NA4 to improve the trending of the parameter. This allows for the indication of damage both at initiation and also as the damage progresses. The NA4* parameter was verified and compared to the NA4 and FM4 parameters using experimental data from single mesh spur and spiral bevel gear fatigue rigs. The primary failure mode for the test cases was naturally occurring tooth surface pitting. The NA4* parameter is shown to be a more robust indicator of damage.

Evaluation of serological diagnostic tests for typhoid fever in Papua New Guinea using a composite reference standard.

PubMed

Siba, Valentine; Horwood, Paul F; Vanuga, Kilagi; Wapling, Johanna; Sehuko, Rebecca; Siba, Peter M; Greenhill, Andrew R

2012-11-01

Typhoid fever remains a major global health problem. A major impediment to improving outcomes is the lack of appropriate diagnostic tools, which have not significantly improved in low-income settings for 100 years. We evaluated two commercially available rapid diagnostic tests (Tubex and TyphiDot), a prototype (TyphiRapid TR-02), and the commonly used single-serum Widal test in a previously reported high-burden area of Papua New Guinea. Samples were collected from 530 outpatients with axillary temperatures of ≥37.5°C, and analysis was conducted on all malaria-negative samples (n = 500). A composite reference standard of blood culture and PCR was used, by which 47 participants (9.4%) were considered typhoid fever positive. The sensitivity and specificity of the Tubex (51.1% and 88.3%, respectively) and TyphiDot (70.0% and 80.1%, respectively) tests were not high enough to warrant their ongoing use in this setting; however, the sensitivity and specificity for the TR-02 prototype were promising (89.4% and 85.0%, respectively). An axillary temperature of ≥38.5°C correlated with typhoid fever (P = 0.014). With an appropriate diagnostic test, conducting typhoid fever diagnosis only on patients with high-grade fever could dramatically decrease the costs associated with diagnosis while having no detrimental impact on the ability to accurately diagnose the illness.

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders.

PubMed

Stark, Zornitza; Tan, Tiong Y; Chong, Belinda; Brett, Gemma R; Yap, Patrick; Walsh, Maie; Yeung, Alison; Peters, Heidi; Mordaunt, Dylan; Cowie, Shannon; Amor, David J; Savarirayan, Ravi; McGillivray, George; Downie, Lilian; Ekert, Paul G; Theda, Christiane; James, Paul A; Yaplito-Lee, Joy; Ryan, Monique M; Leventer, Richard J; Creed, Emma; Macciocca, Ivan; Bell, Katrina M; Oshlack, Alicia; Sadedin, Simon; Georgeson, Peter; Anderson, Charlotte; Thorne, Natalie; Melbourne Genomics Health Alliance; Gaff, Clara; White, Susan M

2016-11-01

To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease. Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated. Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies. This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

Neurocognitive pattern analysis reveals classificatory hierarchy of attention deficits in schizophrenia.

PubMed

Shen, Christina; Popescu, Florin C; Hahn, Eric; Ta, Tam T M; Dettling, Michael; Neuhaus, Andres H

2014-07-01

Attention deficits, among other cognitive deficits, are frequently observed in schizophrenia. Although valid and reliable neurocognitive tasks have been established to assess attention deficits in schizophrenia, the hierarchical value of those tests as diagnostic discriminants on a single-subject level remains unclear. Thus, much research is devoted to attention deficits that are unlikely to be translated into clinical practice. On the other hand, a clear hierarchy of attention deficits in schizophrenia could considerably aid diagnostic decisions and may prove beneficial for longitudinal monitoring of therapeutic advances. To propose a diagnostic hierarchy of attention deficits in schizophrenia, we investigated several facets of attention in 86 schizophrenia patients and 86 healthy controls using a set of established attention tests. We applied state-of-the-art machine learning algorithms to determine attentive test variables that enable an automated differentiation between schizophrenia patients and healthy controls. After feature preranking, hypothesis building, and hypothesis validation, the polynomial support vector machine classifier achieved a classification accuracy of 90.70% ± 2.9% using psychomotor speed and 3 different attention parameters derived from sustained and divided attention tasks. Our study proposes, to the best of our knowledge, the first hierarchy of attention deficits in schizophrenia by identifying the most discriminative attention parameters among a variety of attention deficits found in schizophrenia patients. Our results offer a starting point for hierarchy building of schizophrenia-associated attention deficits and contribute to translating these concepts into diagnostic and therapeutic practice on a single-subject level. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The Diagnostic Value of the Clarke Sign in Assessing Chondromalacia Patella

PubMed Central

Doberstein, Scott T; Romeyn, Richard L; Reineke, David M

2008-01-01

Context: Various techniques have been described for assessing conditions that cause pain at the patellofemoral (PF) joint. The Clarke sign is one such test, but the diagnostic value of this test in assessing chondromalacia patella is unknown. Objective: To (1) investigate the diagnostic value of the Clarke sign in assessing the presence of chondromalacia patella using arthroscopic examination of the PF joint as the “gold standard,” and (2) provide a historical perspective of the Clarke sign as a clinical diagnostic test. Design: Validation study. Setting: All patients of one of the investigators who had knee pain or injuries unrelated to the patellofemoral joint and were scheduled for arthroscopic surgery were recruited for this study. Patients or Other Participants: A total of 106 otherwise healthy individuals with no history of patellofemoral pain or dysfunction volunteered. Main Outcome Measure(s): The Clarke sign was performed on the surgical knee by a single investigator in the clinic before surgery. A positive test was indicated by the presence of pain sufficient to prevent the patient from maintaining a quadriceps muscle contraction against manual resistance for longer than 2 seconds. The preoperative result was compared with visual evidence of chondromalacia patella during arthroscopy. Results: Sensitivity was 0.39, specificity was 0.67, likelihood ratio for a positive test was 1.18, likelihood ratio for a negative test was 0.91, positive predictive value was 0.25, and negative predictive value was 0.80. Conclusions: Diagnostic validity values for the use of the Clarke sign in assessing chondromalacia patella were unsatisfactory, supporting suggestions that it has poor diagnostic value as a clinical examination technique. Additionally, an extensive search of the available literature for the Clarke sign reveals multiple problems with the test, causing significant confusion for clinicians. Therefore, the use of the Clarke sign as a routine part of a knee examination is not beneficial, and its use should be discontinued. PMID:18345345

The diagnostic value of the Clarke sign in assessing chondromalacia patella.

PubMed

Doberstein, Scott T; Romeyn, Richard L; Reineke, David M

2008-01-01

Various techniques have been described for assessing conditions that cause pain at the patellofemoral (PF) joint. The Clarke sign is one such test, but the diagnostic value of this test in assessing chondromalacia patella is unknown. To (1) investigate the diagnostic value of the Clarke sign in assessing the presence of chondromalacia patella using arthroscopic examination of the PF joint as the "gold standard," and (2) provide a historical perspective of the Clarke sign as a clinical diagnostic test. Validation study. All patients of one of the investigators who had knee pain or injuries unrelated to the patellofemoral joint and were scheduled for arthroscopic surgery were recruited for this study. A total of 106 otherwise healthy individuals with no history of patellofemoral pain or dysfunction volunteered. The Clarke sign was performed on the surgical knee by a single investigator in the clinic before surgery. A positive test was indicated by the presence of pain sufficient to prevent the patient from maintaining a quadriceps muscle contraction against manual resistance for longer than 2 seconds. The preoperative result was compared with visual evidence of chondromalacia patella during arthroscopy. Sensitivity was 0.39, specificity was 0.67, likelihood ratio for a positive test was 1.18, likelihood ratio for a negative test was 0.91, positive predictive value was 0.25, and negative predictive value was 0.80. Diagnostic validity values for the use of the Clarke sign in assessing chondromalacia patella were unsatisfactory, supporting suggestions that it has poor diagnostic value as a clinical examination technique. Additionally, an extensive search of the available literature for the Clarke sign reveals multiple problems with the test, causing significant confusion for clinicians. Therefore, the use of the Clarke sign as a routine part of a knee examination is not beneficial, and its use should be discontinued.

VLPs of HCV local isolates for HCV immunoassay diagnostic approach in Indonesia

NASA Astrophysics Data System (ADS)

Prasetyo, Afiono Agung

2017-01-01

Hepatitis C Virus (HCV) infection is a major global disease which often leads to morbidity and mortality. Low survival is related to the lack of adequate diagnostic because HCV infection is frequently asymptomatic and there are no specific diagnostic tests due to the fast transformation of the virus. Here, we investigated the VLPs (virus-like particles) of HCV local isolate as an immunoassay diagnostic approach to detect HCV infection, especially in Indonesia. The core, E1, and E2 of HCV local isolate genes were cloned and molecular analyzed, either as single or in recombinant-VLP form, to determine the molecular and chemical characteristics of each VLPs related to their potential use as an immunoassay detection method for HCV infection. The results indicated the molecular and chemical character of each VLPs are comparable. Conclusion: VLPs of HCV has the potential as an immunoassay diagnostic approach to detect HCV infection.

New directions in diagnostic evaluation of insect allergy.

PubMed

Golden, David B K

2014-08-01

Diagnosis of insect sting allergy and prediction of risk of sting anaphylaxis are often difficult because tests for venom-specific IgE antibodies have a limited positive predictive value and do not reliably predict the severity of sting reactions. Component-resolved diagnosis using recombinant venom allergens has shown promise in improving the specificity of diagnostic testing for insect sting allergy. Basophil activation tests have been explored as more sensitive assays for identification of patients with insect allergy and for prediction of clinical outcomes. Measurement of mast cell mediators reflects the underlying risk for more severe reactions and limited clinical response to treatment. Measurement of IgE to recombinant venom allergens can distinguish cross-sensitization from dual sensitization to honeybee and vespid venoms, thus helping to limit venom immunotherapy to a single venom instead of multiple venoms in many patients. Basophil activation tests can detect venom allergy in patients who show no detectable venom-specific IgE in standard diagnostic tests and can predict increased risk of systemic reactions to venom immunotherapy, and to stings during and after stopping venom immunotherapy. The risk of severe or fatal anaphylaxis to stings can also be predicted by measurement of baseline serum tryptase or other mast cell mediators.

Crack identification for reinforced concrete using PZT based smart rebar active sensing diagnostic network

NASA Astrophysics Data System (ADS)

Song, N. N.; Wu, F.

2016-04-01

An active sensing diagnostic system using PZT based smart rebar for SHM of RC structure has been currently under investigation. Previous test results showed that the system could detect the de-bond of concrete from reinforcement, and the diagnostic signals were increased exponentially with the de-bonding size. Previous study also showed that the smart rebar could function well like regular reinforcement to undertake tension stresses. In this study, a smart rebar network has been used to detect the crack damage of concrete based on guided waves. Experimental test has been carried out for the study. In the test, concrete beams with 2 reinforcements have been built. 8 sets of PZT elements were mounted onto the reinforcement bars in an optimized way to form an active sensing diagnostic system. A 90 kHz 5-cycle Hanning-windowed tone burst was used as input. Multiple cracks have been generated on the concrete structures. Through the guided bulk waves propagating in the structures from actuators and sensors mounted from different bars, crack damage could be detected clearly. Cases for both single and multiple cracks were tested. Different crack depths from the surface and different crack numbers have been studied. Test result shows that the amplitude of sensor output signals is deceased linearly with a propagating crack, and is decreased exponentially with increased crack numbers. From the study, the active sensing diagnostic system using PZT based smart rebar network shows a promising way to provide concrete crack damage information through the "talk" among sensors.

Multiple sclerosis - etiology and diagnostic potential.

PubMed

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Calibration techniques for a fast duo-spectrometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, J.T.; Den Hartog, D.J.

1996-06-01

The authors have completed the upgrade and calibration of the Ion Dynamics Spectrometer (IDS), a high-speed Doppler duo-spectrometer which measures ion flow and temperature in the MST Reversed-field Pinch. This paper describes an in situ calibration of the diagnostic`s phase and frequency response. A single clock was employed to generate both a digital test signal and a digitizer trigger thus avoiding frequency drift and providing a highly resolved measurement over the system bandwidth. Additionally, they review the measurement of the spectrometer instrument function and absolute intensity response. This calibration and subsequent performance demonstrate the IDS to be one of themore » fastest, highest throughput diagnostics of its kind. Typical measurements are presented.« less

Periprosthetic infection: where do we stand with regard to Gram stain?

PubMed

Ghanem, Elie; Ketonis, Constantinos; Restrepo, Camilo; Joshi, Ashish; Barrack, Robert; Parvizi, Javad

2009-02-01

One of the routinely used intraoperative tests for diagnosis of periprosthetic infection (PPI) is the Gram stain. It is not known if the result of this test can vary according to the type of joint affected or the number of specimen samples collected. We examined the role of this diagnostic test in a large cohort of patients from a single institution. A positive gram stain was defined as the visualization of bacterial cells or "many neutrophils" (> 5 per high-power field) in the smear. The sensitivity, specificity, and predictive values of each individual diagnostic arm of Gram stain were determined. Combinations were performed in series, which required both tests to be positive to confirm infection, and also in parallel, which necessitated both tests to be negative to rule out infection. The presence of organisms and "many" neutrophils on a Gram smear had high specificity (98-100%) and positive predictive value (89-100%) in both THA and TKA. The sensitivities (30-50%) and negative predictive values (70-79%) of the 2 tests were low for both joint types. When the 2 tests were combined in series, the specificity and positive predictive value were absolute (100%). The sensitivity and the negative predictive value improved for both THA and TKA (43-64% and 82%, respectively). Although the 2 diagnostic arms of Gram staining can be combined to achieve improved negative predictive value (82%), Gram stain continues to have little value in ruling out PPI. With the advances in the field of molecular biology, novel diagnostic modalities need to be designed that can replace these traditional and poor tests.

Aquifer test interpretation using derivative analysis and diagnostic plots

NASA Astrophysics Data System (ADS)

Hernández-Espriú, Antonio; Real-Rangel, Roberto; Cortés-Salazar, Iván; Castro-Herrera, Israel; Luna-Izazaga, Gabriela; Sánchez-León, Emilio

2017-04-01

Pumping tests remain a method of choice to deduce fundamental aquifer properties and to assess well condition. In the oil and gas (O&G) industry, well testing has been the core technique in examining reservoir behavior over the last 50 years. The pressure derivative by Bourdet, it is perhaps, the most significant single development in the history of well test analysis. Recently, the so-called diagnostics plots (e.g. drawdown and drawdown derivative in a log-log plot) have been successfully tested in aquifers. However, this procedure is still underutilized by groundwater professionals. This research illustrates the applicability range, advantages and drawbacks (e.g. smoothing procedures) of diagnostic plots using field examples from a wide spectrum of tests (short/long tests, constant/variable flow rates, drawdown/buildup stages, pumping well/observation well) in dissimilar geological conditions. We analyze new and pre-existent aquifer tests in Mexico, USA, Canada, Germany, France and Saudi Arabia. In constant flow rate tests, our results show that derivative analysis is an easy, robust and powerful tool to assess near-borehole damage effects, formation heterogeneity, boundaries, flow regimes, infinite-acting radial stages, i.e., valid Theisian framework, and fracture-driven flow. In step tests, the effectiveness relies on high-frequency drawdown measurements. Moreover, we adapt O&G analytical solutions to cater for the conditions in groundwater systems. In this context, further parameters can be computed analytically from the plots, such as skin factor, head losses, wellbore storage, distance to the boundary, channel-aquifer and/or fracture zone width, among others. Therefore, diagnostic plots should be considered a mandatory tool for pumping tests analysis among hydrogeologists. This project has been supported by DGAPA (UNAM) under the research project PAPIIT IN-112815.

Sensitivity, Specificity, Predictive Values, and Accuracy of Three Diagnostic Tests to Predict Inferior Alveolar Nerve Blockade Failure in Symptomatic Irreversible Pulpitis

PubMed Central

Rodríguez-Wong, Laura; Noguera-González, Danny; Esparza-Villalpando, Vicente; Montero-Aguilar, Mauricio

2017-01-01

Introduction The inferior alveolar nerve block (IANB) is the most common anesthetic technique used on mandibular teeth during root canal treatment. Its success in the presence of preoperative inflammation is still controversial. The aim of this study was to evaluate the sensitivity, specificity, predictive values, and accuracy of three diagnostic tests used to predict IANB failure in symptomatic irreversible pulpitis (SIP). Methodology A cross-sectional study was carried out on the mandibular molars of 53 patients with SIP. All patients received a single cartridge of mepivacaine 2% with 1 : 100000 epinephrine using the IANB technique. Three diagnostic clinical tests were performed to detect anesthetic failure. Anesthetic failure was defined as a positive painful response to any of the three tests. Sensitivity, specificity, predictive values, accuracy, and ROC curves were calculated and compared and significant differences were analyzed. Results IANB failure was determined in 71.7% of the patients. The sensitivity scores for the three tests (lip numbness, the cold stimuli test, and responsiveness during endodontic access) were 0.03, 0.35, and 0.55, respectively, and the specificity score was determined as 1 for all of the tests. Clinically, none of the evaluated tests demonstrated a high enough accuracy (0.30, 0.53, and 0.68 for lip numbness, the cold stimuli test, and responsiveness during endodontic access, resp.). A comparison of the areas under the curve in the ROC analyses showed statistically significant differences between the three tests (p < 0.05). Conclusion None of the analyzed tests demonstrated a high enough accuracy to be considered a reliable diagnostic tool for the prediction of anesthetic failure. PMID:28694714

2D imaging X-ray diagnostic for measuring the current density distribution in a wide-area electron beam produced in a multiaperture diode with plasma cathode

NASA Astrophysics Data System (ADS)

Kurkuchekov, V.; Kandaurov, I.; Trunev, Y.

2018-05-01

A simple and inexpensive X-ray diagnostic tool was designed for measuring the cross-sectional current density distribution in a low-relativistic pulsed electron beam produced in a source based on an arc-discharge plasma cathode and multiaperture diode-type electron optical system. The beam parameters were as follows: Uacc = 50–110 kV, Ibeam = 20–100 A, τbeam = 0.1–0.3 ms. The beam effective diameter was ca. 7 cm. Based on a pinhole camera, the diagnostic allows one to obtain a 2D profile of electron beam flux distribution on a flat metal target in a single shot. The linearity of the diagnostic system response to the electron flux density was established experimentally. Spatial resolution of the diagnostic was also estimated in special test experiments. The optimal choice of the main components of the diagnostic technique is discussed.

A single mini-barcode test to screen for Australian mammalian predators from environmental samples

PubMed Central

MacDonald, Anna J; Sarre, Stephen D

2017-01-01

Abstract Identification of species from trace samples is now possible through the comparison of diagnostic DNA fragments against reference DNA sequence databases. DNA detection of animals from non-invasive samples, such as predator faeces (scats) that contain traces of DNA from their species of origin, has proved to be a valuable tool for the management of elusive wildlife. However, application of this approach can be limited by the availability of appropriate genetic markers. Scat DNA is often degraded, meaning that longer DNA sequences, including standard DNA barcoding markers, are difficult to recover. Instead, targeted short diagnostic markers are required to serve as diagnostic mini-barcodes. The mitochondrial genome is a useful source of such trace DNA markers because it provides good resolution at the species level and occurs in high copy numbers per cell. We developed a mini-barcode based on a short (178 bp) fragment of the conserved 12S ribosomal ribonucleic acid mitochondrial gene sequence, with the goal of discriminating amongst the scats of large mammalian predators of Australia. We tested the sensitivity and specificity of our primers and can accurately detect and discriminate amongst quolls, cats, dogs, foxes, and devils from trace DNA samples. Our approach provides a cost-effective, time-efficient, and non-invasive tool that enables identification of all 8 medium-large mammal predators in Australia, including native and introduced species, using a single test. With modification, this approach is likely to be of broad applicability elsewhere. PMID:28810700

Detecting gear tooth fracture in a high contact ratio face gear mesh

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.; Handschuh, Robert F.; Lewicki, David G.; Decker, Harry J.

1995-01-01

This paper summarized the results of a study in which three different vibration diagnostic methods were used to detect gear tooth fracture in a high contact ratio face gear mesh. The NASA spiral bevel gear fatigue test rig was used to produce unseeded fault, natural failures of four face gear specimens. During the fatigue tests, which were run to determine load capacity and primary failure mechanisms for face gears, vibration signals were monitored and recorded for gear diagnostic purposes. Gear tooth bending fatigue and surface pitting were the primary failure modes found in the tests. The damage ranged from partial tooth fracture on a single tooth in one test to heavy wear, severe pitting, and complete tooth fracture of several teeth on another test. Three gear fault detection techniques, FM4, NA4*, and NB4, were applied to the experimental data. These methods use the signal average in both the time and frequency domain. Method NA4* was able to conclusively detect the gear tooth fractures in three out of the four fatigue tests, along with gear tooth surface pitting and heavy wear. For multiple tooth fractures, all of the methods gave a clear indication of the damage. It was also found that due to the high contact ratio of the face gear mesh, single tooth fractures did not significantly affect the vibration signal, making this type of failure difficult to detect.

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

PubMed

Pena, Loren D M; Jiang, Yong-Hui; Schoch, Kelly; Spillmann, Rebecca C; Walley, Nicole; Stong, Nicholas; Rapisardo Horn, Sarah; Sullivan, Jennifer A; McConkie-Rosell, Allyn; Kansagra, Sujay; Smith, Edward C; El-Dairi, Mays; Bellet, Jane; Keels, Martha Ann; Jasien, Joan; Kranz, Peter G; Noel, Richard; Nagaraj, Shashi K; Lark, Robert K; Wechsler, Daniel S G; Del Gaudio, Daniela; Leung, Marco L; Hendon, Laura G; Parker, Collette C; Jones, Kelly L; Goldstein, David B; Shashi, Vandana

2018-04-01

PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses.

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases

PubMed Central

Pena, Loren DM; Jiang, Yong-Hui; Schoch, Kelly; Spillmann, Rebecca C.; Walley, Nicole; Stong, Nicholas; Horn, Sarah Rapisardo; Sullivan, Jennifer A.; McConkie-Rosell, Allyn; Kansagra, Sujay; Smith, Edward C.; El-Dairi, Mays; Bellet, Jane; Ann Keels, Martha; Jasien, Joan; Kranz, Peter G.; Noel, Richard; Nagaraj, Shashi K.; Lark, Robert K.; Wechsler, Daniel SG; del Gaudio, Daniela; Leung, Marco L.; Hendon, Laura G.; Parker, Collette C.; Jones, Kelly L.; Goldstein, David B.; Shashi, Vandana

2017-01-01

Purpose To describe examples of missed pathogenic variants on whole exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing. Methods Guided by phenotypic information, three children with negative WES underwent targeted single gene testing. Results Individual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and an NGS-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the non-coding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity and MRI changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, likely missed due to failure of alignment. Conclusions These cases illustrate potential pitfalls of WES/NGS testing, and the importance of phenotype-guided molecular testing in yielding diagnoses. PMID:28914269

Causes of vomiting in dogs and usefulness of clinical investigations.

PubMed

Rosé, A; Neiger, R

2013-01-01

To find the most common diagnoses of dogs where vomiting was the main reason for referral and to determine the usefulness of various diagnostic investigations. 213 dogs referred for vomiting as main or one of the main causes were analysed retrospectively. Diagnosis was reassessed and categorized into six groups, namely gastrointestinal, systemic, non-gastrointestinal abdominal, neurological, miscellaneous or no diagnosis. All diagnostic investigations were reviewed to assess their usefulness to reach a diagnosis. The usefulness of a diagnostic investigation was scored into the following four groups: enabled a diagnosis; assisted a diagnosis; no assistance, diagnosis reached by another procedure; no assistance, no final diagnosis made. In 203 dogs (95.3%) a diagnosis was reached and was categorised as gastrointestinal (43.7%), systemic (27.7%), non-gastrointestinal abdominal (16.4%), neurological (1.4%) and miscellaneous (6.1%). Laboratory tests enabling or assisting a diagnosis as blood tests in 12.2%; 26.8%, as faecal analysis in 6.6%; 1.4%, as ultrasound in 5.2%; 17%, as cytology in 3.3%; 4.2%, as urinalysis in 2.3%; 9.9% and as radiographs in 1.9%; 8.5% of all cases. Overall, there was a high incidence of dogs referred for vomiting with non-gastrointestinal diseases. Amongst them, renal problems were most commonly seen, which emphasises the need to perform a urinalysis in most dogs with vomiting as major complaint. However, vomiting can be due to a large variety of underlying pathophysiological mechanisms and no single problem seems to be much more common compared to other problems in a referral institution. Based on this investigation it is not possible to clearly state a most useful single diagnostic test in dogs with emesis, however, it could clearly been shown that more than one test is often needed to reach a final diagnosis. This is important for owners to understand but also for referring veterinarians.

A Perturbation Based Decomposition of Compound-Evoked Potentials for Characterization of Nerve Fiber Size Distributions.

PubMed

Szlavik, Robert B

2016-02-01

The characterization of peripheral nerve fiber distributions, in terms of diameter or velocity, is of clinical significance because information associated with these distributions can be utilized in the differential diagnosis of peripheral neuropathies. Electro-diagnostic techniques can be applied to the investigation of peripheral neuropathies and can yield valuable diagnostic information while being minimally invasive. Nerve conduction velocity studies are single parameter tests that yield no detailed information regarding the characteristics of the population of nerve fibers that contribute to the compound-evoked potential. Decomposition of the compound-evoked potential, such that the velocity or diameter distribution of the contributing nerve fibers may be determined, is necessary if information regarding the population of contributing nerve fibers is to be ascertained from the electro-diagnostic study. In this work, a perturbation-based decomposition of compound-evoked potentials is proposed that facilitates determination of the fiber diameter distribution associated with the compound-evoked potential. The decomposition is based on representing the single fiber-evoked potential, associated with each diameter class, as being perturbed by contributions, of varying degree, from all the other diameter class single fiber-evoked potentials. The resultant estimator of the contributing nerve fiber diameter distribution is valid for relatively large separations in diameter classes. It is also useful in situations where the separation between diameter classes is small and the concomitant single fiber-evoked potentials are not orthogonal.

Fan fault diagnosis based on symmetrized dot pattern analysis and image matching

NASA Astrophysics Data System (ADS)

Xu, Xiaogang; Liu, Haixiao; Zhu, Hao; Wang, Songling

2016-07-01

To detect the mechanical failure of fans, a new diagnostic method based on the symmetrized dot pattern (SDP) analysis and image matching is proposed. Vibration signals of 13 kinds of running states are acquired on a centrifugal fan test bed and reconstructed by the SDP technique. The SDP pattern templates of each running state are established. An image matching method is performed to diagnose the fault. In order to improve the diagnostic accuracy, the single template, multiple templates and clustering fault templates are used to perform the image matching.

Demystifying the Clinical Diagnosis of Greater Trochanteric Pain Syndrome in Women.

PubMed

Ganderton, Charlotte; Semciw, Adam; Cook, Jill; Pizzari, Tania

2017-06-01

To evaluate the diagnostic accuracy of 10 clinical tests that can be used in the diagnosis of greater trochanteric pain syndrome (GTPS) in women, and to compare these clinical tests to magnetic resonance imaging (MRI) findings. Twenty-eight participants with GTPS (49.5 ± 22.0 years) and 18 asymptomatic participants (mean age ± standard deviation [SD], 52.5 ± 22.8 years) were included. A blinded physiotherapist performed 10 pain provocation tests potentially diagnostic for GTPS-palpation of the greater trochanter, resisted external derotation test, modified resisted external derotation test, standard and modified Ober's tests, Patrick's or FABER test, resisted hip abduction, single-leg stance test, and the resisted hip internal rotation test. A sample of 16 symptomatic and 17 asymptomatic women undertook a hip MRI scan. Gluteal tendons were evaluated and categorized as no pathology, mild tendinosis, moderate tendinosis/partial tear, or full-thickness tear. Clinical test analyses show high specificity, high positive predictive value, low to moderate sensitivity, and negative predictive value for most clinical tests. All symptomatic and 88% of asymptomatic participants had pathological gluteal tendon changes on MRI, from mild tendinosis to full-thickness tear. The study found the Patrick's or FABER test, palpation of the greater trochanter, resisted hip abduction, and the resisted external derotation test to have the highest diagnostic test accuracy for GTPS. Tendon pathology on MRI is seen in both symptomatic and asymptomatic women.

Survey of diagnostic tools for detection of viroids and impacts of test results on the seed industry

USDA-ARS?s Scientific Manuscript database

Viroids are unencapsidated, single-stranded, covalently closed circular, highly structured noncoding RNAs of 239 – 401 nucleotides that are replicated by host enzymes and cause disease in several economically important crop plants. Although viroids are primarily and easily transmitted mechanically t...

Multispectral optical tweezers for molecular diagnostics of single biological cells

NASA Astrophysics Data System (ADS)

Butler, Corey; Fardad, Shima; Sincore, Alex; Vangheluwe, Marie; Baudelet, Matthieu; Richardson, Martin

2012-03-01

Optical trapping of single biological cells has become an established technique for controlling and studying fundamental behavior of single cells with their environment without having "many-body" interference. The development of such an instrument for optical diagnostics (including Raman and fluorescence for molecular diagnostics) via laser spectroscopy with either the "trapping" beam or secondary beams is still in progress. This paper shows the development of modular multi-spectral imaging optical tweezers combining Raman and Fluorescence diagnostics of biological cells.

Comparison of the Performance of Skin Prick, ImmunoCAP, and ISAC Tests in the Diagnosis of Patients with Allergy.

PubMed

Griffiths, Rebecca L M; El-Shanawany, Tariq; Jolles, Stephen R A; Selwood, Clive; Heaps, Adrian G; Carne, Emily M; Williams, Paul E

2017-01-01

Allergy is diagnosed from typical symptoms, and tests are performed to incriminate the suspected precipitant. Skin prick tests (SPTs) are commonly performed, inexpensive, and give immediate results. Laboratory tests (ImmunoCAP) for serum allergen-specific IgE antibodies are usually performed more selectively. The immuno-solid phase allergen chip (ISAC) enables testing for specific IgE against multiple allergen components in a multiplex assay. We retrospectively analysed clinic letters, case notes, and laboratory results of 118 patients attending the National Adult Allergy Service at the University Hospital of Wales who presented diagnostic difficulty, to evaluate which testing strategy (SPT, ImmunoCAP, or ISAC) was the most appropriate to use to confirm the diagnosis in these complex patients, evaluated in a "real-life" clinical service setting. In patients with nut allergy, the detection rates of SPTs (56%) and ISAC (65%) were lower than those of ImmunoCAP (71%). ISAC had a higher detection rate (88%) than ImmunoCAP (69%) or SPT (33%) in the diagnosis of oral allergy syndrome. ImmunoCAP test results identified all 9 patients with anaphylaxis due to wheat allergy (100%), whereas ISAC was positive in only 6 of these 9 (67%). In this difficult diagnostic group, the ImmunoCAP test should be the preferred single test for possible allergy to nuts, wheat, other specific foods, and anaphylaxis of any cause. In these conditions, SPT and ISAC tests give comparable results. The most useful single test for oral allergy syndrome is ISAC, and SPT should be the preferred test for latex allergy. © 2017 S. Karger AG, Basel.

Assessment of the Usefulness of Multiplex Real-Time PCR Tests in the Diagnostic and Therapeutic Process of Pneumonia in Hospitalized Children: A Single-Center Experience.

PubMed

Gowin, Ewelina; Bartkowska-Śniatkowska, Alicja; Jończyk-Potoczna, Katarzyna; Wysocka-Leszczyńska, Joanna; Bobkowski, Waldemar; Fichna, Piotr; Sobkowiak, Paulina; Mazur-Melewska, Katarzyna; Bręborowicz, Anna; Wysocki, Jacek; Januszkiewicz-Lewandowska, Danuta

2017-01-01

The aim of the study was assessment of the usefulness of multiplex real-time PCR tests in the diagnostic and therapeutic process in children hospitalized due to pneumonia and burdened with comorbidities. Methods . The study group included 97 children hospitalized due to pneumonia at the Karol Jonscher Teaching Hospital in Poznań, in whom multiplex real-time PCR tests (FTD respiratory pathogens 33; fast-track diagnostics) were used. Results . Positive test results of the test were achieved in 74 patients (76.3%). The average age in the group was 56 months. Viruses were detected in 61 samples (82% of all positive results); bacterial factors were found in 29 samples (39% of all positive results). The presence of comorbidities was established in 90 children (92.78%). On the basis of the obtained results, 5 groups of patients were established: viral etiology of infection, 34 patients; bacterial etiology, 7 patients; mixed etiology, 23 patients; pneumocystis, 9 patients; and no etiology diagnosed, 24 patients. Conclusions . Our analysis demonstrated that the participation of viruses in causing severe lung infections is significant in children with comorbidities. Multiplex real-time PCR tests proved to be more useful in establishing the etiology of pneumonia in hospitalized children than the traditional microbiological examinations.

Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?

PubMed

Ooi, Chee Y; Dupuis, Annie; Ellis, Lynda; Jarvi, Keith; Martin, Sheelagh; Ray, Peter N; Steele, Leslie; Kortan, Paul; Gonska, Tanja; Dorfman, Ruslan; Solomon, Melinda; Zielenski, Julian; Corey, Mary; Tullis, Elizabeth; Durie, Peter

2014-03-01

The phenotypic spectrum of cystic fibrosis (CF) has expanded to include patients affected by single-organ diseases. Extensive genotyping and nasal potential difference (NPD) testing have been proposed to assist in the diagnosis of CF when sweat testing is inconclusive. However, the diagnostic yield of extensive genotyping and NPD and the concordance between NPD and the sweat test have not been carefully evaluated. We evaluated the diagnostic outcomes of genotyping (with 122 mutations included as disease causing), sweat testing and NPD in a prospectively ascertained cohort of undiagnosed patients who presented with chronic sino-pulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP). 202 patients (68 RESP, 42 PANC and 92 AZOOSP) were evaluated; 17.3%, 22.8% and 59.9% had abnormal, borderline and normal sweat chloride results, respectively. Only 17 (8.4%) patients were diagnosable as having CF by genotyping. Compared to sweat testing, NPD identified more patients as having CF (33.2%) with fewer borderline results (18.8%). The level of agreement according to kappa statistics (and the observed percentage of agreement) between sweat chloride and NPD in RESP, PANC and AZOOSP subjects was 'moderate' (65% observed agreement), 'poor' (33% observed agreement) and 'fair' (28% observed agreement), respectively. The degree of agreement only improved marginally when subjects with borderline sweat chloride results were excluded from the analysis. The diagnosis of CF or its exclusion is not always straightforward and may remain elusive even with comprehensive evaluation, particularly among individuals who present at an older age with single-organ manifestations suggestive of CF.

Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents.

PubMed

Broger, Tobias; Basu Roy, Robindra; Filomena, Angela; Greef, Charles H; Rimmele, Stefanie; Havumaki, Joshua; Danks, David; Schneiderhan-Marra, Nicole; Gray, Christen M; Singh, Mahavir; Rosenkrands, Ida; Andersen, Peter; Husar, Gregory M; Joos, Thomas O; Gennaro, Maria L; Lochhead, Michael J; Denkinger, Claudia M; Perkins, Mark D

2017-04-01

Development of rapid diagnostic tests for tuberculosis is a global priority. A whole proteome screen identified Mycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. We used World Health Organization (WHO) target product profile (TPP) criteria for a detection test and triage test to evaluate these antigens. Consecutive patients presenting to microscopy centers and district hospitals in Peru and to outpatient clinics at a tuberculosis reference center in Vietnam were recruited. We tested blood samples from 755 HIV-uninfected adults with presumptive pulmonary tuberculosis to measure IgG antibody responses to 57 M. tuberculosis antigens using a field-based multiplexed serological assay and a 132-antigen bead-based reference assay. We evaluated single antigen performance and models of all possible 3-antigen combinations and multiantigen combinations. Three-antigen and multiantigen models performed similarly and were superior to single antigens. With specificity set at 90% for a detection test, the best sensitivity of a 3-antigen model was 35% (95% confidence interval [CI], 31-40). With sensitivity set at 85% for a triage test, the specificity of the best 3-antigen model was 34% (95% CI, 29-40). The reference assay also did not meet study targets. Antigen performance differed significantly between the study sites for 7/22 of the best-performing antigens. Although M. tuberculosis antigens were recognized by the IgG response during tuberculosis, no single antigen or multiantigen set performance approached WHO TPP criteria for clinical utility among HIV-uninfected adults with presumed tuberculosis in high-volume, urban settings in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Paraneoplastic autoantibody panels: sensitivity and specificity, a retrospective cohort.

PubMed

Albadareen, Rawan; Gronseth, Gary; Goeden, Marcie; Sharrock, Matthew; Lechtenberg, Colleen; Wang, Yunxia

2017-06-01

Experts in the autoimmune paraneoplastic field recommend autoantibody testing as "panels" to improve the poor sensitivity of individual autoantibodies in detecting paraneoplastic neurological syndromes (PNS). The sensitivity of those panels was not reported to date in a fashion devoid of incorporation bias. We aimed to assess the collective sensitivity and specificity of one of the commonly used panels in detecting PNS. A single-centered retrospective cohort of all patients tested for paraneoplastic evaluation panel (PAVAL; test ID: 83380) over one year for the suspicion of PNS. Case adjudication was based on newly proposed diagnostic criteria in line with previously published literature, but modified to exclude serological status to avoid incorporation bias. Measures of diagnostic accuracy were subsequently calculated. Cases that failed to show association with malignancy within the follow-up time studied, reflecting a possibly pure autoimmune process was considered paraneoplastic-like syndromes. Out of 321 patients tested, 51 patients tested positive. Thirty-two patients met diagnostic criteria for paraneoplastic/paraneoplastic-like syndromes. The calculated collective sensitivity was 34% (95% CI: 17-53), specificity was 86% (95% CI: 81-90), Youden's index 0.2 and a positive clinical utility index 0.07 suggesting poor utility for case-detection. This is the first reported diagnostic accuracy measures of paraneoplastic panels without incorporation bias. Despite recommended panel testing to improve detection of PNS, sensitivity remains low with poor utility for case-detection. The high-calculated specificity suggests a possible role in confirming the condition in difficult cases suspicious for PNS, when enough supportive evidence is lacking on ancillary testing.

Dust measurements in tokamaks (invited).

PubMed

Rudakov, D L; Yu, J H; Boedo, J A; Hollmann, E M; Krasheninnikov, S I; Moyer, R A; Muller, S H; Pigarov, A Yu; Rosenberg, M; Smirnov, R D; West, W P; Boivin, R L; Bray, B D; Brooks, N H; Hyatt, A W; Wong, C P C; Roquemore, A L; Skinner, C H; Solomon, W M; Ratynskaia, S; Fenstermacher, M E; Groth, M; Lasnier, C J; McLean, A G; Stangeby, P C

2008-10-01

Dust production and accumulation present potential safety and operational issues for the ITER. Dust diagnostics can be divided into two groups: diagnostics of dust on surfaces and diagnostics of dust in plasma. Diagnostics from both groups are employed in contemporary tokamaks; new diagnostics suitable for ITER are also being developed and tested. Dust accumulation in ITER is likely to occur in hidden areas, e.g., between tiles and under divertor baffles. A novel electrostatic dust detector for monitoring dust in these regions has been developed and tested at PPPL. In the DIII-D tokamak dust diagnostics include Mie scattering from Nd:YAG lasers, visible imaging, and spectroscopy. Laser scattering is able to resolve particles between 0.16 and 1.6 microm in diameter; using these data the total dust content in the edge plasmas and trends in the dust production rates within this size range have been established. Individual dust particles are observed by visible imaging using fast framing cameras, detecting dust particles of a few microns in diameter and larger. Dust velocities and trajectories can be determined in two-dimension with a single camera or three-dimension using multiple cameras, but determination of particle size is challenging. In order to calibrate diagnostics and benchmark dust dynamics modeling, precharacterized carbon dust has been injected into the lower divertor of DIII-D. Injected dust is seen by cameras, and spectroscopic diagnostics observe an increase in carbon line (CI, CII, C(2) dimer) and thermal continuum emissions from the injected dust. The latter observation can be used in the design of novel dust survey diagnostics.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudakov, D. L.; Yu, J. H.; Boedo, J. A.

Dust production and accumulation present potential safety and operational issues for the ITER. Dust diagnostics can be divided into two groups: diagnostics of dust on surfaces and diagnostics of dust in plasma. Diagnostics from both groups are employed in contemporary tokamaks; new diagnostics suitable for ITER are also being developed and tested. Dust accumulation in ITER is likely to occur in hidden areas, e.g., between tiles and under divertor baffles. A novel electrostatic dust detector for monitoring dust in these regions has been developed and tested at PPPL. In the DIII-D tokamak dust diagnostics include Mie scattering from Nd:YAG lasers,more » visible imaging, and spectroscopy. Laser scattering is able to resolve particles between 0.16 and 1.6 {mu}m in diameter; using these data the total dust content in the edge plasmas and trends in the dust production rates within this size range have been established. Individual dust particles are observed by visible imaging using fast framing cameras, detecting dust particles of a few microns in diameter and larger. Dust velocities and trajectories can be determined in two-dimension with a single camera or three-dimension using multiple cameras, but determination of particle size is challenging. In order to calibrate diagnostics and benchmark dust dynamics modeling, precharacterized carbon dust has been injected into the lower divertor of DIII-D. Injected dust is seen by cameras, and spectroscopic diagnostics observe an increase in carbon line (CI, CII, C{sub 2} dimer) and thermal continuum emissions from the injected dust. The latter observation can be used in the design of novel dust survey diagnostics.« less

[The use of the orthostatic test for determining the work capacity of convalescents].

PubMed

Reshetiuk, A L; Volkova, P S; Zemskaia, L I; Gdal', V A

1990-06-01

The course of responses to the orthostatic test is analyzed in convalescents with a history of different diseases. Diagnostic factors were singled out characteristic of different groups of diseases including values of the cardiovascular, neuromuscular systems of the body. On the basis of obtained data a decimal classification of the working capacity of convalescents was worked out by their reaction to orthostatic effects.

Diagnostic accuracy of the Thessaly test, standardised clinical history and other clinical examination tests (Apley's, McMurray's and joint line tenderness) for meniscal tears in comparison with magnetic resonance imaging diagnosis.

PubMed

Blyth, Mark; Anthony, Iain; Francq, Bernard; Brooksbank, Katriona; Downie, Paul; Powell, Andrew; Jones, Bryn; MacLean, Angus; McConnachie, Alex; Norrie, John

2015-08-01

Reliable non-invasive diagnosis of meniscal tears is difficult. Magnetic resonance imaging (MRI) is often used but is expensive and incidental findings are problematic. There are a number of physical examination tests for the diagnosis of meniscal tears that are simple, cheap and non-invasive. To determine the diagnostic accuracy of the Thessaly test and to determine if the Thessaly test (alone or in combination with other physical tests) can obviate the need for further investigation by MRI or arthroscopy for patients with a suspected meniscal tear. Single-centre prospective diagnostic accuracy study. Although the study was performed in a secondary care setting, it was designed to replicate the results that would have been achieved in a primary care setting. Two cohorts of patients were recruited: patients with knee pathology (n = 292) and a control cohort with no knee pathology (n = 75). Sensitivity, specificity and diagnostic accuracy of the Thessaly test in determining the presence of meniscal tears. Participants were assessed by both a primary care clinician and a musculoskeletal clinician. Both clinicians performed the Thessaly test, McMurray's test, Apley's test, joint line tenderness test and took a standardised clinical history from the patient. The Thessaly test had a sensitivity of 0.66, a specificity of 0.39 and a diagnostic accuracy of 54% when utilised by primary care clinicians. This compared with a sensitivity of 0.62, a specificity of 0.55 and diagnostic accuracy of 59% when used by musculoskeletal clinicians. The diagnostics accuracy of the other tests when used by primary care clinicians was 54% for McMurray's test, 53% for Apley's test, 54% for the joint line tenderness test and 55% for clinical history. For primary care clinicians, age and past history of osteoarthritis were both significant predictors of MRI diagnosis of meniscal tears. For musculoskeletal clinicians age and a positive diagnosis of meniscal tears on clinical history taking were significant predictors of MRI diagnosis. No physical tests were significant predictors of MRI diagnosis in our multivariate models. The specificity of MRI diagnosis was tested in subgroup of patients who went on to have a knee arthroscopy and was found to be low [0.53 (95% confidence interval 0.28 to 0.77)], although the sensitivity was 1.0. The Thessaly test was no better at diagnosing meniscal tears than other established physical tests. The sensitivity, specificity and diagnostic accuracy of all physical tests was too low to be of routine clinical value as an alternative to MRI. Caution needs to be exercised in the indiscriminate use of MRI scanning in the identification of meniscal tears in the diagnosis of the painful knee, due to the low specificity seen in the presence of concomitant knee pathology. Further research is required to determine the true diagnostic accuracy and cost-effectiveness of MRI for the detection of meniscal tears. Current Controlled Trial ISRCTN43527822. The National Institute for Health Research Health Technology Assessment programme.

Superior Diagnostic Performance of Malaria Rapid Diagnostic Tests as compared to Blood Smears in U.S. Clinical Practice

PubMed Central

Stauffer, William M.; Cartwright, Charles P.; Olson, Douglas; Juni, Billie Anne; Taylor, Charlotte M; Bowers, Susan H.; Hanson, Kevan L.; Rosenblatt, Jon E.; Boulware, David R.

2010-01-01

Background Approximately 4 million U.S. travelers to developing countries are ill enough to seek healthcare with 1,500 malaria cases reported in the U.S. annually. The diagnosis of malaria is frequently delayed due to the time to prepare malaria blood films and lack of technical expertise. An easy, reliable rapid diagnostic test (RDT) with high sensitivity and negative predictive value (NPV), particularly for Plasmodium falciparum, would be clinically useful. The study objective was to determine the diagnostic performance of the FDA-approved NOW® Malaria Test in comparison to traditional thick and thin blood smears for malaria diagnosis. Methods This prospective study tested 852 consecutive blood samples sent for thick and thin smears with blinded, malaria rapid tests at three hospital laboratories during 2003–2006. Polymerase chain reaction (PCR) verified positive tests and discordant results. Results Malaria occurred in 11% (95/852). The rapid test had superior performance than the standard Giemsa thick blood smear (P=.003). The rapid test’s sensitivity for all malaria was 97% (92/95) vs. 85% (81/95) by blood smear, and the RDT had superior NPV of 99.6% vs. 98.2% (P=.001). The P. falciparum performance was excellent with 100% rapid test sensitivity versus only 88% (65/74) by blood smear (P=.003). Conclusions This operational study demonstrates the FDA-approved rapid malaria test is superior to a single set of blood smears performed under routine U.S. clinical laboratory conditions. The most valuable clinical role of the RDT is in the rapid diagnosis or the exclusion of P. falciparum malaria, which is particularly useful in outpatient settings when evaluating febrile travelers. PMID:19686072

Multiple dopant injection system for small rocket engines

NASA Technical Reports Server (NTRS)

Sakala, G. G.; Raines, N. G.

1992-01-01

The Diagnostics Test Facility (DTF) at NASA's Stennis Space Center (SSC) was designed and built to provide a standard rocket engine exhaust plume for use in the research and development of engine health monitoring instrumentation. A 1000 lb thrust class liquid oxygen (LOX)-gaseous hydrogen (GH2) fueled rocket engine is used as the subscale plume source to simulate the SSME during experimentation and instrument development. The ability of the DTF to provide efficient, and low cost test operations makes it uniquely suited for plume diagnostic experimentation. The most unique feature of the DTF is the Multiple Dopant Injection System (MDIS) that is used to seed the exhaust plume with the desired element or metal alloy. The dopant injection takes place at the fuel injector, yielding a very uniform and homogeneous distribution of the seeding material in the exhaust plume. The MDIS allows during a single test firing of the DTF, the seeding of the exhaust plume with up to three different dopants and also provides distilled water base lines between the dopants. A number of plume diagnostic-related experiments have already utilized the unique capabilities of the DTF.

Loopback Tester: a synchronous communications circuit diagnostic device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maestas, J.H.

1986-07-01

The Loopback Tester is an Intel SBC 86/12A Single Board Computer and an Intel SBC 534 Communications Expansion Board configured and programmed to perform various basic or less. These tests include: (1) Data Communications Equipment (DCE) transmit timing detection (2) data rate measurement (3) instantaneous loopback indication and (4) bit error rate testing. It requires no initial setup after plug in, and can be used to locate the source of communications loss in a circuit. It can also be used to determine when crypto variable mismatch problems are the source of communications loss. This report discusses the functionality of themore » Loopback Tester as a diagnostic device. It also discusses the hardware and software which implements this simple yet reliable device.« less

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

PubMed Central

2013-01-01

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology. PMID:24090398

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.

PubMed

Canonica, Giorgio Walter; Ansotegui, Ignacio J; Pawankar, Ruby; Schmid-Grendelmeier, Peter; van Hage, Marianne; Baena-Cagnani, Carlos E; Melioli, Giovanni; Nunes, Carlos; Passalacqua, Giovanni; Rosenwasser, Lanny; Sampson, Hugh; Sastre, Joaquin; Bousquet, Jean; Zuberbier, Torsten

2013-10-03

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.

Clinical utility of a single-item test for DSM-5 alcohol use disorder among outpatients with anxiety and depressive disorders.

PubMed

Bartoli, Francesco; Crocamo, Cristina; Biagi, Enrico; Di Carlo, Francesco; Parma, Francesca; Madeddu, Fabio; Capuzzi, Enrico; Colmegna, Fabrizia; Clerici, Massimo; Carrà, Giuseppe

2016-08-01

There is a lack of studies testing accuracy of fast screening methods for alcohol use disorder in mental health settings. We aimed at estimating clinical utility of a standard single-item test for case finding and screening of DSM-5 alcohol use disorder among individuals suffering from anxiety and mood disorders. We recruited adults consecutively referred, in a 12-month period, to an outpatient clinic for anxiety and depressive disorders. We assessed the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single-item test, using the Mini- International Neuropsychiatric Interview (MINI), plus an additional item of Composite International Diagnostic Interview (CIDI) for craving, as reference standard to diagnose a current DSM-5 alcohol use disorder. We estimated sensitivity and specificity of the single-item test, as well as positive and negative Clinical Utility Indexes (CUIs). 242 subjects with anxiety and mood disorders were included. The NIAAA single-item test showed high sensitivity (91.9%) and specificity (91.2%) for DSM-5 alcohol use disorder. The positive CUI was 0.601, whereas the negative one was 0.898, with excellent values also accounting for main individual characteristics (age, gender, diagnosis, psychological distress levels, smoking status). Testing for relevant indexes, we found an excellent clinical utility of the NIAAA single-item test for screening true negative cases. Our findings support a routine use of reliable methods for rapid screening in similar mental health settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

PubMed

Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

2016-07-01

New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

An approach to analyzing a single subject's scores obtained in a standardized test with application to the Aachen Aphasia Test (AAT).

PubMed

Willmes, K

1985-08-01

Methods for the analysis of a single subject's test profile(s) proposed by Huber (1973) are applied to the Aachen Aphasia Test (AAT). The procedures are based on the classical test theory model (Lord & Novick, 1968) and are suited for any (achievement) test with standard norms from a large standardization sample and satisfactory reliability estimates. Two test profiles of a Wernicke's aphasic, obtained before and after a 3-month period of speech therapy, are analyzed using inferential comparisons between (groups of) subtest scores on one test application and between two test administrations for single (groups of) subtests. For each of these comparisons, the two aspects of (i) significant (reliable) differences in performance beyond measurement error and (ii) the diagnostic validity of that difference in the reference population of aphasic patients are assessed. Significant differences between standardized subtest scores and a remarkably better preserved reading and writing ability could be found for both test administrations using the multiple test procedure of Holm (1979). Comparison of both profiles revealed an overall increase in performance for each subtest as well as changes in level of performance relations between pairs of subtests.

Identification of facilitators and barriers to residents' use of a clinical reasoning tool.

