Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice.

PubMed

Trevethan, Robert

2017-01-01

Within the context of screening tests, it is important to avoid misconceptions about sensitivity, specificity, and predictive values. In this article, therefore, foundations are first established concerning these metrics along with the first of several aspects of pliability that should be recognized in relation to those metrics. Clarification is then provided about the definitions of sensitivity, specificity, and predictive values and why researchers and clinicians can misunderstand and misrepresent them. Arguments are made that sensitivity and specificity should usually be applied only in the context of describing a screening test's attributes relative to a reference standard; that predictive values are more appropriate and informative in actual screening contexts, but that sensitivity and specificity can be used for screening decisions about individual people if they are extremely high; that predictive values need not always be high and might be used to advantage by adjusting the sensitivity and specificity of screening tests; that, in screening contexts, researchers should provide information about all four metrics and how they were derived; and that, where necessary, consumers of health research should have the skills to interpret those metrics effectively for maximum benefit to clients and the healthcare system.

Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice

PubMed Central

Trevethan, Robert

2017-01-01

Within the context of screening tests, it is important to avoid misconceptions about sensitivity, specificity, and predictive values. In this article, therefore, foundations are first established concerning these metrics along with the first of several aspects of pliability that should be recognized in relation to those metrics. Clarification is then provided about the definitions of sensitivity, specificity, and predictive values and why researchers and clinicians can misunderstand and misrepresent them. Arguments are made that sensitivity and specificity should usually be applied only in the context of describing a screening test’s attributes relative to a reference standard; that predictive values are more appropriate and informative in actual screening contexts, but that sensitivity and specificity can be used for screening decisions about individual people if they are extremely high; that predictive values need not always be high and might be used to advantage by adjusting the sensitivity and specificity of screening tests; that, in screening contexts, researchers should provide information about all four metrics and how they were derived; and that, where necessary, consumers of health research should have the skills to interpret those metrics effectively for maximum benefit to clients and the healthcare system. PMID:29209603

Airway hyperresponsiveness to methacholine in 7-year-old children: sensitivity and specificity for pediatric allergist-diagnosed asthma.

PubMed

Carlsten, Chris; Dimich-Ward, Helen; Ferguson, Alexander; Becker, Allan; Dybuncio, Anne; Chan-Yeung, Moira

2011-02-01

The operating characteristics of PC(20) values used as cut-offs to define airway hyperresponsiveness, as it informs the diagnosis of asthma in children, are poorly understood. We examine data from a unique cohort to inform this concern. Determine the sensitivity and specificity of incremental PC(20) cut-offs for allergist-diagnosed asthma. Airway reactivity at age 7 was assessed in children within a birth cohort at high risk for asthma; PC(20) for methacholine was determined by standard technique including interpolation. The diagnosis of asthma was considered by the pediatric allergist without knowledge of the methacholine challenge results. Sensitivity and specificity were calculated using a cross-tabulation of asthma diagnosis with incremental PC(20) cut-off values, from 1.0 to 8.0 mg/ml, and plotted as receiver operator characteristic (ROC) curves. The "optimal" cut-off was defined as that PC(20) conferring maximal value for sensitivity plus specificity while the "balanced" cut-off was defined as that PC(20) at which sensitivity and specificity were most equal. 70/348 children (20.1%) were diagnosed with asthma. The optimal and balanced PC(20) cut-offs, both for all children and for females alone, were respectively 3 mg/ml (sensitivity 80.0%, specificity 49.1%) and 2 mg/ml (sensitivity 63.1%, specificity 64.7%). For males alone, the "optimal" and "balanced" PC(20) cut-offs were both 2 mg/ml. For this cohort of 7-year olds at high risk for asthma, methacholine challenge testing using a cut-off value of PC(20) 3 mg/ml conferred the maximal sum of specificity plus sensitivity. For contexts in which higher sensitivity or specificity is desired, other cut-offs may be preferred. Copyright © 2011 Wiley-Liss, Inc.

Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low fat but not a low carbohydrate diet in obese women

PubMed Central

Gray, Dona L.; O’Brien, Kevin D.; D’Alessio, David A.; Brehm, Bonnie J.; Deeg, Mark A.

2013-01-01

Context Although circulating glycosylphosphatidylinositol-specific phospholipase D, a minor high density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of weight loss or changes in insulin sensitivity on circulating glycosylphosphatidylinositol-specific phospholipase D levels. Objective Determine the effect of weight loss and changes in insulin sensitivity on plasma glycosylphosphatidylinositol-specific phospholipase D levels. Participants Forty two non-diabetic obese women. Intervention Three month dietary intervention randomizing patients to a low fat or a low carbohydrate diet. Main outcome measures Plasma glycosylphosphatidylinositol-specific phospholipase D levels and insulin sensitivity as estimated by the homeostasis model assessment. Results The very low carbohydrate diet group lost more weight after 3 months (−7.6 ± 3.2 vs. −4.2 ± 3.5 kg, P < 0.01) although the decrease in insulin resistance was similar between groups. Weight loss with either diet did not alter plasma glycosylphosphatidylinositol-specific phospholipase D levels. However, baseline glycosylphosphatidylinositol-specific phospholipase D levels correlated with the change in insulin sensitivity in response to the low fat diet while baseline insulin sensitivity correlated the change in insulin sensitivity in response to the low carbohydrate diet. Conclusions Plasma GPI-PLD may serve as a clinical tool to determine the effect of a low fat diet on insulin sensitivity. PMID:18328347

Simplified HCC-ART score for highly sensitive detection of small-sized and early-stage hepatocellular carcinoma in the widely used Okuda, CLIP, and BCLC staging systems.

PubMed

Attallah, Abdelfattah M; Omran, Mohamed M; Attallah, Ahmed A; Abdelrazek, Mohamed A; Farid, Khaled; El-Dosoky, Ibrahim

2017-04-01

Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC. 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC. Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8). The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

PubMed

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L

2016-01-01

Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi

PubMed Central

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L.

2016-01-01

Background Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. Objective To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Methods Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Results Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). Conclusion The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis. PMID:27171380

Comparison of loop-mediated isothermal amplification assay and smear microscopy with culture for the diagnostic accuracy of tuberculosis.

PubMed

Gelaw, Baye; Shiferaw, Yitayal; Alemayehu, Marta; Bashaw, Abate Assefa

2017-01-17

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required. Hence, we assessed the diagnostic performance of Loop-mediated isothermal amplification (LAMP) assay in detecting M.tuberculosis infection in sputum sample compared to LED fluorescent smear microscopy and culture. A cross-sectional study was conducted at the University of Gondar Hospital from June 01, 2015 to August 30, 2015. Pulmonary TB diagnosis using sputum LED fluorescence smear microscopy, TB-LAMP assay and culture were done. A descriptive analysis was used to determine demographic characteristics of the study participants. Analysis of sensitivity and specificity for smear microscopy and TB-LAMP compared with culture as a reference test was performed. Cohen's kappa was calculated as a measure of agreement between the tests. A total of 78 pulmonary presumptive TB patients sputum sample were analyzed. The overall sensitivity and specificity of LAMP were 75 and 98%, respectively. Among smear negative sputum samples, 33.3% sensitivity and 100% specificity of LAMP were observed. Smear microscopy showed 78.6% sensitivity and 98% specificity. LAMP and smear in series had sensitivity of 67.8% and specificity of 100%. LAMP and smear in parallel had sensitivity of 85.7% and specificity of 96%. The agreement between LAMP and fluorescent smear microscopy tests was very good (κ = 0.83, P-value ≤0.0001). TB-LAMP showed similar specificity but a slightly lower sensitivity with LED fluorescence microscopy. The specificity of LAMP and smear microscopy in series was high. The sensitivity of LAMP was insufficient for smear negative sputum samples.

Sensitivity and specificity of a brief personality screening instrument in predicting future substance use, emotional, and behavioral problems: 18-month predictive validity of the Substance Use Risk Profile Scale.

PubMed

Castellanos-Ryan, Natalie; O'Leary-Barrett, Maeve; Sully, Laura; Conrod, Patricia

2013-01-01

This study assessed the validity, sensitivity, and specificity of the Substance Use Risk Profile Scale (SURPS), a measure of personality risk factors for substance use and other behavioral problems in adolescence. The concurrent and predictive validity of the SURPS was tested in a sample of 1,162 adolescents (mean age: 13.7 years) using linear and logistic regressions, while its sensitivity and specificity were examined using the receiver operating characteristics curve analyses. Concurrent and predictive validity tests showed that all 4 brief scales-hopelessness (H), anxiety sensitivity (AS), impulsivity (IMP), and sensation seeking (SS)-were related, in theoretically expected ways, to measures of substance use and other behavioral and emotional problems. Results also showed that when using the 4 SURPS subscales to identify adolescents "at risk," one can identify a high number of those who developed problems (high sensitivity scores ranging from 72 to 91%). And, as predicted, because each scale is related to specific substance and mental health problems, good specificity was obtained when using the individual personality subscales (e.g., most adolescents identified at high risk by the IMP scale developed conduct or drug use problems within the next 18 months [a high specificity score of 70 to 80%]). The SURPS is a valuable tool for identifying adolescents at high risk for substance misuse and other emotional and behavioral problems. Implications of findings for the use of this measure in future research and prevention interventions are discussed. Copyright © 2012 by the Research Society on Alcoholism.

Performance of a time-resolved fluorescence immunoassay for measuring varicella-zoster virus immunoglobulin G levels in adults and comparison with commercial enzyme immunoassays and Merck glycoprotein enzyme immunoassay.

PubMed

Maple, P A C; Gray, J; Breuer, J; Kafatos, G; Parker, S; Brown, D

2006-02-01

Highly sensitive and specific, quantitative assays are needed to detect varicella-zoster virus (VZV) immunoglobulin G in human sera, particularly for determining immune status and response following vaccination. A time-resolved fluorescence immunoassay (TRFIA) has been developed, and its performance was compared to that of two commercial enzyme immunoassays (EIAs) and Merck glycoprotein EIA (gpEIA). The TRFIA had equivalent sensitivity (97.8%) and high specificity (93.5%) in relation to gpEIA. A commercial (Behring) EIA compared favorably with TRFIA in terms of sensitivity (98.4%) but had lower specificity (80.7%). Another commercial EIA (Diamedix) had high specificity (97.1%) but low sensitivity (76.4%) compared to TRFIA if equivocal test results were treated as negative for VZV antibody. A novel feature of the TRFIA was that the cutoff was generated using population mixture modeling and was expressed in mIU/ml, as the assay was calibrated using the British standard VZV antibody.

Clinical inquiries. What test is the best for diagnosing infectious mononucleosis?

PubMed

Bell, Amy Trelease; Fortune, Barbara; Sheeler, Robert

2006-09-01

Tests for antibodies to Epstein-Barr viral capsid antigen or Epstein-Barr nuclear antigen are the most sensitive, are highly specific, and are also the most expensive for diagnosing infectious mononucleosis (strength of recommendation [SOR]: C, based on validating cohort study). Heterophile antibody tests have similar specificity and are cheaper, but are less sensitive in children or in adults during the early days of the illness (SOR: C, based on validating cohort study). The polymerase chain reaction assay for Epstein-Barr virus DNA is more sensitive than the heterophile antibody test in children, is highly specific, but is also expensive (SOR: C, based on validating cohort study). The percentages of atypical lymphocytes and total lymphocytes on a complete blood count provide another specific and moderately sensitive, yet inexpensive, test (SOR: C, based on validating cohort study).

Glaucoma progression detection: agreement, sensitivity, and specificity of expert visual field evaluation, event analysis, and trend analysis.

PubMed

Antón, Alfonso; Pazos, Marta; Martín, Belén; Navero, José Manuel; Ayala, Miriam Eleonora; Castany, Marta; Martínez, Patricia; Bardavío, Javier

2013-01-01

To assess sensitivity, specificity, and agreement among automated event analysis, automated trend analysis, and expert evaluation to detect glaucoma progression. This was a prospective study that included 37 eyes with a follow-up of 36 months. All had glaucomatous disks and fields and performed reliable visual fields every 6 months. Each series of fields was assessed with 3 different methods: subjective assessment by 2 independent teams of glaucoma experts, glaucoma/guided progression analysis (GPA) event analysis, and GPA (visual field index-based) trend analysis. Kappa agreement coefficient between methods and sensitivity and specificity for each method using expert opinion as gold standard were calculated. The incidence of glaucoma progression was 16% to 18% in 3 years but only 3 cases showed progression with all 3 methods. Kappa agreement coefficient was high (k=0.82) between subjective expert assessment and GPA event analysis, and only moderate between these two and GPA trend analysis (k=0.57). Sensitivity and specificity for GPA event and GPA trend analysis were 71% and 96%, and 57% and 93%, respectively. The 3 methods detected similar numbers of progressing cases. The GPA event analysis and expert subjective assessment showed high agreement between them and moderate agreement with GPA trend analysis. In a period of 3 years, both methods of GPA analysis offered high specificity, event analysis showed 83% sensitivity, and trend analysis had a 66% sensitivity.

Head-To-Head Comparison Between High- and Standard-b-Value DWI for Detecting Prostate Cancer: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Kim, Sang Youn; Cho, Jeong Yeon; Kim, Seung Hyup

2018-01-01

The purpose of this study was to perform a head-to-head comparison between high-b-value (> 1000 s/mm 2 ) and standard-b-value (800-1000 s/mm 2 ) DWI regarding diagnostic performance in the detection of prostate cancer. The MEDLINE and EMBASE databases were searched up to April 1, 2017. The analysis included diagnostic accuracy studies in which high- and standard-b-value DWI were used for prostate cancer detection with histopathologic examination as the reference standard. Methodologic quality was assessed with the revised Quality Assessment of Diagnostic Accuracy Studies tool. Sensitivity and specificity of all studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Meta-regression and multiple-subgroup analyses were performed to compare the diagnostic performances of high- and standard-b-value DWI. Eleven studies (789 patients) were included. High-b-value DWI had greater pooled sensitivity (0.80 [95% CI, 0.70-0.87]) (p = 0.03) and specificity (0.92 [95% CI, 0.87-0.95]) (p = 0.01) than standard-b-value DWI (sensitivity, 0.78 [95% CI, 0.66-0.86]); specificity, 0.87 [95% CI, 0.77-0.93] (p < 0.01). Multiple-subgroup analyses showed that specificity was consistently higher for high- than for standard-b-value DWI (p ≤ 0.05). Sensitivity was significantly higher for high- than for standard-b-value DWI only in the following subgroups: peripheral zone only, transition zone only, multiparametric protocol (DWI and T2-weighted imaging), visual assessment of DW images, and per-lesion analysis (p ≤ 0.04). In a head-to-head comparison, high-b-value DWI had significantly better sensitivity and specificity for detection of prostate cancer than did standard-b-value DWI. Multiple-subgroup analyses showed that specificity was consistently superior for high-b-value DWI.

Brief assessment of food insecurity accurately identifies high-risk US adults.

PubMed

Gundersen, Craig; Engelhard, Emily E; Crumbaugh, Amy S; Seligman, Hilary K

2017-06-01

To facilitate the introduction of food insecurity screening into clinical settings, we examined the test performance of two-item screening questions for food insecurity against the US Department of Agriculture's Core Food Security Module. We examined sensitivity, specificity and accuracy of various two-item combinations of questions assessing food insecurity in the general population and high-risk population subgroups. 2013 Current Population Survey December Supplement, a population-based US survey. All survey participants from the general population and high-risk subgroups. The test characteristics of multiple two-item combinations of questions assessing food insecurity had adequate sensitivity (>97 %) and specificity (>70 %) for widespread adoption as clinical screening measures. We recommend two specific items for clinical screening programmes based on their widespread current use and high sensitivity for detecting food insecurity. These items query how often the household 'worried whether food would run out before we got money to buy more' and how often 'the food that we bought just didn't last and we didn't have money to get more'. The recommended items have sensitivity across high-risk population subgroups of ≥97 % and a specificity of ≥74 % for food insecurity.

Self-diagnosis of active head lice infestation by individuals from an impoverished community: high sensitivity and specificity.

PubMed

Pilger, Daniel; Khakban, Adak; Heukelbach, Jorg; Feldmeier, Hermann

2008-01-01

To compare sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-diagnosis for head lice infestation with visual inspection, we conducted a study in an urban slum in Brazil. Individuals were asked about active head lice infestation (self-diagnosis); we performed visual inspection and thereafter wet combing (gold standard). Of the 175 individuals included, 77 (44%) had an active head lice infestation. For self-diagnosis, sensitivity (80.5%), specificity (91.8%), PPV (88.6%) and NPV (85.7%) were high. Sensitivity of visual inspection was 35.1%. Public health professionals can use self-diagnosis as a diagnostic tool, to estimate accurately prevalence of pediculosis in a community, and to monitor ongoing intervention strategies.

Sensitivity and specificity: twin goals of proteomics assays. Can they be combined?

PubMed

Wilson, Robert

2013-04-01

A major ambition of proteomics is the provision of assays that can diagnose disease and monitor therapies. These assays are required to be sensitive and specific for individual proteins, and in most cases to quantify more than one protein in the same sample. The two main technologies currently used for proteomics assays are based on mass spectrometry and panels of affinity molecules such as antibodies. In the first part of this review the most sensitive existing assays based on these technologies are described and compared with the gold standard of ELISA. Analytical sensitivity is defined and related to the limit of detection, and analytical specificity is defined and shown to depend on molecular proofreading steps, similar to those applied in living systems whenever there is a need for high fidelity. It is shown that at present neither mass spectrometry nor panels of affinity molecules offer the necessary combination of sensitivity and specificity required for multiplexed assays. In the second part of this review the growing numbers of assays that use additional proofreading steps to combine sensitivity with specificity are described. These include assays based on proximity ligation and slow off-rate modified aptamers. Finally the review considers what improvements might be possible in the near future, and concludes that further development of proteomics assays incorporating advanced proofreading steps are most likely to provide the necessary combination of sensitivity and specificity, without incurring high development costs.

Nested PCR Assay for Eight Pathogens: A Rapid Tool for Diagnosis of Bacterial Meningitis.

PubMed

Bhagchandani, Sharda P; Kubade, Sushant; Nikhare, Priyanka P; Manke, Sonali; Chandak, Nitin H; Kabra, Dinesh; Baheti, Neeraj N; Agrawal, Vijay S; Sarda, Pankaj; Mahajan, Parikshit; Ganjre, Ashish; Purohit, Hemant J; Singh, Lokendra; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

2016-02-01

Bacterial meningitis is a dreadful infectious disease with a high mortality and morbidity if remained undiagnosed. Traditional diagnostic methods for bacterial meningitis pose a challenge in accurate identification of pathogen, making prognosis difficult. The present study is therefore aimed to design and evaluate a specific and sensitive nested 16S rDNA genus-based polymerase chain reaction (PCR) assay using clinical cerebrospinal fluid (CSF) for rapid diagnosis of eight pathogens causing the disease. The present work was dedicated to development of an in-house genus specific 16S rDNA nested PCR covering pathogens of eight genera responsible for causing bacterial meningitis using newly designed as well as literature based primers for respective genus. A total 150 suspected meningitis CSF obtained from the patients admitted to Central India Institute of Medical Sciences (CIIMS), India during the period from August 2011 to May 2014, were used to evaluate clinical sensitivity and clinical specificity of optimized PCR assays. The analytical sensitivity and specificity of our newly designed genus-specific 16S rDNA PCR were found to be ≥92%. With such a high sensitivity and specificity, our in-house nested PCR was able to give 100% sensitivity in clinically confirmed positive cases and 100% specificity in clinically confirmed negative cases indicating its applicability in clinical diagnosis. Our in-house nested PCR system therefore can diagnose the accurate pathogen causing bacterial meningitis and therefore be useful in selecting a specific treatment line to minimize morbidity. Results are obtained within 24 h and high sensitivity makes this nested PCR assay a rapid and accurate diagnostic tool compared to traditional culture-based methods.

High Sensitivity and Specificity of Clinical Microscopy in Rural Health Facilities in Western Kenya Under an External Quality Assurance Program

PubMed Central

Wafula, Rebeccah; Sang, Edna; Cheruiyot, Olympia; Aboto, Angeline; Menya, Diana; O'Meara, Wendy Prudhomme

2014-01-01

Microscopic diagnosis of malaria is a well-established and inexpensive technique that has the potential to provide accurate diagnosis of malaria infection. However, it requires both training and experience. Although it is considered the gold standard in research settings, the sensitivity and specificity of routine microscopy for clinical care in the primary care setting has been reported to be unacceptably low. We established a monthly external quality assurance program to monitor the performance of clinical microscopy in 17 rural health centers in western Kenya. The average sensitivity over the 12-month period was 96% and the average specificity was 88%. We identified specific contextual factors that contributed to inadequate performance. Maintaining high-quality malaria diagnosis in high-volume, resource-constrained health facilities is possible. PMID:24935953

Highly sensitive and specific colorimetric detection of cancer cells via dual-aptamer target binding strategy.

PubMed

Wang, Kun; Fan, Daoqing; Liu, Yaqing; Wang, Erkang

2015-11-15

Simple, rapid, sensitive and specific detection of cancer cells is of great importance for early and accurate cancer diagnostics and therapy. By coupling nanotechnology and dual-aptamer target binding strategies, we developed a colorimetric assay for visually detecting cancer cells with high sensitivity and specificity. The nanotechnology including high catalytic activity of PtAuNP and magnetic separation & concentration plays a vital role on the signal amplification and improvement of detection sensitivity. The color change caused by small amount of target cancer cells (10 cells/mL) can be clearly distinguished by naked eyes. The dual-aptamer target binding strategy guarantees the detection specificity that large amount of non-cancer cells and different cancer cells (10(4) cells/mL) cannot cause obvious color change. A detection limit as low as 10 cells/mL with detection linear range from 10 to 10(5) cells/mL was reached according to the experimental detections in phosphate buffer solution as well as serum sample. The developed enzyme-free and cost effective colorimetric assay is simple and no need of instrument while still provides excellent sensitivity, specificity and repeatability, having potential application on point-of-care cancer diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensitivity and specificity of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen and optic disc oedema: optic disc drusen and oedema.

PubMed

Gili, Pablo; Flores-Rodríguez, Patricia; Yangüela, Julio; Orduña-Azcona, Javier; Martín-Ríos, María Dolores

2013-03-01

Evaluation of the efficacy of monochromatic photography of the ocular fundus in differentiating optic nerve head drusen (ONHD) and optic disc oedema (ODE). Sixty-six patients with ONHD, 31 patients with ODE and 70 healthy subjects were studied. Colour and monochromatic fundus photography with different filters (green, red and autofluorescence) were performed. The results were analysed blindly by two observers. The sensitivity, specificity and interobserver agreement (k) of each test were assessed. Colour photography offers 65.5 % sensitivity and 100 % specificity for the diagnosis of ONHD. Monochromatic photography improves sensitivity and specificity and provides similar results: green filter (71.20 % sensitivity, 96.70 % specificity), red filter (80.30 % sensitivity, 96.80 % specificity), and autofluorescence technique (87.8 % sensitivity, 100 % specificity). The interobserver agreement was good with all techniques used: autofluorescence (k = 0.957), green filter (k = 0.897), red filter (k = 0.818) and colour (k = 0.809). Monochromatic fundus photography permits ONHD and ODE to be differentiated, with good sensitivity and very high specificity. The best results were obtained with autofluorescence and red filter study.

Enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii based on enhanced chemiluminescence.

PubMed Central

Crouch, C F

1995-01-01

AIMS--To evaluate the clinical performance of enzyme immunoassays for IgG and IgM antibodies to Toxoplasma gondii based on enhanced chemiluminescence. METHODS--Classification of routine clinical samples from the originating laboratories was compared with that obtained using the chemiluminescence based assays. Resolution of discordant results was achieved by testing in alternative enzyme immunoassays (IgM) or by an independent laboratory using the dye test (IgG). RESULTS--Compared with resolved data, the IgM assay was found to be highly specific (100%) with a cut off selected to give optimal performance with respect to both the early detection of specific IgM and the detection of persistent levels of specific IgM (sensitivity 98%). Compared with resolved data, the IgG assay was shown to have a sensitivity and a specificity of 99.4%. CONCLUSIONS--The Amerlite Toxo IgM assay possesses high levels of sensitivity and specificity. Assay interference due to rheumatoid factor like substances is not a problem. The Amerlite Toxo IgG assay possesses good sensitivity and specificity, but is less sensitive for the detection of seroconversion than methods detecting both IgG and IgM. PMID:7560174

Novel approach based on one-tube nested PCR and a lateral flow strip for highly sensitive diagnosis of tuberculous meningitis.

PubMed

Sun, Yajuan; Chen, Jiajun; Li, Jia; Xu, Yawei; Jin, Hui; Xu, Na; Yin, Rui; Hu, Guohua

2017-01-01

Rapid and sensitive detection of Mycobacterium tuberculosis (M. Tb) in cerebrospinal fluid is crucial in the diagnosis of tuberculous meningitis (TBM), but conventional diagnostic technologies have limited sensitivity and specificity or are time-consuming. In this work, a novel, highly sensitive molecular diagnostic method, one-tube nested PCR-lateral flow strip test (OTNPCR-LFST), was developed for detecting M. tuberculosis. This one-tube nested PCR maintains the sensitivity of conventional two-step nested PCR and reduces both the chance of cross-contamination and the time required for analysis. The PCR product was detected by a lateral flow strip assay, which provided a basis for migration of the test to a point-of-care (POC) microfluidic format. The developed assay had an improved sensitivity compared with traditional PCR, and the limit of detection was up to 1 fg DNA isolated from M. tuberculosis. The assay was also specific for M. tuberculosis, and no cross-reactions were found in other non-target bacteria. The application of this technique to clinical samples was successfully evaluated, and OTNPCR-LFST showed 89% overall sensitivity and 100% specificity for TBM patients. This one-tube nested PCR-lateral flow strip assay is useful for detecting M. tuberculosis in TBM due to its rapidity, high sensitivity and simple manipulation.

Real-Time, Single-Step Bioassay Using Nanoplasmonic Resonator With Ultra-High Sensitivity

NASA Technical Reports Server (NTRS)

Zhang, Xiang (Inventor); Chen, Fanqing Frank (Inventor); Su, Kai-Hang (Inventor); Wei, Qi-Huo (Inventor); Ellman, Jonathan A. (Inventor); Sun, Cheng (Inventor)

2014-01-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

Real-time, single-step bioassay using nanoplasmonic resonator with ultra-high sensitivity

DOEpatents

Zhang, Xiang; Ellman, Jonathan A; Chen, Fanqing Frank; Su, Kai-Hang; Wei, Qi-Huo; Sun, Cheng

2014-04-01

A nanoplasmonic resonator (NPR) comprising a metallic nanodisk with alternating shielding layer(s), having a tagged biomolecule conjugated or tethered to the surface of the nanoplasmonic resonator for highly sensitive measurement of enzymatic activity. NPRs enhance Raman signals in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at picomolar sensitivity levels. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background in real-time single-step detection in very small sample volumes.

The role of oncogenic human papillomavirus determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM.

PubMed

Burgos, Joaquin; Hernández-Losa, Javier; Landolfi, Stefania; Guelar, Ana; Dinares, MªCarmen; Villar, Judith; Navarro, Jordi; Ribera, Esteve; Falcó, Vicenç; Curran, Adria

2017-10-23

To assess the oncogenic human papillomavirus (HPV) determination and the cotesting HPV and anal cytology value to detect high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-MSM. Prospective study of HIV-infected MSM who underwent screening for anal dysplasia. Screening program includes anal cytology, HPV testing, and high-resolution anoscopy (HRA) at each visit. Histological samples were obtained if suspicious lesions were revealed by HRA. Sensitivity and specificity of the different tests were calculated by using histological results of HRA-guided biopsy as the reference test for HGAIN diagnosis. From May 2009 to August 2016, 692 HIV-infected MSM underwent 1827 anal cytologies, 1841 HRA examinations, and 1607 HPV testing. At first screening visit, anal cytology results were abnormal in 418 (60.4%) of 692 patients, and oncogenic HPV genotypes were found in 482 (79.5%) of 606 patients. Anal cytology showed a sensitivity of 89.2% [95% confidence interval (CI); 80.7-94.2] and a specificity of 44.2% (95% CI; 40.2-48.2) to detect HGAIN. Oncogenic HPV testing had 90.4% sensitivity (95% CI; 82-86.8) and 24.4% specificity (95% CI; 20.8-28.3). Cotesting showed a 97.4% sensitivity (95% CI; 91-99.3) and 14% specificity (95% CI; 11.2-17.3). In patients with atypical squamous cells of uncertain significance on cytology, oncogenic HPV testing had 91.3% sensitivity and 28.3% specificity to detect HGAIN. Abnormal cytology and oncogenic HPV determination showed similar sensitivity for detecting HGAIN. The two tests used together improved the sensitivity but with lowered specificity. In our opinion, HPV testing does not improve HGAIN detection and should not replace anal cytology as a standard screening test for HIV-infected MSM.

Bacteriophage-based assays for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a meta-analysis.

PubMed

Pai, Madhukar; Kalantri, Shriprakash; Pascopella, Lisa; Riley, Lee W; Reingold, Arthur L

2005-10-01

To summarize, using meta-analysis, the accuracy of bacteriophage-based assays for the detection of rifampicin resistance in Mycobacterium tuberculosis. By searching multiple databases and sources we identified a total of 21 studies eligible for meta-analysis. Of these, 14 studies used phage amplification assays (including eight studies on the commercial FASTPlaque-TB kits), and seven used luciferase reporter phage (LRP) assays. Sensitivity, specificity, and agreement between phage assay and reference standard (e.g. agar proportion method or BACTEC 460) results were the main outcomes of interest. When performed on culture isolates (N=19 studies), phage assays appear to have relatively high sensitivity and specificity. Eleven of 19 (58%) studies reported sensitivity and specificity estimates > or =95%, and 13 of 19 (68%) studies reported > or =95% agreement with reference standard results. Specificity estimates were slightly lower and more variable than sensitivity; 5 of 19 (26%) studies reported specificity <90%. Only two studies performed phage assays directly on sputum specimens; although one study reported sensitivity and specificity of 100 and 99%, respectively, another reported sensitivity of 86% and specificity of 73%. Current evidence is largely restricted to the use of phage assays for the detection of rifampicin resistance in culture isolates. When used on culture isolates, these assays appear to have high sensitivity, but variable and slightly lower specificity. In contrast, evidence is lacking on the accuracy of these assays when they are directly applied to sputum specimens. If phage-based assays can be directly used on clinical specimens and if they are shown to have high accuracy, they have the potential to improve the diagnosis of MDR-TB. However, before phage assays can be successfully used in routine practice, several concerns have to be addressed, including unexplained false positives in some studies, potential for contamination and indeterminate results.

A blood tumor marker combination assay produces high sensitivity and specificity for cancer according to the natural history.

PubMed

Kobayashi, Tsuneo

2018-03-01

Diagnosis using a specific tumor marker is difficult because the sensitivity of this detection method is under 20%. Herein, a tumor marker combination assay, combining growth-related tumor marker and associated tumor marker (Cancer, 73(7), 1994), was employed. This double-blind tumor marker combination assay (TMCA) showed 87.5% sensitivity as the results, but a low specificity, ranging from 30 to 76%. To overcome this low specificity, we exploited complex markers, a multivariate analysis and serum fractionation by biochemical biopsy. Thus, in this study, a combination of new techniques was used to re-evaluate these serum samples. Three serum panels, containing 90, 120, and 97 samples were obtained from the Mayo Clinic. The final results showed 80-90% sensitivity, 84-85% specificity, and 83-88% accuracy. We demonstrated a notable tumor marker combination assay with high accuracy. This TMCA should be applicable for primary cancer detection and recurrence prevention. © 2018 The Author. Cancer Medicine published by John Wiley & Sons Ltd.

Point-of-care test for cervical cancer in LMICs.

PubMed

Mohammed, Sulma I; Ren, Wen; Flowers, Lisa; Rajwa, Bartek; Chibwesha, Carla J; Parham, Groesbeck P; Irudayaraj, Joseph M K

2016-04-05

Cervical cancer screening using Papanicolaou's smear test has been highly effective in reducing death from this disease. However, this test is unaffordable in low- and middle-income countries, and its complexity has limited wide-scale uptake. Alternative tests, such as visual inspection with acetic acid or Lugol's iodine and human papillomavirus DNA, are sub-optimal in terms of specificity and sensitivity, thus sensitive and affordable tests with high specificity for on-site reporting are needed. Using proteomics and bioinformatics, we have identified valosin-containing protein (VCP) as differentially expressed between normal specimens and those with cervical intra-epithelial neoplasia grade 2/3 (CIN2/CIN3+) or worse. VCP-specific immunohistochemical staining (validated by a point-of-care technology) provided sensitive (93%) and specific (88%) identification of CIN2/CIN3+ and may serve as a critical biomarker for cervical-cancer screening. Future efforts will focus on further refinements to enhance analytic sensitivity and specificity of our proposed test, as well as on prototype development.

Fundamentals of nuclear medicine

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

Alazraki, N.P.; Mishkin, F.S.

1988-01-01

The book begins with basic science and statistics relevant to nuclear medicine, and specific organ systems are addressed in separate chapters. A section of the text also covers imaging of groups of disease processes (eg, trauma, cancer). The authors present a comparison between nuclear medicine techniques and other diagnostic imaging studies. A table is given which comments on sensitivities and specificities of common nuclear medicine studies. The sensitivities and specificities are categorized as very high, high, moderate, and so forth.

High correlation of specific IgE sensitization between birch pollen, soy and apple allergens indicates pollen-food allergy syndrome among birch pollen allergic patients in northern China.

PubMed

Hao, Guo-Dong; Zheng, Yi-Wu; Wang, Zhi-Xiang; Kong, Xing-Ai; Song, Zhi-Jing; Lai, Xu-Xin; Spangfort, Michael D

2016-05-01

Birch pollen sensitization and associated pollen-food syndrome among Chinese allergic patients have not been investigated. Sera from 203 allergic patients from the northern part of China and collected during February to July 2014 were investigated. Specific immunoglobulin E (IgE) against birch pollen extract Bet v and major birch pollen allergen Bet v 1 were measured using the ADVIA Centaur. The presence of major apple allergen Mal d 1 and soy bean allergen Gly m 4 specific IgE was measured by ImmunoCAP 100. Among the 203 sera, 34 sera (16.7%) had specific IgE to Bet v and of these, 28 sera (82.4%) contained Bet v 1-specific IgE. Among the 28 sera with Bet v 1-specific IgE, 27 sera (96.4%) contained Mal d 1-specific IgE and 22 sera (78.6%) contained Gly m 4-specific IgE. Of the 34 Bet v-positive sera, 6 sera (17.6%) contained no specific IgE for Bet v 1, Mal d 1, or Gly m 4. Almost all Bet v-positive sera were donated during the birch pollen season. The prevalence of birch allergy among patients visiting health care during pollen season can be as high as 16.7% in Tangshan City. The majority of Chinese birch allergic patients are IgE-sensitized to the major birch pollen allergen Bet v 1 as well as to the major apple allergen Mal d 1 and soy bean allergen Gly m 4. A relatively high number of patients (17.6%) are IgE-sensitized to birch pollen allergen(s) other than Bet v 1. The high prevalence of specific IgE to Mal d 1 and Gly m 4 among Bet v 1-sensitized patients indicates that pollen-food allergy syndrome could be of clinical relevance in China.

High sensitivity and specificity of clinical microscopy in rural health facilities in western Kenya under an external quality assurance program.

PubMed

Wafula, Rebeccah; Sang, Edna; Cheruiyot, Olympia; Aboto, Angeline; Menya, Diana; O'Meara, Wendy Prudhomme

2014-09-01

Microscopic diagnosis of malaria is a well-established and inexpensive technique that has the potential to provide accurate diagnosis of malaria infection. However, it requires both training and experience. Although it is considered the gold standard in research settings, the sensitivity and specificity of routine microscopy for clinical care in the primary care setting has been reported to be unacceptably low. We established a monthly external quality assurance program to monitor the performance of clinical microscopy in 17 rural health centers in western Kenya. The average sensitivity over the 12-month period was 96% and the average specificity was 88%. We identified specific contextual factors that contributed to inadequate performance. Maintaining high-quality malaria diagnosis in high-volume, resource-constrained health facilities is possible. © The American Society of Tropical Medicine and Hygiene.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis.

PubMed

van Dijken, Bart R J; van Laar, Peter Jan; Holtman, Gea A; van der Hoorn, Anouk

2017-10-01

Treatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas. Databases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included. Anatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51-81) and 77% (45-93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60-80) and specificity of 87% (77-93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82-91) with a specificity of 86% (77-91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73-98) and specificity was 85% (76-92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79-97) and specificity was 95% (65-99). Advanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas. • Treatment response assessment in high-grade gliomas with anatomical MRI is unreliable • Novel advanced MRI techniques have been studied, but diagnostic accuracy is unknown • Meta-analysis demonstrates that advanced MRI showed higher diagnostic accuracy than anatomical MRI • Highest diagnostic accuracy for spectroscopy and perfusion MRI • Supports the incorporation of advanced MRI in high-grade glioma treatment response assessment.

Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data.

PubMed

Kroenke, Candyce H; Chubak, Jessica; Johnson, Lisa; Castillo, Adrienne; Weltzien, Erin; Caan, Bette J

2016-03-01

The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women's Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms-one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV-using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this "triangulation." Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data

PubMed Central

Chubak, Jessica; Johnson, Lisa; Castillo, Adrienne; Weltzien, Erin; Caan, Bette J.

2016-01-01

Abstract Background: The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. Methods: We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women’s Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms—one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV—using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this “triangulation.” Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. Results: The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Conclusions: Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs. PMID:26582243

Blinded study determination of high sensitivity and specificity microchip electrophoresis–SSCP/HA to detect mutations in the p53 gene

PubMed Central

Hestekin, Christa N.; Lin, Jennifer S.; Senderowicz, Lionel; Jakupciak, John P.; O’Connell, Catherine; Rademaker, Alfred; Barron, Annelise E.

2012-01-01

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA-based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor-intensive, time-consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here we demonstrate the first blinded study using microchip electrophoresis-SSCP/HA. We demonstrate the ability of microchip electrophoresis-SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5–9 in a blinded study in an analysis time of less than 10 minutes. PMID:22002021

The ClASsification for Psoriatic ARthritis (CASPAR) criteria--a retrospective feasibility, sensitivity, and specificity study.

PubMed

Tillett, William; Costa, Luisa; Jadon, Deepak; Wallis, Dinny; Cavill, Charlotte; McHugh, Jessica; Korendowych, Eleanor; McHugh, Neil

2012-01-01

To evaluate the sensitivity, specificity, and feasibility of the ClASsification criteria for Psoriatic ARthritis (CASPAR) to retrospectively classify an existing research cohort. In total, 480 patient records were reviewed from the Royal National Hospital for Rheumatic Diseases Psoriatic Arthritis (PsA) cohort and for 100 consecutive controls with inflammatory arthritis from a general rheumatology clinic. The CASPAR score was modified for retrospective use; both "inflammation" and "current psoriasis" were recorded as present if they had ever been confirmed in the rheumatology clinic. Sensitivity and specificity of the CASPAR criteria were compared with expert clinical diagnosis. A total of 480 database records were identified. Nine sets of records had been lost or destroyed. The diagnoses had changed in 15 cases, which were transferred to the control arm, leaving 456 patients with an expert diagnosis of PsA. Of 115 controls, 96 had rheumatoid arthritis, 5 osteoarthritis, 3 reactive arthritis, 3 seronegative arthritis, 3 undifferentiated arthralgia, 2 ankylosing spondylitis, 1 spondyloarthritis, and 2 systemic sclerosis. Sensitivity (99.7%) and specificity (99.1%) were both high and equivalent to previous reports. Sensitivity remained high even after inclusion of 7 PsA patients with insufficient data to complete the CASPAR assessment (sensitivity 98.2%, specificity 99.1%). The criteria were found to be easy and practical to apply to case records. Our study demonstrates that the feasibility, specificity, and sensitivity of the CASPAR are maintained when adapted for retrospective use to classify an established research cohort.

Differential Sensitivity Between a Virtual Reality Balance Module and Clinically Used Concussion Balance Modalities.

PubMed

Teel, Elizabeth F; Gay, Michael R; Arnett, Peter A; Slobounov, Semyon M

2016-03-01

Balance assessments are part of the recommended clinical concussion evaluation, along with computerized neuropsychological testing and self-reported symptoms checklists. New technology has allowed for the creation of virtual reality (VR) balance assessments to be used in concussion care, but there is little information on the sensitivity and specificity of these evaluations. The purpose of this study is to establish the sensitivity and specificity of a VR balance module for detecting lingering balance deficits clinical concussion care. Retrospective case-control study. Institutional research laboratory. Normal controls (n = 94) and concussed participants (n = 27). All participants completed a VR balance assessment paradigm. Concussed participants were diagnosed by a Certified Athletic Trainer or physician (with 48 hours postinjury) and tested in the laboratory between 7 and 10 days postinjury. Receiver operating characteristic curves were performed to establish the VR module's sensitivity and specificity for detecting lingering balance deficits. Final balance score. For the VR balance module, a cutoff score of 8.25 was established to maximize sensitivity at 85.7% and specificity at 87.8%. The VR balance module has high sensitivity and specificity for detecting subacute balance deficits after concussive injury. The VR balance has a high subacute sensitivity and specificity as a stand-alone balance assessment tool and may detect ongoing balance deficits not readily detectable by the Balance Error Scoring System or Sensory Organization Test. Virtual reality balance modules may be a beneficial addition to the current clinical concussion diagnostic battery.