PubMed

DiNardo, Deborah; Tilstra, Sarah; McNeil, Melissa; Follansbee, William; Zimmer, Shanta; Farris, Coreen; Barnato, Amber E

2018-03-28

While there is some experimental evidence to support the use of cognitive forcing strategies to reduce diagnostic error in residents, the potential usability of such strategies in the clinical setting has not been explored. We sought to test the effect of a clinical reasoning tool on diagnostic accuracy and to obtain feedback on its usability and acceptability. We conducted a randomized behavioral experiment testing the effect of this tool on diagnostic accuracy on written cases among post-graduate 3 (PGY-3) residents at a single internal medical residency program in 2014. Residents completed written clinical cases in a proctored setting with and without prompts to use the tool. The tool encouraged reflection on concordant and discordant aspects of each case. We used random effects regression to assess the effect of the tool on diagnostic accuracy of the independent case sets, controlling for case complexity. We then conducted audiotaped structured focus group debriefing sessions and reviewed the tapes for facilitators and barriers to use of the tool. Of 51 eligible PGY-3 residents, 34 (67%) participated in the study. The average diagnostic accuracy increased from 52% to 60% with the tool, a difference that just met the test for statistical significance in adjusted analyses (p=0.05). Residents reported that the tool was generally acceptable and understandable but did not recognize its utility for use with simple cases, suggesting the presence of overconfidence bias. A clinical reasoning tool improved residents' diagnostic accuracy on written cases. Overconfidence bias is a potential barrier to its use in the clinical setting.

An Integrated Quantum Dot Barcode Smartphone Optical Device for Wireless Multiplexed Diagnosis of Infected Patients

NASA Astrophysics Data System (ADS)

Ming, Kevin

Integrating mobile-cellular devices with multiplex molecular diagnostics can potentially provide the most powerful platform for tracking, managing and preventing the transmission of infectious diseases. With over 6.9 billion subscriptions globally, handheld mobile-cellular devices can be programmed to spatially map, temporally track, and transmit information on infections over wide geographical space and boundaries. Current cell phone diagnostic technologies have poor limit of detection, dynamic range, and cannot detect multiple pathogen targets simultaneously, limiting their utility to single infections with high load. Here we combined recent advances in quantum dot barcode technology for molecular detection with smartphones to engineer a simple and low-cost chip-based wireless multiplex diagnostic device. We validated our device using a variety of synthetic genomic targets for the respiratory virus and blood-borne pathogens, and demonstrated that it could detect clinical samples after simple amplification. More importantly, we confirmed that the device is capable of detecting patients infected with a single or multiple infectious pathogens (e.g., HIV and hepatitis B) in a single test. This device advances the capacity for global surveillance of infectious diseases and has the potential to accelerate knowledge exchange-transfer of emerging or exigent disease threats with healthcare and military organizations in real-time.

Periprosthetic infection: where do we stand with regard to Gram stain?

PubMed Central

Ghanem, Elie; Ketonis, Constantinos; Restrepo, Camilo; Joshi, Ashish; Barrack, Robert

2009-01-01

Background and purpose One of the routinely used intraoperative tests for diagnosis of periprosthetic infection (PPI) is the Gram stain. It is not known if the result of this test can vary according to the type of joint affected or the number of specimen samples collected. We examined the role of this diagnostic test in a large cohort of patients from a single institution. Materials and methods A positive gram stain was defined as the visualization of bacterial cells or “many neutrophils” (> 5 per high-power field) in the smear. The sensitivity, specificity, and predictive values of each individual diagnostic arm of Gram stain were determined. Combinations were performed in series, which required both tests to be positive to confirm infection, and also in parallel, which necessitated both tests to be negative to rule out infection. Results The presence of organisms and “many” neutrophils on a Gram smear had high specificity (98–100%) and positive predictive value (89–100%) in both THA and TKA. The sensitivities (30–50%) and negative predictive values (70–79%) of the 2 tests were low for both joint types. When the 2 tests were combined in series, the specificity and positive predictive value were absolute (100%). The sensitivity and the negative predictive value improved for both THA and TKA (43–64% and 82%, respectively). Interpretation Although the 2 diagnostic arms of Gram staining can be combined to achieve improved negative predictive value (82%), Gram stain continues to have little value in ruling out PPI. With the advances in the field of molecular biology, novel diagnostic modalities need to be designed that can replace these traditional and poor tests. PMID:19297787

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation.

PubMed

Schechner, Vered; Carmeli, Yehuda; Leshno, Moshe

2017-01-01

Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics.

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation

PubMed Central

Carmeli, Yehuda; Leshno, Moshe

2017-01-01

Background Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. Methods We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. Results Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. Conclusions CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics. PMID:28187144

Cost-effectiveness of coronary CT angiography in patients with chest pain: Comparison with myocardial single photon emission tomography.

PubMed

Lee, Seung-Pyo; Jang, Eun Jin; Kim, Yong-Jin; Cha, Myung-Jin; Park, Sun-Young; Song, Hyun Jin; Choi, Ji Eun; Shim, Jung-Im; Ahn, Jeonghoon; Lee, Hyun Joo

2015-01-01

Coronary CT angiography (CCTA) has been proven accurate and is incorporated in clinical recommendations for coronary artery disease (CAD) diagnosis workup, but cost-effectiveness data, especially in comparison to other methods such as myocardial single photon emission CT (SPECT) are insufficient. To compare the cost-effectiveness of CCTA and myocardial SPECT in a real-world setting. We performed a retrospective cohort study on consecutive patients with suspected CAD and a pretest probability between 10% and 90%. Test accuracy was compared by correcting referral bias to coronary angiography depending on noninvasive test results based on the Bayes' theorem and also by incorporating 1-year follow-up results. Cost-effectiveness was analyzed using test accuracy and quality-adjusted life year (QALY). The model using diagnostic accuracy used the number of patients accurately diagnosed among 1000 persons as the effect and contained only expenses for diagnostic testing as the cost. In the model using QALY, a decision tree was developed, and the time horizon was 1 year. CCTA was performed in 635 patients and SPECT in 997 patients. An accurate diagnosis per 1000 patients was achieved in 725 patients by CCTA vs 661 patients by SPECT. In the model using diagnostic accuracy, CCTA was more effective and less expensive than SPECT ($725.38 for CCTA vs $661.46 for SPECT). In the model using QALY, CCTA was generally more effective in terms of life quality (0.00221 QALY) and cost ($513) than SPECT. However, cost utility varied among subgroups, with SPECT outperforming CCTA in patients with a pretest probability of 30% to 60% (0.01890 QALY; $113). These results suggest that CCTA may be more cost-effective than myocardial SPECT. Copyright © 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Streptococcus A in paediatric accident and emergency: are rapid streptococcal tests and clinical examination of any help?

PubMed

Van Limbergen, J; Kalima, P; Taheri, S; Beattie, T F

2006-01-01

Rapid streptococcal tests (RSTs) for streptococcal pharyngitis have made diagnosis at once simpler and more complicated. The American Academy of Pediatrics recommends that all RSTs be confirmed by a follow up throat culture unless local validation has proved the RST to be equally sensitive. To evaluate (a) RST as a single diagnostic tool, compared with RST with or without throat culture; (b) clinical diagnosis and the relative contribution of different symptoms. The study included 213 patients with clinical signs of pharyngitis. Throat swabs were analysed using Quickvue+ Strep A Test; negative RSTs were backed up by throat culture. Thirteen clinical features commonly associated with strep throat were analysed using backward stepwise logistic regression. Positive results (RST or throat culture) were obtained in 33 patients; RST correctly identified 21. Eleven samples were false negative on RST. At a strep throat prevalence of 15.9%, sensitivity of RST was 65.6% (95% CI 46.8% to 81.4%) and specificity 99.4% (96.7% to 99.9%). Sensitivity of clinical diagnosis alone was 57% (34% to 78%) and specificity 71% (61% to 80%). Clinically, only history of sore throat, rash, and pyrexia contributed to the diagnosis of strep throat (p<0.05). The high specificity of RST facilitates early diagnosis of strep throat. However, the low sensitivity of RST does not support its use as a single diagnostic tool. The sensitivity in the present study is markedly different from that reported by the manufacturer. Clinical examination is of limited value in the diagnosis of strep throat. It is important to audit the performance of new diagnostic tests, previously validated in different settings.

Streptococcus A in paediatric accident and emergency: are rapid streptococcal tests and clinical examination of any help?

PubMed Central

Van Limbergen, J; Kalima, P; Taheri, S; Beattie, T F

2006-01-01

Background Rapid streptococcal tests (RSTs) for streptococcal pharyngitis have made diagnosis at once simpler and more complicated. The American Academy of Pediatrics recommends that all RSTs be confirmed by a follow up throat culture unless local validation has proved the RST to be equally sensitive. Aims To evaluate (a) RST as a single diagnostic tool, compared with RST with or without throat culture; (b) clinical diagnosis and the relative contribution of different symptoms. Methods The study included 213 patients with clinical signs of pharyngitis. Throat swabs were analysed using Quickvue+ Strep A Test; negative RSTs were backed up by throat culture. Thirteen clinical features commonly associated with strep throat were analysed using backward stepwise logistic regression. Results Positive results (RST or throat culture) were obtained in 33 patients; RST correctly identified 21. Eleven samples were false negative on RST. At a strep throat prevalence of 15.9%, sensitivity of RST was 65.6% (95% CI 46.8% to 81.4%) and specificity 99.4% (96.7% to 99.9%). Sensitivity of clinical diagnosis alone was 57% (34% to 78%) and specificity 71% (61% to 80%). Clinically, only history of sore throat, rash, and pyrexia contributed to the diagnosis of strep throat (p<0.05). Conclusion The high specificity of RST facilitates early diagnosis of strep throat. However, the low sensitivity of RST does not support its use as a single diagnostic tool. The sensitivity in the present study is markedly different from that reported by the manufacturer. Clinical examination is of limited value in the diagnosis of strep throat. It is important to audit the performance of new diagnostic tests, previously validated in different settings. PMID:16373800

TIDBIT: portable diagnostics of multiplexed nutrition deficiencies: iron, vitamin A and inflammation status (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lu, Zhengda; Erickson, David

2017-03-01

Vitamin A and iron deficiency are common malnutrition affecting billions of people worldwide. However, in infrastructure limited settings, access to blood vitamin A and iron status test is limited because of the complexity and cost of traditional diagnostic methods. Direct measurements of vitamin A and iron level is not easy to perform, and it is necessary to measure approximate marker for obtaining vitamin A and iron deficiency status. Measurement of inflammatory marker is also necessary because the vitamin A and iron level are altered by inflammation status. Here we introduced a multiplex rapid point-of-care (POC) diagnostic devices that simultaneously characterize three markers relevant to vitamin A, iron and inflammation status: retinol binding protein 4, ferritin and C-reactive protein with lateral flow immunoassay test strips. Level of retinol binding protein 4, ferritin and C-reactive protein are indicated by excitation intensity of fluorescence tags with three different colors. The test can be done within 15 minutes and a complete sample-answer quantitative results of vitamin A, iron and inflammation status level can be obtained with assists of a smartphone and an external device. We also demonstrated the device is able to perform colorimetric analysis on single test area. which gives the device potential to perform more tests simultaneously at the same time.

Preliminary development of an ultrabrief two-item bedside test for delirium.

PubMed

Fick, Donna M; Inouye, Sharon K; Guess, Jamey; Ngo, Long H; Jones, Richard N; Saczynski, Jane S; Marcantonio, Edward R

2015-10-01

Delirium is common, morbid, and costly, yet is greatly under-recognized among hospitalized older adults. To identify the best single and pair of mental status test items that predict the presence of delirium. Diagnostic test evaluation study that enrolled medicine inpatients aged 75 years or older at an academic medical center. Patients underwent a clinical reference standard assessment involving a patient interview, medical record review, and interviews with family members and nurses to determine the presence or absence of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition defined delirium. Participants also underwent the three-dimensional Confusion Assessment Method (3D-CAM), a brief, validated assessment for delirium. Individual items and pairs of items from the 3D-CAM were evaluated to determine sensitivity and specificity relative to the reference standard delirium diagnosis. Of the 201 participants (mean age 84 years, 62% female), 42 (21%) had delirium based on the clinical reference standard. The single item with the best test characteristics was "months of the year backwards" with a sensitivity of 83% (95% confidence interval [CI]: 69%-93%) and specificity of 69% (95% CI: 61%-76%). The best 2-item screen was the combination of "months of the year backwards" and "what is the day of the week?" with a sensitivity of 93% (95% CI: 81%-99%) and specificity of 64% (95% CI: 56%-70%). We identified a single item with >80% and pair of items with >90% sensitivity for delirium. If validated prospectively, these items will serve as an initial innovative screening step for delirium identification in hospitalized older adults. © 2015 Society of Hospital Medicine.

New nucleic acid testing devices to diagnose infectious diseases in resource-limited settings.

PubMed

Maffert, P; Reverchon, S; Nasser, W; Rozand, C; Abaibou, H

2017-10-01

Point-of-care diagnosis based on nucleic acid testing aims to incorporate all the analytical steps, from sample preparation to nucleic acid amplification and detection, in a single device. This device needs to provide a low-cost, robust, sensitive, specific, and easily readable analysis. Microfluidics has great potential for handling small volumes of fluids on a single platform. Microfluidic technology has recently been applied to paper, which is already used in low-cost lateral flow tests. Nucleic acid extraction from a biological specimen usually requires cell filtration and lysis on specific membranes, while affinity matrices, such as chitosan or polydiacetylene, are well suited to concentrating nucleic acids for subsequent amplification. Access to electricity is often difficult in resource-limited areas, so the amplification step needs to be equipment-free. Consequently, the reaction has to be isothermal to alleviate the need for a thermocycler. LAMP, NASBA, HDA, and RPA are examples of the technologies available. Nucleic acid detection techniques are currently based on fluorescence, colorimetry, or chemiluminescence. For point-of-care diagnostics, the results should be readable with the naked eye. Nowadays, interpretation and communication of results to health professionals could rely on a smartphone, used as a telemedicine device. The major challenge of creating an "all-in-one" diagnostic test involves the design of an optimal solution and a sequence for each analytical step, as well as combining the execution of all these steps on a single device. This review provides an overview of available materials and technologies which seem to be adapted to point-of-care nucleic acid-based diagnosis, in low-resource areas.

Single Measure and Gated Screening Approaches for Identifying Students At-Risk for Academic Problems: Implications for Sensitivity and Specificity

ERIC Educational Resources Information Center

Van Norman, Ethan R.; Nelson, Peter M.; Klingbeil, David A.

2017-01-01

Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state…

Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.

PubMed

Arenillas, Leonor; Mallo, Mar; Ramos, Fernando; Guinta, Kathryn; Barragán, Eva; Lumbreras, Eva; Larráyoz, María-José; De Paz, Raquel; Tormo, Mar; Abáigar, María; Pedro, Carme; Cervera, José; Such, Esperanza; José Calasanz, María; Díez-Campelo, María; Sanz, Guillermo F; Hernández, Jesús María; Luño, Elisa; Saumell, Sílvia; Maciejewski, Jaroslaw; Florensa, Lourdes; Solé, Francesc

2013-12-01

Cytogenetic aberrations identified by metaphase cytogenetics (MC) have diagnostic, prognostic, and therapeutic implications in myelodysplastic syndromes (MDS). However, in some MDS patients MC study is unsuccesful. Single nucleotide polymorphism array (SNP-A) based karyotyping could be helpful in these cases. We performed SNP-A in 62 samples from bone marrow or peripheral blood of primary MDS with an unsuccessful MC study. SNP-A analysis enabled the detection of aberrations in 31 (50%) patients. We used the copy number alteration information to apply the International Prognostic Scoring System (IPSS) and we observed differences in survival between the low/intermediate-1 and intermediate-2/high risk patients. We also saw differences in survival between very low/low/intermediate and the high/very high patients when we applied the revised IPSS (IPSS-R). In conclusion, SNP-A can be used successfully in PB samples and the identification of CNA by SNP-A improve the diagnostic and prognostic evaluation of this group of MDS patients. Copyright © 2013 Wiley Periodicals, Inc.

Tissue microarrays and quantitative tissue-based image analysis as a tool for oncology biomarker and diagnostic development.

PubMed

Dolled-Filhart, Marisa P; Gustavson, Mark D

2012-11-01

Translational oncology has been improved by using tissue microarrays (TMAs), which facilitate biomarker analysis of large cohorts on a single slide. This has allowed for rapid analysis and validation of potential biomarkers for prognostic and predictive value, as well as for evaluation of biomarker prevalence. Coupled with quantitative analysis of immunohistochemical (IHC) staining, objective and standardized biomarker data from tumor samples can further advance companion diagnostic approaches for the identification of drug-responsive or resistant patient subpopulations. This review covers the advantages, disadvantages and applications of TMAs for biomarker research. Research literature and reviews of TMAs and quantitative image analysis methodology have been surveyed for this review (with an AQUA® analysis focus). Applications such as multi-marker diagnostic development and pathway-based biomarker subpopulation analyses are described. Tissue microarrays are a useful tool for biomarker analyses including prevalence surveys, disease progression assessment and addressing potential prognostic or predictive value. By combining quantitative image analysis with TMAs, analyses will be more objective and reproducible, allowing for more robust IHC-based diagnostic test development. Quantitative multi-biomarker IHC diagnostic tests that can predict drug response will allow for greater success of clinical trials for targeted therapies and provide more personalized clinical decision making.

Single-shot Z(eff) dense plasma diagnostic through simultaneous refraction and attenuation measurements with a Talbot-Lau x-ray moiré deflectometer.

PubMed

Valdivia, M P; Stutman, D; Finkenthal, M

2015-04-01

The Talbot-Lau x-ray moiré deflectometer is a powerful plasma diagnostic capable of delivering simultaneous refraction and attenuation information through the accurate detection of x-ray phase shift and intensity. The diagnostic can provide the index of refraction n=1-δ+iβ of an object (dense plasma, for example) placed in the x-ray beam by independently measuring both δ and β, which are directly related to the electron density n(e) and the attenuation coefficient μ, respectively. Since δ and β depend on the effective atomic number Z(eff), a map can be obtained from the ratio between phase and absorption images acquired in a single shot. The Talbot-Lau x-ray moiré deflectometer and its corresponding data acquisition and processing are briefly described to illustrate how the above is achieved; Z(eff) values of test objects within the 4-12 range were obtained experimentally through simultaneous refraction and attenuation measurements. We show that Z(eff) mapping of objects does not require previous knowledge of sample length or shape. The determination of Z(eff) from refraction and attenuation measurements with moiré deflectometry could be of high interest to various domains of high energy density research, such as shocked materials and inertial confinement fusion experiments, as well as material science and nondestructive testing.

Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers.

PubMed

Aljakna, Aleksandra; Fracasso, Tony; Sabatasso, Sara

2018-03-01

Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of blood flow to part of the myocardium) remains a challenge for clinical and forensic pathologists. Several immunohistochemical markers have been proposed for improving postmortem detection of early myocardial ischemia; however, no single marker appears to be both sufficiently specific as well as sensitive. This review summarizes the diverse categories of molecular tissue markers that have been investigated in human autopsy samples with acute myocardial infarction as well as in the well-established and widely used in vivo animal model of early myocardial ischemia (permanent ligation of the coronary artery). Recently identified markers appearing during the initial 2 h of myocardial ischemia are highlighted. Among them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, heart fatty acid binding protein, connexin 43, and JunB). Despite the discovery of several potentially promising markers (in terms of early expression and specificity), many of them remain to be tested and validated for application in routine diagnostics in clinical and forensic pathology. In particular, research investigating the postmortem stability of these markers is required before any might be implemented into routine diagnostics. Establishing a standardized panel of immunohistochemical markers may be more useful for improving sensitivity and specificity than searching for a single marker.

High Speed Optical Diagnostics in a High Pressure, GOx/RP 2 Combustor

DTIC Science & Technology

2017-07-10

Similarly, the German Aerospace Center (DLR) at Lampoldshausen conducted research on LOX/LH2 propellants in the Combustion Chamber C experimental ...facility. This single element, optically accessible liquid rocket engine test article was designed to operate up to 1,450 psi, however most research was...significant result of this work was the acquisition of data at pressures up to 2400 psi. T 3 II. Experimental Facility This testing was

Real Time Fault Detection and Diagnostics Using FPGA-Based Architectures

DTIC Science & Technology

2010-03-01

vector sets sent to the DUT. The testing platform combines a myriad of testing and measuring equipment and work hours onto one small reprogrammable ...recently few reprogrammable devices have been used on spacecraft due to their sensitivity to involuntary reconfiguration due to Single Event Upsets...Determination of Nuclear Yield from Thermal Degradation of Automobile Paint MS Thesis. AFIT/GWM/ENP/10-M10. Wright-Patterson AFB OH: Graduate School of

An SSP-PCR method for the rapid detection of disease-associated alleles HLA-A*29 and HLA-B*51.

PubMed

Amstutz, U; Schaerer, D; Andrey, G; Wirthmueller, U; Largiadèr, C R

2018-05-15

HLA-A*29 and HLA-B*51 are associated with birdshot uveitis and Behçet's disease, respectively, and are used as a diagnostic criterion in patients with suspected disease, requiring their detection in diagnostic laboratories. While commercial tests for individual HLA alleles are available for other disease-associated HLA variants, no similar allele-specific assays are available for HLA-A*29 and -B*51. Here, we report SSP-PCR methods for the detection of HLA-A*29 and -B*51 using a single PCR reaction per allele. The assays were tested in 30 and 32 previously HLA-typed samples, respectively, representing >97% of HLA-A alleles and >93% of HLA-B alleles in a European population. A concordance of 100% was observed with previous typing results, validating these methods for use in a diagnostic or research context. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Dilution testing using rapid diagnostic tests in a HIV diagnostic algorithm: a novel alternative for confirmation testing in resource limited settings.

PubMed

Shanks, Leslie; Siddiqui, M Ruby; Abebe, Almaz; Piriou, Erwan; Pearce, Neil; Ariti, Cono; Masiga, Johnson; Muluneh, Libsework; Wazome, Joseph; Ritmeijer, Koert; Klarkowski, Derryck

2015-05-14

Current WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results. Participants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result. 2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %. This study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false negative results due to seroconversion or misclassification by the lower sensitivity dilution test. Further research is needed to determine if these results can be replicated in other settings. ClinicalTrials.gov, NCT01716299 .

Hotspot mutations in cancer genes may be missed in routine diagnostics due to neighbouring sequence variants.

PubMed

Bartels, Stephan; Schipper, Elisa; Hasemeier, Britta; Kreipe, Hans; Lehmann, Ulrich

2018-05-27

The detection of hotspot mutations in key cancer genes is now an essential part of the diagnostic work-up in molecular pathology. Nearly all assays for mutation detection involve an amplification step. A second single nucleotide variant (SNV) on the same allele adjacent to a mutational hotspot can interfere with primer binding, leading to unnoticed allele-specific amplification of the wild type allele and thereby false-negative mutation testing. We present two diagnostic cases with false negative sequence results for JAK2 and SRSF2. In both cases mutations would have escaped detection if only one strand of DNA had been analysed. Because many commercially available diagnostic kits rely on the analysis of only one DNA strand they are prone to fail in cases like these. Detailed protocols and quality control measures to prevent corresponding pitfalls are presented. Copyright © 2017. Published by Elsevier Inc.

Simultaneous-Fault Diagnosis of Gearboxes Using Probabilistic Committee Machine

PubMed Central

Zhong, Jian-Hua; Wong, Pak Kin; Yang, Zhi-Xin

2016-01-01

This study combines signal de-noising, feature extraction, two pairwise-coupled relevance vector machines (PCRVMs) and particle swarm optimization (PSO) for parameter optimization to form an intelligent diagnostic framework for gearbox fault detection. Firstly, the noises of sensor signals are de-noised by using the wavelet threshold method to lower the noise level. Then, the Hilbert-Huang transform (HHT) and energy pattern calculation are applied to extract the fault features from de-noised signals. After that, an eleven-dimension vector, which consists of the energies of nine intrinsic mode functions (IMFs), maximum value of HHT marginal spectrum and its corresponding frequency component, is obtained to represent the features of each gearbox fault. The two PCRVMs serve as two different fault detection committee members, and they are trained by using vibration and sound signals, respectively. The individual diagnostic result from each committee member is then combined by applying a new probabilistic ensemble method, which can improve the overall diagnostic accuracy and increase the number of detectable faults as compared to individual classifiers acting alone. The effectiveness of the proposed framework is experimentally verified by using test cases. The experimental results show the proposed framework is superior to existing single classifiers in terms of diagnostic accuracies for both single- and simultaneous-faults in the gearbox. PMID:26848665

Simultaneous-Fault Diagnosis of Gearboxes Using Probabilistic Committee Machine.

PubMed

Zhong, Jian-Hua; Wong, Pak Kin; Yang, Zhi-Xin

2016-02-02

This study combines signal de-noising, feature extraction, two pairwise-coupled relevance vector machines (PCRVMs) and particle swarm optimization (PSO) for parameter optimization to form an intelligent diagnostic framework for gearbox fault detection. Firstly, the noises of sensor signals are de-noised by using the wavelet threshold method to lower the noise level. Then, the Hilbert-Huang transform (HHT) and energy pattern calculation are applied to extract the fault features from de-noised signals. After that, an eleven-dimension vector, which consists of the energies of nine intrinsic mode functions (IMFs), maximum value of HHT marginal spectrum and its corresponding frequency component, is obtained to represent the features of each gearbox fault. The two PCRVMs serve as two different fault detection committee members, and they are trained by using vibration and sound signals, respectively. The individual diagnostic result from each committee member is then combined by applying a new probabilistic ensemble method, which can improve the overall diagnostic accuracy and increase the number of detectable faults as compared to individual classifiers acting alone. The effectiveness of the proposed framework is experimentally verified by using test cases. The experimental results show the proposed framework is superior to existing single classifiers in terms of diagnostic accuracies for both single- and simultaneous-faults in the gearbox.

21 CFR 870.1435 - Single-function, preprogrammed diagnostic computer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Single-function, preprogrammed diagnostic computer. 870.1435 Section 870.1435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1435...

Notes on the design of experiments and beam diagnostics with synchrotron light detected by a gated photomultiplier for the Fermilab superconducting electron linac and for the Integrable Optics Test Accelerator (IOTA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stancari, Giulio; Romanov, Aleksandr; Ruan, Jinhao

We outline the design of beam experiments for the electron linac at the Fermilab Accelerator Science and Technology (FAST) facility and for the Integrable Optics Test Accelerator (IOTA), based on synchrotron light emitted by the electrons in bend dipoles, detected with gated microchannel-plate photomultipliers (MCP-PMTs). The system can be used both for beam diagnostics (e.g., beam intensity with full dynamic range, turn-by-turn beam vibrations, etc.) and for scientific experiments, such as the direct observation of the time structure of the radiation emitted by single electrons in a storage ring. The similarity between photon pulses and spectrum at the downstream endmore » of the electron linac and in the IOTA ring allows one to test the apparatus during commissioning of the linac.« less

CT coronary angiography and exercise ECG in a population with chest pain and low-to-intermediate pre-test likelihood of coronary artery disease.

PubMed

Maffei, Erica; Seitun, Sara; Martini, Chiara; Palumbo, Alessandro; Tarantini, Giuseppe; Berti, Elena; Grilli, Roberto; Tedeschi, Carlo; Messalli, Giancarlo; Guaricci, Andrea; Weustink, Annick C; Mollet, Nico Ra; Cademartiri, Filippo

2010-12-01

To evaluate diagnostic accuracy of exercise ECG (ex-ECG) versus 64-slice CT coronary angiography (CT-CA) for the detection of significant coronary artery stenosis in a population with low-to-intermediate pre-test likelihood of coronary artery disease (CAD). Retrospective single centre. Tertiary academic hospital. 177 consecutive patients (88 men, 89 women, mean age 53.5±7.6 years) with chest pain and low-to-intermediate pre-test likelihood of CAD were retrospectively enrolled. All patients underwent ex-ECG, CT-CA and invasive coronary angiography (ICA). A lumen diameter reduction of ≥50% was considered as significant stenosis for CT-CA. Ex-ECG was classified as positive, negative or non-diagnostic. were compared with ICA. Diagnostic accuracy of CT-CA and ex-ECG was calculated using ICA as the reference standard. A parallel comparative analysis using a cut-off value of 70% for significant lumen reduction was also performed too. Results ICA disclosed an absence of significant stenosis (≥50% luminal narrowing) in 85.3% (151/177) patients, single-vessel disease in 9.0% (16/177) patients and multivessel disease in 5.6% (10/177) patients. Prevalence of obstructive disease at ICA was 14.7% (26/177). Sensitivity, specificity, positive and negative predictive values at the patient level were 100.0%, 98.7%, 92.9%, 100%, respectively, for CT-CA and 46.2%, 16.6%, 8.7%, 64.1%, respectively, for ex-ECG. Agreement between CT-CA and ex-ECG was 20.9%. CT-CA performed equally well in men and women, while ex-ECG had a better performance in men. After considering the cut-off value of 70% for significant stenosis, the difference between CT-CA and ex-ECG remained significant (p<0.01), with a low agreement (21.5%). CT-CA provides optimal diagnostic performance in patients with atypical chest pain and low-to-intermediate risk of CAD. Ex-ECG has poor diagnostic accuracy in this population. Concerns are related to risk of radiation dose versus the benefits of correct disease stratification.

Single-cell proteomics: potential implications for cancer diagnostics.

PubMed

Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T

2016-01-01

Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.

Pediatric colonic volvulus: A single-institution experience and review.

PubMed

Tannouri, Sami; Hendi, Aditi; Gilje, Elizabeth; Grissom, Leslie; Katz, Douglas

2017-06-01

Pediatric colonic volvulus is both rare and underreported. Existing literature consists only of case reports and small series. We present an analysis of cases (n=11) over 15 years at a single institution, focusing on workup and diagnosis. This was an institutional review board approved single-institution retrospective chart review of 11 cases of large bowel volvulus occurring over 15 years (2000-2015). In our series, the most common presenting symptoms were abdominal pain and distention. Afflicted patients often had prior abdominal surgery, a neurodevelopmental disorder or chronic constipation. Of the imaging modalities utilized in the 11 patients studied, colonic volvulus was correctly diagnosed by barium enema in 100% of both cases, CT in 55.6% of cases and by plain radiography of the abdomen in only 22.2%of cases. Colonic volvulus was confirmed by laparotomy in all cases. The cecum (n=5) was the most often affected colonic segment, followed by the sigmoid (n=3). Operative treatment mainly consisted of resection (63.6%) and ostomy creation (36.4%). Colopexy was performed in 18.2% of cases. Plain abdominal radiography may be performed as an initial diagnostic study, however, it should be followed CT or air or contrast enema in children where there is high clinical suspicion and who do not have indications for immediate laparotomy. CT may be the most specific and useful test in diagnosis of colonic volvulus and has the added advantage of detection of complications including bowel ischemia. We demonstrate a range of diagnostic and therapeutic modalities for pediatric colonic volvulus. This underscores the need for further study to draft standard best practices for this life-threatening condition. Prognosis Study: Level IV. Study of a Diagnostic Test: Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of isolated-check visual evoked potential and standard automated perimetry in early glaucoma and high-risk ocular hypertension

PubMed Central

Chen, Xiang-Wu; Zhao, Ying-Xi

2017-01-01

AIM To compare the diagnostic performance of isolated-check visual evoked potential (icVEP) and standard automated perimetry (SAP), for evaluating the application values of icVEP in the detection of early glaucoma. METHODS Totally 144 subjects (288 eyes) were enrolled in this study. icVEP testing was performed with the Neucodia visual electrophysiological diagnostic system. A 15% positive-contrast (bright) condition pattern was used in this device to differentiate between glaucoma patients and healthy control subjects. Signal-to-noise ratios (SNR) were derived based on a multivariate statistic. The eyes were judged as abnormal if the test yielded an SNR≤1. SAP testing was performed with the Humphrey Field Analyzer II. The visual fields were deemed as abnormality if the glaucoma hemifield test results outside normal limits; or the pattern standard deviation with P<0.05; or the cluster of three or more non-edge points on the pattern deviation plot in a single hemifield with P<0.05, one of which must have a P<0.01. Disc photographs were graded as either glaucomatous optic neuropathy or normal by two experts who were masked to all other patient information. Moorfields regression analysis (MRA) used as a separate diagnostic classification was performed by Heidelberg retina tomograph (HRT). RESULTS When the disc photograph grader was used as diagnostic standard, the sensitivity for SAP and icVEP was 32.3% and 38.5% respectively and specificity was 82.3% and 77.8% respectively. When the MRA Classifier was used as the diagnostic standard, the sensitivity for SAP and icVEP was 48.6% and 51.4% respectively and specificity was 84.1% and 78.0% respectively. When the combined structural assessment was used as the diagnostic standard, the sensitivity for SAP and icVEP was 59.2% and 53.1% respectively and specificity was 84.2% and 84.6% respectivlely. There was no statistical significance between the sensitivity or specificity of SAP and icVEP, regardless of which diagnostic standard was based on. CONCLUSION The diagnostic performance of icVEP is not better than that of SAP in the detection of early glaucoma. PMID:28503434

Component-Level Electronic-Assembly Repair (CLEAR) Synthetic Instrument Capabilities Assessment and Test Report

NASA Technical Reports Server (NTRS)

Oeftering, Richard C.; Bradish, Martin A.

2011-01-01

The role of synthetic instruments (SIs) for Component-Level Electronic-Assembly Repair (CLEAR) is to provide an external lower-level diagnostic and functional test capability beyond the built-in-test capabilities of spacecraft electronics. Built-in diagnostics can report faults and symptoms, but isolating the root cause and performing corrective action requires specialized instruments. Often a fault can be revealed by emulating the operation of external hardware. This implies complex hardware that is too massive to be accommodated in spacecraft. The SI strategy is aimed at minimizing complexity and mass by employing highly reconfigurable instruments that perform diagnostics and emulate external functions. In effect, SI can synthesize an instrument on demand. The SI architecture section of this document summarizes the result of a recent program diagnostic and test needs assessment based on the International Space Station. The SI architecture addresses operational issues such as minimizing crew time and crew skill level, and the SI data transactions between the crew and supporting ground engineering searching for the root cause and formulating corrective actions. SI technology is described within a teleoperations framework. The remaining sections describe a lab demonstration intended to show that a single SI circuit could synthesize an instrument in hardware and subsequently clear the hardware and synthesize a completely different instrument on demand. An analysis of the capabilities and limitations of commercially available SI hardware and programming tools is included. Future work in SI technology is also described.

Reliability and diagnostic accuracy of history and physical examination for diagnosing glenoid labral tears.

PubMed

Walsworth, Matthew K; Doukas, William C; Murphy, Kevin P; Mielcarek, Billie J; Michener, Lori A

2008-01-01

Glenoid labral tears provide a diagnostic challenge. Combinations of items in the patient history and physical examination will provide stronger diagnostic accuracy to suggest the presence or absence of glenoid labral tear than will individual items. Cohort study (diagnosis); Level of evidence, 1. History and examination findings in patients with shoulder pain (N = 55) were compared with arthroscopic findings to determine diagnostic accuracy and intertester reliability. The intertester reliability of the crank, anterior slide, and active compression tests was 0.20 to 0.24. A combined history of popping or catching and positive crank or anterior slide results yielded specificities of 0.91 and 1.00 and positive likelihood ratios of 3.0 and infinity, respectively. A positive anterior slide result combined with either a positive active compression or crank result yielded specificities of 0.91 and positive likelihood ratio of 2.75 and 3.75, respectively. Requiring only a single positive finding in the combination of popping or catching and the anterior slide or crank yielded sensitivities of 0.82 and 0.89 and negative likelihood ratios of 0.31 and 0.33, respectively. The diagnostic accuracy of individual tests in previous studies is quite variable, which may be explained in part by the modest reliability of these tests. The combination of popping or catching with a positive crank or anterior slide result or a positive anterior slide result with a positive active compression or crank test result suggests the presence of a labral tear. The combined absence of popping or catching and a negative anterior slide or crank result suggests the absence of a labral tear.

Diagnosis of Helicobacter pylori infection: Current options and developments

PubMed Central

Wang, Yao-Kuang; Kuo, Fu-Chen; Liu, Chung-Jung; Wu, Meng-Chieh; Shih, Hsiang-Yao; Wang, Sophie SW; Wu, Jeng-Yih; Kuo, Chao-Hung; Huang, Yao-Kang; Wu, Deng-Chyang

2015-01-01

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes. PMID:26523098

Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study.

PubMed

Kim, Min-Hye; Song, Woo-Jung; Kim, Tae-Wan; Jin, Hyun-Jung; Sin, You-Seob; Ye, Young-Min; Kim, Sang-Heon; Park, Heung-Woo; Lee, Byung-Jae; Park, Hae-Sim; Yoon, Ho-Joo; Choi, Dong-Chull; Min, Kyung-Up; Cho, Sang-Heon

2014-08-01

Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests. Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity and specificity for asthma diagnosis. Response-dose ratio was also compared. A total of 50 asthmatic adults and 54 controls were enrolled (mean age 43.8 years). The sensitivity and specificity of mannitol challenge (defined by a PD15 of <635 mg) were 48.0% and 92.6%, respectively, whereas those of methacholine (defined by a PC20 of <16 mg/mL) were 42.0% and 98.1%, respectively. Twenty asthmatic participants (24%) showed positive response to a single agonist only. In the receiver operating curve analyses using response-dose ratio values, area under the curve was 0.77 (95% confidence interval (CI): 0.68-0.86) for mannitol, and 0.89 (95% CI: 0.83-0.95) for methacholine. The correlations between log- transformed mannitol and methacholine response-dose ratios were significant but moderate (r = 0.683, P < 0.001). The present study demonstrated overall similar diagnostic properties of two diagnostic tests, but also suggested their intercomplementary roles for asthma. The clinical trial registration number at ClinicalTrial.gov is NCT02104284. © 2014 Asian Pacific Society of Respirology.

Innovative single-shot diagnostics for electrons accelerated through laser-plasma interaction at FLAME

NASA Astrophysics Data System (ADS)

Bisesto, F. G.; Anania, M. P.; Chiadroni, E.; Cianchi, A.; Costa, G.; Curcio, A.; Ferrario, M.; Galletti, M.; Pompili, R.; Schleifer, E.; Zigler, A.

2017-05-01

Plasma wakefield acceleration is the most promising acceleration technique known nowadays, able to provide very high accelerating fields (> 100 GV/m), enabling acceleration of electrons to GeV energy in few centimeters. Here we present all the plasma related activities currently underway at SPARC LAB exploiting the high power laser FLAME. In particular, we will give an overview of the single shot diagnostics employed: Electro Optic Sampling (EOS) for temporal measurement and optical transition radiation (OTR) for an innovative one shot emittance measurements. In detail, the EOS technique has been employed to measure for the first time the longitudinal profile of electric field of fast electrons escaping from a solid target, driving the ions and protons acceleration, and to study the impact of using different target shapes. Moreover, a novel scheme for one shot emittance measurements based on OTR, developed and tested at SPARC LAB LINAC, will be shown.

Single element of the matrix source of negative hydrogen ions: Measurements of the extracted currents combined with diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yordanov, D., E-mail: yordanov@phys.uni-sofia.bg; Lishev, St.; Shivarova, A.

2016-02-15

Combining measurements of the extracted currents with probe and laser-photodetachment diagnostics, the study is an extension of recent tests of factors and gas-discharge conditions stimulating the extraction of volume produced negative ions. The experiment is in a single element of a rf source with the design of a matrix of small-radius inductively driven discharges. The results are for the electron and negative-ion densities, for the plasma potential and for the electronegativity in the vicinity of the plasma electrode as well as for the currents of the extracted negative ions and electrons. The plasma-electrode bias and the rf power have beenmore » varied. Necessity of a high bias to the plasma electrode and stable linear increase of the extracted currents with the rf power are the main conclusions.« less

Juvenile retinoschisis: a model for molecular diagnostic testing of X-linked ophthalmic disease.

PubMed

Sieving, P A; Yashar, B M; Ayyagari, R

1999-01-01

X-linked juvenile retinoschisis (RS) provides a starting point to define clinical paradigms and understand the limitations of diagnostic molecular testing. The RS phenotype is specific, but the broad severity range is clinically confusing. Molecular diagnostic testing obviates unnecessary examinations for boys at-risk and identifies carrier females who otherwise show no clinical signs. The XLRS1 gene has 6 exons of 26-196 base-pair size. Each exon is amplified by a single polymerase chain reaction and then sequenced, starting with exons 4 through 6, which contain mutation "hot spots." The 6 XLRS1 exons are sequenced serially. If alterations are found, they are compared with mutations in our > 120 XLRS families and with the > 300 mutations reported worldwide. Point mutations, small deletions, or rearrangements are identified in nearly 90% of males with a clinical diagnosis of RS. XLRS1 has very few sequence polymorphisms. Carrier-state testing produces 1 of 3 results: (1) positive, in which the woman has the same mutation as an affected male relative or known in other RS families; (2) negative, in which she lacks the mutation of her affected male relative; and (3) uninformative, in which no known mutation is identified or no information exists about the familial mutation. Molecular RS screening is an effective diagnostic tool that complements the clinician's skills for early detection of at-risk males. Useful outcomes of carrier testing depend on several factors: (1) a male relative with a clear clinical diagnosis; (2) a well-defined inheritance pattern; (3) high disease penetrance; (4) size and organization of the gene; and (5) the types of disease-associated mutations. Ethical questions include molecular diagnostic testing of young at-risk females before the age of consent, the impact of this information on the emotional health of the patient and family, and issues of employability and insurance coverage.

Juvenile retinoschisis: a model for molecular diagnostic testing of X-linked ophthalmic disease.

PubMed Central

Sieving, P A; Yashar, B M; Ayyagari, R

1999-01-01

BACKGROUND AND PURPOSE: X-linked juvenile retinoschisis (RS) provides a starting point to define clinical paradigms and understand the limitations of diagnostic molecular testing. The RS phenotype is specific, but the broad severity range is clinically confusing. Molecular diagnostic testing obviates unnecessary examinations for boys at-risk and identifies carrier females who otherwise show no clinical signs. METHODS: The XLRS1 gene has 6 exons of 26-196 base-pair size. Each exon is amplified by a single polymerase chain reaction and then sequenced, starting with exons 4 through 6, which contain mutation "hot spots." RESULTS: The 6 XLRS1 exons are sequenced serially. If alterations are found, they are compared with mutations in our > 120 XLRS families and with the > 300 mutations reported worldwide. Point mutations, small deletions, or rearrangements are identified in nearly 90% of males with a clinical diagnosis of RS. XLRS1 has very few sequence polymorphisms. Carrier-state testing produces 1 of 3 results: (1) positive, in which the woman has the same mutation as an affected male relative or known in other RS families; (2) negative, in which she lacks the mutation of her affected male relative; and (3) uninformative, in which no known mutation is identified or no information exists about the familial mutation. CONCLUSIONS: Molecular RS screening is an effective diagnostic tool that complements the clinician's skills for early detection of at-risk males. Useful outcomes of carrier testing depend on several factors: (1) a male relative with a clear clinical diagnosis; (2) a well-defined inheritance pattern; (3) high disease penetrance; (4) size and organization of the gene; and (5) the types of disease-associated mutations. Ethical questions include molecular diagnostic testing of young at-risk females before the age of consent, the impact of this information on the emotional health of the patient and family, and issues of employability and insurance coverage. Images FIGURE 2A FIGURE 2B PMID:10703138

Students' Concept of Force: The Importance of Understanding Newton's Third Law.

ERIC Educational Resources Information Center

Brown, David E.

This paper analyzes the misconceptions high school students have about force and suggests that the misunderstanding of Newton's third law is the key to these misconceptions. Clinical interview and diagnostic test data (N=104) indicates that many students have a naive view of force as an acquired or innate property of single objects rather than…

Single and combination diagnostic test efficiency and cost analysis for detection and isolation of avian influenza virus from wild bird cloacal swabs

USDA-ARS?s Scientific Manuscript database

Effective laboratory methods for identifying avian influenza virus (AIV) in wild bird populations are crucial to understanding the ecology of this pathogen. The gold standard method has been AIV isolation in chorioallantoic sac (CAS) of specific-pathogen-free (SPF) embryonating chicken eggs (ECE), ...

Use of diagnostic accuracy as a metric for evaluating laboratory proficiency with microarray assays using mixed-tissue RNA reference samples.

PubMed

Pine, P S; Boedigheimer, M; Rosenzweig, B A; Turpaz, Y; He, Y D; Delenstarr, G; Ganter, B; Jarnagin, K; Jones, W D; Reid, L H; Thompson, K L

2008-11-01

Effective use of microarray technology in clinical and regulatory settings is contingent on the adoption of standard methods for assessing performance. The MicroArray Quality Control project evaluated the repeatability and comparability of microarray data on the major commercial platforms and laid the groundwork for the application of microarray technology to regulatory assessments. However, methods for assessing performance that are commonly applied to diagnostic assays used in laboratory medicine remain to be developed for microarray assays. A reference system for microarray performance evaluation and process improvement was developed that includes reference samples, metrics and reference datasets. The reference material is composed of two mixes of four different rat tissue RNAs that allow defined target ratios to be assayed using a set of tissue-selective analytes that are distributed along the dynamic range of measurement. The diagnostic accuracy of detected changes in expression ratios, measured as the area under the curve from receiver operating characteristic plots, provides a single commutable value for comparing assay specificity and sensitivity. The utility of this system for assessing overall performance was evaluated for relevant applications like multi-laboratory proficiency testing programs and single-laboratory process drift monitoring. The diagnostic accuracy of detection of a 1.5-fold change in signal level was found to be a sensitive metric for comparing overall performance. This test approaches the technical limit for reliable discrimination of differences between two samples using this technology. We describe a reference system that provides a mechanism for internal and external assessment of laboratory proficiency with microarray technology and is translatable to performance assessments on other whole-genome expression arrays used for basic and clinical research.

The dimensionality of alcohol use disorders and alcohol consumption in a cross-national perspective

PubMed Central

Borges, Guilherme; Ye, Yu; Bond, Jason; Cherpitel, Cheryl J.; Cremonte, Mariana; Moskalewicz, Jacek; Swiatkiewicz, Grazyna; Rubio-Stipec, Maritza

2009-01-01

Aims To replicate the finding that there is a single dimension trait in alcohol use disorders and to test whether usual 5+ drinks for men and/4+ drinks for women and other measures of alcohol consumption help to improve alcohol use disorder criteria in a series of diverse patients from Emergency Departments (EDs) in four countries. Design Cross-sectional surveys of patient 18 and older that reflected consecutive arrival at the ED. The Composite International Diagnostic Interview Core was used to obtain a diagnosis of DSM-IV alcohol dependence and alcohol abuse. Quantity and frequency of drinking and drunkenness as well as usual number of drinks consumed during the last year. Setting Participants were 5,195 injured and non-injured patients attending 7 EDs in 4 countries, Argentina, Mexico, Poland the U.S., (between 1995-2001). Findings Using exploratory factor analyses alcohol use disorders can be described as a single, unidimensional continuum without any clear cut distinction between the criterions for dependence and abuse in all sites. Results from item response theory analyses showed that the current DSM-IV criterions tap people in the middle-upper end of the alcohol use disorder continuum. Alcohol consumption (amount and frequency of use) can be used in all EDs with the current DSM-IV diagnostic criterions to help tap the middle-lower part of this continuum. Even though some specific diagnostic criterions and some alcohol consumption variables showed differential item function across sites, test response curves were invariant for ED sites and their inclusion would not impact the final (total) performance of the diagnostic system. Conclusions DSM-IV abuse and dependence form a unidimensional continuum in ED patients regardless of country of survey. Alcohol consumption variables, if added, would help to tap patients with more moderate severity. DSM diagnostic system for alcohol use disorders showed invariance and performed extremely well in these samples. PMID:20078482

Alternative Confidence Interval Methods Used in the Diagnostic Accuracy Studies

PubMed Central

Gülhan, Orekıcı Temel

2016-01-01

Background/Aim. It is necessary to decide whether the newly improved methods are better than the standard or reference test or not. To decide whether the new diagnostics test is better than the gold standard test/imperfect standard test, the differences of estimated sensitivity/specificity are calculated with the help of information obtained from samples. However, to generalize this value to the population, it should be given with the confidence intervals. The aim of this study is to evaluate the confidence interval methods developed for the differences between the two dependent sensitivity/specificity values on a clinical application. Materials and Methods. In this study, confidence interval methods like Asymptotic Intervals, Conditional Intervals, Unconditional Interval, Score Intervals, and Nonparametric Methods Based on Relative Effects Intervals are used. Besides, as clinical application, data used in diagnostics study by Dickel et al. (2010) has been taken as a sample. Results. The results belonging to the alternative confidence interval methods for Nickel Sulfate, Potassium Dichromate, and Lanolin Alcohol are given as a table. Conclusion. While preferring the confidence interval methods, the researchers have to consider whether the case to be compared is single ratio or dependent binary ratio differences, the correlation coefficient between the rates in two dependent ratios and the sample sizes. PMID:27478491

Alternative Confidence Interval Methods Used in the Diagnostic Accuracy Studies.

PubMed

Erdoğan, Semra; Gülhan, Orekıcı Temel

2016-01-01

Background/Aim. It is necessary to decide whether the newly improved methods are better than the standard or reference test or not. To decide whether the new diagnostics test is better than the gold standard test/imperfect standard test, the differences of estimated sensitivity/specificity are calculated with the help of information obtained from samples. However, to generalize this value to the population, it should be given with the confidence intervals. The aim of this study is to evaluate the confidence interval methods developed for the differences between the two dependent sensitivity/specificity values on a clinical application. Materials and Methods. In this study, confidence interval methods like Asymptotic Intervals, Conditional Intervals, Unconditional Interval, Score Intervals, and Nonparametric Methods Based on Relative Effects Intervals are used. Besides, as clinical application, data used in diagnostics study by Dickel et al. (2010) has been taken as a sample. Results. The results belonging to the alternative confidence interval methods for Nickel Sulfate, Potassium Dichromate, and Lanolin Alcohol are given as a table. Conclusion. While preferring the confidence interval methods, the researchers have to consider whether the case to be compared is single ratio or dependent binary ratio differences, the correlation coefficient between the rates in two dependent ratios and the sample sizes.

Vaccine allergy and pseudo-allergy.

PubMed

Ponvert, Claude; Scheinmann, Pierre

2003-01-01

Allergic and pseudo-allergic reactions to vaccines frequently involve the skin, and can be generalized systemic symptoms (urticaria/angioedema, serum sickness, flares of eczema) or localized at the sites of vaccination (persistent nodules, abcesses, granulomas). Diagnosis of Arthus-type reactions is based on clinical history and specific IgM/IgG anti-toxoid determination. For other local reactions, diagnostic value of non-immediate responses in skin tests varies with clinical symptoms and substances involved. Immediate responses in skin tests and specific IgE determination have good diagnostic and/or predictive value in anaphylaxis and immediate/accelerated urticaria/angioedema to toxoid-, pneumococcus-, and egg- and gelatin-containing vaccines. Diagnosis of reactions to dextran in BCG is based on specific IgM/IgG determination. Most non-immediate generalized reactions result from non-specific inflammation, except for gelatin-containing vaccines, but the diagnostic value of immuno-allergological tests with the vaccines and gelatin are controversial. Withholding booster injections is advised if specific IgM/IgG levels are high. If the levels are low, sequential injections of vaccines containing a single vaccinating agent are usually tolerated. However, injections of the vaccine should be performed using a " desensitization " procedure in patients reporting anaphylaxis and immediate/accelerated urticaria/angioedema.

Evaluation of the diagnostic value of serologic microagglutination testing and a polymerase chain reaction assay for diagnosis of acute leptospirosis in dogs in a referral center.

PubMed

Fraune, Claudia Kümmerle; Schweighauser, Ariane; Francey, Thierry

2013-05-15

To determine the diagnostic value of a serologic microagglutination test (MAT) and a PCR assay on urine and blood for the diagnosis of leptospirosis in dogs with acute kidney injury (AKI). Cross-sectional study. Animals-76 dogs with AKI in a referral hospital (2008 to 2009). Dogs' leptospirosis status was defined with a paired serologic MAT against a panel of 11 Leptospira serovars as leptospirosis-associated (n = 30) or nonleptospirosis-associated AKI (12). In 34 dogs, convalescent serologic testing was not possible, and leptospirosis status was classified as undetermined. The diagnostic value of the MAT single acute or convalescent blood sample was determined in dogs in which leptospirosis status could be classified. The diagnostic value of a commercially available genus-specific PCR assay was evaluated by use of 36 blood samples and 20 urine samples. Serologic acute testing of an acute blood sample had a specificity of 100% (95% CI, 76% to 100%), a sensitivity of 50% (33% to 67%), and an accuracy of 64% (49% to 77%). Serologic testing of a convalescent blood sample had a specificity of 92% (65% to 99%), a sensitivity of 100% (87% to 100%), and an accuracy of 98% (88% to 100%). Results of the Leptospira PCR assay were negative for all samples from dogs for which leptospirosis status could be classified. Serologic MAT results were highly accurate for diagnosis of leptospirosis in dogs, despite a low sensitivity for early diagnosis. In this referral setting of dogs pretreated with antimicrobials, testing of blood and urine samples with a commercially available genus-specific PCR assay did not improve early diagnosis.

PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians

PubMed Central

Cui, Zhaolei; Xiao, Zhenzhou; Hu, Minhua; Jiang, Chuanhui; Lin, Yingying; Chen, Yansong

2016-01-01

Background Epigenetic alterations of gene or DNA methylation have been highlighted as promising biomarkers for early cervical cancer screening. Herein, we evaluated the diagnostic performance of paired boxed gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) methylation for cervical cancer detection. Methods Eligible studies were retrieved by searching the electronic databases. Study quality was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 12.0 software. Results The pooled sensitivity of PAX1 methylation was estimated to be 0.73 [95% confidence interval (CI): 0.70–0.75] in differentiating patients with HSIL (high-grade squamous intraepithelial lesion) or CIN3+ (cervical intraepithelial neoplasia type III/worse) or cervical cancer from normal individuals, corresponding to a specificity of 0.87 (95% CI: 0.85–0.89) and area under the curve (AUC) of 0.91. The SOX1 methylation test yielded an AUC of 0.82, under which, the pooled sensitivity was 0.71 (95% CI: 0.67–0.74) and specificity was 0.64 (95% CI: 0.61–0.67). Notably, the stratified analysis suggested that combing parallel testing of PAX1 methylation and human papillomavirus (HPV) DNA (AUC, sensitivity, and specificity of 0.89, 0.75, and 0.81, respectively) achieved higher accuracy than single HPV DNA testing (AUC, sensitivity, and specificity of 0.77, 0.81, and 0.70, respectively). Conclusions PAX1 or SOX1 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening, and parallel testing of PAX1 methylation and HPV DNA in cervical swabs confers an improved diagnostic accuracy than single HPV DNA testing. PMID:27826568

Clinical classification in low back pain: best-evidence diagnostic rules based on systematic reviews.

PubMed

Petersen, Tom; Laslett, Mark; Juhl, Carsten

2017-05-12

Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization. A sensitive electronic search strategy using MEDLINE, EMBASE and CINAHL databases was combined with hand searching and citation tracking to identify eligible studies. Criteria for inclusion were: persons with low back pain with or without related leg symptoms, history or physical examination findings suitable for use in primary care, comparison with acceptable reference standards, and statistical reporting permitting calculation of diagnostic value. Quality assessments were made independently by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies tool. Clinical examination findings that were investigated by at least two studies were included and results that met our predefined threshold of positive likelihood ratio ≥ 2 or negative likelihood ratio ≤ 0.5 were considered for the CDR. Sixty-four studies satisfied our eligible criteria. We were able to construct promising CDRs for symptomatic intervertebral disc, sacroiliac joint, spondylolisthesis, disc herniation with nerve root involvement, and spinal stenosis. Single clinical test appear not to be as useful as clusters of tests that are more closely in line with clinical decision making. This is the first comprehensive systematic review of diagnostic accuracy studies that evaluate clinical examination findings for their ability to identify the most common patho-anatomical disorders in the lumbar spine. In some diagnostic categories we have sufficient evidence to recommend a CDR. In others, we have only preliminary evidence that needs testing in future studies. Most findings were tested in secondary or tertiary care. Thus, the accuracy of the findings in a primary care setting has yet to be confirmed.

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening

PubMed Central

Condell, Orla; Wasunna, Christine; Kpaka, Jonathan; Zwizwai, Ruth; Nuha, Mahmood; Fallah, Mosoka; Freeman, Maxwell; Harris, Victoria; Miller, Mark; Baller, April; Massaquoi, Moses; Katawera, Victoria; Saindon, John; Bemah, Philip; Hamblion, Esther; Castle, Evelyn; Williams, Desmond; Gasasira, Alex; Nyenswah, Tolbert

2018-01-01

The 2014–16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64–100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region. PMID:29304039

Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening.

PubMed

Raftery, Philomena; Condell, Orla; Wasunna, Christine; Kpaka, Jonathan; Zwizwai, Ruth; Nuha, Mahmood; Fallah, Mosoka; Freeman, Maxwell; Harris, Victoria; Miller, Mark; Baller, April; Massaquoi, Moses; Katawera, Victoria; Saindon, John; Bemah, Philip; Hamblion, Esther; Castle, Evelyn; Williams, Desmond; Gasasira, Alex; Nyenswah, Tolbert

2018-01-01

The 2014-16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64-100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region.

Gas gun shock experiments with single-pulse x-ray phase contrast imaging and diffraction at the Advanced Photon Source

NASA Astrophysics Data System (ADS)

Luo, S. N.; Jensen, B. J.; Hooks, D. E.; Fezzaa, K.; Ramos, K. J.; Yeager, J. D.; Kwiatkowski, K.; Shimada, T.

2012-07-01

The highly transient nature of shock loading and pronounced microstructure effects on dynamic materials response call for in situ, temporally and spatially resolved, x-ray-based diagnostics. Third-generation synchrotron x-ray sources are advantageous for x-ray phase contrast imaging (PCI) and diffraction under dynamic loading, due to their high photon fluxes, high coherency, and high pulse repetition rates. The feasibility of bulk-scale gas gun shock experiments with dynamic x-ray PCI and diffraction measurements was investigated at the beamline 32ID-B of the Advanced Photon Source. The x-ray beam characteristics, experimental setup, x-ray diagnostics, and static and dynamic test results are described. We demonstrate ultrafast, multiframe, single-pulse PCI measurements with unprecedented temporal (<100 ps) and spatial (˜2 μm) resolutions for bulk-scale shock experiments, as well as single-pulse dynamic Laue diffraction. The results not only substantiate the potential of synchrotron-based experiments for addressing a variety of shock physics problems, but also allow us to identify the technical challenges related to image detection, x-ray source, and dynamic loading.

High-resolution melting PCR assay, applicable for diagnostics and screening studies, allowing detection and differentiation of several Babesia spp. infecting humans and animals.

PubMed

Rozej-Bielicka, Wioletta; Masny, Aleksander; Golab, Elzbieta

2017-10-01

The goal of the study was to design a single tube PCR test for detection and differentiation of Babesia species in DNA samples obtained from diverse biological materials. A multiplex, single tube PCR test was designed for amplification of approximately 400 bp region of the Babesia 18S rRNA gene. Universal primers were designed to match DNA of multiple Babesia spp. and to have low levels of similarity to DNA sequences of other intracellular protozoa and Babesia hosts. The PCR products amplified from Babesia DNA isolated from human, dog, rodent, deer, and tick samples were subjected to high-resolution melting analysis for Babesia species identification. The designed test allowed detection and differentiation of four Babesia species, three zoonotic (B. microti, B. divergens, B. venatorum) and one that is generally not considered zoonotic-Babesia canis. Both detection and identification of all four species were possible based on the HRM curves of the PCR products in samples obtained from the following: humans, dogs, rodents, and ticks. No cross-reactivity with DNA of Babesia hosts or Plasmodium falciparum and Toxoplasma gondii was observed. The lack of cross-reactivity with P. falciparum DNA might allow using the assay in endemic malaria areas. The designed assay is the first PCR-based test for detection and differentiation of several Babesia spp. of medical and veterinary importance, in a single tube reaction. The results of the study show that the designed assay for Babesia detection and identification could be a practical and inexpensive tool for diagnostics and screening studies of diverse biological materials.

Single-shot Z eff dense plasma diagnostic through simultaneous refraction and attenuation measurements with a Talbot–Lau x-ray moiré deflectometer

DOE PAGES

Valdivia, M. P.; Stutman, D.; Finkenthal, M.

2015-03-23

The Talbot–Lau x-ray moiré deflectometer is a powerful plasma diagnostic capable of delivering simultaneous refraction and attenuation information through the accurate detection of x-ray phase shift and intensity. The diagnostic can provide the index of refraction n=1₋δ + iβ of an object (dense plasma, for example) placed in the x-ray beam by independently measuring both δ and β, which are directly related to the electron density n e and the attenuation coefficient μ respectively. Since δ and β depend on the effective atomic number Z eff, a map can be obtained from the ratio between phase and absorption images acquiredmore » in a single shot. The Talbot–Lau x-ray moiré deflectometer and its corresponding data acquisition and processing are briefly described to illustrate how the above is achieved; Z eff values of test objects within the 4₋12 range were obtained experimentally through simultaneous refraction and attenuation measurements. We show that Z eff mapping of objects does not require previous knowledge of sample length or shape. In conclusion, the determination of Z eff from refraction and attenuation measurements with moiré deflectometry could be of high interest to various domains of high energy density research, such as shocked materials and inertial confinement fusion experiments, as well as material science and nondestructive testing.« less

Single-shot Z eff dense plasma diagnostic through simultaneous refraction and attenuation measurements with a Talbot–Lau x-ray moiré deflectometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdivia, M. P.; Stutman, D.; Finkenthal, M.

The Talbot–Lau x-ray moiré deflectometer is a powerful plasma diagnostic capable of delivering simultaneous refraction and attenuation information through the accurate detection of x-ray phase shift and intensity. The diagnostic can provide the index of refraction n=1₋δ + iβ of an object (dense plasma, for example) placed in the x-ray beam by independently measuring both δ and β, which are directly related to the electron density n e and the attenuation coefficient μ respectively. Since δ and β depend on the effective atomic number Z eff, a map can be obtained from the ratio between phase and absorption images acquiredmore » in a single shot. The Talbot–Lau x-ray moiré deflectometer and its corresponding data acquisition and processing are briefly described to illustrate how the above is achieved; Z eff values of test objects within the 4₋12 range were obtained experimentally through simultaneous refraction and attenuation measurements. We show that Z eff mapping of objects does not require previous knowledge of sample length or shape. In conclusion, the determination of Z eff from refraction and attenuation measurements with moiré deflectometry could be of high interest to various domains of high energy density research, such as shocked materials and inertial confinement fusion experiments, as well as material science and nondestructive testing.« less

HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites

PubMed Central

Kosack, Cara S.; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng’ang’a, Anne; Andre, Bita; Zahinda, Jean-Paul BN; Fransen, Katrien; Page, Anne-Laure

2017-01-01

Abstract Introduction: We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. Methods: In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. Results: Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. Conclusions: The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy. PMID:28691437

HIV misdiagnosis in sub-Saharan Africa: performance of diagnostic algorithms at six testing sites.

PubMed

Kosack, Cara S; Shanks, Leslie; Beelaert, Greet; Benson, Tumwesigye; Savane, Aboubacar; Ng'ang'a, Anne; Andre, Bita; Zahinda, Jean-Paul Bn; Fransen, Katrien; Page, Anne-Laure

2017-07-03

We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub-Saharan African countries. In this prospective multisite diagnostic evaluation study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state-of-the-art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme-linked immuno-sorbent assay, a line-immunoassay, a single antigen-enzyme immunoassay and a DNA polymerase chain reaction test. Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false-positive and 8 false-negative results. Six false-negative specimens were retested with the on-site algorithm on the same sample and were found to be positive. Conversely, 13 false-positive specimens were retested: 8 remained false-positive with the on-site algorithm. The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false-positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy.

Extended Testability Analysis Tool

NASA Technical Reports Server (NTRS)

Melcher, Kevin; Maul, William A.; Fulton, Christopher

2012-01-01

The Extended Testability Analysis (ETA) Tool is a software application that supports fault management (FM) by performing testability analyses on the fault propagation model of a given system. Fault management includes the prevention of faults through robust design margins and quality assurance methods, or the mitigation of system failures. Fault management requires an understanding of the system design and operation, potential failure mechanisms within the system, and the propagation of those potential failures through the system. The purpose of the ETA Tool software is to process the testability analysis results from a commercial software program called TEAMS Designer in order to provide a detailed set of diagnostic assessment reports. The ETA Tool is a command-line process with several user-selectable report output options. The ETA Tool also extends the COTS testability analysis and enables variation studies with sensor sensitivity impacts on system diagnostics and component isolation using a single testability output. The ETA Tool can also provide extended analyses from a single set of testability output files. The following analysis reports are available to the user: (1) the Detectability Report provides a breakdown of how each tested failure mode was detected, (2) the Test Utilization Report identifies all the failure modes that each test detects, (3) the Failure Mode Isolation Report demonstrates the system s ability to discriminate between failure modes, (4) the Component Isolation Report demonstrates the system s ability to discriminate between failure modes relative to the components containing the failure modes, (5) the Sensor Sensor Sensitivity Analysis Report shows the diagnostic impact due to loss of sensor information, and (6) the Effect Mapping Report identifies failure modes that result in specified system-level effects.

Surveillance of intestinal schistosomiasis during control: a comparison of four diagnostic tests across five Ugandan primary schools in the Lake Albert region.

PubMed

Al-Shehri, Hajri; Koukounari, Artemis; Stanton, Michelle C; Adriko, Moses; Arinaitwe, Moses; Atuhaire, Aaron; Kabatereine, Narcis B; Stothard, J Russell

2018-03-21

Programmatic surveillance of intestinal schistosomiasis during control can typically use four diagnostic tests, either singularly or in combination, but these have yet to be cross-compared directly. Our study assembled a complete diagnostic dataset, inclusive of infection intensities, from 258 children from five Ugandan primary schools. The schools were purposely selected as typical of the endemic landscape near Lake Albert and reflective of high- and low-transmission settings. Overall prevalence was: 44.1% (95% CI 38.0-50.2) by microscopy of duplicate Kato-Katz smears from two consecutive stools, 56.9% (95% CI 50.8-63.0) by urine-circulating cathodic antigen (CCA) dipstick, 67.4% (95% CI 61.6-73.1) by DNA-TaqMan® and 75.1% (95% CI 69.8-80.4) by soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA). A cross-comparison of diagnostic sensitivities, specificities, positive and negative predictive values was undertaken, inclusive of a latent class analysis (LCA) with a LCA-model estimate of prevalence by each school. The latter ranged from 9.6% to 100.0%, and prevalence by school for each diagnostic test followed a static ascending order or monotonic series of Kato-Katz, urine-CCA dipstick, DNA-TaqMan® and SEA-ELISA. We confirm that Kato-Katz remains a satisfactory diagnostic standalone in high-transmission settings but in low-transmission settings should be augmented or replaced by urine-CCA dipsticks. DNA-TaqMan® appears suitable in both endemic settings though is only implementable if resources permit. In low-transmission settings, SEA-ELISA remains the method of choice to evidence an absence infection. We discuss the pros and cons of each method concluding that future surveillance of intestinal schistosomiasis would benefit from a flexible, context-specific approach both in choice and application of each diagnostic method, rather than a single one-size fits all approach.

Electron Beam Transport in Advanced Plasma Wave Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Ronald L

2013-01-31

The primary goal of this grant was to develop a diagnostic for relativistic plasma wave accelerators based on injecting a low energy electron beam (5-50keV) perpendicular to the plasma wave and observing the distortion of the electron beam's cross section due to the plasma wave's electrostatic fields. The amount of distortion would be proportional to the plasma wave amplitude, and is the basis for the diagnostic. The beat-wave scheme for producing plasma waves, using two CO2 laser beam, was modeled using a leap-frog integration scheme to solve the equations of motion. Single electron trajectories and corresponding phase space diagrams weremore » generated in order to study and understand the details of the interaction dynamics. The electron beam was simulated by combining thousands of single electrons, whose initial positions and momenta were selected by random number generators. The model was extended by including the interactions of the electrons with the CO2 laser fields of the beat wave, superimposed with the plasma wave fields. The results of the model were used to guide the design and construction of a small laboratory experiment that may be used to test the diagnostic idea.« less

The rapid evolution of molecular genetic diagnostics in neuromuscular diseases.

PubMed

Volk, Alexander E; Kubisch, Christian

2017-10-01

The development of massively parallel sequencing (MPS) has revolutionized molecular genetic diagnostics in monogenic disorders. The present review gives a brief overview of different MPS-based approaches used in clinical diagnostics of neuromuscular disorders (NMDs) and highlights their advantages and limitations. MPS-based approaches like gene panel sequencing, (whole) exome sequencing, (whole) genome sequencing, and RNA sequencing have been used to identify the genetic cause in NMDs. Although gene panel sequencing has evolved as a standard test for heterogeneous diseases, it is still debated, mainly because of financial issues and unsolved problems of variant interpretation, whether genome sequencing (and to a lesser extent also exome sequencing) of single patients can already be regarded as routine diagnostics. However, it has been shown that the inclusion of parents and additional family members often leads to a substantial increase in the diagnostic yield in exome-wide/genome-wide MPS approaches. In addition, MPS-based RNA sequencing just enters the research and diagnostic scene. Next-generation sequencing increasingly enables the detection of the genetic cause in highly heterogeneous diseases like NMDs in an efficient and affordable way. Gene panel sequencing and family-based exome sequencing have been proven as potent and cost-efficient diagnostic tools. Although clinical validation and interpretation of genome sequencing is still challenging, diagnostic RNA sequencing represents a promising tool to bypass some hurdles of diagnostics using genomic DNA.

[Telomerase in lung cancer. Testing the activity of the "immortaligy enzyme" bronchial biopsies increases the diagnostic yield in cases of suspected peripheral bronchogenic carcinomas].

PubMed

Freitag, L; Litterst, P; Obertrifter, B; Velehorschi, V; Kemmer, H P; Linder, A; Brightman, I

2000-11-01

The proliferative capability is time-limited in normal somatic cells by the shortening of their chromosomal ends, the telomeres (Hayflick limit). An important feature of malignant cells is their immortality. The probably most common mechanism of tumour cells to achieve unlimited replicability is the activation of the enzyme telomerase. The reverse transcriptase can compensate the loss of telomeres. Using a PCR-based TRAP assay we found telomerase activity in tumour biopsies, exsudates and bronchial washings in various thoracic malignancies. In 38 of 47 patients with suspected peripheral lung cancer eventually surgery or invasive procedures proved a malignancy. In fluoroscopically guided bronchial brushings from 25 of these 38 patients (66%) the TRAP assay revealed telomerase activity. There was a single false positive case (tuberculosis) and with a single exception, the simultaneously taken brushes of the contralateral lobes were all telomerase negative. In 23 patients (61%) tumour cells were found in the cytological examination. In 33 patients at least one marker was positive. Thus the combination of cytology and telomerase test in bronchial brush biopsies attained a diagnostic yield of 87%.

The diagnostic accuracy and outcomes after coronary computed tomography angiography vs. conventional functional testing in patients with stable angina pectoris: a systematic review and meta-analysis.

PubMed

Nielsen, Lene H; Ortner, Nino; Nørgaard, Bjarne L; Achenbach, Stephan; Leipsic, Jonathon; Abdulla, Jawdat

2014-09-01

To systematically review and perform a meta-analysis of the diagnostic accuracy and post-test outcomes of conventional exercise electrocardiography (XECG) and single-photon emission computed tomography (SPECT) compared with coronary computed tomography angiography (coronary CTA) in patients suspected of stable coronary artery disease (CAD). We systematically searched for studies published from January 2002 to February 2013 examining the diagnostic accuracy (defined as at least ≥50% luminal obstruction on invasive coronary angiography) and outcomes of coronary CTA (≥16 slice) in comparison with XECG and SPECT. The search revealed 11 eligible studies (N = 1575) comparing the diagnostic accuracy and 7 studies (N = 216.603) the outcomes of coronary CTA vs. XECG or/and SPECT. The per-patient sensitivity [95% confidence interval (95% CI)] to identify significant CAD was 98% (93-99%) for coronary CTA vs. 67% (54-78%) (P < 0.001) for XECG and 99% (96-100%) vs. 73% (59-83%) (P = 0.001) for SPECT. The specificity (95% CI) of coronary CTA was 82% (63-93%) vs. 46% (30-64%) (P < 0.001) for XECG and 71% (60-80%) vs. 48% (31-64%) (P = 0.14) for SPECT. The odds ratio (OR) of downstream test utilization (DTU) for coronary CTA vs. XECG/SPECT was 1.38 (1.33-1.43, P < 0.001), for revascularization 2.63 (2.50-2.77, P < 0.001), for non-fatal myocardial infarction 0.53 (0.39-0.72, P < 0.001), and for all-cause mortality 1.01 (0.87-1.18, P = 0.87). The up-front diagnostic performance of coronary CTA is higher than of XECG and SPECT. When compared with XECG/SPECT testing, coronary CTA testing is associated with increased DTU and coronary revascularization. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Multiple-taper spectral analysis: A stand-alone C-subroutine

NASA Astrophysics Data System (ADS)

Lees, Jonathan M.; Park, Jeffrey

1995-03-01

A simple set of subroutines in ANSI-C are presented for multiple taper spectrum estimation. The multitaper approach provides an optimal spectrum estimate by minimizing spectral leakage while reducing the variance of the estimate by averaging orthogonal eigenspectrum estimates. The orthogonal tapers are Slepian nπ prolate functions used as tapers on the windowed time series. Because the taper functions are orthogonal, combining them to achieve an average spectrum does not introduce spurious correlations as standard smoothed single-taper estimates do. Furthermore, estimates of the degrees of freedom and F-test values at each frequency provide diagnostics for determining levels of confidence in narrow band (single frequency) periodicities. The program provided is portable and has been tested on both Unix and Macintosh systems.

A systematic review and meta-analysis of studies evaluating the performance and operational characteristics of dual point-of-care tests for HIV and syphilis.

PubMed

Gliddon, Harriet D; Peeling, Rosanna W; Kamb, Mary L; Toskin, Igor; Wi, Teodora E; Taylor, Melanie M

2017-12-01

Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality. To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use. Systematic review and meta-analysis. We searched seven electronic bibliographic databases from 2012 to December 2016 with no language restrictions. Search keywords included HIV, syphilis and diagnosis. We included studies that evaluated the operational characteristics of dual HIV/syphilis RDTs. Outcomes included diagnostic test accuracy, cost effectiveness, ease of use and interpretation and acceptability. All studies were assessed against quality criteria and assessed for risk of bias. Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost and the requirement of a single finger prick as important characteristics of dual RDTs. The results of this systematic review and meta-analysis can be used by policy-makers and national programme managers who are considering implementing dual RDTs for HIV and syphilis. PROSPERO 2016:CRD42016049168. © World Health Organization 2017. Licensee BMJ Publishing Group Limited. This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (https://creativecommons.org/licenses/by/3.0/igo), which permits use, distribution, and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.

The value of multiple tests of respiratory muscle strength

PubMed Central

Steier, Joerg; Kaul, Sunny; Seymour, John; Jolley, Caroline; Rafferty, Gerrard; Man, William; Luo, Yuan M; Roughton, Michael; Polkey, Michael I; Moxham, John

2007-01-01

Background Respiratory muscle weakness is an important clinical problem. Tests of varying complexity and invasiveness are available to assess respiratory muscle strength. The relative precision of different tests in the detection of weakness is less clear, as is the value of multiple tests. Methods The respiratory muscle function tests of clinical referrals who had multiple tests assessed in our laboratories over a 6‐year period were analysed. Thresholds for weakness for each test were determined from published and in‐house laboratory data. The patients were divided into three groups: those who had all relevant measurements of global inspiratory muscle strength (group A, n = 182), those with full assessment of diaphragm strength (group B, n = 264) and those for whom expiratory muscle strength was fully evaluated (group C, n = 60). The diagnostic outcome of each inspiratory, diaphragm and expiratory muscle test, both singly and in combination, was studied and the impact of using more than one test to detect weakness was calculated. Results The clinical referrals were primarily for the evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal inspiratory mouth pressure (Pimax) was recorded in 40.1% of referrals in group A, while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory strength with the combination of all three tests, 29.6% of patients had weakness. Using the two non‐invasive tests (Pimax and Sniff Pnasal) in combination, a similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%) and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory muscle weakness as measured by maximum expiratory pressure (Pemax) compared with 36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3% when assessed by Twitch T10. Combining all three expiratory muscle tests reduced the number of patients diagnosed as having expiratory muscle weakness to 16.7%. Conclusion The use of single tests such as Pimax, Pemax and other available individual tests of inspiratory, diaphragm and expiratory muscle strength tends to overdiagnose weakness. Combinations of tests increase diagnostic precision and, in the population studied, they reduced the diagnosis of inspiratory, specific diaphragm and expiratory muscle weakness by 19–56%. Measuring both Pimax and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple tests of respiratory muscle function available both increases diagnostic precision and makes assessment possible in a range of clinical circumstances. PMID:17557772

A Ribeiroia spp. (Class: Trematoda) - Specific PCR-based diagnostic

USGS Publications Warehouse

Reinitz, David M.; Yoshino, T.P.; Cole, Rebecca A.

2007-01-01

Increased reporting of amphibian malformations in North America has been noted with concern in light of reports that amphibian numbers and species are declining worldwide. Ribeiroia ondatrae has been shown to cause a variety of types of malformations in amphibians. However, little is known about the prevalence of R. ondatrae in North America. To aid in conducting field studies of Ribeiroia spp., we have developed a polymerase chain reaction (PCR)-based diagnostic. Herein, we describe the development of an accurate, rapid, simple, and cost-effective diagnostic for detection of Ribeiroia spp. infection in snails (Planorbella trivolvis). Candidate oligonucleotide primers for PCR were designed via DNA sequence analyses of multiple ribosomal internal transcribed spacer-2 regions from Ribeiroia spp. and Echinostoma spp. Comparison of consensus sequences determined from both genera identified areas of sequence potentially unique to Ribeiroia spp. The PCR reliably produced a diagnostic 290-base pair (bp) product in the presence of a wide concentration range of snail or frog DNA. Sensitivity was examined with DNA extracted from single R. ondatrae cercaria. The single-tube PCR could routinely detect less than 1 cercariae equivalent, because DNA isolated from a single cercaria could be diluted at least 1:50 and still yield a positive result via gel electrophoresis. An even more sensitive nested PCR also was developed that routinely detected 100 fg of the 290-bp fragment. The assay did not detect furcocercous cercariae of certain Schistosomatidae, Echinostoma sp., or Sphaeridiotrema globulus nor adults of Clinostomum sp. or Cyathocotyle bushiensis. Field testing of 137 P. trivolvis identified 3 positives with no overt environmental cross-reactivity, and results concurred with microscopic examinations in all cases. ?? American Society of Parasitologists 2007.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Procedural Terminology published by the American Medical Association. (vii) Diagnostic tests performed by a... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Procedural Terminology published by the American Medical Association. (vii) Diagnostic tests performed by a... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases.

PubMed

Ducancelle, Alexandra; Leroy, Vincent; Vergniol, Julien; Sturm, Nathalie; Le Bail, Brigitte; Zarski, Jean Pierre; Nguyen Khac, Eric; Salmon, Dominique; de Ledinghen, Victor; Calès, Paul

2017-08-01

International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.

Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

PubMed

Escudero, A I; Sánchez-Guerrero, I M; Mora, A M; Soriano, V; López, J D; García, F J; Negro, J M; Hernández, J; Pagán, J A

1993-01-01

This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

A practical, evidence-based, comprehensive (PEC) physical examination for diagnosing pathology of the long head of the biceps.

PubMed

Rosas, Samuel; Krill, Michael K; Amoo-Achampong, Kelms; Kwon, KiHyun; Nwachukwu, Benedict U; McCormick, Frank

2017-08-01

Clinical examination of the shoulder joint has gained attention as clinicians aim to use an evidence-based examination of the biceps tendon, with the desire for a proper diagnosis while minimizing costly imaging procedures. The purpose of this study is to create a decision tree analysis that enables the development of a clinical algorithm for diagnosing long head of biceps (LHB) pathology. A literature review of Level I and II diagnostic studies was conducted to extract characteristics of clinical tests for LHB pathology through a systematic review of PubMed, Medline, Ovid, and Cochrane Review databases. Tests were combined in series and parallel to determine sensitivities and specificities, and positive and negative likelihood ratios were determined for each combination using a subjective pretest probability. The "gold standard" for diagnosis in all included studies was arthroscopy or arthrotomy. The optimal testing modality was use of the uppercut test combined with the tenderness to palpation of the biceps tendon test. This combination achieved a sensitivity of 88.4% when performed in parallel and a specificity of 93.8% when performed in series. These tests used in combination optimize post-test probability accuracy greater than any single individual test. Performing the uppercut test and biceps groove tenderness to palpation test together has the highest sensitivity and specificity of known physical examinations maneuvers to aid in the diagnosis of LHB pathology compared with diagnostic arthroscopy (practical, evidence-based, comprehensive examination). A decision tree analysis aides in the practical, evidence-based, comprehensive examination diagnostic accuracy post-testing based on the ordinal scale pretest probability. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Multi-method automated diagnostics of rotating machines

NASA Astrophysics Data System (ADS)

Kostyukov, A. V.; Boychenko, S. N.; Shchelkanov, A. V.; Burda, E. A.

2017-08-01

The automated machinery diagnostics and monitoring systems utilized within the petrochemical plants are an integral part of the measures taken to ensure safety and, as a consequence, the efficiency of these industrial facilities. Such systems are often limited in their functionality due to the specifics of the diagnostic techniques adopted. As the diagnostic techniques applied in each system are limited, and machinery defects can have different physical nature, it becomes necessary to combine several diagnostics and monitoring systems to control various machinery components. Such an approach is inconvenient, since it requires additional measures to bring the diagnostic results in a single view of the technical condition of production assets. In this case, we mean by a production facility a bonded complex of a process unit, a drive, a power source and lines. A failure of any of these components will cause an outage of the production asset, which is unacceptable. The purpose of the study is to test a combined use of vibration diagnostics and partial discharge techniques within the diagnostic systems of enterprises for automated control of the technical condition of rotating machinery during maintenance and at production facilities. The described solutions allow you to control the condition of mechanical and electrical components of rotating machines. It is shown that the functionality of the diagnostics systems can be expanded with minimal changes in technological chains of repair and operation of rotating machinery. Automation of such systems reduces the influence of the human factor on the quality of repair and diagnostics of the machinery.

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

PubMed

Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha

2017-02-01

To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

Multiplanar lumbopelvic control in patients with low back pain: is multiplanar assessment better than single plane assessment in discriminating between patients and healthy controls?

PubMed

Nelson-Wong, E; Gallant, P; Alexander, S; Dehmer, K; Ingvalson, S; McClenahan, B; Piatte, A; Poupore, K; Davis, A M

2016-02-01

Patients with low back pain (LBP) commonly have lumbopelvic control deficits. Lumbopelvic assessment during sagittal motion is incorporated into commonly used clinical examination algorithms for Treatment Based Classification. The purpose of this study was to investigate whether combined assessment of lumbopelvic control during sagittal and frontal plane motion discriminates between people with and without LBP better than single plane assessment alone. Nineteen patients with LBP and 18 healthy control participants volunteered for this study. The active straight leg raise (ASLR) and active hip abduction (AHAbd) tests were used to assess lumbopelvic control during sagittal and frontal plane motion, respectively. The tests were scored as positive or negative using published scoring criteria. Contingency tables were created for each test alone and for the combined tests (both positive/both negative) with presence/absence of LBP as the reference standard to calculate accuracy statistics of sensitivity (sn), specificity (sp), likelihood (+LR and -LR), and diagnostic odds ratios (OR). Active straight leg raise and AHAbd tests alone had sn of 0·63, 0·74, respectively, sp of 0·61, 0·50, respectively, and OR of 2·7, 2·8, respectively. The combined tests had sn = 0·89, sp = 0·60, and OR = 12·0. Forty percent of patients with LBP had control deficits in both planes of motion. The AHAbd and ALSR tests appear to have greater diagnostic discrimination when used in combination than when used independently. A percentage of patients with LBP had control deficits in both planes, while others demonstrated uniplanar deficits only. These findings highlight the importance of multiplanar assessment in patients with LBP.

Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis

PubMed Central

Morris, R K; Riley, R D; Doug, M; Deeks, J J

2012-01-01

Objective To determine the diagnostic accuracy of two “spot urine” tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Design Systematic review and meta-analysis. Data sources Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Inclusion criteria Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Data extraction Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Results Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67). Conclusion The maternal “spot urine” estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome. PMID:22777026

Photoacoustic sensor for medical diagnostics

NASA Astrophysics Data System (ADS)

Wolff, Marcus; Groninga, Hinrich G.; Harde, Hermann

2004-03-01

The development of new optical sensor technologies has a major impact on the progress of diagnostic methods. Of the permanently increasing number of non-invasive breath tests, the 13C-Urea Breath Test (UBT) for the detection of Helicobacter pylori is the most prominent. However, many recent developments, like the detection of cancer by breath test, go beyond gastroenterological applications. We present a new detection scheme for breath analysis that employs an especially compact and simple set-up. Photoacoustic Spectroscopy (PAS) represents an offset-free technique that allows for short absorption paths and small sample cells. Using a single-frequency diode laser and taking advantage of acoustical resonances of the sample cell, we performed extremely sensitive and selective measurements. The smart data processing method contributes to the extraordinary sensitivity and selectivity as well. Also, the reasonable acquisition cost and low operational cost make this detection scheme attractive for many biomedical applications. The experimental set-up and data processing method, together with exemplary isotope-selective measurements on carbon dioxide, are presented.

A standard test case suite for two-dimensional linear transport on the sphere: results from a collection of state-of-the-art schemes

NASA Astrophysics Data System (ADS)

Lauritzen, P. H.; Ullrich, P. A.; Jablonowski, C.; Bosler, P. A.; Calhoun, D.; Conley, A. J.; Enomoto, T.; Dong, L.; Dubey, S.; Guba, O.; Hansen, A. B.; Kaas, E.; Kent, J.; Lamarque, J.-F.; Prather, M. J.; Reinert, D.; Shashkin, V. V.; Skamarock, W. C.; Sørensen, B.; Taylor, M. A.; Tolstykh, M. A.

2013-09-01

Recently, a standard test case suite for 2-D linear transport on the sphere was proposed to assess important aspects of accuracy in geophysical fluid dynamics with a "minimal" set of idealized model configurations/runs/diagnostics. Here we present results from 19 state-of-the-art transport scheme formulations based on finite-difference/finite-volume methods as well as emerging (in the context of atmospheric/oceanographic sciences) Galerkin methods. Discretization grids range from traditional regular latitude-longitude grids to more isotropic domain discretizations such as icosahedral and cubed-sphere tessellations of the sphere. The schemes are evaluated using a wide range of diagnostics in idealized flow environments. Accuracy is assessed in single- and two-tracer configurations using conventional error norms as well as novel diagnostics designed for climate and climate-chemistry applications. In addition, algorithmic considerations that may be important for computational efficiency are reported on. The latter is inevitably computing platform dependent, The ensemble of results from a wide variety of schemes presented here helps shed light on the ability of the test case suite diagnostics and flow settings to discriminate between algorithms and provide insights into accuracy in the context of global atmospheric/ocean modeling. A library of benchmark results is provided to facilitate scheme intercomparison and model development. Simple software and data-sets are made available to facilitate the process of model evaluation and scheme intercomparison.

A standard test case suite for two-dimensional linear transport on the sphere: results from a collection of state-of-the-art schemes

NASA Astrophysics Data System (ADS)

Lauritzen, P. H.; Ullrich, P. A.; Jablonowski, C.; Bosler, P. A.; Calhoun, D.; Conley, A. J.; Enomoto, T.; Dong, L.; Dubey, S.; Guba, O.; Hansen, A. B.; Kaas, E.; Kent, J.; Lamarque, J.-F.; Prather, M. J.; Reinert, D.; Shashkin, V. V.; Skamarock, W. C.; Sørensen, B.; Taylor, M. A.; Tolstykh, M. A.

2014-01-01

Recently, a standard test case suite for 2-D linear transport on the sphere was proposed to assess important aspects of accuracy in geophysical fluid dynamics with a "minimal" set of idealized model configurations/runs/diagnostics. Here we present results from 19 state-of-the-art transport scheme formulations based on finite-difference/finite-volume methods as well as emerging (in the context of atmospheric/oceanographic sciences) Galerkin methods. Discretization grids range from traditional regular latitude-longitude grids to more isotropic domain discretizations such as icosahedral and cubed-sphere tessellations of the sphere. The schemes are evaluated using a wide range of diagnostics in idealized flow environments. Accuracy is assessed in single- and two-tracer configurations using conventional error norms as well as novel diagnostics designed for climate and climate-chemistry applications. In addition, algorithmic considerations that may be important for computational efficiency are reported on. The latter is inevitably computing platform dependent. The ensemble of results from a wide variety of schemes presented here helps shed light on the ability of the test case suite diagnostics and flow settings to discriminate between algorithms and provide insights into accuracy in the context of global atmospheric/ocean modeling. A library of benchmark results is provided to facilitate scheme intercomparison and model development. Simple software and data sets are made available to facilitate the process of model evaluation and scheme intercomparison.

Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways.

PubMed

Verhoef, Talitha I; Hill, Melissa; Drury, Suzanne; Mason, Sarah; Jenkins, Lucy; Morris, Stephen; Chitty, Lyn S

2016-07-01

Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice. Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders. For autosomal dominant conditions, where NIPD molecular techniques are straightforward, NIPD cost £314 less than invasive testing. NIPD for autosomal recessive and X-linked conditions requires more complicated technical approaches and total costs were more than invasive testing, e.g. NIPD for spinal muscular atrophy was £1090 more than invasive testing. Impact of test uptake on costs was assessed using sickle cell disorder as an example. Anticipated high uptake of NIPD resulted in an incremental cost of NIPD over invasive testing of £48 635 per 100 pregnancies at risk of sickle cell disorder. Total costs of NIPD are dependent upon the complexity of the testing technique required. Anticipated increased demand for testing may have economic implications for prenatal diagnostic services. Ethical issues requiring further consideration are highlighted including directing resources to NIPD when used for information only and restricting access to safe tests if it is not cost-effective to develop NIPD for rare conditions. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

PubMed Central

Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

2015-01-01

Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P < .001), lower cartilage FF (P < .001), and similar cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P < .05) after consideration of age differences between groups of subjects. Diagnostic performance was higher with FF than with T2Single for distinguishing between normal and degenerative cartilage (P < .05), with greater areas under the curve at receiver operating characteristic analysis. Conclusion Patients with osteoarthritis of the knee had significantly higher cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that FF may allow greater diagnostic performance than that with T2Single for distinguishing between normal and degenerative cartilage. © RSNA, 2015 Online supplemental material is available for this article. PMID:26024307

Important clinical descriptors to include in the examination and assessment of patients with femoroacetabular impingement syndrome: an international and multi-disciplinary Delphi survey.

PubMed

Reiman, M P; Thorborg, K; Covington, K; Cook, C E; Hölmich, P

2017-06-01

Determine which examination findings are key clinical descriptors of femoroacetabular impingement syndrome (FAIS) through use of an international, multi-disciplinary expert panel. A three-round Delphi survey utilizing an international, multi-disciplinary expert panel operationally defined from international publications and presentations was utilized. All six domains (subjective examination, patient-reported outcome measures, physical examination, special tests, physical performance measures, and diagnostic imaging) had at least one descriptor with 75% consensus agreement for diagnosis and assessment of FAIS. Diagnostic imaging was the domain with the highest level of agreement. Domains such as patient-reported outcome measures (PRO's) and physical examination were identified as non-diagnostic measures (rather as assessments of disease impact). Although it also had the greatest level of variability in description of examination domains, diagnostic imaging continues to be the preeminent diagnostic measure for FAIS. No single domain should be utilized as the sole diagnostic or assessment parameter for FAIS. While not all investigated domains provide diagnostic capability for FAIS, those that do not are able to serve purpose as a measure of disease impact (e.g., impairments and activity limitations). The clinical relevance of this Delphi survey is the understanding that a comprehensive assessment measuring both diagnostic capability and disease impact most accurately reflects the patient with FAIS. V.

T cell lymphomatoid contact dermatitis: a challenging case and review of the literature.

PubMed

Knackstedt, Thomas J; Zug, Kathryn A

2015-02-01

Lymphomatoid contact dermatitis is a pseudolymphoma with clinical and histological features of allergic contact dermatitis and cutaneous T cell lymphoma. Incorrect diagnosis may lead to unnecessary testing, unnecessary treatment, or patient harm. The objective of this study is to present a case to demonstrate the diagnostic challenge and overlap between allergic contact dermatitis and cutaneous T cell lymphoma in a patient with lymphomatoid contact dermatitis caused by methylchoroisothiazolinone/methylisothiazolinone and paraben mix, and to review the existing literature in order to summarize the demographics, clinical features, allergens and treatments reported for lymphomatoid contact dermatitis. A search of major scientific databases was conducted for English-language articles reporting cases of lymphomatoid contact dermatitis or additional synonymous search headings. Nineteen articles with a total of 23 patients were analysed. Lymphomatoid contact dermatitis was more common in men, with an average age of 58.5 years. Fourteen unique allergens were identified and confirmed by patch testing. However, no single test or study was diagnostic of lymphomatoid contact dermatitis. Allergen avoidance was the most useful management tool, but selected patients required topical or systemic immunosuppression. In conclusion, without specific diagnostic features, evaluation for lymphomatoid contact dermatitis should include a thorough history and examination, patch testing, and biopsy with immunohistochemistry and clonality studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The diagnostic accuracy of the rapid dipstick test to predict asymptomatic urinary tract infection of pregnancy.

PubMed

Eigbefoh, J O; Isabu, P; Okpere, E; Abebe, J

2008-07-01

Untreated urinary tract infection can have devastating maternal and neonatal effects. Thus, routine screening for bacteriuria is advocated. This study was designed to evaluate the diagnostic accuracy of the rapid dipstick test to predict urinary tract infection in pregnancy with the gold standard of urine microscopy, culture and sensitivity acting as the control. The urine dipstick test uses the leucocyte esterase, nitrite and test for protein singly and in combination. The result of the dipstick was compared with the gold standard, urine microscopy, culture and sensitivity using confidence interval for proportions. The reliability and validity of the urine dipstick was also evaluated. Overall, the urine dipstick test has a poor correlation with urine culture (p = 0.125, CI 95%). The same holds true for individual components of the dipstick test. The overall sensitivity of the urine dipstick test was poor at 2.3%. Individual sensitivity of the various components varied between 9.1% for leucocyte esterase and the nitrite test to 56.8% for leucocyte esterase alone. The other components of the dipstick test, the test of nitrite, test for protein and combination of the test (leucocyte esterase, nitrite and proteinuria) appear to decrease the sensitivity of the leucocyte esterase test alone. The ability of the urine dipstick test to correctly rule out urinary tract infection (specificity) was high. The positive predictive value for the dipstick test was high, with the leucocyte esterase test having the highest positive predictive value compared with the other components of the dipstick test. The negative predictive value (NPV) was expectedly highest for the leucocyte esterase test alone with values higher than the other components of the urine dipstick test singly and in various combinations. Compared with the other parameters of the urine dipstick test, singly and in combination, leucocyte esterase appears to be the most accurate (90.25%). The dipstick test has a limited use in screening for asymptomatic bacteriuria. The leucocyte esterase test component of the dipstick test appears to have the highest reliability and validity. The other parameters of the dipstick test decreases the reliability and validity of the leucocyte esterase test. A positive test merits empirical antibiotics, while a negative test is an indication for urine culture. The urine dipstick test if positive will also be useful in follow-up of patient after treatment of urinary tract infection. This is useful in poor resource setting especially in the third world where there is a dearth of trained personnel and equipment for urine culture.

Agreement between diagnoses reached by clinical examination and available reference standards: a prospective study of 216 patients with lumbopelvic pain

PubMed Central

Laslett, Mark; McDonald, Barry; Tropp, Hans; Aprill, Charles N; Öberg, Birgitta

2005-01-01

Background The tissue origin of low back pain (LBP) or referred lower extremity symptoms (LES) may be identified in about 70% of cases using advanced imaging, discography and facet or sacroiliac joint blocks. These techniques are invasive and availability varies. A clinical examination is non-invasive and widely available but its validity is questioned. Diagnostic studies usually examine single tests in relation to single reference standards, yet in clinical practice, clinicians use multiple tests and select from a range of possible diagnoses. There is a need for studies that evaluate the diagnostic performance of clinical diagnoses against available reference standards. Methods We compared blinded clinical diagnoses with diagnoses based on available reference standards for known causes of LBP or LES such as discography, facet, sacroiliac or hip joint blocks, epidurals injections, advanced imaging studies or any combination of these tests. A prospective, blinded validity design was employed. Physiotherapists examined consecutive patients with chronic lumbopelvic pain and/or referred LES scheduled to receive the reference standard examinations. When diagnoses were in complete agreement regardless of complexity, "exact" agreement was recorded. When the clinical diagnosis was included within the reference standard diagnoses, "clinical agreement" was recorded. The proportional chance criterion (PCC) statistic was used to estimate agreement on multiple diagnostic possibilities because it accounts for the prevalence of individual categories in the sample. The kappa statistic was used to estimate agreement on six pathoanatomic diagnoses. Results In a sample of chronic LBP patients (n = 216) with high levels of disability and distress, 67% received a patho-anatomic diagnosis based on available reference standards, and 10% had more than one tissue origin of pain identified. For 27 diagnostic categories and combinations, chance clinical agreement (PCC) was estimated at 13%. "Exact" agreement between clinical and reference standard diagnoses was 32% and "clinical agreement" 51%. For six pathoanatomic categories (disc, facet joint, sacroiliac joint, hip joint, nerve root and spinal stenosis), PCC was 33% with actual agreement 56%. There was no overlap of 95% confidence intervals on any comparison. Diagnostic agreement on the six most common patho-anatomic categories produced a kappa of 0.31. Conclusion Clinical diagnoses agree with reference standards diagnoses more often than chance. Using available reference standards, most patients can have a tissue source of pain identified. PMID:15943873

Disk Crack Detection for Seeded Fault Engine Test

NASA Technical Reports Server (NTRS)

Luo, Huageng; Rodriguez, Hector; Hallman, Darren; Corbly, Dennis; Lewicki, David G. (Technical Monitor)

2004-01-01

Work was performed to develop and demonstrate vibration diagnostic techniques for the on-line detection of engine rotor disk cracks and other anomalies through a real engine test. An existing single-degree-of-freedom non-resonance-based vibration algorithm was extended to a multi-degree-of-freedom model. In addition, a resonance-based algorithm was also proposed for the case of one or more resonances. The algorithms were integrated into a diagnostic system using state-of-the- art commercial analysis equipment. The system required only non-rotating vibration signals, such as accelerometers and proximity probes, and the rotor shaft 1/rev signal to conduct the health monitoring. Before the engine test, the integrated system was tested in the laboratory by using a small rotor with controlled mass unbalances. The laboratory tests verified the system integration and both the non-resonance and the resonance-based algorithm implementations. In the engine test, the system concluded that after two weeks of cycling, the seeded fan disk flaw did not propagate to a large enough size to be detected by changes in the synchronous vibration. The unbalance induced by mass shifting during the start up and coast down was still the dominant response in the synchronous vibration.

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

PubMed

Calès, Paul; Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

2018-04-01

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter V2G ) with those of a test targeted for cirrhosis (CirrhoMeter V2G ). In the derivation CHC population, we first compared Multi-FibroMeter V2G to FibroMeter V2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter V2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter V2G and FibroMeter V2G were the following: cirrhosis AUROC, 0.906 versus 0.878 ( P < 0.001; versus CirroMeter V2G , 0.897, P = 0.014); Obuchowski index, 0.795 versus 0.791 ( P = 0.059); classification, 86.0% versus 82.1% ( P < 0.001); significant fibrosis AUROC, 0.833 versus 0.832 ( P = 0.366). Multi-FibroMeter V2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi-FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ ( P = 0.938). Conclusion: Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single-targeted blood tests. ( Hepatology Communications 2018;2:455-466).

Unraveling of Enigmatic Hearing-Impaired GJB2 Single Heterozygotes by Massive Parallel Sequencing: DFNB1 or Not?

PubMed Central

Kim, So Young; Kim, Ah Reum; Kim, Nayoung K. D.; Lee, Chung; Kim, Min Young; Jeon, Eun-Hee; Park, Woong-Yang; Choi, Byung Yoon

2016-01-01

Abstract The molecular etiology of nonsyndromic sensorineural hearing loss (SNHL) in subjects with only one detectable autosomal recessive GJB2 mutation is unclear. Here, we report GJB2 single heterozygotes with various final genetic diagnoses and suggest appropriate diagnostic strategies. A total of 160 subjects with SNHL without phenotypic markers were screened for GJB2 mutations. Single-nucleotide variants or structural variations within the DFNB1 locus or in other deafness genes were examined by Sanger sequencing, breakpoint PCR, and targeted exome sequencing (TES) of 129 deafness genes. We identified 27 subjects with two mutations and 10 subjects with only one detectable mutation in GJB2. The detection rate of the single GJB2 mutation among the 160 SNHL subjects in the present study (6.25%) was higher than 2.58% in normal hearing controls in Korean. The DFNB1 was clearly excluded as a molecular etiology in four (40%) subjects: other recessive deafness genes (N = 3) accounted for SNHL and the causative gene for the other non-DFNB1 subject (N = 1) was not identified. The etiology of additional two subjects was potentially explained by digenic etiology (N = 2) of GJB2 with MITF and GJB3, respectively. The contribution of the single GJB2 mutation in the four remaining subjects is unclear. Comprehensive diagnostic testing including TES is prerequisite for understanding GJB2 single heterozygotes. PMID:27057829

What is an ROC curve?

PubMed

Hoo, Zhe Hui; Candlish, Jane; Teare, Dawn

2017-06-01

The paper by Body et al is concerned with the evaluation of decision aids, which can be used to identify potential acute coronary syndromes (ACS) in the ED. The authors previously developed the Manchester Acute Coronary Syndromes model (MACS) decision aid, which uses several clinical variables and two biomarkers to 'rule in' and 'rule out' ACS. However, one of the two biomarkers (heart-type fatty acid bindingprotein, H-FABP) is not widely used so a revised decision aid has been developed (Troponin-only Manchester Acute Coronary Syndromes, T-MACS), which include a single biomarker hs-cTnT. In this issue, the authors show how they derive a revised decision aid and describe its performance in a number of independent diagnostic cohort studies. Decision aids (as well as other types of 'diagnostic tests') are often evaluated in terms of diagnostic testing parameters such as the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. In this article, we explain how the ROC analysis is conducted and why it is an essential step towards developing a test with the desirable levels of sensitivity and specificity. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Antibody detection tests improve the sensitivity of tuberculosis diagnosis in cattle.

PubMed

Casal, C; Infantes, J A; Risalde, M A; Díez-Guerrier, A; Domínguez, M; Moreno, I; Romero, B; de Juan, L; Sáez, J L; Juste, R; Gortázar, C; Domínguez, L; Bezos, J

2017-06-01

We evaluated the sensitivity (Se) of the single cervical intradermal tuberculin (SIT) test, two interferon-gamma (IFN-γ) assays and three different antibody detection techniques for bovine tuberculosis (bTB) diagnosis in 131 mixed beef breed cattle. The results of the diagnostic techniques performed over the whole herd, and over the animals confirmed as infected based on the presence of lesions compatible with the disease and/or M. bovis isolation were compared to determine apparent prevalence (AP) and Se. The Se of the SIT test (severe interpretation) was 63.7% (95% CI, 54.54-72.00), while the Se of the IFN-γ assays ranged between 60.2% and 92%. The proportion of infected cattle detected by the different antibody detection techniques ranged from 65.5% to 87.6%. Three of the antibody detection techniques yielded a significant higher (p<0.05) Se than that achieved with the official diagnostic techniques. In addition, the interpretation in parallel of cellular and antibody detection techniques reached the highest Se: 98.2% (95% CI, 93.78-99.51) suggesting that the use of diagnostic techniques detecting both cellular and humoral responses could be considered as an alternative in the control of bTB outbreaks in high prevalence settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

eSensor: an electrochemical detection-based DNA microarray technology enabling sample-to-answer molecular diagnostics

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Longiaru, Mathew

2009-05-01

DNA microarrays are becoming a widespread tool used in life science and drug screening due to its many benefits of miniaturization and integration. Microarrays permit a highly multiplexed DNA analysis. Recently, the development of new detection methods and simplified methodologies has rapidly expanded the use of microarray technologies from predominantly gene expression analysis into the arena of diagnostics. Osmetech's eSensor® is an electrochemical detection platform based on a low-to- medium density DNA hybridization array on a cost-effective printed circuit board substrate. eSensor® has been cleared by FDA for Warfarin sensitivity test and Cystic Fibrosis Carrier Detection. Other genetic-based diagnostic and infectious disease detection tests are under development. The eSensor® platform eliminates the need for an expensive laser-based optical system and fluorescent reagents. It allows one to perform hybridization and detection in a single and small instrument without any fluidic processing and handling. Furthermore, the eSensor® platform is readily adaptable to on-chip sample-to-answer genetic analyses using microfluidics technology. The eSensor® platform provides a cost-effective solution to direct sample-to-answer genetic analysis, and thus have a potential impact in the fields of point-of-care genetic analysis, environmental testing, and biological warfare agent detection.

Focus characterization at an X-ray free-electron laser by coherent scattering and speckle analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sikorski, Marcin; Song, Sanghoon; Schropp, Andreas

2015-04-14

X-ray focus optimization and characterization based on coherent scattering and quantitative speckle size measurements was demonstrated at the Linac Coherent Light Source. Its performance as a single-pulse free-electron laser beam diagnostic was tested for two typical focusing configurations. The results derived from the speckle size/shape analysis show the effectiveness of this technique in finding the focus' location, size and shape. In addition, its single-pulse compatibility enables users to capture pulse-to-pulse fluctuations in focus properties compared with other techniques that require scanning and averaging.

40 CFR 85.2223 - On-board diagnostic test report.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false On-board diagnostic test report. 85... Tests § 85.2223 On-board diagnostic test report. (a) Motorists whose vehicles fail the on-board diagnostic test described in § 85.2222 shall be provided with the on-board diagnostic test results, including...

40 CFR 85.2223 - On-board diagnostic test report.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false On-board diagnostic test report. 85... Tests § 85.2223 On-board diagnostic test report. (a) Motorists whose vehicles fail the on-board diagnostic test described in § 85.2222 shall be provided with the on-board diagnostic test results, including...

The role of computerized diagnostic proposals in the interpretation of the 12-lead electrocardiogram by cardiology and non-cardiology fellows.

PubMed

Novotny, Tomas; Bond, Raymond; Andrsova, Irena; Koc, Lumir; Sisakova, Martina; Finlay, Dewar; Guldenring, Daniel; Spinar, Jindrich; Malik, Marek

2017-05-01

Most contemporary 12-lead electrocardiogram (ECG) devices offer computerized diagnostic proposals. The reliability of these automated diagnoses is limited. It has been suggested that incorrect computer advice can influence physician decision-making. This study analyzed the role of diagnostic proposals in the decision process by a group of fellows of cardiology and other internal medicine subspecialties. A set of 100 clinical 12-lead ECG tracings was selected covering both normal cases and common abnormalities. A team of 15 junior Cardiology Fellows and 15 Non-Cardiology Fellows interpreted the ECGs in 3 phases: without any diagnostic proposal, with a single diagnostic proposal (half of them intentionally incorrect), and with four diagnostic proposals (only one of them being correct) for each ECG. Self-rated confidence of each interpretation was collected. Availability of diagnostic proposals significantly increased the diagnostic accuracy (p<0.001). Nevertheless, in case of a single proposal (either correct or incorrect) the increase of accuracy was present in interpretations with correct diagnostic proposals, while the accuracy was substantially reduced with incorrect proposals. Confidence levels poorly correlated with interpretation scores (rho≈2, p<0.001). Logistic regression showed that an interpreter is most likely to be correct when the ECG offers a correct diagnostic proposal (OR=10.87) or multiple proposals (OR=4.43). Diagnostic proposals affect the diagnostic accuracy of ECG interpretations. The accuracy is significantly influenced especially when a single diagnostic proposal (either correct or incorrect) is provided. The study suggests that the presentation of multiple computerized diagnoses is likely to improve the diagnostic accuracy of interpreters. Copyright © 2017 Elsevier B.V. All rights reserved.

Elevated human chorionic gonadotropin levels in patients with chronic kidney disease: Case series and review of literature.

PubMed

Soni, S; Menon, M C; Bhaskaran, M; Jhaveri, K D; Molmenti, E; Muoio, V

2013-11-01

Women are often subjected to serum human chorionic gonadotropin (HCG) testing prior to diagnostic and therapeutic interventions. A positive result leads to further testing to rule out pregnancy and avoid possible fetal teratogenicity. The impact of chronic kidney disease (CKD) on HCG testing has not been studied. We report a series of 5 women out of 62 with CKD, who had a positive HCG test on routine pre-transplant screening at a single transplant center. We analyzed their case records retrospectively. Despite aggressive investigation, their elevated HCG levels remained unexplained. The positive test contributed to delays in transplantation and increased overall cost of treatment.

[Insect venom allergies : Update 2016 for otorhinolaryngologists].

PubMed

Klimek, L; Dippold, N; Sperl, A

2016-12-01

Due to the increasing incidence of hymenoptera venom allergies and the potentially life-threatening reactions, it is important for otolaryngologists working in allergology to have an understanding of modern diagnostic and treatment standards for this allergic disease. Molecular diagnosis with recombinant single allergens from bee and wasp venom components improves the diagnostics of insect venom allergies, particularly in patients with double-positive extract-based test results. Detection of specific sensitizations to bee or wasp venom enables double sensitizations to be better distinguished from cross-reactivity. Based on patient history and test results, the patient is initially advised on avoidance strategies and prescribed an emergency medication kit. Then, the indication for allergen-specific immunotherapy (AIT) is evaluated. The dose-increase phase can be performed using conventional, cluster, rush, or ultra-rush schedules, whereby rapid desensitization (rush AIT) performed in the clinic seems to be particularly effective as initial treatment.

Improving utility of brain tumor confocal laser endomicroscopy: objective value assessment and diagnostic frame detection with convolutional neural networks

NASA Astrophysics Data System (ADS)

Izadyyazdanabadi, Mohammadhassan; Belykh, Evgenii; Martirosyan, Nikolay; Eschbacher, Jennifer; Nakaji, Peter; Yang, Yezhou; Preul, Mark C.

2017-03-01

Confocal laser endomicroscopy (CLE), although capable of obtaining images at cellular resolution during surgery of brain tumors in real time, creates as many non-diagnostic as diagnostic images. Non-useful images are often distorted due to relative motion between probe and brain or blood artifacts. Many images, however, simply lack diagnostic features immediately informative to the physician. Examining all the hundreds or thousands of images from a single case to discriminate diagnostic images from nondiagnostic ones can be tedious. Providing a real time diagnostic value assessment of images (fast enough to be used during the surgical acquisition process and accurate enough for the pathologist to rely on) to automatically detect diagnostic frames would streamline the analysis of images and filter useful images for the pathologist/surgeon. We sought to automatically classify images as diagnostic or non-diagnostic. AlexNet, a deep-learning architecture, was used in a 4-fold cross validation manner. Our dataset includes 16,795 images (8572 nondiagnostic and 8223 diagnostic) from 74 CLE-aided brain tumor surgery patients. The ground truth for all the images is provided by the pathologist. Average model accuracy on test data was 91% overall (90.79 % accuracy, 90.94 % sensitivity and 90.87 % specificity). To evaluate the model reliability we also performed receiver operating characteristic (ROC) analysis yielding 0.958 average for area under ROC curve (AUC). These results demonstrate that a deeply trained AlexNet network can achieve a model that reliably and quickly recognizes diagnostic CLE images.

42 CFR 415.180 - Teaching setting requirements for the interpretation of diagnostic radiology and other diagnostic...

Code of Federal Regulations, 2011 CFR

2011-10-01

... interpretation of diagnostic radiology and other diagnostic tests. 415.180 Section 415.180 Public Health CENTERS... for the interpretation of diagnostic radiology and other diagnostic tests. (a) General rule. Physician fee schedule payment is made for the interpretation of diagnostic radiology and other diagnostic tests...

42 CFR 415.180 - Teaching setting requirements for the interpretation of diagnostic radiology and other diagnostic...

Code of Federal Regulations, 2010 CFR

2010-10-01

... interpretation of diagnostic radiology and other diagnostic tests. 415.180 Section 415.180 Public Health CENTERS... for the interpretation of diagnostic radiology and other diagnostic tests. (a) General rule. Physician fee schedule payment is made for the interpretation of diagnostic radiology and other diagnostic tests...

Innovative single-shot diagnostics for electrons from laser wakefield acceleration at FLAME

NASA Astrophysics Data System (ADS)

Bisesto, F. G.; Anania, M. P.; Cianchi, A.; Chiadroni, E.; Curcio, A.; Ferrario, M.; Pompili, R.; Zigler, A.

2017-07-01

Plasma wakefield acceleration is the most promising acceleration technique known nowadays, able to provide very high accelerating fields (> 100 GV/m), enabling acceleration of electrons to GeV energy in few centimeters. Here we present all the plasma related activities currently underway at SPARC_LAB exploiting the high power laser FLAME. In particular, we will give an overview of the single shot diagnostics employed: Electro Optic Sampling (EOS) for temporal measurement and Optical Transition Radiation (OTR) for an innovative one shot emittance measurements. In detail, the EOS technique has been employed to measure for the first time the longitudinal profile of electric field of fast electrons escaping from a solid target, driving the ions and protons acceleration, and to study the impact of using different target shapes. Moreover, a novel scheme for one shot emittance measurements based on OTR, developed and tested at SPARC_LAB LINAC, used in an experiment on electrons from laser wakefield acceleration still undergoing, will be shown.

Thioaptamer Diagnostic System (TDS)

NASA Technical Reports Server (NTRS)

Yang, Xianbin

2015-01-01

AM Biotechnologies, LLC, in partnership with Sandia National Laboratories, has developed a diagnostic device that quickly detects sampled biomarkers. The TDS quickly quantifies clinically relevant biomarkers using only microliters of a single sample. The system combines ambient-stable, long shelf-life affinity assays with handheld, microfluidic gel electrophoresis affinity assay quantification technology. The TDS is easy to use, operates in microgravity, and permits simultaneous quantification of 32 biomarkers. In Phase I of the project, the partners demonstrated that a thioaptamer assay used in the microfluidic instrument could quantify a specific biomarker in serum in the low nanomolar range. The team also identified novel affinity agents to bone-specific alkaline phosphatase (BAP) and demonstrated their ability to detect BAP with the microfluidic instrument. In Phase II, AM Biotech expanded the number of ambient affinity agents and demonstrated a TDS prototype. In the long term, the clinical version of the TDS will provide a robust, flight-tested diagnostic capability for space exploration missions.

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus

PubMed Central

Martinek, Jan; Maluskova, Jana; Stefanova, Magdalena; Tuckova, Inna; Suchanek, Stepan; Vackova, Zuzana; Krajciova, Jana; Kollar, Marek; Zavoral, Miroslav; Spicak, Julius

2015-01-01

AIM: To assess the sampling quality of four different forceps (three large capacity and one jumbo) in patients with Barrett’s esophagus. METHODS: This was a prospective, single-blind study. A total of 37 patients with Barrett’s esophagus were enrolled. Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy. The following forceps were tested: A: FB-220K disposable large capacity; B: BI01-D3-23 reusable large capacity; C: GBF-02-23-180 disposable large capacity; and jumbo: disposable Radial Jaw 4 jumbo. The primary outcome measurement was specimen adequacy, defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa. RESULTS: A total of 436 biopsy samples were analyzed. We found a significantly higher proportion of adequate biopsy samples with jumbo forceps (71%) (P < 0.001 vs forceps A: 26%, forceps B: 17%, and forceps C: 18%). Biopsies with jumbo forceps had the largest diameter (median 2.4 mm) (P < 0.001 vs forceps A: 2 mm, forceps B: 1.6 mm, and forceps C: 2mm). There was a trend for higher diagnostic yield per biopsy with jumbo forceps (forceps A: 0.20, forceps B: 0.22, forceps C: 0.27, and jumbo: 0.28). No complications related to specimen sampling were observed with any of the four tested forceps. CONCLUSION: Jumbo biopsy forceps, when used with a diagnostic endoscope, provide more adequate specimens as compared to large-capacity forceps in patients with Barrett’s esophagus. PMID:25954107

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus.

PubMed

Martinek, Jan; Maluskova, Jana; Stefanova, Magdalena; Tuckova, Inna; Suchanek, Stepan; Vackova, Zuzana; Krajciova, Jana; Kollar, Marek; Zavoral, Miroslav; Spicak, Julius

2015-05-07

To assess the sampling quality of four different forceps (three large capacity and one jumbo) in patients with Barrett's esophagus. This was a prospective, single-blind study. A total of 37 patients with Barrett's esophagus were enrolled. Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy. The following forceps were tested: A: FB-220K disposable large capacity; B: BI01-D3-23 reusable large capacity; C: GBF-02-23-180 disposable large capacity; and jumbo: disposable Radial Jaw 4 jumbo. The primary outcome measurement was specimen adequacy, defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa. A total of 436 biopsy samples were analyzed. We found a significantly higher proportion of adequate biopsy samples with jumbo forceps (71%) (P < 0.001 vs forceps A: 26%, forceps B: 17%, and forceps C: 18%). Biopsies with jumbo forceps had the largest diameter (median 2.4 mm) (P < 0.001 vs forceps A: 2 mm, forceps B: 1.6 mm, and forceps C: 2mm). There was a trend for higher diagnostic yield per biopsy with jumbo forceps (forceps A: 0.20, forceps B: 0.22, forceps C: 0.27, and jumbo: 0.28). No complications related to specimen sampling were observed with any of the four tested forceps. Jumbo biopsy forceps, when used with a diagnostic endoscope, provide more adequate specimens as compared to large-capacity forceps in patients with Barrett's esophagus.

DIFFERENTIAL DIAGNOSTIC PROCESS AND CLINICAL DECISION MAKING IN A YOUNG ADULT FEMALE WITH LATERAL HIP PAIN: A CASE REPORT.

PubMed

Livingston, Jennifer I; Deprey, Sara M; Hensley, Craig P

2015-10-01

differential diagnosis and clinical decision making. Young adults with lateral hip pain are often referred to physical therapy (PT). A thorough examination is required to obtain a diagnosis and guide management. The purpose of this case report is to describe the physical therapist's differential diagnostic process and clinical decision making for a subject with the referring diagnosis of trochanteric bursitis. A 29-year-old female presented to PT with limited sitting and running tolerance secondary to right lateral hip pain. Her symptoms began three months prior when she abruptly changed her running intensity and frequency of weight bearing activities, including running and low impact plyometrics for the lower extremity. Physical examination revealed a positive Trendelenburg sign, manual muscle test that was weak and painless of the right hip abductors, and pain elicited when performing a vertical hop on a concrete surface (+single leg hop test), but pain-free when performing the same single leg hop on a foam surface. Examination findings warranted discussion with the referring physician for further diagnostic imaging. Magnetic resonance imaging revealed a focus of edema in the posterior acetabulum, suspicious for an acetabular stress fracture. The subject was subsequently diagnosed with an acetabular stress fracture and restricted from running and plyometrics for four weeks. Thorough examination and appropriate clinical decision making by the physical therapist at the initial examination led to the diagnosis of an acetabular stress fracture in this subject. Clinicians must be aware of symptoms and signs which place the subject at risk for stress fracture for timely referral and management. 4.

Evaluation of molecular markers for Phytophthora ramorum detection and identification: testing for specificity using a standardized library of isolates.

PubMed

Martin, F N; Coffey, M D; Zeller, K; Hamelin, R C; Tooley, P; Garbelotto, M; Hughes, K J D; Kubisiak, T; Bilodeau, G J; Levy, L; Blomquist, C; Berger, P H

2009-04-01

Given the importance of Phytophthora ramorum from a regulatory standpoint, it is imperative that molecular markers for pathogen detection are fully tested to evaluate their specificity in detection of the pathogen. In an effort to evaluate 11 reported diagnostic techniques, we assembled a standardized DNA library using accessions from the World Phytophthora Genetic Resource Collection for 315 isolates representing 60 described Phytophthora spp. as well as 11 taxonomically unclassified isolates. These were sent blind to collaborators in seven laboratories to evaluate published diagnostic procedures using conventional (based on internal transcribed spacer [ITS] and cytochrome oxidase gene [cox]1 and 2 spacer regions) and real-time polymerase chain reaction (based on ITS and cox1 and 2 spacer regions as well as beta-tubulin and elicitin genes). Single-strand conformation polymorphism (SSCP) analysis using an automated sequencer for data collection was also evaluated for identification of all species tested. In general, the procedures worked well, with varying levels of specificity observed among the different techniques. With few exceptions, all assays correctly identified all isolates of P. ramorum and low levels of false positives were observed for the mitochondrial cox spacer markers and most of the real-time assays based on nuclear markers (diagnostic specificity between 96.9 and 100%). The highest level of false positives was obtained with the conventional nested ITS procedure; however, this technique is not stand-alone and is used in conjunction with two other assays for diagnostic purposes. The results indicated that using multiple assays improved the accuracy of the results compared with looking at a single assay alone, in particular when the markers represented different genetic loci. The SSCP procedure accurately identified P. ramorum and was helpful in classification of a number of isolates to a species level. With one exception, all procedures accurately identified P. ramorum in blind evaluations of 60 field samples that included examples of plant infection by 11 other Phytophthora spp. The SSCP analysis identified eight of these species, with three identified to a species group.

Development of a Novel and Rapid Fully Automated Genetic Testing System.

PubMed

Uehara, Masayuki

2016-01-01

We have developed a rapid genetic testing system integrating nucleic acid extraction, purification, amplification, and detection in a single cartridge. The system performs real-time polymerase chain reaction (PCR) after nucleic acid purification in a fully automated manner. RNase P, a housekeeping gene, was purified from human nasal epithelial cells using silica-coated magnetic beads and subjected to real-time PCR using a novel droplet-real-time-PCR machine. The process was completed within 13 min. This system will be widely applicable for research and diagnostic uses.

Novel applications of array comparative genomic hybridization in molecular diagnostics.

PubMed

Cheung, Sau W; Bi, Weimin

2018-05-31

In 2004, the implementation of array comparative genomic hybridization (array comparative genome hybridization [CGH]) into clinical practice marked a new milestone for genetic diagnosis. Array CGH and single-nucleotide polymorphism (SNP) arrays enable genome-wide detection of copy number changes in a high resolution, and therefore microarray has been recognized as the first-tier test for patients with intellectual disability or multiple congenital anomalies, and has also been applied prenatally for detection of clinically relevant copy number variations in the fetus. Area covered: In this review, the authors summarize the evolution of array CGH technology from their diagnostic laboratory, highlighting exonic SNP arrays developed in the past decade which detect small intragenic copy number changes as well as large DNA segments for the region of heterozygosity. The applications of array CGH to human diseases with different modes of inheritance with the emphasis on autosomal recessive disorders are discussed. Expert commentary: An exonic array is a powerful and most efficient clinical tool in detecting genome wide small copy number variants in both dominant and recessive disorders. However, whole-genome sequencing may become the single integrated platform for detection of copy number changes, single-nucleotide changes as well as balanced chromosomal rearrangements in the near future.

Diagnostic utility of a one-item question to screen for depressive disorders: results from the KORA F3 study.

PubMed

Blozik, Eva; Scherer, Martin; Lacruz, Maria E; Ladwig, Karl-Heinz

2013-12-23

Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders ("Have you felt depressed or sad much of the time in the past year?") in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with "depressive mood" and "major depressive disorder" defined according to PHQ-9 (both interviewer-administered versions). In comparison to PHQ-9 "depressive mood", sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for "major depressive disorder", sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice.

Diagnostic utility of a one-item question to screen for depressive disorders: results from the KORA F3 study

PubMed Central

2013-01-01

Background Screening for depressive disorders in the general adult population is recommended, however, it is unclear which instruments combine user friendliness and diagnostic utility. We evaluated the test performance of a yes/no single item screener for depressive disorders (“Have you felt depressed or sad much of the time in the past year?”) in comparison to the depressive disorder module of the Patient Health Questionnaire (PHQ-9). Methods Data from 3184 participants of the population-based KORA F3 survey in Augsburg/ Germany were used to analyse sensitivity, specificity, ROC area, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), and negative predictive value (NPV) of the single item screener in comparison with “depressive mood” and “major depressive disorder” defined according to PHQ-9 (both interviewer-administered versions). Results In comparison to PHQ-9 “depressive mood”, sensitivity was low (46%) with an excellent specificity (94%), (PPV 76%; NPV 82%; LR + 8.04; LR- .572, ROC area .702). When using the more conservative definition for “major depressive disorder”, sensitivity increased to 83% with a specificity of 88%. The PPV under the conservative definition was low (32%), but NPV was 99% (LR + 6.65; LR- .196; ROC area .852). Results varied across age groups and between males and females. Conclusions The single item screener is able to moderately decrease post-test probability of major depressive disorders and to identify populations that should undergo additional, more detailed evaluation for depression. It may have limited utility in combination with additional screening tests or for selection of at-risk populations, but cannot be recommended for routine use as a screening tool in clinical practice. PMID:24359193

Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray

PubMed Central

List, Claudia; Qi, Weihong; Maag, Eva; Gottstein, Bruno; Müller, Norbert; Felger, Ingrid

2010-01-01

Background Production of native antigens for serodiagnosis of helminthic infections is laborious and hampered by batch-to-batch variation. For serodiagnosis of echinococcosis, especially cystic disease, most screening tests rely on crude or purified Echinococcus granulosus hydatid cyst fluid. To resolve limitations associated with native antigens in serological tests, the use of standardized and highly pure antigens produced by chemical synthesis offers considerable advantages, provided appropriate diagnostic sensitivity and specificity is achieved. Methodology/Principal Findings Making use of the growing collection of genomic and proteomic data, we applied a set of bioinformatic selection criteria to a collection of protein sequences including conceptually translated nucleotide sequence data of two related tapeworms, Echinococcus multilocularis and Echinococcus granulosus. Our approach targeted alpha-helical coiled-coils and intrinsically unstructured regions of parasite proteins potentially exposed to the host immune system. From 6 proteins of E. multilocularis and 5 proteins of E. granulosus, 45 peptides between 24 and 30 amino acids in length were designed. These peptides were chemically synthesized, spotted on microarrays and screened for reactivity with sera from infected humans. Peptides reacting above the cut-off were validated in enzyme-linked immunosorbent assays (ELISA). Peptides identified failed to differentiate between E. multilocularis and E. granulosus infection. The peptide performing best reached 57% sensitivity and 94% specificity. This candidate derived from Echinococcus multilocularis antigen B8/1 and showed strong reactivity to sera from patients infected either with E. multilocularis or E. granulosus. Conclusions/Significance This study provides proof of principle for the discovery of diagnostically relevant peptides by bioinformatic selection complemented with screening on a high-throughput microarray platform. Our data showed that a single peptide cannot provide sufficient diagnostic sensitivity whereas pooling several peptide antigens improved sensitivity; thus combinations of several peptides may lead the way to new diagnostic tests that replace, or at least complement conventional immunodiagnosis of echinococcosis. Our strategy could prove useful for diagnostic developments in other pathogens. PMID:20689813

Cautions regarding the fitting and interpretation of survival curves: examples from NICE single technology appraisals of drugs for cancer.

PubMed

Connock, Martin; Hyde, Chris; Moore, David

2011-10-01

The UK National Institute for Health and Clinical Excellence (NICE) has used its Single Technology Appraisal (STA) programme to assess several drugs for cancer. Typically, the evidence submitted by the manufacturer comes from one short-term randomized controlled trial (RCT) demonstrating improvement in overall survival and/or in delay of disease progression, and these are the pre-eminent drivers of cost effectiveness. We draw attention to key issues encountered in assessing the quality and rigour of the manufacturers' modelling of overall survival and disease progression. Our examples are two recent STAs: sorafenib (Nexavar®) for advanced hepatocellular carcinoma, and azacitidine (Vidaza®) for higher-risk myelodysplastic syndromes (MDS). The choice of parametric model had a large effect on the predicted treatment-dependent survival gain. Logarithmic models (log-Normal and log-logistic) delivered double the survival advantage that was derived from Weibull models. Both submissions selected the logarithmic fits for their base-case economic analyses and justified selection solely on Akaike Information Criterion (AIC) scores. AIC scores in the azacitidine submission failed to match the choice of the log-logistic over Weibull or exponential models, and the modelled survival in the intervention arm lacked face validity. AIC scores for sorafenib models favoured log-Normal fits; however, since there is no statistical method for comparing AIC scores, and differences may be trivial, it is generally advised that the plausibility of competing models should be tested against external data and explored in diagnostic plots. Function fitting to observed data should not be a mechanical process validated by a single crude indicator (AIC). Projective models should show clear plausibility for the patients concerned and should be consistent with other published information. Multiple rather than single parametric functions should be explored and tested with diagnostic plots. When trials have survival curves with long tails exhibiting few events then the robustness of extrapolations using information in such tails should be tested.

A single-question screening test for drug use in primary care.

PubMed

Smith, Peter C; Schmidt, Susan M; Allensworth-Davies, Donald; Saitz, Richard

2010-07-12

Drug use (illicit drug use and nonmedical use of prescription drugs) is common but underrecognized in primary care settings. We validated a single-question screening test for drug use and drug use disorders in primary care. Adult patients recruited from primary care waiting rooms were asked the single screening question, "How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?" A response of at least 1 time was considered positive for drug use. They were also asked the 10-item Drug Abuse Screening Test (DAST-10). The reference standard was the presence or absence of current (past year) drug use or a drug use disorder (abuse or dependence) as determined by a standardized diagnostic interview. Drug use was also determined by oral fluid testing for common drugs of abuse. Of 394 eligible primary care patients, 286 (73%) completed the interview. The single screening question was 100% sensitive (95% confidence interval [CI], 90.6%-100%) and 73.5% specific (95% CI, 67.7%-78.6%) for the detection of a drug use disorder. It was less sensitive for the detection of self-reported current drug use (92.9%; 95% CI, 86.1%-96.5%) and drug use detected by oral fluid testing or self-report (81.8%; 95% CI, 72.5%-88.5%). Test characteristics were similar to those of the DAST-10 and were affected very little by participant demographic characteristics. The single screening question accurately identified drug use in this sample of primary care patients, supporting the usefulness of this brief screen in primary care.

Draw your assay: Fabrication of low-cost paper-based diagnostic and multi-well test zones by drawing on a paper.

PubMed

Oyola-Reynoso, Stephanie; Heim, Andrew P; Halbertsma-Black, Julian; Zhao, C; Tevis, Ian D; Çınar, Simge; Cademartiri, Rebecca; Liu, Xinyu; Bloch, Jean-Francis; Thuo, Martin M

2015-11-01

Interest in low-cost diagnostic devices has recently gained attention, in part due to the rising cost of healthcare and the need to serve populations in resource-limited settings. A major challenge in the development of such devices is the need for hydrophobic barriers to contain polar bio-fluid analytes. Key approaches in lowering the cost in diagnostics have centered on (i) development of low-cost fabrication techniques/processes, (ii) use of affordable materials, or, (iii) minimizing the need for high-tech tools. This communication describes a simple, low-cost, adaptable, and portable method for patterning paper and subsequent use of the patterned paper in diagnostic tests. Our approach generates hydrophobic regions using a ball-point pen filled with a hydrophobizing molecule suspended in a solvent carrier. An empty ball-point pen was filled with a solution of trichloro perfluoroalkyl silane in hexanes (or hexadecane), and the pen used to draw lines on Whatman® chromatography 1 paper. The drawn regions defined the test zones since the trichloro silane reacts with the paper to give a hydrophobic barrier. The formation of the hydrophobic barriers is reaction kinetic and diffusion-limited, ensuring well defined narrow barriers. We performed colorimetric glucose assays and enzyme-linked immuno-sorbent assay (ELISA) using the created test zones. To demonstrate the versatility of this approach, we fabricated multiple devices on a single piece of paper and demonstrated the reproducibility of assays on these devices. The overall cost of devices fabricated by drawing are relatively lower (

Diagnostic value of serum Golgi protein 73 for HBV-related primary hepatic carcinoma

PubMed Central

Gao, Guosheng; Dong, Feibo; Xu, Xiaozhen; Hu, Airong; Hu, Yaoren

2015-01-01

Background: Alpha-fetoprotein (AFP) levels are routinely used for diagnosis and monitoring of hepatic diseases, but it has a limited value. Golgi protein 73 (GP73) has been suggested as a new marker for hepatic diseases. Objective: To explore the clinical value of serum GP73 in different diseases associated with hepatitis B virus (HBV) infection. Method: Between January 2010 and August 2014, serum samples from 88 patients with chronic hepatitis B (CHB), 78 patients with HBV-related liver cirrhosis (LC), and 194 patients with HBV-related primary hepatic cancer (PHC) were collected. Serum samples from 30 healthy volunteers were used as controls. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of serum GP73 and AFP for PHC. Results: For the diagnosis of PHC, GP73 showed a sensitivity of 65.5% and specificity of 66.3%, while AFP levels showed sensitivity of 64.4% and specificity of 76.5%. Serial testing (both tests are positive) could increase the specificity (sensitivity of 45.9% and specificity of 85.5%) while parallel testing (any single positive test result) could increase the sensitivity (sensitivity of 84.0% and specificity of 57.2%). Serum GP73 and AFP levels were significantly different between Child-Pugh grades (P<0.001 for GP73 and P=0.044 for AFP). Significant differences in serum GP73 and AFP were found between TNM stages (all P<0.001). Conclusion: Serum GP73 had limited diagnostic value for HBV-related PHC. The combined use of serum GP73 and AFP levels improved the diagnostic efficacy. PMID:26617863

Urine tests for Down's syndrome screening.

PubMed

Alldred, S Kate; Guo, Boliang; Takwoingi, Yemisi; Pennant, Mary; Wisniewski, Susanna; Deeks, Jonathan J; Neilson, James P; Alfirevic, Zarko

2015-12-10

Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome. We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles. Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses. We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR). Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.

Diagnostic accuracy of fungal PCR and β-d-glucan for detection of candidaemia: a preliminary evaluation.

PubMed

McKeating, Cara; White, P Lewis; Posso, Raquel; Palmer, Michael; Johnson, Elizabeth; McMullan, Ronan

2018-05-01

Although treatment for candidaemia is time critical, culture-based tests prolong turnaround times and may promote underdiagnosis. Non-culture-based tests have the potential to overcome these difficulties but are in limited clinical use. The aim of this work was to undertake an initial evaluation of two non-culture-based tests for diagnosis of candidaemia. Patients with candidaemia were identified prospectively over a 4-month period. Sera drawn from case (candidaemic) and control (non-candidaemic) patients on the same day as the positive blood culture were tested with both the Renishaw RenDx Fungiplex test and a commercial β-d-glucan (BDG) assay (Fungitell, Associates of Cape Cod). Sensitivity and specificity were calculated independently and in combination, using paired blood culture as the reference standard. There were 10 eligible case patients and 39 negative controls. PCR sensitivity and specificity were found to be 44.4% (95% CI 18.9% to 73.3%) and 87.2% (72.8% to 94.8%), respectively. BDG sensitivity and specificity were 80% (47.9% to 95.4%) and 89.7% (75.9% to 96.5%), respectively. When combining PCR and BDG, sensitivity was 90% (95% CI 57.4% to 100%) and specificity was 79.5% (64.2% to 89.5%). When two sequential specimens were tested, PCR sensitivity increased to 60% (95% CI 31.2% to 83.3%) and BDG sensitivity to 90% (54.7% to 100%). A combination of tests, or a single test at multiple time points, may be preferable to relying on one test at a single time point. This should be accounted for in design of future diagnostic accuracy studies of tests for invasive candidosis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

What's in a Label? Is Diagnosis the Start or the End of Clinical Reasoning?

PubMed

Ilgen, Jonathan S; Eva, Kevin W; Regehr, Glenn

2016-04-01

Diagnostic reasoning has received substantial attention in the literature, yet what we mean by "diagnosis" may vary. Diagnosis can align with assignment of a "label," where a constellation of signs, symptoms, and test results is unified into a solution at a single point in time. This "diagnostic labeling" conceptualization is embodied in our case-based learning curricula, published case reports, and research studies, all of which treat diagnostic accuracy as the primary outcome. However, this conceptualization may oversimplify the richly iterative and evolutionary nature of clinical reasoning in many settings. Diagnosis can also represent a process of guiding one's thoughts by "making meaning" from data that are intrinsically dynamic, experienced idiosyncratically, negotiated among team members, and rich with opportunities for exploration. Thus, there are two complementary constructions of diagnosis: 1) the correct solution resulting from a diagnostic reasoning process, and 2) a dynamic aid to an ongoing clinical reasoning process. This article discusses the importance of recognizing these two conceptualizations of "diagnosis," outlines the unintended consequences of emphasizing diagnostic labeling as the primary goal of clinical reasoning, and suggests how framing diagnosis as an ongoing process of meaning-making might change how we think about teaching and assessing clinical reasoning.

Joint confidence region estimation for area under ROC curve and Youden index.

PubMed

Yin, Jingjing; Tian, Lili

2014-03-15

In the field of diagnostic studies, the area under the ROC curve (AUC) serves as an overall measure of a biomarker/diagnostic test's accuracy. Youden index, defined as the overall correct classification rate minus one at the optimal cut-off point, is another popular index. For continuous biomarkers of binary disease status, although researchers mainly evaluate the diagnostic accuracy using AUC, for the purpose of making diagnosis, Youden index provides an important and direct measure of the diagnostic accuracy at the optimal threshold and hence should be taken into consideration in addition to AUC. Furthermore, AUC and Youden index are generally correlated. In this paper, we initiate the idea of evaluating diagnostic accuracy based on AUC and Youden index simultaneously. As the first step toward this direction, this paper only focuses on the confidence region estimation of AUC and Youden index for a single marker. We present both parametric and non-parametric approaches for estimating joint confidence region of AUC and Youden index. We carry out extensive simulation study to evaluate the performance of the proposed methods. In the end, we apply the proposed methods to a real data set. Copyright © 2013 John Wiley & Sons, Ltd.

Investigation of Dysphagia After Antireflux Surgery by High-resolution Manometry: Impact of Multiple Water Swallows and a Solid Test Meal on Diagnosis, Management, and Clinical Outcome.

PubMed

Wang, Yu Tien; Tai, Ling Fung; Yazaki, Etsuro; Jafari, Jafar; Sweis, Rami; Tucker, Emily; Knowles, Kevin; Wright, Jeff; Ahmad, Saqib; Kasi, Madhavi; Hamlett, Katharine; Fox, Mark R; Sifrim, Daniel

2015-09-01

Management of patients with dysphagia, regurgitation, and related symptoms after antireflux surgery is challenging. This prospective, case-control study tested the hypothesis that compared with standard high-resolution manometry (HRM) with single water swallows (SWS), adding multiple water swallows (MWS) and a solid test meal increases diagnostic yield and clinical impact of physiological investigations. Fifty-seven symptomatic and 12 asymptomatic patients underwent HRM with SWS, MWS, and a solid test meal. Dysphagia and reflux were assessed by validated questionnaires. Diagnostic yield of standard and full HRM studies with 24-hour pH-impedance monitoring was compared. Pneumatic dilatation was performed for outlet obstruction on HRM studies. Clinical outcome was assessed by questionnaires and an analogue scale with "satisfactory" defined as at least 40% symptom improvement requiring no further treatment. Postoperative esophagogastric junction pressure was similar in all groups. Abnormal esophagogastric junction morphology (double high pressure band) was more common in symptomatic than in control patients (13 of 57 vs 0 of 12, P = .004). Diagnostic yield of HRM was 11 (19%), 11 (19%), and 33 of 57 (58%), with SWS, MWS, and solids, respectively (P < .001); it was greatest for solids in patients with dysphagia (19 of 27, 70%). Outlet obstruction was present in 4 (7%), 11 (19%), and 15 of 57 patients (26%) with SWS, MWS, and solids, respectively (P < .009). No asymptomatic control had clinically relevant dysfunction on solid swallows. Dilatation was performed in 12 of 15 patients with outlet obstruction during the test meal. Symptom response was satisfactory, good, or excellent in 7 of 12 (58%) with no serious complications. The addition of MWS and a solid test meal increases the diagnostic yield of HRM studies in patients with symptoms after fundoplication and identifies additional patients with outlet obstruction who benefit from endoscopic dilatation. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Predictive potential of IL-28B genetic testing for interferon based hepatitis C virus therapy in Pakistan: Current scenario and future perspective.

PubMed

Afzal, Muhammad Sohail

2016-09-18

In Pakistan which ranked second in terms of hepatitis C virus (HCV) infection, it is highly needed to have an established diagnostic test for antiviral therapy response prediction. Interleukin 28B (IL-28B) genetic testing is widely used throughout the world for interferon based therapy prediction for HCV patients and is quite helpful not only for health care workers but also for the patients. There is a strong relationship between single nucleotide polymorphisms at or near the IL-28B gene and the sustained virological response with pegylated interferon plus ribavirin treatment for chronic hepatitis C. Pakistan is a resource limited country, with very low per capita income and there is no proper social security (health insurance) system. The allocated health budget by the government is very low and is used on other health emergencies like polio virus and dengue virus infection. Therefore it is proposed that there should be a well established diagnostic test on the basis of IL-28B which can predict the antiviral therapy response to strengthen health care set-up of Pakistan. This test once established will help in better management of HCV infected patients.

Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

PubMed

Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

2016-07-15

In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Single measure and gated screening approaches for identifying students at-risk for academic problems: Implications for sensitivity and specificity.

PubMed

Van Norman, Ethan R; Nelson, Peter M; Klingbeil, David A

2017-09-01

Educators need recommendations to improve screening practices without limiting students' instructional opportunities. Repurposing previous years' state test scores has shown promise in identifying at-risk students within multitiered systems of support. However, researchers have not directly compared the diagnostic accuracy of previous years' state test scores with data collected during fall screening periods to identify at-risk students. In addition, the benefit of using previous state test scores in conjunction with data from a separate measure to identify at-risk students has not been explored. The diagnostic accuracy of 3 types of screening approaches were tested to predict proficiency on end-of-year high-stakes assessments: state test data obtained during the previous year, data from a different measure administered in the fall, and both measures combined (i.e., a gated model). Extant reading and math data (N = 2,996) from 10 schools in the Midwest were analyzed. When used alone, both measures yielded similar sensitivity and specificity values. The gated model yielded superior specificity values compared with using either measure alone, at the expense of sensitivity. Implications, limitations, and ideas for future research are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[Genetic diseases:recent scientific findings and health and ethical problems].

PubMed

Taruscio, D; D'Agnolo, G

1999-01-01

Genetic diseases are very numerous, even though rare as single conditions: therefore, overall they represent a significant portion of morbidity at population level. The improvement of molecular genetic techniques has brought a great increase in the diagnostic potential toward genetic diseases, concerning either symptomatic or pre-symptomatic individuals and healthy carriers. However, this has frequently unforeseen consequences, such as a discrepancy between diagnostic and therapeutic potentials. Moreover, the development of genetic tests has raised a number of questions regarding ethical, legal e social problems. The Italian guidelines for genetic tests (available on the Internet site of Istituto Superiore di Sanità: http:@www.iss.it) have been elaborated in 1998 to define general principles for performing and managing genetic tests as well as for programming and promoting genetic testing within the public health system. In accordance with recommendations by international bodies (WHO, EU), the Guidelines give emphasis to the appropriate use of both safe and efficacious tests, the performance in laboratories with high quality standards. A further crucial point is the relationship between the health system and individuals: authonomy of decision, psychological and social assistance, as well as adequate attention to ethical and privacy problems should be guaranteed.

Impact of GeneXpert MTB/RIF assay on triage of respiratory isolation rooms for inpatients with presumed tuberculosis: a hypothetical trial.

PubMed

Chaisson, Lelia H; Roemer, Marguerite; Cantu, David; Haller, Barbara; Millman, Alexander J; Cattamanchi, Adithya; Davis, J Lucian

2014-11-15

Placing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms. We prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies. Among 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43-60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%-100%) and similar specificity (99% [95% CI, 96%-100%] vs 100% [95% CI, 97%-100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24-36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35-46 hours). Replacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hierarchical mixture of experts and diagnostic modeling approach to reduce hydrologic model structural uncertainty: STRUCTURAL UNCERTAINTY DIAGNOSTICS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moges, Edom; Demissie, Yonas; Li, Hong-Yi

2016-04-01

In most water resources applications, a single model structure might be inadequate to capture the dynamic multi-scale interactions among different hydrological processes. Calibrating single models for dynamic catchments, where multiple dominant processes exist, can result in displacement of errors from structure to parameters, which in turn leads to over-correction and biased predictions. An alternative to a single model structure is to develop local expert structures that are effective in representing the dominant components of the hydrologic process and adaptively integrate them based on an indicator variable. In this study, the Hierarchical Mixture of Experts (HME) framework is applied to integratemore » expert model structures representing the different components of the hydrologic process. Various signature diagnostic analyses are used to assess the presence of multiple dominant processes and the adequacy of a single model, as well as to identify the structures of the expert models. The approaches are applied for two distinct catchments, the Guadalupe River (Texas) and the French Broad River (North Carolina) from the Model Parameter Estimation Experiment (MOPEX), using different structures of the HBV model. The results show that the HME approach has a better performance over the single model for the Guadalupe catchment, where multiple dominant processes are witnessed through diagnostic measures. Whereas, the diagnostics and aggregated performance measures prove that French Broad has a homogeneous catchment response, making the single model adequate to capture the response.« less

Ultrafast Single-Shot Optical Oscilloscope based on Time-to-Space Conversion due to Temporal and Spatial Walk-Off Effects in Nonlinear Mixing Crystal

NASA Astrophysics Data System (ADS)

Takagi, Yoshihiro; Yamada, Yoshifumi; Ishikawa, Kiyoshi; Shimizu, Seiji; Sakabe, Shuji

2005-09-01

A simple method for single-shot sub-picosecond optical pulse diagnostics has been demonstrated by imaging the time evolution of the optical mixing onto the beam cross section of the sum-frequency wave when the interrogating pulse passes over the tested pulse in the mixing crystal as a result of the combined effect of group-velocity difference and walk-off beam propagation. A high linearity of the time-to-space projection is deduced from the process solely dependent upon the spatial uniformity of the refractive indices. A snap profile of the accidental coincidence between asynchronous pulses from separate mode-locked lasers has been detected, which demonstrates the single-shot ability.

Prevalence of tick-borne haemoparasites in small ruminants in Turkey and diagnostic sensitivity of single-PCR and RLB.

PubMed

Bilgic, Huseyin Bilgin; Bakırcı, Serkan; Kose, Onur; Unlu, Ahmet Hakan; Hacılarlıoglu, Selin; Eren, Hasan; Weir, William; Karagenc, Tulin

2017-04-27

Tick-borne haemoparasitic diseases (TBHDs), caused by Theileria, Babesia, Anaplasma and Ehrlichia, are common in regions of the world where the distributions of host, pathogen and vector overlap. Many of these diseases threaten livestock production and some also represent a concern to human public health. The primary aim of this study was to determine the prevalence of the above-mentioned pathogens in a large number of blood samples (n = 1979) collected from sheep (n = 1727) and goats (n = 252) in Turkey. A secondary aim was to assess the diagnostic sensitivity of a number of species-specific polymerase chain reaction (PCR) tests and the reverse line blotting (RLB) assay. DNA samples were screened using species-specific PCR for the presence of Theileria ovis, Theileria sp. MK, T. lestoquardi, T. uilenbergi, T. luwenshuni, Babesia ovis, Anaplasma ovis and A. phagocytophilum while RLB was undertaken to test for the presence of all known Theileria, Babesia, Anaplasma and Ehrlichia species. The diagnostic sensitivity of these two approaches was then compared in terms of their ability to detect single species and mixed infections. Overall, 84 and 74.43% of the small ruminants sampled were identified as hosting one or more pathogen(s) by species-specific PCR and RLB respectively. The presence of Theileria sp. OT1, T. luwenshuni and T. uilenbergi in Turkey was revealed for the first time while the presence of Babesia motasi, B. crassa and T. separata in Turkish small ruminants was confirmed using molecular methods. A high prevalence of mixed infection was evident, with PCR and RLB approaches indicating that 52.24 and 35.42% of animals were co-infected with multiple species, respectively. More than 80% of the mixed infections contained T. ovis and/or A. ovis. The RLB approach was found to be capable of detecting mixed infections with species such as Theileria sp. OT1, Theileria sp. OT3, T. separata, B. crassa and Babesia spp. The results indicated that pathogens causing TBHDs are highly prevalent in sheep and goats in Turkey. The diagnostic sensitivity of species-specific single PCR was generally higher than that of RLB. However, the latter approach was still capable of identifying a high proportion of individuals containing mixed-species infections. The use of species-specific single PCR is recommended to accurately estimate pathogen prevalence and to identify co-infected hosts.

The current and future state of companion diagnostics

PubMed Central

Agarwal, Amit; Ressler, Dan; Snyder, Glenn

2015-01-01

Companion diagnostics are an indispensable part of personalized medicine and will likely continue to rapidly increase in number and application to disease areas. The first companion diagnostics were launched in the 1980s and in the face of significant initial skepticism from drug developers as to whether segmenting a drug’s market through a diagnostic was advisable. The commercial success of drugs such as Herceptin® (trastuzumab) and Gleevec® (imatinib), which both require testing with companion diagnostics before they can be prescribed, has moved the entire companion diagnostic field forward. From an initial start of a handful of oncology drugs with corresponding diagnostics, the field has expanded to include multiple therapeutic areas, and the number of combinations has grown by 12-fold. Based on drugs in clinical trials, the rapid growth will likely continue for the foreseeable future. This expansion of companion diagnostics will also have a global component as markets in Europe will evolve in a similar but not identical pattern as the US. One of the greatest challenges to future growth in companion diagnostics is aligning the incentives of all stakeholders. A major driver of growth will continue to be the economic incentives for drug developers to pair their products with diagnostics. However, diagnostic companies are caught between the conflicting demands of two major stakeholders, pharmaceutical companies on one hand and payers/providers on the other. Regulators are also becoming more demanding in aligning development time lines between drugs and diagnostics. In order to survive and prosper, diagnostic companies will need to think more broadly about companion diagnostics than the historical match between a specific drug and a single diagnostic. They will also have to continue the process of consolidation and global expansion that the industry has already begun. Despite these potential obstacles, companion diagnostics have become one of the hottest areas of deal making in the diagnostic space in recent years, and the future trends continue to look bright. PMID:25897259

Experimental Investigation of Shock-Cell Noise Reduction for Single Stream Nozzles in Simulated Flight

NASA Technical Reports Server (NTRS)

Yamamoto, K.; Brausch, J. F.; Balsa, T. F.; Janardan, B. A.; Knott, P. R.

1984-01-01

Seven single stream model nozzles were tested in the Anechoic Free-Jet Acoustic Test Facility to evaluate the effectiveness of convergent divergent (C-D) flowpaths in the reduction of shock-cell noise under both static and mulated flight conditions. The test nozzles included a baseline convergent circular nozzle, a C-D circular nozzle, a convergent annular plug nozzle, a C-D annular plug nozzle, a convergent multi-element suppressor plug nozzle, and a C-D multi-element suppressor plug nozzle. Diagnostic flow visualization with a shadowgraph and aerodynamic plume measurements with a laser velocimeter were performed with the test nozzles. A theory of shock-cell noise for annular plug nozzles with shock-cells in the vicinity of the plug was developed. The benefit of these C-D nozzles was observed over a broad range of pressure ratiosin the vicinity of their design conditions. At the C-D design condition, the C-D annual nozzle was found to be free of shock-cells on the plug.

Fluoroscopically Guided Diagnostic and Therapeutic Intra-Articular Sacroiliac Joint Injections: A Systematic Review.

PubMed

Kennedy, David J; Engel, Andrew; Kreiner, D Scott; Nampiaparampil, Devi; Duszynski, Belinda; MacVicar, John

2015-08-01

To assess the validity of fluoroscopically guided diagnostic intra-articular injections of local anesthetic and effectiveness of intra-articular steroid injections in treating sacroiliac joint (SIJ) pain. Systematic review. Ten reviewers independently assessed 45 publications on diagnostic validity or effectiveness of fluoroscopically guided intra-articular SIJ injections. For diagnostic injections, the primary outcome was validity; for therapeutic injections, analgesia. Secondary outcomes were also described. Of 45 articles reviewed, 39 yielded diagnostic data on physical exam findings, provocation tests, and SIJ injections for diagnosing SIJ pain, and 15 addressed therapeutic effectiveness. When confirmed by comparative local anesthetic blocks with a high degree of pain relief, no single physical exam maneuver predicts response to diagnostic injections. When at least three physical exam findings are present, sensitivity, and specificity increases significantly. The prevalence of SIJ pain is likely 20-30% among patients that have suspected SIJ pain based on history and physical examination. This estimate may be higher in certain subgroups such as the elderly and fusion patients. Two randomized controlled trials and multiple observational studies supported the effectiveness of therapeutic sacroiliac joint injections. Based on this literature, it is unclear whether image-guided intra-articular diagnostic injections of local anesthetic predict positive responses to therapeutic agents. The overall quality of evidence is moderate for the effectiveness of therapeutic SIJ injections. Wiley Periodicals, Inc.

Diagnostic Tools for Performance Evaluation of Innovative In-Situ Remediation Technologies at Chlorinated Solvent-Contaminated Sites

DTIC Science & Technology

2011-07-01

fluid resistivity , temperature logging, and flow metering at other sites that typically indicated only two or three active fractures in each hole...was consistent with results of conventional borehole fluid resistivity , temperature logging, and flow metering at other sites that typically indicated...following tests were performed in each boundary monitoring well: ■ Gamma Ray; ■ Spontaneous Potential (SP); ■ Single Point Resistance (SPR

Evidence-based Diagnostics: Adult Septic Arthritis

PubMed Central

Carpenter, Christopher R.; Schuur, Jeremiah D.; Everett, Worth W.; Pines, Jesse M.

2011-01-01

Background Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality. Objectives The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy. Methods Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits. Results The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 109–25 × 109/ L was 0.33; for 25 × 109–50 × 109/L, 1.06; for 50 × 109–100 × 109/L, 3.59; and exceeding 100 × 109/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (−LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 109/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%. Conclusions Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 109/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate. PMID:21843213

Evidence-based diagnostics: adult septic arthritis.

PubMed

Carpenter, Christopher R; Schuur, Jeremiah D; Everett, Worth W; Pines, Jesse M

2011-08-01

Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality. The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy. Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits. The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 10(9)-25 × 10(9)/L was 0.33; for 25 × 10(9)-50 × 10(9)/L, 1.06; for 50 × 10(9)-100 × 10(9)/L, 3.59; and exceeding 100 × 10(9)/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (-LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 10(9)/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%. Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 10(9)/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate. © 2011 by the Society for Academic Emergency Medicine.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in the 80000 series of the Current Procedural Terminology published by the American Medical... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Procedural Terminology published by the American Medical Association. (3) Levels of supervision. Except where... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

A hybrid Bayesian hierarchical model combining cohort and case-control studies for meta-analysis of diagnostic tests: Accounting for partial verification bias.

PubMed

Ma, Xiaoye; Chen, Yong; Cole, Stephen R; Chu, Haitao

2016-12-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities, and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. © The Author(s) 2014.

A Hybrid Bayesian Hierarchical Model Combining Cohort and Case-control Studies for Meta-analysis of Diagnostic Tests: Accounting for Partial Verification Bias

PubMed Central

Ma, Xiaoye; Chen, Yong; Cole, Stephen R.; Chu, Haitao

2014-01-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. PMID:24862512

Bayesian modeling and inference for diagnostic accuracy and probability of disease based on multiple diagnostic biomarkers with and without a perfect reference standard.

PubMed

Jafarzadeh, S Reza; Johnson, Wesley O; Gardner, Ian A

2016-03-15

The area under the receiver operating characteristic (ROC) curve (AUC) is used as a performance metric for quantitative tests. Although multiple biomarkers may be available for diagnostic or screening purposes, diagnostic accuracy is often assessed individually rather than in combination. In this paper, we consider the interesting problem of combining multiple biomarkers for use in a single diagnostic criterion with the goal of improving the diagnostic accuracy above that of an individual biomarker. The diagnostic criterion created from multiple biomarkers is based on the predictive probability of disease, conditional on given multiple biomarker outcomes. If the computed predictive probability exceeds a specified cutoff, the corresponding subject is allocated as 'diseased'. This defines a standard diagnostic criterion that has its own ROC curve, namely, the combined ROC (cROC). The AUC metric for cROC, namely, the combined AUC (cAUC), is used to compare the predictive criterion based on multiple biomarkers to one based on fewer biomarkers. A multivariate random-effects model is proposed for modeling multiple normally distributed dependent scores. Bayesian methods for estimating ROC curves and corresponding (marginal) AUCs are developed when a perfect reference standard is not available. In addition, cAUCs are computed to compare the accuracy of different combinations of biomarkers for diagnosis. The methods are evaluated using simulations and are applied to data for Johne's disease (paratuberculosis) in cattle. Copyright © 2015 John Wiley & Sons, Ltd.

Intense ion beam diagnostics for ICF

NASA Astrophysics Data System (ADS)

Yasuike, K.; Cuneo, M. E.; Wenger, D. F.; Bailey, J. E.; Hanson, D. L.; Mehlhorn, T. A.; Imasaki, K.; Nakai, S.; Mima, K.