Comparison of sensitivity and specificity among 15 criteria for chronic inflammatory demyelinating polyneuropathy.

PubMed

Breiner, Ari; Brannagan, Thomas H

2014-07-01

There have been 15 formal sets of criteria published for the diagnosis of CIDP. No study to date has compared the sensitivity and specificity of all published criteria in the same patient population. We conducted a retrospective chart review of patients with CIDP (n = 56) and controls with diabetic polyneuropathy (n = 37) or amyotrophic lateral sclerosis (n = 39) who were followed in an academic neuromuscular practice. The sensitivity and specificity of each CIDP criterion was calculated, including clinical, laboratory, and electrodiagnostic components. Sensitivities ranged from 1.8% to 87.5%; the Dyck (87.5%), Neuropathy Association (75%), and European Federation of Neurological Societies (EFNS; 73.2%) criteria ranked highest. Specificities ranged from 65.6% to 100% and, among the 3 most sensitive criteria, the EFNS (90.8%) and Neuropathy Association (82.9%) criteria were most specific. In our patient population, the EFNS and Neuropathy Association criteria stand out due to high sensitivity and specificity. Copyright © 2013 Wiley Periodicals, Inc.

Magnetic relaxometry as applied to sensitive cancer detection and localization

DOE PAGES

De Haro, Leyma P.; Karaulanov, Todor; Vreeland, Erika C.; ...

2015-06-02

Abstract Here we describe superparamagnetic relaxometry (SPMR), a technology that utilizes highly sensitive magnetic sensors and superparamagnetic nanoparticles for cancer detection. Using SPMR, we sensitively and specifically detect nanoparticles conjugated to biomarkers for various types of cancer. SPMR offers high contrast In SPMR measurements, a brief magnetizing pulse is used to align superparamagnetic nanoparticles of a discrete size. Following the pulse, an array of superconducting quantum interference detectors (SQUID) sensors detect the decaying magnetization field. NP size is chosen so that, when bound, the induced field decays in seconds. They are functionalized with specific biomarkers and incubated with cancer cellsmore » As a result, superparamagnetic NPs developed here have small size dispersion. Cell incubation studies measure specificity for different cell lines and antibodies with very high contrast.« less

Diagnostic sensitivity and specificity of a participatory disease surveillance method for highly pathogenic avian influenza in household chicken flocks in Indonesia.

PubMed

Robyn, M; Priyono, W B; Kim, L M; Brum, E

2012-06-01

A study was conducted to assess the diagnostic sensitivity and specificity of a disease surveillance method for diagnosis of highly pathogenic avian influenza (HPAI) outbreaks in household chicken flocks used by participatory disease surveillance (PDS) teams in Yogyakarta Province, Indonesia. The Government of Indonesia, in partnership with the Food and Agriculture Organization of the United Nations, has implemented a PDS method for the detection of HPAI outbreaks in poultry since 2006. The PDS method in Indonesia utilizes both a clinical case definition (CD) and the result of a commercial rapid antigen test kit Yogyakarta 55611, to diagnose HPAI outbreaks, primarily in backyard chicken flocks. The following diagnostic sensitivities and specificities were obtained relative to real-time reverse transcription-PCR as the gold standard diagnostic test: 1) 89% sensitivity (CI95: 75%-97%) and 96% specificity (CI95: 89%-99%) for the PDS CD alone; 2) 86% sensitivity (CI95: 71%-95%) and 99% specificity (CI95: 94%-100%) for the rapid antigen test alone; and 3) 84% sensitivity (CI95: 68%-94%) and 100% specificity (CI95: 96%-100%) for the PDS CD result combined with the rapid antigen test result. Based on these results, HPAI outbreaks in extensively raised household chickens can be diagnosed with sufficient sensitivity and specificity using the PDS method as implemented in Indonesia. Subject to further field evaluation, data from this study suggest that the diagnostic sensitivity of the PDS method may be improved by expanding the PDS CD to include more possible clinical presentations of HPAI and by increasing the number of rapid antigen tests to three different birds with HPAI-compatible signs of same flock.

Systematic review: Comparison of Xpert MTB/RIF, LAMP and SAT methods for the diagnosis of pulmonary tuberculosis.

PubMed

Yan, Liping; Xiao, Heping; Zhang, Qing

2016-01-01

Technological advances in nucleic acid amplification have led to breakthroughs in the early detection of PTB compared to traditional sputum smear tests. The sensitivity and specificity of loop-mediated isothermal amplification (LAMP), simultaneous amplification testing (SAT), and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis were evaluated. A critical review of previous studies of LAMP, SAT, and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis that used laboratory culturing as the reference method was carried out together with a meta-analysis. In 25 previous studies, the pooled sensitivity and specificity of the diagnosis of tuberculosis were 93% and 94% for LAMP, 96% and 88% for SAT, and 89% and 98% for Xpert MTB/RIF. The I(2) values for the pooled data were >80%, indicating significant heterogeneity. In the smear-positive subgroup analysis of LAMP, the sensitivity increased from 93% to 98% (I(2) = 2.6%), and specificity was 68% (I(2) = 38.4%). In the HIV-infected subgroup analysis of Xpert MTB/RIF, the pooled sensitivity and specificity were 79% (I(2) = 72.9%) and 99% (I(2) = 64.4%). In the HIV-negative subgroup analysis for Xpert MTB/RIF, the pooled sensitivity and specificity were 72% (I(2) = 49.6%) and 99% (I(2) = 64.5%). LAMP, SAT and Xpert MTB/RIF had comparably high levels of sensitivity and specificity for the diagnosis of tuberculosis. The diagnostic sensitivity and specificity of three methods were similar, with LAMP being highly sensitive for the diagnosis of smear-positive PTB. The cost effectiveness of LAMP and SAT make them particularly suitable tests for diagnosing PTB in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Highly sensitive chemiluminescent aptasensor for detecting HBV infection based on rapid magnetic separation and double-functionalized gold nanoparticles.

PubMed

Xi, Zhijiang; Gong, Quan; Wang, Chao; Zheng, Bing

2018-06-21

Hepatitis B virus (HBV) infection is a major global public health problem and one of the leading causes of chronic liver disease. HBsAg is the first serological marker to appear in the blood and is the most important marker of HBV infection. Detection of HBsAg in serum samples is commonly carried out using an immunoassay such as an enzyme-linked immunosorbent assay (ELISA), which is complex to perform, time-consuming, and unsatisfactory for testing sensitivity. Therefore, new methods for highly sensitive detection of HBV infection are urgently needed. Aptamers are specific recognition molecules with high affinity and specificity toward their targets. Biosensors that employ aptamers as biorecognition elements are known as aptasensors. In this study, we select an HBsAg-specific aptamer and use it to develop a new chemiluminescent aptasensor based on rapid magnetic separation and double-functionalized gold nanoparticles. This sensor enables rapid magnetic separation and highly sensitive detection of HBsAg in HBV-positive serum. The detection limit of this HBsAg-detecting chemiluminescent aptasensor is as low as 0.05 ng/mL, which is much lower than the 0.5 ng/mL limit of a typical ELISA used in hospitals. Furthermore, this aptasensor works well and is highly specific to HBV infection.

Macular Diagnostic Ability in OCT for Assessing Glaucoma in High Myopia.

PubMed

Hung, Kuo-Chi; Wu, Pei-Chang; Poon, Yi-Chieh; Chang, Hsueh-Wen; Lai, Ing-Chou; Tsai, Jen-Chia; Lin, Pei-Wen; Teng, Mei-Ching

2016-02-01

To compare the diagnostic abilities of spectral-domain optical coherence tomography (SD-OCT; Spectralis OCT) and time-domain OCT (TD-OCT; Stratus OCT). Changes in macular parameters in highly myopic eyes of glaucoma patients and highly myopic eyes of glaucoma suspects were evaluated and compared. We collected data from 72 highly myopic eyes (spherical equivalent, ≤-6.0D). Forty-one eyes had perimetric glaucoma and 31 eyes were suspected to have glaucoma (control group). All eyes underwent SD-OCT and TD-OCT imaging. Area under the receiver operating characteristic (AUROC) curve and sensitivity were examined on macular volume and thickness parameters at a fixed specificity and compared between groups. The highest TD-OCT AUROC curves were found using outer inferior sector macular thickness (AUROC curve, 0.911) and volume (AUROC curve, 0.909). The highest SD-OCT AUROC curves were found using outer inferior region thickness (AUROC curve, 0.836) and volume (AUROC curve, 0.834). The difference between the two imaging modalities was not statistically significant (thickness, p = 0.141; volume, p = 0.138). The sensitivity of TD-OCT macular outer inferior average thickness was highest and was 88.2%, with a specificity of 80.4%. The sensitivity of TD-OCT average volume measurements in this same region was 76.5%, with a specificity of 91.3%. The SD-OCT average thickness measurements also had the highest sensitivity in this region, which was 78.6%, with a specificity of 82.1%. The SD-OCT volume measurements had a sensitivity of 67.9%, with a specificity of 92.3%. Both SD-OCT and TD-OCT measurements of outer inferior macular thickness and volume can differentiate between eyes of glaucoma patients and glaucoma suspects with high myopia. These independent predictors all had good sensitivity. Based on our results, SD-OCT and TD-OCT have similar diagnostic abilities. These parameters may provide useful additional data in highly myopic eyes to complement standard glaucoma diagnosis tools.

ELISA-PLA: A novel hybrid platform for the rapid, highly sensitive and specific quantification of proteins and post-translational modifications.

PubMed

Tong, Qing-He; Tao, Tao; Xie, Li-Qi; Lu, Hao-Jie

2016-06-15

Detection of low-abundance proteins and their post-translational modifications (PTMs) remains a great challenge. A conventional enzyme-linked immunosorbent assay (ELISA) is not sensitive enough to detect low-abundance PTMs and suffers from nonspecific detection. Herein, a rapid, highly sensitive and specific platform integrating ELISA with a proximity ligation assay (PLA), termed ELISA-PLA, was developed. Using ELISA-PLA, the specificity was improved by the simultaneous and proximate recognition of targets through multiple probes, and the sensitivity was significantly improved by rolling circle amplification (RCA). For GFP, the limit of detection (LOD) was decreased by two orders of magnitude compared to that of ELISA. Using site-specific phospho-antibody and pan-specific phospho-antibody, ELISA-PLA was successfully applied to quantify the phosphorylation dynamics of ERK1/2 and the overall tyrosine phosphorylation level of ERK1/2, respectively. ELISA-PLA was also used to quantify the O-GlcNAcylation of AKT, c-Fos, CREB and STAT3, which is faster and more sensitive than the conventional immunoprecipitation and western blotting (IP-WB) method. As a result, the sample consumption of ELISA-PLA was reduced 40-fold compared to IP-WB. Therefore, ELISA-PLA could be a promising platform for the rapid, sensitive and specific detection of proteins and PTMs. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison between esophagography and chest computed tomography for evaluation of leaks after esophagectomy and gastric pull-through.

PubMed

Lantos, Joshua E; Levine, Marc S; Rubesin, Stephen E; Lau, Charles T; Torigian, Drew A

2013-03-01

To assess the diagnostic performance of esophagography and chest computed tomography (CT) for detecting leaks after esophagectomy and gastric pull-through. Our database revealed 29 patients who had undergone esophagography and chest CT after esophagectomy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for postoperative leaks were determined for esophagography and CT, separately and combined, on the basis of a retrospective image review. Patients were also stratified for esophagograms with water-soluble contrast alone versus water-soluble contrast and high-density barium and for CT with and without oral contrast. Our findings were retrospectively compared with those reported at initial image interpretation. Clinically relevant leaks were present in 14 (48%) of 29 patients after esophagectomy. Esophagography had a sensitivity of 79%, specificity of 73%, PPV of 73%, and NPV of 79% for detecting leaks, whereas CT had a sensitivity of 86%, specificity of 33%, PPV of 55%, and NPV of 71% and esophagography and CT combined had a sensitivity of 100%, specificity of 27%, PPV of 56%, and NPV of 100%. The sensitivity of esophagography increased with high-density barium, whereas the sensitivity of CT was the same with and without oral contrast agent. Finally, esophagography and CT were seen to have a higher sensitivity and lower specificity on retrospective review compared with the results reported at initial image interpretation. Esophagography had a slightly lower sensitivity and substantially higher specificity compared with CT for detecting leaks after esophagectomy, whereas esophagography and CT combined had a sensitivity of 100% for detecting leaks. Therefore, postoperative leaks can be excluded with confidence after esophagectomy when both tests are negative.

An automated quantitative DNA image cytometry system detects abnormal cells in cervical cytology with high sensitivity.

PubMed

Wong, O G; Ho, M W; Tsun, O K; Ng, A K; Tsui, E Y; Chow, J N; Ip, P P; Cheung, A N

2018-03-26

To evaluate the performance of an automated DNA-image-cytometry system as a tool to detect cervical carcinoma. Of 384 liquid-based cervical cytology samples with available biopsy follow-up were analyzed by both the Imager System and a high-risk HPV test (Cobas). The sensitivity and specificity of Imager System for detecting biopsy proven high-grade squamous intraepithelial lesion (HSIL, cervical intraepithelial neoplasia [CIN]2-3) and carcinoma were 89.58% and 56.25%, respectively, compared to 97.22% and 23.33% of HPV test but additional HPV 16/18 genotyping increased the specificity to 69.58%. The sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions among atypical squamous cells of undetermined significance samples were 80.00% and 70.53%, respectively, compared to 100% and 11.58% of HPV test whilst the HPV 16/18 genotyping increased the specificity to 77.89%. Among atypical squamous cells-cannot exclude HSIL, the sensitivity and specificity of Imager System for predicting HSIL+ (CIN2-3+) lesions upon follow up were 82.86% and 33.33%%, respectively, compared to 97.14% and 4.76% of HPV test and the HPV 16/18 genotyping increased the specificity to 19.05%. Among low-grade squamous intraepithelial lesion cases, the sensitivity and specificity of the Imager System for predicting HSIL+ (CIN2-3+) lesions were 66.67% and 35.71%%, respectively, compared to 66.67% and 29.76% of HPV test while HPV 16/18 genotyping increased the specificity to 79.76%. The overall results of imager and high-risk HPV test agreed in 69.43% (268) of all samples. The automated imager system and HPV 16/18 genotyping can enhance the specificity of detecting HSIL+ (CIN2-3+) lesions. © 2018 John Wiley & Sons Ltd.

A Novel Real-Time PCR Assay of microRNAs Using S-Poly(T), a Specific Oligo(dT) Reverse Transcription Primer with Excellent Sensitivity and Specificity

PubMed Central

Kang, Kang; Zhang, Xiaoying; Liu, Hongtao; Wang, Zhiwei; Zhong, Jiasheng; Huang, Zhenting; Peng, Xiao; Zeng, Yan; Wang, Yuna; Yang, Yi; Luo, Jun; Gou, Deming

2012-01-01

Background MicroRNAs (miRNAs) are small, non-coding RNAs capable of postranscriptionally regulating gene expression. Accurate expression profiling is crucial for understanding the biological roles of miRNAs, and exploring them as biomarkers of diseases. Methodology/Principal Findings A novel, highly sensitive, and reliable miRNA quantification approach,termed S-Poly(T) miRNA assay, is designed. In this assay, miRNAs are subjected to polyadenylation and reverse transcription with a S-Poly(T) primer that contains a universal reverse primer, a universal Taqman probe, an oligo(dT)11 sequence and six miRNA-specific bases. Individual miRNAs are then amplified by a specific forward primer and a universal reverse primer, and the PCR products are detected by a universal Taqman probe. The S-Poly(T) assay showed a minimum of 4-fold increase in sensitivity as compared with the stem-loop or poly(A)-based methods. A remarkable specificity in discriminating among miRNAs with high sequence similarity was also obtained with this approach. Using this method, we profiled miRNAs in human pulmonary arterial smooth muscle cells (HPASMC) and identified 9 differentially expressed miRNAs associated with hypoxia treatment. Due to its outstanding sensitivity, the number of circulating miRNAs from normal human serum was significantly expanded from 368 to 518. Conclusions/Significance With excellent sensitivity, specificity, and high-throughput, the S-Poly(T) method provides a powerful tool for miRNAs quantification and identification of tissue- or disease-specific miRNA biomarkers. PMID:23152780

Novel approach based on one-tube nested PCR and a lateral flow strip for highly sensitive diagnosis of tuberculous meningitis

PubMed Central

Sun, Yajuan; Chen, Jiajun; Li, Jia; Xu, Yawei; Jin, Hui; Xu, Na; Yin, Rui

2017-01-01

Rapid and sensitive detection of Mycobacterium tuberculosis (M. Tb) in cerebrospinal fluid is crucial in the diagnosis of tuberculous meningitis (TBM), but conventional diagnostic technologies have limited sensitivity and specificity or are time-consuming. In this work, a novel, highly sensitive molecular diagnostic method, one-tube nested PCR-lateral flow strip test (OTNPCR-LFST), was developed for detecting M. tuberculosis. This one-tube nested PCR maintains the sensitivity of conventional two-step nested PCR and reduces both the chance of cross-contamination and the time required for analysis. The PCR product was detected by a lateral flow strip assay, which provided a basis for migration of the test to a point-of-care (POC) microfluidic format. The developed assay had an improved sensitivity compared with traditional PCR, and the limit of detection was up to 1 fg DNA isolated from M. tuberculosis. The assay was also specific for M. tuberculosis, and no cross-reactions were found in other non-target bacteria. The application of this technique to clinical samples was successfully evaluated, and OTNPCR-LFST showed 89% overall sensitivity and 100% specificity for TBM patients. This one-tube nested PCR-lateral flow strip assay is useful for detecting M. tuberculosis in TBM due to its rapidity, high sensitivity and simple manipulation. PMID:29084241

Combining two serological assays optimises sensitivity and specificity for the identification of Streptococcus equi subsp. equi exposure.

PubMed

Robinson, Carl; Steward, Karen F; Potts, Nicola; Barker, Colin; Hammond, Toni-ann; Pierce, Karen; Gunnarsson, Eggert; Svansson, Vilhjálmur; Slater, Josh; Newton, J Richard; Waller, Andrew S

2013-08-01

The detection of anti-Streptococcus equi antibodies in the blood serum of horses can assist with the identification of apparently healthy persistently infected carriers and the prevention of strangles outbreaks. The aim of the current study was to use genome sequencing data to develop an indirect enzyme linked immunosorbent assay (iELISA) that targets two S. equi-specific protein fragments. The sensitivity and specificity of the antigen A and antigen C iELISAs were compared to an SeM-based iELISA marketed by IDvet - diagnostic Vétérinaire (IDvet). Individually, each assay compromised specificity in order to achieve sufficient sensitivity (SeM iELISA had a sensitivity of 89.9%, but a specificity of only 77.0%) or sensitivity to achieve high specificity. However, combining the results of the antigen A and antigen C iELISAs permitted optimisation of both sensitivity (93.3%) and specificity (99.3%), providing a robust assay for the identification of horses exposed to S. equi. Copyright © 2013 Elsevier Ltd. All rights reserved.

Assessing sensitivity and specificity of the Manchester Triage System in the evaluation of acute coronary syndrome in adult patients in emergency care: a systematic review.

PubMed

Nishi, Fernanda Ayache; de Oliveira Motta Maia, Flávia; de Souza Santos, Itamar; de Almeida Lopes Monteiro da Cruz, Dina

2017-06-01

Triage is the first assessment and sorting process used to prioritize patients arriving in the emergency department (ED). As a triage tool, the Manchester Triage System (MTS) must have a high sensitivity to minimize the occurrence of under-triage, but must not compromise specificity to avoid the occurrence of overtriage. Sensitivity and specificity of the MTS can be calculated using the frequency of appropriately assigned clinical priority levels for patients presenting to the ED. However, although there are well established criteria for the prioritization of patients with suspected acute coronary syndrome (ACS), several studies have reported difficulties when evaluating patients with this condition. The objective of this review was to synthesize the best available evidence on assessing the sensitivity and specificity of the MTS for screening high-level priority adult patients presenting to the ED with ACS. The current review considered studies that evaluated the use of the MTS in the risk classification of adult patients in the ED. In this review, studies that investigated the priority level, as established by the MTS to screen patients under suspicion of ACS or the sensitivity and specificity of the MTS, for screening patients before the medical diagnosis of ACS were included. This review included both experimental and epidemiological study designs. The results were presented in a narrative synthesis. Six studies were appraised by the independent reviewers. All appraised studies enrolled a consecutive or random sample of patients and presented an overall moderate methodological quality, and all of them were included in this review. A total of 54,176 participants were included in the six studies. All studies were retrospective. Studies included in this review varied in content and data reporting. Only two studies reported sensitivity and specificity values or all the necessary data to calculate sensitivity and specificity. The remaining four studies presented either a sensitivity analysis or the number of true positives and false negatives. However, these four studies were conducted considering only data from patients diagnosed with ACS. Sensitivity values were relatively uniform among the studies: 0.70-0.80. A specificity of 0.59 was reported in the study including only patients with non-traumatic chest pain. On the other hand, in the study that included patients with any complaint, the specificity of MTS to screen patients with ACS was 0.97. The current review demonstrates that the MTS has a moderate sensitivity to evaluate patients with ACS. This may compromise time to treatment in the ED, an important variable in the prognosis of ACS. Atypical presentation of ACS, or high specificity, may also explain the moderate sensitivity demonstrated in this review. However, because of minimal data, it is not possible to confirm this hypothesis. It is difficult to determine the acceptable level of sensitivity or specificity to ensure that a certain triage system is safe.

Reinforcement Sensitivity and Risk for Psychopathology Following Exposure to Violence: A Vulnerability-Specificity Model in Latino Youth

ERIC Educational Resources Information Center

Gudino, Omar G.; Nadeem, Erum; Kataoka, Sheryl H.; Lau, Anna S.

2012-01-01

Urban Latino youth are exposed to high rates of violence, which increases risk for diverse forms of psychopathology. The current study aims to increase specificity in predicting responses by testing the hypothesis that youths' reinforcement sensitivity--behavioral inhibition (BIS) and behavioral approach (BAS)--is associated with specific clinical…

Cost Effectiveness of Field Trauma Triage among Injured Adults Served by Emergency Medical Services

PubMed Central

Newgard, Craig D; Yang, Zhuo; Nishijima, Daniel; McConnell, K John; Trent, Stacy; Holmes, James F; Daya, Mohamud; Mann, N Clay; Hsia, Renee Y; Rea, Tom; Wang, N Ewen; Staudenmayer, Kristan; Delgado, M Kit

2016-01-01

Background The American College of Surgeons Committee on Trauma sets national targets for the accuracy of field trauma triage at ≥ 95% sensitivity and ≥ 65% specificity, yet the cost-effectiveness of realizing these goals is unknown. We evaluated the cost-effectiveness of current field trauma triage practices compared to triage strategies consistent with the national targets. Study Design This was a cost-effectiveness analysis using data from 79,937 injured adults transported by 48 emergency medical services (EMS) agencies to 105 trauma and non-trauma hospitals in 6 regions of the Western U.S. from 2006 through 2008. Incremental differences in survival, quality adjusted life years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER; costs per QALY gained) were estimated for each triage strategy over a 1-year and lifetime horizon using a decision analytic Markov model. We considered an ICER threshold of less than $100,000 to be cost-effective. Results For these 6 regions, a high sensitivity triage strategy consistent with national trauma policy (sensitivity 98.6%, specificity 17.1%) would cost $1,317,333 per QALY gained, while current triage practices (sensitivity 87.2%, specificity 64.0%) cost $88,000 per QALY gained compared to a moderate sensitivity strategy (sensitivity 71.2%, specificity 66.5%). Refining EMS transport patterns by triage status improved cost-effectiveness. At the trauma system level, a high-sensitivity triage strategy would save 3.7 additional lives per year at a 1-year cost of $8.78 million, while a moderate sensitivity approach would cost 5.2 additional lives and save $781,616 each year. Conclusions A high-sensitivity approach to field triage consistent with national trauma policy is not cost effective. The most cost effective approach to field triage appears closely tied to triage specificity and adherence to triage-based EMS transport practices. PMID:27178369

Detecting High Hyperopia: The Plus Lens Test and the Spot Vision Screener.

PubMed

Feldman, Samuel; Peterseim, Mae Millicent W; Trivedi, Rupal H; Edward Wilson, M; Cheeseman, Edward W; Papa, Carrie E

2017-05-01

To evaluate the usefulness of the Plus Lens (Goodlite Company, Elgin, IL) test and the Spot Vision Screener (Welch Allyn, Skaneateles Falls, NY) in detecting high hyperopia in a pediatric population. Between June and August 2015, patients were screened with the Spot Vision Screener and the Plus Lens test prior to a scheduled pediatric ophthalmology visit. The following data were analyzed: demographic data, Plus Lens result, Spot Vision Screener result, cycloplegic refraction, and examination findings. Sensitivity/specificity and positive/negative predictive values were calculated for the Plus Lens test and Spot Vision Screener in detecting hyperopia as determined by the "gold-standard" cycloplegic refraction. A total of 109 children (average age: 82 months) were included. Compared to the ophthalmologist's cycloplegic refraction, the Spot Vision Screener sensitivity for +3.50 diopters (D) hyperopia was 31.25% and the specificity was 100%. The Plus Lens sensitivity for +3.50 D hyperopia was 43.75% and the specificity was 89.25%. Spot Vision Screener sensitivity increased with higher degrees of hyperopia. In this preliminary study, the Plus Lens test and the Spot Vision Screener demonstrated moderate sensitivity with good specificity in detecting high hyperopia. [J Pediatr Ophthalmol Strabismus. 2017;54(3):163-167.]. Copyright 2017, SLACK Incorporated.

GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly

PubMed Central

Do, Hongdo; Molania, Ramyar

2017-01-01

The identification of genomic rearrangements with high sensitivity and specificity using massively parallel sequencing remains a major challenge, particularly in precision medicine and cancer research. Here, we describe a new method for detecting rearrangements, GRIDSS (Genome Rearrangement IDentification Software Suite). GRIDSS is a multithreaded structural variant (SV) caller that performs efficient genome-wide break-end assembly prior to variant calling using a novel positional de Bruijn graph-based assembler. By combining assembly, split read, and read pair evidence using a probabilistic scoring, GRIDSS achieves high sensitivity and specificity on simulated, cell line, and patient tumor data, recently winning SV subchallenge #5 of the ICGC-TCGA DREAM8.5 Somatic Mutation Calling Challenge. On human cell line data, GRIDSS halves the false discovery rate compared to other recent methods while matching or exceeding their sensitivity. GRIDSS identifies nontemplate sequence insertions, microhomologies, and large imperfect homologies, estimates a quality score for each breakpoint, stratifies calls into high or low confidence, and supports multisample analysis. PMID:29097403

Improving guideline sensitivity and specificity for the identification of proactive gastrostomy placement in patients with head and neck cancer.

PubMed

Brown, Teresa E; Crombie, Jane; Spurgin, Ann-Louise; Tripcony, Lee; Keller, Jacqui; Hughes, Brett G M; Dickie, Graeme; Kenny, Lizbeth Moira; Hodge, Robert A

2016-04-01

Swallowing and nutrition guidelines for patients with head and neck cancer are available for identification of proactive gastrostomy placement in patients with high nutritional risk. The purpose of this study was to investigate improvements to the validity of these guidelines. A multivariate analysis was fitted to the original dataset (n = 501) to examine the variables that may predict gastrostomy placement (eg, tumor site, treatment, sex, and age). Using these factors, the high risk category was modified and retrospectively validated in the same cohort to provide new measures of sensitivity and specificity. The following were positive predictors of gastrostomy placement: T3 (p = .01), T4 (p < .001), and chemoradiotherapy (p < .001). Laryngeal (p = .02) and skin cancer (p < .001) were negative predictors. Modification of the high risk definition improved sensitivity to 58% and maintained specificity at 92%. Minor modifications to the high risk definition in the guidelines have improved the guideline sensitivity for future use. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1163-E1171, 2016. © 2015 Wiley Periodicals, Inc.

Biomimetic self-templating optical structures fabricated by genetically engineered M13 bacteriophage.

PubMed

Kim, Won-Geun; Song, Hyerin; Kim, Chuntae; Moon, Jong-Sik; Kim, Kyujung; Lee, Seung-Wuk; Oh, Jin-Woo

2016-11-15

Here, we describe a highly sensitive and selective surface plasmon resonance sensor system by utilizing self-assembly of genetically engineered M13 bacteriophage. About 2700 copies of genetically expressed peptide copies give superior selectivity and sensitivity to M13 phage-based SPR sensor. Furthermore, the sensitivity of the M13 phage-based SPR sensor was enhanced due to the aligning of receptor matrix in specific direction. Incorporation of specific binding peptide (His Pro Gln: HPQ) gives M13 bacteriophage high selectivity for the streptavidin. Our M13 phage-based SPR sensor takes advantage of simplicity of self-assembly compared with relatively complex photolithography techniques or chemical conjugations. Additionally, designed structure which is composed of functionalized M13 bacteriophage can simultaneously improve the sensitivity and selectivity of SPR sensor evidently. By taking advantages of the genetic engineering and self-assembly, we propose the simple method for fabricating novel M13 phage-based SPR sensor system which has a high sensitivity and high selectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of immunity to varicella zoster virus with a novel double antigen sandwich enzyme-linked immunosorbent assay.

PubMed

Liu, Jian; Chen, Chunye; Zhu, Rui; Ye, Xiangzhong; Jia, Jizong; Yang, Lianwei; Wang, Yongmei; Wang, Wei; Ye, Jianghui; Li, Yimin; Zhu, Hua; Zhao, Qinjian; Zhang, Jun; Cheng, Tong; Xia, Ningshao

2016-11-01

Varicella is a highly contagious disease caused by primary infection of Varicella zoster virus (VZV). Varicella can be severe or even lethal in susceptible adults, immunocompromised patients and neonates. Determination of the status of immunity to VZV is recommended for these high-risk populations. Furthermore, measurement of population immunity to VZV can help in developing proper varicella vaccination programmes. VZV glycoprotein E (gE) is an antigen that has been demonstrated to be a highly accurate indicator of VZV-specific immunity. In this study, recombinant gE (rgE) was used to establish a double antigen sandwich enzyme-linked immunosorbent assay (ELISA). The established sandwich ELISA showed high specificity and sensitivity in the detection of human sera, and it could detect VZV-specific antibodies at a concentration of 11.25 m IU/mL with a detection linearity interval of 11.25 to 360 m IU/mL (R 2  = 0.9985). The double gE antigen sandwich ELISA showed a sensitivity of 95.08 % and specificity of 100 % compared to the fluorescent-antibody-to-membrane-antigen (FAMA) test, and it showed a sensitivity of 100 % and a specificity of 94.74 % compared to a commercial neutralizing antibody detection kit. Thus, the established double antigen sandwich ELISA can be used as a sensitive and specific quantitative method to evaluate immunity to VZV.

A novel restriction endonuclease GlaI for rapid and highly sensitive detection of DNA methylation coupled with isothermal exponential amplification reaction.

PubMed

Sun, Yueying; Sun, Yuanyuan; Tian, Weimin; Liu, Chenghui; Gao, Kejian; Li, Zhengping

2018-02-07

Sensitive and accurate detection of site-specific DNA methylation is of critical significance for early diagnosis of human diseases, especially cancers. Herein, for the first time we employ a novel methylation-dependent restriction endonuclease GlaI to detect site-specific DNA methylation in a highly specific and sensitive way by coupling with isothermal exponential amplification reaction (EXPAR). GlaI can only cut the methylated target site with excellent selectivity but leave the unmethylated DNA intact. Then the newly exposed end fragments of methylated DNA can trigger EXPAR for highly efficient signal amplification while the intact unmethylated DNA will not initiate EXPAR at all. As such, only the methylated DNA is quantitatively and faithfully reflected by the real-time fluorescence signal of the GlaI-EXPAR system, and the potential false positive interference from unmethylated DNA can be effectively eliminated. Therefore, by integrating the unique features of GlaI for highly specific methylation discrimination and EXPAR for rapid and powerful signal amplification, the elegant GlaI-EXPAR assay allows the direct quantification of methylated DNA with ultrahigh sensitivity and accuracy. The detection limit of methylated DNA target has been pushed down to the aM level and the whole detection process of GlaI-EXPAR can be accomplished within a short time of 2 h. More importantly, ultrahigh specificity is achieved and as low as 0.01% methylated DNA can be clearly identified in the presence of a large excess of unmethylated DNA. This GlaI-EXPAR is also demonstrated to be capable of determining site-specific DNA methylations in real genomic DNA samples. Sharing the distinct advantages of ultrahigh sensitivity, outstanding specificity and facile operation, this new GlaI-EXPAR strategy may provide a robust and reliable platform for the detection of site-specific DNA methylations with low abundances.

Development and clinical performance of high throughput loop-mediated isothermal amplification for detection of malaria

PubMed Central

Perera, Rushini S.; Ding, Xavier C.; Tully, Frank; Oliver, James; Bright, Nigel; Bell, David; Chiodini, Peter L.; Gonzalez, Iveth J.; Polley, Spencer D.

2017-01-01

Background Accurate and efficient detection of sub-microscopic malaria infections is crucial for enabling rapid treatment and interruption of transmission. Commercially available malaria LAMP kits have excellent diagnostic performance, though throughput is limited by the need to prepare samples individually. Here, we evaluate the clinical performance of a newly developed high throughput (HTP) sample processing system for use in conjunction with the Eiken malaria LAMP kit. Methods The HTP system utilised dried blood spots (DBS) and liquid whole blood (WB), with parallel sample processing of 94 samples per run. The system was evaluated using 699 samples of known infection status pre-determined by gold standard nested PCR. Results The sensitivity and specificity of WB-HTP-LAMP was 98.6% (95% CI, 95.7–100), and 99.7% (95% CI, 99.2–100); sensitivity of DBS-HTP-LAMP was 97.1% (95% CI, 93.1–100), and specificity 100% against PCR. At parasite densities greater or equal to 2 parasites/μL, WB and DBS HTP-LAMP showed 100% sensitivity and specificity against PCR. At densities less than 2 p/μL, WB-HTP-LAMP sensitivity was 88.9% (95% CI, 77.1–100) and specificity was 99.7% (95% CI, 99.2–100); sensitivity and specificity of DBS-HTP-LAMP was 77.8% (95% CI, 54.3–99.5) and 100% respectively. Conclusions The HTP-LAMP system is a highly sensitive diagnostic test, with the potential to allow large scale population screening in malaria elimination campaigns. PMID:28166235

Is there a place for extended assessments in addressing child sexual abuse allegations? How sensitivity and specificity impact professional perspectives.

PubMed

Williams, Javonda; Nelson-Gardell, Debra; Coulborn Faller, Kathleen; Tishelman, Amy; Cordisco-Steele, Linda

2014-01-01

Using data from a survey of perceptions of 932 child welfare professionals about the utility of extended assessments, the researchers constructed a scale to measure respondents' views about sensitivity (ensuring sexually abused children are correctly identified) and specificity (ensuring nonabused children are correctly identified) in child sexual abuse evaluations. On average, respondents scored high (valuing sensitivity) on the sensitivity versus specificity scale. Next, the researchers undertook bivariate analyses to identify independent variables significantly associated with the sensitivity versus specificity scale. Then those variables were entered into a multiple regression. Four independent variables were significantly related to higher sensitivity scores: encountering cases requiring extended assessments, valuing extended assessments among scarce resources, less concern about proving cases in court, and viewing the goal of extended assessments as understanding needs of child and family (adjusted R2 = .34).

Prevalence of anxiety disorders among Finnish primary care high utilizers and validation of Finnish translation of GAD-7 and GAD-2 screening tools.

PubMed

Kujanpää, Tero; Ylisaukko-Oja, Tero; Jokelainen, Jari; Hirsikangas, Sari; Kanste, Outi; Kyngäs, Helvi; Timonen, Markku

2014-06-01

To analyse the prevalence of GAD and other anxiety disorders, as well as sensitivity and specificity of GAD-7 among high utilizers of health care. Four municipal health centres in Northern Finland. A psychiatric interview was conducted for 150 high utilizers of health care. Prevalence of GAD as well as sensitivity and specificity of GAD-7. The prevalence of GAD was 4% in this study group of Finnish high utilizers of health care. The sensitivity of GAD-7 was 100.0% (95% CI 54.1-100.0) and the specificity of GAD-7 was 82.6% (95% CI 75.4-88.4) with a cut-off point of 7 or more. GAD is rather common among high utilizers of primary care, although the prevalence of 4% is lower than that previously reported. GAD-7 is a valid and useful tool for detecting GAD among primary health care patients.

Electrocardiographic Criteria for Left Ventricular Hypertrophy in Asians Differs from Criteria Derived from Western Populations--Community-based Data from an Asian Population.

PubMed

Xu, Chang Fen; Tan, Eugene S J; Feng, Liang; Santhanakrishnan, Rajalakshmi; Chan, Michelle M Y; Nyunt, Shwe Zin; Ng, Tze Pin; Ling, Lieng Hsi; Richards, A Mark; Lam, Carolyn S P; Lim, Toon Wei

2015-08-01

Electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH), such as the Cornell and Sokolow-Lyon voltage criteria were derived from Western populations. However, their utility and accuracy for diagnosing echocardiographic LVH in Asian populations is unclear. The objective of this study was to assess the accuracy of ECG criteria for LVH in Asians and to determine if alternative gender-specific ECG cut-offs may improve its diagnostic accuracy. ECG and echocardiographic assessments were performed on 668 community-dwelling Asian adults (50.9% women; 57 ± 10 years) in Singapore. The accuracy of ECG voltage criteria was compared to echocardiographic LVH criteria based on the American Society of Echocardiography guidelines, and Asian ethnicity and gender-specific partition values. Echocardiographic LVH was present in 93 (13.6%) adults. Cornell criteria had low sensitivity (5.5%) and high specificity (98.9%) for diagnosing LVH. Modified gender specific cut-offs (18 mm in women, 22 mm in men) improved sensitivity (8.8% to 17.5%, 0% to 14.7%, respectively) whilst preserving specificity (98.2% to 94.2%, 100% to 95.8%). Similarly, Sokolow-Lyon criteria had poor sensitivity (7.7%) and high specificity (96.1%) for diagnosing LVH. Lowering the cut-off value from 35 mm to 31 mm improved the sensitivity in women from 3.5% to 14% while preserving specificity at 94.2%. A cut-off of 36 mm was optimal in men (sensitivity of 14.7%, specificity of 95.5%). Current ECG criteria for LVH derived in Western cohorts have limited sensitivity in Asian populations. Our data suggests that ethnicity- and gender-specific ECG criteria may be needed.

Pathological-Condition-Driven Construction of Supramolecular Nanoassemblies for Bacterial Infection Detection.

PubMed

Li, Li-Li; Ma, Huai-Lei; Qi, Guo-Bin; Zhang, Di; Yu, Faquan; Hu, Zhiyuan; Wang, Hao

2016-01-13

A pyropheophorbide-α-based building block (Ppa-PLGVRG-Van) can be used to construct self-aggregated superstructures in vivo for highly specific and sensitive diagnosis of bacterial infection by noninvasive photoacoustic tomography. This in vivo supramolecular chemistry approach opens a new avenue for efficient, rapid, and early-stage disease diagnosis with high sensitivity and specificity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Do We Know Who Will Drop out?: A Review of the Predictors of Dropping out of High School--Precision, Sensitivity, and Specificity

ERIC Educational Resources Information Center

Bowers, Alex J.; Sprott, Ryan; Taff, Sherry A.

2013-01-01

The purpose of this study is to review the literature on the most accurate indicators of students at risk of dropping out of high school. We used Relative Operating Characteristic (ROC) analysis to compare the sensitivity and specificity of 110 dropout flags across 36 studies. Our results indicate that 1) ROC analysis provides a means to compare…

Reliability of high- and low-field magnetic resonance imaging systems for detection of cartilage and bone lesions in the equine cadaver fetlock.