1998-11-01

Development of diagnostic methods for high intensity ion beams for ICF is crucial for understanding the ion diode physics. At Osaka University, an arrayed pinhole camera (APC) diagnostic method had been developed to measure the proton beams with an energy of 1 MeV and a J_i. of 100 A/cm^2. on Reiden-SHVS. The APC measures spatial distributions of the beam divergence in r and θ drection and the intensity distribution. An ion image detector capable to acquire a whole temporal evolution within a shot is necessary to measure the higher intensity beams. A fast scintillator with photo-multiplier tubes has been chosen as the image detector. The detector is being tested on a single pinhole camera using a Lithium beam with a particle energy of 5 MeV, a J_i. of 0.5-1 kA/cm^2. and duration of 50 ns, which are very close to the parameters required from ICF, on the SABRE at Sandia National Labs. We will present the diagnostic design and preliminary experiments from SABRE and also present the experimental results from Reiden-SHVS.

42 CFR 414.508 - Payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Payment for a new clinical diagnostic laboratory... SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.508 Payment for a new clinical diagnostic laboratory test. For a new clinical diagnostic laboratory test that is assigned a new or...

20 CFR 404.1519m - Diagnostic tests or procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Diagnostic tests or procedures. 404.1519m... Report Content § 404.1519m Diagnostic tests or procedures. We will request the results of any diagnostic... will not order diagnostic tests or procedures that involve significant risk to you, such as myelograms...

42 CFR 414.508 - Payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Payment for a new clinical diagnostic laboratory... SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.508 Payment for a new clinical diagnostic laboratory test. For a new clinical diagnostic laboratory test that is assigned a new or...

Prevalence of posttraumatic growth hormone deficiency is highly dependent on the diagnostic set-up: results from The Danish National Study on Posttraumatic Hypopituitarism.

PubMed

Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jourgita; Lehman Christensen, Louise; Frystyk, Jan; Andersen, Marianne; Laurberg, Peter; Christiansen, Jens Sandahl; Feldt-Rasmussen, Ulla

2014-01-01

Recent international guidelines suggest pituitary screening in patients with moderate and severe traumatic brain injury (TBI). Predominantly isolated GH deficiency (GHD) was reported in the literature, raising the question of potential methodological bias. Our objective was to assess the prevalence of GHD in patients admitted in 2008 with TBI, with concurrent assessment of methodological bias. We conducted a nationwide population-based cohort study at tertiary referral university hospitals. Participants were Danish patients with a head trauma diagnosis from the Danish Board of Health diagnostic code registry; 439 patients and 124 healthy controls underwent dynamic assessment of GH secretion 2.5 years (median) after TBI. We evaluated the prevalence of GHD given use of 1) local versus guideline cutoffs, 2) insulin tolerance test (ITT), pyridostigmine (PD)-GHRH or GHRH-arginine (arg) test, 3) single versus repeated testing, and 4) GH assessment by assays with different isoform specificities. The prevalence of GHD was lower by local than by guideline cutoffs (12% vs 19% [PD-GHRH/GHRH-arg, P<.001]; 4.5% vs 5% [ITT, P=.9]), and by ITT than by PD-GHRH/GHRH-arg (P=.006 [local cutoffs]; P<.001 [guideline cutoffs]). Only 1% of patients had GHD according to 2 tests. GH assessment by the Immulite or iSYS assay caused no significant diagnostic differences. The study confirmed a high risk of bias in the management of pituitary testing of patients with TBI and stresses the importance of a proper control group and stringent GH testing including confirmatory testing in cohorts with low a priori likelihood of GHD such as in TBI. Our results question the evidence for newly introduced recommendations for routine pituitary assessment in TBI.

CONSISTENCY OF FIELD-BASED MEASURES OF NEUROMUSCULAR CONTROL USING FORCE PLATE DIAGNOSTICS IN ELITE MALE YOUTH SOCCER PLAYERS

PubMed Central

READ, PAUL; OLIVER, JON L.; DE STE CROIX, MARK B.A.; MYER, GREGORY D.; LLOYD, RHODRI S.

2016-01-01

Deficits in neuromuscular control during movement patterns such as landing are suggested pathomechanics that underlie sport-related injury. A common mode of assessment is measurement of landing forces during jumping tasks; however, these measures have been used less frequently in male youth soccer players and reliability data is sparse. The aim of this study was to examine the reliability of a field-based neuromuscular control screening battery using force plate diagnostics in this cohort. Twenty six pre-peak height velocity (PHV) and twenty five post-PHV elite male youth soccer players completed a drop vertical jump (DVJ), single leg 75% horizontal hop and stick (75%HOP) and single leg countermovement jump (SLCMJ). Measures of peak landing vertical ground reaction force (pVGRF), time to stabilisation (TTS), time to pVGRF, and pVGRF asymmetry were recorded. A test, re-test design was used and reliability statistics included: change in mean, intraclass correlation coefficient (ICC) and coefficient of variation (CV). No significant differences in mean score were reported for any of the assessed variables between test sessions. In both groups, pVGRF and asymmetry during the 75%HOP and SLCMJ demonstrated largely acceptable reliability (CV ≤ 10%). Greater variability was evident in DVJ pVGRF and all other assessed variables, across the three protocols (CV range = 13.8 – 49.7%). ICC values ranged from small to large and were generally higher in the post-PHV players. The results of this study suggest that pVGRF and asymmetry can be reliably assessed using a 75%HOP and SLCMJ in this cohort. These measures could be utilized to support a screening battery for elite male youth soccer players and for test re-test comparison. PMID:27075641

Space Laboratory on a Table Top: A Next Generative ECLSS design and diagnostic tool

NASA Technical Reports Server (NTRS)

Ramachandran, N.

2005-01-01

This paper describes the development plan for a comprehensive research and diagnostic tool for aspects of advanced life support systems in space-based laboratories. Specifically it aims to build a high fidelity tabletop model that can be used for the purpose of risk mitigation, failure mode analysis, contamination tracking, and testing reliability. We envision a comprehensive approach involving experimental work coupled with numerical simulation to develop this diagnostic tool. It envisions a 10% scale transparent model of a space platform such as the International Space Station that operates with water or a specific matched index of refraction liquid as the working fluid. This allows the scaling of a 10 ft x 10 ft x 10 ft room with air flow to 1 ft x 1 ft x 1 ft tabletop model with water/liquid flow. Dynamic similitude for this length scale dictates model velocities to be 67% of full-scale and thereby the time scale of the model to represent 15% of the full- scale system; meaning identical processes in the model are completed in 15% of the full- scale-time. The use of an index matching fluid (fluid that matches the refractive index of cast acrylic, the model material) allows making the entire model (with complex internal geometry) transparent and hence conducive to non-intrusive optical diagnostics. So using such a system one can test environment control parameters such as core flows (axial flows), cross flows (from registers and diffusers), potential problem areas such as flow short circuits, inadequate oxygen content, build up of other gases beyond desirable levels, test mixing processes within the system at local nodes or compartments and assess the overall system performance. The system allows quantitative measurements of contaminants introduced in the system and allows testing and optimizing the tracking process and removal of contaminants. The envisaged system will be modular and hence flexible for quick configuration change and subsequent testing. The data and inferences from the tests will allow for improvements in the development and design of next generation life support systems and configurations. Preliminary experimental and modeling work in this area will be presented. This involves testing of a single inlet-exit model with detailed 3-D flow visualization and quantitative diagnostics and computational modeling of the system.

30 CFR 250.525 - What do I submit if my casing diagnostic test requires action?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What do I submit if my casing diagnostic test... if my casing diagnostic test requires action? Within 14 days after you perform a casing diagnostic... Corrective Action Plan within 30 days of the diagnostic test. (b) a casing pressure request, Regional...

"Combined Diagnostic Tool" APPlication to a Retrospective Series of Patients Undergoing Total Joint Revision Surgery.

PubMed

Gallazzi, Enrico; Drago, Lorenzo; Baldini, Andrea; Stockley, Ian; George, David A; Scarponi, Sara; Romanò, Carlo L

2017-01-01

Background : Differentiating between septic and aseptic joint prosthesis may be challenging, since no single test is able to confirm or rule out infection. The choice and interpretation of the panel of tests performed in any case often relies on empirical evaluation and poorly validated scores. The "Combined Diagnostic Tool (CDT)" App, a smartphone application for iOS, was developed to allow to automatically calculate the probability of having a of periprosthetic joint infection, on the basis of the relative sensitivity and specificity of the positive and negative diagnostic tests performed in any given patient. Objective : The aim of the present study was to apply the CDT software to investigate the ability of the tests routinely performed in three high-volume European centers to diagnose a periprosthetic infection. Methods : This three-center retrospective study included 120 consecutive patients undergoing total hip or knee revision, and included 65 infected patients (Group A) and 55 patients without infection (Group B). The following parameters were evaluated: number and type of positive and negative diagnostic tests performed pre-, intra- and post-operatively and resultant probability calculated by the CDT App of having a peri-prosthetic joint infection, based on pre-, intra- and post-operative combined tests. Results : Serological tests were the most common performed, with an average 2.7 tests per patient for Group A and 2.2 for Group B, followed by joint aspiration (0.9 and 0.8 tests per patient, respectively) and imaging techniques (0.5 and 0.2 test per patient). Mean CDT App calculated probability of having an infection based on pre-operative tests was 79.4% for patients in Group A and 35.7 in Group B. Twenty-nine patients in Group A had > 10% chance of not having an infection, and 29 of Group B had > 10% chance of having an infection. Conclusion : This is the first retrospective study focused on investigating the number and type of tests commonly performed prior to joint revision surgery and aimed at evaluating their combined ability to diagnose a peri-prosthetic infection. CDT App allowed us to demonstrate that, on average, the routine combination of commonly used tests is unable to diagnose pre-operatively a peri-prosthetic infection with a probability higher than 90%.

A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.

PubMed

Harding-Esch, E M; Cousins, E C; Chow, S-L C; Phillips, L T; Hall, C L; Cooper, N; Fuller, S S; Nori, A V; Patel, R; Thomas-William, S; Whitlock, G; Edwards, S J E; Green, M; Clarkson, J; Arlett, B; Dunbar, J K; Lowndes, C M; Sadiq, S T

2018-02-01

Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min. Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Consistency of Field-Based Measures of Neuromuscular Control Using Force-Plate Diagnostics in Elite Male Youth Soccer Players.

PubMed

Read, Paul J; Oliver, Jon L; Croix, Mark Ba De Ste; Myer, Gregory D; Lloyd, Rhodri S

2016-12-01

Read, P, Oliver, JL, Croix, MD, Myer, GD, and Lloyd, RS. Consistency of field-based measures of neuromuscular control using force-plate diagnostics in elite male youth soccer players. J Strength Cond Res 30(12): 3304-3311, 2016-Deficits in neuromuscular control during movement patterns such as landing are suggested pathomechanics that underlie sport-related injury. A common mode of assessment is measurement of landing forces during jumping tasks; however, these measures have been used less frequently in male youth soccer players, and reliability data are sparse. The aim of this study was to examine the reliability of a field-based neuromuscular control screening battery using force-plate diagnostics in this cohort. Twenty-six pre-peak height velocity (PHV) and 25 post-PHV elite male youth soccer players completed a drop vertical jump (DVJ), single-leg 75% horizontal hop and stick (75%HOP), and single-leg countermovement jump (SLCMJ). Measures of peak landing vertical ground reaction force (pVGRF), time to stabilization, time to pVGRF, and pVGRF asymmetry were recorded. A test-retest design was used, and reliability statistics included change in mean, intraclass correlation coefficient, and coefficient of variation (CV). No significant differences in mean score were reported for any of the assessed variables between test sessions. In both groups, pVGRF and asymmetry during the 75%HOP and SLCMJ demonstrated largely acceptable reliability (CV ≤ 10%). Greater variability was evident in DVJ pVGRF and all other assessed variables, across the 3 protocols (CV range = 13.8-49.7%). Intraclass correlation coefficient values ranged from small to large and were generally higher in the post-PHV players. The results of this study suggest that pVGRF and asymmetry can be reliably assessed using a 75%HOP and SLCMJ in this cohort. These measures could be used to support a screening battery for elite male youth soccer players and for test-retest comparison.

Evaluating diagnostic tests for bovine tuberculosis in the southern part of Germany: A latent class analysis

PubMed Central

Knubben-Schweizer, Gabriela; Döpfer, Dörte; Groll, Andreas; Hafner-Marx, Angela; Hörmansdorfer, Stefan; Sauter-Louis, Carola; Straubinger, Reinhard K.; Zimmermann, Pia; Hartnack, Sonja

2017-01-01

Germany has been officially free of bovine tuberculosis since 1996. However, in the last years there has been an increase of bovine tuberculosis cases, particularly in the southern part of Germany, in the Allgäu region. As a consequence a one-time tuberculosis surveillance program was revisited with different premortal and postmortal tests. The aim of this paper was to estimate diagnostic sensitivities and specificities of the different tests used within this surveillance program. In the absence of a perfect test with 100% sensitivity and 100% specificity, thus in the absence of a gold standard, a Bayesian latent class approach with two different datasets was performed. The first dataset included 389 animals, tested with single intra-dermal comparative cervical tuberculin (SICCT) test, PCR and pathology; the second dataset contained 175 animals, tested with single intra-dermal cervical tuberculin (SICT) test, Bovigam® assay, pathology and culture. Two-way conditional dependencies were considered within the models. Additionally, inter-laboratory agreement (five officially approved laboratories) of the Bovigam® assay was assessed with Cohen's kappa test (21 blood samples). The results are given in posterior means and 95% credibility intervals. The specificities of the SICT test, SICCT test, PCR and pathology ranged between 75.8% [68.8–82.2%] and 99.0% [96.8–100%]. The Bovigam® assay stood out with a very low specificity (6.9% [3.6–11.1%]), though it had the highest sensitivity (95.7% [91.3–99.2%]). The sensitivities of the SICCT test, PCR, SICT test, pathology and culture varied from 57.8% [48.0–67.6%] to 88.9% [65.5–99.7%]. The prevalences were 19.8% [14.6–26.5%] (three-test dataset) and 7.7% [4.2–12.3%] (four-test dataset). Among all pairwise comparisons the highest agreement was 0.62 [0.15–1]). In conclusion, the specificity of the Bovigam® assay and the inter-laboratory agreement were lower than expected. PMID:28640908

[Triorchidism: which therapy?

PubMed

Piro, Eugenia; Abati, Laura; Zocca, Veronica; Brugnoni, Marta; D'Alessio, Antonio

2017-06-23

Polyorchidism is an anomaly characterized by more than two gonads; triorchidism is the most common variant. Its management is controversial, mostly when surgical treatment is occasional. CB, 14 year-old, came to the hospital due to right-sided testicular torsion. During surgery, testis was rotated and the contralateral testis, which presented as an anatomically continuum with a gonadic structure similar to the other testes but with a smaller diameter, was fixed. We performed biopsy on both left testes and decided to preserve the supernumerary one. Following the anatomic and functional classification of polyorchidism by Singer, preservation is justified on the grounds of the presence of a supernumerary testis that drains into the epididymis of the normal testis, merging into one single deferent duct (Singer Type 1). At biopsy, both testes had a valid spermatogenic asset. The diagnostic follow-up at 6 and 12 months did not show any pathological alteration. Diagnosis of polyorchidism is occasional. Its treatment varies depending on the site, dimension, and anatomy of the drainage system of the supernumerary testis. If the supernumerary testis is preserved, a standardized diagnostic follow-up is recommended.

Using Combined Diagnostic Test Results to Hindcast Trends of Infection from Cross-Sectional Data

PubMed Central

Rydevik, Gustaf; Innocent, Giles T.; Marion, Glenn; White, Piran C. L.; Billinis, Charalambos; Barrow, Paul; Mertens, Peter P. C.; Gavier-Widén, Dolores; Hutchings, Michael R.

2016-01-01

Infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. Following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. It is thus critical to obtain accurate information concerning the origin of the outbreak and its forward trajectory. However, there is often a lack of situational awareness that may lead to over- or under-reaction. There is a widening range of tests available for detecting pathogens, with typically different temporal characteristics, e.g. in terms of when peak test response occurs relative to time of exposure. We have developed a statistical framework that combines response level data from multiple diagnostic tests and is able to ‘hindcast’ (infer the historical trend of) an infectious disease epidemic. Assuming diagnostic test data from a cross-sectional sample of individuals infected with a pathogen during an outbreak, we use a Bayesian Markov Chain Monte Carlo (MCMC) approach to estimate time of exposure, and the overall epidemic trend in the population prior to the time of sampling. We evaluate the performance of this statistical framework on simulated data from epidemic trend curves and show that we can recover the parameter values of those trends. We also apply the framework to epidemic trend curves taken from two historical outbreaks: a bluetongue outbreak in cattle, and a whooping cough outbreak in humans. Together, these results show that hindcasting can estimate the time since infection for individuals and provide accurate estimates of epidemic trends, and can be used to distinguish whether an outbreak is increasing or past its peak. We conclude that if temporal characteristics of diagnostics are known, it is possible to recover epidemic trends of both human and animal pathogens from cross-sectional data collected at a single point in time. PMID:27384712

Single-Center Experience with a Targeted Next Generation Sequencing Assay for Assessment of Relevant Somatic Alterations in Solid Tumors.

PubMed

Paasinen-Sohns, Aino; Koelzer, Viktor H; Frank, Angela; Schafroth, Julian; Gisler, Aline; Sachs, Melanie; Graber, Anne; Rothschild, Sacha I; Wicki, Andreas; Cathomas, Gieri; Mertz, Kirsten D

2017-03-01

Companion diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. Here we report the clinical application and validation of the Oncomine Focus Assay (OFA), an integrated, commercially available next-generation sequencing (NGS) assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance. Two independent patient cohorts were investigated to define the workflow, turnaround times, feasibility, and reliability of OFA targeted sequencing in clinical application and using archival material. Cohort I consisted of 59 diagnostic clinical samples from the daily routine submitted for molecular testing over a 4-month time period. Cohort II consisted of 39 archival melanoma samples that were up to 15years old. Libraries were prepared from isolated nucleic acids and sequenced on the Ion Torrent PGM sequencer. Sequencing datasets were analyzed using the Ion Reporter software. Genomic alterations were identified and validated by orthogonal conventional assays including pyrosequencing and immunohistochemistry. Sequencing results of both cohorts, including archival formalin-fixed, paraffin-embedded material stored up to 15years, were consistent with published variant frequencies. A concordance of 100% between established assays and OFA targeted NGS was observed. The OFA workflow enabled a turnaround of 3½ days. Taken together, OFA was found to be a convenient tool for fast, reliable, broadly applicable and cost-effective targeted NGS of tumor samples in routine diagnostics. Thus, OFA has strong potential to become an important asset for precision oncology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Diagnostic value of a pattern of exhaled breath condensate biomarkers in asthmatic children.

PubMed

Maloča Vuljanko, I; Turkalj, M; Nogalo, B; Bulat Lokas, S; Plavec, D

Diagnosing asthma in children is a challenge and using a single biomarker from exhaled breath condensate (EBC) showed the lack of improvement in it. The aim of this study was to assess the diagnostic potential of a pattern of simple chemical biomarkers from EBC in diagnosing asthma in children in a real-life setting, its association with lung function and gastroesophageal reflux disease (GERD). In 75 consecutive children aged 5-7 years with asthma-like symptoms the following tests were performed: skin prick tests, spirometry, impulse oscillometry (IOS), exhaled NO (F E NO), 24-hour oesophageal pH monitoring and EBC collection with subsequent analysis of pH, carbon dioxide tension, oxygen tension, and concentrations of magnesium, calcium, iron and urates. No significant differences were found for individual EBC biomarkers between asthmatics and non-asthmatics (p>0.05 for all). A pattern of six EBC biomarkers showed a statistically significant (p=0.046) predictive model for asthma (AUC=0.698, PPV=84.2%, NPV=38.9%). None to moderate association (R 2 up to 0.43) between EBC biomarkers and lung function measures and F E NO was found, with IOS parameters showing the best association with EBC biomarkers. A significantly higher EBC Fe was found in children with asthma and GERD compared to asthmatics without GERD (p=0.049). An approach that involves a pattern of EBC biomarkers had a better diagnostic accuracy for asthma in children in real-life settings compared to a single one. Poor to moderate association of EBC biomarkers with lung function suggests a complementary value of EBC analysis for asthma diagnosis in children. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

40 CFR 85.2222 - On-board diagnostic test procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 19 2013-07-01 2013-07-01 false On-board diagnostic test procedures... Warranty Short Tests § 85.2222 On-board diagnostic test procedures. The test sequence for the inspection of on-board diagnostic systems on 1996 and newer light-duty vehicles and light-duty trucks shall consist...

40 CFR 85.2222 - On-board diagnostic test procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false On-board diagnostic test procedures... Warranty Short Tests § 85.2222 On-board diagnostic test procedures. The test sequence for the inspection of on-board diagnostic systems on 1996 and newer light-duty vehicles and light-duty trucks shall consist...

40 CFR 85.2231 - On-board diagnostic test equipment requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false On-board diagnostic test equipment... Warranty Short Tests § 85.2231 On-board diagnostic test equipment requirements. (a) The test system interface to the vehicle shall include a plug that conforms to SAE J1962 “Diagnostic Connector.” The...

40 CFR 85.2222 - On-board diagnostic test procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false On-board diagnostic test procedures... Warranty Short Tests § 85.2222 On-board diagnostic test procedures. The test sequence for the inspection of on-board diagnostic systems on 1996 and newer light-duty vehicles and light-duty trucks shall consist...

40 CFR 85.2231 - On-board diagnostic test equipment requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false On-board diagnostic test equipment... Warranty Short Tests § 85.2231 On-board diagnostic test equipment requirements. (a) The test system interface to the vehicle shall include a plug that conforms to SAE J1962 “Diagnostic Connector.” The...

40 CFR 85.2231 - On-board diagnostic test equipment requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 19 2013-07-01 2013-07-01 false On-board diagnostic test equipment... Warranty Short Tests § 85.2231 On-board diagnostic test equipment requirements. (a) The test system interface to the vehicle shall include a plug that conforms to SAE J1962 “Diagnostic Connector.” The...

Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinson's disease).

PubMed

Schwarz, Stefan T; Xing, Yue; Naidu, Saadnah; Birchall, Jim; Skelly, Rob; Perkins, Alan; Evans, Jonathan; Sare, Gill; Martin-Bastida, Antonio; Bajaj, Nin; Gowland, Penny; Piccini, Paola; Auer, Dorothee P

2017-12-14

Parkinson's disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson's can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD. In a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson's from three movement disorder centres in the UK to take part in the study. We will record the Movement Disorder Society - Unified Parkinson's Disease Rating Scale, and participants will undergo DaTSCAN and high-resolution susceptibility weighted MRI at a field strength of 3T. DaTSCANs will be assessed visually and semiquantitatively; MRI scans will be visually assessed for signal loss in nigrosome-1 by blinded investigators. We will compare how the diagnosis suggested by MRI compares with the diagnosis based on DaTSCAN and will also validate the diagnosis based on the two tests with a clinical examination performed at least 1 year after the initial presentation as a surrogate gold standard diagnostic test. The local ethics commission (Health Research Authority East Midlands - Derby Research Ethics Committee) has approved this study (REC ref.: 16/EM/0229). The study is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. We have included a number of 15 research-funded DaTSCAN in the research protocol. This is to compensate for study site-specific National Health Service funding for this investigation in affected patients. We therefore have also obtained approval from the Administration of Radioactive Substances Administration Committee (ARSAC Ref 253/3629/35864). All findings will be presented at relevant scientific meetings and published in peer-reviewed journals, on the study website, and disseminated in lay and social media where appropriate. NCT03022357; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A whole-heart motion-correction algorithm: Effects on CT image quality and diagnostic accuracy of mechanical valve prosthesis abnormalities.

PubMed

Suh, Young Joo; Kim, Young Jin; Kim, Jin Young; Chang, Suyon; Im, Dong Jin; Hong, Yoo Jin; Choi, Byoung Wook

2017-11-01

We aimed to determine the effect of a whole-heart motion-correction algorithm (new-generation snapshot freeze, NG SSF) on the image quality of cardiac computed tomography (CT) images in patients with mechanical valve prostheses compared to standard images without motion correction and to compare the diagnostic accuracy of NG SSF and standard CT image sets for the detection of prosthetic valve abnormalities. A total of 20 patients with 32 mechanical valves who underwent wide-coverage detector cardiac CT with single-heartbeat acquisition were included. The CT image quality for subvalvular (below the prosthesis) and valvular regions (valve leaflets) of mechanical valves was assessed by two observers on a four-point scale (1 = poor, 2 = fair, 3 = good, and 4 = excellent). Paired t-tests or Wilcoxon signed rank tests were used to compare image quality scores and the number of diagnostic phases (image quality score≥3) between the standard image sets and NG SSF image sets. Diagnostic performance for detection of prosthetic valve abnormalities was compared between two image sets with the final diagnosis set by re-operation or clinical findings as the standard reference. NG SSF image sets had better image quality scores than standard image sets for both valvular and subvalvular regions (P < 0.05 for both). The number of phases that were of diagnostic image quality per patient was significantly greater in the NG SSF image set than standard image set for both valvular and subvalvular regions (P < 0.0001). Diagnostic performance of NG SSF image sets for the detection of prosthetic abnormalities (20 pannus and two paravalvular leaks) was greater than that of standard image sets (P < 0.05). Application of NG SSF can improve CT image quality and diagnostic accuracy in patients with mechanical valves compared to standard images. Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Long-term Cost-Effectiveness of Diagnostic Tests for Assessing Stable Chest Pain: Modeled Analysis of Anatomical and Functional Strategies.

PubMed

Bertoldi, Eduardo G; Stella, Steffan F; Rohde, Luis E; Polanczyk, Carisi A

2016-05-01

Several tests exist for diagnosing coronary artery disease, with varying accuracy and cost. We sought to provide cost-effectiveness information to aid physicians and decision-makers in selecting the most appropriate testing strategy. We used the state-transitions (Markov) model from the Brazilian public health system perspective with a lifetime horizon. Diagnostic strategies were based on exercise electrocardiography (Ex-ECG), stress echocardiography (ECHO), single-photon emission computed tomography (SPECT), computed tomography coronary angiography (CTA), or stress cardiac magnetic resonance imaging (C-MRI) as the initial test. Systematic review provided input data for test accuracy and long-term prognosis. Cost data were derived from the Brazilian public health system. Diagnostic test strategy had a small but measurable impact in quality-adjusted life-years gained. Switching from Ex-ECG to CTA-based strategies improved outcomes at an incremental cost-effectiveness ratio of 3100 international dollars per quality-adjusted life-year. ECHO-based strategies resulted in cost and effectiveness almost identical to CTA, and SPECT-based strategies were dominated because of their much higher cost. Strategies based on stress C-MRI were most effective, but the incremental cost-effectiveness ratio vs CTA was higher than the proposed willingness-to-pay threshold. Invasive strategies were dominant in the high pretest probability setting. Sensitivity analysis showed that results were sensitive to costs of CTA, ECHO, and C-MRI. Coronary CT is cost-effective for the diagnosis of coronary artery disease and should be included in the Brazilian public health system. Stress ECHO has a similar performance and is an acceptable alternative for most patients, but invasive strategies should be reserved for patients at high risk. © 2016 Wiley Periodicals, Inc.

The Quantitative Science of Evaluating Imaging Evidence.

PubMed

Genders, Tessa S S; Ferket, Bart S; Hunink, M G Myriam

2017-03-01

Cardiovascular diagnostic imaging tests are increasingly used in everyday clinical practice, but are often imperfect, just like any other diagnostic test. The performance of a cardiovascular diagnostic imaging test is usually expressed in terms of sensitivity and specificity compared with the reference standard (gold standard) for diagnosing the disease. However, evidence-based application of a diagnostic test also requires knowledge about the pre-test probability of disease, the benefit of making a correct diagnosis, the harm caused by false-positive imaging test results, and potential adverse effects of performing the test itself. To assist in clinical decision making regarding appropriate use of cardiovascular diagnostic imaging tests, we reviewed quantitative concepts related to diagnostic performance (e.g., sensitivity, specificity, predictive values, likelihood ratios), as well as possible biases and solutions in diagnostic performance studies, Bayesian principles, and the threshold approach to decision making. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Evaluating Diagnostic Point-of-Care Tests in Resource-Limited Settings

PubMed Central

Drain, Paul K; Hyle, Emily P; Noubary, Farzad; Freedberg, Kenneth A; Wilson, Douglas; Bishai, William; Rodriguez, William; Bassett, Ingrid V

2014-01-01

Diagnostic point-of-care (POC) testing is intended to minimize the time to obtain a test result, thereby allowing clinicians and patients to make an expeditious clinical decision. As POC tests expand into resource-limited settings (RLS), the benefits must outweigh the costs. To optimize POC testing in RLS, diagnostic POC tests need rigorous evaluations focused on relevant clinical outcomes and operational costs, which differ from evaluations of conventional diagnostic tests. Here, we reviewed published studies on POC testing in RLS, and found no clearly defined metric for the clinical utility of POC testing. Therefore, we propose a framework for evaluating POC tests, and suggest and define the term “test efficacy” to describe a diagnostic test’s capacity to support a clinical decision within its operational context. We also proposed revised criteria for an ideal diagnostic POC test in resource-limited settings. Through systematic evaluations, comparisons between centralized diagnostic testing and novel POC technologies can be more formalized, and health officials can better determine which POC technologies represent valuable additions to their clinical programs. PMID:24332389

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

PubMed

Hamblin, Angela; Wordsworth, Sarah; Fermont, Jilles M; Page, Suzanne; Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V; Housby, Nick; Tomlinson, Ian; Taylor, Jenny C; Schuh, Anna

2017-02-01

Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers.

[Diagnostic test scale SI5: Assessment of sacroiliac joint dysfunction].

PubMed

Acevedo González, Juan C; Quintero Oliveros, Silvia

2015-01-01

Sacroiliac joint dysfunction is a known cause of low back pain. We think that a diagnostic score scale (SI5) may be performed to assess diagnostic utility of clinical signs of sacroiliac joint dysfunction. The primary aim of the present study was to conduct the pilot study of our new diagnostic score scale, the SI5, for sacroiliac joint syndrome. We reviewed the literature on clinical characteristics, diagnostic tests and imaging most commonly used in diagnosing sacroiliac joint dysfunction. Our group evaluated the diagnostic utility of these aspects and we used those considered most representative to develop the SI5 diagnostic scale. The SI5 scale was applied to 22 patients with low back pain; afterwards, the standard test for diagnosing this pathology (selective blockage of the SI joint) was also performed on these patients. The sensitivity and specificity for each sign were also assessed and the diagnostic scale called SI5 was then proposed, based on these data. The most sensitive clinical tests for diagnosing SI joint dysfunction were 2 patient-reported clinical characteristics, the Laguerre Test, sacroiliac rocking test and Yeomans test (greater than 80% sensitivity). The tests with greatest diagnostic specificity (>80%) were the Lewitt test, Piedallu test and Gillet test. The proposed SI5 test score scale showed sensitivity of 73% and specificity of 71%. Sacroiliac joint syndrome has been shown to produce low back pain frequently; however, the diagnostic value of examination tests for sacroiliac joint pain has been questioned by other authors. The pilot study on the SI5 diagnostic score scale showed good sensitivity and specificity. However, the process of statistical validation of the SI5 needs to be continued. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

How to Use the DX SYSTEM of Diagnostic Testing. Methodology Project.

ERIC Educational Resources Information Center

McArthur, David; Cabello, Beverly

The DX SYSTEM of Diagnostic Testing is an easy-to-use computerized system for developing and administering diagnostic tests. A diagnostic test measures a student's mastery of a specific domain (skill or content area). It examines the necessary subskills hierarchically from the most to the least complex. The DX SYSTEM features tailored testing with…

The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

PubMed

Leeflang, M M G; Ang, C W; Berkhout, J; Bijlmer, H A; Van Bortel, W; Brandenburg, A H; Van Burgel, N D; Van Dam, A P; Dessau, R B; Fingerle, V; Hovius, J W R; Jaulhac, B; Meijer, B; Van Pelt, W; Schellekens, J F P; Spijker, R; Stelma, F F; Stanek, G; Verduyn-Lunel, F; Zeller, H; Sprong, H

2016-03-25

Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

Measures of accuracy and performance of diagnostic tests.

PubMed

Drobatz, Kenneth J

2009-05-01

Diagnostic tests are integral to the practice of veterinary cardiology, any other specialty, and general veterinary medicine. Developing and understanding diagnostic tests is one of the cornerstones of clinical research. This manuscript describes the diagnostic test properties including sensitivity, specificity, predictive value, likelihood ratio, receiver operating characteristic curve. Review of practical book chapters and standard statistics manuscripts. Diagnostics such as sensitivity, specificity, predictive value, likelihood ratio, and receiver operating characteristic curve are described and illustrated. Basic understanding of how diagnostic tests are developed and interpreted is essential in reviewing clinical scientific papers and understanding evidence based medicine.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... Nonphysician practitioners (that is, clinical nurse specialists, clinical psychologists, clinical social... that do not involve the use of contrast media; and (iii) Diagnostic mammograms if the approved portable...

What Do Diagnostic Reading Tests Really Diagnose?

ERIC Educational Resources Information Center

Winkley, Carol K.

A study was made of nine reading tests, including both group and individually-administered measures, which are claimed to be chiefly diagnostic. Instruments analyzed were the following: Silent Reading Diagnostic Tests (Bond, Balow, and Hoyt), Botel Reading Inventory, Durrell Analysis of Reading Difficulty, Gates-McKillop Reading Diagnostic Tests,…

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2012 CFR

2012-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2013 CFR

2013-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2014 CFR

2014-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2010 CFR

2010-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

9 CFR 93.404 - Import permits for ruminants and for ruminant test specimens for diagnostic purposes; and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... ruminant test specimens for diagnostic purposes; and reservation fees for space at quarantine facilities... for ruminants and for ruminant test specimens for diagnostic purposes; and reservation fees for space...) For ruminants and ruminant test specimens for diagnostic screening purposes intended for importation...

Diagnostic test accuracy of nutritional tools used to identify undernutrition in patients with colorectal cancer: a systematic review.

PubMed

Håkonsen, Sasja Jul; Pedersen, Preben Ulrich; Bath-Hextall, Fiona; Kirkpatrick, Pamela

2015-05-15

Effective nutritional screening, nutritional care planning and nutritional support are essential in all settings, and there is no doubt that a health service seeking to increase safety and clinical effectiveness must take nutritional care seriously. Screening and early detection of malnutrition is crucial in identifying patients at nutritional risk. There is a high prevalence of malnutrition in hospitalized patients undergoing treatment for colorectal cancer. To synthesize the best available evidence regarding the diagnostic test accuracy of nutritional tools (sensitivity and specificity) used to identify malnutrition (specifically undernutrition) in patients with colorectal cancer (such as the Malnutrition Screening Tool and Nutritional Risk Index) compared to reference tests (such as the Subjective Global Assessment or Patient Generated Subjective Global Assessment). Patients with colorectal cancer requiring either (or all) surgery, chemotherapy and/or radiotherapy in secondary care. Focus of the review: The diagnostic test accuracy of validated assessment tools/instruments (such as the Malnutrition Screening Tool and Nutritional Risk Index) in the diagnosis of malnutrition (specifically under-nutrition) in patients with colorectal cancer, relative to reference tests (Subjective Global Assessment or Patient Generated Subjective Global Assessment). Types of studies: Diagnostic test accuracy studies regardless of study design. Studies published in English, German, Danish, Swedish and Norwegian were considered for inclusion in this review. Databases were searched from their inception to April 2014. Methodological quality was determined using the Quality Assessment of Diagnostic Accuracy Studies checklist. Data was collected using the data extraction form: the Standards for Reporting Studies of Diagnostic Accuracy checklist for the reporting of studies of diagnostic accuracy. The accuracy of diagnostic tests is presented in terms of sensitivity, specificity, positive and negative predictive values. In addition, the positive likelihood ratio (sensitivity/ [1 - specificity]) and negative likelihood ratio (1 - sensitivity)/ specificity), were also calculated and presented in this review to provide information about the likelihood that a given test result would be expected when the target condition is present compared with the likelihood that the same result would be expected when the condition is absent. Not all trials reported true positive, true negative, false positive and false negative rates, therefore these rates were calculated based on the data in the published papers. A two-by-two truth table was reconstructed for each study, and sensitivity, specificity, positive predictive value, negative predictive value positive likelihood ratio and negative likelihood ratio were calculated for each study. A summary receiver operator characteristics curve was constructed to determine the relationship between sensitivity and specificity, and the area under the summary receiver operator characteristics curve which measured the usefulness of a test was calculated. Meta-analysis was not considered appropriate, therefore data was synthesized in a narrative summary. 1. One study evaluated the Malnutrition Screening Tool against the reference standard Patient-Generated Subjective Global Assessment. The sensitivity was 56% and the specificity 84%. The positive likelihood ratio was 3.100, negative likelihood ratio was 0.59, the diagnostic odds ratio (CI 95%) was 5.20 (1.09-24.90) and the Area Under the Curve (AUC) represents only a poor to fair diagnostic test accuracy. A total of two studies evaluated the diagnostic accuracy of Malnutrition Universal Screening Tool (MUST) (index test) compared to both Subjective Global Assessment (SGA) (reference standard) and PG-SGA (reference standard) in patients with colorectal cancer. In MUST vs SGA the sensitivity of the tool was 96%, specificity was 75%, LR+ 3.826, LR- 0.058, diagnostic OR (CI 95%) 66.00 (6.61-659.24) and AUC represented excellent diagnostic accuracy. In MUST vs PG-SGA the sensitivity of the tool was 72%, specificity 48.9%, LR+ 1.382, LR- 0.579, diagnostic OR (CI 95%) 2.39 (0.87-6.58) and AUC indicated that the tool failed as a diagnostic test to identify patients with colorectal cancer at nutritional risk,. The Nutrition Risk Index (NRI) was compared to SGA representing a sensitivity of 95.2%, specificity of 62.5%, LR+ 2.521, LR- 0.087, diagnostic OR (CI 95%) 28.89 (6.93-120.40) and AUC represented good diagnostic accuracy. In regard to NRI vs PG-SGA the sensitivity of the tool was 68%, specificity 64%, LR+ 1.947, LR- 0.487, diagnostic OR (CI 95%) 4.00 (1.23-13.01) and AUC indicated poor diagnostic test accuracy. There are no single, specific tools used to screen or assess the nutritional status of colorectal cancer patients. All tools showed varied diagnostic accuracies when compared to the reference standards SGA and PG-SGA. Hence clinical judgment combined with perhaps the SGA or PG-SGA should play a major role. The PG-SGA offers several advantages over the SGA tool: 1) the patient completes the medical history component, thereby decreasing the amount of time involved; 2) it contains more nutrition impact symptoms, which are important to the patient with cancer; and 3) it has a scoring system that allows patients to be triaged for nutritional intervention. Therefore, the PG-SGA could be used as a nutrition assessment tool as it allows quick identification and prioritization of colorectal cancer patients with malnutrition in combination with other parameters. This systematic review highlights the need for the following: Further studies needs to investigate the diagnostic accuracy of already existing nutritional screening tools in the context of colorectal cancer patients. If new screenings tools are developed, they should be developed and validated in the specific clinical context within the same patient population (colorectal cancer patients). The Joanna Briggs Institute.

Uptake of prenatal diagnostic testing and the effectiveness of prenatal screening for Down syndrome.

PubMed

Jaques, Alice M; Collins, Veronica R; Muggli, Evelyne E; Amor, David J; Francis, Ivan; Sheffield, Leslie J; Halliday, Jane L

2010-06-01

To map prenatal screening and diagnostic testing pathways in Victorian pregnant women during 2003 to 2004; measure the impact of prenatal diagnostic testing uptake on the effectiveness of prenatal screening for Down syndrome; and assess factors influencing uptake of diagnostic testing following screening. State-wide data collections of prenatal screening and diagnostic tests were linked to all Victorian births and pregnancy terminations for birth defects. Overall, 52% of women had a prenatal test (65 692/126 305); screening (44.9%), diagnostic testing (3.9%), or both (3.2%). Uptake of diagnostic testing was 71.4% (2390/3349) after an increased risk screen result, and 2.5% (1381/54 286) after a low risk result. Variation in uptake of diagnostic testing reduced the effectiveness of the screening program by 11.2%: from 87.4% (sensitivity - 125/143) to 76.2% (prenatal diagnoses of Down syndrome - 109/143). In both the increased and low risk groups, uptake was influenced by absolute numerical risk, as well as by the change in numerical risk from a priori risk. This comprehensive follow-up demonstrates clearly that numerical risk is being used to aid in decision making about confirmatory diagnostic testing. Collectively, these fundamental individual decisions will impact on the overall effectiveness of screening programmes for Down syndrome.

Use of recombinant purified protein derivative (PPD) antigens as specific skin test for tuberculosis.

PubMed

Stavri, Henriette; Bucurenci, Nadia; Ulea, Irina; Costache, Adriana; Popa, Loredana; Popa, Mircea Ioan

2012-11-01

Purified protein derivative (PPD) is currently the only available skin test reagent used worldwide for the diagnosis of tuberculosis (TB). The aim of this study was to develop a Mycobacterium tuberculosis specific skin test reagent, without false positive results due to Bacillus Calmette-Guerin (BCG) vaccination using recombinant antigens. Proteins in PPD IC-65 were analyzed by tandem mass spectrometry and compared to proteins in M. tuberculosis culture filtrate; 54 proteins were found in common. Top candidates MPT64, ESAT 6, and CFP 10 were overexpressed in Escherichia coli expression strains and purified as recombinant proteins. To formulate optimal immunodiagnostic PPD cocktails, the antigens were evaluated by skin testing guinea pigs sensitized with M. tuberculosis H37Rv and BCG. For single antigens and a cocktail mixture of these antigens, best results were obtained using 3 μg/0.1 ml, equivalent to 105 TU (tuberculin units). Each animal was simultaneously tested with PPD IC-65, 2 TU/0.1 ml, as reference. Reactivity of the multi-antigen cocktail was greater than that of any single antigen. The skin test results were between 34.3 and 76.6 per cent the level of reactivity compared to that of the reference when single antigens were tested and 124 per cent the level of reactivity compared to the reference for the multi-antigen cocktail. Our results showed that this specific cocktail could represent a potential candidate for a new skin diagnostic test for TB.

Production and Evaluation of a Purified Adenovirus Group-Specific (Hexon) Antigen for Use in the Diagnostic Complement Fixation Test

PubMed Central

Dowdle, W. R.; Lambriex, M.; Hierholzer, J. C.

1971-01-01

A simple procedure for the production of large volumes of purified adenovirus group-specific complement-fixing (CF) (hexon) antigen by selective adsorption to and elution from CaHPO4 is described. Results of immunodiffusion tests, electrophoresis, electron microscopy, and tests for hemagglutination and infectivity indicate that the purified antigen consisted of a single virus component (hexon). The purified product contained little host materials. Unlike the crude virus harvest usually employed for serodiagnostic CF tests, the purified antigen demonstrated no anticomplementary activity and did not develop such activity during storage. The purified antigen was equal to or slightly more sensitive than crude virus harvests for serodiagnosis of adenovirus infections. Images PMID:4325021

Costs of genetic testing: Supporting Brazilian Public Policies for the incorporating of molecular diagnostic technologies

PubMed Central

Schlatter, Rosane Paixão; Matte, Ursula; Polanczyk, Carisi Anne; Koehler-Santos, Patrícia; Ashton-Prolla, Patricia

2015-01-01

This study identifies and describes the operating costs associated with the molecular diagnosis of diseases, such as hereditary cancer. To approximate the costs associated with these tests, data informed by Standard Operating Procedures for various techniques was collected from hospital software and a survey of market prices. Costs were established for four scenarios of capacity utilization to represent the possibility of suboptimal use in research laboratories. Cost description was based on a single site. The results show that only one technique was not impacted by rising costs due to underutilized capacity. Several common techniques were considerably more expensive at 30% capacity, including polymerase chain reaction (180%), microsatellite instability analysis (181%), gene rearrangement analysis by multiplex ligation probe amplification (412%), non-labeled sequencing (173%), and quantitation of nucleic acids (169%). These findings should be relevant for the definition of public policies and suggest that investment of public funds in the establishment of centralized diagnostic research centers would reduce costs to the Public Health System. PMID:26500437

Single-phase dual-energy CT allows for characterization of renal masses as benign or malignant.

PubMed

Graser, Anno; Becker, Christoph R; Staehler, Michael; Clevert, Dirk A; Macari, Michael; Arndt, Niko; Nikolaou, Konstantin; Sommer, Wieland; Stief, Christian; Reiser, Maximilian F; Johnson, Thorsten R C

2010-07-01

To evaluate the diagnostic accuracy of dual-energy CT (DECT) in renal mass characterization using a single-phase acquisition. A total of 202 patients (148 males, 54 females; 63 +/- 13 years) with ultrasound-based suspicion of a renal mass underwent unenhanced single energy and nephrographic phase DECT on a dual source scanner (Siemens Somatom Definition Dual Source, n = 174; Somatom Definition Flash, n = 28). Scan parameters for DECT were: tube potential, 80/100 and 100/Sn140 kVp; exposure, 404/300 and 96/232 effective mAs; collimation, 14 x 1.2/32 x 0.6 mm. Two abdominal radiologists assessed DECT and SECT image quality and noise on a 5-point visual analogue scale. Using solely the DE acquisition including virtual nonenhanced (VNE) and color coded iodine images that enable direct visualization of iodine, masses were characterized as benign or malignant. In a second reading session after 34 to 72 (average: 55) days, the same assessment was again performed using both the true nonenhanced (TNE) and nephrographic phase scans thereby simulating conventional single-energy CT. Sensitivities, specificities, diagnostic accuracies, and interpretation times and were recorded for both reading paradigms. Dose reduction of a single-phase over a dual-phase protocol was calculated. Results were tested for statistical significance using the paired Wilcoxon signed rank test and student t test. Differences in sensitivities were tested for significance using the McNemar test. Of the 202 patients, 115 (56.9%) underwent surgical resection of renal masses. Histopathology showed malignancy in 99 and benign tumors in 18 patients, in 48 patients (23.7%), follow-up imaging showed size stability of lesions diagnosed as benign, and 37 patients (18.3%) had no mass. Based on DECT only, 95/99 (96.0%) patients with malignancy and 96/103 (93.2%) patients without malignancy were correctly identified, for an overall accuracy of 94.6%. The dual-phase approach identified 96/99 (97.0%) and 98/103 (95.1%), accuracy 96.0%, P > 0.05 for both. Mean interpretation time was 2.2 +/- 0.8 minutes for DECT, and 3.5 +/- 1.0 minutes for the dual-phase protocol, P < 0.001. Mean VNE/TNE image quality was 1.68 +/- 0.65/1.30 +/- 0.59, noise was 2.03 +/- 0.57/1.18 +/- 0.29, P < 0.001 for both. Omission of the true unenhanced phase lead to a 48.9 +/- 7.0% dose reduction. DECT allows for fast and accurate characterization of renal masses in a single-phase acquisition. Interpretation of color coded images significantly reduces interpretation time. Omission of a nonenhanced acquisition can reduce radiation exposure by almost 50%.

Preliminary assessment of the diagnostic performances of a new rapid diagnostic test for the serodiagnosis of human cystic echinococcosis.

PubMed

Vola, Ambra; Tamarozzi, Francesca; Noordin, Rahmah; Yunus, Muhammad Hafiznur; Khanbabaie, Sam; De Silvestri, Annalisa; Brunetti, Enrico; Mariconti, Mara

2018-04-14

Rapid diagnostic tests for cystic echinococcosis (CE) are convenient to support ultrasound diagnosis in uncertain cases, especially in resource-limited settings. We found comparable diagnostic performances of the experimental Hyd Rapid Test and the commercial VIRapid HYDATIDOSIS Test, used in our diagnostic laboratory, using samples from well-characterized hepatic CE cases. Copyright © 2018 Elsevier Inc. All rights reserved.

Curved diamond-crystal spectrographs for x-ray free-electron laser noninvasive diagnostics.

PubMed

Terentyev, Sergey; Blank, Vladimir; Kolodziej, Tomasz; Shvyd'ko, Yuri

2016-12-01

We report on the manufacturing and X-ray tests of bent diamond-crystal X-ray spectrographs, designed for noninvasive diagnostics of the X-ray free-electron laser (XFEL) spectra in the spectral range from 5 to 15 keV. The key component is a curved, 20-μm thin, single crystalline diamond triangular plate in the (110) orientation. The radius of curvature can be varied between R = 0.6 m and R = 0.1 m in a controlled fashion, ensuring imaging in a spectral window of up to 60 eV for ≃8 keV X-rays. All of the components of the bending mechanism (about 10 parts) are manufactured from diamond, thus ensuring safe operations in intense XFEL beams. The spectrograph is transparent to 88% for 5-keV photons and to 98% for 15-keV photons. Therefore, it can be used for noninvasive diagnostics of the X-ray spectra during XFEL operations.

Extreme ultraviolet spectroscopy diagnostics of low-temperature plasmas based on a sliced multilayer grating and glass capillary optics.

PubMed

Kantsyrev, V L; Safronova, A S; Williamson, K M; Wilcox, P; Ouart, N D; Yilmaz, M F; Struve, K W; Voronov, D L; Feshchenko, R M; Artyukov, I A; Vinogradov, A V

2008-10-01

New extreme ultraviolet (EUV) spectroscopic diagnostics of relatively low-temperature plasmas based on the application of an EUV spectrometer and fast EUV diodes combined with glass capillary optics is described. An advanced high resolution dispersive element sliced multilayer grating was used in the compact EUV spectrometer. For monitoring of the time history of radiation, filtered fast EUV diodes were used in the same spectral region (>13 nm) as the EUV spectrometer. The radiation from the plasma was captured by using a single inexpensive glass capillary that was transported onto the spectrometer entrance slit and EUV diode. The use of glass capillary optics allowed placement of the spectrometer and diodes behind the thick radiation shield outside the direction of a possible hard x-ray radiation beam and debris from the plasma source. The results of the testing and application of this diagnostic for a compact laser plasma source are presented. Examples of modeling with parameters of plasmas are discussed.

Curved diamond-crystal spectrographs for x-ray free-electron laser noninvasive diagnostics

DOE PAGES

Terentyev, Sergey; Blank, Vladimir; Kolodziej, Tomasz; ...

2016-12-29

Here, we report on the manufacturing and X-ray tests of bent diamond-crystal X-ray spectrographs, designed for noninvasive diagnostics of the X-ray free-electron laser (XFEL) spectra in the spectral range from 5 to 15 keV. The key component is a curved, 20-µm thin, single crystalline diamond triangular plate in the (110) orientation. The radius of curvature can be varied between R = 0.6 m and R = 0.1 m in a controlled fashion, ensuring imaging in a spectral window of up to 60 eV for ' 8 keV X-rays. All of the components of the bending mechanism (about 10 parts) aremore » manufactured from diamond, thus ensuring safe operations in intense XFEL beams. The spectrograph is transparent to 88% for 5-keV photons, and to 98% for 15-keV photons. Therefore, it can be used for noninvasive diagnostics of the X-ray spectra during XFEL operations.« less

Curved diamond-crystal spectrographs for x-ray free-electron laser noninvasive diagnostics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terentyev, Sergey; Blank, Vladimir; Kolodziej, Tomasz

Here, we report on the manufacturing and X-ray tests of bent diamond-crystal X-ray spectrographs, designed for noninvasive diagnostics of the X-ray free-electron laser (XFEL) spectra in the spectral range from 5 to 15 keV. The key component is a curved, 20-µm thin, single crystalline diamond triangular plate in the (110) orientation. The radius of curvature can be varied between R = 0.6 m and R = 0.1 m in a controlled fashion, ensuring imaging in a spectral window of up to 60 eV for ' 8 keV X-rays. All of the components of the bending mechanism (about 10 parts) aremore » manufactured from diamond, thus ensuring safe operations in intense XFEL beams. The spectrograph is transparent to 88% for 5-keV photons, and to 98% for 15-keV photons. Therefore, it can be used for noninvasive diagnostics of the X-ray spectra during XFEL operations.« less

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

PubMed Central

Urabe, Naohisa; Sano, Go; Suzuki, Junko; Hebisawa, Akira; Nakamura, Yasuhiko; Koyama, Kazuya; Ishii, Yoshikazu; Tateda, Kazuhiro; Homma, Sakae

2017-01-01

ABSTRACT We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β-d-glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA. PMID:28330887

Diagnostic test accuracy and prevalence inferences based on joint and sequential testing with finite population sampling.

PubMed

Su, Chun-Lung; Gardner, Ian A; Johnson, Wesley O

2004-07-30

The two-test two-population model, originally formulated by Hui and Walter, for estimation of test accuracy and prevalence estimation assumes conditionally independent tests, constant accuracy across populations and binomial sampling. The binomial assumption is incorrect if all individuals in a population e.g. child-care centre, village in Africa, or a cattle herd are sampled or if the sample size is large relative to population size. In this paper, we develop statistical methods for evaluating diagnostic test accuracy and prevalence estimation based on finite sample data in the absence of a gold standard. Moreover, two tests are often applied simultaneously for the purpose of obtaining a 'joint' testing strategy that has either higher overall sensitivity or specificity than either of the two tests considered singly. Sequential versions of such strategies are often applied in order to reduce the cost of testing. We thus discuss joint (simultaneous and sequential) testing strategies and inference for them. Using the developed methods, we analyse two real and one simulated data sets, and we compare 'hypergeometric' and 'binomial-based' inferences. Our findings indicate that the posterior standard deviations for prevalence (but not sensitivity and specificity) based on finite population sampling tend to be smaller than their counterparts for infinite population sampling. Finally, we make recommendations about how small the sample size should be relative to the population size to warrant use of the binomial model for prevalence estimation. Copyright 2004 John Wiley & Sons, Ltd.

Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement.

PubMed

McInnes, Matthew D F; Moher, David; Thombs, Brett D; McGrath, Trevor A; Bossuyt, Patrick M; Clifford, Tammy; Cohen, Jérémie F; Deeks, Jonathan J; Gatsonis, Constantine; Hooft, Lotty; Hunt, Harriet A; Hyde, Christopher J; Korevaar, Daniël A; Leeflang, Mariska M G; Macaskill, Petra; Reitsma, Johannes B; Rodin, Rachel; Rutjes, Anne W S; Salameh, Jean-Paul; Stevens, Adrienne; Takwoingi, Yemisi; Tonelli, Marcello; Weeks, Laura; Whiting, Penny; Willis, Brian H

2018-01-23

Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy. To develop the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test accuracy guideline as a stand-alone extension of the PRISMA statement. Modifications to the PRISMA statement reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies and the abstracts for these reviews. Established standards from the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network were followed for the development of the guideline. The original PRISMA statement was used as a framework on which to modify and add items. A group of 24 multidisciplinary experts used a systematic review of articles on existing reporting guidelines and methods, a 3-round Delphi process, a consensus meeting, pilot testing, and iterative refinement to develop the PRISMA diagnostic test accuracy guideline. The final version of the PRISMA diagnostic test accuracy guideline checklist was approved by the group. The systematic review (produced 64 items) and the Delphi process (provided feedback on 7 proposed items; 1 item was later split into 2 items) identified 71 potentially relevant items for consideration. The Delphi process reduced these to 60 items that were discussed at the consensus meeting. Following the meeting, pilot testing and iterative feedback were used to generate the 27-item PRISMA diagnostic test accuracy checklist. To reflect specific or optimal contemporary systematic review methods for diagnostic test accuracy, 8 of the 27 original PRISMA items were left unchanged, 17 were modified, 2 were added, and 2 were omitted. The 27-item PRISMA diagnostic test accuracy checklist provides specific guidance for reporting of systematic reviews. The PRISMA diagnostic test accuracy guideline can facilitate the transparent reporting of reviews, and may assist in the evaluation of validity and applicability, enhance replicability of reviews, and make the results from systematic reviews of diagnostic test accuracy studies more useful.

Efficacy of a high-resolution consultation system in gastroenterology at an Andalusian hospital center.

PubMed

Zambrana-García, José Luis; Montoro-Caba, María Isabel; Chicano-Gallardo, Maite; Monrobel-Lancho, Ana; Pérez-de-Luque, Daniel Jesús; Peña-Ojeda, José Antonio; Recio-Ramírez, José Manuel

2016-01-01

By high resolution consultation (HRC) we mean an ambulatory process of assistance fulfilled in a single day, by which treatment and diagnosis are established and recorded. To assess to which extent patients with digestive conditions may benefit from a single consultation system. A descriptive study of 179 first visit events, randomly selected as high-resolution consultations in gastroenterology. We discuss the percentage of patients who benefited from HRC and the complementary tests performed. Most common conditions included dyspepsia (16%), a family history of colon cancer (16%) and gastroesophageal reflux disease (GERD) (16%). Seventy-nine (44%) of all first visits became HRCs and 80 (45%) required a diagnostic test (100% abdominal ultrasound) that was reviewed on the same day. Performing a test on the same day significantly increased the percentage of HRCs (57% vs. 34%, p < 0.002). GERD, dyspepsia, cholelithiasis and chronic liver disease were the subjects most commonly leading to HRC. Gastroenterology consultations may largely benefit from an HRC system with only organizational changes and no additional costs.

Assessing FPAR Source and Parameter Optimization Scheme in Application of a Diagnostic Carbon Flux Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, D P; Ritts, W D; Wharton, S

2009-02-26

The combination of satellite remote sensing and carbon cycle models provides an opportunity for regional to global scale monitoring of terrestrial gross primary production, ecosystem respiration, and net ecosystem production. FPAR (the fraction of photosynthetically active radiation absorbed by the plant canopy) is a critical input to diagnostic models, however little is known about the relative effectiveness of FPAR products from different satellite sensors nor about the sensitivity of flux estimates to different parameterization approaches. In this study, we used multiyear observations of carbon flux at four eddy covariance flux tower sites within the conifer biome to evaluate these factors.more » FPAR products from the MODIS and SeaWiFS sensors, and the effects of single site vs. cross-site parameter optimization were tested with the CFLUX model. The SeaWiFs FPAR product showed greater dynamic range across sites and resulted in slightly reduced flux estimation errors relative to the MODIS product when using cross-site optimization. With site-specific parameter optimization, the flux model was effective in capturing seasonal and interannual variation in the carbon fluxes at these sites. The cross-site prediction errors were lower when using parameters from a cross-site optimization compared to parameter sets from optimization at single sites. These results support the practice of multisite optimization within a biome for parameterization of diagnostic carbon flux models.« less

Identifying Students' Mathematical Skills from a Multiple-Choice Diagnostic Test Using an Iterative Technique to Minimise False Positives

ERIC Educational Resources Information Center

Manning, S.; Dix, A.

2008-01-01

There is anecdotal evidence that a significant number of students studying computing related courses at degree level have difficulty with sub-GCE mathematics. Testing of students' skills is often performed using diagnostic tests and a number of computer-based diagnostic tests exist, which work, essentially, by testing one specific diagnostic skill…

[Quality of genetic services--analysis of medical genetic expert opinions solicited by private health insurance companies].

PubMed

Nippert, Reinhardt Peter; Schmidtke, Jörg

2012-01-01

Service quality for patients with genetic conditions can be assessed through the analysis of clinical genetic data sets, as was the case in this study. It represents a secondary analysis of a compilation of a single genetic expert's medical opinions covering the years 2000 to 2009, solicited by private health insurance companies with the intention of probing into medical necessity and adequacy of genetic testing ordered by physicians. Genetic testing has become an increasingly important part of clinical diagnostic services. Controlling these services does not only reduce costs but also saves patients from unwarranted over-utilisation. Therefore, the reasons given by doctors when ordering genetic tests are part of the quality of service delivery. The study revealed that more than 30% of the molecular genetic tests ordered lack sound medical reasoning and 30% of the cases studied show violation or neglect of guidelines and recommendations for diagnostic procedures with respect to genetic testing. In essence, the findings indicate a need for human genetic information among physicians. Their professional organisations are called upon to design and offer CME/CPD programmes in medical genetics to maintain and continually improve the quality of medical genetic care for patients with genetic conditions. Copyright © 2012. Published by Elsevier GmbH.

A new method to address verification bias in studies of clinical screening tests: cervical cancer screening assays as an example.

PubMed

Xue, Xiaonan; Kim, Mimi Y; Castle, Philip E; Strickler, Howard D

2014-03-01

Studies to evaluate clinical screening tests often face the problem that the "gold standard" diagnostic approach is costly and/or invasive. It is therefore common to verify only a subset of negative screening tests using the gold standard method. However, undersampling the screen negatives can lead to substantial overestimation of the sensitivity and underestimation of the specificity of the diagnostic test. Our objective was to develop a simple and accurate statistical method to address this "verification bias." We developed a weighted generalized estimating equation approach to estimate, in a single model, the accuracy (eg, sensitivity/specificity) of multiple assays and simultaneously compare results between assays while addressing verification bias. This approach can be implemented using standard statistical software. Simulations were conducted to assess the proposed method. An example is provided using a cervical cancer screening trial that compared the accuracy of human papillomavirus and Pap tests, with histologic data as the gold standard. The proposed approach performed well in estimating and comparing the accuracy of multiple assays in the presence of verification bias. The proposed approach is an easy to apply and accurate method for addressing verification bias in studies of multiple screening methods. Copyright © 2014 Elsevier Inc. All rights reserved.

A Model-Free Diagnostic for Single-Peakedness of Item Responses Using Ordered Conditional Means

ERIC Educational Resources Information Center

Polak, Marike; De Rooij, Mark; Heiser, Willem J.

2012-01-01

In this article we propose a model-free diagnostic for single-peakedness (unimodality) of item responses. Presuming a unidimensional unfolding scale and a given item ordering, we approximate item response functions of all items based on ordered conditional means (OCM). The proposed OCM methodology is based on Thurstone & Chave's (1929) "criterion…

42 CFR 414.506 - Procedures for public consultation for payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... a new clinical diagnostic laboratory test. 414.506 Section 414.506 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.506 Procedures for public consultation for payment for a new clinical diagnostic laboratory test...

42 CFR 414.506 - Procedures for public consultation for payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... a new clinical diagnostic laboratory test. 414.506 Section 414.506 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.506 Procedures for public consultation for payment for a new clinical diagnostic laboratory test...

Understanding the properties of diagnostic tests - Part 2: Likelihood ratios.

PubMed

Ranganathan, Priya; Aggarwal, Rakesh

2018-01-01

Diagnostic tests are used to identify subjects with and without disease. In a previous article in this series, we examined some attributes of diagnostic tests - sensitivity, specificity, and predictive values. In this second article, we look at likelihood ratios, which are useful for the interpretation of diagnostic test results in everyday clinical practice.

Accuracy of physical examination for chronic lumbar radiculopathy

PubMed Central

2013-01-01

Background Clinical examination of patients with chronic lumbar radiculopathy aims to clarify whether there is nerve root impingement. The aims of this study were to investigate the association between findings at clinical examination and nerve root impingement, to evaluate the accuracy of clinical index tests in a specialised care setting, and to see whether imaging clarifies the cause of chronic radicular pain. Methods A total of 116 patients referred with symptoms of lumbar radiculopathy lasting more than 12 weeks and at least one positive index test were included. The tests were the straight leg raising test, and tests for motor muscle strength, dermatome sensory loss, and reflex impairment. Magnetic resonance imaging (n = 109) or computer tomography (n = 7) were imaging reference standards. Images were analysed at the level of single nerve root(s), and nerve root impingement was classified as present or absent. Sensitivities, specificities, and positive and negative likelihood ratios (LR) for detection of nerve root impingement were calculated for each individual index test. An overall clinical evaluation, concluding on the level and side of the radiculopathy, was performed. Results The prevalence of disc herniation was 77.8%. The diagnostic accuracy of individual index tests was low with no tests reaching positive LR >4.0 or negative LR <0.4. The overall clinical evaluation was slightly more accurate, with a positive LR of 6.28 (95% CI 1.06–37.21) for L4, 1.74 (95% CI 1.04–2.93) for L5, and 1.29 (95% CI 0.97–1.72) for S1 nerve root impingement. An overall clinical evaluation, concluding on the level and side of the radiculopathy was also performed, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) calculation for diagnostic accuracy of this evaluation was performed. Conclusions The accuracy of individual clinical index tests used to predict imaging findings of nerve root impingement in patients with chronic lumbar radiculopathy is low when applied in specialised care, but clinicians’ overall evaluation improves diagnostic accuracy slightly. The tests are not very helpful in clarifying the cause of radicular pain, and are therefore inaccurate for guidance in the diagnostic workup of the patients. The study population was highly selected and therefore the results from this study should not be generalised to unselected patient populations in primary care nor to even more selected surgical populations. PMID:23837886

Custom oligonucleotide array-based CGH: a reliable diagnostic tool for detection of exonic copy-number changes in multiple targeted genes

PubMed Central

Vasson, Aurélie; Leroux, Céline; Orhant, Lucie; Boimard, Mathieu; Toussaint, Aurélie; Leroy, Chrystel; Commere, Virginie; Ghiotti, Tiffany; Deburgrave, Nathalie; Saillour, Yoann; Atlan, Isabelle; Fouveaut, Corinne; Beldjord, Cherif; Valleix, Sophie; Leturcq, France; Dodé, Catherine; Bienvenu, Thierry; Chelly, Jamel; Cossée, Mireille

2013-01-01

The frequency of disease-related large rearrangements (referred to as copy-number mutations, CNMs) varies among genes, and search for these mutations has an important place in diagnostic strategies. In recent years, CGH method using custom-designed high-density oligonucleotide-based arrays allowed the development of a powerful tool for detection of alterations at the level of exons and made it possible to provide flexibility through the possibility of modeling chips. The aim of our study was to test custom-designed oligonucleotide CGH array in a diagnostic laboratory setting that analyses several genes involved in various genetic diseases, and to compare it with conventional strategies. To this end, we designed a 12-plex CGH array (135k; 135 000 probes/subarray) (Roche Nimblegen) with exonic and intronic oligonucleotide probes covering 26 genes routinely analyzed in the laboratory. We tested control samples with known CNMs and patients for whom genetic causes underlying their disorders were unknown. The contribution of this technique is undeniable. Indeed, it appeared reproducible, reliable and sensitive enough to detect heterozygous single-exon deletions or duplications, complex rearrangements and somatic mosaicism. In addition, it improves reliability of CNM detection and allows determination of boundaries precisely enough to direct targeted sequencing of breakpoints. All of these points, associated with the possibility of a simultaneous analysis of several genes and scalability ‘homemade' make it a valuable tool as a new diagnostic approach of CNMs. PMID:23340513

Application of artificial intelligence using a convolutional neural network for detecting gastric cancer in endoscopic images.

PubMed

Hirasawa, Toshiaki; Aoyama, Kazuharu; Tanimoto, Tetsuya; Ishihara, Soichiro; Shichijo, Satoki; Ozawa, Tsuyoshi; Ohnishi, Tatsuya; Fujishiro, Mitsuhiro; Matsuo, Keigo; Fujisaki, Junko; Tada, Tomohiro

2018-07-01

Image recognition using artificial intelligence with deep learning through convolutional neural networks (CNNs) has dramatically improved and been increasingly applied to medical fields for diagnostic imaging. We developed a CNN that can automatically detect gastric cancer in endoscopic images. A CNN-based diagnostic system was constructed based on Single Shot MultiBox Detector architecture and trained using 13,584 endoscopic images of gastric cancer. To evaluate the diagnostic accuracy, an independent test set of 2296 stomach images collected from 69 consecutive patients with 77 gastric cancer lesions was applied to the constructed CNN. The CNN required 47 s to analyze 2296 test images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the 71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive cancers were correctly detected. All missed lesions were superficially depressed and differentiated-type intramucosal cancers that were difficult to distinguish from gastritis even for experienced endoscopists. Nearly half of the false-positive lesions were gastritis with changes in color tone or an irregular mucosal surface. The constructed CNN system for detecting gastric cancer could process numerous stored endoscopic images in a very short time with a clinically relevant diagnostic ability. It may be well applicable to daily clinical practice to reduce the burden of endoscopists.

Perceptions of point-of-care infectious disease testing among European medical personnel, point-of-care test kit manufacturers, and the general public.

PubMed

Kaman, Wendy E; Andrinopoulou, Eleni-Rosalina; Hays, John P

2013-01-01

The proper development and implementation of point-of-care (POC) diagnostics requires knowledge of the perceived requirements and barriers to their implementation. To determine the current requirements and perceived barriers to the introduction of POC diagnostics in the field of medical microbiology (MM)-POC a prospective online survey (TEMPOtest-QC) was established. The TEMPOtest-QC survey was online between February 2011 and July 2012 and targeted the medical community, POC test diagnostic manufacturers, general practitioners, and the general public. In total, 293 individuals responded to the survey, including 91 (31%) medical microbiologists, 39 (13%) nonmedical microbiologists, 25 (9%) employees of POC test manufacturers, and 138 (47%) members of the general public. Responses were received from 18 different European countries, with the largest percentage of these living in The Netherlands (52%). The majority (>50%) of medical specialists regarded the development of MM-POC for blood culture and hospital acquired infections as "absolutely necessary", but were much less favorable towards their use in the home environment. Significant differences in perceptions between medical specialists and the general public included the: (1) Effect on quality of patient care; (2) Ability to better monitor patients; (3) Home testing and the doctor-patient relationship; and (4) MM-POC interpretation. Only 34.7% of the general public is willing to pay more than a€10 ($13) for a single MM-POC test, with 85.5% preferring to purchase their MM-POC test from a pharmacy. The requirements for the proper implementation of MM-POC were found to be generally similar between medical specialists and POC test kit manufacturers. The general public was much more favorable with respect to a perceived improvement in the quality of healthcare that these tests would bring to the hospital and home environment.

Comparing diagnostic tests on benefit-risk.

PubMed

Pennello, Gene; Pantoja-Galicia, Norberto; Evans, Scott

2016-01-01

Comparing diagnostic tests on accuracy alone can be inconclusive. For example, a test may have better sensitivity than another test yet worse specificity. Comparing tests on benefit risk may be more conclusive because clinical consequences of diagnostic error are considered. For benefit-risk evaluation, we propose diagnostic yield, the expected distribution of subjects with true positive, false positive, true negative, and false negative test results in a hypothetical population. We construct a table of diagnostic yield that includes the number of false positive subjects experiencing adverse consequences from unnecessary work-up. We then develop a decision theory for evaluating tests. The theory provides additional interpretation to quantities in the diagnostic yield table. It also indicates that the expected utility of a test relative to a perfect test is a weighted accuracy measure, the average of sensitivity and specificity weighted for prevalence and relative importance of false positive and false negative testing errors, also interpretable as the cost-benefit ratio of treating non-diseased and diseased subjects. We propose plots of diagnostic yield, weighted accuracy, and relative net benefit of tests as functions of prevalence or cost-benefit ratio. Concepts are illustrated with hypothetical screening tests for colorectal cancer with test positive subjects being referred to colonoscopy.

Early Diagnosis of Fibrodysplasia Ossificans Progressiva

PubMed Central

Kaplan, Frederick S.; Xu, Meiqi; Glaser, David L.; Collins, Felicity; Connor, Michael; Kitterman, Joseph; Sillence, David; Zackai, Elaine; Ravitsky, Vardit; Zasloff, Michael; Ganguly, Arupa; Shore, Eileen M.

2012-01-01

BACKGROUND Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes and by progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodys-plasia ossificans progressiva are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures that can cause lifelong disability. Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification. METHODS We recently evaluated 7 children for diagnosis of fibrodysplasia ossificans progressiva before the onset of heterotopic ossification. A medical history, physical examination, and skeletal survey were obtained on all of the patients, as well as clinical genetic testing for the canonical fibrodysplasia ossificans progressiva mutation. RESULTS All 7 of the children (4 girls and 3 boys; ages 3 months to 6 years) had congenital malformations of the great toes, but none had radiographic evidence of heterotopic ossification at the time of evaluation. Five of the 7 children had soft tissue lesions of the neck and back, suggestive of early fibrodysplasia ossificans progressiva flare-ups, 3 of whom had undergone invasive diagnostic procedures that exacerbated their condition. Two children had no history or signs of soft tissue swelling or flare-ups. DNA sequence analysis found that all 7 of the children had the recurrent fibrodysplasia ossificans progressiva missense mutation, a single nucleotide substitution (c.617G>A) at codon 206 in the glycine-serine activation domain of activin receptor IA, a bone morphogenetic protein type 1 receptor. CONCLUSION Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory diagnostic genetic testing, and the avoidance of additional harmful diagnostic and treatment procedures. This is the first report of genetic confirmation of fibrodysplasia ossificans progressiva before the appearance of heterotopic ossification. Pediatricians should be aware of the early diagnostic features of fibrodysplasia ossificans progressiva, even before the appearance of heterotopic ossification. This awareness should prompt early genetic consultation and testing and the institution of assiduous precautions to prevent iatrogenic harm. PMID:18450872

Study on validity of a rapid diagnostic test kit versus light microscopy for malaria diagnosis in Ahmedabad city, India.

PubMed

Vyas, S; Puwar, B; Patel, V; Bhatt, G; Kulkarni, S; Fancy, M

2014-05-01

Light microscopy of blood smears for diagnosis of malaria in the field has several limitations, notably delays in diagnosis. This study in Ahmedabad in Gujarat State, India, evaluated the diagnostic performance of a rapid diagnostic test for malaria (SD Bioline Malaria Ag P.f/Pan) versus blood smear examination as the gold standard. All fever cases presenting at 13 urban health centres were subjected to rapid diagnostic testing and thick and thin blood smears. A total of 677 cases with fever were examined; 135 (20.0%) tested positive by rapid diagnostic test and 86 (12.7%) by blood smear. The sensitivity of the rapid diagnostic test for malaria was 98.8%, specificity was 91.5%, positive predictive value 63.0% and negative predictive value 99.8%. For detection of Plasmodium falciparum the sensitivity of rapid diagnostic test was 100% and specificity was 97.3%. The results show the acceptability of the rapid test as an alternative to light microscopy in the field setting.

MALDI-TOF MS in the Microbiology Laboratory: Current Trends.

PubMed

Schubert, Sören; Kostrzewa, Markus

2017-01-01

Within less than a decade matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become a gold standard for microbial identification in clinical microbiology laboratories. Besides identification of microorganisms the typing of single strains as well as the antibiotic and antimycotic resistance testing has come into focus in order to speed up the microbiological diagnostic. However, the full potential of MALDI-TOF MS has not been tapped yet and future technological advancements will certainly expedite this method towards novel applications and enhancement of current practice. So, the following chapter shall be rather a brainstorming and forecast of how MALDI-TOF MS will develop to influence clinical diagnostics and microbial research in the future. It shall open up the stage for further discussions and does not claim for overall validity.

Dual-Mode Combustion

NASA Technical Reports Server (NTRS)

Goyne, Christopher P.; McDaniel, James C.

2002-01-01

The Department of Mechanical and Aerospace Engineering at the University of Virginia has conducted an investigation of the mixing and combustion processes in a hydrogen fueled dual-mode scramjet combustor. The experiment essentially consisted of the "direct connect" continuous operation of a Mach 2 rectangular combustor with a single unswept ramp fuel injector. The stagnation enthalpy of the test flow simulated a flight Mach number of 5. Measurements were obtained using conventional wall instrumentation and laser based diagnostics. These diagnostics included, pressure and wall temperature measurements, Fuel Plume Imaging (FPI) and Particle Image Velocimetry (PIV). A schematic of the combustor configuration and a summary of the measurements obtained are presented. The experimental work at UVa was parallel by Computational Fluid Dynamics (CFD) work at NASA Langley. The numerical and experiment results are compared in this document.

Single-Tier Testing with the C6 Peptide ELISA Kit Compared with Two-Tier Testing for Lyme Disease

PubMed Central

Wormser, Gary P.; Schriefer, Martin; Aguero-Rosenfeld, Maria E.; Levin, Andrew; Steere, Allen C.; Nadelman, Robert B.; Nowakowski, John; Marques, Adriana; Johnson, Barbara J. B.; Dumler, J. Stephen

2014-01-01

Background The two-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time and labor; and subjectivity in the interpretation of immunoblots. Methods The diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with two-tier testing. Results The C6 ELISA was significantly more sensitive than two-tier testing with sensitivities of 66.5% (95% C.I.:61.7-71.1) and 35.2% (95%C.I.:30.6-40.1), respectively (p<0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to two-tier testing in sera from Lyme disease patients with early neurological manifestations (88.6% vs. 77.3%, p=0.13) or arthritis (98.3% vs. 95.6%, p= 0.38). Te specificities of C6 ELISA and two-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (p<0.05, 95% C.I. surrounding the 0.6 percentage point difference of 0.04 to 1.15). Conclusions Using a reference standard of two-tier testing, the C6 ELISA as a single step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with two-tier testing in routine clinical practice. PMID:23062467

The 2016 Academic Emergency Medicine Consensus Conference, "Shared Decision Making in the Emergency Department: Development of a Policy-relevant Patient-centered Research Agenda" Diagnostic Testing Breakout Session Report.

PubMed

Barrett, Tyler W; Rising, Kristin L; Bellolio, M Fernanda; Hall, M Kennedy; Brody, Aaron; Dodd, Kenneth W; Grieser, Mira; Levy, Phillip D; Raja, Ali S; Self, Wesley H; Weingarten, Gail; Hess, Erik P; Hollander, Judd E

2016-12-01

Diagnostic testing is an integral component of patient evaluation in the emergency department (ED). Emergency clinicians frequently use diagnostic testing to more confidently exclude "worst-case" diagnoses rather than to determine the most likely etiology for a presenting complaint. Increased utilization of diagnostic testing has not been associated with reductions in disease-related mortality but has led to increased overall healthcare costs and other unintended consequences (e.g., incidental findings requiring further workup, unnecessary exposure to ionizing radiation or potentially nephrotoxic contrast). Shared decision making (SDM) presents an opportunity for clinicians to discuss the benefits and harms associated with diagnostic testing with patients to more closely tailor testing to patient risk. This article introduces the challenges and opportunities associated with incorporating SDM into emergency care by summarizing the conclusions of the diagnostic testing group at the 2016 Academic Emergency Medicine Consensus Conference on SDM. Three primary domains emerged: 1) characteristics of a condition or test appropriate for SDM, 2) critical elements of and potential barriers to SDM discussions on diagnostic testing, and 3) financial aspects of SDM applied to diagnostic testing. The most critical research questions to improve engagement of patients in their acute care diagnostic decisions were determined by consensus. © 2016 by the Society for Academic Emergency Medicine.

Carboplatin hypersensitivity: evaluation and successful desensitization protocol.

PubMed

Bruchim, Ilan; Goldberg, Arnon; Fishman, Ami; Confino-Cohen, Ronit

2014-01-01

Carboplatin-induced immediate hypersensitivity reactions are relatively common among patients with gynecological malignancies. Once this occurs, the patient might be at risk for future carboplatin-induced reactions. This study evaluated the efficacy of allergic consultation, carboplatin skin testing and desensitization as a single intervention strategy in this population. Patients with a well-documented immediate reaction to carboplatin were offered allergy consultation, carboplatin skin testing and a desensitization plan in a single visit between scheduled chemotherapy sessions. Fifty-five patients with an immediate reaction were evaluated. After allergist assessment, 44 (89%) of 49 patients skin tested had a positive result. A total of 207 carboplatin desensitization cycles were administered to 49 women. Among them, 10 patients had a mild immediate hypersensitivity reaction during desensitization. Five patients subsequently tolerated carboplatin administered in the prolonged desensitization protocol. In the data presented, we propose a strategy that is both cost effective and very convenient for the patient. The diagnostic procedure, including allergist consultation and skin test, can be completed in less than 2 h. In most cases where carboplatin is indispensable, desensitization can be administered without overnight hospitalization.

A study of interior noise levels, noise sources and transmission paths in light aircraft

NASA Technical Reports Server (NTRS)

Hayden, R. E.; Murray, B. S.; Theobald, M. A.

1983-01-01

The interior noise levels and spectral characteristics of 18 single-and twin-engine propeller-driven light aircraft, and source-path diagnosis of a single-engine aircraft which was considered representative of a large part of the fleet were studied. The purpose of the flight surveys was to measure internal noise levels and identify principal noise sources and paths under a carefully controlled and standardized set of flight procedures. The diagnostic tests consisted of flights and ground tests in which various parts of the aircraft, such as engine mounts, the engine compartment, exhaust pipe, individual panels, and the wing strut were instrumented to determine source levels and transmission path strengths using the transfer function technique. Predominant source and path combinations are identified. Experimental techniques are described. Data, transfer function calculations to derive source-path contributions to the cabin acoustic environment, and implications of the findings for noise control design are analyzed.

Measuring diagnostic and predictive accuracy in disease management: an introduction to receiver operating characteristic (ROC) analysis.

PubMed

Linden, Ariel

2006-04-01

Diagnostic or predictive accuracy concerns are common in all phases of a disease management (DM) programme, and ultimately play an influential role in the assessment of programme effectiveness. Areas, such as the identification of diseased patients, predictive modelling of future health status and costs and risk stratification, are just a few of the domains in which assessment of accuracy is beneficial, if not critical. The most commonly used analytical model for this purpose is the standard 2 x 2 table method in which sensitivity and specificity are calculated. However, there are several limitations to this approach, including the reliance on a single defined criterion or cut-off for determining a true-positive result, use of non-standardized measurement instruments and sensitivity to outcome prevalence. This paper introduces the receiver operator characteristic (ROC) analysis as a more appropriate and useful technique for assessing diagnostic and predictive accuracy in DM. Its advantages include; testing accuracy across the entire range of scores and thereby not requiring a predetermined cut-off point, easily examined visual and statistical comparisons across tests or scores, and independence from outcome prevalence. Therefore the implementation of ROC as an evaluation tool should be strongly considered in the various phases of a DM programme.

Optical non-invasive monitoring of skin blood pulsations

NASA Astrophysics Data System (ADS)

Spīgulis, Jānis

2005-08-01

Time resolved detection and analysis of the skin backscattered optical signals (remission photoplethysmography or PPG) provide rich information on skin blood volume pulsations and can serve for reliable cardiovascular assessment. The single- and multi-channel PPG concepts are discussed in this work. Simultaneous data flow from several body locations allows one to study the heartbeat pulse wave propagation in real time and evaluate the vascular resistance. Portable single-, dual- and four-channel PPG monitoring devices with special software have been designed for real-time data acquisition and processing. The clinical studies confirmed their potential in the monitoring of heart arrhythmias, drug tests, steady-state cardiovascular assessment, body fitness control, and express diagnostics of the arterial occlusions.

Optical noninvasive monitoring of skin blood pulsations

NASA Astrophysics Data System (ADS)

Spigulis, Janis

2005-04-01

Time-resolved detection and analysis of skin backscattered optical signals (remission photoplethysmography or PPG) provide rich information on skin blood volume pulsations and can serve for reliable cardiovascular assessment. Single- and multiple-channel PPG concepts are discussed. Simultaneous data flow from several locations on the human body allows us to study heartbeat pulse-wave propagation in real time and to evaluate vascular resistance. Portable single-, dual-, and four-channel PPG monitoring devices with special software have been designed for real-time data acquisition and processing. The prototype devices have been clinically studied, and their potential for monitoring heart arrhythmias, drug-efficiency tests, steady-state cardiovascular assessment, body fitness control, and express diagnostics of the arterial occlusions has been confirmed.

A systematic review and meta-analysis of the diagnostic accuracy of point-of-care tests for the detection of hyperketonemia in dairy cows.

PubMed

Tatone, Elise H; Gordon, Jessica L; Hubbs, Jessie; LeBlanc, Stephen J; DeVries, Trevor J; Duffield, Todd F

2016-08-01

Several rapid tests for use on farm have been validated for the detection of hyperketonemia (HK) in dairy cattle, however the reported sensitivity and specificity of each method varies and no single study has compared them all. Meta-analysis of diagnostic test accuracy is becoming more common in human medical literature but there are few veterinary examples. The objective of this work was to perform a systematic review and meta-analysis to determine the point-of-care testing method with the highest combined sensitivity and specificity, the optimal threshold for each method, and to identify gaps in the literature. A comprehensive literature search resulted in 5196 references. After removing duplicates and performing relevance screening, 23 studies were included for the qualitative synthesis and 18 for the meta-analysis. The three index tests evaluated in the meta-analysis were: the Precision Xtra(®) handheld device measuring beta-hydroxybutyrate (BHB) concentration in whole blood, and Ketostix(®) and KetoTest(®) semi-quantitative strips measuring the concentration of acetoacetate in urine and BHB in milk, respectively. The diagnostic accuracy of the 3 index tests relative to the reference standard measurement of BHB in serum or whole blood between 1.0-1.4mmol/L was compared using the hierarchical summary receiver operator characteristic (HSROC) method. Subgroup analysis was conducted for each index test to examine the accuracy at different thresholds. The impact of the reference standard threshold, the reference standard method, the prevalence of HK in the population, the primary study source and risk of bias of the primary study was explored using meta-regression. The Precision Xtra(®) device had the highest summary sensitivity in whole blood BHB at 1.2mmol/L, 94.8% (CI95%: 92.6-97.0), and specificity, 97.5% (CI95%: 96.9-98.1). The threshold employed (1.2-1.4mmol/L) did not impact the diagnostic accuracy of the test. The Ketostix(®) and KetoTest(®) strips had the highest summary sensitivity and specificity when the trace and weak positive thresholds were used, respectively. Controlling for the source of publication, HK prevalence and reference standard employed did not impact the estimated sensitivity and specificity of the tests. Including only peer-reviewed studies reduced the number of primary studies evaluating the Precision Xtra(®) by 43% and Ketostix(®) by 33%. Diagnosing HK with blood, urine or milk are valid options, however, the diagnostic inaccuracy of urine and milk should be considered when making economic and treatment decisions. Copyright © 2016 Elsevier B.V. All rights reserved.

Single-particle imaging for biosensor applications

NASA Astrophysics Data System (ADS)

Yorulmaz, Mustafa; Isil, Cagatay; Seymour, Elif; Yurdakul, Celalettin; Solmaz, Berkan; Koc, Aykut; Ünlü, M. Selim

2017-10-01

Current state-of-the-art technology for in-vitro diagnostics employ laboratory tests such as ELISA that consists of a multi-step test procedure and give results in analog format. Results of these tests are interpreted by the color change in a set of diluted samples in a multi-well plate. However, detection of the minute changes in the color poses challenges and can lead to false interpretations. Instead, a technique that allows individual counting of specific binding events would be useful to overcome such challenges. Digital imaging has been applied recently for diagnostics applications. SPR is one of the techniques allowing quantitative measurements. However, the limit of detection in this technique is on the order of nM. The current required detection limit, which is already achieved with the analog techniques, is around pM. Optical techniques that are simple to implement and can offer better sensitivities have great potential to be used in medical diagnostics. Interference Microscopy is one of the tools that have been investigated over years in optics field. More of the studies have been performed in confocal geometry and each individual nanoparticle was observed separately. Here, we achieve wide-field imaging of individual nanoparticles in a large field-of-view ( 166 μm × 250 μm) on a micro-array based sensor chip in fraction of a second. We tested the sensitivity of our technique on dielectric nanoparticles because they exhibit optical properties similar to viruses and cells. We can detect non-resonant dielectric polystyrene nanoparticles of 100 nm. Moreover, we perform post-processing applications to further enhance visibility.

20 CFR 416.919m - Diagnostic tests or procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Diagnostic tests or procedures. 416.919m... for Report Content § 416.919m Diagnostic tests or procedures. We will request the results of any diagnostic tests or procedures that have been performed as part of a workup by your treating source or other...

Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

PubMed

Llorens, Franc; Kruse, Niels; Karch, André; Schmitz, Matthias; Zafar, Saima; Gotzmann, Nadine; Sun, Ting; Köchy, Silja; Knipper, Tobias; Cramm, Maria; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel P; Sánchez-Valle, Raquel; Fischer, Andre; Mollenhauer, Brit; Zerr, Inga

2018-03-01

The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

PubMed

Stemeyer, G; Stähli, P

1996-05-01

This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement in uveitis with opaque media, and incomplete CSNB.

Preventing Data Ambiguity in Infectious Diseases with Four-Dimensional and Personalized Evaluations

PubMed Central

Iandiorio, Michelle J.; Fair, Jeanne M.; Chatzipanagiotou, Stylianos; Ioannidis, Anastasios; Trikka-Graphakos, Eleftheria; Charalampaki, Nikoletta; Sereti, Christina; Tegos, George P.; Hoogesteijn, Almira L.; Rivas, Ariel L.

2016-01-01

Background Diagnostic errors can occur, in infectious diseases, when anti-microbial immune responses involve several temporal scales. When responses span from nanosecond to week and larger temporal scales, any pre-selected temporal scale is likely to miss some (faster or slower) responses. Hoping to prevent diagnostic errors, a pilot study was conducted to evaluate a four-dimensional (4D) method that captures the complexity and dynamics of infectious diseases. Methods Leukocyte-microbial-temporal data were explored in canine and human (bacterial and/or viral) infections, with: (i) a non-structured approach, which measures leukocytes or microbes in isolation; and (ii) a structured method that assesses numerous combinations of interacting variables. Four alternatives of the structured method were tested: (i) a noise-reduction oriented version, which generates a single (one data point-wide) line of observations; (ii) a version that measures complex, three-dimensional (3D) data interactions; (iii) a non-numerical version that displays temporal data directionality (arrows that connect pairs of consecutive observations); and (iv) a full 4D (single line-, complexity-, directionality-based) version. Results In all studies, the non-structured approach revealed non-interpretable (ambiguous) data: observations numerically similar expressed different biological conditions, such as recovery and lack of recovery from infections. Ambiguity was also found when the data were structured as single lines. In contrast, two or more data subsets were distinguished and ambiguity was avoided when the data were structured as complex, 3D, single lines and, in addition, temporal data directionality was determined. The 4D method detected, even within one day, changes in immune profiles that occurred after antibiotics were prescribed. Conclusions Infectious disease data may be ambiguous. Four-dimensional methods may prevent ambiguity, providing earlier, in vivo, dynamic, complex, and personalized information that facilitates both diagnostics and selection or evaluation of anti-microbial therapies. PMID:27411058

A three-gene panel on urine increases PSA specificity in the detection of prostate cancer.

PubMed

Rigau, Marina; Ortega, Israel; Mir, Maria Carmen; Ballesteros, Carlos; Garcia, Marta; Llauradó, Marta; Colás, Eva; Pedrola, Núria; Montes, Melania; Sequeiros, Tamara; Ertekin, Tugce; Majem, Blanca; Planas, Jacques; Ruiz, Anna; Abal, Miguel; Sánchez, Alex; Morote, Juan; Reventós, Jaume; Doll, Andreas

2011-12-01

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy. By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Copyright © 2011 Wiley Periodicals, Inc.

[The inpatient treatment of patients with anorexia nervosa in German clinics].

PubMed

Föcker, Manuel; Heidemann-Eggert, Elke; Antony, Gisela; Becker, Katja; Egberts, Karin; Ehrlich, Stefan; Fleischhaker, Christian; Hahn, Freia; Jaite, Charlotte; Kaess, Michael; M E Schulze, Ulrike; Sinzig, Judith; Wagner, Catharina; Legenbauer, Tanja; Renner, Tobias; Wessing, Ida; Herpertz-Dahlmann, Beate; Hebebrand, Johannes; Bühren, Katharina

2017-09-01

The medium- and long-term effects and side effects of inpatient treatment of patients with anorexia nervosa is still a matter of debate. The German S3-guidelines underline the importance of providing specialized and competent treatment. In this article we focus on the inpatient service structure in German child and adolescent psychiatric clinics with regard to their diagnostic and therapeutic concepts. A self-devised questionnaire was sent to 163 German child and adolescent psychiatric clinics. The questionnaire focused on the characteristics of the respective clinic as well as its diagnostic and therapeutic strategies. All clinics with an inpatient service for patients with anorexia nervosa (N = 84) provide single-therapy, family-based interventions and psychoeducation. A target weight is defined in nearly all clinics, and the mean intended weight gain per week is 486 g (range: 200 g to 700 g/week; SD = 117). Certain diagnostic tests and therapeutic interventions are used heterogeneously. This is the first study investigating the inpatient service structure for patients with anorexia nervosa in German clinics. Despite the provision of guideline-based therapy in all clinics, heterogeneous approaches were apparent with respect to specific diagnostic and therapeutic concepts.

Development of diagnostic test instruments to reveal level student conception in kinematic and dynamics

NASA Astrophysics Data System (ADS)

Handhika, J.; Cari, C.; Suparmi, A.; Sunarno, W.; Purwandari, P.

2018-03-01

The purpose of this research was to develop a diagnostic test instrument to reveal students' conceptions in kinematics and dynamics. The diagnostic test was developed based on the content indicator the concept of (1) displacement and distance, (2) instantaneous and average velocity, (3) zero and constant acceleration, (4) gravitational acceleration (5) Newton's first Law, (6) and Newton's third Law. The diagnostic test development model includes: Diagnostic test requirement analysis, formulating test-making objectives, developing tests, checking the validity of the content and the performance of reliability, and application of tests. The Content Validation Index (CVI) results in the category are highly relevant, with a value of 0.85. Three questions get negative Content Validation Ratio CVR) (-0.6), after revised distractors and clarify visual presentation; the CVR become 1 (highly relevant). This test was applied, obtained 16 valid test items, with Cronbach Alpha value of 0.80. It can conclude that diagnostic test can be used to reveal the level of students conception in kinematics and dynamics.

Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome

PubMed Central

Krawitz, Peter M; Schiska, Daniela; Krüger, Ulrike; Appelt, Sandra; Heinrich, Verena; Parkhomchuk, Dmitri; Timmermann, Bernd; Millan, Jose M; Robinson, Peter N; Mundlos, Stefan; Hecht, Jochen; Gross, Manfred

2014-01-01

Usher syndrome is an autosomal recessive disorder characterized both by deafness and blindness. For the three clinical subtypes of Usher syndrome causal mutations in altogether 12 genes and a modifier gene have been identified. Due to the genetic heterogeneity of Usher syndrome, the molecular analysis is predestined for a comprehensive and parallelized analysis of all known genes by next-generation sequencing (NGS) approaches. We describe here the targeted enrichment and deep sequencing for exons of Usher genes and compare the costs and workload of this approach compared to Sanger sequencing. We also present a bioinformatics analysis pipeline that allows us to detect single-nucleotide variants, short insertions and deletions, as well as copy number variations of one or more exons on the same sequence data. Additionally, we present a flexible in silico gene panel for the analysis of sequence variants, in which newly identified genes can easily be included. We applied this approach to a cohort of 44 Usher patients and detected biallelic pathogenic mutations in 35 individuals and monoallelic mutations in eight individuals of our cohort. Thirty-nine of the sequence variants, including two heterozygous deletions comprising several exons of USH2A, have not been reported so far. Our NGS-based approach allowed us to assess single-nucleotide variants, small indels, and whole exon deletions in a single test. The described diagnostic approach is fast and cost-effective with a high molecular diagnostic yield. PMID:25333064

Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome.

PubMed

Krawitz, Peter M; Schiska, Daniela; Krüger, Ulrike; Appelt, Sandra; Heinrich, Verena; Parkhomchuk, Dmitri; Timmermann, Bernd; Millan, Jose M; Robinson, Peter N; Mundlos, Stefan; Hecht, Jochen; Gross, Manfred

2014-09-01

Usher syndrome is an autosomal recessive disorder characterized both by deafness and blindness. For the three clinical subtypes of Usher syndrome causal mutations in altogether 12 genes and a modifier gene have been identified. Due to the genetic heterogeneity of Usher syndrome, the molecular analysis is predestined for a comprehensive and parallelized analysis of all known genes by next-generation sequencing (NGS) approaches. We describe here the targeted enrichment and deep sequencing for exons of Usher genes and compare the costs and workload of this approach compared to Sanger sequencing. We also present a bioinformatics analysis pipeline that allows us to detect single-nucleotide variants, short insertions and deletions, as well as copy number variations of one or more exons on the same sequence data. Additionally, we present a flexible in silico gene panel for the analysis of sequence variants, in which newly identified genes can easily be included. We applied this approach to a cohort of 44 Usher patients and detected biallelic pathogenic mutations in 35 individuals and monoallelic mutations in eight individuals of our cohort. Thirty-nine of the sequence variants, including two heterozygous deletions comprising several exons of USH2A, have not been reported so far. Our NGS-based approach allowed us to assess single-nucleotide variants, small indels, and whole exon deletions in a single test. The described diagnostic approach is fast and cost-effective with a high molecular diagnostic yield.

Maternal Plasma DNA and RNA Sequencing for Prenatal Testing.

PubMed

Tamminga, Saskia; van Maarle, Merel; Henneman, Lidewij; Oudejans, Cees B M; Cornel, Martina C; Sistermans, Erik A

2016-01-01

Cell-free DNA (cfDNA) testing has recently become indispensable in diagnostic testing and screening. In the prenatal setting, this type of testing is often called noninvasive prenatal testing (NIPT). With a number of techniques, using either next-generation sequencing or single nucleotide polymorphism-based approaches, fetal cfDNA in maternal plasma can be analyzed to screen for rhesus D genotype, common chromosomal aneuploidies, and increasingly for testing other conditions, including monogenic disorders. With regard to screening for common aneuploidies, challenges arise when implementing NIPT in current prenatal settings. Depending on the method used (targeted or nontargeted), chromosomal anomalies other than trisomy 21, 18, or 13 can be detected, either of fetal or maternal origin, also referred to as unsolicited or incidental findings. For various biological reasons, there is a small chance of having either a false-positive or false-negative NIPT result, or no result, also referred to as a "no-call." Both pre- and posttest counseling for NIPT should include discussing potential discrepancies. Since NIPT remains a screening test, a positive NIPT result should be confirmed by invasive diagnostic testing (either by chorionic villus biopsy or by amniocentesis). As the scope of NIPT is widening, professional guidelines need to discuss the ethics of what to offer and how to offer. In this review, we discuss the current biochemical, clinical, and ethical challenges of cfDNA testing in the prenatal setting and its future perspectives including novel applications that target RNA instead of DNA. © 2016 Elsevier Inc. All rights reserved.

Toward a 3D dynamic model of a faulty duplex ball bearing

NASA Astrophysics Data System (ADS)

Kogan, Gideon; Klein, Renata; Kushnirsky, Alex; Bortman, Jacob

2015-03-01

Bearings are vital components for safe and proper operation of machinery. Increasing efficiency of bearing diagnostics usually requires training of health and usage monitoring systems via expensive and time-consuming ground calibration tests. The main goal of this research, therefore, is to improve bearing dynamics modeling tools in order to reduce the time and budget needed to implement the health and usage monitoring approach. The proposed three-dimensional ball bearing dynamic model is based on the classic dynamic and kinematic equations. Interactions between the bodies are simulated using non-linear springs combined with dampers described by Hertz-type contact relation. The force friction is simulated using the hyperbolic-tangent function. The model allows simulation of a wide range of mechanical faults. It is validated by comparison to known bearing behavior and to experimental results. The model results are verified by demonstrating numerical convergence. The model results for the two cases of single and duplex angular ball bearings with axial deformation in the outer ring are presented. The qualitative investigation provides insight into bearing dynamics, the sensitivity study generalizes the qualitative findings for similar cases, and the comparison to the test results validates model reliability. The article demonstrates the variety of the cases that the 3D bearing model can simulate and the findings to which it may lead. The research allowed the identification of new patterns generated by single and duplex bearings with axially deformed outer race. It also enlightened the difference between single and duplex bearing manifestation. In the current research the dynamic model enabled better understanding of the physical behavior of the faulted bearings. Therefore, it is expected that the modeling approach has the potential to simplify and improve the development process of diagnostic algorithms. • A deformed outer race of a single axially loaded bearing is simulated. • The model results are subjected to a sensitivity study. • Duplex bearing with deformed outer race is simulated as well as tested. • The simulation results are in a good agreement with the experimental results.

Measuring multi-configurational character by orbital entanglement

NASA Astrophysics Data System (ADS)

Stein, Christopher J.; Reiher, Markus

2017-09-01

One of the most critical tasks at the very beginning of a quantum chemical investigation is the choice of either a multi- or single-configurational method. Naturally, many proposals exist to define a suitable diagnostic of the multi-configurational character for various types of wave functions in order to assist this crucial decision. Here, we present a new orbital-entanglement-based multi-configurational diagnostic termed Zs(1). The correspondence of orbital entanglement and static (or non-dynamic) electron correlation permits the definition of such a diagnostic. We chose our diagnostic to meet important requirements such as well-defined limits for pure single-configurational and multi-configurational wave functions. The Zs(1) diagnostic can be evaluated from a partially converged, but qualitatively correct, and therefore inexpensive density matrix renormalisation group wave function as in our recently presented automated active orbital selection protocol. Its robustness and the fact that it can be evaluated at low cost make this diagnostic a practical tool for routine applications.

Hollow shaft integrated health monitoring system for railroad wheels

NASA Astrophysics Data System (ADS)

Frankenstein, B.; Hentschel, D.; Pridoehl, E.; Schubert, F.

2005-05-01

The economic efficiency and competitiveness of environment-friendly rail transportation depends on safety, availability and maintenance of single highly loaded structure components. Until now these components have been changed in fixed maintenance intervals irrespective of any usage related conditions. With the knowledge and evaluation of the component conditions, life cycle costs can be reduced by means of optimized maintenance and/or "fit for purpose" design. For example, rail-bound vehicle wheel sets are among the most highly stressed travelling gear components of the bogie. if such a component fails, a serious accident may occur. For this reason, a health monitoring system based on the interpretation of ultrasonic sound signatures has been developed. First, the ultrasonic waves generated by an artificial defect on the outer wheel tread of a railroad wheel towards an acoustic sensor, placed inside the hollow shaft of the railroad axis were simulated with a EFIT (Elastodynamic Finite Integration Technique). The results achieved proved that relevant signals can be found in a frequency range up to 300 kHz. Based on this a diagnostic unit was designed and built for application under rotation conditions, which consists of a piezo-electric sensor, primary electronics, an analog-to-digital converter, a digital signal processor, a trigger unit, and a telemetric transmitter. This diagnostic unit was integrated in the hollow shaft of a railroad wheel axis, a component of a special laboratory test rig. Algorithms which allow for the rotation-synchronized processing of acoustic signals were implemented into the rotating diagnostic unit. After successfully completing a campaign for this test rig, a second test was performed inside the wheel/railroad simulation test rig of the Deutsche Bahn AG under railroad-like conditions. The data generated inside the hollow shaft of the railroad wheel axis by the diagnostic unit were telemetrically transmitted to an industrial computer. The detection of artificial defects of different sizes is shown in correlation with theoretical assumptions.

Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.

PubMed

Zapf, Antonia; Gwinner, Wilfried; Karch, Annika; Metzger, Jochen; Haller, Hermann; Koch, Armin

2015-09-15

Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect acute rejections. This study determines the diagnostic performance of the test in the routine setting of post-transplant patient care, compared to the biopsy-based rejection diagnosis. The next step would be a randomized trial to compare the two diagnostic strategies (including the urine test or not) in relation to patient relevant endpoints. NCT01315067 ; March 14, 2011.

Structure induction in diagnostic causal reasoning.

PubMed

Meder, Björn; Mayrhofer, Ralf; Waldmann, Michael R

2014-07-01

Our research examines the normative and descriptive adequacy of alternative computational models of diagnostic reasoning from single effects to single causes. Many theories of diagnostic reasoning are based on the normative assumption that inferences from an effect to its cause should reflect solely the empirically observed conditional probability of cause given effect. We argue against this assumption, as it neglects alternative causal structures that may have generated the sample data. Our structure induction model of diagnostic reasoning takes into account the uncertainty regarding the underlying causal structure. A key prediction of the model is that diagnostic judgments should not only reflect the empirical probability of cause given effect but should also depend on the reasoner's beliefs about the existence and strength of the link between cause and effect. We confirmed this prediction in 2 studies and showed that our theory better accounts for human judgments than alternative theories of diagnostic reasoning. Overall, our findings support the view that in diagnostic reasoning people go "beyond the information given" and use the available data to make inferences on the (unobserved) causal rather than on the (observed) data level. (c) 2014 APA, all rights reserved.

30 CFR 250.523 - How long do I keep records of casing pressure and diagnostic tests?

Code of Federal Regulations, 2011 CFR

2011-07-01

... and diagnostic tests? 250.523 Section 250.523 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT... long do I keep records of casing pressure and diagnostic tests? Records of casing pressure and diagnostic tests must be kept at the field office nearest the well for a minimum of 2 years. The last casing...

Single line-of-sight dual energy backlighter for mix width experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, K. L., E-mail: baker7@llnl.gov; Glendinning, S. G.; Martinez, D.