PubMed

Smith, M A; Dyson, S J; Murray, R C

2012-11-01

To determine the reliability of 2 magnetic resonance imaging (MRI) systems for detection of cartilage and bone lesions of the equine fetlock. To test the hypotheses that lesions in cartilage, subchondral and trabecular bone of the equine fetlock verified using histopathology can be detected on high- and low-field MR images with a low incidence of false positive or negative results; that low-field images are less reliable than high-field images for detection of cartilage lesions; and that combining results of interpretation from different pulse sequences increases detection of cartilage lesions. High- and low-field MRI was performed on 19 limbs from horses identified with fetlock lameness prior to euthanasia. Grading systems were used to score cartilage, subchondral and trabecular bone on MR images and histopathology. Sensitivity and specificity were calculated for images. High-field T2*-weighted gradient echo (T2*W-GRE) and low-field T2-weighted fast spin echo (T2W-FSE) images had high sensitivity but low specificity for detection of cartilage lesions. All pulse sequences had high sensitivity and low-moderate specificity for detection of subchondral bone lesions and moderate sensitivity and moderate-high specificity for detection of trabecular bone lesions (histopathology as gold standard). For detection of lesions of trabecular bone low-field T2*W-GRE images had higher sensitivity and specificity than T2W-FSE images. There is high likelihood of false positive results using high- or low-field MRI for detection of cartilage lesions and moderate-high likelihood of false positive results for detection of subchondral bone lesions compared with histopathology. Combining results of interpretation from different pulse sequences did not increase detection of cartilage lesions. MRI interpretation of trabecular bone was more reliable than cartilage or subchondral bone in both MR systems. Independent interpretation of a variety of pulse sequences may maximise detection of cartilage and bone lesions in the fetlock. Clinicians should be aware of potential false positive and negative results. © 2012 EVJ Ltd.

Preformed Frequencies of Cytomegalovirus (CMV)–Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients

PubMed Central

Lúcia, Marc; Crespo, Elena; Melilli, Edoardo; Cruzado, Josep M.; Luque, Sergi; Llaudó, Inés; Niubó, Jordi; Torras, Joan; Fernandez, Núria; Grinyó, Josep M.; Bestard, Oriol

2014-01-01

Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers. Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG–seronegative (sR−) and 86 CMV IgG–seropositive (sR+) patients. Clinical outcome was evaluated in both groups. Results. All sR+ patients showed a wide range of CMV-specific memory T- and B-cell responses. High memory T- and B-cell frequencies were also clearly detected in 30% of sR− patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test. Conclusions. Assessment of CMV-specific memory T- and B-cell responses before kidney transplantation among sR− recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection. PMID:25048845

ADHD Is Highly Prevalent in Patients Seeking Treatment for Cannabis Use Disorders.

PubMed

Notzon, Daniel P; Pavlicova, Martina; Glass, Andrew; Mariani, John J; Mahony, Amy L; Brooks, Daniel J; Levin, Frances R

2016-03-31

To estimate the prevalence of ADHD and determine an effective screening test for ADHD in a population-seeking treatment for cannabis use disorders. The Conners Adult ADHD Diagnostic Interview forDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV; CAADID) was used to generate sensitivity and specificity data for ADHD screening tests, which were then administered to 99 participants seeking treatment for cannabis use disorders to estimate ADHD prevalence. The prevalence estimated from the Wender Utah Rating Scale (WURS) was 45% (sensitivity = 0.88, sensitivity of 0.75), from the Conners Adult ADHD Rating Scale (CAARS) 34% (sensitivity = 0.80, specificity = 0.91), from the WURS + CAARS 36% (sensitivity = 0.71, specificity = 0.95), and from the Adult ADHD Self-Report Scale (ASRS) 46% (sensitivity = 0.61, specificity = 0.86). The prevalence of ADHD in adults seeking treatment for cannabis use disorders is estimated to be between 34% and 46%. The WURS paired with the CAARS provides excellent sensitivity and specificity for the diagnosis of ADHD in this population. © The Author(s) 2016.

Lyme Borreliosis--the Utility of Improved Real-Time PCR Assay in the Detection of Borrelia burgdorferi Infections.

PubMed

Bil-Lula, Iwona; Matuszek, Patryk; Pfeiffer, Thomas; Woźniak, Mieczysław

2015-01-01

Infections of Borrelia burgdorferi sensu lato reveal clinical manifestations affecting numerous organs and tissues. The standard diagnostic procedure of these infections is quite simple if a positive history of tick exposure or typical erythema migrans appears. Lack of unequivocal clinical symptoms creates the necessity for further evaluation with laboratory tests. This study discusses the utility of a novel, improved, well-optimized, sensitive and highly specific quantitative real-time PCR assay for the diagnostics of infections caused by Borrelia burgdorferi sensu lato. We designed an improved, specific, highly sensitive real-time quantitative polymerase chain reaction (RQ-PCR) assay for the detection and quantification of all Borrelia burgdorferi genotypes. A wide validation effort was undertaken to ensure confidence in the highly sensitive and specific detection of B. burgdorferi. Due to high sensitivity and great specificity, as low as 1.6×10² copies of Borrelia per mL of whole blood could be detected. As much as 12 (3%) negative ELISA IgM results, 14 (2.8%) negative results of Line blot IgM, 11 (3.1%) and 7 (2.7%) of negative ELISA IgG and Line blot IgG results, respectively, were positive in real-time PCR. The data in this study confirms the high positive predictive value of real-time PCR test in the detection of Borrelia infections.

Sensitivity and specificity of FTDC criteria for behavioral variant frontotemporal dementia.

PubMed

Harris, Jennifer M; Gall, Claire; Thompson, Jennifer C; Richardson, Anna M T; Neary, David; du Plessis, Daniel; Pal, Piyali; Mann, David M A; Snowden, Julie S; Jones, Matthew

2013-05-14

We aimed to assess sensitivity and specificity of the updated criteria for behavioral variant frontotemporal dementia (bvFTD) based on a large autopsy-confirmed cohort of patients with dementia. Two hundred thirty-nine consecutive pathologically confirmed dementia patients, clinically assessed in a specialist cognitive unit were identified. Patients with predominant aphasia, motor disorders, or insufficient clinical information were excluded. Frontotemporal Dementia Consensus criteria were applied to anonymized clinical data taken from patients' initial assessment by raters who were blinded to clinical and pathologic diagnosis. The final study cohort comprised 156 patients with predominantly early-onset dementia. The updated criteria for possible bvFTD had a sensitivity of 95% and specificity of 82%. Probable bvFTD criteria had a sensitivity of 85% and specificity of 95%. False positives were predominantly patients with presenile Alzheimer disease. Revised diagnostic criteria show encouragingly high sensitivity and specificity when applied to patients with early-onset dementia. They therefore provide a useful tool both for specialist researchers and general clinicians. There is a need for further prospective studies of sensitivity and specificity involving a broader spectrum of patients with dementia.

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

How typical are 'typical' tremor characteristics? Sensitivity and specificity of five tremor phenomena.

PubMed

van der Stouwe, A M M; Elting, J W; van der Hoeven, J H; van Laar, T; Leenders, K L; Maurits, N M; Tijssen, M A J

2016-09-01

Distinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five 'typical' tremor phenomena. Retrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on 'typical' characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (FT)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the 'typical' group was compared to the whole group. Most patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FT, whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity. In this study, we retrospectively determined sensitivity and specificity for five 'typical' tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low-cost polarization microscopy for cholesterol crystals

NASA Astrophysics Data System (ADS)

Kim, Kyungmin; Cho, Seonghee; Kim, Taehoon; Park, Hyoeun; Kim, Jinmoo; Lee, Seunghoon; Kang, Yeonsu; Chang, Kiyuk; Kim, Chulhong

2018-02-01

Because cholesterol crystals (Chcs) are a major cause of atherosclerosis, imaging Chcs in tissues with high sensitivity and specificity is important in diagnosing and predicting atherosclerosis. Polarizing microscopy (PM) has been widely used to image crystalline materials in tissues, but it has been difficult to distinguish Chcs from other crystalline materials in tissues. Thus, various methods such as fluorescent dye staining, Raman spectroscopy, and two-photon microscopy (TPM) have been developed to image Chcs with high sensitivity and specificity. However, these methods require expensive equipment or complex processes. Therefore, we have developed a low-cost, easy-to-use PM system using an LED light source that can distinguish Chcs from other crystalline materials with high sensitivity and specificity. Due to the nature of the LED spectrum in our system, collagen is displayed in yellow and Chcs in blue. In addition, we have improved the sensitivity and specificity by creating an aqueous condition on the sample. In the aqueous state, signals of yellowish collagen fibers were reduced and signals of Chcs were highlighted. The Chcs detection capability of our system was verified compared with the TPM image. In addition, clinical feasibility was shown by comparison with existing histological methods.

[Functional endoscopic evaluation of swallowing in infants with deglutition disorders].

PubMed

Partida-Justo, I; Israel Grijalva-Otero, J E; Ramírez-Figueroa, J L; Sepúlveda-Vildosola, A C; Zurita-Cruz, J N

2017-10-25

Functional endoscopic evaluation of swallowing (FEES) is a recognized method for Deglutition Disorders (DD) in adults, with anecdotal experience in children, obtaining not conclusive results. To compare the accuracy of test FEES in infants with high suspicion of altered DD seen in a third level hospital with the gold standard Videofluoroscopic (VF). The results and findings by FEES and VF of 66 children with clinical diagnosis of DD were compared. An estimate of the sensitivity and specificity of FEES was performed. As well as calculating positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios. 60 patients enrolled, 4 and FEES showed high sensitivity to identify the presence of aspiration and penetration (9 98%) and high specificity for the arrest of spillage and waste (94% and 95%). Gastroesophageal reflux to make the diagnosis of DD with FEES had a sensitivity of 80% and specificity of 84%. Spill and penetration had the highest agreement with respect to the gold standard of 0.81. FEES in infants diagnosed with DD had a sensitivity of 80.8% and specificity 85.3%. 0696 concordance regarding to the VFD in the diagnosis of DD, and to identify suction stroke had a kappa of 0815.

Blinded study determination of high sensitivity and specificity microchip electrophoresis-SSCP/HA to detect mutations in the p53 gene.

PubMed

Hestekin, Christa N; Lin, Jennifer S; Senderowicz, Lionel; Jakupciak, John P; O'Connell, Catherine; Rademaker, Alfred; Barron, Annelise E

2011-11-01

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single-strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA-based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor-intensive, time-consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here, we demonstrate the first blinded study using microchip electrophoresis (ME)-SSCP/HA. We demonstrate the ability of ME-SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5-9 in a blinded study in an analysis time of <10 min. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitivity and specificity of the gain short-screener for predicting substance use disorders in a large national sample of emerging adults.

PubMed

Smith, Douglas C; Bennett, Kyle M; Dennis, Michael L; Funk, Rodney R

2017-05-01

Emerging Adults (ages 18-25) have the highest prevalence of substance use disorders and rarely receive treatment from the specialty care system. Thus, it is important to have screening instruments specifically developed for emerging adults for use in Screening, Brief Intervention and Referral to Treatment (SBIRT) models. Optimal cutoffs for the widely-used GAIN Short-Screener's (GAIN-SS) Substance Disorder Screener (SDScrY) are not established specifically for emerging adults. Therefore, this study examined the sensitivity and specificity of the SDScrY in predicting emerging adult (ages 18-25) substance use disorders. We analyzed data from emerging adults in a large clinical sample (n=9,808) who completed both the five-item SDScrY (α=0.85) and the full criteria set for DSM-IV Substance Use Disorders. We estimated the sensitivity, specificity and area under the curve to determine optimal cutoffs. Analyses revealed a high correlation between the SDScrY screener and its longer parent scale (r=0.95, p<0.001). Sensitivity (83%) and specificity (95%) were highest at a cutoff score of two (AUC=94%) on the SDScrY for any past year substance use disorder. Sensitivity (85%) was also high at a cutoff score of two on the SDScrY for any past year alcohol disorder. The five-item Substance Use Disorder Screener is a sensitive and specific screener for emerging adults, and could be used to identify emerging adults who may benefit from SBIRT interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrochemistry-based Approaches to Low Cost, High Sensitivity, Automated, Multiplexed Protein Immunoassays for Cancer Diagnostics

PubMed Central

Dixit, Chandra K.; Kadimisetty, Karteek; Otieno, Brunah A.; Tang, Chi; Malla, Spundana; Krause, Colleen E.; Rusling, James F.

2015-01-01

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. Simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that doesn’t require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for highly sensitive detection of the panel of cancer-specific biomarkers with high specificity and at the same time have the potential to be translated into a POC. PMID:26525998

Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics.

PubMed

Dixit, Chandra K; Kadimisetty, Karteek; Otieno, Brunah A; Tang, Chi; Malla, Spundana; Krause, Colleen E; Rusling, James F

2016-01-21

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. The simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that does not require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for the highly sensitive detection of a panel of cancer-specific biomarkers with high specificity which at the same time has the potential to be translated into POC applications.

MOF-Bacteriophage Biosensor for Highly Sensitive and Specific Detection of Staphylococcus aureus.

PubMed

Bhardwaj, Neha; Bhardwaj, Sanjeev K; Mehta, Jyotsana; Kim, Ki-Hyun; Deep, Akash

2017-10-04

To produce a sensitive and specific biosensor for Staphylococcus aureus, bacteriophages have been interfaced with a water-dispersible and environmentally stable metal-organic framework (MOF), NH 2 -MIL-53(Fe). The conjugation of the MOF with bacteriophages has been achieved through the use of glutaraldehyde as cross-linker. Highly sensitive detection of S. aureus in both synthetic and real samples was realized by the proposed MOF-bacteriophage biosensor based on the photoluminescence quenching phenomena: limit of detection (31 CFU/mL) and range of detection (40 to 4 × 10 8 CFU/mL). This is the first report exploiting the use of an MOF-bacteriophage complex for the biosensing of S. aureus. The results of our study highlight that the proposed biosensor is more sensitive than most of the previous methods while exhibiting some advanced features like specificity, regenerability, extended range of linear detection, and stability for long-term storage (even at room temperature).

Evaluation and construction of diagnostic criteria for inclusion body myositis

PubMed Central

Mammen, Andrew L.; Amato, Anthony A.; Weiss, Michael D.; Needham, Merrilee

2014-01-01

Objective: To use patient data to evaluate and construct diagnostic criteria for inclusion body myositis (IBM), a progressive disease of skeletal muscle. Methods: The literature was reviewed to identify all previously proposed IBM diagnostic criteria. These criteria were applied through medical records review to 200 patients diagnosed as having IBM and 171 patients diagnosed as having a muscle disease other than IBM by neuromuscular specialists at 2 institutions, and to a validating set of 66 additional patients with IBM from 2 other institutions. Machine learning techniques were used for unbiased construction of diagnostic criteria. Results: Twenty-four previously proposed IBM diagnostic categories were identified. Twelve categories all performed with high (≥97%) specificity but varied substantially in their sensitivities (11%–84%). The best performing category was European Neuromuscular Centre 2013 probable (sensitivity of 84%). Specialized pathologic features and newly introduced strength criteria (comparative knee extension/hip flexion strength) performed poorly. Unbiased data-directed analysis of 20 features in 371 patients resulted in construction of higher-performing data-derived diagnostic criteria (90% sensitivity and 96% specificity). Conclusions: Published expert consensus–derived IBM diagnostic categories have uniformly high specificity but wide-ranging sensitivities. High-performing IBM diagnostic category criteria can be developed directly from principled unbiased analysis of patient data. Classification of evidence: This study provides Class II evidence that published expert consensus–derived IBM diagnostic categories accurately distinguish IBM from other muscle disease with high specificity but wide-ranging sensitivities. PMID:24975859

Optimizing the interpretation of CT for appendicitis: modeling health utilities for clinical practice.

PubMed

Blackmore, C Craig; Terasawa, Teruhiko

2006-02-01

Error in radiology can be reduced by standardizing the interpretation of imaging studies to the optimum sensitivity and specificity. In this report, the authors demonstrate how the optimal interpretation of appendiceal computed tomography (CT) can be determined and how it varies in different clinical scenarios. Utility analysis and receiver operating characteristic (ROC) curve modeling were used to determine the trade-off between false-positive and false-negative test results to determine the optimal operating point on the ROC curve for the interpretation of appendicitis CT. Modeling was based on a previous meta-analysis for the accuracy of CT and on literature estimates of the utilities of various health states. The posttest probability of appendicitis was derived using Bayes's theorem. At a low prevalence of disease (screening), appendicitis CT should be interpreted at high specificity (97.7%), even at the expense of lower sensitivity (75%). Conversely, at a high probability of disease, high sensitivity (97.4%) is preferred (specificity 77.8%). When the clinical diagnosis of appendicitis is equivocal, CT interpretation should emphasize both sensitivity and specificity (sensitivity 92.3%, specificity 91.5%). Radiologists can potentially decrease medical error and improve patient health by varying the interpretation of appendiceal CT on the basis of the clinical probability of appendicitis. This report is an example of how utility analysis can be used to guide radiologists in the interpretation of imaging studies and provide guidance on appropriate targets for the standardization of interpretation.

An evaluation of the diagnostic accuracy of the 1991 American College of Chest Physicians/Society of Critical Care Medicine and the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine/American College of Chest Physicians/American Thoracic Society/Surgical Infection Society sepsis definition.

PubMed

Zhao, Huifang; Heard, Stephen O; Mullen, Marie T; Crawford, Sybil; Goldberg, Robert J; Frendl, Gyorgy; Lilly, Craig M

2012-06-01

Limited research has been conducted to compare the test characteristics of the 1991 and 2001 sepsis consensus definitions. This study assessed the accuracy of the two sepsis consensus definitions among adult critically ill patients compared to sepsis case adjudication by three senior clinicians. Observational study of patients admitted to intensive care units. Seven intensive care units of an academic medical center. A random sample of 960 patients from all adult intensive care unit patients between October 2007 and December 2008. None. Sensitivity, specificity, and the area under the receiver operating characteristic curve for the two consensus definitions were calculated by comparing the number of patients who met or did not meet consensus definitions vs. the number of patients who were or were not diagnosed with sepsis by adjudication. The 1991 sepsis definition had a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which were 96.9% and 58.3%, respectively. The areas under the receiver operating characteristic curve for the two definitions were not statistically different (0.778 and 0.776, respectively). The sensitivities and areas under the receiver operating characteristic curve of both definitions were lower at the 24-hr time window level than those of the intensive care unit stay level, though their specificities increased slightly. Fever, high white blood cell count or immature forms, low Glasgow coma score, edema, positive fluid balance, high cardiac index, low PaO2/FIO2 ratio, and high levels of creatinine and lactate were significantly associated with sepsis by both definitions and adjudication. Both the 1991 and the 2001 sepsis definition have a high sensitivity but low specificity; the 2001 definition has a slightly increased sensitivity but a decreased specificity compared to the 1991 definition. The diagnostic performances of both definitions were suboptimal. A parsimonious set of significant predictors for sepsis diagnosis is likely to improve current sepsis case definitions.

Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation.

PubMed

Sellmann, Lea; Rabe, Kim; Bünting, Ivonne; Dammann, Elke; Göhring, Gudrun; Ganser, Arnold; Stadler, Michael; Weissinger, Eva M; Hambach, Lothar

2018-05-02

Conventional analysis of host chimerism (HC) frequently fails to detect relapse before its clinical manifestation in patients with hematological malignancies after allogeneic stem cell transplantation (allo-SCT). Quantitative PCR (qPCR)-based highly-sensitive chimerism analysis extends the detection limit of conventional (short tandem repeats-based) chimerism analysis from 1 to 0.01% host cells in whole blood. To date, the diagnostic value of highly-sensitive chimerism analysis is hardly defined. Here, we applied qPCR-based chimerism analysis to 901 blood samples of 71 out-patients with hematological malignancies after allo-SCT. Receiver operating characteristics (ROC) curves were calculated for absolute HC values and for the increments of HC before relapse. Using the best cut-offs, relapse was detected with sensitivities of 74 or 85% and specificities of 69 or 75%, respectively. Positive predictive values (PPVs) were only 12 or 18%, but the respective negative predictive values were 98 or 99%. Relapse was detected median 38 or 45 days prior to clinical diagnosis, respectively. Considering also durations of steadily increasing HC of more than 28 days improved PPVs to more than 28 or 59%, respectively. Overall, highly-sensitive chimerism analysis excludes relapses with high certainty and predicts relapses with high sensitivity and specificity more than a month prior to clinical diagnosis.

Highly sensitive detection of cancer cells using femtosecond dual-wavelength near-IR two-photon imaging.

PubMed

Starkey, Jean R; Makarov, Nikolay S; Drobizhev, Mikhail; Rebane, Aleksander

2012-07-01

We describe novel imaging protocols that allow detection of small cancer cell colonies deep inside tissue phantoms with high sensitivity and specificity. We compare fluorescence excited in Styryl-9M molecules by femtosecond pulses at near IR wavelengths, where Styryl-9M shows the largest dependence of the two-photon absorption (2PA) cross section on the local environment. We show that by calculating the normalized ratio of the two-photon excited fluorescence (2PEF) intensity at 1200 nm and 1100 nm excitation wavelengths we can achieve high sensitivity and specificity for determining the location of cancer cells surrounded by normal cells. The 2PEF results showed a positive correlation with the levels of MDR1 proteins expressed by the cells, and, for high MDR1 expressors, as few as ten cancer cells could be detected. Similar high sensitivity is also demonstrated for tumor colonies induced in mouse external ears. This technique could be useful in early cancer detection, and, perhaps, also in monitoring dormant cancer deposits.

Low cost automated whole smear microscopy screening system for detection of acid fast bacilli.

PubMed

Law, Yan Nei; Jian, Hanbin; Lo, Norman W S; Ip, Margaret; Chan, Mia Mei Yuk; Kam, Kai Man; Wu, Xiaohua

2018-01-01

In countries with high tuberculosis (TB) burden, there is urgent need for rapid, large-scale screening to detect smear-positive patients. We developed a computer-aided whole smear screening system that focuses in real-time, captures images and provides diagnostic grading, for both bright-field and fluorescence microscopy for detection of acid-fast-bacilli (AFB) from respiratory specimens. To evaluate the performance of dual-mode screening system in AFB diagnostic algorithms on concentrated smears with auramine O (AO) staining, as well as direct smears with AO and Ziehl-Neelsen (ZN) staining, using mycobacterial culture results as gold standard. Adult patient sputum samples requesting for M. tuberculosis cultures were divided into three batches for staining: direct AO-stained, direct ZN-stained and concentrated smears AO-stained. All slides were graded by an experienced microscopist, in parallel with the automated whole smear screening system. Sensitivity and specificity of a TB diagnostic algorithm in using the screening system alone, and in combination with a microscopist, were evaluated. Of 488 direct AO-stained smears, 228 were culture positive. These yielded a sensitivity of 81.6% and specificity of 74.2%. Of 334 direct smears with ZN staining, 142 were culture positive, which gave a sensitivity of 70.4% and specificity of 76.6%. Of 505 concentrated smears with AO staining, 250 were culture positive, giving a sensitivity of 86.4% and specificity of 71.0%. To further improve performance, machine grading was confirmed by manual smear grading when the number of AFBs detected fell within an uncertainty range. These combined results gave significant improvement in specificity (AO-direct:85.4%; ZN-direct:85.4%; AO-concentrated:92.5%) and slight improvement in sensitivity while requiring only limited manual workload. Our system achieved high sensitivity without substantially compromising specificity when compared to culture results. Significant improvement in specificity was obtained when uncertain results were confirmed by manual smear grading. This approach had potential to substantially reduce workload of microscopists in high burden countries.

Diagnosis of knee injuries: comparison of the physical examination and magnetic resonance imaging with the findings from arthroscopy☆

PubMed Central

Orlando Júnior, Nilton; de Souza Leão, Marcos George; de Oliveira, Nelson Henrique Carvalho

2015-01-01

Objectives To ascertain the sensitivity, specificity, accuracy and concordance of the physical examination (PE) and magnetic resonance imaging (MRI) in comparison with arthroscopy, in diagnosing knee injuries. Methods Prospective study on 72 patients, with evaluation and comparison of PE, MRI and arthroscopic findings, to determine the concordance, accuracy, sensitivity and specificity. Results PE showed sensitivity of 75.00%, specificity of 62.50% and accuracy of 69.44% for medial meniscal (MM) lesions, while it showed sensitivity of 47.82%, specificity of 93.87% and accuracy of 79.16% for lateral meniscal (LM) lesions. For anterior cruciate ligament (ACL) injuries, PE showed sensitivity of 88.67%, specificity of 94.73% and accuracy of 90.27%. For MM lesions, MRI showed sensitivity of 92.50%, specificity of 62.50% and accuracy of 69.44%, while for LM injuries, it showed sensitivity of 65.00%, specificity of 88.46% and accuracy of 81.94%. For ACL injuries, MRI showed sensitivity of 86.79%, specificity of 73.68% and accuracy of 83.33%. For ACL injuries, the best concordance was with PE, while for MM and LM lesions, it was with MRI (p < 0.001). Conclusions Meniscal and ligament injuries can be diagnosed through careful physical examination, while requests for MRI are reserved for complex or doubtful cases. PE and MRI used together have high sensitivity for ACL and MM lesions, while for LM lesions the specificity is higher. Level of evidence II – Development of diagnostic criteria on consecutive patients (with universally applied reference “gold” standard). PMID:27218085

[Diagnostic strategies in the Tuberculosis Clinic of the Hospital General La Raza National Medical Center].

PubMed

Flores-Ibarra, Alberto Alejandro; Ochoa-Vázquez, María Dolores; Sánchez-Tec, Georgina Alejandra

2016-01-01

In order to diagnose TB infection, tuberculin skin test and interferon gamma release assay are available. The tuberculin test has a sensitivity of 99 % and a specificity of 95 %. For the detection of interferon gamma in blood there are currently two tests available: TBGold QuantiFERON-In-Tube (with a sensitivity of 0.70 and a specificity of 0.90), and T-SPOT-TB (sensitivity 0.90 and specificity 0.93). To diagnose the disease, a microscopy of direct smears for acid-fast bacilli is used if the physician is facing an extensive cavitary lung disease due to M. tuberculosis (this test has a high sensitivity: 80-90 %). The most common staining techniques used are Ziehl-Neelsen and Kinyoun, and the fluorescent technique, auramine-rhodamine. The culture is the gold standard and it has a sensitivity of 80 % and a specificity over 90 %, but the results take weeks. The nucleic acid amplification test has an overall sensitivity and specificity of 0.85 and 0.97, respectively. In the presence of a pleural effusion is necessary to perform a pleural biopsy for culture with a sensitivity of 85 % if it is percutaneous and 98 % if it was taken by thoracoscopy. The adenosine deaminase can be determined in pleural fluid with a sensitivity and specificity of 95 %.

A New Method for Assessing How Sensitivity and Specificity of Linkage Studies Affects Estimation

PubMed Central

Moore, Cecilia L.; Amin, Janaki; Gidding, Heather F.; Law, Matthew G.

2014-01-01

Background While the importance of record linkage is widely recognised, few studies have attempted to quantify how linkage errors may have impacted on their own findings and outcomes. Even where authors of linkage studies have attempted to estimate sensitivity and specificity based on subjects with known status, the effects of false negatives and positives on event rates and estimates of effect are not often described. Methods We present quantification of the effect of sensitivity and specificity of the linkage process on event rates and incidence, as well as the resultant effect on relative risks. Formulae to estimate the true number of events and estimated relative risk adjusted for given linkage sensitivity and specificity are then derived and applied to data from a prisoner mortality study. The implications of false positive and false negative matches are also discussed. Discussion Comparisons of the effect of sensitivity and specificity on incidence and relative risks indicate that it is more important for linkages to be highly specific than sensitive, particularly if true incidence rates are low. We would recommend that, where possible, some quantitative estimates of the sensitivity and specificity of the linkage process be performed, allowing the effect of these quantities on observed results to be assessed. PMID:25068293

Development of a highly sensitive and specific immunoassay for enrofloxacin based on heterologous coating haptens.

PubMed

Wang, Zhanhui; Zhang, Huiyan; Ni, Hengjia; Zhang, Suxia; Shen, Jianzhong

2014-04-11

In the paper, an enzyme-linked immunosorbent immunoassay (ELISA) for detection of enrofloxacin was described using one new derivative of enrofloxacin as coating hapten, resulting in surprisingly high sensitivity and specificity. Incorporation of aminobutyric acid (AA) in the new derivative of enrofloxacin had decreased the IC50 of the ELISA for enrofloxacin from 1.3 μg L(-1) to as low as 0.07 μg L(-1). The assay showed neglect cross-reactivity for other fluoroquinolones but ofloxacin (8.23%), marbofloxacin (8.97%) and pefloxacin (7.29%). Analysis of enrofloxacin fortified chicken muscle showed average recoveries from 81 to 115%. The high sensitivity and specificity of the assay makes it a suitable screening method for the determination of low levels of enrofloxacin in chicken muscle without clean-up step. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of phenylethanolamine A in tissue and feed samples and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS).

PubMed

Cao, Biyun; He, Guangzhao; Yang, Hong; Chang, Huafang; Li, Shuqun; Deng, Anping

2013-10-15

Phenylethanolamine A (PA) is a new emerged β-adrenergic agonist illegally used as feed additives for growth promotion. In this study, a highly sensitive and specific indirect competitive enzyme-linked immunosorbent assay (ELISA) for the detection of PA in tissue and feed samples was developed and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS). By reduction of nitryl group to amino group, the PA derivative was synthesized and coupled to carrier proteins with diazobenzidine method. The antisera obtained from four immunized rabbits were characterized in terms of sensitivity and specificity. All antisera displayed high sensitivity with IC50 values lower than 0.48 ng mL(-1). The most sensitive ELISA was established with IC50 and limit of detection (LOD) values of 0.049 ng mL(-1) and 0.003 ng mL(-1), respectively. The cross-reactivity (CR) values of the antisera with three frequently used β-adrenergic agonists (clenbuterol, salbutamol and ractopamine) were lesser than 0.39%; there was no CR of the antisera with other six compounds including two structurally related substances (isoproterenol, phenylephrine). To investigate the accuracy and precision of the assay, swine kidney, liver, meat and feed samples were fortified with PA at different content and analyzed by ELISA. Acceptable recovery rates of 92.2-113.7% and intra-assay coefficients of variation of 3.8-10.9% (n=3) were achieved. Seven spiked samples were simultaneously analyzed by ELISA and LC-MS/MS. There was a high correlation coefficient of 0.9956 (n=7) between the two methods. The proposed ELISA proven to be a feasible quantitative/screening method for PA analysis in tissue and feed samples with the properties of high sensitivity and specificity, high sample throughput and low expensive. © 2013 Elsevier B.V. All rights reserved.

Tag Array gene chip rapid diagnosis anti-tuberculosis drug resistance in pulmonary tuberculosis -a feasibility study.

PubMed

Wu, Wenjie; Cheng, Peng; Lyu, Jingtong; Zhang, Zehua; Xu, Jianzhong

2018-05-01

We developed a Tag Array chip for detecting first- and second-line anti tuberculosis drug resistance in pulmonary tuberculosis and compared the analytical performance of the gene chip to that of phenotypic drug susceptibility testing (DST). From November 2011 to April 2016.234 consecutive culture-confirmed, clinically and imaging diagnosed patients with pulmonary tuberculosis from Southwest Hospital, Chongqing were enrolled into the study. Specimens collected during sputum or bronchoalveolar lavage fluid from the pulmonary tuberculosis patients were subjected to M. tuberculosis species identification and drug-resistance detection by the Tag Array gene chip, and evaluate the sensitivity and specificity of chip. A total of 186 patients was diagnosed drug-resistant tuberculosis. The detection of rifampicin (RFP), isoniazid (INH), fluoroquinolones (FQS), streptomycin (SM) resistance genes was highly sensitive and specific: however, for detection of amikacin (AMK), capreomycin (CPM), Kanamycin (KM), specificity was higher, but sensitivity was lower. Sensitivity for the detection of a mutation in the eis promoter region could be improved. The detection sensitivity of the EMB resistance gene was low, therefore it is easy to miss a diagnosis of EMB drug resistance, but its specificity was high. Tag Array chip can achieve rapid, accurate and high-throughput detection of tuberculosis resistance in pulmonary tuberculosis, which has important clinical significance and feasibility. Copyright © 2018. Published by Elsevier Ltd.

Imaging modalities for characterising focal pancreatic lesions.

PubMed

Best, Lawrence Mj; Rawji, Vishal; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-17

Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data. We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

Sensitivity and specificity of General Movements Assessment for diagnostic accuracy of detecting cerebral palsy early in an Australian context.

PubMed

Morgan, Catherine; Crowle, Cathryn; Goyen, Traci-Anne; Hardman, Caroline; Jackman, Michelle; Novak, Iona; Badawi, Nadia

2016-01-01

The aim of this study was to calculate the sensitivity and specificity of the General Movements Assessment (GMA) for estimating diagnostic accuracy in detecting cerebral palsy (CP) in an Australian context by a newly established NSW rater network. A prospective longitudinal cross-sectional study was conducted. The GMA was blind-rated from conventional video by two independent certified raters, blinded to medical history. A third rater resolved disagreements. High-risk population screening for CP using the GMA during the fidgety period (12-20 weeks) was carried out in four neonatal intensive care units and one CP service over a 30-month period (2012-2013). Participants were 259 high-risk infants. Sensitivity and specificity values were calculated with true positives defined as a confirmed diagnosis of CP from a medical doctor. Of the 259 infants assessed, 1-year follow-up data were available for 187. Of these, n = 48 had absent fidgety (high risk for CP), n = 138 had normal fidgety (low risk for CP), and n = 1 had abnormal fidgety (high risk for a neurological disorder). Of the 48 with absent fidgety movements, 39 had received a diagnosis of CP by 18 months and another 6 had an abnormal outcome. Of the n = 138 normal fidgety cases, n = 99 cases had a normal outcome, n = 38 had an abnormal outcome but not CP, and n = 1 had CP. For detecting CP, we had a sensitivity of 98% and specificity of 94%. GMA was feasible in an Australian context and accurately identified CP with a sensitivity and specificity comparable with European standards and published neuroimaging data. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

A highly sensitive and specific capacitive aptasensor for rapid and label-free trace analysis of Bisphenol A (BPA) in canned foods.

PubMed

Mirzajani, Hadi; Cheng, Cheng; Wu, Jayne; Chen, Jiangang; Eda, Shigotoshi; Najafi Aghdam, Esmaeil; Badri Ghavifekr, Habib

2017-03-15

A rapid, highly sensitive, specific and low-cost capacitive affinity biosensor is presented here for label-free and single step detection of Bisphenol A (BPA). The sensor design allows rapid prototyping at low-cost using printed circuit board material by benchtop equipment. High sensitivity detection is achieved through the use of a BPA-specific aptamer as probe molecule and large electrodes to enhance AC-electroelectrothermal effect for long-range transport of BPA molecules toward electrode surface. Capacitive sensing technique is used to determine the bounded BPA level by measuring the sample/electrode interfacial capacitance of the sensor. The developed biosensor can detect BPA level in 20s and exhibits a large linear range from 1 fM to 10 pM, with a limit of detection (LOD) of 152.93 aM. This biosensor was applied to test BPA in canned food samples and could successfully recover the levels of spiked BPA. This sensor technology is demonstrated to be highly promising and reliable for rapid, sensitive and on-site monitoring of BPA in food samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Challenges in Routine Implementation and Quality Control of Rapid Diagnostic Tests for Malaria–Rufiji District, Tanzania

PubMed Central

McMorrow, Meredith L.; Masanja, M. Irene; Abdulla, Salim M. K.; Kahigwa, Elizeus; Kachur, S. Patrick

2018-01-01

Rapid diagnostic tests (RDTs) represent an alternative to microscopy for malaria diagnosis and have shown high sensitivity and specificity in a variety of study settings. Current World Health Organization (WHO) guidelines for quality control of RDTs provide detailed instructions on pre-field testing, but offer little guidance for quality assurance once RDTs are deployed in health facilities. From September 2006 to April 2007, we introduced a histidine-rich protein II (HRP2)-based RDT (Paracheck) for suspected malaria cases five years of age and older in nine health facilities in Rufiji District, Tanzania, to assess sensitivity and specificity of RDTs in routine use at rural health facilities. Thick blood smears were collected for all patients tested with RDTs and stained and read by laboratory personnel in each facility. Thick smears were subsequently reviewed by a reference microscopist to determine RDT sensitivity and specificity. In all nine health facilities, there were significant problems with the quality of staining and microscopy. Sensitivity and specificity of RDTs were difficult to assess given the poor quality of routine blood smear staining. Mean operational sensitivity of RDTs based on reference microscopy was 64.8%, but varied greatly by health facility, range 18.8–85.9%. Sensitivity of RDTs increased with increasing parasite density. Specificity remained high at 87.8% despite relatively poor slide quality. Institution of quality control of RDTs based on poor quality blood smear staining may impede reliable measurement of sensitivity and specificity and undermine confidence in the new diagnostic. There is an urgent need for the development of alternative quality control procedures for rapid diagnostic tests that can be performed at the facility level. PMID:18784230

Evaluation of the highly sensitive chemiluminescent enzyme immunoassay "Lumipulse HBsAg-HQ" for hepatitis B virus screening.

PubMed

Deguchi, Matsuo; Kagita, Masanori; Yoshioka, Nori; Tsukamoto, Hiroko; Takao, Miyuki; Tahara, Kazuko; Maeda, Ikuhiro; Hidaka, Yoh; Yamauchi, Satoshi; Kaneko, Atsushi; Miyakoshi, Hideo; Isomura, Mitsuo

2017-10-06

Ongoing efforts in the development of HBsAg detection kits are focused on improving sensitivity and specificity. The purpose of this study was to evaluate an improved, highly sensitive quantitative assay, "Lumipulse HBsAg-HQ", a chemiluminescent enzyme immunoassay designed for a fully automated instrument, the "Lumipulse G1200". Serum samples for reproducibility, dilution, correlation, sensitivity, and specificity studies were obtained from patients at the Osaka University Hospital. Seroconversion and sensitivity panels were purchased from a commercial vender. Subtype, sensitivity panels, and HBsAg recombinant proteins with one or two amino acid substitutions were prepared in-house. The coefficients of variation for the low, medium, and high concentration samples ranged from 1.93 to 2.55%. The HBsAg-HQ reagent for dilution testing showed good linearity in the 0.005-150 HBsAg IU/mL range and no prozone phenomenon. All 102 HBV carrier samples were positive by HBsAg-HQ, while other commercial reagents showed one or more to be negative. In the seroconversion panel, the 14-day blood sample was positive. The sensitivity against HBsAg-HQ "ad" and "ay" subtypes was 0.025 ng/mL. Comparisons among the HBsAg-HQ, HISCL, and Architect HBsAg reagents were performed using the Bland-Altman plot. Specificity for 1000 seronegative individuals was 99.7%. HBsAg-HQ detected 29 positive serum among 12 231 routinely obtained serum samples, which showed concentrations of 0.005-0.05 HBsAg IU/mL. According to these results, the Lumipulse HBsAg-HQ assay, with a highly sensitive limit of detection of 0.005 IU/mL, may facilitate the development of a better management strategy for a considerable proportion of infected patients. © 2017 Wiley Periodicals, Inc.

Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs.

PubMed

Gulshan, Varun; Peng, Lily; Coram, Marc; Stumpe, Martin C; Wu, Derek; Narayanaswamy, Arunachalam; Venugopalan, Subhashini; Widner, Kasumi; Madams, Tom; Cuadros, Jorge; Kim, Ramasamy; Raman, Rajiv; Nelson, Philip C; Mega, Jessica L; Webster, Dale R

2016-12-13

Deep learning is a family of computational methods that allow an algorithm to program itself by learning from a large set of examples that demonstrate the desired behavior, removing the need to specify rules explicitly. Application of these methods to medical imaging requires further assessment and validation. To apply deep learning to create an algorithm for automated detection of diabetic retinopathy and diabetic macular edema in retinal fundus photographs. A specific type of neural network optimized for image classification called a deep convolutional neural network was trained using a retrospective development data set of 128 175 retinal images, which were graded 3 to 7 times for diabetic retinopathy, diabetic macular edema, and image gradability by a panel of 54 US licensed ophthalmologists and ophthalmology senior residents between May and December 2015. The resultant algorithm was validated in January and February 2016 using 2 separate data sets, both graded by at least 7 US board-certified ophthalmologists with high intragrader consistency. Deep learning-trained algorithm. The sensitivity and specificity of the algorithm for detecting referable diabetic retinopathy (RDR), defined as moderate and worse diabetic retinopathy, referable diabetic macular edema, or both, were generated based on the reference standard of the majority decision of the ophthalmologist panel. The algorithm was evaluated at 2 operating points selected from the development set, one selected for high specificity and another for high sensitivity. The EyePACS-1 data set consisted of 9963 images from 4997 patients (mean age, 54.4 years; 62.2% women; prevalence of RDR, 683/8878 fully gradable images [7.8%]); the Messidor-2 data set had 1748 images from 874 patients (mean age, 57.6 years; 42.6% women; prevalence of RDR, 254/1745 fully gradable images [14.6%]). For detecting RDR, the algorithm had an area under the receiver operating curve of 0.991 (95% CI, 0.988-0.993) for EyePACS-1 and 0.990 (95% CI, 0.986-0.995) for Messidor-2. Using the first operating cut point with high specificity, for EyePACS-1, the sensitivity was 90.3% (95% CI, 87.5%-92.7%) and the specificity was 98.1% (95% CI, 97.8%-98.5%). For Messidor-2, the sensitivity was 87.0% (95% CI, 81.1%-91.0%) and the specificity was 98.5% (95% CI, 97.7%-99.1%). Using a second operating point with high sensitivity in the development set, for EyePACS-1 the sensitivity was 97.5% and specificity was 93.4% and for Messidor-2 the sensitivity was 96.1% and specificity was 93.9%. In this evaluation of retinal fundus photographs from adults with diabetes, an algorithm based on deep machine learning had high sensitivity and specificity for detecting referable diabetic retinopathy. Further research is necessary to determine the feasibility of applying this algorithm in the clinical setting and to determine whether use of the algorithm could lead to improved care and outcomes compared with current ophthalmologic assessment.