2014-11-15

We present a diagnostic technique used to spatially multiplex two x-ray radiographs of an object onto a detector along a single line-of-sight. This technique uses a thin, <2 μm, cosputtered backlighter target to simultaneously produce both Ni and Zn He{sub α} emission. A Ni picket fence filter, 500 μm wide bars and troughs, is then placed in front of the detector to pass only the Ni He{sub α} emission in the bar region and both energies in the trough region thereby spatially multiplexing the two radiographs on a single image. Initial experimental results testing the backlighter spectrum are presented alongmore » with simulated images showing the calculated radiographic images though the nickel picket fence filter which are used to measure the mix width in an accelerated nickel foam.« less

Emerging Rapid Resistance Testing Methods for Clinical Microbiology Laboratories and Their Potential Impact on Patient Management

PubMed Central

Frickmann, Hagen; Zautner, Andreas E.

2014-01-01

Atypical and multidrug resistance, especially ESBL and carbapenemase expressing Enterobacteriaceae, is globally spreading. Therefore, it becomes increasingly difficult to achieve therapeutic success by calculated antibiotic therapy. Consequently, rapid antibiotic resistance testing is essential. Various molecular and mass spectrometry-based approaches have been introduced in diagnostic microbiology to speed up the providing of reliable resistance data. PCR- and sequencing-based approaches are the most expensive but the most frequently applied modes of testing, suitable for the detection of resistance genes even from primary material. Next generation sequencing, based either on assessment of allelic single nucleotide polymorphisms or on the detection of nonubiquitous resistance mechanisms might allow for sequence-based bacterial resistance testing comparable to viral resistance testing on the long term. Fluorescence in situ hybridization (FISH), based on specific binding of fluorescence-labeled oligonucleotide probes, provides a less expensive molecular bridging technique. It is particularly useful for detection of resistance mechanisms based on mutations in ribosomal RNA. Approaches based on MALDI-TOF-MS, alone or in combination with molecular techniques, like PCR/electrospray ionization MS or minisequencing provide the fastest resistance results from pure colonies or even primary samples with a growing number of protocols. This review details the various approaches of rapid resistance testing, their pros and cons, and their potential use for the diagnostic laboratory. PMID:25343142

He Did What?: The role of diagnosticity in revising implicit evaluations

PubMed Central

Cone, Jeremy; Ferguson, Melissa J.

2015-01-01

Research suggests that implicit evaluations are relatively insensitive to single instances of new, countervailing information that contradicts prior learning. In six experiments, however, we identify the critical role of the perceived diagnosticity of that new information: counter-attitudinal information that is deemed highly diagnostic of the target's true nature leads to a complete reversal of the previous implicit evaluation. Experiments 1a and 1b establish this effect by showing that newly-formed implicit evaluations are reversed minutes later with exposure to a single piece of highly diagnostic information. Experiment 2 demonstrates a valence asymmetry in participants’ likelihood of exhibiting rapid reversals of newly formed positive versus negative implicit evaluations. Experiment 3 provides evidence that a target must be personally responsible for the counter-attitudinal behavior and not merely incidentally associated with a negative act. Experiment 4 shows that participants exhibit revision only when they judge the target's counter-attitudinal behavior as offensive and thus diagnostic of his character. Experiment 5 demonstrates the behavioral implications of newly-revised implicit evaluations. These studies show that newly-formed implicit evaluations can be completely overturned through deliberative considerations about a single piece of counter-attitudinal information. PMID:25365037

76 FR 49491 - Medicare Program; Section 3113: The Treatment of Certain Complex Diagnostic Laboratory Tests...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-10

...] Medicare Program; Section 3113: The Treatment of Certain Complex Diagnostic Laboratory Tests Demonstration... code under the Treatment of Certain Complex Diagnostic Laboratory Tests Demonstration. The deadline for... interested parties of an opportunity to participate in the Treatment of Certain Complex Diagnostic Laboratory...

123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma.

PubMed

Bleeker, Gitta; Tytgat, Godelieve A M; Adam, Judit A; Caron, Huib N; Kremer, Leontien C M; Hooft, Lotty; van Dalen, Elvira C

2015-09-29

Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be used for imaging the tumour. Moreover, ¹²³I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of ¹²³I-MIBG scintigraphy to detect neuroblastoma varies according to the literature.Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of ¹²³I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of ¹²³I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose ((18)F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. 1.1 To determine the diagnostic accuracy of ¹²³I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.1.2 To determine the diagnostic accuracy of negative ¹²³I-MIBG scintigraphy in combination with (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. 2.1 To determine the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.2.2 To compare the diagnostic accuracy of ¹²³I-MIBG (SPECT-CT) and (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. This was performed within and between included studies. ¹²³I-MIBG (SPECT-CT) scintigraphy was the comparator test in this case. We searched the databases of MEDLINE/PubMed (1945 to 11 September 2012) and EMBASE/Ovid (1980 to 11 September 2012) for potentially relevant articles. Also we checked the reference lists of relevant articles and review articles, scanned conference proceedings and searched for unpublished studies by contacting researchers involved in this area. We included studies of a cross-sectional design or cases series of proven neuroblastoma, either retrospective or prospective, if they compared the results of ¹²³I-MIBG (SPECT-CT) scintigraphy or (18)F-FDG-PET(-CT) imaging, or both, with the reference standards or with each other. Studies had to be primary diagnostic and report on children aged between 0 to 18 years old with a neuroblastoma of any stage at first diagnosis or at recurrence. One review author performed the initial screening of identified references. Two review authors independently performed the study selection, extracted data and assessed the methodological quality.We used data from two-by-two tables, describing at least the number of patients with a true positive test and the number of patients with a false negative test, to calculate the sensitivity, and if possible, the specificity for each included study.If possible, we generated forest plots showing estimates of sensitivity and specificity together with 95% confidence intervals. Eleven studies met the inclusion criteria. Ten studies reported data on patient level: the scan was positive or negative. One study reported on all single lesions (lesion level). The sensitivity of ¹²³I-MIBG (SPECT-CT) scintigraphy (objective 1.1), determined in 608 of 621 eligible patients included in the 11 studies, varied from 67% to 100%. One study, that reported on a lesion level, provided data to calculate the specificity: 68% in 115 lesions in 22 patients. The sensitivity of ¹²³I-MIBG scintigraphy for detecting metastases separately from the primary tumour in patients with all neuroblastoma stages ranged from 79% to 100% in three studies and the specificity ranged from 33% to 89% for two of these studies.One study reported on the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging (add-on test) in patients with negative ¹²³I-MIBG scintigraphy (objective 1.2). Two of the 24 eligible patients with proven neuroblastoma had a negative ¹²³I-MIBG scan and a positive (18)F-FDG-PET(-CT) scan.The sensitivity of (18)F-FDG-PET(-CT) imaging as a single diagnostic test (objective 2.1) and compared to ¹²³I-MIBG (SPECT-CT) (objective 2.2) was only reported in one study. The sensitivity of (18)F-FDG-PET(-CT) imaging was 100% versus 92% of ¹²³I-MIBG (SPECT-CT) scintigraphy. We could not calculate the specificity for both modalities. The reported sensitivities of ¹²³-I MIBG scintigraphy for the detection of neuroblastoma and its metastases ranged from 67 to 100% in patients with histologically proven neuroblastoma.Only one study in this review reported on false positive findings. It is important to keep in mind that false positive findings can occur. For example, physiological uptake should be ruled out, by using SPECT-CT scans, although more research is needed before definitive conclusions can be made.As described both in the literature and in this review, in about 10% of the patients with histologically proven neuroblastoma the tumour does not accumulate ¹²³I-MIBG (false negative results). For these patients, it is advisable to perform an additional test for staging and assess response to therapy. Additional tests might for example be (18)F-FDG-PET(-CT), but to be certain of its clinical value, more evidence is needed.The diagnostic accuracy of (18)F-FDG-PET(-CT) imaging in case of a negative ¹²³I-MIBG scintigraphy could not be calculated, because only very limited data were available. Also the detection of the diagnostic accuracy of index test (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma tumour and its metastases, and to compare this to comparator test ¹²³I-MIBG (SPECT-CT) scintigraphy, could not be calculated because of the limited available data at time of this search.At the start of this project, we did not expect to find only very limited data on specificity. We now consider it would have been more appropriate to use the term "the sensitivity to assess the presence of neuroblastoma" instead of "diagnostic accuracy" for the objectives.

The Role of Artificial Intelligence in Diagnostic Radiology: A Survey at a Single Radiology Residency Training Program.

PubMed

Collado-Mesa, Fernando; Alvarez, Edilberto; Arheart, Kris

2018-02-21

Advances in artificial intelligence applied to diagnostic radiology are predicted to have a major impact on this medical specialty. With the goal of establishing a baseline upon which to build educational activities on this topic, a survey was conducted among trainees and attending radiologists at a single residency program. An anonymous questionnaire was distributed. Comparisons of categorical data between groups (trainees and attending radiologists) were made using Pearson χ 2 analysis or an exact analysis when required. Comparisons were made using the Wilcoxon rank sum test when the data were not normally distributed. An α level of 0.05 was used. The overall response rate was 66% (69 of 104). Thirty-six percent of participants (n = 25) reported not having read a scientific medical article on the topic of artificial intelligence during the past 12 months. Twenty-nine percent of respondents (n = 12) reported using artificial intelligence tools during their daily work. Trainees were more likely to express doubts on whether they would have pursued diagnostic radiology as a career had they known of the potential impact artificial intelligence is predicted to have on the specialty (P = .0254) and were also more likely to plan to learn about the topic (P = .0401). Radiologists lack exposure to current scientific medical articles on artificial intelligence. Trainees are concerned by the implications artificial intelligence may have on their jobs and desire to learn about the topic. There is a need to develop educational resources to help radiologists assume an active role in guiding and facilitating the development and implementation of artificial intelligence tools in diagnostic radiology. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Surface plasmon resonance biosensing: Approaches for screening and characterising antibodies for food diagnostics.

PubMed

Yakes, B J; Buijs, J; Elliott, C T; Campbell, K

2016-08-15

Research in biosensing approaches as alternative techniques for food diagnostics for the detection of chemical contaminants and foodborne pathogens has increased over the last twenty years. The key component of such tests is the biorecognition element whereby polyclonal or monoclonal antibodies still dominate the market. Traditionally the screening of sera or cell culture media for the selection of polyclonal or monoclonal candidate antibodies respectively has been performed by enzyme immunoassays. For niche toxin compounds, enzyme immunoassays can be expensive and/or prohibitive methodologies for antibody production due to limitations in toxin supply for conjugate production. Automated, self-regenerating, chip-based biosensors proven in food diagnostics may be utilised as rapid screening tools for antibody candidate selection. This work describes the use of both single channel and multi-channel surface plasmon resonance (SPR) biosensors for the selection and characterisation of antibodies, and their evaluation in shellfish tissue as standard techniques for the detection of domoic acid, as a model toxin compound. The key advantages in the use of these biosensor techniques for screening hybridomas in monoclonal antibody production were the real time observation of molecular interaction and rapid turnaround time in analysis compared to enzyme immunoassays. The multichannel prototype instrument was superior with 96 analyses completed in 2h compared to 12h for the single channel and over 24h for the ELISA immunoassay. Antibodies of high sensitivity, IC50's ranging from 4.8 to 6.9ng/mL for monoclonal and 2.3-6.0ng/mL for polyclonal, for the detection of domoic acid in a 1min analysis time were selected. Although there is a progression for biosensor technology towards low cost, multiplexed portable diagnostics for the food industry, there remains a place for laboratory-based SPR instrumentation for antibody development for food diagnostics as shown herein. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypersensitivity to contrast media and dyes.

PubMed

Brockow, Knut; Sánchez-Borges, Mario

2014-08-01

This article updates current knowledge on hypersensitivity reactions to diagnostic contrast media and dyes. After application of a single iodinated radiocontrast medium (RCM), gadolinium-based contrast medium, fluorescein, or a blue dye, a hypersensitivity reaction is not a common finding; however, because of the high and still increasing frequency of those procedures, patients who have experienced severe reactions are nevertheless frequently encountered in allergy departments. Evidence on allergologic testing and management is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein. Skin tests can be helpful in the diagnosis of patients with hypersensitivity reactions to these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Advancing prevention of sexually transmitted infections through point-of-care testing: target product profiles and landscape analysis.

PubMed

Toskin, Igor; Murtagh, Maurine; Peeling, Rosanna W; Blondeel, Karel; Cordero, Joanna; Kiarie, James

2017-12-01

Advancing the field of point-of-care testing (POCT) for STIs can rapidly and substantially improve STI control and prevention by providing targeted, essential STI services (case detection and screening). POCT enables definitive diagnosis and appropriate treatment in a single visit and home and community-based testing. Since 2014, the WHO Department of Reproductive Health and Research, in collaboration with technical partners, has completed four landscape analyses of promising diagnostics for use at or near the point of patient care to detect syphilis, Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis and the human papillomavirus. The analyses comprised a literature review and interviews. Two International Technical Consultations on STI POCTs (2014 and 2015) resulted in the development of target product profiles (TPP). Experts in STI microbiology, laboratory diagnostics, clinical management, public health and epidemiology participated in the consultations with representation from all WHO regions. The landscape analysis identified diagnostic tests that are either available on the market, to be released in the near future or in the pipeline. The TPPs specify 28 analytical and operational characteristics of POCTs for use in different populations for surveillance, screening and case management. None of the tests that were identified in the landscape analysis met all of the targets of the TPPs. More efforts of the global health community are needed to accelerate access to affordable quality-assured STI POCTs, particularly in low- and middle-income countries, by supporting the development of new diagnostic platforms as well as strengthening the validation and implementation of existing diagnostics according to internationally endorsed standards and the best available evidence. © World Health Organization 2017. Licensee BMJ Publishing Group Limited. This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (https://creativecommons.org/licenses/by/3.0/igo), which permits use, distribution,and reproduction for non-commercial purposes in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.

Contamination with HIV antibody may be responsible for false positive results in specimens tested on automated platforms running HIV 4th generation assays in a region of high HIV prevalence.

PubMed

Hardie, Diana Ruth; Korsman, Stephen N; Hsiao, Nei-Yuan; Morobadi, Molefi Daniel; Vawda, Sabeehah; Goedhals, Dominique

2017-01-01

In South Africa where the prevalence of HIV infection is very high, 4th generation HIV antibody/p24 antigen combo immunoassays are the tests of choice for laboratory based screening. Testing is usually performed in clinical pathology laboratories on automated analysers. To investigate the cause of false positive results on 4th generation HIV testing platforms in public sector laboratories, the performance of two automated platforms was compared in a clinical pathology setting, firstly on routine diagnostic specimens and secondly on known sero-negative samples. Firstly, 1181 routine diagnostic specimens were sequentially tested on Siemens and Roche automated 4th generation platforms. HIV viral load, western blot and follow up testing were used to determine the true status of inconclusive specimens. Subsequently, known HIV seronegative samples from a single donor were repeatedly tested on both platforms and an analyser was tested for surface contamination with HIV positive serum to identify how suspected specimen contamination could be occurring. Serial testing of diagnostic specimens yielded 163 weakly positive or discordant results. Only 3 of 163 were conclusively shown to indicate true HIV infection. Specimen contamination with HIV antibody was suspected, based on the following evidence: the proportion of positive specimens increased on repeated passage through the analysers; viral loads were low or undetectable and western blots negative or indeterminate on problem specimens; screen negative, 2nd test positive specimens tested positive when reanalysed on the screening assay; follow up specimens (where available) were negative. Similarly, an increasing number of known negative specimens became (repeatedly) sero-positive on serial passage through one of the analysers. Internal and external analyser surfaces were contaminated with HIV serum, evidence that sample splashes occur during testing. Due to the extreme sensitivity of these assays, contamination with minute amounts of HIV antibody can cause a negative sample to test positive. Better contamination control measures are needed on analysers used in clinical pathology environments, especially in regions where HIV sero-prevalence is high.

Cross-reactions of sera from dogs infected with Angiostrongylus vasorum in commercially available Dirofilaria immitis test kits.

PubMed

Schnyder, Manuela; Deplazes, Peter

2012-11-13

Dirofilaria immitis and Angiostrongylus vasorum are both important potentially fatal canine nematodes with overlapping endemic areas, especially in Europe. The preadult and adult stages of both species are living in the Arteria pulmonalis and the right heart, and diagnostically detectable circulating parasite antigens have been demonstrated for both species. For the detection of D. immitis infections, a variety of commercial tests have been developed, however, they have not been evaluated for cross-reactions against circulating antigens of A. vasorum. In this study, potential cross-reactions of sera from 16 dogs, which were experimentally infected with A. vasorum and which had circulating antigens as confirmed by a species-specific ELISA, were evaluated for the detection of A. vasorum antigen in six commercially available D. immitis test kits. In three fast tests (Witness® Dirofilaria, SensPERT® Canine Heartworm, SNAP® 4Dx® Plus), all sera were negative. One fast membrane ELISA (SNAP® HTWM RT Test) was positive with four sera (25%), and one serum delivered a non-valid result twice. In the PetChek® HTWM PF Test, depending on the interpretation protocol, 5 or 8 dogs (31.2 - 50%) were positive. With the DiroCHEK®-ELISA, a single A. vasorum-infected dog (6.2%) tested positive. Due to potential cross-reactions with A. vasorum in commercially available test kits for the detection of D. immitis antigen, the simultaneous use of highly specific diagnostic methods for the differentiation of these two canine heart worms is recommended.

A new trivalent SnSAG surface antigen chimera for efficient detection of antibodies against Sarcocystis neurona and diagnosis of equine protozoal myeloencephalitis.

PubMed

Yeargan, Michelle; de Assis Rocha, Izabela; Morrow, Jennifer; Graves, Amy; Reed, Stephen M; Howe, Daniel K

2015-05-01

Enzyme-linked immunosorbent assays (ELISAs) based on the SnSAG surface antigens of Sarcocystis neurona provide reliable detection of infection by the parasite. Moreover, accurate serodiagnosis of equine protozoal myeloencephalitis (EPM) is achieved with the SnSAG ELISAs by measuring antibodies in serum and cerebrospinal fluid (CSF) to reveal active infection in the central nervous system. Two independent ELISAs based on recombinant (r)SnSAG2 or a chimeric fusion of SnSAG3 and SnSAG4 (rSnSAG4/3) are currently used together for EPM serodiagnosis to overcome varied antibody responses in different horses. To achieve reliable antibody detection with a single ELISA instead of 2 separate ELISAs, rSnSAG2 was fused with rSnSAG4/3 into a single trivalent protein, designated rSnSAG2/4/3. Paired serum and CSF from 163 horses were tested with all 3 ELISAs. When the consensus antibody titers obtained with the rSnSAG2 and rSnSAG4/3 ELISAs were compared to the single SAG2/4/3 ELISA titers, Spearman rank correlation coefficients of ρ = 0.74 and ρ = 0.90 were obtained for serum and CSF, respectively, indicating strong agreement between the tests. When the rSnSAG2 and rSnSAG4/3 consensus serum-to-CSF titer ratio was compared to the rSnSAG2/4/3 serum-to-CSF titer ratio, the Spearman correlation coefficient was ρ = 0.87, again signifying strong agreement. Importantly, comparing the diagnostic interpretation of the serum-to-CSF titer ratios yielded a Cohen kappa value of 0.77. These findings suggest that the single ELISA based on the trivalent rSnSAG2/4/3 will provide serologic and diagnostic results that are highly comparable to the consensus of the 2 independent ELISAs based on rSnSAG2 and rSnSAG4/3. © 2015 The Author(s).

Feature diagnosticity and task context shape activity in human scene-selective cortex.

PubMed

Lowe, Matthew X; Gallivan, Jason P; Ferber, Susanne; Cant, Jonathan S

2016-01-15

Scenes are constructed from multiple visual features, yet previous research investigating scene processing has often focused on the contributions of single features in isolation. In the real world, features rarely exist independently of one another and likely converge to inform scene identity in unique ways. Here, we utilize fMRI and pattern classification techniques to examine the interactions between task context (i.e., attend to diagnostic global scene features; texture or layout) and high-level scene attributes (content and spatial boundary) to test the novel hypothesis that scene-selective cortex represents multiple visual features, the importance of which varies according to their diagnostic relevance across scene categories and task demands. Our results show for the first time that scene representations are driven by interactions between multiple visual features and high-level scene attributes. Specifically, univariate analysis of scene-selective cortex revealed that task context and feature diagnosticity shape activity differentially across scene categories. Examination using multivariate decoding methods revealed results consistent with univariate findings, but also evidence for an interaction between high-level scene attributes and diagnostic visual features within scene categories. Critically, these findings suggest visual feature representations are not distributed uniformly across scene categories but are shaped by task context and feature diagnosticity. Thus, we propose that scene-selective cortex constructs a flexible representation of the environment by integrating multiple diagnostically relevant visual features, the nature of which varies according to the particular scene being perceived and the goals of the observer. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic Accuracy of MRI-guided Percutaneous Transthoracic Needle Biopsy of Solitary Pulmonary Nodules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Shangang, E-mail: 1198685580@qq.com; Li, Chengli, E-mail: chenglilichina@yeah.net; Yu, Xuejuan, E-mail: yuxuejuan2011@126.com

2015-04-15

ObjectiveThe purpose of our study was to evaluate the diagnostic accuracy of MRI-guided percutaneous transthoracic needle biopsy (PTNB) of solitary pulmonary nodules (SPNs).MethodsRetrospective review of 69 patients who underwent MR-guided PTNB of SPNs was performed. Each case was reviewed for complications. The final diagnosis was established by surgical pathology of the nodule or clinical and imaging follow-up. Pneumothorax rate and diagnostic accuracy were compared between two groups according to nodule diameter (≤2 vs. >2 cm) using χ{sup 2} chest and Fisher’s exact test, respectively.ResultsThe success rate of single puncture was 95.6 %. Twelve (17.4 %) patients had pneumothorax, with 1 (1.4 %) requiring chestmore » tube insertion. Mild hemoptysis occurred in 7 (7.2 %) patients. All of the sample material was sufficient for histological diagnostic evaluation. Pathological analysis of biopsy specimens showed 46 malignant, 22 benign, and 1 nondiagnostic nodule. The final diagnoses were 49 malignant nodules and 20 benign nodules basing on postoperative histopathology and clinical follow-up data. One nondiagnostic sample was excluded from calculating diagnostic performance. A sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in diagnosing SPNs were 95.8, 100, 97.0, 100, and 90.9 %, respectively. Pneumothorax rate, diagnostic sensitivity, and accuracy were not significantly different between the two groups (P > 0.05).ConclusionsMRI-guided PTNB is safe, feasible, and high accurate diagnostic technique for pathologic diagnosis of pulmonary nodules.« less

A micro-scale plasma spectrometer for space and plasma edge applications (invited)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scime, E. E., E-mail: escime@wvu.edu; Keesee, A. M.; Elliott, D.

2016-11-15

A plasma spectrometer design based on advances in lithography and microchip stacking technologies is described. A series of curved plate energy analyzers, with an integrated collimator, is etched into a silicon wafer. Tests of spectrometer elements, the energy analyzer and collimator, were performed with a 5 keV electron beam. The measured collimator transmission and energy selectivity were in good agreement with design targets. A single wafer element could be used as a plasma processing or fusion first wall diagnostic.

Antibodies Expressed by Intratumoral B Cells as the Basis for a Diagnostic Test for Lung Cancer

DTIC Science & Technology

2014-07-01

Kepler , T. B., Denny, T., Moody, M. A., and Haynes, B. F. (2009) High-throughput isolation of immunoglobulin genes from single human B cells and...Parks, R., Foulger, A., Jaeger, F., Donathan, M., Bilska, M., Gray, E. S., Abdool Karim, S. S., Kepler , T. B., Whitesides, J., Montefiori, D., Moody...Vandergrift, N. A., Alam, S. M., Tomaras, G. D., Kepler , T. B., Kelsoe, G., Liao, H. X., and Haynes, B. F. (2011) H3N2 influenza infection elicits

Dependence of Impedance of Embedded Single Cells on Cellular Behaviour

PubMed Central

Cho, Sungbo; Castellarnau, Marc; Samitier, Josep; Thielecke, Hagen

2008-01-01

Non-invasive single cell analyses are increasingly required for the medical diagnostics of test substances or the development of drugs and therapies on the single cell level. For the non-invasive characterisation of cells, impedance spectroscopy which provides the frequency dependent electrical properties has been used. Recently, microfludic systems have been investigated to manipulate the single cells and to characterise the electrical properties of embedded cells. In this article, the impedance of partially embedded single cells dependent on the cellular behaviour was investigated by using the microcapillary. An analytical equation was derived to relate the impedance of embedded cells with respect to the morphological and physiological change of extracellular interface. The capillary system with impedance measurement showed a feasibility to monitor the impedance change of embedded single cells caused by morphological and physiological change of cell during the addition of DMSO. By fitting the derived equation to the measured impedance of cell embedded at different negative pressure levels, it was able to extrapolate the equivalent gap and gap conductivity between the cell and capillary wall representing the cellular behaviour. PMID:27879760

Accuracy, risk and the intrinsic value of diagnostic imaging: a review of the cost-utility literature.

PubMed

Otero, Hansel J; Fang, Chi H; Sekar, Meera; Ward, Robert J; Neumann, Peter J

2012-05-01

The aim of this study was to systematically review the reporting of the value of imaging unrelated to treatment consequences and test characteristics in all imaging-related published cost-utility analyses (CUAs) in the medical literature. All CUAs published between 1976 and 2008 evaluating diagnostic imaging technologies contained in the CEA Registry, a publicly available comprehensive database of health related CUAs, were screened. Publication characteristics, imaging modality, and the inclusion of test characteristics including accuracy, costs, risks, and the potential value unrelated to treatment consequences (eg, reassurance or anxiety) were assessed. Ninety-six published CUAs evaluating 155 different imaging technologies were included in the final sample; 27 studies were published in imaging-specialized journals. Fifty-two studies (54%) evaluated the performance of a single imaging modality, while 44 studies (46%) compared two or more different imaging modalities. The most common areas of interest were cardiovascular (45%) and neuroradiology (17%). Forty-two technologies (27%) concerned ultrasound, while 34 (22%) concerned magnetic resonance. Seventy-nine (51%) technologies used ionizing radiation. Test accuracy was reported or calculated for 90% (n = 133 and n = 5, respectively) and assumed perfect (reference test or gold-standard test without alternative testing strategy to capture false-negatives and false-positives) for 8% (n = 12) of technologies. Only 22 studies (23%) assessing 40 imaging technologies (26%) considered inconclusive or indeterminate results. The risk of testing was reported for 32 imaging technologies (21%). Fifteen studies (16%) considered the value of diagnostic imaging unrelated to treatment. Four studies incorporated it as quality-of-life adjustments, while 10 studies mentioned it only in their discussions or as a limitation. The intrinsic value of imaging (the value of imaging unrelated to treatment) has not been appropriately defined or incorporated in the existing cost-utility literature, which could be due to a lack of evidence on the issue. Thus, more research is needed on metrics for a more comprehensive evaluation of diagnostic imaging. Similarly, the incorporation of variations in imaging tests accuracy, inconclusive results and associated risks has lacked uniformity in the cost-utility literature. Acknowledgment of these characteristics in future cost-utility publications will enhance their value and provide results that more closely resemble routine clinical practice. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

Identifying Inefficient Single-Family Homes With Utility Bill Analysis: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casey, S.; Krarti, M.; Bianchi, M.

2010-08-01

Differentiating between energy-efficient and inefficient single-family homes on a community scale helps identify and prioritize candidates for energy-efficiency upgrades. Prescreening diagnostic procedures can further retrofit efforts by providing efficiency information before a site-visit is conducted. We applied the prescreening diagnostic to a simulated community of homes in Boulder, Colorado and analyzed energy consumption data to identify energy-inefficient homes.

Reporting Diagnostic Scores in Educational Testing: Temptations, Pitfalls, and Some Solutions

ERIC Educational Resources Information Center

Sinharay, Sandip; Puhan, Gautam; Haberman, Shelby J.

2010-01-01

Diagnostic scores are of increasing interest in educational testing due to their potential remedial and instructional benefit. Naturally, the number of educational tests that report diagnostic scores is on the rise, as are the number of research publications on such scores. This article provides a critical evaluation of diagnostic score reporting…

Myasthenia Gravis: Tests and Diagnostic Methods

MedlinePlus

... Focus on MG Newsletter MG Quarterly Test & Diagnostic methods In addition to a complete medical and neurological ... How can I help? About MGFA Test & Diagnostic methods Treatment for MG FAQ's Upcoming Events 2018 MG ...

Low Diagnostic Utility of Rechecking Hemoglobins Within 24 Hours in Hospitalized Patients.

PubMed

Rajkomar, Alvin; McCulloch, Charles E; Fang, Margaret C

2016-11-01

Clinicians often repeat hemoglobin tests within a 24 hour period to detect or monitor anemia. We sought to determine the percentage of hemoglobin tests repeated within a single hospital day that were at least 1.0 g/dL lower than the first test. We performed a retrospective cross-sectional analysis of hospitalized adults on medical or surgical services over 1 year at a single academic hospital. Using patient and laboratory data in the electronic health record, we analyzed the proportion of repeated hemoglobin test results that were at least 1 g/dL less than the initial hemoglobin value of that day, excluding days when transfusions were administered. A total of 88,722 hemoglobin tests were obtained from 12,877 unique patients, who contributed a total of 86,859 hospitalization days. In 12,230 (14.1%) of those days, 2 or more hemoglobin tests were obtained within a single day. In the 6969 days with 2 hemoglobin tests obtained and no transfusions given, 949 (13.5%) were ≥1 g/dL lower than the initial hemoglobin value of that day, and 260 (3.7%) were ≥2 g/dL lower. Repeated tests did not often reach transfusion thresholds: 482 (6.9%) of repeat hemoglobin values were <8 g/dL, and 64 (0.9%) were <7 g/dL. Hemoglobin tests were repeated in 14% of hospital days. For patients who had 2 hemoglobin tests obtained on the same day, 13.5% demonstrated a clinically significant drop. This information may be helpful to clinicians when considering whether repeat testing is appropriate. Copyright © 2016 Elsevier Inc. All rights reserved.

Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

PubMed

Messacar, Kevin; Parker, Sarah K; Todd, James K; Dominguez, Samuel R

2017-03-01

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics. Copyright © 2017 American Society for Microbiology.

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β-d-Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis.

PubMed

Urabe, Naohisa; Sakamoto, Susumu; Sano, Go; Suzuki, Junko; Hebisawa, Akira; Nakamura, Yasuhiko; Koyama, Kazuya; Ishii, Yoshikazu; Tateda, Kazuhiro; Homma, Sakae

2017-06-01

We evaluated the usefulness of an Aspergillus galactomannan (GM) test, a β-d-glucan (βDG) test, and two different Aspergillus PCR assays of bronchoalveolar lavage fluid (BALF) samples for the diagnosis of chronic pulmonary aspergillosis (CPA). BALF samples from 30 patients with and 120 patients without CPA were collected. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each test individually and in combination with other tests. The optical density index values, as determined by receiver operating characteristic analysis, for the diagnosis of CPA were 0.5 and 100 for GM and βDG testing of BALF, respectively. The sensitivity and specificity of the GM test, βDG test, and PCR assays 1 and 2 were 77.8% and 90.0%, 77.8% and 72.5%, 86.7% and 84.2%, and 66.7% and 94.2%, respectively. A comparison of the PCR assays showed that PCR assay 1 had a better sensitivity, a better negative predictive value, and a better negative likelihood ratio and PCR assay 2 had a better specificity, a better positive predictive value, and a better positive likelihood ratio. The combination of the GM and βDG tests had the highest diagnostic odds ratio. The combination of the GM and βDG tests on BALF was more useful than any single test for diagnosing CPA. Copyright © 2017 American Society for Microbiology.

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2).

PubMed

Hailey, James R; Maleeff, Beverly E; Thomas, Heath C; Pearse, Gail; Klapwijk, Jan C; Cristofori, Patrizia G; Berridge, Brian; Kimbrough, Carie L; Parker, George A; Morton, Daniel; Elmore, Susan; Hardisty, Jerry F; Dybdal, Noel O; Rehagen, David A; Fikes, James D; Lamb, Martin; Biddle, Kathleen; Buetow, Bernard S; Carreira, Vinicius; Nyska, Abraham; Tripathi, Niraj K; Workman, Heather C; Bienvenu, Jean-Guy; Brees, Ingrid; Turk, James R; Adler, Rick R

2017-12-01

Spontaneous rodent progressive cardiomyopathy (PCM) in the Sprague Dawley rat may confound identification and/or interpretation of potential test article (TA)-related cardiotoxicity. Pathologists apply diagnostic term(s) and thresholds for diagnosing and assigning severity grades for PCM and/or PCM-like (PCM/like) lesions consistently within a study, which is necessary to identify and interpret TA-related findings. Due to differences in training and/or experiences, diagnostic terms and thresholds may vary between pathologists. Harmonized terminology and thresholds across studies will generate better historical control data, will likely enhance interpretation of study data, and may further enhance our understanding of the spontaneous change. An assessment of the diagnostic approaches of a group of 37 pathologists identified an approach that is relatively easily applied; and if adopted, it could enhance diagnostic consistency across studies. This approach uses the single "slash" term "necrosis/inflammatory cell infiltrate (NICI)" as the diagnosis for the spectrum of lesions seen in younger rats, uses no threshold for diagnosis (e.g., diagnose all lesions clearly identifiable as PCM/like), and uses aggregate lesion size of approximately ≥45% of the field of view (FOV) using a 10×/22 eyepiece and the 40× objective or approximately ≥100% of the FOV using the 60× objective as the criterion separating minimal from mild severities.

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service

PubMed Central

Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V.; Housby, Nick; Taylor, Jenny C.; Schuh, Anna

2017-01-01

Background Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. Methods and findings We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of “real world” data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. Conclusions This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers. PMID:28196074

The Importance of Conditional Probability in Diagnostic Reasoning and Clinical Decision Making: A Primer for the Eye Care Practitioner.

PubMed

Sanfilippo, Paul G; Hewitt, Alex W; Mackey, David A

2017-04-01

To outline and detail the importance of conditional probability in clinical decision making and discuss the various diagnostic measures eye care practitioners should be aware of in order to improve the scope of their clinical practice. We conducted a review of the importance of conditional probability in diagnostic testing for the eye care practitioner. Eye care practitioners use diagnostic tests on a daily basis to assist in clinical decision making and optimizing patient care and management. These tests provide probabilistic information that can enable the clinician to increase (or decrease) their level of certainty about the presence of a particular condition. While an understanding of the characteristics of diagnostic tests are essential to facilitate proper interpretation of test results and disease risk, many practitioners either confuse or misinterpret these measures. In the interests of their patients, practitioners should be aware of the basic concepts associated with diagnostic testing and the simple mathematical rule that underpins them. Importantly, the practitioner needs to recognize that the prevalence of a disease in the population greatly determines the clinical value of a diagnostic test.

Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force.

PubMed

Cox, Linda; Williams, Brock; Sicherer, Scott; Oppenheimer, John; Sher, Larry; Hamilton, Robert; Golden, David

2008-12-01

The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.

42 CFR 414.509 - Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for a new clinical diagnostic laboratory test. 414.509 Section 414.509 Public Health CENTERS FOR... FOR PART B MEDICAL AND OTHER HEALTH SERVICES Payment for New Clinical Diagnostic Laboratory Tests § 414.509 Reconsideration of basis for and amount of payment for a new clinical diagnostic laboratory...

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

PubMed

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

2016-02-11

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. © 2016 by The American Society of Hematology.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes

PubMed Central

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R.; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L.

2016-01-01

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the PlA1/PlA2 polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33+ megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41+ megakaryocyte progenitors derived from these cells expressed the HPA-1b (PlA2) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b–specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. PMID:26634302

Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease.

PubMed

Wormser, Gary P; Schriefer, Martin; Aguero-Rosenfeld, Maria E; Levin, Andrew; Steere, Allen C; Nadelman, Robert B; Nowakowski, John; Marques, Adriana; Johnson, Barbara J B; Dumler, J Stephen

2013-01-01

For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice. Copyright © 2013 Elsevier Inc. All rights reserved.

A comparison of the diagnostic performance of the ST/HR hysteresis with cardiopulmonary stress testing parameters in detecting exercise-induced myocardial ischemia.

PubMed

Zimarino, Marco; Barnabei, Luca; Madonna, Rosalinda; Palmieri, Giuseppe; Radico, Francesco; Tatasciore, Alfonso; Bellisarii, Francesco Iachini; Perrucci, Gianni Mauro; Corazzini, Alessandro; De Caterina, Raffaele

2013-09-30

Because ST segment depression has limited diagnostic performance at exercise electrocardiography (ECG), ST segment depression/heart rate (ST/HR) hysteresis and cardiopulmonary exercise test (CPET)-derived parameters have been proposed as alternatives to diagnose exercise-induced myocardial ischemia. We compared the diagnostic performance of such parameters. We studied 56 subjects (45 men, 11 women, age 59.7 ± 13.6 years) referred for suspected exercise-induced myocardial ischemia with an equivocal ECG exercise test. All subjects serially underwent CPET and a myocardial single-photon emission computerized tomography (SPECT) perfusion imaging (as the gold standard for ischemia). Maximum ST depression at peak exercise (ST-max), the ST/HR hysteresis, ΔVO2/ΔWR b-b1 slope, ΔVO2/ΔWR (aa1-bb1), VO2/HR flattening duration and other CPET parameters were derived in all subjects. On the basis of SPECT, 23 subjects (41%) were considered ischemic and 33 subjects (59%) non-ischemic. ST/HR hysteresis was higher (0.026 mV; 95% CI: 0.003 to 0.049 vs -0.016 mV; 95% CI: -0.031 to -0.001 mV) and ST-max was lower (-0.105 mV; 95% CI: -0.158 to -0.052 vs 0.032 mV; 95% CI: -0.001 to -0.066 mV) in ischemic vs non-ischemic subjects (P=0.004 and P=0.001, respectively). Among CPET parameters, ΔVO2/ΔWR b-b(1) slope was lower (9.4 ± 3.8) and ΔVO2/ΔWR (aa(1)-bb(1)) was higher (2.1 ± 2.6) in ischemic vs non-ischemic subjects (11.4 ± 2.3, P=0.005, and 1.1 ± 1.5, P=0.001, respectively). The ST/HR hysteresis had the highest area under the curve value, better (P<0.05) than any other parameters tested, thus showing the highest overall diagnostic performance. The ST/HR hysteresis is superior to CPET-derived parameters for detecting exercise-induced myocardial ischemia in patients with equivocal ECG exercise test results. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A Novel Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0195 TITLE: A Novel Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis PRINCIPAL INVESTIGATOR...Field-Deployable Point-of-Care Diagnostic Test for Cutaneous Leishmaniasis 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Month % completion Aim 1: To use simulated field conditions to optimize and produce the established RPA lateral flow diagnostic test for POC

Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer.

PubMed

Hout, David R; Schweitzer, Brock L; Lawrence, Kasey; Morris, Stephan W; Tucker, Tracy; Mazzola, Rosetta; Skelton, Rachel; McMahon, Frank; Handshoe, John; Lesperance, Mary; Karsan, Aly; Saltman, David L

2017-08-01

Patients with lung cancers harboring an activating anaplastic lymphoma kinase ( ALK ) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely used screening tests for ALK rearrangements but both methods have limitations. The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay for high throughput and automated interpretation of ALK expression. In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR test (diagnostic cut-off Δ C t of ≤8) was shown to be highly sensitive (100%) when compared to FISH and IHC. Sequencing of RNA detected full-length ALK transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in which ALK expression was detected by the ALK RT-PCR test but negative by FISH and IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases without full-length ALK expression was 94% in comparison to FISH and sequencing. These data support the ALK RT-PCR test as a highly efficient and reliable diagnostic screening approach to identify patients with non-small cell lung cancer whose tumors are driven by oncogenic ALK.

Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer

PubMed Central

Hout, David R.; Lawrence, Kasey; Morris, Stephan W.; Tucker, Tracy; Mazzola, Rosetta; Skelton, Rachel; McMahon, Frank; Handshoe, John; Lesperance, Mary; Karsan, Aly

2017-01-01

Patients with lung cancers harboring an activating anaplastic lymphoma kinase (ALK) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely used screening tests for ALK rearrangements but both methods have limitations. The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay for high throughput and automated interpretation of ALK expression. In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR test (diagnostic cut-off ΔCt of ≤8) was shown to be highly sensitive (100%) when compared to FISH and IHC. Sequencing of RNA detected full-length ALK transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in which ALK expression was detected by the ALK RT-PCR test but negative by FISH and IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases without full-length ALK expression was 94% in comparison to FISH and sequencing. These data support the ALK RT-PCR test as a highly efficient and reliable diagnostic screening approach to identify patients with non-small cell lung cancer whose tumors are driven by oncogenic ALK. PMID:28763012

Special Educator's Complete Guide to 109 Diagnostic Tests: How To Select & Interpret Tests, Use Results in IEPs, and Remediate Specific Difficulties.

ERIC Educational Resources Information Center

Pierangelo, Roger; Giuliani, George

This manual is a guide to the special education diagnostic process and covers the various stages of evaluation, interpretation, diagnosis, prescription, and remediation. Test information includes: explanations of the most commonly used diagnostic tests, coverage of the areas measured by each test, interpretation of test patterns for commonly used…

A simulation model to quantify the value of implementing whole-herd Bovine viral diarrhea virus testing strategies in beef cow-calf herds.

PubMed

Nickell, Jason S; White, Brad J; Larson, Robert L; Renter, David G; Sanderson, Mike W

2011-03-01

Although numerous diagnostic tests are available to identify cattle persistently infected (PI) with Bovine viral diarrhea virus (BVDV) in cow-calf herds, data are sparse when evaluating the economic viability of individual tests or diagnostic strategies. Multiple factors influence BVDV testing in determining if testing should be performed and which strategy to use. A stochastic model was constructed to estimate the value of implementing various whole-herd BVDV cow-calf testing protocols. Three common BVDV tests (immunohistochemistry, antigen-capture enzyme-linked immunosorbent assay, and polymerase chain reaction) performed on skin tissue were evaluated as single- or two-test strategies. The estimated testing value was calculated for each strategy at 3 herd sizes that reflect typical farm sizes in the United States (50, 100, and 500 cows) and 3 probabilities of BVDV-positive herd status (0.077, 0.19, 0.47) based upon the literature. The economic value of testing was the difference in estimated gross revenue between simulated cow-calf herds that either did or did not apply the specific testing strategy. Beneficial economic outcomes were more frequently observed when the probability of a herd being BVDV positive was 0.47. Although the relative value ranking of many testing strategies varied by each scenario, the two-test strategy composed of immunohistochemistry had the highest estimated value in all but one herd size-herd prevalence permutation. These data indicate that the estimated value of applying BVDV whole-herd testing strategies is influenced by the selected strategy, herd size, and the probability of herd BVDV-positive status; therefore, these factors should be considered when designing optimum testing strategies for cow-calf herds.

Advances in the Diagnosis of Human Opisthorchiasis: Development of Opisthorchis viverrini Antigen Detection in Urine

PubMed Central

Duenngai, Kunyarat; Wangboon, Chompunoot; Sithithaworn, Jiraporn; Watwiengkam, Nattaya; Namwat, Nisana; Techasen, Anchalee; Loilome, Watcharin; Yongvanit, Puangrat; Loukas, Alex; Sithithaworn, Paiboon; Bethony, Jeffrey M.

2015-01-01

Background Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV eggs often confused with eggs of minute intestinal flukes (MIFs) in feces. In this study, we developed and evaluated the diagnostic performance of a monoclonal antibody-based enzyme-linked immunosorbent assay for the measurement of OV excretory-secretory (ES) antigens in urine (urine OV-ES assay) for the diagnosis of opisthorchiasis compared to the gold standard detection FECT method. Methodology We tested several methods for pre-treating urine samples prior to testing the diagnostic performance of the urine OV-ES assay. Using trichloroacetic acid (TCA) pre-treated urine, we compared detection and quantification of OV infection using the urine OV-ES assay versus FECT in OV-endemic areas in Northeastern Thailand. Receiver operating characteristic (ROC) curves were used to determine the diagnostic sensitivity and specificity of the urine OV-ES assay using TCA pre-treated urine, and to establish diagnostic positivity thresholds. The Positive Predictive Value as well as the likelihood of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for the established diagnostic positivity threshold. Diagnostic risks (Odds Ratios) were estimated using logistic regression. Results When urine samples were pre-treated with TCA prior to use in the urine OV-ES assay, the analytical sensitivity was significantly improved. Using TCA pre-treatment of urine, the urine OV-ES assay had a limit of detection (LoD) of 39 ng/ml compared to the LoD of 52 ng/mL reported for coprological antigen detection methods. Similarly, the urine OV-ES assay correlated significantly with intensity of OV infection as measured by FECT. The urine OV-ES assay was also able to detect 28 individuals as positive from the 63 (44.4%) individuals previously determined to be negative using FECT. The likelihood of a positive diagnosis of OV infection by urine OV-ES assay increased significantly with the intensity of OV infection as determined by FECT. With reference to FECT, the sensitivity and specificity of the urine OV-ES assay was 81% and 70%, respectively. Conclusion The detection of OV-infection by the urine OV-ES assay showed much greater diagnostic sensitivity and diagnostic specificity than the current "gold standard" FECT method for the detection and quantification of OV infection. Due to its ease-of-use, and noninvasive sample collection (urine), the urine OV-ES assay offers the potential to revolutionize the diagnosis of liver fluke infection and provide an effective tool for control and elimination of these tumorigenic parasites. PMID:26485024

Free jet feasibility study of a thermal acoustic shield concept for AST/VCE application: Single stream nozzles

NASA Technical Reports Server (NTRS)

Majjigi, R. K.; Brausch, J. F.; Janardan, B. A.; Balsa, T. F.; Knott, P. R.; Pickup, N.

1984-01-01

A technology base for the thermal acoustic shield concept as a noise suppression device for single stream exhaust nozzles was developed. Acoustic data for 314 test points for 9 scale model nozzle configurations were obtained. Five of these configurations employed an unsuppressed annular plug core jet and the remaining four nozzles employed a 32 chute suppressor core nozzle. Influence of simulated flight and selected geometric and aerodynamic flow variables on the acoustic behavior of the thermal acoustic shield was determined. Laser velocimeter and aerodynamic measurements were employed to yield valuable diagnostic information regarding the flow field characteristics of these nozzles. An existing theoretical aeroacoustic prediction method was modified to predict the acoustic characteristics of partial thermal acoustic shields.

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis

PubMed Central

Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

2018-01-01

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis‐stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi‐FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeterV2G) with those of a test targeted for cirrhosis (CirrhoMeterV2G). In the derivation CHC population, we first compared Multi‐FibroMeterV2G to FibroMeterV2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis‐stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeterV2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi‐FibroMeterV2G and FibroMeterV2G were the following: cirrhosis AUROC, 0.906 versus 0.878 (P < 0.001; versus CirroMeterV2G, 0.897, P = 0.014); Obuchowski index, 0.795 versus 0.791 (P = 0.059); classification, 86.0% versus 82.1% (P < 0.001); significant fibrosis AUROC, 0.833 versus 0.832 (P = 0.366). Multi‐FibroMeterV2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi‐FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ (P = 0.938). Conclusion: Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single‐targeted blood tests. (Hepatology Communications 2018;2:455‐466) PMID:29619423

Cost-effectiveness of molecular testing for thyroid nodules with atypia of undetermined significance cytology.

PubMed

Lee, Lawrence; How, Jacques; Tabah, Roger J; Mitmaker, Elliot J

2014-08-01

Novel molecular diagnostics, such as the gene expression classifier (GEC) and gene mutation panel (GMP) testing, may improve the management for thyroid nodules with atypia of undetermined significance (AUS) cytology. The cost-effectiveness of an approach combining both tests in different practice settings in North America is unknown. The aim of the study was to determine the cost-effectiveness of two diagnostic molecular tests, singly or in combination, for AUS thyroid nodules. We constructed a microsimulation model to investigate cost-effectiveness from US (Medicare) and Canadian healthcare system perspectives. Low-risk patients with AUS thyroid nodules were simulated. We examined five management strategies: 1) routine GEC; 2) routine GEC + selective GMP; 3) routine GMP; 4) routine GMP + selective GEC; and 5) standard management. Lifetime costs and quality-adjusted life-years were measured. From the US perspective, the routine GEC + selective GMP strategy was the dominant strategy. From the Canadian perspective, routine GEC + selective GMP cost and additional CAN$24 030 per quality-adjusted life-year gained over standard management, and was dominant over the other strategies. Sensitivity analyses reported that the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP. The probability of cost-effectiveness for routine GEC + selective GMP was low. In the US setting, the most cost-effective strategy was routine GEC + selective GMP. In the Canadian setting, standard management was most likely to be cost effective. The cost of these molecular diagnostics will need to be reduced to increase their cost-effectiveness for practice settings outside the United States.

Lipopolysaccharide Specific Immunochromatography Based Lateral Flow Assay for Serogroup Specific Diagnosis of Leptospirosis in India

PubMed Central

Vanithamani, Shanmugam; Shanmughapriya, Santhanam; Narayanan, Ramasamy; Raja, Veerapandian; Kanagavel, Murugesan; Sivasankari, Karikalacholan; Natarajaseenivasan, Kalimuthusamy

2015-01-01

Background Leptospirosis is a re-emerging infectious disease that is under-recognized due to low-sensitivity and cumbersome serological tests. MAT is the gold standard test and it is the only serogroup specific test used till date. Rapid reliable alternative serogroup specific tests are needed for surveillance studies to identify locally circulating serogroups in the study area. Methods/Principal Findings In the present investigation the serological specificity of leptospiral lipopolysaccharides (LPS) was evaluated by enzyme linked immunosorbent assay (ELISA), dot blot assay and rapid immunochromatography based lateral flow assay (ICG-LFA). Sera samples from 120 MAT positive cases, 174 cases with febrile illness other than leptospirosis, and 121 seronegative healthy controls were evaluated for the diagnostic sensitivity and specificity of the developed assays. LPS was extracted from five locally predominant circulating serogroups including: Australis (27.5%), Autumnalis (11.7%), Ballum (25.8%), Grippotyphosa (12.5%), Pomona (10%) and were used as antigens in the diagnostics to detect IgM antibodies in patients’ sera. The sensitivity observed by IgM ELISA and dot blot assay using various leptospiral LPS was >90% for homologous sera. Except for Ballum LPS, no other LPS showed cross-reactivity to heterologous sera. An attempt was made to develop LPS based ICG-LFA for rapid and sensitive serogroup specific diagnostics of leptospirosis. The developed ICG-LFA showed sensitivity in the range between 93 and 100% for homologous sera. The Wilcoxon analysis showed LPS based ICG-LFA did not differ significantly from the gold standard MAT (P>0.05). Conclusion The application of single array of LPS for serogroup specific diagnosis is first of its kind. The developed assay could potentially be evaluated and employed for as MAT alternative. PMID:26340095

How to: evaluate a diagnostic test.

PubMed

Leeflang, Mariska M G; Allerberger, Franz

2018-06-12

The development of an in vitro diagnostic test from a good idea to a clinically relevant tool takes several steps, with more stringent requirements at every step. This article aims to summarize the necessary questions to be asked about a test and to illustrate study designs answering these questions. We also aim to relate the Regulation (EU) 2017/746 to the needs of evidence-based diagnostic testing, where applicable. We used literature on evidence-based diagnostics, a text book on clinical trials in the development and marketing of medical devices and the English version of Regulation 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices. The combination of different test uses and different stages of development determine the required test characteristics and suitability of study designs. In an earlier stage of test development it may be crucial to know whether a test can differentiate diseased persons from healthy controls, while this tells us little about how a test will perform in practice. Later stages focus on the diagnostic accuracy of a test in a clinically relevant situation. However, a test that perfectly distinguishes between patients with and without a certain condition may still have little effect on patient outcomes. Therefore, randomized controlled trials of testing may be needed, as well as post-marketing monitoring. Both researchers and users of tests need to be aware of the limitations of diagnostic test accuracy and realize that accuracy is only indirectly linked to people's health status. Copyright © 2018. Published by Elsevier Ltd.

Overcoming the errors of in-house PCR used in the clinical laboratory for the diagnosis of extrapulmonary tuberculosis.