64 slice-coronary computed tomography sensitivity and specificity in the evaluation of coronary artery bypass graft stenosis: A meta-analysis.

PubMed

Barbero, Umberto; Iannaccone, Mario; d'Ascenzo, Fabrizio; Barbero, Cristina; Mohamed, Abdirashid; Annone, Umberto; Benedetto, Sara; Celentani, Dario; Gagliardi, Marco; Moretti, Claudio; Gaita, Fiorenzo

2016-08-01

A non-invasive approach to define grafts patency and stenosis in the follow-up of coronary artery bypass graft (CABG) patients may be an interesting alternative to coronary angiography. 64-slice-coronary computed tomography is nowadays a diffused non-invasive method that permits an accurate evaluation of coronary stenosis, due to a high temporal and spatial resolution. However, its sensitivity and specificity in CABG evaluation has to be clearly defined, since published studies used different protocols and scanners. We collected all studies investigating patients with stable symptoms and previous CABG and reporting the comparison between diagnostic performances of invasive coronary angiography and 64-slice-coronary computed tomography. As a result, sensitivity and specificity of 64-slice-coronary computed tomography for CABG occlusion were 0.99 (95% CI 0.97-1.00) and 0.99 (95% CI: 0.99-1.00) with an area under the curve (AUC) of 0.99. 64-slice-coronary computed tomography sensitivity and specificity for the presence of any CABG stenosis >50% were 0.98 (95% CI: 0.97-0.99) and 0.98 (95% CI: 0.96-0.98), while AUC was 0.99. At meta-regression, neither the age nor the time from graft implantation had effect on sensitivity and specificity of 64-slice-coronary computed tomography detection of significant CABG stenosis or occlusion. In conclusion 64-slice-coronary computed tomography confirmed its high sensitivity and specificity in CABG stenosis or occlusion evaluation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

PubMed

Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

2016-01-01

Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

Sensitivity and specificity of the method used for ascertainment of healthcare-associated infections in the second Slovenian national prevalence survey.

PubMed

Serdt, Mojca; Lejko Zupanc, Tatjana; Korošec, Aleš; Klavs, Irena

2016-12-01

The second Slovenian national healthcare-associated infections (HAIs) prevalence survey (SNHPS) was conducted in acute-care hospitals in 2011. The objective was to assess the sensitivity and specificity of the method used for the ascertainment of six types of HAIs (bloodstream infections, catheter-associated infections, lower respiratory tract infections, pneumoniae, surgical site infections, and urinary tract infections) in the University Medical Centre Ljubljana (UMCL). A cross-sectional study was conducted in patients surveyed in the SNHPS in the UMCL using a retrospective medical chart review (RMCR) and European HAIs surveillance definitions. Sensitivity and specificity of the method used in the SNHPS using RMCR as a reference was computed for ascertainment of patients with any of the six selected types of HAIs and for individual types of HAIs. Agreement between the SNHPS and RMCR results was analyzed using Cohen's kappa coefficient. 1474 of 1742 (84.6%) patients surveyed in the SNHPS were included in RMCR. The sensitivity of the SNHPS method for detecting any of six HAIs was 90% (95% confidence interval (CI): 81%-95%) and specificity 99% (95% CI: 98%-99%). The sensitivity by type of HAI ranged from 63% (lower respiratory tract infections) to 92% (bloodstream infections). Specificity was at least 99% for all types of HAIs. Agreement between the two data collection approaches for HAIs overall was very good (κ=0.83). The overall sensitivity of SNHPS collection method for ascertaining HAIs overall was high and the specificity was very high. This suggests that the estimated prevalence of HAIs in the SNHPS was credible.

How sensitive and specific is urinalysis 'dipstick' testing for detection of hyperglycaemia and ketosis? An audit of findings from coronial autopsies.

PubMed

Mitchell, Rebecca; Thomas, Sunethra Devika; Langlois, Neil E I

2013-10-01

Biochemical analysis of glucose and ketones in the vitreous humour obtained at post-mortem examination is representative of the levels in the blood prior to death. Elevated levels can be indicative of conditions including diabetic ketoacidosis, which can be a cause for unexpected death. A rapid screening test for such conditions can be performed during the autopsy through urinalysis using test strips (urine 'dipstick' testing). The aim of this study was to assess the utility of urinalysis testing for post-mortem detection of derangements of glucose and ketone levels. The results of vitreous biochemical analysis and urinalysis were collated from 188 forensic autopsy cases. A vitreous glucose result of above 10 mmol/L was regarded as high. When this was compared to urinalysis results it was found that any urinalysis result above negative had a sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5 mmol/L was regarded as significantly elevated; a urinalysis result above negative had a sensitivity of 1, but a specificity of 0.12. Urinalysis ('dipstick' testing) for glucose has a good sensitivity and specificity for high vitreous glucose levels, which are regarded as indicative of pathological hyperglycaemia during life. It was found that urine testing for ketones either has an excellent sensitivity with low specificity or a poor sensitivity with a good specificity; however, this finding has to be viewed in the context of uncertainty of the biochemical level of significant ketosis.

Diagnosis of deep endometriosis: clinical examination, ultrasonography, magnetic resonance imaging, and other techniques.

PubMed

Bazot, Marc; Daraï, Emile

2017-12-01

The aim of the present review was to evaluate the contribution of clinical examination and imaging techniques, mainly transvaginal sonography and magnetic resonance imaging (MRI) to diagnose deep infiltrating (DE) locations using prisma statement recommendations. Clinical examination has a relative low sensitivity and specificity to diagnose DE. Independently of DE locations, for all transvaginal sonography techniques a pooled sensitivity and specificity of 79% and 94% are observed approaching criteria for a triage test. Whatever the protocol and MRI devices, the pooled sensitivity and specificity for pelvic endometriosis diagnosis were 94% and 77%, respectively. For rectosigmoid endometriosis, pooled sensitivity and specificity of MRI were 92% and 96%, respectively fulfilling criteria of replacement test. In conclusion, advances in imaging techniques offer high sensitivity and specificity to diagnose DE with at least triage value and for rectosigmoid endometriosis replacement value imposing a revision of the concept of laparoscopy as the gold standard. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291.

PubMed

Thress, Kenneth S; Brant, Roz; Carr, T Hedley; Dearden, Simon; Jenkins, Suzanne; Brown, Helen; Hammett, Tracey; Cantarini, Mireille; Barrett, J Carl

2015-12-01

To assess the ability of different technology platforms to detect epidermal growth factor receptor (EGFR) mutations, including T790M, from circulating tumor DNA (ctDNA) in advanced non-small cell lung cancer (NSCLC) patients. A comparison of multiple platforms for detecting EGFR mutations in plasma ctDNA was undertaken. Plasma samples were collected from patients entering the ongoing AURA trial (NCT01802632), investigating the safety, tolerability, and efficacy of AZD9291 in patients with EGFR-sensitizing mutation-positive NSCLC. Plasma was collected prior to AZD9291 dosing but following clinical progression on a previous EGFR-tyrosine kinase inhibitor (TKI). Extracted ctDNA was analyzed using two non-digital platforms (cobas(®) EGFR Mutation Test and therascreen™ EGFR amplification refractory mutation system assay) and two digital platforms (Droplet Digital™ PCR and BEAMing digital PCR [dPCR]). Preliminary assessment (38 samples) was conducted using all four platforms. For EGFR-TKI-sensitizing mutations, high sensitivity (78-100%) and specificity (93-100%) were observed using tissue as a non-reference standard. For the T790M mutation, the digital platforms outperformed the non-digital platforms. Subsequent assessment using 72 additional baseline plasma samples was conducted using the cobas(®) EGFR Mutation Test and BEAMing dPCR. The two platforms demonstrated high sensitivity (82-87%) and specificity (97%) for EGFR-sensitizing mutations. For the T790M mutation, the sensitivity and specificity were 73% and 67%, respectively, with the cobas(®) EGFR Mutation Test, and 81% and 58%, respectively, with BEAMing dPCR. Concordance between the platforms was >90%, showing that multiple platforms are capable of sensitive and specific detection of EGFR-TKI-sensitizing mutations from NSCLC patient plasma. The cobas(®) EGFR Mutation Test and BEAMing dPCR demonstrate a high sensitivity for T790M mutation detection. Genomic heterogeneity of T790M-mediated resistance may explain the reduced specificity observed with plasma-based detection of T790M mutations versus tissue. These data support the use of both platforms in the AZD9291 clinical development program. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Highly broad-specific and sensitive enzyme-linked immunosorbent assay for screening sulfonamides: Assay optimization and application to milk samples

USDA-ARS?s Scientific Manuscript database

A broad-specific and sensitive immunoassay for the detection of sulfonamides was developed by optimizing the conditions of an enzyme-linked immunosorbent assay (ELISA) in regard to different monoclonal antibodies (MAbs), assay format, immunoreagents, and several physicochemical factors (pH, salt, de...

Accuracy, Sensitivity and Specificity of Fine Needle Aspiration Biopsy for Salivary Gland Tumors: A Retrospective Study from 2006 to 2011

PubMed

Silva, William P P; Stramandinoli-Zanicotti, Roberta T; Schussel, Juliana L; Ramos, Gyl H A; Ioshi, Sergio O; Sassi, Laurindo M

2016-11-01

Objective: This article concerns evaluation of the sensitivity, specificity and accuracy of FNAB for pre-surgical diagnosis of benign and malignant lesions of major and minor salivary glands of patients treated in the Department of Head and Neck Surgery of Erasto Gartner Hospital. Methods: This retrospective study analyzed medical records from January 2006 to December 2011 from patients with salivary gland lesions who underwent preoperative FNAB and, after surgical excision of the lesion, histopathological examination. Results: The study had a cohort of 130 cases, but 34 cases (26.2%) were considered unsatisfactory regarding cytology analyses. Based on the data, sensitivity was 66.7% (6/9), specificity was 81.6% (71/87), accuracy was 80.2% (77/96), the positive predictive value was 66,7% (6/9) and the negative predictive value was 81.6% (71/87). Conclusion: Despite the high rate of inadequate samples obtained in the FNAB in this study the technique offers high specificity, accuracy and acceptable sensitivity. Creative Commons Attribution License

SENSITIVITY AND SPECIFICITY OF DETECTING POLYPOIDAL CHOROIDAL VASCULOPATHY WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PubMed

de Carlo, Talisa E; Kokame, Gregg T; Kaneko, Kyle N; Lian, Rebecca; Lai, James C; Wee, Raymond

2018-03-20

Determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis with structural en face optical coherence tomography (OCT) and OCT angiography (OCTA). Retrospective review of the medical records of eyes diagnosed with PCV by indocyanine green angiography with review of diagnostic testing with structural en face OCT and OCTA by a trained reader. Structural en face OCT, cross-sectional OCT angiograms alone, and OCTA in its entirety were reviewed blinded to the findings of indocyanine green angiography and each other to determine if they could demonstrate the PCV complex. Sensitivity and specificity of PCV diagnosis was determined for each imaging technique using indocyanine green angiography as the ground truth. Sensitivity and specificity of structural en face OCT were 30.0% and 85.7%, of OCT angiograms alone were 26.8% and 96.8%, and of the entire OCTA were 43.9% and 87.1%, respectively. Sensitivity and specificity were improved for OCT angiograms and OCTA when looking at images taken within 1 month of PCV diagnosis. Sensitivity of detecting PCV was low using structural en face OCT and OCTA but specificity was high. Indocyanine green angiography remains the gold standard for PCV detection.

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy

PubMed Central

Zur, RM; Roy, LM; Ito, S; Beyene, J; Carew, C; Ungar, WJ

2016-01-01

Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3–87.0%) and 98.9% (96.3–100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1–99.4%) and 100.0% (99.9–100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4–95.5%) and 92.6% (86.5–96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6–97.5%) and 99.2% (98.4–99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines. PMID:27217052

Methylation-Sensitive High Resolution Melting (MS-HRM).

PubMed

Hussmann, Dianna; Hansen, Lise Lotte

2018-01-01

Methylation-Sensitive High Resolution Melting (MS-HRM) is an in-tube, PCR-based method to detect methylation levels at specific loci of interest. A unique primer design facilitates a high sensitivity of the assays enabling detection of down to 0.1-1% methylated alleles in an unmethylated background.Primers for MS-HRM assays are designed to be complementary to the methylated allele, and a specific annealing temperature enables these primers to anneal both to the methylated and the unmethylated alleles thereby increasing the sensitivity of the assays. Bisulfite treatment of the DNA prior to performing MS-HRM ensures a different base composition between methylated and unmethylated DNA, which is used to separate the resulting amplicons by high resolution melting.The high sensitivity of MS-HRM has proven useful for detecting cancer biomarkers in a noninvasive manner in urine from bladder cancer patients, in stool from colorectal cancer patients, and in buccal mucosa from breast cancer patients. MS-HRM is a fast method to diagnose imprinted diseases and to clinically validate results from whole-epigenome studies. The ability to detect few copies of methylated DNA makes MS-HRM a key player in the quest for establishing links between environmental exposure, epigenetic changes, and disease.

Assessing the validity and reliability of three indicators self-reported on the pregnancy risk assessment monitoring system survey.

PubMed

Ahluwalia, Indu B; Helms, Kristen; Morrow, Brian

2013-01-01

We investigated the reliability and validity of three self-reported indicators from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey. We used 2008 PRAMS (n=15,646) data from 12 states that had implemented the 2003 revised U.S. Certificate of Live Birth. We estimated reliability by kappa coefficient and validity by sensitivity and specificity using the birth certificate data as the reference for the following: prenatal participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC); Medicaid payment for delivery; and breastfeeding initiation. These indicators were examined across several demographic subgroups. The reliability was high for all three measures: 0.81 for WIC participation, 0.67 for Medicaid payment of delivery, and 0.72 for breastfeeding initiation. The validity of PRAMS indicators was also high: WIC participation (sensitivity = 90.8%, specificity = 90.6%), Medicaid payment for delivery (sensitivity = 82.4%, specificity = 85.6%), and breastfeeding initiation (sensitivity = 94.3%, specificity = 76.0%). The prevalence estimates were higher on PRAMS than the birth certificate for each of the indicators except Medicaid-paid delivery among non-Hispanic black women. Kappa values within most subgroups remained in the moderate range (0.40-0.80). Sensitivity and specificity values were lower for Hispanic women who responded to the PRAMS survey in Spanish and for breastfeeding initiation among women who delivered very low birthweight and very preterm infants. The validity and reliability of the PRAMS data for measures assessed were high. Our findings support the use of PRAMS data for epidemiological surveillance, research, and planning.

Development of a H2 O2 -sensitive quantum dots-based fluorescent sandwich ELISA for sensitive detection of bovine β-lactoglobulin by monoclonal antibody.

PubMed

He, Shengfa; Li, Xin; Gao, Jinyan; Tong, Ping; Chen, Hongbing

2018-01-01

Bovine β-lactoglobulin (BLG) is the major allergen in cows' milk, and the specific epitope plays a key role in food allergy. Developing a method specifically bind to the IgE epitope is necessary for testing BLG and its allergenic residues. The monoclonal antibody (1G9) specific to the IgE linear epitope for BLG was identified as high affinity and specificity. Based on 1G9, a sensitive fluorescent sandwich enzyme-linked immunosorbent assay (sELISA) was successfully developed using catalase-mediated fluorescence quenching of thiolated CdTe quantum dots in the presence of hydrogen peroxide as fluorescent signal output. The fluorescent sELISA showed high sensitivity and specificity, the limit of detection was 0.49 ng mL -1 , which was 16-fold lower than horseradish peroxidase (HRP)-based sELISA. The linear range for BLG detection were 125-4000 ng mL -1 (r = 0.9939) and 0.48-62.5 ng mL -1 (r = 0.9919). The recoveries and coefficients of variation were 94.25-109.83% and 4.38-20.29%, respectively. Allergenic residues were also detected in hydrolysed infant formulas. The results of fluorescent sELISA showed good performance as HRP-based sELISA and commercial sELISA kit. This proposed fluorescent sELISA could be employed to detect BLG and its allergenic residues in food with highly sensitivity, reliability, and recovery. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Performance of the ASAS classification criteria for axial and peripheral spondyloarthritis: a systematic literature review and meta-analysis.

PubMed

Sepriano, Alexandre; Rubio, Roxana; Ramiro, Sofia; Landewé, Robert; van der Heijde, Désirée

2017-05-01

To summarise the evidence on the performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) (also imaging and clinical arm separately), peripheral (p)SpA and the entire set, when tested against the rheumatologist's diagnosis ('reference standard'). A systematic literature review was performed to identify eligible studies. Raw data on SpA diagnosis and classification were extracted or, if necessary, obtained from the authors of the selected publications. A meta-analysis was performed to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood ratios, by fitting random effects models. Nine papers fulfilled the inclusion criteria (N=5739 patients). The entire set of the ASAS SpA criteria yielded a high pooled sensitivity (73%) and specificity (88%). Similarly, good results were found for the axSpA criteria (sensitivity: 82%; specificity: 88%). Splitting the axSpA criteria in 'imaging arm only' and 'clinical arm only' resulted in much lower sensitivity (30% and 23% respectively), but very high specificity was retained (97% and 94% respectively). The pSpA criteria were less often tested than the axSpA criteria and showed a similarly high pooled specificity (87%) but lower sensitivity (63%). Accumulated evidence from studies with more than 5500 patients confirms the good performance of the various ASAS SpA criteria as tested against the rheumatologist's diagnosis. 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/.

A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma[S

PubMed Central

Jiang, Xuntian; Sidhu, Rohini; Porter, Forbes D.; Yanjanin, Nicole M.; Speak, Anneliese O.; te Vruchte, Danielle Taylor; Platt, Frances M.; Fujiwara, Hideji; Scherrer, David E.; Zhang, Jessie; Dietzen, Dennis J.; Schaffer, Jean E.; Ory, Daniel S.

2011-01-01

Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3β,5α,6β-triol (3β,5α,6β-triol) and 7-ketocholesterol (7-KC), were markedly increased in the plasma of human NPC1 subjects, suggesting a role for these oxysterols in diagnosis of NPC1 disease and evaluation of therapeutics in clinical trials. In the present study, we describe the development of a sensitive and specific LC-MS/MS method for quantifying 3β,5α,6β-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine. We show that dimethylglycine derivatization successfully enhanced the ionization and fragmentation of 3β,5α,6β-triol and 7-KC for mass spectrometric detection of the oxysterol species in human plasma. The oxysterol dimethylglycinates were resolved with high sensitivity and selectivity, and enabled accurate quantification of 3β,5α,6β-triol and 7-KC concentrations in human plasma. The LC-MS/MS assay was able to discriminate with high sensitivity and specificity between control and NPC1 subjects, and offers for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease. PMID:21518695

A highly sensitive search strategy for clinical trials in Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) was developed.

PubMed

Manríquez, Juan J

2008-04-01

Systematic reviews should include as many articles as possible. However, many systematic reviews use only databases with high English language content as sources of trials. Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) is an underused source of trials, and there is not a validated strategy for searching clinical trials to be used in this database. The objective of this study was to develop a sensitive search strategy for clinical trials in LILACS. An analytical survey was performed. Several single and multiple-term search strategies were tested for their ability to retrieve clinical trials in LILACS. Sensitivity, specificity, and accuracy of each single and multiple-term strategy were calculated using the results of a hand-search of 44 Chilean journals as gold standard. After combining the most sensitive, specific, and accurate single and multiple-term search strategy, a strategy with a sensitivity of 97.75% (95% confidence interval [CI]=95.98-99.53) and a specificity of 61.85 (95% CI=61.19-62.51) was obtained. LILACS is a source of trials that could improve systematic reviews. A new highly sensitive search strategy for clinical trials in LILACS has been developed. It is hoped this search strategy will improve and increase the utilization of LILACS in future systematic reviews.

External validation of heart-type fatty acid binding protein, high-sensitivity cardiac troponin, and electrocardiography as rule-out for acute myocardial infarction.

PubMed

Van Hise, Christopher B; Greenslade, Jaimi H; Parsonage, William; Than, Martin; Young, Joanna; Cullen, Louise

2018-02-01

To externally validate a clinical decision rule incorporating heart fatty acid binding protein (h-FABP), high-sensitivity troponin (hs-cTn) and electrocardiogram (ECG) for the detection of acute myocardial infarction (AMI) on presentation to the Emergency Department. We also investigated whether this clinical decision rule improved identification of AMI over algorithms incorporating hs-cTn and ECG only. This study included data from 789 patients from the Brisbane ADAPT cohort and 441 patients from the Christchurch TIMI RCT cohort. The primary outcome was index AMI. Sensitivity, specificity, positive predictive value and negative predictive value were used to assess the diagnostic accuracy of the algorithms. 1230 patients were recruited, including 112 (9.1%) with AMI. The algorithm including h-FABP and hs-cTnT had 100% sensitivity and 32.4% specificity. The algorithm utilising h-FABP and hs-cTnI had similar sensitivity (99.1%) and higher specificity (43.4%). The hs-cTnI and hs-cTnT algorithms without h-FABP both had a sensitivity of 98.2%; a result that was not significantly different from either algorithm incorporating h-FABP. Specificity was higher for the hs-cTnI algorithm (68.1%) compared to the hs-cTnT algorithm (33.0%). The specificity of the algorithm incorporating hs-cTnI alone was also significantly higher than both of the algorithms incorporating h-FABP (p<0.01). For patients presenting to the Emergency Department with chest pain, an algorithm incorporating h-FABP, hs-cTn and ECG has high accuracy and can rule out up to 40% of patients. An algorithm incorporating only hs-cTn and ECG has similar sensitivity and may rule out a higher proportion of patients. Each of the algorithms can be used to safely identify patients as low risk for AMI on presentation to the Emergency Department. Copyright © 2017 The Canadian Society of Clinical Chemists. All rights reserved.

Sensitivity, specificity and predictive values of anterior chamber tap in cases of bacterial endophthalmitis.

PubMed

Sjoholm-Gomez de Liano, Carl; Soberon-Ventura, Vidal F; Salcedo-Villanueva, Guillermo; Santos-Palacios, Abril; Guerrero-Naranjo, Jose Luis; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

2017-01-01

To assess the sensitivity, specificity, positive predictive value and negative predictive value of anterior chamber tap for the diagnosis of bacterial endophthalmitis on a population with high prevalence. Retrospective, single centre, case series study. We reviewed all medical records with clinical diagnosis of bacterial endophthalmitis in our hospital from January 1st, 2000 to December 31st 2014. From each record, we documented general demographic data, best corrected visual acuity and vitreous and aqueous tap microbiological results. All cases were further divided according to the endophthalmitis aetiology to perform individual calculations of sensitivity, specificity, positive predictive value, negative predictive value, accuracy and prevalence. We used the results of the vitreous tap as the gold standard for diagnosis of bacterial endophthalmitis. We excluded those records in which the aqueous and vitreous samples were not taken simultaneously or had an incomplete microbiological report. Significance were assessed with chi squared statistics, with an alpha value of 0.05 for statistical significance. A total of 190 cases fulfilled the inclusion/exclusion criteria. Positive culture rate from vitreous samples was 64.74%. Positive culture rate from aqueous sample was 32.11%. Bacteria isolated from aqueous samples matched those isolated from vitreous samples 78.68% of the time. The overall sensitivity was 38.21%, specificity: 75.51%, positive predictive value: 79.66%, negative predictive value: 32.74% ( p  = 0.08). Subgroup analysis showed that anterior chamber taps in cases of post-surgical endophthalmitis had a moderate to low sensitivity (37.73%), high specificity (93%) and high positive predictive value (95%) ( p  < 0.04). The sensitivity and specificity of anterior chamber tap are low and should not be used for critical therapeutic decisions in patients with suspected bacterial endophthalmitis. In cases of post-surgical endophthalmitis, the result of an anterior chamber tap could be used for therapeutic guidance, but only in conjunction with clinical presentation and in the absence of a better method for diagnosis.

Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma.

PubMed

Holzinger, Dana; Wichmann, Gunnar; Baboci, Lorena; Michel, Angelika; Höfler, Daniela; Wiesenfarth, Manuel; Schroeder, Lea; Boscolo-Rizzo, Paolo; Herold-Mende, Christel; Dyckhoff, Gerhard; Boehm, Andreas; Del Mistro, Annarosa; Bosch, Franz X; Dietz, Andreas; Pawlita, Michael; Waterboer, Tim

2017-06-15

To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1 ∧ E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx. © 2017 UICC.

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147

Loop-mediated isothermal amplification for detection of Staphylococcus aureus in dairy cow suffering from mastitis.

PubMed

Tie, Zhang; Chunguang, Wang; Xiaoyuan, Wei; Xinghua, Zhao; Xiuhui, Zhong

2012-01-01

To develop a rapid detection method of Staphylococcus aureus using loop-mediated isothermal amplification (LAMP), four specific primers were designed according to six distinct sequences of the nuc gene. In addition, the specificity and sensitivity of LAMP were verified and compared with those of PCR. Results showed that the LAMP reaction was completed within 45 min at 62.5°C, and ladder bands were appeared in LAMP products analyzed by gel electrophoresis. After adding 1x SYBR Green l, the positive reaction tube showed green color and the negative reaction tube remained orange, indicating that the LAMP has high specificity. The minimal detectable concentration of LAMP was 1 × 10² CFU/mL and that of PCR was 1 × 10⁴ CFU/mL, indicating that the LAMP was 100 times more sensitive than the PCR. The LAMP method for detection of Staphylococcus aureus has many advantages, such as simple operation, high sensitivity, high specificity, and rapid analysis. Therefore, this method is more suitable for the rapid on-site detection of Staphylococcus aureus.

Novel rolling circle amplification and DNA origami-based DNA belt-involved signal amplification assay for highly sensitive detection of prostate-specific antigen (PSA).

PubMed

Yan, Juan; Hu, Chongya; Wang, Ping; Liu, Rui; Zuo, Xiaolei; Liu, Xunwei; Song, Shiping; Fan, Chunhai; He, Dannong; Sun, Gang

2014-11-26

Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts have been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments, and high cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic bead-based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.

The Accuracy of Integrated [18F] Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Detection of Pelvic and Para-aortic Nodal Metastasis in Patients with High Risk Endometrial Cancer

PubMed Central

Gholkar, Nikhil Shirish; Saha, Subhas Chandra; Prasad, GRV; Bhattacharya, Anish; Srinivasan, Radhika; Suri, Vanita

2014-01-01

Lymph nodal (LN) metastasis is the most important prognostic factor in high-risk endometrial cancer. However, the benefit of routine lymphadenectomy in endometrial cancer is controversial. This study was conducted to assess the accuracy of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography ([18F] FDG-PET/CT) in detection of pelvic and para-aortic nodal metastases in high-risk endometrial cancer. 20 patients with high-risk endometrial carcinoma underwent [18F] FDG-PET/CT followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy. The findings on histopathology were compared with [18F] FDG-PET/CT findings to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F] FDG-PET/CT. The pelvic nodal findings were analyzed on a patient and nodal chain based criteria. The para-aortic nodal findings were reported separately. Histopathology documented nodal involvement in two patients (10%). For detection of pelvic nodes, on a patient based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 61.11%, PPV of 22.22%, NPV of 100% and accuracy of 65% and on a nodal chain based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 80%, PPV of 20%, NPV of 100%, and accuracy of 80.95%. For detection of para-aortic nodes, [18F] FDG-PET/CT had sensitivity of 100%, specificity of 66.67%, PPV of 20%, NPV of 100%, and accuracy of 69.23%. Although [18F] FDG-PET/CT has high sensitivity for detection of LN metastasis in endometrial carcinoma, it had moderate accuracy and high false positivity. However, the high NPV is important in selecting patients in whom lymphadenectomy may be omitted. PMID:25538488

Sensitivity, accuracy, and precision issues in opto-electronic holography based on fiber optics and high-spatial- and high-digitial-resolution cameras

NASA Astrophysics Data System (ADS)

Furlong, Cosme; Yokum, Jeffrey S.; Pryputniewicz, Ryszard J.

2002-06-01

Sensitivity, accuracy, and precision characteristics in quantitative optical metrology techniques, and specifically in optoelectronic holography based on fiber optics and high-spatial and high-digital resolution cameras, are discussed in this paper. It is shown that sensitivity, accuracy, and precision dependent on both, the effective determination of optical phase and the effective characterization of the illumination-observation conditions. Sensitivity, accuracy, and precision are investigated with the aid of National Institute of Standards and Technology (NIST) traceable gages, demonstrating the applicability of quantitative optical metrology techniques to satisfy constantly increasing needs for the study and development of emerging technologies.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease, an Endemic Osteoarthritis, in China.

PubMed

Yu, Fang Fang; Ping, Zhi Guang; Yao, Chong; Wang, Zhi Wen; Wang, Fu Qi; Guo, Xiong

2017-02-01

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease (KBD) using six clinical markers: flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling. The survey included baseline characteristics and clinical diagnoses, and the sensitivity and specificity of the new criteria was evaluated. We identified 3,459 KBD patients, of which 69 had early stage KBD, 1,952 had stage I, 1,132 had stage II, and 306 had stage III. A screening test classified enlarged finger joints as stage I KBD, with a sensitivity and specificity of 0.978 and 0.045, respectively. Shortened fingers were classified as stage II KBD, with a sensitivity and specificity of 0.969 and 0.844, respectively, and dwarfism was classified as stage III KBD with a sensitivity and specificity of 0.951 and 0.992, respectively. Serial screening test revealed that the new clinical classification of KBD classified stages I, II, and III KBD with sensitivities of 0.949, 0.945, and 0.925 and specificities of 0.967, 0.970, and 0.993, respectively. The screening tests revealed that enlarged finger joints, shortened fingers, and dwarfism were appropriate markers for the clinical diagnosis and classification of KBD with high sensitivity and specificity. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Factors affecting the sensitivity and specificity of the Heidelberg Retina Tomograph parameters to glaucomatous progression in disc photographs.

PubMed

Saarela, Ville; Falck, Aura; Airaksinen, P Juhani; Tuulonen, Anja

2012-03-01

To evaluate the factors affecting the sensitivity and specificity of the stereometric optic nerve head (ONH) parameters of the Heidelberg Retina Tomograph (HRT) to glaucomatous progression in stereoscopic ONH photographs. The factors affecting the sensitivity and specificity of the vertical cup : disc ratio, the cup : disc area ratio, the cup volume, the rim area and a linear discriminant function to progression were analysed. These parameters were the best indicators of progression in a retrospective study of 476 eyes. The reference standard for progression was the masked evaluation of stereoscopic ONH photographs. The factors having the most significant effect on the sensitivity and specificity of the stereometric ONH parameters were the reference height difference and the mean topography standard deviation (TSD), indicating image quality. Also, the change in the TSD and age showed consistent, but variably significant, influence on all parameters tested. The sensitivity and specificity improved when there was little change in the reference height, the image quality was good and stable, and the patients were younger. The sensitivity and specificity of the vertical cup : disc ratio was improved by a large disc area and high baseline cup : disc area ratio. The rim area showed a better sensitivity and specificity for progression with a small disc area and low baseline cup : disc area ratio. The factors affecting the sensitivity and specificity of the stereometric ONH parameters to glaucomatous progression in disc photographs are essentially the same as those affecting the measurement variability of the HRT. © 2010 The Authors. Acta Ophthalmologica © 2010 Acta Ophthalmologica Scandinavica Foundation.

Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease.

PubMed

Kaszás, B; Kovács, N; Balás, I; Kállai, J; Aschermann, Z; Kerekes, Z; Komoly, S; Nagy, F; Janszky, J; Lucza, T; Karádi, K

2012-06-01

Among the non-motor features of Parkinson's disease (PD), cognitive impairment is one of the most troublesome problems. Highly sensitive and specific screening instruments for detecting dementia in PD (PDD) are required in the clinical practice. In our study we evaluated the sensitivity and specificity of different neuropsychological tests (Addenbrooke's Cognitive Examination, ACE; Frontal Assessment Battery, FAB and Mattis Dementia Rating Scale, MDRS) in 73 Parkinson's disease patients without depression. By receiver operating characteristic curve analysis, these screening instruments were tested against the recently established clinical diagnostic criteria of PDD. Best cut-off score for ACE to identify PDD was 80 points (sensitivity = 74.0%, specificity = 78.1%). For FAB the most optimal cut-off value was 12 points (sensitivity = 66.3%, specificity = 72.2%); whereas for MDRS it was 125 points (sensitivity = 89.8%, specificity = 98.3%). Among the examined test batteries, MDRS had the best clinicometric profile for detecting PDD. Although the types of applied screening instruments might differ from movement disorder clinic to clinic within a country, determination of the most specific and sensitive test for the given population remains to be an important task. Our results demonstrated that the specificity and sensitivity of MDRS was better than those of ACE, FAB and MMSE in Hungary. However, further studies with larger sample size and more uniform criteria for participation are required to determine the most suitable screening instrument for cognitive impairment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of highly conserved hsp65-specific nested PCR primers for diagnosing Mycobacterium tuberculosis.

PubMed

Priyadarshini, P; Tiwari, K; Das, A; Kumar, D; Mishra, M N; Desikan, P; Nath, G

2017-02-01

To evaluate the sensitivity and specificity of a new nested set of primers designed for the detection of Mycobacterium tuberculosis complex targeting a highly conserved heat shock protein gene (hsp65). The nested primers were designed using multiple sequence alignment assuming the nucleotide sequence of the M. tuberculosis H37Rv hsp65 genome as base. Multidrug-resistant Mycobacterium species along with other non-mycobacterial and fungal species were included to evaluate the specificity of M. tuberculosis hsp65 gene-specific primers. The sensitivity of the primers was determined using serial 10-fold dilutions, and was 100% as shown by the bands in the case of M. tuberculosis complex. None of the other non M. tuberculosis complex bacterial and fungal species yielded any band on nested polymerase chain reaction (PCR). The first round of amplification could amplify 0.3 ng of the template DNA, while nested PCR could detect 0.3 pg. The present hsp65-specific primers have been observed to be sensitive, specific and cost-effective, without requiring interpretation of biochemical tests, real-time PCR, sequencing or high-performance liquid chromatography. These primer sets do not have the drawbacks associated with those protocols that target insertion sequence 6110, 16S rDNA, rpoB, recA and MPT 64.

Evaluation of the Kodak Surecell Chlamydia test for the laboratory diagnosis of adult inclusion conjunctivitis.

PubMed

Tantisira, J G; Kowalski, R P; Gordon, Y J

1995-07-01

The Kodak Surecell Chlamydia test, a rapid enzyme immunoassay, has been reported to be highly sensitive (93%) and specific (96%) for detecting chlamydial lipopolysaccharide antigen in conjunctival specimens from infants, but has not been evaluated previously in adult conjunctival specimens. This study was designed to determine the efficacy of the Kodak Surecell Chlamydia test for the laboratory diagnosis of adult inclusion conjunctivitis. Twenty Chlamydia culture-positive conjunctival specimens from adults (true-positives) and 20 true-negative specimens were tested with the Kodak Surecell Chlamydia test. The Kodak Surecell Chlamydia test was 40% (8/20) sensitive, 100% (20/20) specific, and 70% (28/40) efficient. This study indicates that the Kodak Surecell Chlamydia test, though highly specific, is less sensitive in its ability to diagnose chlamydial conjunctivitis in adults than has been reported previously in infants.

Highly Sensitive Multiplex Assay for Detection of Human Immunodeficiency Virus Type 1 and Hepatitis C Virus RNA

PubMed Central

Giachetti, C.; Linnen, J. M.; Kolk, D. P.; Dockter, J.; Gillotte-Taylor, K.; Park, M.; Ho-Sing-Loy, M.; McCormick, M. K.; Mimms, L. T.; McDonough, S. H.

2002-01-01

Various nucleic acid assays have been developed and implemented for diagnostics and therapeutic monitoring of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections. The high-throughput, semiautomated assays described here were developed to provide a method suitable for screening plasma specimens for the presence of HIV-1 and HCV RNAs. Three assays were developed: a multiplex HIV-1/HCV assay for simultaneous detection of HIV-1 and HCV, and discriminatory assays for specific detection of HIV-1 and HCV. The assay systems utilize three proprietary technologies: (i) target capture-based sample preparation, (ii) transcription-mediated amplification (TMA), and (iii) hybridization protection assay (HPA). An internal control is incorporated into each reaction to control for every step of the assay and identify random false-negative reactions. The assays demonstrated a sensitivity of at least 100 copies/ml for each target, and they detected with similar sensitivity all major variants of HCV and HIV-1, including HIV-1 group O strains. Assay sensitivity for one virus was not affected by the presence of the other. The specificity of these TMA-driven assays was ≥99.5% in both normal donor specimens and plasma containing potentially interfering substances or other blood-borne pathogens. Statistical receiver operating characteristic plots of 1 − specificity versus sensitivity data determined very wide analyte cutoff values for each assay at the point at which the assay specificity and sensitivity were both ≥99.5%. The sensitivity, specificity, and throughput capability predict that these assays will be valuable for large-volume plasma screening, either in a blood bank setting or in other diagnostic applications. PMID:12089255

Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nehal, Kishwer S.; Rajadhyaksha, Milind

2016-02-01

Latest advances in confocal microscopy of skin cancers toward guiding patient care: a Mohs surgeon's review and perspective About 350 publications worldwide have reported the ability of reflectance confocal microscopy (RCM) imaging to detect melanocytic skin lesions in vivo with specificity of 84-88% and sensitivity of 71-92%, and non-melanocytic skin lesions with specificity of 85-97% and sensitivity 100-92%. Lentigo maligna melanoma can be detected with sensitivity of 93% and specificity 82%. While the sensitivity is comparable to that of dermoscopy, the specificity is 2X superior, especially for lightly- and non-pigmented lesions. Dermoscopy combined with RCM imaging is proving to be both highly sensitive and highly specific. Recent studies have reported that the ratio of equivocal (i.e., would have been biopsied) lesions to detected melanomas dropped by ~2X when guided by dermoscopy and RCM imaging, compared to that with dermoscopy alone. Dermoscopy combined with RCM imaging is now being implemented to guide noninvasive diagnosis (to rule out malignancy and biopsy) and to also guide treatment, with promising initial impact: thus far, about 3,000 patients have been saved from biopsies of benign lesions. These are currently under follow-up monitoring. With fluorescence confocal microscopy (FCM) mosaicing, residual basal cell carcinomas can be detected in Mohs surgically excised fresh tissue ex vivo, with sensitivity of 94-97% and specificity 89-94%. FCM mosaicing is now being implemented for guiding Mohs surgery. To date, about 600 Mohs procedures have been performed, guided with mosaicing, and with pathology being performed in parallel to confirm the final outcome. These latest advances demonstrate the promising ability of RCM and FCM to guide patient care.

Diagnostic performance of body mass index to identify excess body fat in children with cerebral palsy.

PubMed

Duran, Ibrahim; Schulze, Josefa; Martakis, KyriakoS; Stark, Christina; Schoenau, Eckhard

2018-03-07

To assess the diagnostic performance of body mass index (BMI) cut-off values according to recommendations of the World Health Organization (WHO), the World Obesity Federation (WOF), and the German Society for Adiposity (DAG) to identify excess body fat in children with cerebral palsy (CP). The present study was a monocentric retrospective analysis of prospectively collected data among children and adolescents with CP participating in a rehabilitation programme. Excess body fat was defined as a body fat percentage above the 85th centile assessed by dual-energy X-ray absorptiometry. In total, 329 children (181 males, 148 females) with CP were eligible for analysis. The mean age was 12 years 4 months (standard deviation 2y 9mo). The BMI cut-off values for 'overweight' according to the WHO, WOF, and DAG showed the following sensitivities and specificities for the prediction of excess body fat in our population: WHO: sensitivity 0.768 (95% confidence interval [CI] 0.636-0.870), specificity 0.894 (95% CI 0.851-0.928); WOF: sensitivity 0.696 (95% CI 0.559-0.812), specificity 0.934 (95% CI 0.898-0.960); DAG: sensitivity 0.411 (95% CI 0.281-0.550), specificity 0.993 (95% CI 0.974-0.999). Body mass index showed high specificity, but low sensitivity in children with CP. Thus, 'normal-weight obese' children with CP were overlooked, when assessing excess body fat only using BMI. Excess body fat in children with cerebral palsy (CP) is less common than previously reported. Body mass index (BMI) had high specificity but low sensitivity in detecting excess body fat in children with CP. BMI evaluation criteria of the German Society for Adiposity could be improved in children with CP. © 2018 Mac Keith Press.

Home oximetry to screen for obstructive sleep apnoea in Down syndrome.

PubMed

Hill, Catherine M; Elphick, Heather E; Farquhar, Michael; Gringras, Paul; Pickering, Ruth M; Kingshott, Ruth N; Martin, Jane; Reynolds, Janine; Joyce, Anna; Gavlak, Johanna C; Evans, Hazel J

2018-05-14

Children with Down syndrome are at high risk of obstructive sleep apnoea (OSA) and screening is recommended. Diagnosis of OSA should be confirmed with multichannel sleep studies. We aimed to determine whether home pulse oximetry (HPO) discriminates children at high risk of OSA, who need further diagnostic multichannel sleep studies. Cross-sectional prospective study in a training sample recruited through three UK centres. Validation sample used single-centre retrospective analysis of clinical data. Children with Down syndrome aged 0.5-6 years. Diagnostic multichannel sleep study and HPO. Sensitivity and specificity of HPO to predict moderate-to-severe OSA. 161/202 children with Down syndrome met quality criteria for inclusion and 25 had OSA. In this training sample, the best HPO parameter predictors of OSA were the delta 12 s index >0.555 (sensitivity 92%, specificity 65%) and 3% oxyhaemoglobin (SpO 2 ) desaturation index (3% ODI)>6.15 dips/hour (sensitivity 92%, specificity 63%). Combining variables (delta 12 s index, 3% ODI, mean and minimum SpO 2 ) achieved sensitivity of 96% but reduced specificity to 52%. All predictors retained or improved sensitivity in a clinical validation sample of 50 children with variable loss of specificity, best overall was the delta 12 s index, a measure of baseline SpO 2 variability (sensitivity 92%; specificity 63%). HPO screening could halve the number of children with Down syndrome needing multichannel sleep studies and reduce the burden on children, families and health services alike. This approach offers a practical universal screening approach for OSA in Down syndrome that is accessible to the non-specialist paediatrician. © 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.

Optimal CINAHL search strategies for identifying therapy studies and review articles.

PubMed

Wong, Sharon S L; Wilczynski, Nancy L; Haynes, R Brian

2006-01-01

To design optimal search strategies for locating sound therapy studies and review articles in CiNAHL in the year 2000. An analytic survey was conducted, comparing hand searches of 75 journals with retrievals from CINAHL for 5,020 candidate search terms and 17,900 combinations for therapy and 5,977 combinations for review articles. All articles were rated with purpose and quality indicators. Candidate search strategies were used in CINAHL, and the retrievals were compared with results of the hand searches. The proposed search strategies were treated as "diagnostic tests" for sound studies and the manual review of the literature was treated as the "gold standard." Operating characteristics of the search strategies were calculated. Of the 1,383 articles about treatment, 506 (36.6%) met basic criteria for scientific merit and 127 (17.9%) of the 711 articles classified as a review met the criteria for systematic reviews. For locating sound treatment studies, a three-term strategy maximized sensitivity at 99.4% but with compromised specificity at 58.3%, and a two-term strategy maximized specificity at 98.5% but with compromised sensitivity at 52.0%. For detecting systematic reviews, a three-term strategy maximized sensitivity at 91.3% while keeping specificity high at 95.4%, and a single-term strategy maximized specificity at 99.6% but with compromised sensitivity at 42.5%. Three-term search strategies optimizing sensitivity and specificity achieved these values over 91% for detecting sound treatment studies and over 76% for detecting systematic reviews. Search strategies combining indexing terms and text words can achieve high sensitivity and specificity for retrieving sound treatment studies and review articles in CINAHL.

Moderate sensitivity and high specificity of emergency department administrative data for transient ischemic attacks.

PubMed

Yu, Amy Y X; Quan, Hude; McRae, Andrew; Wagner, Gabrielle O; Hill, Michael D; Coutts, Shelagh B

2017-09-18

Validation of administrative data case definitions is key for accurate passive surveillance of disease. Transient ischemic attack (TIA) is a condition primarily managed in the emergency department. However, prior validation studies have focused on data after inpatient hospitalization. We aimed to determine the validity of the Canadian 10th International Classification of Diseases (ICD-10-CA) codes for TIA in the national ambulatory administrative database. We performed a diagnostic accuracy study of four ICD-10-CA case definition algorithms for TIA in the emergency department setting. The study population was obtained from two ongoing studies on the diagnosis of TIA and minor stroke versus stroke mimic using serum biomarkers and neuroimaging. Two reference standards were used 1) the emergency department clinical diagnosis determined by chart abstractors and 2) the 90-day final diagnosis, both obtained by stroke neurologists, to calculate the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the ICD-10-CA algorithms for TIA. Among 417 patients, emergency department adjudication showed 163 (39.1%) TIA, 155 (37.2%) ischemic strokes, and 99 (23.7%) stroke mimics. The most restrictive algorithm, defined as a TIA code in the main position had the lowest sensitivity (36.8%), but highest specificity (92.5%) and PPV (76.0%). The most inclusive algorithm, defined as a TIA code in any position with and without query prefix had the highest sensitivity (63.8%), but lowest specificity (81.5%) and PPV (68.9%). Sensitivity, specificity, PPV, and NPV were overall lower when using the 90-day diagnosis as reference standard. Emergency department administrative data reflect diagnosis of suspected TIA with high specificity, but underestimate the burden of disease. Future studies are necessary to understand the reasons for the low to moderate sensitivity.

Nucleic Acid-Based Approaches for Detection of Viral Hepatitis

PubMed Central

Behzadi, Payam; Ranjbar, Reza; Alavian, Seyed Moayed

2014-01-01

Context: To determining suitable nucleic acid diagnostics for individual viral hepatitis agent, an extensive search using related keywords was done in major medical library and data were collected, categorized, and summarized in different sections. Results: Various types of molecular biology tools can be used to detect and quantify viral genomic elements and analyze the sequences. These molecular assays are proper technologies for rapidly detecting viral agents with high accuracy, high sensitivity, and high specificity. Nonetheless, the application of each diagnostic method is completely dependent on viral agent. Conclusions: Despite rapidity, automation, accuracy, cost-effectiveness, high sensitivity, and high specificity of molecular techniques, each type of molecular technology has its own advantages and disadvantages. PMID:25789132

Data mining methods in the prediction of Dementia: A real-data comparison of the accuracy, sensitivity and specificity of linear discriminant analysis, logistic regression, neural networks, support vector machines, classification trees and random forests

PubMed Central

2011-01-01

Background Dementia and cognitive impairment associated with aging are a major medical and social concern. Neuropsychological testing is a key element in the diagnostic procedures of Mild Cognitive Impairment (MCI), but has presently a limited value in the prediction of progression to dementia. We advance the hypothesis that newer statistical classification methods derived from data mining and machine learning methods like Neural Networks, Support Vector Machines and Random Forests can improve accuracy, sensitivity and specificity of predictions obtained from neuropsychological testing. Seven non parametric classifiers derived from data mining methods (Multilayer Perceptrons Neural Networks, Radial Basis Function Neural Networks, Support Vector Machines, CART, CHAID and QUEST Classification Trees and Random Forests) were compared to three traditional classifiers (Linear Discriminant Analysis, Quadratic Discriminant Analysis and Logistic Regression) in terms of overall classification accuracy, specificity, sensitivity, Area under the ROC curve and Press'Q. Model predictors were 10 neuropsychological tests currently used in the diagnosis of dementia. Statistical distributions of classification parameters obtained from a 5-fold cross-validation were compared using the Friedman's nonparametric test. Results Press' Q test showed that all classifiers performed better than chance alone (p < 0.05). Support Vector Machines showed the larger overall classification accuracy (Median (Me) = 0.76) an area under the ROC (Me = 0.90). However this method showed high specificity (Me = 1.0) but low sensitivity (Me = 0.3). Random Forest ranked second in overall accuracy (Me = 0.73) with high area under the ROC (Me = 0.73) specificity (Me = 0.73) and sensitivity (Me = 0.64). Linear Discriminant Analysis also showed acceptable overall accuracy (Me = 0.66), with acceptable area under the ROC (Me = 0.72) specificity (Me = 0.66) and sensitivity (Me = 0.64). The remaining classifiers showed overall classification accuracy above a median value of 0.63, but for most sensitivity was around or even lower than a median value of 0.5. Conclusions When taking into account sensitivity, specificity and overall classification accuracy Random Forests and Linear Discriminant analysis rank first among all the classifiers tested in prediction of dementia using several neuropsychological tests. These methods may be used to improve accuracy, sensitivity and specificity of Dementia predictions from neuropsychological testing. PMID:21849043

Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis.

PubMed

Horita, Nobuyuki; Miyazawa, Naoki; Kojima, Ryota; Kimura, Naoko; Inoue, Miyo; Ishigatsubo, Yoshiaki; Kaneko, Takeshi

2013-11-01

Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies ('specificity (other)'). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies ('specificity (unknown and other)') using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high; however, the specificity (unknown and other) remained unclear. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Sensitivity and specificity of radiographic methods for predicting insertion torque of dental implants.

PubMed

Cortes, Arthur Rodriguez Gonzalez; Eimar, Hazem; Barbosa, Jorge de Sá; Costa, Claudio; Arita, Emiko Saito; Tamimi, Faleh

2015-05-01

Subjective radiographic classifications of alveolar bone have been proposed and correlated with implant insertion torque (IT). The present diagnostic study aims to identify quantitative bone features influencing IT and to use these findings to develop an objective radiographic classification for predicting IT. Demographics, panoramic radiographs (taken at the beginning of dental treatment), and cone-beam computed tomographic scans (taken for implant surgical planning) of 25 patients receiving 31 implants were analyzed. Bone samples retrieved from implant sites were assessed with dual x-ray absorptiometry, microcomputed tomography, and histology. Odds ratio, sensitivity, and specificity of all variables to predict high peak IT were assessed. A ridge cortical thickness >0.75 mm and a normal appearance of the inferior mandibular cortex were the most sensitive variables for predicting high peak IT (87.5% and 75%, respectively). A classification based on the combination of both variables presented high sensitivity (90.9%) and specificity (100%) for predicting IT. Within the limitations of this study, the results suggest that it is possible to predict IT accurately based on radiographic findings of the patient. This could be useful in the treatment plan of immediate loading cases.

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

Rapid Magnetic Nanobiosensor for the detection of Serratia marcescen

NASA Astrophysics Data System (ADS)

Aljabali, Alaa A. A.; Hussein, Emad; Aljumaili, Omar; Zoubi, Mazhar Al; Altrad, Bahaa; Albatayneh, Khaled; Al-razaq, Mutaz A. Abd

2018-02-01

The development of rapid, sensitive, accurate and reliable bacterial detection methods are of keen interest to ensure food safety and hospital security. Therefore, the development of a fast, specific, low-cost and trusted methods is in high demand. Magnetic nanoparticles with their unique material properties have been utilized as a tool for pathogen detection. Here, we present a novel iron oxide nanoparticles labeled with specific targeting antibodies to improve specificity and extend the use of nanoparticles as nanosensors. The results indicated that antibody labeled iron oxide platform that binds specifically to Serriata marcescenst in a straightforward method is very specific and sensitive. The system is capable of rapid and specific detection of various clinically relevant bacterial species, with sensitivity down to single bacteria. The generic platform could be used to identify pathogens for a variety of applications rapidly.

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

PubMed Central

Scherer, Luciene Cardoso; Sperhacke, Rosa Dea; Jarczewski, Carla; Cafrune, Patrícia I; Minghelli, Simone; Ribeiro, Marta Osório; Mello, Fernanda CQ; Ruffino-Netto, Antonio; Rossetti, Maria LR; Kritski, Afrânio L

2007-01-01

Background Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection. Methods To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB. Results In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. Conclusion PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital. PMID:18096069

High-performance information search filters for acute kidney injury content in PubMed, Ovid Medline and Embase.

PubMed

Hildebrand, Ainslie M; Iansavichus, Arthur V; Haynes, R Brian; Wilczynski, Nancy L; Mehta, Ravindra L; Parikh, Chirag R; Garg, Amit X

2014-04-01

We frequently fail to identify articles relevant to the subject of acute kidney injury (AKI) when searching the large bibliographic databases such as PubMed, Ovid Medline or Embase. To address this issue, we used computer automation to create information search filters to better identify articles relevant to AKI in these databases. We first manually reviewed a sample of 22 992 full-text articles and used prespecified criteria to determine whether each article contained AKI content or not. In the development phase (two-thirds of the sample), we developed and tested the performance of >1.3-million unique filters. Filters with high sensitivity and high specificity for the identification of AKI articles were then retested in the validation phase (remaining third of the sample). We succeeded in developing and validating high-performance AKI search filters for each bibliographic database with sensitivities and specificities in excess of 90%. Filters optimized for sensitivity reached at least 97.2% sensitivity, and filters optimized for specificity reached at least 99.5% specificity. The filters were complex; for example one PubMed filter included >140 terms used in combination, including 'acute kidney injury', 'tubular necrosis', 'azotemia' and 'ischemic injury'. In proof-of-concept searches, physicians found more articles relevant to topics in AKI with the use of the filters. PubMed, Ovid Medline and Embase can be filtered for articles relevant to AKI in a reliable manner. These high-performance information filters are now available online and can be used to better identify AKI content in large bibliographic databases.

A split recognition mode combined with cascade signal amplification strategy for highly specific, sensitive detection of microRNA.

PubMed

Wang, Rui; Wang, Lei; Zhao, Haiyan; Jiang, Wei

2016-12-15

MicroRNAs (miRNAs) are vital for many biological processes and have been regarded as cancer biomarkers. Specific and sensitive detection of miRNAs is essential for cancer diagnosis and therapy. Herein, a split recognition mode combined with cascade signal amplification strategy is developed for highly specific and sensitive detection of miRNA. The split recognition mode possesses two specific recognition processes, which are based on toehold-mediated strand displacement reaction (TSDR) and direct hybridization reaction. Two recognition probes, hairpin probe (HP) with overhanging toehold domain and assistant probe (AP), are specially designed. Firstly, the toehold domain of HP and AP recognize part of miRNA simultaneously, accompanied with TSDR to unfold the HP and form the stable DNA Y-shaped junction structure (YJS). Then, the AP in YJS can further act as primer to initiate strand displacement amplification, releasing numerous trigger sequences. Finally, the trigger sequences hybridize with padlock DNA to initiate circular rolling circle amplification and generate enhanced fluorescence responses. In this strategy, the dual recognition effect of split recognition mode guarantees the excellent selectivity to discriminate let-7b from high-homology sequences. Furthermore, the high amplification efficiency of cascade signal amplification guarantees a high sensitivity with the detection limit of 3.2 pM and the concentration of let-7b in total RNA sample extracted from Hela cells is determined. These results indicate our strategy will be a promising miRNA detection strategy in clinical diagnosis and disease treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Screening markers for chronic atrophic gastritis in Chiapas, Mexico.

PubMed

Ley, C; Mohar, A; Guarner, J; Herrera-Goepfert, R; Figueroa, L S; Halperin, D; Parsonnet, J

2001-02-01

Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling.

PubMed

Plagnol, Vincent; Woodhouse, Samuel; Howarth, Karen; Lensing, Stefanie; Smith, Matt; Epstein, Michael; Madi, Mikidache; Smalley, Sarah; Leroy, Catherine; Hinton, Jonathan; de Kievit, Frank; Musgrave-Brown, Esther; Herd, Colin; Baker-Neblett, Katherine; Brennan, Will; Dimitrov, Peter; Campbell, Nathan; Morris, Clive; Rosenfeld, Nitzan; Clark, James; Gale, Davina; Platt, Jamie; Calaway, John; Jones, Greg; Forshew, Tim

2018-01-01

Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications.

Analytical validation of a next generation sequencing liquid biopsy assay for high sensitivity broad molecular profiling

PubMed Central

Howarth, Karen; Lensing, Stefanie; Smith, Matt; Epstein, Michael; Madi, Mikidache; Smalley, Sarah; Leroy, Catherine; Hinton, Jonathan; de Kievit, Frank; Musgrave-Brown, Esther; Herd, Colin; Baker-Neblett, Katherine; Brennan, Will; Dimitrov, Peter; Campbell, Nathan; Morris, Clive; Rosenfeld, Nitzan; Clark, James; Gale, Davina; Platt, Jamie; Calaway, John; Jones, Greg

2018-01-01

Circulating tumor DNA (ctDNA) analysis is being incorporated into cancer care; notably in profiling patients to guide treatment decisions. Responses to targeted therapies have been observed in patients with actionable mutations detected in plasma DNA at variant allele fractions (VAFs) below 0.5%. Highly sensitive methods are therefore required for optimal clinical use. To enable objective assessment of assay performance, detailed analytical validation is required. We developed the InVisionFirst™ assay, an assay based on enhanced tagged amplicon sequencing (eTAm-Seq™) technology to profile 36 genes commonly mutated in non-small cell lung cancer (NSCLC) and other cancer types for actionable genomic alterations in cell-free DNA. The assay has been developed to detect point mutations, indels, amplifications and gene fusions that commonly occur in NSCLC. For analytical validation, two 10mL blood tubes were collected from NSCLC patients and healthy volunteer donors. In addition, contrived samples were used to represent a wide spectrum of genetic aberrations and VAFs. Samples were analyzed by multiple operators, at different times and using different reagent Lots. Results were compared with digital PCR (dPCR). The InVisionFirst assay demonstrated an excellent limit of detection, with 99.48% sensitivity for SNVs present at VAF range 0.25%-0.33%, 92.46% sensitivity for indels at 0.25% VAF and a high rate of detection at lower frequencies while retaining high specificity (99.9997% per base). The assay also detected ALK and ROS1 gene fusions, and DNA amplifications in ERBB2, FGFR1, MET and EGFR with high sensitivity and specificity. Comparison between the InVisionFirst assay and dPCR in a series of cancer patients showed high concordance. This analytical validation demonstrated that the InVisionFirst assay is highly sensitive, specific and robust, and meets analytical requirements for clinical applications. PMID:29543828

A proposed cutoff point of waist-to-height ratio for metabolic risk in African township adolescents.

PubMed

Kruger, H Salome; Faber, Mieke; Schutte, Aletta E; Ellis, Suria M

2013-03-01

A waist:height ratio (WHtR) higher than 0.5 has been proposed as a cutoff point for abdominal obesity in both sexes and at all ages. It is unknown if this cutoff point is appropriate for previously undernourished adolescents. We assessed the cutoff value of the WHtR associated with an increased metabolic risk in 178 black South African 14- to 18-y-old adolescents (69 boys, 109 girls). We measured weight, height, waist circumference, fasting plasma glucose and insulin levels, serum high-sensitivity C-reactive protein, and blood pressure and calculated the WHtR and homeostasis model assessment of insulin resistance (HOMA-IR). Using receiver operating characteristics curve analyses, we assessed the WHtR with the highest sensitivity and specificity to discriminate adolescents with increased fasting plasma glucose, HOMA-IR, serum high-sensitivity C-reactive protein, and blood pressure from those with "normal" values. The WHtR cutoff points derived from the receiver operating characteristics curves ranged from 0.40 to 0.41, with best diagnostic value at 0.41. A WHtR of 0.40 had 80% sensitivity and 38.5% specificity to classify adolescents with fasting blood glucose level higher than 5.6 mmol/L (area under the curve [AUC] 0.57). A WHtR of 0.41 had 64% sensitivity and 58.5% specificity for a HOMA-IR higher than 3.4 (AUC 0.66), 55% sensitivity and 55.6% specificity for a high-sensitivity C-reactive protein level higher than 1 mg/L (AUC 0.57), and 64% sensitivity and 50.2% specificity for a blood pressure higher than the age-, sex-, and height-specific 90th percentiles (AUC 0.56). Adolescents with a WHtR higher than 0.41 had an odds ratio of 2.46 (95% confidence interval 0.96-6.30) for having a HOMA-IR higher than 3.4. The WHtR cutoff to indicate metabolic risk for black South African adolescents is 0.41, which is lower than the proposed international cutoff of 0.5. The WHtR can be used for screening adolescents with components of the metabolic syndrome in intervention programs. Copyright © 2013 Elsevier Inc. All rights reserved.

Duodenal endoscopic findings and histopathologic confirmation of intestinal lymphangiectasia in dogs.

PubMed

Larson, R N; Ginn, J A; Bell, C M; Davis, M J; Foy, D S

2012-01-01

The diagnosis of intestinal lymphangiectasia (IL) has been associated with characteristic duodenal mucosal changes. However, the sensitivity and specificity of the endoscopic duodenal mucosal appearance for the diagnosis of IL are not reported. To evaluate the utility of endoscopic images of the duodenum for diagnosis of IL. Endoscopic appearance of the duodenal mucosal might predict histopathologic diagnosis of IL with a high degree of sensitivity and specificity. 51 dogs that underwent upper gastrointestinal (GI) endoscopy and endoscopic biopsies. Retrospective review of images acquired during endoscopy. Dogs were included if adequate biopsies were obtained during upper GI endoscopy and digital images were saved during the procedure. Images were assessed for the presence and severity of IL. Using histopathology as the gold standard, the sensitivity and specificity of endoscopy for diagnosing IL were calculated. Intestinal lymphangiectasia (IL) was diagnosed in 25/51 dogs. Gross endoscopic appearance of the duodenal mucosa had a sensitivity and specificity (95% confidence interval) of 68% (46%, 84%) and 42% (24%, 63%), respectively for diagnosis of IL. Endoscopic images in cases with lymphopenia, hypocholesterolemia, and hypoalbuminemia had a sensitivity of 80%. Endoscopic duodenal mucosa appearance alone lacks specificity and has only a moderate sensitivity for diagnosis of IL. Evaluation of biomarkers associated with PLE improved the sensitivity; however, poor specificity for diagnosis of IL supports the need for histopathologic confirmation. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark

PubMed Central

Dellon, Evan S; Erichsen, Rune; Pedersen, Lars; Shaheen, Nicholas J; Baron, John A; Sørensen, Henrik T; Vyberg, Mogens

2013-01-01

AIM: To develop and validate a case definition of eosinophilic esophagitis (EoE) in the linked Danish health registries. METHODS: For case definition development, we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern Denmark. All International Classification of Diseases-10 (ICD-10) and prescription codes were obtained, and archived pathology slides were obtained and re-reviewed to determine case status. We used an iterative process to select inclusion/exclusion codes, refine the case definition, and optimize sensitivity and specificity. We then re-queried the registries from 2008-2009 to yield a validation set. The case definition algorithm was applied, and sensitivity and specificity were calculated. RESULTS: Of the 51 and 49 candidate cases identified in both the development and validation sets, 21 and 24 had EoE, respectively. Characteristics of EoE cases in the development set [mean age 35 years; 76% male; 86% dysphagia; 103 eosinophils per high-power field (eos/hpf)] were similar to those in the validation set (mean age 42 years; 83% male; 67% dysphagia; 77 eos/hpf). Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of cases. Two registry-based case algorithms based on pathology, ICD-10, and pharmacy codes were successfully generated in the development set, one that was sensitive (90%) and one that was specific (97%). When these algorithms were applied to the validation set, they remained sensitive (88%) and specific (96%). CONCLUSION: Two registry-based definitions, one highly sensitive and one highly specific, were developed and validated for the linked Danish national health databases, making future population-based studies feasible. PMID:23382628

Gene expression analysis using a highly sensitive DNA microarray for colorectal cancer screening.

PubMed

Koga, Yoshikatsu; Yamazaki, Nobuyoshi; Takizawa, Satoko; Kawauchi, Junpei; Nomura, Osamu; Yamamoto, Seiichiro; Saito, Norio; Kakugawa, Yasuo; Otake, Yosuke; Matsumoto, Minori; Matsumura, Yasuhiro

2014-01-01

Half of all patients with small, right-sided, non-metastatic colorectal cancer (CRC) have negative results for the fecal occult blood test (FOBT). In the present study, the usefulness of CRC screening with a highly sensitive DNA microarray was evaluated in comparison with that by FOBT using fecal samples. A total of 53 patients with CRC and 61 healthy controls were divided into "training" and "validation sets". For the gene profiling, total RNA extracted from 0.5 g of feces was hybridized to a highly sensitive DNA chip. The expressions of 43 genes were significantly higher in the patients with CRC than in healthy controls (p<0.05). In the training set, the sensitivity and specificity of the DNA chip assay using six genes were 85.4% and 85.2%, respectively. On the other hand, in the validation set, the sensitivity and specificity of the DNA chip assay were 85.2% and 85.7%, respectively. The sensitivities of the DNA chip assay were higher than those of FOBT in cases of the small, right-sided, early-CRC, tumor invading up to the muscularis propria (i.e. surface tumor) subgroups. In particular, the sensitivities of the DNA chip assay in the surface tumor and early-CRC subgroups were significantly higher than those of FOBT (p=0.023 and 0.019, respectively.). Gene profiling assay using a highly sensitive DNA chip was more effective than FOBT at detecting patients with small, right-sided, surface tumor, and early-stage CRC.

Intrauterine sensitization of allergen-specific IgE analyzed by a highly sensitive new allergen microarray.

PubMed

Kamemura, Norio; Tada, Hitomi; Shimojo, Naoki; Morita, Yoshinori; Kohno, Yoichi; Ichioka, Takao; Suzuki, Koichi; Kubota, Kenji; Hiyoshi, Mineyoshi; Kido, Hiroshi

2012-07-01

To design a rational allergy prevention program, it is important to determine whether allergic sensitization starts in utero under the maternal immune system. To investigate the origin of allergen-specific IgE antibodies in cord blood (CB) and maternofetal transfer of immunoglobulins. The levels of food and inhalant allergen-specific IgE, IgA, IgG, and IgG(4) antibodies in CB and maternal blood (MB) from 92 paired neonates and mothers were measured by using a novel allergen microarray of diamond-like-carbon-coated chip, with high-sensitivity detection of allergen-specific antibodies and allergen profiles. The levels of allergen-specific IgE antibodies against food and inhalant allergens and allergen profiles were identical in CB and newborn blood, but the levels and profiles, specifically against inhalant allergens, were different from those in MB. The level of allergen-specific IgA antibodies was below the detection levels in CB despite clear detection in MB. Therefore, contamination with MB in CB was excluded on the basis of extremely low levels of IgA antibodies in CB and the obvious mismatch of the allergen-specific IgE and IgA profiles between CB and MB. However, the levels of allergen-specific IgG and IgG(4) antibodies and their allergen profiles were almost identical in both MB and CB. Allergen-specific levels of IgE and IgA antibodies and their allergen profiles analyzed by the diamond-like-carbon allergen chip indicate that IgE antibodies in CB are of fetal origin. Food-allergen specific IgE antibodies were detected more often than inhalant-allergen specific IgE antibodies in CB, the reason of which remains unclarified. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Correlation between the immunological condition and the results of immunoenzymatic tests in diagnosing infectious mononucleosis.

PubMed

Tamaro, Giorgio; Donato, Michela; Princi, Tanja; Parco, Sergio

2009-04-01

A symptom-based diagnosis of infectious mononucleosis is not sufficiently accurate, since some clinical symptoms of infectious mononucleosis are also detected in other virally induced diseases. Moreover, not all patients suffering from infectious mononucleosis show circulating atypical lymphocytes, which are considered characteristic of this disease. Therefore, when this disorder is suspected, serum analyses are carried out to detect the presence of certain immunoglobulins associated with infectious mononucleosis in the patient's blood. The aim of this study was to evaluate the sensitivity and the specificity of a rapid test detecting heterophil antibodies in diagnosing infectious mononucleosis in a paediatric population. We considered 163 paediatric patients with suspected infectious mononucleosis and we tested their serums to detect heterophil antibodies (using an inexpensive and rapid test) and specific immunoglobulins directed against Epstein-Barr virus (EBV) (these assays are known to be characterized by high sensitivity and specificity, but are more expensive and time-consuming). By comparing the results of the rapid test with those of the other assays, we found that the sensitivity of the first test was 61.8%, whereas its specificity was sufficiently high (about 90%). We show that, in paediatric patients, the detection of heterophil antibodies is not a very sensitive test, therefore the determination of immunoglobulins against specific antigens of EBV is recommended.

Efficacy of species-specific recA PCR tests in the identification of Burkholderia cepacia complex environmental isolates.

PubMed

Dalmastri, Claudia; Pirone, Luisa; Tabacchioni, Silvia; Bevivino, Annamaria; Chiarini, Luigi

2005-05-01

In this study, we evaluated if recA species-specific PCR assays could be successfully applied to identify environmental isolates of the widespread Burkholderia cepacia complex (Bcc) species. A total of 729 Bcc rhizosphere isolates collected in different samplings were assigned to the species B. cepacia genomovar I (61), B. cenocepacia recA lineage IIIB (514), B. ambifaria (124) and B. pyrrocinia (30), by means of recA (RFLP) analysis, and PCR tests were performed to assess sensitivity and specificity of recA species-specific primers pairs. B. cepacia genomovar I specific primers produced the expected amplicon with all isolates of the corresponding species (sensitivity, 100%), and cross-reacted with all B. pyrrocinia isolates. On the contrary, B. cenocepacia IIIB primers did not give the expected amplicon in 164 B. cenocepacia IIIB isolates (sensitivity, 68.1%), and isolates of distinct populations showed different sensitivity. B. ambifaria primers failed to amplify a recA-specific fragment only in a few isolates of this species (sensitivity, 93.5%). The absence of specific amplification in a high number of B. cenocepacia rhizosphere isolates indicates that recA specific PCR assays can lead to an underestimation of environmental microorganisms belonging to this bacterial species.

Ultrasound Fracture Diagnosis in Space

NASA Technical Reports Server (NTRS)

Dulchavsky, Scott A.; Amponsah, David; Sargsyan, Ashot E.; Garcia, Kathleen M.; Hamilton, Douglas R.; vanHolsbeeck, Marnix

2010-01-01

Introduction: This ground-based investigation accumulated high-level clinical evidence on the sensitivity and specificity of point of care ultrasound performed by expert and novice users for the rapid diagnosis of musculoskeletal (MSK) injuries. We developed preliminary educational methodologies to provide just-in-time training of novice users by creating multi-media training tools and imaging procedures for non expert operators and evaluated the sensitivity and specificity of non-expert performed musculoskeletal ultrasound to diagnose acute injuries in a Level 1 Trauma Center. Methods: Patients with potential MSK injuries were identified in the emergency room. A focused MSK ultrasound was performed by expert operators and compared to standard radiographs. A repeat examination was performed by non-expert operators who received a short, just-in-time multimedia education aid. The sensitivity and specificity of the expert and novice ultrasound examinations were compared to gold standard radiography. Results: Over 800 patients were enrolled in this study. The sensitivity and specificity of expert performed ultrasound exceeded 98% for MSK injuries. Novice operators achieved 97% sensitivity and 99% specificity for targeted examinations with the greatest error in fractures involving the hand and foot. Conclusion: Point of care ultrasound is a sensitive and specific diagnostic test for MSK injury when performed by experts and just-in-time trained novice operators.

Single quantum dot analysis enables multiplexed point mutation detection by gap ligase chain reaction.

PubMed

Song, Yunke; Zhang, Yi; Wang, Tza-Huei

2013-04-08

Gene point mutations present important biomarkers for genetic diseases. However, existing point mutation detection methods suffer from low sensitivity, specificity, and a tedious assay processes. In this report, an assay technology is proposed which combines the outstanding specificity of gap ligase chain reaction (Gap-LCR), the high sensitivity of single-molecule coincidence detection, and the superior optical properties of quantum dots (QDs) for multiplexed detection of point mutations in genomic DNA. Mutant-specific ligation products are generated by Gap-LCR and subsequently captured by QDs to form DNA-QD nanocomplexes that are detected by single-molecule spectroscopy (SMS) through multi-color fluorescence burst coincidence analysis, allowing for multiplexed mutation detection in a separation-free format. The proposed assay is capable of detecting zeptomoles of KRAS codon 12 mutation variants with near 100% specificity. Its high sensitivity allows direct detection of KRAS mutation in crude genomic DNA without PCR pre-amplification. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ADHD Diagnosis: As Simple As Administering a Questionnaire or a Complex Diagnostic Process?

PubMed

Parker, Ashton; Corkum, Penny

2016-06-01

The present study investigated the validity of using the Conners' Teacher and Parent Rating Scales (CTRS/CPRS) or semistructured diagnostic interviews (Parent Interview for Child Symptoms and Teacher Telephone Interview) to predict a best-practices clinical diagnosis of ADHD. A total of 279 children received a clinical diagnosis based on a best-practices comprehensive assessment (including diagnostic parent and teacher interviews, collection of historical information, rating scales, classroom observations, and a psychoeducational assessment) at a specialty ADHD Clinic in Truro, Nova Scotia, Canada. Sensitivity and specificity with clinical diagnosis were determined for the ratings scales and diagnostic interviews. Sensitivity and specificity values were high for the diagnostic interviews (91.8% and 70.7%, respectively). However, while sensitivity of the CTRS/CPRS was relatively high (83.5%), specificity was poor (35.7%). The low specificity of the CPRS/CTRS is not sufficient to be used alone to diagnose ADHD. (J. of Att. Dis. 2016; 20(6) 478-486). © The Author(s) 2013.

Rapid and sensitive detection of Yersinia pestis using amplification of plague diagnostic bacteriophages monitored by real-time PCR.

PubMed

Sergueev, Kirill V; He, Yunxiu; Borschel, Richard H; Nikolich, Mikeljon P; Filippov, Andrey A

2010-06-28

Yersinia pestis, the agent of plague, has caused many millions of human deaths and still poses a serious threat to global public health. Timely and reliable detection of such a dangerous pathogen is of critical importance. Lysis by specific bacteriophages remains an essential method of Y. pestis detection and plague diagnostics. The objective of this work was to develop an alternative to conventional phage lysis tests--a rapid and highly sensitive method of indirect detection of live Y. pestis cells based on quantitative real-time PCR (qPCR) monitoring of amplification of reporter Y. pestis-specific bacteriophages. Plague diagnostic phages phiA1122 and L-413C were shown to be highly effective diagnostic tools for the detection and identification of Y. pestis by using qPCR with primers specific for phage DNA. The template DNA extraction step that usually precedes qPCR was omitted. phiA1122-specific qPCR enabled the detection of an initial bacterial concentration of 10(3) CFU/ml (equivalent to as few as one Y. pestis cell per 1-microl sample) in four hours. L-413C-mediated detection of Y. pestis was less sensitive (up to 100 bacteria per sample) but more specific, and thus we propose parallel qPCR for the two phages as a rapid and reliable method of Y. pestis identification. Importantly, phiA1122 propagated in simulated clinical blood specimens containing EDTA and its titer rise was detected by both a standard plating test and qPCR. Thus, we developed a novel assay for detection and identification of Y. pestis using amplification of specific phages monitored by qPCR. The method is simple, rapid, highly sensitive, and specific and allows the detection of only live bacteria.

Radionuclide Methods and Instrumentation for Breast Cancer Detection and Diagnosis

PubMed Central

Surti, Suleman

2013-01-01

Breast cancer mammography is a well-acknowledged technique for patient screening due to its high sensitivity. However, in addition to its low specificity the sensitivity of mammography is limited when imaging patients with dense breasts. Radionuclide imaging techniques, such as coincidence photon-based positron emission tomography and single photon emission computed tomography or scintimammography, can play a role in assisting screening of such patients. Radionuclide techniques can also be useful in assessing treatment response of patients with breast cancer to therapy, and staging of patients to diagnose the disease extent. However, the performance of these imaging modalities is generally limited because of the poor spatial resolution and sensitivity of the commercially available multipurpose imaging systems. Here, we describe some of the dedicated imaging systems (positron emission mammography [PEM] and breast-specific gamma imaging [BSGI]) that have been developed both commercially and in research laboratories for radionuclide imaging of breast cancer. Clinical studies with dedicated PEM scanners show improved sensitivity to detecting cancer in patients when using PEM in conjunction with additional imaging modalities, such as magnetic resonance imaging or mammography or both, as well as improved disease staging that can have an effect on surgical planning. High-resolution BSGI systems are more widely available commercially and several clinical studies have shown very high sensitivity and specificity in detecting cancer in high-risk patients. Further development of dedicated PEM and BSGI systems is ongoing, promising further expansion of radionuclide imaging techniques in the realm of breast cancer detection and treatment. PMID:23725989

Four human Plasmodium species quantification using droplet digital PCR.

PubMed

Srisutham, Suttipat; Saralamba, Naowarat; Malleret, Benoit; Rénia, Laurent; Dondorp, Arjen M; Imwong, Mallika

2017-01-01

Droplet digital polymerase chain reaction (ddPCR) is a partial PCR based on water-oil emulsion droplet technology. It is a highly sensitive method for detecting and delineating minor alleles from complex backgrounds and provides absolute quantification of DNA targets. The ddPCR technology has been applied for detection of many pathogens. Here the sensitive assay utilizing ddPCR for detection and quantification of Plasmodium species was investigated. The assay was developed for two levels of detection, genus specific for all Plasmodium species and for specific Plasmodium species detection. The ddPCR assay was developed based on primers and probes specific to the Plasmodium genus 18S rRNA gene. Using ddPCR for ultra-sensitive P. falciparum assessment, the lower level of detection from concentrated DNA obtained from a high volume (1 mL) blood sample was 11 parasites/mL. For species identification, in particular for samples with mixed infections, a duplex reaction was developed for detection and quantification P. falciparum/ P. vivax and P. malariae/ P. ovale. Amplification of each Plasmodium species in the duplex reaction showed equal sensitivity to singleplex single species detection. The duplex ddPCR assay had higher sensitivity to identify minor species in 32 subpatent parasitaemia samples from Cambodia, and performed better than real-time PCR. The ddPCR assay shows high sensitivity to assess very low parasitaemia of all human Plasmodium species. This provides a useful research tool for studying the role of the asymptomatic parasite reservoir for transmission in regions aiming for malaria elimination.

Methods for assessing patient-clinician communication about depression in primary care: what you see depends on how you look.

PubMed

Henry, Stephen G; Feng, Bo; Franks, Peter; Bell, Robert A; Tancredi, Daniel J; Gottfeld, Dustin; Kravitz, Richard L

2014-10-01

To advance research on depression communication and treatment by comparing assessments of communication about depression from patient report, clinician report, and chart review to assessments from transcripts. One hundred sixty-four primary care visits from seven health care systems (2010-2011). Presence or absence of discussion about depressive symptoms, treatment recommendations, and follow-up was measured using patient and clinician postvisit questionnaires, chart review, and coding of audio transcripts. Sensitivity and specificity of indirect measures compared to transcripts were calculated. Patient report was sensitive for mood (83 percent) and sleep (83 percent) but not suicide (55 percent). Patient report was specific for suicide (86 percent) but not for other symptoms (44-75 percent). Clinician report was sensitive for all symptoms (83-98 percent) and specific for sleep, memory, and suicide (80-87 percent), but not for other symptoms (45-48 percent). Chart review was not sensitive for symptoms (50-73 percent), but it was specific for sleep, memory, and suicide (88-96 percent). All indirect measures had low sensitivity for treatment recommendations (patient report: 24-42 percent, clinician report 38-50 percent, chart review 49-67 percent) but high specificity (89-96 percent). For definite follow-up plans, all three indirect measures were sensitive (82-96 percent) but not specific (40-57 percent). Clinician report and chart review generally had the most favorable sensitivity and specificity for measuring discussion of depressive symptoms and treatment recommendations, respectively. © Health Research and Educational Trust.

Sensitivity and specificity of the Percentage of Consonants Correct-Revised in the identification of speech sound disorder.

PubMed

Barrozo, Tatiane Faria; Pagan-Neves, Luciana de Oliveira; Pinheiro da Silva, Joyce; Wertzner, Haydée Fiszbein

2017-05-22

The purpose of the study was to determine the sensitivity and specificity, and to establish cutoff points for the severity index Percentage of Consonants Correct - Revised (PCC-R) in Brazilian Portuguese-speaking children with and without speech sound disorders. 72 children between 5:00 and 7:11 years old - 36 children without speech and language complaints and 36 children with speech sound disorders. The PCC-R was applied to the figure naming and word imitation tasks that are part of the ABFW Child Language Test. Results were statistically analyzed. The ROC curve was performed and sensitivity and specificity values ​​of the index were verified. The group of children without speech sound disorders presented greater PCC-R values in both tasks, regardless of the gender of the participants. The cutoff value observed for the picture naming task was 93.4%, with a sensitivity value of 0.89 and specificity of 0.94 (age independent). For the word imitation task, results were age-dependent: for age group ≤6:5 years old, the cutoff value was 91.0% (sensitivity of 0.77 and specificity of 0.94) and for age group >6:5 years-old, the cutoff value was 93.9% (sensitivity of 0.93 and specificity of 0.94). Given the high sensitivity and specificity of PCC-R, we can conclude that the index was effective in discriminating and identifying children with and without speech sound disorders.