PubMed

Kunakorn, M; Raksakai, K; Pracharktam, R; Sattaudom, C

1999-03-01

Our experiences from 1993 to 1997 in the development and use of IS6110 base PCR for the diagnosis of extrapulmonary tuberculosis in a routine clinical setting revealed that error-correcting processes can improve existing diagnostic methodology. The reamplification method initially used had a sensitivity of 90.91% and a specificity of 93.75%. The concern was focused on the false positive results of this method caused by product-carryover contamination. This method was changed to single round PCR with carryover prevention by uracil DNA glycosylase (UDG), resulting in a 100% specificity but only 63% sensitivity. Dot blot hybridization was added after the single round PCR, increasing the sensitivity to 87.50%. However, false positivity resulted from the nonspecific dot blot hybridization signal, reducing the specificity to 89.47%. The hybridization of PCR was changed to a Southern blot with a new oligonucleotide probe giving the sensitivity of 85.71% and raising the specificity to 99.52%. We conclude that the PCR protocol for routine clinical use should include UDG for carryover prevention and hybridization with specific probes to optimize diagnostic sensitivity and specificity in extrapulmonary tuberculosis testing.

Biomedical Diagnostics Enabled by Integrated Organic and Printed Electronics.

PubMed

Ahmadraji, Termeh; Gonzalez-Macia, Laura; Ritvonen, Tapio; Willert, Andreas; Ylimaula, Satu; Donaghy, David; Tuurala, Saara; Suhonen, Mika; Smart, Dave; Morrin, Aoife; Efremov, Vitaly; Baumann, Reinhard R; Raja, Munira; Kemppainen, Antti; Killard, Anthony J

2017-07-18

Organic and printed electronics integration has the potential to revolutionize many technologies, including biomedical diagnostics. This work demonstrates the successful integration of multiple printed electronic functionalities into a single device capable of the measurement of hydrogen peroxide and total cholesterol. The single-use device employed printed electrochemical sensors for hydrogen peroxide electroreduction integrated with printed electrochromic display and battery. The system was driven by a conventional electronic circuit designed to illustrate the complete integration of silicon integrated circuits via pick and place or using organic electronic circuits. The device was capable of measuring 8 μL samples of both hydrogen peroxide (0-5 mM, 2.72 × 10 -6 A·mM -1 ) and total cholesterol in serum from 0 to 9 mM (1.34 × 10 -8 A·mM -1 , r 2 = 0.99, RSD < 10%, n = 3), and the result was output on a semiquantitative linear bar display. The device could operate for 10 min via a printed battery, and display the result for many hours or days. A mobile phone "app" was also capable of reading the test result and transmitting this to a remote health care provider. Such a technology could allow improved management of conditions such as hypercholesterolemia.

ACER Physics Unit Tests: Unit Tests, Diagnostic Aids, [and] Teachers Handbook.

ERIC Educational Resources Information Center

Australian Council for Educational Research, Hawthorn.

The Physics Unit Tests are designed to assist in the diagnostic evaluation of students' progress in the study of physics during the last two years of secondary schooling. They consist of a collection of 21 separate tests, each related to a different topic, and 21 diagnostic aids corresponding to the tests. The topics covered are: physical…

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

PubMed

Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

2018-01-01

Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India

PubMed Central

Raizada, Neeraj; Khaparde, Sunil D.; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M.; Singh, Varinder; Umadevi, K. R.; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C. H. Surya; Mall, Shalini; Singh, Pooja; Saha, B. K.; Denkinger, Claudia M.; Boehme, Catharina

2018-01-01

Background Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. Methods A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. Results The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65–8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9–9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. Conclusion The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population. PMID:29489887

Current and future molecular diagnostics for ocular infectious diseases.

PubMed

Doan, Thuy; Pinsky, Benjamin A

2016-11-01

Confirmation of ocular infections can pose great challenges to the clinician. A fundamental limitation is the small amounts of specimen that can be obtained from the eye. Molecular diagnostics can circumvent this limitation and have been shown to be more sensitive than conventional culture. The purpose of this review is to describe new molecular methods and to discuss the applications of next-generation sequencing-based approaches in the diagnosis of ocular infections. Efforts have focused on improving the sensitivity of pathogen detection using molecular methods. This review describes a new molecular target for Toxoplasma gondii-directed polymerase chain reaction assays. Molecular diagnostics for Chlamydia trachomatis and Acanthamoeba species are also discussed. Finally, we describe a hypothesis-free approach, metagenomic deep sequencing, which can detect DNA and RNA pathogens from a single specimen in one test. In some cases, this method can provide the geographic location and timing of the infection. Pathogen-directed PCRs have been powerful tools in the diagnosis of ocular infections for over 20 years. The use of next-generation sequencing-based approaches, when available, will further improve sensitivity of detection with the potential to improve patient care.

Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays.

PubMed

Goay, Yuan Xin; Chin, Kai Ling; Tan, Clarissa Ling Ling; Yeoh, Chiann Ying; Ja'afar, Ja'afar Nuhu; Zaidah, Abdul Rahman; Chinni, Suresh Venkata; Phua, Kia Kien

2016-01-01

Salmonella Typhi ( S . Typhi) causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S . Typhi with other enteric pathogens was performed, and 6 S . Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico . Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro . The diagnostic sensitivities and specificities of each assay were determined using 39 S . Typhi, 62 non-Typhi Salmonella , and 10 non- Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39) and 100% specificity (0/72). The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

Diagnosis of pheochromocytoma in the setting of Parkinson disease.

PubMed

Mehta, Shyamal H; Prakash, Rajan; Prisant, L Michael; Isales, Carlos M; Morgan, John C; Williams, Hadyn; Sethi, Kapil D

2009-06-01

A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

Current and future molecular approaches in the diagnosis of cystic fibrosis.

PubMed

Bergougnoux, Anne; Taulan-Cadars, Magali; Claustres, Mireille; Raynal, Caroline

2018-05-01

Cystic Fibrosis is among the first diseases to have general population genetic screening tests and one of the most common indications of prenatal and preimplantation genetic diagnosis for single gene disorders. During the past twenty years, thanks to the evolution of diagnostic techniques, our knowledge of CFTR genetics and pathophysiological mechanisms involved in cystic fibrosis has significantly improved. Areas covered: Sanger sequencing and quantitative methods greatly contributed to the identification of more than 2,000 sequence variations reported worldwide in the CFTR gene. We are now entering a new technological age with the generalization of high throughput approaches such as Next Generation Sequencing and Droplet Digital PCR technologies in diagnostics laboratories. These powerful technologies open up new perspectives for scanning the entire CFTR locus, exploring modifier factors that possibly influence the clinical evolution of patients, and for preimplantation and prenatal diagnosis. Expert commentary: Such breakthroughs would, however, require powerful bioinformatics tools and relevant functional tests of variants for analysis and interpretation of the resulting data. Ultimately, an optimal use of all those resources may improve patient care and therapeutic decision-making.

Simultaneous sensing of temperature, CO, and CO2 in a scramjet combustor using quantum cascade laser absorption spectroscopy

NASA Astrophysics Data System (ADS)

Spearrin, R. M.; Goldenstein, C. S.; Schultz, I. A.; Jeffries, J. B.; Hanson, R. K.

2014-07-01

A mid-infrared laser absorption sensor was developed for gas temperature and carbon oxide (CO, CO2) concentrations in high-enthalpy, hydrocarbon combustion flows. This diagnostic enables non-intrusive, in situ measurements in harsh environments produced by hypersonic propulsion ground test facilities. The sensing system utilizes tunable quantum cascade lasers capable of probing the fundamental mid-infrared absorption bands of CO and CO2 in the 4-5 µm wavelength domain. A scanned-wavelength direct absorption technique was employed with two lasers, one dedicated to each species, free-space fiber-coupled using a bifurcated hollow-core fiber for remote light delivery on a single line of sight. Scanned-wavelength modulation spectroscopy with second-harmonic detection was utilized to extend the dynamic range of the CO measurement. The diagnostic was field-tested on a direct-connect scramjet combustor for ethylene-air combustion. Simultaneous, laser-based measurements of carbon monoxide and carbon dioxide provide a basis for evaluating combustion completion or efficiency with temporal and spatial resolution in practical hydrocarbon-fueled engines.

[Clinical examination of the hip joint in adults].

PubMed

Grifka, J; Keshmiri, A; Maderbacher, G; Craiovan, B

2014-12-01

Complaints in the region of the hips and pelvis are often difficult to classify. This is due to the fact that pain projection and overlapping can occur; therefore, the complete region of the lumbar spine, pelvis and hips must be considered as a single entity in which alterations can result in radiation throughout the whole region. There are many different anatomical structures within the pelvic region so that the function of various muscle components can be impaired and cause pathological alterations to positional relationships of bony structures or even alterations to other soft tissues, such as ligaments, tendons and labra. In terms of differential diagnostics the groin must be seen as the weak point of the peritoneum and vascular system and taken into consideration. Therefore, a detailed and targeted medical history, functional testing and specific examinations and tests are necessary to narrow down the pathology in question and reach a definitive diagnosis. Orthopedic surgeons must know which conspicuous features can lead to which problems and which anatomical structures are likely to be affected by irritation. The results of the clinical examination are the basis for targeted imaging diagnostics and subsequent therapy.

[Clinical examination of the hip joint in adults].

PubMed

Grifka, J; Keshmiri, A; Maderbacher, G; Craiovan, B

2015-07-01

Complaints in the region of the hips and pelvis are often difficult to classify. This is due to the fact that pain projection and overlapping can occur; therefore, the complete region of the lumbar spine, pelvis and hips must be considered as a single entity in which alterations can result in radiation throughout the whole region. There are many different anatomical structures within the pelvic region so that the function of various muscle components can be impaired and cause pathological alterations to positional relationships of bony structures or even alterations to other soft tissues, such as ligaments, tendons and labra. In terms of differential diagnostics the groin must be seen as the weak point of the peritoneum and vascular system and taken into consideration. Therefore, a detailed and targeted medical history, functional testing and specific examinations and tests are necessary to narrow down the pathology in question and reach a definitive diagnosis. Orthopedic surgeons must know which conspicuous features can lead to which problems and which anatomical structures are likely to be affected by irritation. The results of the clinical examination are the basis for targeted imaging diagnostics and subsequent therapy.

Efficient fault diagnosis of helicopter gearboxes

NASA Technical Reports Server (NTRS)

Chin, H.; Danai, K.; Lewicki, D. G.

1993-01-01

Application of a diagnostic system to a helicopter gearbox is presented. The diagnostic system is a nonparametric pattern classifier that uses a multi-valued influence matrix (MVIM) as its diagnostic model and benefits from a fast learning algorithm that enables it to estimate its diagnostic model from a small number of measurement-fault data. To test this diagnostic system, vibration measurements were collected from a helicopter gearbox test stand during accelerated fatigue tests and at various fault instances. The diagnostic results indicate that the MVIM system can accurately detect and diagnose various gearbox faults so long as they are included in training.

Ambiguous genitalia: what prenatal genetic testing is practical?

PubMed

Adam, Margaret P; Fechner, Patricia Y; Ramsdell, Linda A; Badaru, Angela; Grady, Richard E; Pagon, Roberta A; McCauley, Elizabeth; Cheng, Edith Y; Parisi, Melissa A; Shnorhavorian, Margarett

2012-06-01

Concern for ambiguous genitalia or chromosome-phenotype discordance detected in a prenatal setting has increased over the last two decades. Practitioners faced with this prenatal finding have a variety of genetic tests available to them; however, it is unclear to what extent prenatal testing for disorders of sex development (DSD) is useful or practical. We undertook a retrospective review of the medical records of 140 individuals evaluated through the DSD clinic at Seattle Children's Hospital with birthdates from 01/01/1994 through 08/16/2011 to determine the rate of prenatal detection of ambiguous genitalia in individuals with DSD, what prenatal diagnostic workup was undertaken, and the postnatal outcome, including whether a postnatal genetic diagnosis was confirmed. Of all 140 subjects, 34 (24%) were identified prenatally. The most common postnatal diagnoses were penoscrotal hypospadias with transposition of the scrotum with no known genetic cause (24/140; 17%) and 21-hydroxylase deficiency (20/140; 14%). Apart from these, no single diagnosis comprised more than a few cases. Prenatal diagnostic testing varied widely, from no tests to multiple molecular tests with amniotic fluid hormone concentrations. In the absence of other fetal anomalies or growth retardation on ultrasound, prenatal karyotype with fluorescence in situ hybridization for the SRY gene is the most useful test when ambiguous genitalia is suspected. Further prenatal testing for Smith-Lemli-Opitz syndrome in 46,XY individuals and congenital adrenal hyperplasia in 46,XX individuals may be considered. However, targeted molecular testing for rare DSD conditions in the absence of a family history of DSD has a low yield. Copyright © 2012 Wiley Periodicals, Inc.

The impact of new trends in POCTs for companion diagnostics, non-invasive testing and molecular diagnostics.

PubMed

Huckle, David

2015-06-01

Point-of-care diagnostics have been slowly developing over several decades and have taken on a new importance in current healthcare delivery for both diagnostics and development of new drugs. Molecular diagnostics have become a key driver of technology change and opened up new areas in companion diagnostics for use alongside pharmaceuticals and in new clinical approaches such as non-invasive testing. Future areas involving smartphone and other information technology advances, together with new developments in molecular biology, microfluidics and surface chemistry are adding to advances in the market. The focus for point-of-care tests with molecular diagnostic technologies is focused on advancing effective applications.

Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens

PubMed Central

Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert

2018-01-01

Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae. Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae, N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology. PMID:29425124

Evaluation of an Internally Controlled Multiplex Tth Endonuclease Cleavage Loop-Mediated Isothermal Amplification (TEC-LAMP) Assay for the Detection of Bacterial Meningitis Pathogens.

PubMed

Higgins, Owen; Clancy, Eoin; Cormican, Martin; Boo, Teck Wee; Cunney, Robert; Smith, Terry J

2018-02-09

Bacterial meningitis infection is a leading global health concern for which rapid and accurate diagnosis is essential to reduce associated morbidity and mortality. Loop-mediated isothermal amplification (LAMP) offers an effective low-cost diagnostic approach; however, multiplex LAMP is difficult to achieve, limiting its application. We have developed novel real-time multiplex LAMP technology, TEC-LAMP, using Tth endonuclease IV and a unique LAMP primer/probe. This study evaluates the analytical specificity, limit of detection (LOD) and clinical application of an internally controlled multiplex TEC-LAMP assay for detection of leading bacterial meningitis pathogens: Streptococcus pneumoniae , Neisseria meningitidis and Haemophilus influenzae . Analytical specificities were established by testing 168 bacterial strains, and LODs were determined using Probit analysis. The TEC-LAMP assay was 100% specific, with LODs for S. pneumoniae , N. meningitidis and H. influenzae of 39.5, 17.3 and 25.9 genome copies per reaction, respectively. Clinical performance was evaluated by testing 65 archived PCR-positive samples. Compared to singleplex real-time PCR, the multiplex TEC-LAMP assay demonstrated diagnostic sensitivity and specificity of 92.3% and 100%, respectively. This is the first report of a single-tube internally controlled multiplex LAMP assay for bacterial meningitis pathogen detection, and the first report of Tth endonuclease IV incorporation into nucleic acid amplification diagnostic technology.

[Laboratory diagnostics and monitoring of virus circulation in surveillance system for rubella in Belarus].

PubMed

Samoĭlovich, E O; Semeĭko, G V; Ermolovich, M A; Svirchevskaia, E Iu

2010-01-01

To summarize data on laboratory diagnostics of prenatal and postnatal rubella and molecular monitoring of rubella virus circulation in Belarus obtained during implementation of rubella elimination program. Serum samples from 2314 persons were tested on the presence of IgM to rubella virus and measles virus (in case of negative result on rubella) using respective enzyme immunoassays. Virological testing using RT-PCR as well as genotyping on the basis of E1 gene fragment sequencing were also performed. Two viruses isolated in Belarus were set as reference strains of genotypes 1G and 1h. Implementation of laboratory diagnostics allowed to differentiate cases of rubella from other exanthematous infections, significantly increase the number of laboratory-confirmed cases among all reported cases, and show presence of endemic circulation of rubella virus strains of 3 different genotypes (1G, 1E, and 1h) in Belarus (2004-2006). In 2006, when relatively high incidence of rubella was reported in the country (24.39 per 100,000 population), the risk of congenital rubella syndrome was not less than 9 per 100,000 births. Conducted in October 2005-May 2006 additional rounds of immunization against rubella (>1 million people were vaccinated) decreased incidence to single cases. Obtained data show achievability of indigenous rubella elemination by 2010. Revealed genetic diversity of rubella virus strains allowed to update the International classification of wild rubella viruses.

A facility for gas- and condensed-phase measurements behind shock waves

NASA Astrophysics Data System (ADS)

Petersen, Eric L.; Rickard, Matthew J. A.; Crofton, Mark W.; Abbey, Erin D.; Traum, Matthew J.; Kalitan, Danielle M.

2005-09-01

A shock-tube facility consisting of two, single-pulse shock tubes for the study of fundamental processes related to gas-phase chemical kinetics and the formation and reaction of solid and liquid aerosols at elevated temperatures is described. Recent upgrades and additions include a new high-vacuum system, a new gas-handling system, a new control system and electronics, an optimized velocity-detection scheme, a computer-based data acquisition system, several optical diagnostics, and new techniques and procedures for handling experiments involving gas/powder mixtures. Test times on the order of 3 ms are possible with reflected-shock pressures up to 100 atm and temperatures greater than 4000 K. Applications for the shock-tube facility include the study of ignition delay times of fuel/oxidizer mixtures, the measurement of chemical kinetic reaction rates, the study of fundamental particle formation from the gas phase, and solid-particle vaporization, among others. The diagnostic techniques include standard differential laser absorption, FM laser absorption spectroscopy, laser extinction for particle volume fraction and size, temporally and spectrally resolved emission from gas-phase species, and a scanning mobility particle sizer for particle size distributions. Details on the set-up and operation of the shock tube and diagnostics are given, the results of a detailed uncertainty analysis on the accuracy of the test temperature inferred from the incident-shock velocity are provided, and some recent results are presented.

Adverse Food Reaction and Functional Gastrointestinal Disorders: Role of the Dietetic Approach.

PubMed

Pasqui, Francesca; Poli, Carolina; Colecchia, Antonio; Marasco, Giovanni; Festi, Davide

2015-09-01

Bloating, abdominal discomfort or pain, disturbed bowel habits are very common symptoms, frequently reported by the patients soon after food ingestion. These symptoms may occur in different clinical conditions, such as functional bowel disorders, food adverse reactions, gluten-related syndromes, which frequently are interrelated. Consequently, in clinical practice, it is necessary to perform a correct diagnosis in order to identify, for the single patient, the most appropriate therapeutic strategy, which may include not only specific drugs, but also, and mainly, life style changes (healthy nutritional behavior and constant physical activity). The aim of this review is to provide to the general physician, according to the available evidence, the most appropriate diagnostic work-ups for recognizing the different clinical scenarios (i.e. food allergy and intolerance, functional bowel diseases, gluten-related syndromes), to identify their clinical interrelationships and to suggest the most appropriate management. In fact, as far as food intolerances are concerned, it is well known that the number of patients who believe that their symptoms are related to food intolerance is increasing and consequently they restrict their diet, possibly causing nutritional deficiencies. Furthermore, there is an increasing use of unconventional diagnostic tests for food intolerance which lack accurate scientific evidence; the application of their results may induce misdiagnosis and unhealthy therapeutic choices. Consequently the recognition of food intolerance has to be performed on the basis of reliable tests within an agreed diagnostic workup.

Evaluation of the Parasight Platform for Malaria Diagnosis

PubMed Central

Eshel, Yochay; Houri-Yafin, Arnon; Benkuzari, Hagai; Lezmy, Natalie; Soni, Mamta; Charles, Malini; Swaminathan, Jayanthi; Solomon, Hilda; Sampathkumar, Pavithra; Premji, Zul; Mbithi, Caroline; Nneka, Zaitun; Onsongo, Simon; Maina, Daniel; Levy-Schreier, Sarah; Cohen, Caitlin Lee; Gluck, Dan; Pollak, Joseph Joel

2016-01-01

ABSTRACT The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site. PMID:27974542

42 CFR 419.2 - Basis of payment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... prospective payment system establishes a national payment rate, standardized for geographic wage differences...) Capital-related costs; (9) Implantable items used in connection with diagnostic X-ray tests, diagnostic laboratory tests, and other diagnostic tests; (10) Durable medical equipment that is implantable; (11...

Comparison of the Diagnostic Accuracy of Three Rapid Tests for the Serodiagnosis of Hepatic Cystic Echinococcosis in Humans

PubMed Central

Tamarozzi, Francesca; Covini, Ilaria; Mariconti, Mara; Narra, Roberta; Tinelli, Carmine; De Silvestri, Annalisa; Manzoni, Federica; Casulli, Adriano; Ito, Akira; Neumayr, Andreas; Brunetti, Enrico

2016-01-01

Background The diagnosis of cystic echinococcosis (CE) is based primarily on imaging, in particular with ultrasound for abdominal CE, complemented by serology when imaging results are unclear. In rural endemic areas, where expertise in ultrasound may be scant and conventional serology techniques are unavailable due to lack of laboratory equipment, Rapid Diagnostic Tests (RDTs) are appealing. Methodology/Principal Findings We evaluated the diagnostic accuracy of 3 commercial RDTs for the diagnosis of hepatic CE. Sera from 59 patients with single hepatic CE cysts in well-defined ultrasound stages (gold standard) and 25 patients with non-parasitic cysts were analyzed by RDTs VIRapid HYDATIDOSIS (Vircell, Spain), Echinococcus DIGFA (Unibiotest, China), ADAMU-CE (ICST, Japan), and by RIDASCREEN Echinococcus IgG ELISA (R-Biopharm, Germany). Sensitivity, specificity and ROC curves were compared with McNemar and t-test. For VIRapid and DIGFA, correlation between semiquantitative results and ELISA OD values were evaluated by Spearman’s coefficient. Reproducibility was assessed on 16 randomly selected sera with Cohen’s Kappa coefficient. Sensitivity and Specificity of VIRapid (74%, 96%) and ADAMU-CE (57%, 100%) did not differ from ELISA (69%, 96%) while DIGFA (72%, 72%) did (p = 0.045). ADAMU-CE was significantly less sensitive in the diagnosis of active cysts (p = 0.019) while DIGFA was significantly less specific (p = 0.014) compared to ELISA. All tests were poorly sensitive in diagnosing inactive cysts (33.3% ELISA and ADAMU-CE, 42.8% DIGFA, 47.6% VIRapid). The reproducibility of all RDTs was good-very good. Band intensity of VIRapid and DIGFA correlated with ELISA OD values (r = 0.76 and r = 0.79 respectively, p<0.001). Conclusions/Significance RDTs may be useful in resource-poor settings to complement ultrasound diagnosis of CE in uncertain cases. VIRapid test appears to perform best among the examined kits, but all tests are poorly sensitive in the presence of inactive cysts, which may pose problems with accurate diagnosis. PMID:26871432

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study.

PubMed

Timper, Katharina; Fenske, Wiebke; Kühn, Felix; Frech, Nica; Arici, Birsen; Rutishauser, Jonas; Kopp, Peter; Allolio, Bruno; Stettler, Christoph; Müller, Beat; Katan, Mira; Christ-Crain, Mirjam

2015-06-01

The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging. The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome. This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia. A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response. Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity. This study was limited by incorporation bias from including AVP levels as a diagnostic criterion. Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

PubMed

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

High sensitivity Troponin T: an audit of implementation of its protocol in a district general hospital.

PubMed

Kalim, Shahid; Nazir, Shaista; Khan, Zia Ullah

2013-01-01

Protocols based on newer high sensitivity Troponin T (hsTropT) assays can rule in a suspected Acute Myocardial Infarction (AMI) as early as 3 hours. We conducted this study to audit adherence to our Trust's newly introduced AMI diagnostic protocol based on paired hsTropT testing at 0 and 3 hours. We retrospectively reviewed data of all patients who had hsTropT test done between 1st and 7th May 2012. Patient's demographics, utility of single or paired samples, time interval between paired samples, patient's presenting symptoms and ECG findings were noted and their means, medians, Standard deviations and proportions were calculated. A total of 66 patients had hsTropT test done during this period. Mean age was 63.30 +/- 17.46 years and 38 (57.57%) were males. Twenty-four (36.36%) patients had only single, rather than protocol recommended paired hsTropT samples, taken. Among the 42 (63.63%) patients with paired samples, the mean time interval was found to be 4.41 +/- 5.7 hours. Contrary to the recommendations, 15 (22.73%) had a very long whereas 2 (3.03%) had a very short time interval between two samples. A subgroup analysis of patients with single samples, found only 2 (3.03%) patient with ST-segment elevation, appropriate for single testing. Our study confirmed that in a large number of patients the protocol for paired sampling or a recommended time interval of 3 hours between 2 samples was not being followed.

Aptima HIV-1 Quant Dx--A fully automated assay for both diagnosis and quantification of HIV-1.

PubMed

Nair, Sangeetha Vijaysri; Kim, Hee Cheol; Fortunko, Jacqueline; Foote, Tracy; Peling, Tashi; Tran, Cuong; Nugent, Charles Thomas; Joo, Sunghae; Kang, Youna; Wilkins, Bana; Lednovich, Kristen; Worlock, Andrew

2016-04-01

Separate assays are available for diagnosis and viral load (VL) monitoring of HIV-1. Studies have shown that using a single test for both confirmatory diagnosis and VL increases linkage to care. To validate a single assay for both diagnosis and VL monitoring of HIV-1 on the fully automated Panther platform. Validate the assay by assessing specificity, sensitivity, subtype detection, seroconversion, reproducibility and linearity. Also assess diagnostic agreement with the Procleix(®) Ultrio Elite™ discriminatory assay (Procleix), and agreement of VL results (method comparison) with Ampliprep/COBAS TaqMan HIV-1 version 2.0 (CAP/CTM), using clinical samples. The assay was specific (100%) and sensitive with a 95% limit of detection of 12 copies/mL with the 3rd WHO standards. Aptima detected HIV in seroconversion panels 6 and 11 days before p24 antigen and antibody tests, respectively. Diagnostic agreement with Procleix, was 100%. Regression analysis showed good agreement of VL results between Aptima and CAP/CTM with a slope of 1.02, intercept of 0.07, and correlation coefficient (R(2)) of 0.97. Aptima was more sensitive than CAP/CTM. Equivalent quantification was seen on testing clinical samples and isolates belonging to HIV group M, N, O and P and commercially available subtype panels. Assay results were linear (R(2) 0.9994) with standard deviation of <0.17 log copies across assay range. The good specificity, sensitivity, precision, subtype performance and clinical agreement with other assays demonstrated by Aptima combined with the complete automation provided by the Panther platform makes Aptima a good candidate for both VL monitoring and diagnosis of HIV-1. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Device for wavelength-selective imaging

DOEpatents

Frangioni, John V.

2010-09-14

An imaging device captures both a visible light image and a diagnostic image, the diagnostic image corresponding to emissions from an imaging medium within the object. The visible light image (which may be color or grayscale) and the diagnostic image may be superimposed to display regions of diagnostic significance within a visible light image. A number of imaging media may be used according to an intended application for the imaging device, and an imaging medium may have wavelengths above, below, or within the visible light spectrum. The devices described herein may be advantageously packaged within a single integrated device or other solid state device, and/or employed in an integrated, single-camera medical imaging system, as well as many non-medical imaging systems that would benefit from simultaneous capture of visible-light wavelength images along with images at other wavelengths.

9 CFR 93.406 - Diagnostic tests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Diagnostic tests. 93.406 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Ruminants § 93.406 Diagnostic tests. (a) Tuberculosis and brucellosis tests of cattle. Except as provided in paragraph (d) of this section and in §§ 93.418, 93.427(d), and 93...

9 CFR 93.406 - Diagnostic tests.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Diagnostic tests. 93.406 Section 93... CONVEYANCE AND SHIPPING CONTAINERS Ruminants § 93.406 Diagnostic tests. (a) Tuberculosis and brucellosis tests of cattle. Except as provided in paragraph (d) of this section and in §§ 93.418, 93.427(d), and 93...

Primary care validation of a single-question alcohol screening test.

PubMed

Smith, Peter C; Schmidt, Susan M; Allensworth-Davies, Donald; Saitz, Richard

2009-07-01

Unhealthy alcohol use is prevalent but under-diagnosed in primary care settings. To validate, in primary care, a single-item screening test for unhealthy alcohol use recommended by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Cross-sectional study. Adult English-speaking patients recruited from primary care waiting rooms. Participants were asked the single screening question, “How many times in the past year have you had X or more drinks in a day?”, where X is 5 for men and 4 for women, and a response of 1 or greater [corrected] is considered positive. Unhealthy alcohol use was defined as the presence of an alcohol use disorder, as determined by a standardized diagnostic interview, or risky consumption, as determined using a validated 30-day calendar method. Of 394 eligible primary care patients, 286 (73%) completed the interview. The single-question screen was 81.8% sensitive (95% confidence interval (CI) 72.5% to 88.5%) and 79.3% specific (95% CI 73.1% to 84.4%) for the detection of unhealthy alcohol use. It was slightly more sensitive (87.9%, 95% CI 72.7% to 95.2%) but was less specific (66.8%, 95% CI 60.8% to 72.3%) for the detection of a current alcohol use disorder. Test characteristics were similar to that of a commonly used three-item screen, and were affected very little by subject demographic characteristics. The single screening question recommended by the NIAAA accurately identified unhealthy alcohol use in this sample of primary care patients. These findings support the use of this brief screen in primary care.

A Three-Tier Diagnostic Test to Assess Pre-Service Teachers' Misconceptions about Global Warming, Greenhouse Effect, Ozone Layer Depletion, and Acid Rain

ERIC Educational Resources Information Center

Arslan, Harika Ozge; Cigdemoglu, Ceyhan; Moseley, Christine

2012-01-01

This study describes the development and validation of a three-tier multiple-choice diagnostic test, the atmosphere-related environmental problems diagnostic test (AREPDiT), to reveal common misconceptions of global warming (GW), greenhouse effect (GE), ozone layer depletion (OLD), and acid rain (AR). The development of a two-tier diagnostic test…

Improving clinical cognitive testing

PubMed Central

Gale, Seth A.; Barrett, A.M.; Boeve, Bradley F.; Chatterjee, Anjan; Coslett, H. Branch; D'Esposito, Mark; Finney, Glen R.; Gitelman, Darren R.; Hart, John J.; Lerner, Alan J.; Meador, Kimford J.; Pietras, Alison C.; Voeller, Kytja S.; Kaufer, Daniel I.

2015-01-01

Objective: To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment. Methods: Behavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain. Results: Demographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE. Conclusions: We identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment. PMID:26163433

Development and evaluation of an in-house single step loop-mediated isothermal amplification (SS-LAMP) assay for the detection of Mycobacterium tuberculosis complex in sputum samples from Moroccan patients.

PubMed

Bentaleb, El Mehdi; Abid, Mohammed; El Messaoudi, My Driss; Lakssir, Brahim; Ressami, El Mostafa; Amzazi, Saaïd; Sefrioui, Hassan; Ait Benhassou, Hassan

2016-09-27

Tuberculosis (TB) is a major global health problem and remains the leading cause of morbidity and mortality in developing countries. Routinely used TB diagnostic methods, in most endemic areas, are time-consuming, often less-sensitive, expensive and inaccessible to most patients. Therefore, there is an urgent need for the development of early, easy to use and effective diagnosis tools of TB, which can be effectively integrated into resource limited settings, to anticipate the early treatment and limit further spread of the disease. Over the last decade, Loop-mediated isothermal amplification (LAMP) assays have become a powerful tool for rapid diagnosis of infectious diseases because of the simplicity of device requirements. Indeed, LAMP is a simple, quick and cost effective Isothermal Nucleic Acid Amplification diagnostic test (INAAT) that has the potential to be used in TB endemic settings of resource-poor countries. In the present study, we have developed a simple and rapid TB molecular diagnostic test using a Single-Step Loop-mediated isothermal DNA amplification (SS-LAMP) method for the detection of Mycobacterium tuberculosis complex (MTBC) strains, with a simplified sample preparation procedure, eliminating DNA extraction prior to LAMP amplification, DNA initial denaturation and enzymatic inactivation steps during the amplification process. To perform our in-house SS-LAMP assay, a set of six specific primers was specifically designed to recognize eight distinct regions on the MTBC species-specific repetitive insertion sequence 6110 (IS6110). The amplification of the targeted DNA was carried out under isothermal conditions at 65 °C within 1 h. Our protocol was firstly optimized using 60 of confirmed MTBC isolates and a recombinant pGEMeasy-IS6110 vector for sensitivity testing. Thereafter, the assay was evaluated on liquefied sputum specimens collected from 157 Moroccan patients suspected of having TB. Our SS-LAMP developed assay was able to detect MTBC DNA directly from liquefied sputum samples without any prior DNA extraction, denaturation nor the final enzymatic inactivation step. When compared to routinely used Löwenstein Jensen (LJ) Culture method, our SS-LAMP assay is rapid and showed specificity and sensitivity of 99.14 % and 82.93 % respectively which are within the international standards. In addition, the limit of detection of our assay was found to be as little as 10 copies of bacterial DNA. To our knowledge, this is the first study using a single step LAMP (SS-LAMP) procedure as a rapid, easy to perform and cost effective testing for TB early detection. This innovative assay could be suitable for low-income countries with restricted health equipment facilities.

In Vitro Measures for Assessing Boar Semen Fertility.

PubMed

Jung, M; Rüdiger, K; Schulze, M

2015-07-01

Optimization of artificial insemination (AI) for pig production and evaluation of the fertilizing capacity of boar semen are highly related. Field studies have demonstrated significant variation in semen quality and fertility. The semen quality of boars is primarily affected by breed and season. AI centres routinely examine boar semen to predict male fertility. Overall, the evaluation of classical parameters, such as sperm morphology, sperm motility, sperm concentration and ejaculate volume, allows the identification of ejaculates corresponding to poor fertility but not high-efficiency prediction of field fertility. The development of new sperm tests for measuring certain sperm functions has attempted to solve this problem. Fluorescence staining can categorize live and dead spermatozoa in the ejaculate and identify spermatozoa with active mitochondria. Computer-assisted semen analysis (CASA) provides an objective assessment of multiple kinetic sperm parameters. However, sperm tests usually assess only single factors involved in the fertilization process. Thus, basing prediction of fertilizing capacity on a selective collection of sperm tests leads to greater accuracy than using single tests. In the present brief review, recent diagnostic laboratory methods that directly relate to AI performance as well as the development of a new boar fertility in vitro index are discussed. © 2015 Blackwell Verlag GmbH.

Setting up a probe based, closed tube real-time PCR assay for focused detection of variable sequence alterations.

PubMed

Becságh, Péter; Szakács, Orsolya

2014-10-01

During diagnostic workflow when detecting sequence alterations, sometimes it is important to design an algorithm that includes screening and direct tests in combination. Normally the use of direct test, which is mainly sequencing, is limited. There is an increased need for effective screening tests, with "closed tube" during the whole process and therefore decreasing the risk of PCR product contamination. The aim of this study was to design such a closed tube, detection probe based screening assay to detect different kind of sequence alterations in the exon 11 of the human c-kit gene region. Inside this region there are variable possible deletions and single nucleotide changes. During assay setup, more probe chemistry formats were screened and tested. After some optimization steps the taqman probe format was selected.

Investigation of Singly Ionized Iodine Spectroscopy in Support of Electrostatic Propulsion Diagnostics Development

DTIC Science & Technology

2012-07-02

from complex user interactions due to the use of liquid lasing medium with finite lifetime. Solid state lasers such as titanium sapphire (Ti:Sapphire...transitions for laser -induced fluorescence of an accelerated atomic iodine singly charged ion (I+). While the second spectrum of iodine has been analyzed...diagnostics tools, such as laser -induced fluorescence (LIF), to examine the plasma acceleration within an electro-static plasma propulsion thruster. While

Usefulness of the ARCHITECT Chagas® assay as a single test for the diagnosis of chronic Chagas disease.

PubMed

Pérez-Ayala, Ana; Fradejas, Isabel; Rebollo, Lourdes; Lora-Pablos, David; Lizasoain, Manuel; Herrero-Martínez, Juan María

2018-06-01

Imported Chagas disease (CD) is an emerging health problem in Europe due to immigration from endemic countries. Although WHO currently recommends two different serological methods to establish diagnosis, new tools like the ARCHITECT Chagas assay have potential for use as a single diagnostic test. Our objective was to determine an optimal signal-to-cut-off (S/CO) value for the ARCHITECT Chagas assay to diagnose CD with a single test. A retrospective study conducted at the 12 de Octubre University Hospital (Madrid, Spain). All patients with requests for Chagas screening between January 2014 and August 2017 were consecutively included. All samples were routinely tested with the ARCHITECT assay. Negative samples (S/CO < 0.8) required no further testing. Immunochromatographic testing (ICT) and/or indirect immunofluorescence (IFI) was used to confirm samples with S/CO ≥ 0.8. Receiver operator characteristic (ROC) curve analysis determined the ARCHITECT S/CO value that yielded 100% specificity and positive predictive value. SPSS software, version 22.0 was used for data analysis. A total of 4153 samples were analysed; 361 (8.69%) gave a reactive ARCHITECT Chagas result. 261/361 (72.3%) were women; median age was 38 years old (2-79). 92.8% were Bolivian. A total of 307 (85.0%) were confirmed as cases of Chagas; 52 (14.4%) were not infected; two (0.6%) were not evaluable. Seroprevalence was 7.39%. An S/CO ≥ 3.80 yielded 100% specificity (95% confidence interval [CI], 0.93-1.00) and 100% positive predictive value (95% CI, 0.99-1.00). Using S/CO ≥ 3.80, the ARCHITECT Chagas could be used as a single test for diagnosis of chronic CD in Bolivian immigrants. Patients with S/CO between 0.80 and 3.80 would require additional testing. © 2018 John Wiley & Sons Ltd.

Diagnostic methods for insect sting allergy.

PubMed

Hamilton, Robert G

2004-08-01

This review overviews advances from mid-2002 to the present in the validation and performance methods used in the diagnosis of Hymenoptera venom-induced immediate-type hypersensitivity. The general diagnostic algorithm for insect sting allergy is initially discussed with an examination of the AAAAI's 2003 revised practice parameter guidelines. Changes as a result of a greater recognition of skin test negative systemic reactors include repeat analysis of all testing and acceptance of serology as a complementary diagnostic test to the skin test. Original data examining concordance of venom-specific IgE results produced by the second-generation Pharmacia CAP System with the Johns Hopkins University radioallergosorbent test are presented. Diagnostic performance of honeybee venom-specific IgE assays used in clinical laboratories in North America is discussed using data from the Diagnostic Allergy Proficiency Survey conducted by the College of American Pathologists. Validity of venom-specific IgE antibody in postmortem blood specimens is demonstrated. The utility of alternative in-vivo (provocation) and in-vitro (basophil-based) diagnostic testing methods is critiqued. This overview supports the following conclusions. Improved practice parameter guidelines include serology and skin test as complementary in supporting a positive clinical history during the diagnostic process. Data are provided which support the analytical performance of commercially available venom-specific IgE antibody serology-based assays. Intentional sting challenge in-vivo provocation, in-vitro basophil flow cytometry (CD63, CD203c) based assays, and in-vitro basophil histamine and sulfidoleukotriene release assays have their utility in the study of difficult diagnostic cases, but their use will remain as supplementary, secondary diagnostic tests.

Comparison of diagnostic methods in the evaluation of onychomycosis.

PubMed

Haghani, Iman; Shokohi, Tahereh; Hajheidari, Zohreh; Khalilian, Alireza; Aghili, Seyed Reza

2013-04-01

Onychomycosis is a common nail problem, accounting for up to half of all nail diseases. Several nail disorders may mimic the onychomycosis clinically. Therefore, a sensitive, quick, and inexpensive test is essential for screening nail specimens for the administration of the proper drug. The aim of this study was to compare 4 different diagnostic methods in the evaluation of onychomycosis and to determine their sensitivity, specificity, positive predictive value, and negative predictive value. In a cross-sectional study, nail specimens were collected from 101 patients suspected to have onychomycosis during a 14-month period. The nail specimens were examined using potassium hydroxide (KOH) 20 %, KOH-treated nail clipping stained with periodic acid-Schiff (KONCPA), and calcofluor white (CFW) stain, and grew a fungal culture. The culture was chosen as the gold standard for statistical analysis using the McNemar and chi-square tests. Out of 101 patients, 100 (99 %) patients had at least 1 of the 4 diagnostic methods positive for the presence of organisms. The positive rates for the fungal culture, KOH preparation, CFW, and KONCPA were 74.2, 85.1, 91.09, and 99.01 %, respectively. The sensitivity and negative predictive value of KONCPA was 100 %. KONCPA was the most sensitive among the tests and was also superior to other methods in its negative predictive value. KONCPA was easy to perform, rapid, and gave significantly higher rates of detection of onychomycosis compared to the standard methods of KOH preparation and fungal culture. Therefore, KONCPA should be the single method of choice for the evaluation of onychomycosis.

Normal pressure hydrocephalus: survey on contemporary diagnostic algorithms and therapeutic decision-making in clinical practice.

PubMed

Krauss, J K; Halve, B

2004-04-01

There is no agreement on the best diagnostic criteria for selecting patients with normal pressure hydrocephalus (NPH) for CSF shunting. The primary objective of the present study was to provide a contemporary survey on diagnostic algorithms and therapeutic decision-making in clinical practice. The secondary objective was to estimate the incidence of NPH. Standardized questionnaires with sections on the incidence of NPH and the frequency of shunting, evaluation of clinical symptoms, and signs, diagnostic studies, therapeutic decision-making and operative techniques, postoperative outcome and complications, and the profiles of different centers, were sent to 82 neurosurgical centers in Germany known to participate in the care of patients with NPH. Data were analyzed from 49 of 53 centers which responded to the survey (65%). The estimated annual incidence of NPH was 1.8 cases/100.000 inhabitants. Gait disturbance was defined as the most important sign of NPH (61%). There was a wide variety in the choice of diagnostic tests. Cisternography was performed routinely only in single centers. Diagnostic CSF removal was used with varying frequency by all centers except one, but the amount of CSF removed by lumbar puncture differed markedly between centers. There was poor agreement on criteria for evaluation of continuous intracranial pressure recordings regarding both the amplitude and the relative frequency of B-waves. Both periventricular and deep white matter lesions were present in about 50% of patients being shunted, indicating that vascular comorbidity in NPH patients has gained more acceptance. Programmable shunts were used by more than half of the centers, and newer valve types such as gravitational valves have become more popular. According to the present survey, new diagnostic and therapeutic concepts on NPH have penetrated daily routine to a certain extent. Wide variability, however, still exists among different neurosurgical centers.

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

WE-AB-206-01: Diagnostic Ultrasound Imaging Quality Assurance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zagzebski, J.

The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. The goal of this ultrasound hands-on workshop is to demonstrate quality control (QC) testing in diagnostic ultrasound and to provide updates in ACR ultrasound accreditation requirements. The first half of this workshop will include two presentations reviewing diagnostic ultrasound QA/QC and ACR ultrasound accreditation requirements. The second half of the workshop will include live demonstrations of basic QC tests. An array of ultrasound testing phantoms and ultrasound scanners will be available for attendees to learn diagnostic ultrasound QC in a hands-on environmentmore » with live demonstrations and on-site instructors. The targeted attendees are medical physicists in diagnostic imaging. Learning Objectives: Gain familiarity with common elements of a QA/QC program for diagnostic ultrasound imaging dentify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools Learn ACR ultrasound accreditation requirements Jennifer Walter is an employee of American College of Radiology on Ultrasound Accreditation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maestas, J.H.

The Loopback Tester is an Intel SBC 86/12A Single Board Computer and an Intel SBC 534 Communications Expansion Board configured and programmed to perform various basic or less. These tests include: (1) Data Communications Equipment (DCE) transmit timing detection (2) data rate measurement (3) instantaneous loopback indication and (4) bit error rate testing. It requires no initial setup after plug in, and can be used to locate the source of communications loss in a circuit. It can also be used to determine when crypto variable mismatch problems are the source of communications loss. This report discusses the functionality of themore » Loopback Tester as a diagnostic device. It also discusses the hardware and software which implements this simple yet reliable device.« less

Combining destination diversion decisions and critical in-flight event diagnosis in computer aided testing of pilots

NASA Technical Reports Server (NTRS)

Rockwell, T. H.; Giffin, W. C.; Romer, D. J.

1984-01-01

Rockwell and Giffin (1982) and Giffin and Rockwell (1983) have discussed the use of computer aided testing (CAT) in the study of pilot response to critical in-flight events. The present investigation represents an extension of these earlier studies. In testing pilot responses to critical in-flight events, use is made of a Plato-touch CRT system operating on a menu based format. In connection with the typical diagnostic problem, the pilot was presented with symptoms within a flight scenario. In one problem, the pilot has four minutes for obtaining the information which is needed to make a diagnosis of the problem. In the reported research, the attempt has been made to combine both diagnosis and diversion scenario into a single computer aided test. Tests with nine subjects were conducted. The obtained results and their significance are discussed.

Use of a three-band HRP2/pLDH combination rapid diagnostic test increases diagnostic specificity for falciparum malaria in Ugandan children.

PubMed

Hawkes, Michael; Conroy, Andrea L; Opoka, Robert O; Namasopo, Sophie; Liles, W Conrad; John, Chandy C; Kain, Kevin C

2014-02-01

Rapid diagnostic tests (RDTs) for malaria provide a practical alternative to light microscopy for malaria diagnosis in resource-limited settings. Three-band RDTs incorporating two parasite antigens may have enhanced diagnostic specificity, relative to two-band RDTs with a single parasite antigen (typically histidine-rich protein 2 [HRP2]). Phase 1: 2,000 children, two months to five years of age, admitted to a referral hospital in Jinja, Uganda, with acute febrile illness were enrolled. A WHO highly rated three-band RDT was compared to light microscopy of thick peripheral blood films read by local expert microscopists.Phase 2: the three-band RDT was used as a screening tool for inclusion of patients in a clinical trial, and subjects with three positive RDT bands were tested by microscopy using blood samples drawn in parallel. Discordant results were adjudicated by PCR. Phase 1: 1,648 children had both a RDT and peripheral blood smear performed. The specificity of a RDT with all three bands positive was 82% (95% CI: 79-85%) compared to 62% (95% CI: 59-66%) for HRP2 alone. The sensitivity was 88% (95% CI: 85-89%) and 94% (95% CI: 92-95%) for three-band positive RDT and HRP2 antigen, respectively. 119 patients (7.2%) had a positive HRP2 band, but negative parasite lactate dehydrogenase (pLHD) band and negative peripheral smear, and 72 (61%) of these had received pre-treatment with anti-malarials, suggesting a false positive HRP2 result (p = 0.002).Phase 2: the positive predictive value (PPV) of the three-band RDT was 94% (95% CI 89%-97%) using microscopy as the reference standard. However, microscopy-discordant results were shown to be positive for P. falciparum by PCR in all cases, suggesting that the PPV was in fact higher. The pLDH antigen on three-band RDTs, used in combination with HRP2, provides added diagnostic specificity for malaria parasitaemia and may be useful to distinguish acute infection from recently treated infection. In situations where diagnostic specificity is desirable (e.g., for selection of malaria-infected participants in clinical trials), a three-band RDT should be considered in a sub-Saharan African setting.

2012 HIV Diagnostics Conference: the molecular diagnostics perspective.

PubMed

Branson, Bernard M; Pandori, Mark

2013-04-01

2012 HIV Diagnostic Conference Atlanta, GA, USA, 12-14 December 2012. This report highlights the presentations and discussions from the 2012 National HIV Diagnostic Conference held in Atlanta (GA, USA), on 12-14 December 2012. Reflecting changes in the evolving field of HIV diagnostics, the conference provided a forum for evaluating developments in molecular diagnostics and their role in HIV diagnosis. In 2010, the HIV Diagnostics Conference concluded with the proposal of a new diagnostic algorithm which included nucleic acid testing to resolve discordant screening and supplemental antibody test results. The 2012 meeting, picking up where the 2010 meeting left off, focused on scientific presentations that assessed this new algorithm and the role played by RNA testing and new developments in molecular diagnostics, including detection of total and integrated HIV-1 DNA, detection and quantification of HIV-2 RNA, and rapid formats for detection of HIV-1 RNA.

Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline

PubMed Central

Kapur, Vishesh K.; Auckley, Dennis H.; Chowdhuri, Susmita; Kuhlmann, David C.; Mehra, Reena; Ramar, Kannan; Harrod, Christopher G.

2017-01-01

Introduction: This guideline establishes clinical practice recommendations for the diagnosis of obstructive sleep apnea (OSA) in adults and is intended for use in conjunction with other American Academy of Sleep Medicine (AASM) guidelines on the evaluation and treatment of sleep-disordered breathing in adults. Methods: The AASM commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use. In addition, the task force adopted foundational recommendations from prior guidelines as “good practice statements”, that establish the basis for appropriate and effective diagnosis of OSA. The AASM Board of Directors approved the final recommendations. Recommendations: The following recommendations are intended as a guide for clinicians diagnosing OSA in adults. Under GRADE, a STRONG recommendation is one that clinicians should follow under most circumstances. A WEAK recommendation reflects a lower degree of certainty regarding the outcome and appropriateness of the patient-care strategy for all patients. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. Good Practice Statements: Diagnostic testing for OSA should be performed in conjunction with a comprehensive sleep evaluation and adequate follow-up. Polysomnography is the standard diagnostic test for the diagnosis of OSA in adult patients in whom there is a concern for OSA based on a comprehensive sleep evaluation. Recommendations: We recommend that clinical tools, questionnaires and prediction algorithms not be used to diagnose OSA in adults, in the absence of polysomnography or home sleep apnea testing. (STRONG)We recommend that polysomnography, or home sleep apnea testing with a technically adequate device, be used for the diagnosis of OSA in uncomplicated adult patients presenting with signs and symptoms that indicate an increased risk of moderate to severe OSA. (STRONG)We recommend that if a single home sleep apnea test is negative, inconclusive, or technically inadequate, polysomnography be performed for the diagnosis of OSA. (STRONG)We recommend that polysomnography, rather than home sleep apnea testing, be used for the diagnosis of OSA in patients with significant cardiorespiratory disease, potential respiratory muscle weakness due to neuromuscular condition, awake hypoventilation or suspicion of sleep related hypoventilation, chronic opioid medication use, history of stroke or severe insomnia. (STRONG)We suggest that, if clinically appropriate, a split-night diagnostic protocol, rather than a full-night diagnostic protocol for polysomnography be used for the diagnosis of OSA. (WEAK)We suggest that when the initial polysomnogram is negative and clinical suspicion for OSA remains, a second polysomnogram be considered for the diagnosis of OSA. (WEAK) Citation: Kapur VK, Auckley DH, Chowdhuri S, Kuhlmann DC, Mehra R, Ramar K, Harrod CG. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(3):479–504. PMID:28162150

Diagnosis of aphasia in stroke populations: A systematic review of language tests

PubMed Central

2018-01-01

Background and purpose Accurate aphasia diagnosis is important in stroke care. A wide range of language tests are available and include informal assessments, tests developed by healthcare institutions and commercially published tests available for purchase in pre-packaged kits. The psychometrics of these tests are often reported online or within the purchased test manuals, not the peer-reviewed literature, therefore the diagnostic capabilities of these measures have not been systematically evaluated. This review aimed to identify both commercial and non-commercial language tests and tests used in stroke care and to examine the diagnostic capabilities of all identified measures in diagnosing aphasia in stroke populations. Methods Language tests were identified through a systematic search of 161 publisher databases, professional and resource websites and language tests reported to be used in stroke care. Two independent reviewers evaluated test manuals or associated resources for cohort or cross-sectional studies reporting the tests’ diagnostic capabilities (sensitivity, specificity, likelihood ratios or diagnostic odds ratios) in differentiating aphasic and non-aphasic stroke populations. Results Fifty-six tests met the study eligibility criteria. Six “non-specialist” brief screening tests reported sensitivity and specificity information, however none of these measures reported to meet the specific diagnostic needs of speech pathologists. The 50 remaining measures either did not report validity data (n = 7); did not compare patient test performance with a comparison group (n = 17); included non-stroke participants within their samples (n = 23) or did not compare stroke patient performance against a language reference standard (n = 3). Diagnostic sensitivity analysis was completed for six speech pathology measures (WAB, PICA, CADL-2, ASHA-FACS, Adult FAVRES and EFA-4), however all studies compared aphasic performance with that of non-stroke healthy controls and were consequently excluded from the review. Conclusions No speech pathology test was found which reported diagnostic data for identifying aphasia in stroke populations. A diagnostically validated post-stroke aphasia test is needed. PMID:29566043