The Diagnostic Accuracy of Special Tests for Rotator Cuff Tear: The ROW Cohort Study

PubMed Central

Jain, Nitin B.; Luz, Jennifer; Higgins, Laurence D.; Dong, Yan; Warner, Jon J.P.; Matzkin, Elizabeth; Katz, Jeffrey N.

2016-01-01

Objective The aim was to assess diagnostic accuracy of 15 shoulder special tests for rotator cuff tears. Design From 02/2011 to 12/2012, 208 participants with shoulder pain were recruited in a cohort study. Results Among tests for supraspinatus tears, Jobe’s test had a sensitivity of 88% (95% CI=80% to 96%), specificity of 62% (95% CI=53% to 71%), and likelihood ratio of 2.30 (95% CI=1.79 to 2.95). The full can test had a sensitivity of 70% (95% CI=59% to 82%) and a specificity of 81% (95% CI=74% to 88%). Among tests for infraspinatus tears, external rotation lag signs at 0° had a specificity of 98% (95% CI=96% to 100%) and a likelihood ratio of 6.06 (95% CI=1.30 to 28.33), and the Hornblower’s sign had a specificity of 96% (95% CI=93% to 100%) and likelihood ratio of 4.81 (95% CI=1.60 to 14.49). Conclusions Jobe’s test and full can test had high sensitivity and specificity for supraspinatus tears and Hornblower’s sign performed well for infraspinatus tears. In general, special tests described for subscapularis tears have high specificity but low sensitivity. These data can be used in clinical practice to diagnose rotator cuff tears and may reduce the reliance on expensive imaging. PMID:27386812

A simple and rapid DNA extraction method for Chlamydia trachomatis detection from urogenital swabs.

PubMed

Butzler, Matthew A; Reed, Jennifer L; McFall, Sally M

2017-11-01

A highly sensitive and specific Chlamydia trachomatis (CT) diagnostic test was developed by combining filtration isolation of nucleic acid (FINA) extraction with quantitative polymerase chain reaction including an internal control to identify test inhibition. A pilot study of 40 clinical specimens yielded 100% sensitivity and specificity. Copyright © 2017 Elsevier Inc. All rights reserved.

Accuracy of a disability instrument to identify workers likely to develop upper extremity musculoskeletal disorders.

PubMed

Stover, Bert; Silverstein, Barbara; Wickizer, Thomas; Martin, Diane P; Kaufman, Joel

2007-06-01

Work related upper extremity musculoskeletal disorders (MSD) result in substantial disability, and expense. Identifying workers or jobs with high risk can trigger intervention before workers are injured or the condition worsens. We investigated a disability instrument, the QuickDASH, as a workplace screening tool to identify workers at high risk of developing upper extremity MSDs. Subjects included workers reporting recurring upper extremity MSD symptoms in the past 7 days (n = 559). The QuickDASH was reasonably accurate at baseline with sensitivity of 73% for MSD diagnosis, and 96% for symptom severity. Specificity was 56% for diagnosis, and 53% for symptom severity. At 1-year follow-up sensitivity and specificity for MSD diagnosis was 72% and 54%, respectively, as predicted by the baseline QuickDASH score. For symptom severity, sensitivity and specificity were 86% and 52%. An a priori target sensitivity of 70% and specificity of 50% was met by symptom severity, work pace and quality, and MSD diagnosis. The QuickDASH may be useful for identifying jobs or workers with increased risk for upper extremity MSDs. It may provide an efficient health surveillance screening tool useful for targeting early workplace intervention for prevention of upper extremity MSD problems.

Limits to Sensitivity in Laser Enhanced Ionization.

ERIC Educational Resources Information Center

Travis, J. C.

1982-01-01

Laser enhanced ionization (LEI) occurs when a tunable dye laser is used to excite a specific atomic population in a flame. Explores the origin of LEI's high sensitivity and identifies possible avenues to higher sensitivity by describing instrument used and experimental procedures and discussing ion formation/detection. (Author/JN)

[Screening interview for early detection of high-functioning autism spectrum disorders].

PubMed

Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge

2015-05-01

Various different questionnaires are available for the screening of autism spectrum disorders (ASD). These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process.

Evaluation of a newly developed quantitative heart-type fatty acid binding protein assay based on fluorescence immunochromatography using specific monoclonal antibodies.

PubMed

Kang, Keren; Wu, Peidian; Li, Wenmei; Tang, Shixing; Wang, Jihua; Luo, Xiaochun; Xie, Mingquan

2015-01-01

To develop a rapid, sensitive and specific assay for quantification of serum heart-type fatty acid binding protein (H-FABP) based on immunofluorescence of specific monoclonal antibodies. We generated novel H-FABP-directed monoclonal antibodies by cloning of spleen cells of mice immunized with H-FABP. Epitopes were mapped and antigen affinity was assessed by surface plasmon resonance (SPR). The H-FABP specific monoclonal antibodies were coupled to fluorescent beads and sprayed onto a nitrocellulose membrane facilitating quantification of H-FABP by immunofluorescence. Reagent cross-reactivity, interference resistance, accuracy and sensitivity were examined. A total of 103 clinical samples were used to compare the sensitivity and specificity of the new assay to a commercially available Randox kit. This new assay could be finished within 15 min, with sensitivity reaching 1 ng/ml. In a trial of 103 clinical serum samples, the new testing kit results were highly correlated with those from the Randox kit (R(2) = 0.9707). Using the Randox kit as the reference kit, the sensitivity of the new assay was 98.25%, and specificity was 100%. An immunofluorescence-based H-FABP assay employing novel monoclonal antibodies could rapidly, specifically and sensitively detect H-FABP in serum samples, providing an effective method for rapid clinical assessment of H-FABP index in the clinic.

The sensitivity and specificity of the Middlesex Elderly Assessment of Mental State (MEAMS) for detecting cognitive impairment after stroke.

PubMed

Cartoni, A; Lincoln, N B

2005-03-01

The aim of the study was to assess the sensitivity and specificity of the MEAMS (Golding, 1989) for detecting cognitive impairment after stroke. Stroke patients admitted to hospital received a cognitive screening assessment, the MEAMS, and a detailed cognitive assessment. The information obtained from the detailed assessment was summarised in a structured written report. From the conclusions in these reports, patients were classified as "impaired" or "not impaired" in perception, memory, executive function and language. The sensitivity and specificity of the MEAMS subtests and the overall number of tests passed were determined in relation to the presence of impairment, as given in the overall conclusion of the written reports. There were 30 stroke patients, aged 58 to 92 (mean 75.80, SD 7.94) years. Of these, 17 were men and 13 were women. The sensitivity of the MEAMS subtests ranged from 11% to 100% and the specificity ranged from 69% to 100%. The sensitivity of the overall MEAMS score was 52% and the specificity was 100%, using a cut-off score of 3 or more fails to indicate impairment. Three subtests, Orientation, Naming and Unusual views had 81% sensitivity and 50% specificity for detecting problems in language, perception or memory. The MEAMS was not a sensitive screen for overall cognitive impairment or for memory, perceptual, language, or executive function problems after stroke, but it was specific. Although screening for cognitive impairment is important, the MEAMS is not recommended as the sole method, as it produces an unacceptably high false negative rate. Three subtests (Orientation, Naming and Unusual views) had 81% sensitivity and 50% specificity for detecting cognitive problems in language, perception or memory after stroke.

Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample.

PubMed

Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Kraft, Peter; Loda, Massimo; Fuchs, Charles S

2007-07-01

The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation is a distinct phenotype in colorectal cancer. However, a choice of markers for CIMP has been controversial. A recent extensive investigation has selected five methylation markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) as surrogate markers for epigenomic aberrations in tumor. The use of these markers as a CIMP-specific panel needs to be validated by an independent, large dataset. Using MethyLight assays on 920 colorectal cancers from two large prospective cohort studies, we quantified DNA methylation in eight CIMP-specific markers [the above five plus CDKN2A (p16), CRABP1, and MLH1]. A CIMP-high cutoff was set at > or = 6/8 or > or = 5/8 methylated promoters, based on tumor distribution and BRAF/KRAS mutation frequencies. All but two very specific markers [MLH1 (98% specific) and SOCS1 (93% specific)] demonstrated > or = 85% sensitivity and > or = 80% specificity, indicating overall good concordance in methylation patterns and good performance of these markers. Based on sensitivity, specificity, and false positives and negatives, the eight markers were ranked in order as: RUNX3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1, and CDKN2A. In conclusion, a panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP-high.

Early life IgE responses in children living in the tropics: a prospective analysis.

PubMed

Zakzuk, Josefina; Acevedo, Nathalie; Cifuentes, Liliana; Bornacelly, Adriana; Sánchez, Jorge; Ahumada, Velky; Ring, Johannes; Ollert, Markus; Caraballo, Luis

2013-12-01

There are few birth cohort studies analyzing IgE sensitization in the tropics. We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Establishment and Application of a Loop-Mediated Isothermal Amplification Method for Simple, Specific, Sensitive and Rapid Detection of Toxoplasma gondii

PubMed Central

CAO, Lili; CHENG, Ronghua; YAO, Lin; YUAN, Shuxian; YAO, Xinhua

2013-01-01

ABSTRACT The Loop-mediated isothermal amplification (LAMP) method amplifies DNA with high simply, specificity, sensitivity and rapidity. In this study, A LAMP assay with 6 primers targeting a highly conserved region of the GRA1 gene was developed to diagnose Toxoplasma gondii. The reaction time of the LAMP assay was shortened to 30 min after optimizing the reaction system. The LAMP assay was found to be highly specific and stable. The detection limit of the LAMP assay was 10 copies, the same as that of the conventional PCR. We used the LAMP assay to develop a real-time fluorogenic protocol to quantitate T. gondii DNA and generated a log-linear regression plot by plotting the time-to-threshold values against genomic equivalent copies. Furthermore, the LAMP assay was applied to detect T. gondii DNA in 423 blood samples and 380 lymph node samples from 10 pig farms, and positive results were obtained for 7.8% and 8.2% of samples, respectively. The results showed that the LAMP method is slightly more sensitive than conventional PCR (6.1% and 7.6%). Positive samples obtained from 6 pig farms. The LAMP assay established in this study resulted in simple, specific, sensitive and rapid detection of T. gondii DNA and is expected to play an important role in clinical detection of T. gondii. PMID:23965849

New Perspectives on the Diagnosis of Allergy to Anisakis spp.

PubMed

Moneo, Ignacio; Carballeda-Sangiao, Noelia; González-Muñoz, Miguel

2017-05-01

To compare the prevalence of sensitization in different countries based on specific IgE values and to evaluate the use of isolated native or recombinant allergens for diagnosis. Isolated allergens help in the diagnosis of truly sensitized patients avoiding false positives due to cross-reactions. Their use is therefore highly recommended, especially when used as a combination of several relevant allergens. The use of purified allergens allows an accurate diagnosis and this has led to three important findings: (1) in addition to the digestive route of sensitization, occupational and non-digestive exposure seems to be clinically relevant. (2) The parasite appears as an important agent for chronic urticaria. And (3) in endemic countries, the amount of highly sensitized subjects in the general population could be as high as 7%. Adequate information to asymptomatic patients on fish consumption habits would avoid new contacts with parasite allergens and decrease their specific IgE levels and consequently the appearance of acute or chronic episodes induced by the parasite.

Label-Free Electrical Immunosensor for Highly Sensitive and Specific Detection of Microcystin-LR in Water Samples.

PubMed

Tan, Feng; Saucedo, Nuvia Maria; Ramnani, Pankaj; Mulchandani, Ashok

2015-08-04

Microcystin-LR (MCLR) is one of the most commonly detected and toxic cyclic heptapeptide cyanotoxins released by cyanobacterial blooms in surface waters, for which sensitive and specific detection methods are necessary to carry out its recognition and quantification. Here, we present a single-walled carbon nanotube (SWCNTs)-based label-free chemiresistive immunosensor for highly sensitive and specific detection of MCLR in different source waters. MCLR was initially immobilized on SWCNTs modified interdigitated electrode, followed by incubation with monoclonal anti-MCLR antibody. The competitive binding of MCLR in sample solutions induced departure of the antibody from the antibody-antigen complexes formed on SWCNTs, resulting in change in the conductivity between source and drain of the sensor. The displacement assay greatly improved the sensitivity of the sensor compared with direct immunoassay on the same device. The immunosensor exhibited a wide linear response to log value of MCLR concentration ranging from 1 to 1000 ng/L, with a detection limit of 0.6 ng/L. This method showed good reproducibility, stability and recovery. The proposed method provides a powerful tool for rapid and sensitive monitoring of MCLR in environmental samples.

Applying Classification Trees to Hospital Administrative Data to Identify Patients with Lower Gastrointestinal Bleeding

PubMed Central

Siddique, Juned; Ruhnke, Gregory W.; Flores, Andrea; Prochaska, Micah T.; Paesch, Elizabeth; Meltzer, David O.; Whelan, Chad T.

2015-01-01

Background Lower gastrointestinal bleeding (LGIB) is a common cause of acute hospitalization. Currently, there is no accepted standard for identifying patients with LGIB in hospital administrative data. The objective of this study was to develop and validate a set of classification algorithms that use hospital administrative data to identify LGIB. Methods Our sample consists of patients admitted between July 1, 2001 and June 30, 2003 (derivation cohort) and July 1, 2003 and June 30, 2005 (validation cohort) to the general medicine inpatient service of the University of Chicago Hospital, a large urban academic medical center. Confirmed cases of LGIB in both cohorts were determined by reviewing the charts of those patients who had at least 1 of 36 principal or secondary International Classification of Diseases, Ninth revision, Clinical Modification (ICD-9-CM) diagnosis codes associated with LGIB. Classification trees were used on the data of the derivation cohort to develop a set of decision rules for identifying patients with LGIB. These rules were then applied to the validation cohort to assess their performance. Results Three classification algorithms were identified and validated: a high specificity rule with 80.1% sensitivity and 95.8% specificity, a rule that balances sensitivity and specificity (87.8% sensitivity, 90.9% specificity), and a high sensitivity rule with 100% sensitivity and 91.0% specificity. Conclusion These classification algorithms can be used in future studies to evaluate resource utilization and assess outcomes associated with LGIB without the use of chart review. PMID:26406318

Sensitivity and specificity of the AdenoPlus point-of-care system in detecting adenovirus in conjunctivitis patients at an ophthalmic emergency department: a diagnostic accuracy study.

PubMed

Kam, K Y Ronald; Ong, Hon Shing; Bunce, Catey; Ogunbowale, Lola; Verma, Seema

2015-09-01

To estimate the diagnostic accuracy (sensitivity and specificity) of the AdenoPlus point-of-care adenoviral test compared to PCR in an ophthalmic accident and emergency service. These findings were compared with those of a previous study. This was a prospective diagnostic accuracy study on 121 patients presenting to an emergency eye unit with a clinical picture of acute adenoviral conjunctivitis. AdenoPlus testing was carried out on one eye of each patient and a PCR analysis was also performed on a swab taken from the same eye. AdenoPlus and PCR results were interpreted by masked personnel. Sensitivity and specificity for the AdenoPlus test were calculated using PCR results as the reference standard. 121 patients were enrolled and 109 met the inclusion criteria. 43 patients (39.4%) tested positive for adenovirus by PCR analysis. The sensitivity of the AdenoPlus swab in detecting adenovirus was 39.5% (17/43, 95% CI 26% to 54%) and specificity was 95.5% (63/66, 95% CI 87% to 98%) compared to PCR. The AdenoPlus test has a high specificity for diagnosing adenoviral conjunctivitis, but in this clinical setting, we could not reproduce the high sensitivity that has been previously published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A method for identifying color vision deficiency malingering.

PubMed

Pouw, Andrew; Karanjia, Rustum; Sadun, Alfredo

2017-03-01

To propose a new test to identify color vision deficiency malingering. An online survey was distributed to 130 truly color vision deficient participants and 160 participants willing to simulate color vision deficiency. The survey contained three sets of six color-adjusted versions of the standard Ishihara color plates each, as well as one set of six control plates. The plates that best discriminated both participant groups were selected for a "balanced" test emphasizing both sensitivity and specificity. A "specific" test that prioritized high specificity was also created by selecting from these plates. Statistical measures of the test (sensitivity, specificity, and Youden index) were assessed at each possible cut-off threshold, and a receiver operating characteristic (ROC) function with its area under the curve (AUC) charted. The redshift plate set was identified as having the highest difference of means between groups (-58%, CI: -64 to -52%), as well as the widest gap between group modes. Statistical measures of the "balanced" test show an optimal cut-off of at least two incorrectly identified plates to suggest malingering (Youden index: 0.773, sensitivity: 83.3%, specificity: 94.0%, AUC of ROC 0.918). The "specific" test was able to identify color vision deficiency simulators with a specificity of 100% when using a cut-off of at least two incorrectly identified plates (Youden index 0.599, sensitivity 59.9%, specificity 100%, AUC of ROC 0.881). Our proposed test for identifying color vision deficiency malingering demonstrates a high degree of reliability with AUCs of 0.918 and 0.881 for the "balanced" and "specific" tests, respectively. A cut-off threshold of at least two missed plates on the "specific" test was able to identify color vision deficiency simulators with 100% specificity.

The Detection of Protein via ZnO Resonant Raman Scattering Signal

NASA Astrophysics Data System (ADS)

Shan, Guiye; Yang, Guoliang; Wang, Shuang; Liu, Yichun

2008-03-01

Detecting protein with high sensitivity and specificity is essential for disease diagnostics, drug screening and other application. Semiconductor nanoparticles show better properties than organic dye molecules when used as markers for optical measurements. We used ZnO nanoparticles as markers for detecting protein in resonant Raman scattering measurements. The highly sensitive detection of proteins was achieved by an antibody-based sandwich assay. A probe for the target protein was constructed by binding the ZnO/Au nanoparticles to a primary antibody by eletrostatic interaction between Au and the antibody. A secondary antibody, which could be specifically recognized by target protein, was attached to a solid surface. The ZnO/Au-antibody probe could specifically recognize and bind to the complex of the target protein and secondary antibody. Our measurements using the resonant Raman scattering signal of ZnO nanoparticles showed good selectivity and sensitivity for the target protein.

Search strategies for identifying qualitative studies in CINAHL.

PubMed

Wilczynski, Nancy L; Marks, Susan; Haynes, R Brian

2007-05-01

Nurses, allied health professionals, clinicians, and researchers increasingly use online access to evidence in the course of patient care or when conducting reviews on a particular topic. Qualitative research has an important role in evidence-based health care. Online searching for qualitative studies can be difficult, however, resulting in the need to develop search filters. The objective of this study was to develop optimal search strategies to retrieve qualitative studies in CINAHL for the 2000 publishing year. The authors conducted an analytic survey comparing hand searches of journals with retrievals from CINAHL for candidate search terms and combinations. Combinations of search terms reached peak sensitivities of 98.9% and peak specificities of 99.5%. Combining search terms optimized both sensitivity and specificity at 94.2%. Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and high specificity for retrieving qualitative studies from CINAHL.

Multi-modal approach using Raman spectroscopy and optical coherence tomography for the discrimination of colonic adenocarcinoma from normal colon

PubMed Central

Ashok, Praveen C.; Praveen, Bavishna B.; Bellini, Nicola; Riches, Andrew; Dholakia, Kishan; Herrington, C. Simon

2013-01-01

We report a multimodal optical approach using both Raman spectroscopy and optical coherence tomography (OCT) in tandem to discriminate between colonic adenocarcinoma and normal colon. Although both of these non-invasive techniques are capable of discriminating between normal and tumour tissues, they are unable individually to provide both the high specificity and high sensitivity required for disease diagnosis. We combine the chemical information derived from Raman spectroscopy with the texture parameters extracted from OCT images. The sensitivity obtained using Raman spectroscopy and OCT individually was 89% and 78% respectively and the specificity was 77% and 74% respectively. Combining the information derived using the two techniques increased both sensitivity and specificity to 94% demonstrating that combining complementary optical information enhances diagnostic accuracy. These data demonstrate that multimodal optical analysis has the potential to achieve accurate non-invasive cancer diagnosis. PMID:24156073

Anxiety sensitivity class membership moderates the effects of pre-quit reduction in anxiety sensitivity on quit-day tobacco craving.

PubMed

Bakhshaie, Jafar; Zvolensky, Michael J; Langdon, Kirsten J; Leventhal, Adam M; Smits, Jasper A J; Allan, Nicholas; Schmidt, Norman B

2016-04-01

Although anxiety sensitivity has been primarily conceptualized as a dimensional latent construct, empirical evidence suggests that it also maintains a latent class structure, reflecting low-, moderate-, and high-risk underlying classes. The present study sought to explore whether these anxiety sensitivity classes moderated the relations between the degree of pre-quit reductions in anxiety sensitivity and the severity of nicotine withdrawal symptoms and craving experienced on quit-day. Participants included 195 adult smokers (47% female; Mage=39.4) participating in a larger "anxiety sensitivity reduction-smoking cessation" intervention trial. Anxiety sensitivity class significantly moderated relations between pre-quit reduction in anxiety sensitivity and quit-day craving. Specifically, smokers within the anxiety sensitivity high-risk class, who also demonstrated lesser pre-quit reductions in anxiety sensitivity, experienced the highest levels of craving on quit-day. These findings highlight the importance of 'high-risk' classes of anxiety sensitivity to better understand the experience of craving on quit day. Copyright © 2016. Published by Elsevier Ltd.

[Sorting role of p16(INK4a)/Ki-67 double immunostaining in the cervical cytology specimens of ASCUS and LSIL cases].

PubMed

Yu, J; Zhu, H T; Zhao, J J; Su, J Z; Xia, Y D

2017-05-08

Objective: To investigate the sorting effect of p16(INK4a)/Ki-67 double immunostaining method in patients with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology results. Methods: Four-hundred and twenty cases collected during April 2014 to February 2015 of cervical cytology of ASCUS ( n =318) and LSIL ( n =102) were selected, and residual liquid-based cytology specimens were used for p16(INK4a)/Ki-67 double immunostaining. The sensitivity and specificity of the detection of cervical precancerous lesions and cervical cancer were calculated, and the results were compared with high risk HPV. Taking histological follow-up as the gold standard, the test was considered positive when at least one cell exhibited p16(INK4a)/Ki-67 co-staining, without requirement of adjunct morphologic interpretation of positive cells. Results: Further screening CIN2+ in cytology ASCUS and LSIL group , the sensitivity of p16(INK4a)/Ki-67 double immunostaining was slightly lower than high risk HPV (84.2% vs . 94.7%), while the specificity was higher (84.0% vs . 53.9%). For ASCUS patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 82.6% and 91.3%, and the specificity was 88.8% and 63.7%, respectively. For LSIL patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 86.7% and 100.0%, and the specificity was 67.8% and 20.7%, respectively. For patients younger and older than 30 years, specificity of p16(INK4a)/Ki-67 double immunostaining was both higher than that of high risk HPV (80.8% vs . 42.3%; 84.6% vs . 56.9%). Conclusions: p16(INK4a)/Ki-67 double immunostaining can effectively identify the high risk population in ASCUS or LSIL, with higher specificity than high risk HPV test. p16(INK4a)/Ki-67 double immunostaining may benefit patients younger than 30 years of age as a preliminary or potential cytology-combining screening tool.

Geochemistry of biomolecules

NASA Technical Reports Server (NTRS)

Bonner, J.

1976-01-01

A highly sensitive fluorometric technique is developed for the determination of biological and geo-organic compounds in ancient sediments and extraterrestrial samples. This technique is used to establish chemical evidence for fossil pigments in an extraterrestrial sample. Also developed is a highly sensitive and specific fluorometric method for the determination of total primary amine nitrogen in soil samples.

Development of a sensitive Luminex xMAP-based microsphere immunoassay for specific detection of Iris yellow spot virus.

PubMed

Yu, Cui; Yang, Cuiyun; Song, Shaoyi; Yu, Zixiang; Zhou, Xueping; Wu, Jianxiang

2018-04-04

Iris yellow spot virus (IYSV) is an Orthotospovirus that infects most Allium species. Very few approaches for specific detection of IYSV from infected plants are available to date. We report the development of a high-sensitive Luminex xMAP-based microsphere immunoassay (MIA) for specific detection of IYSV. The nucleocapsid (N) gene of IYSV was cloned and expressed in Escherichia coli to produce the His-tagged recombinant N protein. A panel of monoclonal antibodies (MAbs) against IYSV was generated by immunizing the mice with recombinant N protein. Five specific MAbs (16D9, 11C6, 7F4, 12C10, and 14H12) were identified and used for developing the Luminex xMAP-based MIA systems along with a polyclonal antibody against IYSV. Comparative analyses of their sensitivity and specificity in detecting IYSV from infected tobacco leaves identified 7F4 as the best-performed MAb in MIA. We then optimized the working conditions of Luminex xMAP-based MIA in specific detection of IYSV from infected tobacco leaves by using appropriate blocking buffer and proper concentration of biotin-labeled antibodies as well as the suitable ratio between the antibodies and the streptavidin R-phycoerythrin (SA-RPE). Under the optimized conditions the Luminex xMAP-based MIA was able to specifically detect IYSV with much higher sensitivity than conventional enzyme-linked immunosorbent assay (ELISA). Importantly, the Luminex xMAP-based MIA is time-saving and the whole procedure could be completed within 2.5 h. We generated five specific MAbs against IYSV and developed the Luminex xMAP-based MIA method for specific detection of IYSV in plants. This assay provides a sensitive, high-specific, easy to perform and likely cost-effective approach for IYSV detection from infected plants, implicating potential broad usefulness of MIA in plant virus diagnosis.

Noise sensitivity: Symptoms, health status, illness behavior and co-occurring environmental sensitivities

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

Baliatsas, Christos, E-mail: c.baliatsas@nivel.nl

Epidemiological evidence on the symptomatic profile, health status and illness behavior of people with subjective sensitivity to noise is still scarce. Also, it is unknown to what extent noise sensitivity co-occurs with other environmental sensitivities such as multi-chemical sensitivity and sensitivity to electromagnetic fields (EMF). A cross-sectional study performed in the Netherlands, combining self-administered questionnaires and electronic medical records of non-specific symptoms (NSS) registered by general practitioners (GP) allowed us to explore this further. The study sample consisted of 5806 participants, drawn from 21 general practices. Among participants, 722 (12.5%) responded “absolutely agree” to the statement “I am sensitive tomore » noise”, comprising the high noise-sensitive (HNS) group. Compared to the rest of the sample, people in the HNS group reported significantly higher scores on number and duration of self-reported NSS, increased psychological distress, decreased sleep quality and general health, more negative symptom perceptions and higher prevalence of healthcare contacts, GP-registered NSS and prescriptions for antidepressants and benzodiazepines. These results remained robust after adjustment for demographic, residential and lifestyle characteristics, objectively measured nocturnal noise exposure from road-traffic and GP-registered morbidity. Co-occurrence rates with other environmental sensitivities varied between 9% and 50%. Individuals with self-declared sensitivity to noise are characterized by high prevalence of multiple NSS, poorer health status and increased illness behavior independently of noise exposure levels. Findings support the notion that different types of environmental sensitivities partly overlap. - Highlights: • People with self-reported noise sensitivity experience multiple non-specific symptoms. • They also report comparatively poorer health and increased illness behavior. • Co-occurrence with other environmental sensitivities is moderate to high. • Road-traffic noise and GP-registered morbidity did not account for these results.« less

Targeting Conserved Genes in Fusarium Species.

PubMed

Gil-Serna, Jéssica; Patiño, Belén; Jurado, Miguel; Mirete, Salvador; Vázquez, Covadonga; González-Jaén, M Teresa

2017-01-01

Fumonisins are important mycotoxins contaminating foods and feeds which are mainly produced by F. verticillioides and F. proliferatum. Additionally, both are pathogens of maize and other cereals. We describe two highly sensitive, rapid, and species-specific PCR protocols which enable detection and discrimination of these closely related species in cereal flour or grain samples. The specific primer pairs of these assays were based on the intergenic spacer region of the multicopy rDNA unit which highly improves the sensitivity of the PCR assay in comparison with single-copy target regions.

Evaluation of Leishmania species reactivity in human serologic diagnosis of leishmaniasis.

PubMed

Silvestre, Ricardo; Santarém, Nuno; Teixeira, Lúcia; Cunha, Joana; Schallig, Henk; Cordeiro-da-Silva, Anabela

2009-08-01

The sensitivities and specificities of IgG-ELISA and IgG flow cytometry based techniques using different Leishmania species were determined using sera collected from 40 cutaneous or visceral leishmaniasis patients. The flow cytometry technique, using promastigote parasite forms, performed better than total soluble extract IgG-ELISA. At the species level, the use of Leishmania amazonensis and Leishmania major as antigens in enzyme linked immunosorbent assay (ELISA) decreased the overall sensitivity. To assess the specificity of these tests, sera from malaria, toxoplasmosis, amoebiasis, schistosomiasis, and leprosy patients were used. We also included sera from Leishmania non-infected endemic individuals. The cutaneous species displayed a decreased specificity in both assays. Although more sensitive, flow cytometry using promastigote parasite forms generally presented lower levels of specificity when compared with total extract of IgG-ELISA. Overall, the results of the study show the potential of IgG flow cytometry for the diagnosis of leishmaniasis. Although highly sensitive, a refinement of the flow cytometry method should be performed to improve the overall specificity.

Highly specific detection of genetic modification events using an enzyme-linked probe hybridization chip.

PubMed

Zhang, M Z; Zhang, X F; Chen, X M; Chen, X; Wu, S; Xu, L L

2015-08-10

The enzyme-linked probe hybridization chip utilizes a method based on ligase-hybridizing probe chip technology, with the principle of using thio-primers for protection against enzyme digestion, and using lambda DNA exonuclease to cut multiple PCR products obtained from the sample being tested into single-strand chains for hybridization. The 5'-end amino-labeled probe was fixed onto the aldehyde chip, and hybridized with the single-stranded PCR product, followed by addition of a fluorescent-modified probe that was then enzymatically linked with the adjacent, substrate-bound probe in order to achieve highly specific, parallel, and high-throughput detection. Specificity and sensitivity testing demonstrated that enzyme-linked probe hybridization technology could be applied to the specific detection of eight genetic modification events at the same time, with a sensitivity reaching 0.1% and the achievement of accurate, efficient, and stable results.

Molecular Tools for Diagnosis of Visceral Leishmaniasis: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

PubMed Central

de Ruiter, C. M.; van der Veer, C.; Leeflang, M. M. G.; Deborggraeve, S.; Lucas, C.

2014-01-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. PMID:24829226

A comparison of five serological tests for bovine brucellosis.

PubMed Central

Dohoo, I R; Wright, P F; Ruckerbauer, G M; Samagh, B S; Robertson, F J; Forbes, L B

1986-01-01

Five serological assays: the buffered plate antigen test, the standard tube agglutination test, the complement fixation test, the hemolysis-in-gel test and the indirect enzyme immunoassay were diagnostically evaluated. Test data consisted of results from 1208 cattle in brucellosis-free herds, 1578 cattle in reactor herds of unknown infection status and 174 cattle from which Brucella abortus had been cultured. The complement fixation test had the highest specificity in both nonvaccinated and vaccinated cattle. The indirect enzyme immunoassay, if interpreted at a high threshold, also exhibited a high specificity in both groups of cattle. The hemolysis-in-gel test had a very high specificity when used in nonvaccinated cattle but quite a low specificity among vaccinates. With the exception of the complement fixation test, all tests had high sensitivities if interpreted at the minimum threshold. However, the sensitivities of the standard tube agglutination test and indirect enzyme immunoassay, when interpreted at high thresholds were comparable to that of the complement fixation test. A kappa statistic was used to measure the agreement between the various tests. In general the kappa statistics were quite low, suggesting that the various tests may detect different antibody isotypes. There was however, good agreement between the buffered plate antigen test and standard tube agglutination test (the two agglutination tests evaluated) and between the complement fixation test and the indirect enzyme immunoassay when interpreted at a high threshold. With the exception of the buffered plate antigen test, all tests were evaluated as confirmatory tests by estimating their specificity and sensitivity on screening-test positive samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3539295

Age-related differences in recommended anthropometric cut-off point validity to identify cardiovascular risk factors in ostensibly healthy women

PubMed Central

Björkelund, Cecilia; Guo, Xinxin; Skoog, Ingmar; Bosaeus, Ingvar; Lissner, Lauren

2014-01-01

Aim: To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. Methods: A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. Results: The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. Conclusions: Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women. PMID:25294689

Age-related differences in recommended anthropometric cut-off point validity to identify cardiovascular risk factors in ostensibly healthy women.

PubMed

Subramoney, Sreevidya; Björkelund, Cecilia; Guo, Xinxin; Skoog, Ingmar; Bosaeus, Ingvar; Lissner, Lauren

2014-12-01

To investigate validity of widely recommended anthropometric and total fat percentage cut-off points in screening for cardiovascular risk factors in women of different ages. A population-based sample of 1002 Swedish women aged 38, 50, 75 (younger, middle-aged and elderly, respectively) underwent anthropometry, health examinations and blood tests. Total fat was estimated (bioimpedance) in 670 women. Sensitivity, specificity of body mass index (BMI; ≥25 and ≥30), waist circumference (WC; ≥80 cm and ≥88 cm) and total fat percentage (TF; ≥35%) cut-off points for cardiovascular risk factors (dyslipidaemias, hypertension and hyperglycaemia) were calculated for each age. Cut-off points yielding high sensitivity together with modest specificity were considered valid. Women reporting hospital admission for cardiovascular disease were excluded. The sensitivity of WC ≥80 cm for one or more risk factors was ~60% in younger and middle-aged women, and 80% in elderly women. The specificity of WC ≥80 cm for one or more risk factors was 69%, 57% and 40% at the three ages (p < .05 for age trends). WC ≥80 cm yielded ~80% sensitivity for two or more risk factors across all ages. However, specificity decreased with increasing age (p < .0001), being 33% in elderly. WC ≥88 cm provided better specificity in elderly women. BMI and TF % cut-off points were not better than WC. Validity of recommended anthropometric cut-off points in screening asymptomatic women varies with age. In younger and middle-age, WC ≥80 cm yielded high sensitivity and modest specificity for two or more risk factors, however, sensitivity for one or more risk factor was less than optimal. WC ≥88 cm showed better validity than WC ≥80 cm in elderly. Our results support age-specific screening cut-off points for women. © 2014 the Nordic Societies of Public Health.

Highly Sensitive Droplet Digital PCR Method for Detection of EGFR-Activating Mutations in Plasma Cell-Free DNA from Patients with Advanced Non-Small Cell Lung Cancer.

PubMed

Zhu, Guanshan; Ye, Xin; Dong, Zhengwei; Lu, Ya Chao; Sun, Yun; Liu, Yi; McCormack, Rose; Gu, Yi; Liu, Xiaoqing

2015-05-01

Epidermal growth factor receptor (EGFR) mutation testing in plasma cell-free DNA from lung cancer patients is an emerging clinical tool. However, compared with tissue testing, the sensitivity of plasma testing is not yet satisfactory because of the highly fragmented nature of plasma cell-free DNA, low fraction of tumor DNA, and limitations of available detection technologies. We therefore developed a highly sensitive and specific droplet digital PCR method for plasma EGFR mutation (exon19 deletions and L858R) testing. Plasma from 86 EGFR-tyrosine kinase inhibitor-naive lung cancer patients was tested and compared with EGFR mutation status of matched tumor tissues tested by amplification refractory mutation system. By using EGFR mutation-positive cell DNA, we optimized the droplet digital PCR assays to reach 0.04% sensitivity. The plasma testing sensitivity and specificity, compared with the matched tumor tissues tested by amplification refractory mutation system, were 81.82% (95% CI, 59.72%-94.81%) and 98.44% (95% CI, 91.60%-99.96%), respectively, for exon19 deletions, with 94.19% concordance rate (κ = 0.840; 95% CI, 0.704-0.976; P < 0.0001), whereas they were 80.00% (95% CI, 51.91%-95.67%) and 95.77% (95% CI, 88.14%-99.12%), respectively, for L858R, with 93.02% concordance rate (κ = 0.758; 95% CI, 0.571-0.945; P < 0.0001). The reported highly sensitive and specific droplet digital PCR assays for EGFR mutation detection have potential in clinical blood testing. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Assessment of nodal involvement in non-small-cell lung cancer with 18F-FDG-PET/CT: mediastinal blood pool cut-off has the highest sensitivity and tumour SUVmax/2 has the highest specificity.

PubMed

Mallorie, Amy; Goldring, James; Patel, Anant; Lim, Eric; Wagner, Thomas

2017-08-01

Lymph node involvement in non-small-cell lung cancer (NSCLC) is a major factor in determining management and prognosis. We aimed to evaluate the accuracy of fluorine-18-fluorodeoxyglucose-PET/computed tomography (CT) for the assessment of nodal involvement in patients with NSCLC. In this retrospective study, we included 61 patients with suspected or confirmed resectable NSCLC over a 2-year period from April 2013 to April 2015. 221 nodes with pathological staging from surgery or endobronchial ultrasound-guided transbronchial needle aspiration were assessed using a nodal station-based analysis with original clinical reports and three different cut-offs: mediastinal blood pool (MBP), liver background and tumour standardized uptake value maximal (SUVmax)/2. Using nodal station-based analysis for activity more than tumour SUVmax/2, the sensitivity was 45%, the specificity was 89% and the negative predictive value (NPV) was 87%. For activity more than MBP, the sensitivity was 93%, the specificity was 72% and NPV was 98%. For activity more than liver background, the sensitivity was 83%, the specificity was 84% and NPV was 96%. Using a nodal staging-based analysis for accuracy at detecting N2/3 disease, for activity more than tumour SUVmax/2, the sensitivity was 59%, the specificity was 85% and NPV was 80%. For activity more than MBP, the sensitivity was 95%, the specificity was 61% and NPV was 96%. For activity more than liver background, the sensitivity was 86%, the specificity was 81% and NPV was 92%. Receiver-operating characteristic analysis showed the optimal nodal SUVmax to be more than 6.4 with a sensitivity of 45% and a specificity of 95%, with an area under the curve of 0.85. Activity more than MBP was the most sensitive cut-off with the highest sensitivity and NPV. Activity more than primary tumour SUVmax/2 was the most specific cut-off. Nodal SUVmax more than 6.4 has a high specificity of 95%.

Gravimetric chemical sensors based on silica-based mesoporous organic-inorganic hybrids.

PubMed

Xu, Jiaqiang; Zheng, Qi; Zhu, Yongheng; Lou, Huihui; Xiang, Qun; Cheng, Zhixuan

2014-09-01

Silica-based mesoporous organic-inorganic hybrid material modified quartz crystal microbalance (QCM) sensors have been examined for their ability to achieve highly sensitive and selective detection. Mesoporous silica SBA-15 serves as an inorganic host with large specific surface area, facilitating gas adsorption, and thus leads to highly sensitive response; while the presence of organic functional groups contributes to the greatly improved specific sensing property. In this work, we summarize our efforts in the rational design and synthesis of novel sensing materials for the detection of hazardous substances, including simulant nerve agent, organic vapor, and heavy metal ion, and develop high-performance QCM-based chemical sensors.

Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus.

PubMed

Joly, P; Richard, C; Gilbert, D; Courville, P; Chosidow, O; Roujeau, J C; Beylot-Barry, M; D'incan, M; Martel, P; Lauret, P; Tron, F

2000-10-01

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease characterized by the production of autoantibodies mainly directed against proteins of the plakin family. An overlapping distribution of autoantibody specificities has been recently reported between PNP, pemphigus vulgaris (PV), and pemphigus foliaceus (PF), which suggests a relationship between the different types of pemphigus. Our purpose was to evaluate the sensitivity and the specificity of clinical, histologic, and immunologic features in the diagnosis of PNP. The clinical, histologic, and immunologic features of 22 PNP patients were retrospectively reviewed and compared with those of 81 PV and PF patients without neoplasia and of 8 PV and 4 PF patients with various neoplasms. One clinical and 2 biologic features had both high sensitivity (82%-86%) and high specificity (83%-100%) whatever the control group considered: (1) association with a lymphoproliferative disorder, (2) indirect immunofluorescence (IIF) labeling of rat bladder, and (3) recognition of the envoplakin and/or periplakin bands in immunoblotting. Two clinicopathologic and two biologic features had high specificity (87%-100%) but poor sensitivity (27%-59%): (1) clinical presentation associating erosive oral lesions with erythema multiforme-like, bullous pemphigoid-like, or lichen planus-like cutaneous lesions; (2) histologic picture of suprabasal acantholysis with keratinocyte necrosis, interface changes, or lichenoid infiltrate; (3) presence of both anti-epithelial cell surface and anti-basement membrane zone antibodies by IIF; and (4) recognition of the desmoplakin I and/or BPAG1 bands in immunoblotting. Interestingly, 45% of patients with PNP presented initially with isolated oral erosions that were undistinguishable from those seen in PV patients, and 27% had histologic findings of only suprabasal acantholysis, which was in accordance with the frequent detection of anti-desmoglein 3 antibodies in PNP sera. The association with a lymphoproliferative disorder, the IIF labeling of rat bladder, and the immunoblotting recognition of envoplakin and/or periplakin are both sensitive and specific features in the diagnosis of PNP.

Development, Evaluation and Implementation of Chief Complaint Groupings to Activate Data Collection: A Multi-Center Study of Clinical Decision Support for Children with Head Trauma.

PubMed

Deakyne, S J; Bajaj, L; Hoffman, J; Alessandrini, E; Ballard, D W; Norris, R; Tzimenatos, L; Swietlik, M; Tham, E; Grundmeier, R W; Kuppermann, N; Dayan, P S

2015-01-01

Overuse of cranial computed tomography scans in children with blunt head trauma unnecessarily exposes them to radiation. The Pediatric Emergency Care Applied Research Network (PECARN) blunt head trauma prediction rules identify children who do not require a computed tomography scan. Electronic health record (EHR) based clinical decision support (CDS) may effectively implement these rules but must only be provided for appropriate patients in order to minimize excessive alerts. To develop, implement and evaluate site-specific groupings of chief complaints (CC) that accurately identify children with head trauma, in order to activate data collection in an EHR. As part of a 13 site clinical trial comparing cranial computed tomography use before and after implementation of CDS, four PECARN sites centrally developed and locally implemented CC groupings to trigger a clinical trial alert (CTA) to facilitate the completion of an emergency department head trauma data collection template. We tested and chose CC groupings to attain high sensitivity while maintaining at least moderate specificity. Due to variability in CCs available, identical groupings across sites were not possible. We noted substantial variability in the sensitivity and specificity of seemingly similar CC groupings between sites. The implemented CC groupings had sensitivities greater than 90% with specificities between 75-89%. During the trial, formal testing and provider feedback led to tailoring of the CC groupings at some sites. CC groupings can be successfully developed and implemented across multiple sites to accurately identify patients who should have a CTA triggered to facilitate EHR data collection. However, CC groupings will necessarily vary in order to attain high sensitivity and moderate-to-high specificity. In future trials, the balance between sensitivity and specificity should be considered based on the nature of the clinical condition, including prevalence and morbidity, in addition to the goals of the intervention being considered.

High-resolution mapping of transcription factor binding sites on native chromatin

PubMed Central

Kasinathan, Sivakanthan; Orsi, Guillermo A.; Zentner, Gabriel E.; Ahmad, Kami; Henikoff, Steven

2014-01-01

Sequence-specific DNA-binding proteins including transcription factors (TFs) are key determinants of gene regulation and chromatin architecture. Formaldehyde cross-linking and sonication followed by Chromatin ImmunoPrecipitation (X-ChIP) is widely used for profiling of TF binding, but is limited by low resolution and poor specificity and sensitivity. We present a simple protocol that starts with micrococcal nuclease-digested uncross-linked chromatin and is followed by affinity purification of TFs and paired-end sequencing. The resulting ORGANIC (Occupied Regions of Genomes from Affinity-purified Naturally Isolated Chromatin) profiles of Saccharomyces cerevisiae Abf1 and Reb1 provide highly accurate base-pair resolution maps that are not biased toward accessible chromatin, and do not require input normalization. We also demonstrate the high specificity of our method when applied to larger genomes by profiling Drosophila melanogaster GAGA Factor and Pipsqueak. Our results suggest that ORGANIC profiling is a widely applicable high-resolution method for sensitive and specific profiling of direct protein-DNA interactions. PMID:24336359

[Comparative research into sensitivity and specificity of immune-enzyme analysis with chemiluminescence and colorimetric detection for detecting antigens and antibodies to avian influenza viruses and newcastle disease].

PubMed

Vitkova, O N; Kapustina, T P; Mikhailova, V V; Safonov, G A; Vlasova, N N; Belousova, R V

2015-01-01

The goal of this work was to demonstrate the results of the development of the enzyme-linked immunosorbent tests with chemiluminescence detection and colorimetric detection of specific viral antigens and antibodies for identifying the avian influenza and the Newcastle disease viruses: high sensitivity and specificity of the immuno- chemiluminescence assay, which are 10-50 times higher than those of the ELISA colorimetric method. The high effectiveness of the results and the automation of the process of laboratory testing (using a luminometer) allow these methods to be recommended for including in primary screening tests for these infectious diseases.

High IgE sensitization to maize and rice pollen in the highlands of Madagascar

PubMed Central

Ramavovololona; Sénéchal, Hélène; Andrianarisoa, Ange; Rakotoarimanana, Vololona; Godfrin, Dominique; Peltre, Gabriel; Poncet, Pascal; Sutra, Jean-Pierre

2014-01-01

Introduction Maize and rice are two crops constituting the main food supply in many under-developed and developing countries. Despite the large area devoted to the culture, the sensitization to the pollen from these plants is reported to be low and often considered as an occupational allergy. Methods Sixty five Malagasy pollen allergic patients were clinically and immunochemically investigated with regard to maize and rice pollen allergens. Pollen extracts were electrophoretically separated in 1 and 2 dimensions and IgE and IgG reactivities detected upon immunoblotting. Results When exploring the sensitization profile of Malagasy allergic patients to maize and rice pollen, it appears that a high proportion of these patients consulting during grass pollinating season were sensitized to both pollen as revealed by skin prick testing (62 vs. 59%) and IgE immunoblotting (85 vs. 40%). Several clinically relevant allergens were recognized by patients’ serum IgE in maize and rice pollen extracts. Conclusion The high levels of maize and rice pollen sensitization should be related, in this tropical region, to a specific environmental exposure including i) a proximity of the population to the allergenic sources and ii) a putative exacerbating effect of a highly polluted urban atmosphere on pollen allergenicity. Cross-reactivities between wild and cultivated grasses and also between rice and maize pollen are involved as well as some specific maize sensitizations. The presence of dense urban and peri-urban agriculture, in various African regions and worldwide, could be a high environmental risk factor for people sensitive to maize pollen. PMID:25870739

Development of a species-specific coproantigen ELISA for human Taenia solium taeniasis.

PubMed

Guezala, Maria-Claudia; Rodriguez, Silvia; Zamora, Humberto; Garcia, Hector H; Gonzalez, Armando E; Tembo, Alice; Allan, James C; Craig, Philip S

2009-09-01

Taenia solium causes human neurocysticercosis and is endemic in underdeveloped countries where backyard pig keeping is common. Microscopic fecal diagnostic methods for human T. solium taeniasis are not very sensitive, and Taenia saginata and Taenia solium eggs are indistinguishable under the light microscope. Coproantigen (CoAg) ELISA methods are very sensitive, but currently only genus (Taenia) specific. This paper describes the development of a highly species-specific coproantigen ELISA test to detect T. solium intestinal taeniasis. Sensitivity was maintained using a capture antibody of rabbit IgG against T. solium adult whole worm somatic extract, whereas species specificity was achieved by utilization of an enzyme-conjugated rabbit IgG against T. solium adult excretory-secretory (ES) antigen. A known panel of positive and negative human fecal samples was tested with this hybrid sandwich ELISA. The ELISA test gave 100% specificity and 96.4% sensitivity for T. solium tapeworm carriers (N = 28), with a J index of 0.96. This simple ELISA incorporating anti-adult somatic and anti-adult ES antibodies provides the first potentially species-specific coproantigen test for human T. solium taeniasis.

Nucleic acid detection system and method for detecting influenza

DOEpatents

Cai, Hong; Song, Jian

2015-03-17

The invention provides a rapid, sensitive and specific nucleic acid detection system which utilizes isothermal nucleic acid amplification in combination with a lateral flow chromatographic device, or DNA dipstick, for DNA-hybridization detection. The system of the invention requires no complex instrumentation or electronic hardware, and provides a low cost nucleic acid detection system suitable for highly sensitive pathogen detection. Hybridization to single-stranded DNA amplification products using the system of the invention provides a sensitive and specific means by which assays can be multiplexed for the detection of multiple target sequences.

[Primary cervical cancer screening].

PubMed

Vargas-Hernández, Víctor Manuel; Vargas-Aguilar, Víctor Manuel; Tovar-Rodríguez, José María

2015-01-01

Cervico-uterine cancer screening with cytology decrease incidence by more than 50%. The cause of this cancer is the human papilloma virus high risk, and requires a sensitive test to provide sufficient sensitivity and specificity for early detection and greater interval period when the results are negative. The test of the human papilloma virus high risk, is effective and safe because of its excellent sensitivity, negative predictive value and optimal reproducibility, especially when combined with liquid-based cytology or biomarkers with viral load, with higher sensitivity and specificity, by reducing false positives for the detection of cervical intraepithelial neoplasia grade 2 or greater injury, with excellent clinical benefits to cervical cancer screening and related infection of human papilloma virus diseases, is currently the best test for early detection infection of human papillomavirus and the risk of carcinogenesis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

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.

Different sensitization to storage mites depending on the co-exposure to house dust mites.

PubMed

Morales, María; Iraola, Victor; Leonor, José Ramón; Bartra, Joan; Rodríguez, Fernando; Boquete, Manuel; Huertas, Ángel Julio; Paniagua, María Josefa; Pinto, Helder; Carnés, Jerónimo

2015-01-01

Co-sensitization to house dust mites (HDMs) and storage mites (SMs) is very frequent, although the clinical relevance is not well established. To describe the pattern of sensitization and immunologic characterization of patients with positive skin prick test reactions to HDMs and SMs in 4 areas of Spain, selected according to high exposure to HDMs and variable exposure to SMs. One hundred sixty-nine individuals with positive skin prick test reactions to HDMs and SMs were included. Specific IgE levels to different mite species and to Der p 1, Der p 2, and Der p 10 were determined. Immunoblots to Dermatophagoides pteronyssinus, Lepidoglyphus destructor, and Tyrophagus putrescentiae extracts were carried out, and allergograms were obtained. Results of different areas were compared. A high rate of polysensitization to SMs was observed, although 12% of participants did not have specific IgE to any SM species. Sensitization to Dermatophagoides species, Der p 2, and L destructor were predominant, although significant differences were observed among areas depending on the grade of exposure to SMs. In areas with high exposure, the SM allergogram showed greater recognition of group 2 allergen. Sensitization patterns to SMs in patients sensitized to HDMs and SMs differ depending on the exposure to SMs. Sensitization, mainly to L destructor, seems to exist in areas with high exposure, possibly with group 2 allergens mainly involved. However, in areas with low SM populations, sensitizations observed by skin prick testing appear to be related to HDM exposure. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Sensitivity and Specificity of CT and Its signs for Diagnosis of Strangulation in Patients with Acute Small Bowel Obstruction.

PubMed

Jha, Ashwini Kumar; Tang, Wen Hao; Bai, Zhi Bin; Xiao, Jia Quan

2014-01-01

To perform a meta-analysis to review the sensitivity and specificity of computed tomography and different known computed yomography signs for the diagnosis of strangulation in patients with acute small bowel obstruction. A comprehensive Pubmed search was performed for all reports that evaluated the use of CT and discussed different CT criteria for the diagnosis of acute SBO. Articles published in English language from January 1978 to June 2008 were included. Review articles, case reports, pictorial essays and articles without original data were excluded. The bivariate random effect model was used to obtain pooled sensitivity and pooled specificity. Summary receiver operating curve was calculated using Meta-Disc. Software Openbugs 3.0.3 was used to summarize the data. A total of 12 studies fulfilled the inclusion criteria. The pooled sensitivity and specificity of CT in the diagnosis of strangulation was 0.720 (95% CI 0.674 to 0.763) and 0.866 (95% CI 0.837 to 0.892) respectively. Among different CT signs, mesenteric edema had highest Pooled sensitivity of 0. 741 and lack of bowel wall enhancement had highest pooled specificity of 0.991. This review demonstrates that CT is highly sensitive as well as specific in the preoperative diagnosis of strangulation SBO which are in accordance with the published studies. Our analysis also shows that "presence of mesenteric fluid" is most sensitive, and "lack of bowel wall enhancement" is most specific CT sign of strangulation, and also justifies need of large scale prospective studies to validate the results obtained as well as to determine a clinical protocol.

Performance of homeostasis model assessment and serum high-sensitivity C-reactive protein for prediction of isolated post-load hyperglycaemia.

PubMed

Lai, Y-C; Li, H-Y; Hung, C-S; Lin, M-S; Shih, S-R; Ma, W-Y; Hua, C-H; Chuang, L-M; Sung, F-C; Wei, J-N

2013-03-01

To evaluate whether homeostasis model assessment and high-sensitivity C-reactive protein improve the prediction of isolated post-load hyperglycaemia. The subjects were 1458 adults without self-reported diabetes recruited between 2006 and 2010. Isolated post-load hyperglycaemia was defined as fasting plasma glucose < 7 mmol/l and 2-h post-load plasma glucose ≥ 11.1 mmol/l. Risk scores of isolated post-load hyperglycaemia were constructed by multivariate logistic regression. An independent group (n = 154) was enrolled from 2010 to 2011 to validate the models' performance. One hundred and twenty-three subjects (8.28%) were newly diagnosed as having diabetes mellitus. Among those with undiagnosed diabetes, 64 subjects (52%) had isolated post-load hyperglycaemia. Subjects with isolated post-load hyperglycaemia were older, more centrally obese and had higher blood pressure, HbA(1c), fasting plasma glucose, triglycerides, LDL cholesterol, high-sensitivity C-reactive protein and homeostasis model assessment of insulin resistance and lower homeostasis model assessment of β-cell function than those without diabetes. The risk scores included age, gender, BMI, homeostasis model assessment, high-sensitivity C-reactive protein and HbA(1c). The full model had high sensitivity (84%) and specificity (87%) and area under the receiver operating characteristic curve (0.91), with a cut-off point of 23.81; validation in an independent data set showed 88% sensitivity, 77% specificity and an area under curve of 0.89. Over half of those with undiagnosed diabetes had isolated post-load hyperglycaemia. Homeostasis model assessment and high-sensitivity C-reactive protein are useful to identify subjects with isolated post-load hyperglycaemia, with improved performance over fasting plasma glucose or HbA(1c) alone. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Differential sensitivity between a virtual reality (VR) balance module and clinically used concussion balance modalities

PubMed Central

Teel, Elizabeth F; Gay, Michael R; Arnett, Peter A; Slobounov, Semyon M

2015-01-01

Objective Balance assessments are part of the recommended clinical concussion evaluation, along with computerized neuropsychological testing and self-reported symptoms checklists. New technology has allowed for the creation of virtual reality (VR) balance assessments to be used in concussion care, but there is little information on the sensitivity and specificity of these evaluations. The purpose of this study is to establish the sensitivity and specificity of a VR balance module for detecting lingering balance deficits clinical concussion care. Design Retrospective, case-control study Setting Institutional research laboratory Participants Normal controls (n=94) and concussed participants (n=27) Interventions All participants completed a VR balance assessment paradigm. Concussed participants were diagnosed by a Certified Athletic Trainer or physician (with 48 hours post-injury) and tested in the lab between 7-10 days post-injury. ROC curves were performed in order to establish the VR module’s sensitivity and specificity for detecting lingering balance deficits. Main Outcome Measures Final balance score Results For the VR balance module, a cutoff score of 8.25 was established to maximize sensitivity at 85.7% and specificity at 87.8%. Conclusions The VR balance module has high sensitivity and specificity for detecting sub-acute balance deficits after concussive injury. PMID:26505696

Sensitivity and specificity of detecting reticular pseudodrusen in multimodal imaging in Japanese patients.

PubMed

Ueda-Arakawa, Naoko; Ooto, Sotaro; Tsujikawa, Akitaka; Yamashiro, Kenji; Oishi, Akio; Yoshimura, Nagahisa

2013-03-01

To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD. This study included 220 eyes from 114 patients with newly diagnosed age-related macular degeneration. Patients underwent fundus photography, IR, fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and SD-OCT in both eyes. Eyes were diagnosed with RPD if they showed reticular patterns on at least two of the seven imaging modalities. Thirty-seven eyes were diagnosed with RPD. However, SD-OCT and IR had the highest sensitivity (94.6%), and at the same time, SD-OCT had a high specificity (98.4%). The blue channel of color fundus photography, confocal blue reflectance, and indocyanine green angiography had a specificity of 100% but had lower sensitivity than that of SD-OCT and IR. For detecting RPD, IR and SD-OCT had the highest sensitivity. Although SD-OCT had the highest sensitivity and specificity, RPD detection should be confirmed using more than one modality for increased accuracy.

Comparative diagnostic evaluation of OMP31 gene based TaqMan® real-time PCR assay with visual LAMP assay and indirect ELISA for caprine brucellosis.

PubMed

Saini, Suman; Gupta, V K; Gururaj, K; Singh, D D; Pawaiya, R V S; Gangwar, N K; Mishra, A K; Dwivedi, Deepak; Andani, Dimple; Kumar, Ashok; Goswami, T K

2017-08-01

Brucellosis is one of the leading causes of abortion in domestic animals that imposes costs on both economy and society. The disease is highly zoonotic and poses risk to animal handlers due to its zoonotic nature. It causes stillbirth, loss of kids and abortion in last term of pregnancy. Reproductive damage includes infertility in does and orchitis and epididymitis in breeding bucks, which result in high financial losses to farmers and the agriculture industry as a whole. It requires highly sensitive and specific assays to diagnose the disease at field level. In the current study, a visual loop-mediated isothermal amplification (LAMP) assay and the TaqMan® real-time PCR were developed with high sensitivity and specificity. For the TaqMan® probe, real-time PCR primers were developed using Omp31 gene as target and primers were designed using discontiguous conserved sequences of Omp31 gene. The Omp31 probes were designed by attaching 6-FAM reporter dye at the 5' end and BHQ-1 quencher at the 3' end. Published primers were used for visual LAMP assay targeting the Omp25 gene. Sensitivity of the standardized visual LAMP assay and TaqMan® real-time PCR assay was determined by serial dilution of positive Brucella melitensis DNA (10 2 to 10 -4  ng) obtained from standard culture. The TaqMan® probe real-time assay can detect as low as 100 fg of B. melitensis DNA, whereas culture from vaginal swab washings has a limit of detection (LOD) of only 1 cfu/ml. Similarly, the visual LAMP assay can detect as low as 10 fg of B. melitensis DNA as compared to an LOD of 30 cfu/ml from culture of vaginal swab washings. Both assays were compared with serological tests (serum tube agglutination test (STAT) and indirect enzyme-linked immunosorbent assay (iELISA)) for diagnostic sensitivity and specificity. Diagnostic sensitivities and specificities for TaqMan® real-time PCR vs. LAMP assays were 98 and 100% vs. 100 and 97.8%, respectively. Results of visual LAMP assay indicated that LAMP is a fast, specific, sensitive, inexpensive and suitable method for diagnosis of B. melitensis infection under field conditions. On the other hand, Omp31 TaqMan® probe real-time assay can be used in conjunction with the other field-based diagnostic tests due to its high specificity.

The psychometric properties, sensitivity and specificity of the geriatric anxiety inventory, hospital anxiety and depression scale, and rating anxiety in dementia scale in aged care residents.

PubMed

Creighton, Alexandra S; Davison, Tanya E; Kissane, David W

2018-02-22

Limited research has been conducted into the identification of a valid and reliable screening measure for anxiety in aged care settings, despite it being one of the most common psychological conditions. This study aimed to determine an appropriate anxiety screening tool for aged care by comparing the reliability and validity of three commonly used measures and identifying specific cut-offs for the identification of generalized anxiety disorder (GAD). One-hundred and eighty nursing home residents (M age = 85.39 years) completed the GAI, HADS-A, and RAID, along with a structured diagnostic interview. Twenty participants (11.1%) met DSM-5 criteria for GAD. All measures had good psychometric properties , although reliability estimates for the HADS-A were sub-optimal. Privileging sensitivity , the GAI cut-off score of 9 gave sensitivity of 90.0% and specificity of 86.3%; HADS-A cut-off of 6 gave sensitivity of 90.0% and specificity of 80.6%; and RAID cut-off of 11 gave sensitivity of 85.0% and specificity of 72.5%. While all three measures had adequate reliability, validity, and cut-scores with high levels of sensitivity and specificity to detect anxiety within aged care, the GAI was the most consistently reliable and valid measure for screening for GAD.

Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers

PubMed Central

Steenkeste, Nicolas; Incardona, Sandra; Chy, Sophy; Duval, Linda; Ekala, Marie-Thérèse; Lim, Pharath; Hewitt, Sean; Sochantha, Tho; Socheat, Doung; Rogier, Christophe; Mercereau-Puijalon, Odile; Fandeur, Thierry; Ariey, Frédéric

2009-01-01

Background Several strategies are currently deployed in many countries in the tropics to strengthen malaria control toward malaria elimination. To measure the impact of any intervention, there is a need to detect malaria properly. Mostly, decisions still rely on microscopy diagnosis. But sensitive diagnosis tools enabling to deal with a large number of samples are needed. The molecular detection approach offers a much higher sensitivity, and the flexibility to be automated and upgraded. Methods Two new molecular methods were developed: dot18S, a Plasmodium-specific nested PCR based on the 18S rRNA gene followed by dot-blot detection of species by using species-specific probes and CYTB, a Plasmodium-specific nested PCR based on cytochrome b gene followed by species detection using SNP analysis. The results were compared to those obtained with microscopic examination and the "standard" 18S rRNA gene based nested PCR using species specific primers. 337 samples were diagnosed. Results Compared to the microscopy the three molecular methods were more sensitive, greatly increasing the estimated prevalence of Plasmodium infection, including P. malariae and P. ovale. A high rate of mixed infections was uncovered with about one third of the villagers infected with more than one malaria parasite species. Dot18S and CYTB sensitivity outranged the "standard" nested PCR method, CYTB being the most sensitive. As a consequence, compared to the "standard" nested PCR method for the detection of Plasmodium spp., the sensitivity of dot18S and CYTB was respectively 95.3% and 97.3%. Consistent detection of Plasmodium spp. by the three molecular methods was obtained for 83% of tested isolates. Contradictory results were mostly related to detection of Plasmodium malariae and Plasmodium ovale in mixed infections, due to an "all-or-none" detection effect at low-level parasitaemia. Conclusion A large reservoir of asymptomatic infections was uncovered using the molecular methods. Dot18S and CYTB, the new methods reported herein are highly sensitive, allow parasite DNA extraction as well as genus- and species-specific diagnosis of several hundreds of samples, and are amenable to high-throughput scaling up for larger sample sizes. Such methods provide novel information on malaria prevalence and epidemiology and are suited for active malaria detection. The usefulness of such sensitive malaria diagnosis tools, especially in low endemic areas where eradication plans are now on-going, is discussed in this paper. PMID:19402894

Detection of Entamoeba histolytica by Recombinase Polymerase Amplification

PubMed Central

Nair, Gayatri; Rebolledo, Mauricio; White, A. Clinton; Crannell, Zachary; Richards-Kortum, R. Rebecca; Pinilla, A. Elizabeth; Ramírez, Juan David; López, M. Consuelo; Castellanos-Gonzalez, Alejandro

2015-01-01

Amebiasis is an important cause of diarrheal disease worldwide and has been associated with childhood malnutrition. Traditional microscopy approaches are neither sensitive nor specific for Entamoeba histolytica. Antigen assays are more specific, but many cases are missed unless tested by molecular methods. Although polymerase chain reaction (PCR) is effective, the need for sophisticated, expensive equipment, infrastructure, and trained personnel limits its usefulness, especially in the resource-limited, endemic areas. Here, we report development of a recombinase polymerase amplification (RPA) method to detect E. histolytica specifically. Using visual detection by lateral flow (LF), the test was highly sensitive and specific and could be performed without additional equipment. The availability of this inexpensive, sensitive, and field-applicable diagnostic test could facilitate rapid diagnosis and treatment of amebiasis in endemic regions. PMID:26123960

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

PubMed Central

Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

2013-01-01

The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

PubMed

Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

2013-06-01

The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

Highly sensitive protein detection by biospecific AFM-based fishing with pulsed electrical stimulation.

PubMed

Pleshakova, Tatyana O; Malsagova, Kristina A; Kaysheva, Anna L; Kopylov, Arthur T; Tatur, Vadim Yu; Ziborov, Vadim S; Kanashenko, Sergey L; Galiullin, Rafael A; Ivanov, Yuri D

2017-08-01

We report here the highly sensitive detection of protein in solution at concentrations from 10 -15 to 10 -18 m using the combination of atomic force microscopy (AFM) and mass spectrometry. Biospecific detection of biotinylated bovine serum albumin was carried out by fishing out the protein onto the surface of AFM chips with immobilized avidin, which determined the specificity of the analysis. Electrical stimulation was applied to enhance the fishing efficiency. A high sensitivity of detection was achieved by application of nanosecond electric pulses to highly oriented pyrolytic graphite placed under the AFM chip. A peristaltic pump-based flow system, which is widely used in routine bioanalytical assays, was employed throughout the analysis. These results hold promise for the development of highly sensitive protein detection methods using nanosensor devices.

Recombinase Polymerase Amplification Compared to Real-Time Polymerase Chain Reaction Test for the Detection of Fasciola hepatica in Human Stool

PubMed Central

Cabada, Miguel M.; Malaga, Jose L.; Castellanos-Gonzalez, Alejandro; Bagwell, Kelli A.; Naeger, Patrick A.; Rogers, Hayley K.; Maharsi, Safa; Mbaka, Maryann; White, A. Clinton

2017-01-01

Fasciola hepatica is the most widely distributed trematode infection in the world. Control efforts may be hindered by the lack of diagnostic capacity especially in remote endemic areas. Polymerase chain reaction (PCR)–based methods offer high sensitivity and specificity but require expensive technology. However, the recombinase polymerase amplification (RPA) is an efficient isothermal method that eliminates the need for a thermal cycler and has a high deployment potential to resource-limited settings. We report on the characterization of RPA and PCR tests to detect Fasciola infection in clinical stool samples with low egg burdens. The sensitivity of the RPA and PCR were 87% and 66%, respectively. Both tests were 100% specific showing no cross-reactivity with trematode, cestode, or nematode parasites. In addition, RPA and PCR were able to detect 47% and 26% of infections not detected by microscopy, respectively. The RPA adapted to a lateral flow platform was more sensitive than gel-based detection of the reaction products. In conclusion, the Fasciola RPA is a highly sensitive and specific test to diagnose chronic infection using stool samples. The Fasciola RPA lateral flow has the potential for deployment to endemic areas after further characterization. PMID:27821691

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography.

PubMed

Ernst, Marielle; Romero, Javier M; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54-95%) while specificity was high 91% (95%-CI, 82-96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60-98%) and specificity of 84% (95%-CI, 74-90%). In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT.

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

Relationship between esophageal clinical symptoms and manometry findings in patients with esophageal motility disorders: a cross-sectional study.

PubMed

FakhreYaseri, Hashem; FakhreYaseri, Ali Mohammad; Baradaran Moghaddam, Ali; Soltani Arabshhi, Seyed Kamran

2015-01-01

Manometry is the gold-standard diagnostic test for motility disorders in the esophagus. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The diagnostic value of particular esophageal clinical symptoms among patients suspected of esophageal motor disorders (EMDs) is still unknown. The aim of this study was to explore the sensitivity, specificity, and predictive accuracy of presenting esophageal symptoms between abnormal and normal esophageal manometry findings. We conducted a cross-sectional study of 623 patients aged 11-80 years. Data were collected from clinical examinations as well as patient questionnaires. The sensitivity, specificity, and accuracy were calculated after high-resolution manometry plots were reviewed according to the most recent Chicago Criteria. The clinical symptoms were not sensitive enough to discriminate between EMDs. Nevertheless, dysphagia, noncardiac chest pain, hoarseness, vomiting, and weight loss had high specificity and high accuracy to distinguish EMDs from normal findings. Regurgitation and heartburn did not have good accuracy for the diagnosis of EMDs. Clinical symptoms are not reliable enough to discriminate between EMDs. Clinical symptoms can, however, discriminate between normal findings and EMDs, especially achalasia.

Fluorescence-based assay as a new screening tool for toxic chemicals

PubMed Central

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-01-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients. PMID:27653274

Fluorescence-based assay as a new screening tool for toxic chemicals.

PubMed

Moczko, Ewa; Mirkes, Evgeny M; Cáceres, César; Gorban, Alexander N; Piletsky, Sergey

2016-09-22

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Fluorescence-based assay as a new screening tool for toxic chemicals

NASA Astrophysics Data System (ADS)

Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey

2016-09-01

Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

Remembering rejection: specificity and linguistic styles of autobiographical memories in borderline personality disorder and depression.

PubMed

Rosenbach, Charlotte; Renneberg, Babette

2015-03-01

High levels of rejection sensitivity are assumed to be the result of early and prolonged experiences of rejection. Aim of this study was to investigate autobiographical memories of rejection in clinical samples high in rejection sensitivity (Borderline Personality Disorder, BPD, and Major Depressive Disorder, MDD) and to identify group differences in the quality of the memories. Memories of rejection were retrieved using an adapted version of the Autobiographical Memory Test (AMT; five positive cue words, five cue words referring to rejection). Specificity of memories and linguistic word usage was analyzed in 30 patients with BPD, 27 patients with MDD and 30 healthy controls. Patients with BPD retrieved less specific memories compared to the healthy control group, whereas patients with MDD did not differ from controls in this regard. The group difference was no longer significant when controlling for rejection sensitivity. Linguistic analysis indicated that compared to both other groups, patients with BPD showed a higher self-focus, used more anger-related words, referred more frequently to social environments, and rated memories of rejection as more relevant for today's life. Clinical symptoms were not assessed in the control group. Moreover, the written form of the AMT might reduce the total number of specific memories. The level of rejection sensitivity influenced the specificity of the retrieved memories. Analysis of linguistic styles revealed specific linguistic patterns in BPD compared to non-clinical as well as depressed participants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sensitivity and Specificity of Histoplasma Antigen Detection by Enzyme Immunoassay.

PubMed

Cunningham, Lauren; Cook, Audrey; Hanzlicek, Andrew; Harkin, Kenneth; Wheat, Joseph; Goad, Carla; Kirsch, Emily

2015-01-01

The objective of this study was to evaluate the sensitivity and specificity of an antigen enzyme immunoassay (EIA) on urine samples for the diagnosis of histoplasmosis in dogs. This retrospective medical records review included canine cases with urine samples submitted for Histoplasma EIA antigen assay between 2007 and 2011 from three veterinary institutions. Cases for which urine samples were submitted for Histoplasma antigen testing were reviewed and compared to the gold standard of finding Histoplasma organisms or an alternative diagnosis on cytology or histopathology. Sensitivity, specificity, negative predictive value, positive predictive value, and the kappa coefficient and associated confidence interval were calculated for the EIA-based Histoplasma antigen assay. Sixty cases met the inclusion criteria. Seventeen cases were considered true positives based on identification of the organism, and 41 cases were considered true negatives with an alternative definitive diagnosis. Two cases were considered false negatives, and there were no false positives. Sensitivity was 89.47% and the negative predictive value was 95.35%. Specificity and the positive predictive value were both 100%. The kappa coefficient was 0.9207 (95% confidence interval, 0.8131-1). The Histoplasma antigen EIA test demonstrated high specificity and sensitivity for the diagnosis of histoplasmosis in dogs.

Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity.

PubMed

Fafin-Lefevre, Mélanie; Morlais, Fabrice; Guittet, Lydia; Clin, Bénédicte; Launoy, Guy; Galateau-Sallé, Françoise; Plancoulaine, Benoît; Herlin, Paulette; Letourneux, Marc

2011-08-01

To identify which morphologic or densitometric parameters are modified in cell nuclei from bronchopulmonary cancer based on 18 parameters involving shape, intensity, chromatin, texture, and DNA content and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei. A total of 25 sputum samples from controls and 22 bronchial aspiration samples from patients presenting with bronchopulmonary cancer who were professionally exposed to cancer were used. After Feulgen staining, 18 morphologic and DNA content parameters were measured on cell nuclei, via image cytom- etry. A method was developed for analyzing distribution quantiles, compared with simply interpreting mean values, to characterize morphologic modifications in cell nuclei. Distribution analysis of parameters enabled us to distinguish 13 of 18 parameters that demonstrated significant differences between controls and cancer cases. These parameters, used alone, enabled us to distinguish two population types, with both sensitivity and specificity > 70%. Three parameters offered 100% sensitivity and specificity. When mean values offered high sensitivity and specificity, comparable or higher sensitivity and specificity values were observed for at least one of the corresponding quantiles. Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum.

Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging.

PubMed

McDonnell, Liam A; Heeren, Ron M A; de Lange, Robert P J; Fletcher, Ian W

2006-09-01

To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided approximately 15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield approximately 3.8 and approximately 8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.

Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma.

PubMed

Nagata, Satoshi; Hamada, Tomofumi; Yamada, Norishige; Yokoyama, Seiya; Kitamoto, Sho; Kanmura, Yuji; Nomura, Masahiro; Kamikawa, Yoshiaki; Yonezawa, Suguru; Sugihara, Kazumasa

2012-09-01

The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARβ), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARβ, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC. Copyright © 2012 American Cancer Society.

Analysis of Serum Total and Free PSA Using Immunoaffinity Depletion Coupled to SRM: Correlation with Clinical Immunoassay Tests

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

Liu, Tao; Hossain, Mahmud; Schepmoes, Athena A.

2012-08-03

Sandwich immunoassay is the standard technique used in clinical labs for quantifying protein biomarkers for disease detection, monitoring and therapeutic intervention. Albeit highly sensitive, the development of a specific immunoassay is rather time-consuming and associated with extremely high cost due to the requirement for paired immunoaffinity reagents of high specificity. Recently, mass spectrometry-based methods, specifically selected reaction monitoring mass spectrometry (SRM-MS), have been increasingly applied to measure low abundance biomarker candidates in tissue and biofluids, owing to high sensitivity and specificity, simplicity of assay configuration, and great multiplexing capability. In this study, we report for the first time the developmentmore » of immunoaffinity depletion-based workflows and SRM-MS assays that enable sensitive and accurate quantification of total and free prostate-specific antigen (PSA) in serum without the requirement for specific PSA antibodies. With stable isotope dilution and external calibration, low ng/mL level detection of both total and free PSA was consistently achieved in both PSA-spiked female serum samples and actual patient serum samples. Moreover, comparison of the results obtained when SRM PSA assays and conventional immunoassays were applied to the same samples showed very good correlation (R2 values ranging from 0.90 to 0.99) in several independent clinical serum sample sets, including a set of 33 samples assayed in a blinded test. These results demonstrate that the workflows and SRM assays developed here provide an attractive alternative for reliably measuring total and free PSA in human blood. Furthermore, simultaneous measurement of free and total PSA and many other biomarkers can be performed in a single analysis using high-resolution liquid chromatographic separation coupled with SRM-MS.« less

Direct detection of falciparum and non-falciparum malaria DNA from a drop of blood with high sensitivity by the dried-LAMP system.

PubMed

Hayashida, Kyoko; Kajino, Kiichi; Simukoko, Humphrey; Simuunza, Martin; Ndebe, Joseph; Chota, Amos; Namangala, Boniface; Sugimoto, Chihiro

2017-01-13

Because of the low sensitivity of conventional rapid diagnostic tests (RDTs) for malaria infections, the actual prevalence of the diseases, especially those caused by non-Plasmodium falciparum (non-Pf) species, in asymptomatic populations remain less defined in countries lacking in well-equipped facilities for accurate diagnoses. Our direct blood dry LAMP system (CZC-LAMP) was applied to the diagnosis of malaria as simple, rapid and highly sensitive method as an alternative for conventional RDTs in malaria endemic areas where laboratory resources are limited. LAMP primer sets for mitochondria DNAs of Plasmodium falciparum (Pf) and human-infective species other than Pf (non-Pf; P. vivax, P. ovale, P. malariae) were designed and tested by using human blood DNA samples from 74 residents from a malaria endemic area in eastern Zambia. These malaria dry-LAMPs were optimized for field or point-of-care operations, and evaluated in the field at a malaria endemic area in Zambia with 96 human blood samples. To determine the sensitivities and specificities, results obtained by the on-site LAMP diagnosis were compared with those by the nested PCR and nucleotide sequencing of its product. The dry LAMPs showed the sensitivities of 89.7% for Pf and 85.7% for non-Pf, and the specificities of 97.2% for Pf and 100% for non-Pf, with purified blood DNA samples. The direct blood LAMP diagnostic methods, in which 1 μl of anticoagulated blood were used as the template, showed the sensitivities of 98.1% for Pf, 92.1% for non-Pf, and the specificities of 98.1% for Pf, 100% for non-Pf. The prevalences of P. falciparum, P. malariae and P. ovale in the surveyed area were 52.4, 25.3 and 10.6%, respectively, indicating high prevalence of asymptomatic carriers in endemic areas in Zambia. We have developed new field-applicable malaria diagnostic tests. The malaria CZC-LAMPs showed high sensitivity and specificity to both P. falciparum and non-P. falciparum. These malaria CZC-LAMPs provide new means for rapid, sensitive and reliable point-of-care diagnosis for low-density malaria infections, and are expected to help update current knowledge of malaria epidemiology, and can contribute to the elimination of malaria from endemic areas.

Sensitivity and specificity of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium: A single-center study in Japan.

PubMed

Nishimura, Katsuji; Yokoyama, Kanako; Yamauchi, Noriko; Koizumi, Masako; Harasawa, Nozomi; Yasuda, Taeko; Mimura, Chizuru; Igita, Hazuki; Suzuki, Eriko; Uchiide, Yoko; Seino, Yusuke; Nomura, Minoru; Yamazaki, Kenji; Ishigooka, Jun

2016-01-01

To compare the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) for detecting post-cardiac surgery delirium. These tools have not been tested in a specialized cardio-surgical ICU. Sensitivities and specificities of each tool were assessed in a cardio-surgical ICU in Japan by two trained nurses independently. Results were compared with delirium diagnosed by psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. There were 110 daily, paired assessments in 31 patients. The CAM-ICU showed 38% sensitivity and 100% specificity for both nurses. All 20 false-negative cases resulted from high scores in the auditory attention screening in CAM-ICU. The ICDSC showed 97% and 94% sensitivity, and 97% and 91% specificity for the two nurses (cutoff ≥4). In a Japanese cardio-surgical ICU, the ICDSC had a higher sensitivity than the CAM-ICU. Copyright © 2016 Elsevier Inc. All rights reserved.

High performance of a new PCR-based urine assay for HPV-DNA detection and genotyping.

PubMed

Tanzi, Elisabetta; Bianchi, Silvia; Fasolo, Maria Michela; Frati, Elena R; Mazza, Francesca; Martinelli, Marianna; Colzani, Daniela; Beretta, Rosangela; Zappa, Alessandra; Orlando, Giovanna

2013-01-01

Human papillomavirus (HPV) testing has been proposed as a means of replacing or supporting conventional cervical screening (Pap test). However, both methods require the collection of cervical samples. Urine sample is easier and more acceptable to collect and could be helpful in facilitating cervical cancer screening. The aim of this study was to evaluate the sensitivity and specificity of urine testing compared to conventional cervical smear testing using a PCR-based method with a new, designed specifically primer set. Paired cervical and first voided urine samples collected from 107 women infected with HIV were subjected to HPV-DNA detection and genotyping using a PCR-based assay and a restriction fragment length polymorphism method. Sensitivity, specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were calculated using the McNemar's test for differences. Concordance between tests was assessed using the Cohen's unweighted Kappa (k). HPV DNA was detected in 64.5% (95% CI: 55.1-73.1%) of both cytobrush and urine samples. High concordance rates of HPV-DNA detection (k = 0.96; 95% CI: 0.90-1.0) and of high risk-clade and low-risk genotyping in paired samples (k = 0.80; 95% CI: 0.67-0.92 and k = 0.74; 95% CI: 0.60-0.88, respectively) were observed. HPV-DNA detection in urine versus cervix testing revealed a sensitivity of 98.6% (95% CI: 93.1-99.9%) and a specificity of 97.4% (95% CI: 87.7-99.9%), with a very high NPV (97.4%; 95% CI: 87.7-99.9%). The PCR-based assay utilized in this study proved highly sensitive and specific for HPV-DNA detection and genotyping in urine samples. These data suggest that a urine-based assay would be a suitable and effective tool for epidemiological surveillance and, most of all, screening programs. Copyright © 2012 Wiley Periodicals, Inc.

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging

PubMed Central

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging. PMID:27004542

Detecting prostate cancer and prostatic calcifications using advanced magnetic resonance imaging.

PubMed

Dou, Shewei; Bai, Yan; Shandil, Ankit; Ding, Degang; Shi, Dapeng; Haacke, E Mark; Wang, Meiyun

2017-01-01

Prostate cancer and prostatic calcifications have a high incidence in elderly men. We aimed to investigate the diagnostic capabilities of susceptibility-weighted imaging in detecting prostate cancer and prostatic calcifications. A total number of 156 men, including 34 with prostate cancer and 122 with benign prostate were enrolled in this study. Computed tomography, conventional magnetic resonance imaging, diffusion-weighted imaging, and susceptibility-weighted imaging were performed on all the patients. One hundred and twelve prostatic calcifications were detected in 87 patients. The sensitivities and specificities of the conventional magnetic resonance imaging, apparent diffusion coefficient, and susceptibility-filtered phase images in detecting prostate cancer and prostatic calcifications were calculated. McNemar's Chi-square test was used to compare the differences in sensitivities and specificities between the techniques. The results showed that the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic cancer were greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). In addition, the sensitivity and specificity of susceptibility-filtered phase images in detecting prostatic calcifications were comparable to that of computed tomography and greater than that of conventional magnetic resonance imaging and apparent diffusion coefficient (P < 0.05). Given the high incidence of susceptibility-weighted imaging (SWI) abnormality in prostate cancer, we conclude that susceptibility-weighted imaging is more sensitive and specific than conventional magnetic resonance imaging, diffusion-weighted imaging, and computed tomography in detecting prostate cancer. Furthermore, susceptibility-weighted imaging can identify prostatic calcifications similar to computed tomography, and it is much better than conventional magnetic resonance imaging and diffusion-weighted imaging.

CSF lactate alone is not a reliable indicator of bacterial ventriculitis in patients with ventriculostomies.

PubMed

Hill, Emily; Bleck, Thomas P; Singh, Kamaljit; Ouyang, Bichun; Busl, Katharina M

2017-06-01

In a febrile patient with a ventriculostomy, diagnosing or excluding bacterial or microbial ventriculitis is difficult, as conventional markers in analysis of cerebrospinal fluid (CSF) are not applicable due to presence of blood and inflammation. CSF lactate has been shown to be a useful indicator of bacterial meningitis in CSF obtained via lumbar puncture, but little and heterogenous data exist on patients with ventriculostomies. We reviewed all CSF analyses obtained via ventriculostomy in patients admitted to our tertiary medical center between 2008 and 2013, and constructed receiver operating characteristic (ROC) curves to evaluate the accuracy of CSF lactate concentration in discriminating a positive CSF culture from a negative one in setting of ventriculostomy and prophylactic antibiosis. Among 467 CSF lactate values, there were 22 corresponding CSF cultures with bacterial growth. Sensitivities and specificities for CSF lactate at threshold values 3, 4, 5 and 6mmol/L showed sensitivity and specificity greater than 70% for CSF lactate threshold 4mmol/L. The lowest threshold value of 3mmol/L resulted in higher sensitivity of 81.8%, and the highest chosen threshold value resulted in high specificity of 94.2%, but these values had poor corresponding specificity and sensitivity, respectively. The area under the curve was 0.82 (95% CI 0.72, 0.91). Our data from a large sample of CSF studies in patients with ventriculostomy indicate that no single value of CSF lactate provided both sensitivity and specificity high enough to be regarded as reliable test. Copyright © 2017 Elsevier B.V. All rights reserved.

Accuracy of line probe assays for the diagnosis of pulmonary and multidrug-resistant tuberculosis: a systematic review and meta-analysis

PubMed Central

Cudahy, Patrick G.T; Schumacher, Samuel G.; Steingart, Karen R.; Pai, Madhukar; Denkinger, Claudia M.

2017-01-01

Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed. This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing. Results for RIF and INH resistance were compared to phenotypic and composite (incorporating sequencing) reference standards. M. tuberculosis detection results were compared to culture. 74 unique studies were included. For RIF resistance (21 225 samples), pooled sensitivity and specificity (with 95% confidence intervals) were 96.7% (95.6–97.5%) and 98.8% (98.2–99.2%). For INH resistance (20 954 samples), pooled sensitivity and specificity were 90.2% (88.2–91.9%) and 99.2% (98.7–99.5%). Results were similar for direct and indirect testing and across LPAs. Using a composite reference standard, specificity increased marginally. For M. tuberculosis detection (3451 samples), pooled sensitivity was 94% (89.4–99.4%) for smear-positive specimens and 44% (20.2–71.7%) for smear-negative specimens. In patients with pulmonary TB, LPAs have high sensitivity and specificity for RIF resistance and high specificity and good sensitivity for INH resistance. This meta-analysis provides evidence for policy and practice. PMID:28100546

Quantitative image cytometry measurements of lipids, DNA, CD45 and cytokeratin for circulating tumor cell identification in a model system

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Qamar, Lubna; Behbakht, Kian; Gibson, Emily A.

2016-04-01

Circulating tumor cell (CTC) identification has applications in both early detection and monitoring of solid cancers. The rarity of CTCs, expected at ~1-50 CTCs per million nucleated blood cells (WBCs), requires identifying methods based on biomarkers with high sensitivity and specificity for accurate identification. Discovery of biomarkers with ever higher sensitivity and specificity to CTCs is always desirable to potentially find more CTCs in cancer patients thus increasing their clinical utility. Here, we investigate quantitative image cytometry measurements of lipids with the biomarker panel of DNA, Cytokeratin (CK), and CD45 commonly used to identify CTCs. We engineered a device for labeling suspended cell samples with fluorescent antibodies and dyes. We used it to prepare samples for 4 channel confocal laser scanning microscopy. The total data acquired at high resolution from one sample is ~ 1.3 GB. We developed software to perform the automated segmentation of these images into regions of interest (ROIs) containing individual cells. We quantified image features of total signal, spatial second moment, spatial frequency second moment, and their product for each ROI. We performed measurements on pure WBCs, cancer cell line MCF7 and mixed samples. Multivariable regressions and feature selection were used to determine combination features that are more sensitive and specific than any individual feature separately. We also demonstrate that computation of spatial characteristics provides higher sensitivity and specificity than intensity alone. Statistical models allowed quantification of the required sensitivity and specificity for detecting small levels of CTCs in a human blood sample.

Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005).

PubMed

Lennon, Elizabeth M; Boyle, Tonya E; Hutchins, Rae Grace; Friedenthal, Arit; Correa, Maria T; Bissett, Sally A; Moses, Lorra S; Papich, Mark G; Birkenheuer, Adam J

2007-08-01

To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. Retrospective case-control study. 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. Sensitivity and specificity of basal serum or plasma cortisol concentrations of either 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is

Meat authentication: a new HPLC-MS/MS based method for the fast and sensitive detection of horse and pork in highly processed food.

PubMed

von Bargen, Christoph; Brockmeyer, Jens; Humpf, Hans-Ulrich

2014-10-01

Fraudulent blending of food products with meat from undeclared species is a problem on a global scale, as exemplified by the European horse meat scandal in 2013. Routinely used methods such as ELISA and PCR can suffer from limited sensitivity or specificity when processed food samples are analyzed. In this study, we have developed an optimized method for the detection of horse and pork in different processed food matrices using MRM and MRM(3) detection of species-specific tryptic marker peptides. Identified marker peptides were sufficiently stable to resist thermal processing of different meat products and thus allow the sensitive and specific detection of pork or horse in processed food down to 0.24% in a beef matrix system. In addition, we were able to establish a rapid 2-min extraction protocol for the efficient protein extraction from processed food using high molar urea and thiourea buffers. Together, we present here the specific and sensitive detection of horse and pork meat in different processed food matrices using MRM-based detection of marker peptides. Notably, prefractionation of proteins using 2D-PAGE or off-gel fractionation is not necessary. The presented method is therefore easily applicable in analytical routine laboratories without dedicated proteomics background.

Comparison of Sofia Legionella FIA and BinaxNOW® Legionella urinary antigen card in two national reference centers.

PubMed

Beraud, L; Gervasoni, K; Freydiere, A M; Descours, G; Ranc, A G; Vandenesch, F; Lina, G; Gaia, V; Jarraud, S

2015-09-01

The Sofia Legionella Fluorescence Immunoassay (FIA; Quidel) is a recently introduced rapid immunochromatographic diagnostic test for Legionnaires' disease using immunofluorescence technology designed to enhance its sensitivity. The aim of this study was to evaluate its performance for the detection of urinary antigens for Legionella pneumophila serogroup 1 in two National Reference Centers for Legionella. The sensitivity and specificity of the Sofia Legionella FIA test were determined in concentrated and nonconcentrated urine samples, before and after boiling, in comparison with the BinaxNOW® Legionella Urinary Antigen Card (UAC; Alere). Compared with BinaxNOW® Legionella UAC, the sensitivity of the Sofia Legionella test was slightly higher in nonconcentrated urine samples and was identical in concentrated urine samples. The specificity of the Sofia Legionella FIA test was highly reduced by the concentration of urine samples. In nonconcentrated samples, a lack of specificity was observed in 2.3 % of samples, all of them resolved by heat treatment. The Sofia Legionella FIA is a sensitive test for detecting Legionella urinary antigens with no previous urine concentration. However, all positive samples have to be re-tested after boiling to reach a high specificity. The reading is automatized on the Sofia analyzer, which can be connected to laboratory information systems, facilitating accurate and rapid reporting of results.

Sensitivity and specificity enhanced enzyme-linked immunosorbent assay by rational hapten modification and heterogeneous antibody/coating antigen combinations for the detection of melamine in milk, milk powder and feed samples.

PubMed

Cao, Biyun; Yang, Hong; Song, Juan; Chang, Huafang; Li, Shuqun; Deng, Anping

2013-11-15

The adulteration of food products with melamine has led to an urgent requirement for sensitive, specific, rapid and reliable quantitative/screening methods. To enhance the sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) for the detection of melamine in milk, milk powder and feed samples, rational hapten modification and heterogeneous antibody/coating antigen combinations were adopted. Three melamine derivatives with different length of carboxylic spacer at the end were synthesized and linked to carrier proteins for the production of immunogens and coating antigens. Monoclonal antibody against melamine was produced by hybridoma technology. Under optimal experimental conditions, the standard curves of the ELISAs for melamine were constructed in range of 0.1-100 ng mL(-1). The sensitivity was 10-300 times enhanced compared to those in the published literatures. The cross-reactivity values of the ELISAs also demonstrated the assays exhibited high specificity. Five samples were spiked with melamine at different concentrations and detected by the ELISA. The recovery rates of 72.8-123.0% and intra-assay coefficients of variation of 0.8-18.9% (n=3) were obtained. The ELISA for milk sample was confirmed by high-performance liquid chromatography with a high correlation coefficient of 0.9902 (n=6). The proposed ELISA was proven to be a feasible quantitative/screening method for melamine analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

New Uses for Sensitivity Analysis: How Different Movement Tasks Effect Limb Model Parameter Sensitivity

NASA Technical Reports Server (NTRS)

Winters, J. M.; Stark, L.

1984-01-01

Original results for a newly developed eight-order nonlinear limb antagonistic muscle model of elbow flexion and extension are presented. A wider variety of sensitivity analysis techniques are used and a systematic protocol is established that shows how the different methods can be used efficiently to complement one another for maximum insight into model sensitivity. It is explicitly shown how the sensitivity of output behaviors to model parameters is a function of the controller input sequence, i.e., of the movement task. When the task is changed (for instance, from an input sequence that results in the usual fast movement task to a slower movement that may also involve external loading, etc.) the set of parameters with high sensitivity will in general also change. Such task-specific use of sensitivity analysis techniques identifies the set of parameters most important for a given task, and even suggests task-specific model reduction possibilities.

Detection of prostate-specific antigen with biomolecule-gated AlGaN/GaN high electron mobility transistors

NASA Astrophysics Data System (ADS)

Li, Jia-dong; Cheng, Jun-jie; Miao, Bin; Wei, Xiao-wei; Xie, Jie; Zhang, Jin-cheng; Zhang, Zhi-qiang; Wu, Dong-min

2014-07-01

In order to improve the sensitivity of AlGaN/GaN high electron mobility transistor (HEMT) biosensors, a simple biomolecule-gated AlGaN/GaN HEMT structure was designed and successfully fabricated for prostate specific antigen (PSA) detection. UV/ozone was used to oxidize the GaN surface and then a 3-aminopropyl trimethoxysilane (APTES) self-assembled monolayer was bound to the sensing region. This monolayer serves as a binding layer for attachment of the prostate specific antibody (anti-PSA). The biomolecule-gated AlGaN/GaN HEMT sensor shows a rapid and sensitive response when the target prostate-specific antigen in buffer solution was added to the antibody-immobilized sensing area. The current change showed a logarithm relationship against the PSA concentration from 0.1 pg/ml to 0.993 ng/ml. The sensitivity of 0.215% is determined for 0.1 pg/ml PSA solution. The above experimental result of the biomolecule-gated AlGaN/GaN HEMT biosensor suggested that this biosensor might be a useful tool for prostate cancer screening.

Management of neonatal sepsis at Muhimbili National Hospital in Dar es Salaam: diagnostic accuracy of C-reactive protein and newborn scale of sepsis and antimicrobial resistance pattern of etiological bacteria.

PubMed

Mkony, Martha Franklin; Mizinduko, Mucho Michael; Massawe, Augustine; Matee, Mecky

2014-12-05

We determined the accuracy of Rubarth's newborn scale of sepsis and C- reactive protein in diagnosing neonatal sepsis and assessed antimicrobial susceptibility pattern of etiological bacteria. This cross sectional study was conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania between July 2012 and March 2013. Neonates suspected to have sepsis underwent physical examination using Rubarth's newborn scale of sepsis (RNSOS). Blood was taken for culture and antimicrobial sensitivity testing, full blood picture and C - reactive protein (CRP) performed 12 hours apart. The efficacy of RNSOS and serial CRP was assessed by calculating sensitivity, specificity, negative and positive predictive values, receiver operating characteristics (ROC) analysis as well as likelihood ratios (LHR) with blood culture result used as a gold standard. Out of 208 blood samples, 19.2% had a positive blood culture. Single CRP had sensitivity and specificity of 87.5% and 70.9% respectively, while RNSOS had sensitivity of 65% and specificity of 79.7%. Serial CRP had sensitivity of 69.0% and specificity of 92.9%. Combination of CRP and RNSOS increased sensitivity to 95.6% and specificity of 56.4%. Combination of two CRP and RNSOS decreased sensitivity to 89.1% but increased specificity to 74%. ROC for CRP was 0.86; and for RNSOS was 0.81. For CRP the LHR for positive test was 3 while for negative test was 0.18, while for RNSOS the corresponding values were 3.24 and for negative test was 0.43. Isolated bacteria were Klebsiella spp 14 (35%), Escherichia coli 12 (22.5%), Coagulase negative staphlococci 9 (30%), Staphylococcus aureus 4 (10%), and Pseudomonas spp 1 (2.5%). The overall resistance to the WHO recommended first line antibiotics was 100%, 92% and 42% for cloxacillin, ampicillin and gentamicin, respectively. For the second line drugs resistance was 45%, 40%, and 7% for ceftriaxone, vancomycin and amikacin respectively. Single CRP in combination with RNSOS can be used for rapid identification of neonates with sepsis due to high sensitivity (95.6%) but cannot exclude those without sepsis due to low specificity (56.4%). Serial CRP done 12hrs apart can be used to exclude non-cases. This study demonstrated very high levels of resistance to the first-line antibiotics.

Sensitivity and specificity of subacute computerized neurocognitive testing and symptom evaluation in predicting outcomes after sports-related concussion.

PubMed

Lau, Brian C; Collins, Michael W; Lovell, Mark R

2011-06-01

Concussions affect an estimated 136 000 high school athletes yearly. Computerized neurocognitive testing has been shown to be appropriately sensitive and specific in diagnosing concussions, but no studies have assessed its utility to predict length of recovery. Determining prognosis during subacute recovery after sports concussion will help clinicians more confidently address return-to-play and academic decisions. To quantify the prognostic ability of computerized neurocognitive testing in combination with symptoms during the subacute recovery phase from sports-related concussion. Cohort study (prognosis); Level of evidence, 2. In sum, 108 male high school football athletes completed a computer-based neurocognitive test battery within 2.23 days of injury and were followed until returned to play as set by international guidelines. Athletes were grouped into protracted recovery (>14 days; n = 50) or short-recovery (≤14 days; n = 58). Separate discriminant function analyses were performed using total symptom score on Post-Concussion Symptom Scale, symptom clusters (migraine, cognitive, sleep, neuropsychiatric), and Immediate Postconcussion Assessment and Cognitive Testing neurocognitive scores (verbal memory, visual memory, reaction time, processing speed). Multiple discriminant function analyses revealed that the combination of 4 symptom clusters and 4 neurocognitive composite scores had the highest sensitivity (65.22%), specificity (80.36%), positive predictive value (73.17%), and negative predictive value (73.80%) in predicting protracted recovery. Discriminant function analyses of total symptoms on the Post-Concussion Symptom Scale alone had a sensitivity of 40.81%; specificity, 79.31%; positive predictive value, 62.50%; and negative predictive value, 61.33%. The 4 symptom clusters alone discriminant function analyses had a sensitivity of 46.94%; specificity, 77.20%; positive predictive value, 63.90%; and negative predictive value, 62.86%. Discriminant function analyses of the 4 computerized neurocognitive scores alone had a sensitivity of 53.20%; specificity, 75.44%; positive predictive value, 64.10%; and negative predictive value, 66.15%. The use of computerized neurocognitive testing in conjunction with symptom clusters results improves sensitivity, specificity, positive predictive value, and negative predictive value of predicting protracted recovery compared with each used alone. There is also a net increase in sensitivity of 24.41% when using neurocognitive testing and symptom clusters together compared with using total symptoms on Post-Concussion Symptom Scale alone.

Automatic detection of ECG cable interchange by analyzing both morphology and interlead relations.

PubMed

Han, Chengzong; Gregg, Richard E; Feild, Dirk Q; Babaeizadeh, Saeed

2014-01-01

ECG cable interchange can generate erroneous diagnoses. For algorithms detecting ECG cable interchange, high specificity is required to maintain a low total false positive rate because the prevalence of interchange is low. In this study, we propose and evaluate an improved algorithm for automatic detection and classification of ECG cable interchange. The algorithm was developed by using both ECG morphology information and redundancy information. ECG morphology features included QRS-T and P-wave amplitude, frontal axis and clockwise vector loop rotation. The redundancy features were derived based on the EASI™ lead system transformation. The classification was implemented using linear support vector machine. The development database came from multiple sources including both normal subjects and cardiac patients. An independent database was used to test the algorithm performance. Common cable interchanges were simulated by swapping either limb cables or precordial cables. For the whole validation database, the overall sensitivity and specificity for detecting precordial cable interchange were 56.5% and 99.9%, and the sensitivity and specificity for detecting limb cable interchange (excluding left arm-left leg interchange) were 93.8% and 99.9%. Defining precordial cable interchange or limb cable interchange as a single positive event, the total false positive rate was 0.7%. When the algorithm was designed for higher sensitivity, the sensitivity for detecting precordial cable interchange increased to 74.6% and the total false positive rate increased to 2.7%, while the sensitivity for detecting limb cable interchange was maintained at 93.8%. The low total false positive rate was maintained at 0.6% for the more abnormal subset of the validation database including only hypertrophy and infarction patients. The proposed algorithm can detect and classify ECG cable interchanges with high specificity and low total false positive rate, at the cost of decreased sensitivity for certain precordial cable interchanges. The algorithm could also be configured for higher sensitivity for different applications where a lower specificity can be tolerated. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensitivity and specificity of noncontrast magnetic resonance imaging reports in the diagnosis of type-II superior labral anterior-posterior lesions in the community setting.

PubMed

Connolly, Keith P; Schwartzberg, Randy S; Reuss, Bryan; Crumbie, David; Homan, Brad M

2013-02-20

Magnetic resonance imaging (MRI) has been suggested to be of high accuracy at academic institutions in the identification of superior labral tears; however, many Type-II superior labral anterior-posterior (SLAP) lesions encountered during arthroscopy have not been previously diagnosed with noncontrast images. This study evaluated the accuracy of diagnosing Type-II SLAP lesions in a community setting with use of noncontrast MRI and analyzed the effect that radiologist training and the scanner type or magnet strength had on sensitivity and specificity. One hundred and forty-four patients requiring repair of an arthroscopically confirmed Type-II SLAP lesion who had a noncontrast MRI examination performed within twelve months before the procedure were included in the sensitivity analysis. An additional 100 patients with arthroscopically confirmed, normal superior labral anatomy were identified for specificity analysis. The transcribed interpretations of the images by the radiologists were used to document the diagnosis of a SLAP lesion and were compared with the operative report. The magnet strength, type of MRI system (open or closed), and whether the radiologist had completed a musculoskeletal fellowship were also recorded. Noncontrast MRI identified SLAP lesions in fifty-four of 144 shoulders, yielding an overall sensitivity of 38% (95% confidence interval [CI] = 30%, 46%). Specificity was 94% (95% CI = 87%, 98%), with six SLAP lesions diagnosed in 100 shoulders that did not contain the lesion. Musculoskeletal fellowship-trained radiologists performed with higher sensitivity than those who had not completed the fellowship (46% versus 19%; p = 0.009). Our results demonstrate a low sensitivity and high specificity in the diagnosis of Type-II SLAP lesions with noncontrast MRI in this community setting. Musculoskeletal fellowship-trained radiologists had significantly higher sensitivities in accurately diagnosing the lesion than did radiologists without such training. Noncontrast MRI is not a reliable diagnostic tool for Type-II SLAP lesions in a community setting.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Genotypic, Phenotypic and Clinical Validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India

PubMed Central

Singh, Urvashi B.; Pandey, Pooja; Mehta, Girija; Bhatnagar, Anuj K.; Mohan, Anant; Goyal, Vinay; Ahuja, Vineet; Ramachandran, Ranjani; Sachdeva, Kuldeep S.; Samantaray, Jyotish C.

2016-01-01

Background Newer molecular diagnostics have brought paradigm shift in early diagnosis of tuberculosis [TB]. WHO recommended use of GeneXpert MTB/RIF [Xpert] for Extra-pulmonary [EP] TB; critics have since questioned its efficiency. Methods The present study was designed to assess the performance of GeneXpert in 761 extra-pulmonary and 384 pulmonary specimens from patients clinically suspected of TB and compare with Phenotypic, Genotypic and Composite reference standards [CRS]. Results Comparison of GeneXpert results to CRS, demonstrated sensitivity of 100% and 90.68%, specificity of 100% and 99.62% for pulmonary and extra-pulmonary samples. On comparison with culture, sensitivity for Rifampicin [Rif] resistance detection was 87.5% and 81.82% respectively, while specificity was 100% for both pulmonary and extra-pulmonary TB. On comparison to sequencing of rpoB gene [Rif resistance determining region, RRDR], sensitivity was respectively 93.33% and 90% while specificity was 100% in both pulmonary and extra-pulmonary TB. GeneXpert assay missed 533CCG mutation in one sputum and dual mutation [517 & 519] in one pus sample, detected by sequencing. Sequencing picked dual mutation [529, 530] in a sputum sample sensitive to Rif, demonstrating, not all RRDR mutations lead to resistance. Conclusions Current study reports observations in a patient care setting in a high burden region, from a large collection of pulmonary and extra-pulmonary samples and puts to rest questions regarding sensitivity, specificity, detection of infrequent mutations and mutations responsible for low-level Rif resistance by GeneXpert. Improvements in the assay could offer further improvement in sensitivity of detection in different patient samples; nevertheless it may be difficult to improve sensitivity of Rif resistance detection if only one gene is targeted. Assay specificity was high both for TB detection and Rif resistance detection. Despite a few misses, the assay offers major boost to early diagnosis of TB and MDR-TB, in difficult to diagnose pauci-bacillary TB. PMID:26894283

The impact of high-resolution ultrasound in the differential diagnosis of non-hemolytic jaundice.

PubMed

Rauh, Peter; Neye, Holger; Mönkemüller, Klaus; Malfertheiner, Peter; Rickes, Steffen

2010-12-01

Because jaundice is a common reason for hospital admission. A fast and correct differential diagnosis is very important to increase treatment efficacy. The aim of our study was to evaluate the impact of the high-resolution ultrasound in this kind of clinical setting. In a prospective study we included 30 patients and we divided them in patients with extrahepatic jaundice and patients with intrahepatic jaundice. We observed a high accuracy of the high-resolution sonography, with a sensitivity of 95% and a specificity of 100% for extrahepatic jaundice, and a sensitivity of 100% and a specificity of 95% for intrahepatic jaundice. We conclude that the high-resolution ultrasound should be used in the very beginning of the diagnostic algorithm for the evaluation of patients with unclear jaundice.

[How good are clinical investigative procedures for diagnosing meniscus lesions?].

PubMed

Jerosch, J; Riemer, S

2004-06-01

The purpose of this study was to evaluate different clinical meniscus tests. During 13 months we evaluated 64 patients with a suspected meniscus lesion in a prospective study. The age ranged from 16 to 76 years (average: 38.5 years). 66 % were male patients. Between the clinical examination and the arthroscopy there was no additional trauma to the knee. All patients were clinically examined in a standard manner by two independent orthopaedic surgeons. Clinical findings of the menisci were documented according to 12 well-described and commonly used meniscus tests. The arthroscopy was performed by a single surgeon who was not aware of the results of the clinical examination. This surgeon documented the intraarticular findings in a standardized operating report. A meniscus lesion/degeneration was documented when this was evident either by inspection or by palpation. The results showed either clinical meniscus tests with a high specificity and a low sensitivity or tests with a high sensitivity, but only a low specificity. We were not able to identify meniscus tests which showed both a high sensitivity and a high specificity. Even with access to MRI the clinical findings in knee joint with injured menisci still have a high diagnostic value. However, it seems to be necessary to combine different tests.

Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy.

PubMed

de Ruiter, C M; van der Veer, C; Leeflang, M M G; Deborggraeve, S; Lucas, C; Adams, E R

2014-09-01

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Analysis of different anthropometric indicators in the detection of high blood pressure in school adolescents: a cross-sectional study with 8295 adolescents.

PubMed

Christofaro, Diego G D; Farah, Breno Q; Vanderlei, Luiz Carlos M; Delfino, Leandro D; Tebar, William R; Barros, Mauro Virgílio G de; Ritti-Dias, Raphael M

High blood pressure is strongly associated with obesity in different populations. However, it is unclear whether different anthropometric indicators of obesity can satisfactorily predict high blood pressure in the school setting. This study evaluated the sensitivity and specificity of body mass index, waist circumference, and waist to height ratio in the detection of high blood pressure in adolescents. The sample consisted of 8295 adolescents aged 10-17 years. Weight was measured using a digital scale, height with a stadiometer, and waist circumference using a tape measure. Blood pressure was measured by an automatic blood pressure measuring device. ROC curves were used for the analysis of sensitivity and specificity of the three anthropometric indices in identifying high blood pressure. Binary Logistic Regression was used to assess the association of body mass index, waist circumference, and waist to height ratio with high blood pressure. Low values of sensitivity were observed for body mass index (0.35), waist circumference (0.37), and waist to height ratio (0.31) and high values of specificity for body mass index (0.86), waist circumference (0.82), and waist to height ratio (0.83) in the detection of high blood pressure. An association was observed between adolescents classified with high body mass index (OR=3.57 [95% CI=3.10-4.10]), waist cirumference (OR=3.24 [95% CI=2.83-3.72]), and waist to height ratio (OR=2.94 [95% CI=2.54-3.40]) with high blood pressure. Body mass index, waist circumference, and waist to height ratio presented low sensitivity to identify adolescents with high blood pressure. However, adolescents classified with high body mass index, waist circumference, and waist to height ratio demonstrated a high association of presenting high blood pressure. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Detection of compression vessels in trigeminal neuralgia by surface-rendering three-dimensional reconstruction of 1.5- and 3.0-T magnetic resonance imaging.

PubMed

Shimizu, Masahiro; Imai, Hideaki; Kagoshima, Kaiei; Umezawa, Eriko; Shimizu, Tsuneo; Yoshimoto, Yuhei

2013-01-01

Surface-rendered three-dimensional (3D) 1.5-T magnetic resonance (MR) imaging is useful for presurgical simulation of microvascular decompression. This study compared the sensitivity and specificity of 1.5- and 3.0-T surface-rendered 3D MR imaging for preoperative identification of the compression vessels of trigeminal neuralgia. One hundred consecutive patients underwent microvascular decompression for trigeminal neuralgia. Forty and 60 patients were evaluated by 1.5- and 3.0-T MR imaging, respectively. Three-dimensional MR images were constructed on the basis of MR imaging, angiography, and venography data and evaluated to determine the compression vessel before surgery. MR imaging findings were compared with the microsurgical findings to compare the sensitivity and specificity of 1.5- and 3.0-T MR imaging. The agreement between MR imaging and surgical findings depended on the compression vessels. For superior cerebellar artery, 1.5- and 3.0-T MR imaging had 84.4% and 82.7% sensitivity and 100% and 100% specificity, respectively. For anterior inferior cerebellar artery, 1.5- and 3.0-T MR imaging had 33.3% and 50% sensitivity and 92.9% and 95% specificity, respectively. For the petrosal vein, 1.5- and 3.0-T MR imaging had 75% and 64.3% sensitivity and 79.2% and 78.1% specificity, respectively. Complete pain relief was obtained in 36 of 40 and 55 of 60 patients undergoing 1.5- and 3.0-T MR imaging, respectively. The present study showed that both 1.5- and 3.0-T MR imaging provided high sensitivity and specificity for preoperative assessment of the compression vessels of trigeminal neuralgia. Preoperative 3D imaging provided very high quality presurgical simulation, resulting in excellent clinical outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

A highly sensitive and specific combined clinical and sonographic score to diagnose appendicitis.

PubMed

Reddy, Swathi B; Kelleher, Michael; Bokhari, S A Jamal; Davis, Kimberly A; Schuster, Kevin M

2017-10-01

Computed tomography (CT) scanning reduces the negative appendectomy rate however it exposes the patient to ionizing radiation. Ultrasound (US) does not carry this risk but may be nondiagnostic. We hypothesized that a clinical-US scoring system would improve diagnostic accuracy. We conducted a retrospective review of all patients (age, >15 years) who presented through the emergency department with suspected appendicitis and underwent initial US. A US score was developed using odds ratios for appendicitis given appendiceal diameter, compressibility, hyperemia, free fluid, and focal or diffuse tenderness. The US score was then combined with the Alvarado score. Final diagnosis of appendicitis was assigned by pathology reports. Three hundred patients who underwent US as initial imaging were identified. Thirty-two patients with evident nonappendiceal pathology on US were excluded. In 114 (38%), the appendix was not visualized and partially visualized in 36 (12%). Fifty-seven (21.3%) had an appendectomy with 1 (1.7%) negative. Six nonvisualized appendicies underwent appendectomy, with no negative cases. Sensitivity and specificity for the sonographic score were 86% and 90%, respectively, at a score of 1.5. The combined score demonstrated 98% sensitivity and 82% specificity at 6.5, and 95% sensitivity, and 87% specificity at a score of 7.5. Sensitivity and specificity were confirmed by bootstrap resampling for validation. Area under receiver operating characteristic (ROC) curves for our new US score were similar to the ROC curve for the Alvarado score (91.9 and 91.1, p = 0.8). The combined US and Alvarado score yielded an area under the ROC curve of 97.1, significantly better than either score alone (p = 0.017 and p < 0.001, respectively). Our scoring system based entirely on US findings was highly sensitive and specific for appendicitis, and it significantly improved when combined with the Alvarado score. After prospective evaluation, the combined US-Alvarado score might replace the need for computed tomography imaging in a majority of patients. Diagnostic Test, Level III.

Self-rating inventory for posttraumatic stress disorder: review of the psychometric properties of a new brief Dutch screening instrument.

PubMed

Hovens, J E; Bramsen, I; van der Ploeg, H M

2002-06-01

The Self-rating Inventory for Posttraumatic Stress Disorder of 22 items was developed for use with populations without identified traumatic experiences. The inventory has been used extensively in survey research in The Netherlands. This paper examines the psychometric properties. In four different groups (trauma and psychiatric patients, elderly Dutch subjects, former peacekeepers, and medical students) internal consistency, test-retest reliability, concurrent and discriminant validity, and sensitivity and specificity are analyzed. The inventory showed good internal consistency, test-retest reliability, concurrent and discriminant validity, and high sensitivity and specificity. It appears to be valuable for survey research on posttraumatic stress in nonselected populations. As a screening device, high sensitivity for PTSD symptoms is evident even when the traumatic event has not been defined.

Novel designs for application specific MEMS pressure sensors.

PubMed

Fragiacomo, Giulio; Reck, Kasper; Lorenzen, Lasse; Thomsen, Erik V

2010-01-01

In the framework of developing innovative microfabricated pressure sensors, we present here three designs based on different readout principles, each one tailored for a specific application. A touch mode capacitive pressure sensor with high sensitivity (14 pF/bar), low temperature dependence and high capacitive output signal (more than 100 pF) is depicted. An optical pressure sensor intrinsically immune to electromagnetic interference, with large pressure range (0-350 bar) and a sensitivity of 1 pm/bar is presented. Finally, a resonating wireless pressure sensor power source free with a sensitivity of 650 KHz/mmHg is described. These sensors will be related with their applications in harsh environment, distributed systems and medical environment, respectively. For many aspects, commercially available sensors, which in vast majority are piezoresistive, are not suited for the applications proposed.

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data

PubMed Central

Real, Ruben G. L.; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings. PMID:25309308

Studentized continuous wavelet transform (t-CWT) in the analysis of individual ERPs: real and simulated EEG data.

PubMed

Real, Ruben G L; Kotchoubey, Boris; Kübler, Andrea

2014-01-01

This study aimed at evaluating the performance of the Studentized Continuous Wavelet Transform (t-CWT) as a method for the extraction and assessment of event-related brain potentials (ERP) in data from a single subject. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the t-CWT were assessed and compared to a variety of competing procedures using simulated EEG data at six low signal-to-noise ratios. Results show that the t-CWT combines high sensitivity and specificity with favorable PPV and NPV. Applying the t-CWT to authentic EEG data obtained from 14 healthy participants confirmed its high sensitivity. The t-CWT may thus be well suited for the assessment of weak ERPs in single-subject settings.

Oxidative tryptophan modification by terpene- and squalene-hydroperoxides and a possible link to cross-reactions in diagnostic tests.

PubMed

Natsch, Andreas; Emter, Roger; Badertscher, Remo P; Brunner, Gerhard; Granier, Thierry; Kern, Susanne; Ellis, Graham

2015-06-15

Hydroperoxides can act as specific haptens and oxidatively modify proteins. Terpene hydroperoxides trigger unusually high frequencies of positive skin reactions in human patients if tested at high concentrations. It is unknown whether this is due to specific hapten formation. Here, we show that both terpene hydroperoxides and the endogenous hydroperoxide formed from squalene can oxidatively modify tryptophan. Oxidative modifications of Trp were recently postulated to explain cross-sensitization between unrelated photosensitizers. Current observations may extend this hypothesis: Oxidative events triggered by endogenous hydroperoxides and hydroperoxides/oxidants derived from xenobiotics might lead to a sensitized state detected by patch tests with high concentrations of hydroperoxides.

Symptoms and signs associated with benign and malignant proximal fibular tumors: a clinicopathological analysis of 52 cases.

PubMed

Sun, Tao; Wang, Lingxiang; Guo, Changzhi; Zhang, Guochuan; Hu, Wenhai

2017-05-02

Malignant tumors in the proximal fibula are rare but life-threatening; however, biopsy is not routine due to the high risk of peroneal nerve injury. Our aim was to determine preoperative clinical indicators of malignancy. Between 2004 and 2016, 52 consecutive patients with proximal fibular tumors were retrospectively reviewed. Details of the clinicopathological characteristics including age, gender, location of tumors, the presenting symptoms, the duration of symptoms, and pathological diagnosis were collected. Descriptive statistics were calculated, and univariate and multivariate regression were performed. Of these 52 patients, 84.6% had benign tumors and 15.4% malignant tumors. The most common benign tumors were osteochondromas (46.2%), followed by enchondromas (13.5%) and giant cell tumors (13.5%). The most common malignancy was osteosarcomas (11.5%). The most common presenting symptoms were a palpable mass (52.0%) and pain (46.2%). Pain was the most sensitive (100%) and fourth specific (64%); both high skin temperature and peroneal nerve compression had the highest specificity (98%) and third sensitivity (64%); change in symptoms had the second highest specificity (89%) while 50% sensitivity. Using multivariate regression, palpable pain, high skin temperature, and peroneal nerve compression symptoms were predictors of malignancy. Most tumors in the proximal fibula are benign, and the malignancy is rare. Palpable pain, peroneal nerve compression symptoms, and high skin temperature were specific in predicting malignancy.

Engineering 'cell robots' for parallel and highly sensitive screening of biomolecules under in vivo conditions.

PubMed

Song, Lifu; Zeng, An-Ping

2017-11-09

Cells are capable of rapid replication and performing tasks adaptively and ultra-sensitively and can be considered as cheap "biological-robots". Here we propose to engineer cells for screening biomolecules in parallel and with high sensitivity. Specifically, we place the biomolecule variants (library) on the bacterial phage M13. We then design cells to screen the library based on cell-phage interactions mediated by a specific intracellular signal change caused by the biomolecule of interest. For proof of concept, we used intracellular lysine concentration in E. coli as a signal to successfully screen variants of functional aspartate kinase III (AK-III) under in vivo conditions, a key enzyme in L-lysine biosynthesis which is strictly inhibited by L-lysine. Comparative studies with flow cytometry method failed to distinguish the wild-type from lysine resistance variants of AK-III, confirming a higher sensitivity of the method. It opens up a new and effective way of in vivo high-throughput screening for functional molecules and can be easily implemented at low costs.

Application of photostable quantum dots for indirect immunofluorescent detection of specific bacterial serotypes on small marine animals

NASA Astrophysics Data System (ADS)

Decho, Alan W.; Beckman, Erin M.; Chandler, G. Thomas; Kawaguchi, Tomohiro

2008-06-01

An indirect immunofluorescence approach was developed using semiconductor quantum dot nanocrystals to label and detect a specific bacterial serotype of the bacterial human pathogen Vibrio parahaemolyticus, attached to small marine animals (i.e. benthic harpacticoid copepods), which are suspected pathogen carriers. This photostable labeling method using nanotechnology will potentially allow specific serotypes of other bacterial pathogens to be detected with high sensitivity in a range of systems, and can be easily applied for sensitive detection to other Vibrio species such as Vibrio cholerae.

Multi-Country Evaluation of the Sensitivity and Specificity of Two Commercially-Available NS1 ELISA Assays for Dengue Diagnosis

PubMed Central

Guzman, Maria G.; Jaenisch, Thomas; Gaczkowski, Roger; Ty Hang, Vo Thi; Sekaran, Shamala Devi; Kroeger, Axel; Vazquez, Susana; Ruiz, Didye; Martinez, Eric; Mercado, Juan C.; Balmaseda, Angel; Harris, Eva; Dimano, Efren; Leano, Prisca Susan A.; Yoksan, Sutee; Villegas, Elci; Benduzu, Herminia; Villalobos, Iris; Farrar, Jeremy; Simmons, Cameron P.

2010-01-01

Background Early diagnosis of dengue can assist patient triage and management and prevent unnecessary treatments and interventions. Commercially available assays that detect the dengue virus protein NS1 in the plasma/serum of patients offers the possibility of early and rapid diagnosis. Methodology/Principal Findings The sensitivity and specificity of the Pan-E Dengue Early ELISA and the Platelia™ Dengue NS1 Ag assays were compared against a reference diagnosis in 1385 patients in 6 countries in Asia and the Americas. Platelia was more sensitive (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by geographic region, with both assays generally being more sensitive in patients from SE Asia than the Americas. Both kits were more sensitive for specimens collected within the first few days of illness onset relative to later time points. Pan-E and Platelia were both 100% specific in febrile patients without evidence of acute dengue. In patients with other confirmed diagnoses and healthy blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia, when either the NS1 test or the IgM test on the acute sample was positive, the sensitivity versus the reference result was 82% in samples collected in the first four days of fever. NS1 sensitivity was not associated to disease severity (DF or DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases was seen in the Pan-E test (however combined with lower overall sensitivity). Conclusions/Significance Collectively, this multi-country study suggests that the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%, range 34–76%) and high specificity (100%) for the diagnosis of dengue. The poor sensitivity of the evaluated assays in some geographical regions suggests further assessments are needed. The combination of NS1 and IgM detection in samples collected in the first few days of fever increased the overall dengue diagnostic sensitivity. PMID:20824173

Evaluation of a Myopic Normative Database for Analysis of Retinal Nerve Fiber Layer Thickness.

PubMed

Biswas, Sayantan; Lin, Chen; Leung, Christopher K S

2016-09-01

Analysis of retinal nerve fiber layer (RNFL) abnormalities with optical coherence tomography in eyes with high myopia has been complicated by high rates of false-positive errors. An understanding of whether the application of a myopic normative database can improve the specificity for detection of RNFL abnormalities in eyes with high myopia is relevant. To evaluate the diagnostic performance of a myopic normative database for detection of RNFL abnormalities in eyes with high myopia (spherical equivalent, -6.0 diopters [D] or less). In this cross-sectional study, 180 eyes with high myopia (mean [SD] spherical equivalent, -8.0 [1.8] D) from 180 healthy individuals were included in the myopic normative database. Another 46 eyes with high myopia from healthy individuals (mean [SD] spherical equivalent, -8.1 [1.8] D) and 74 eyes from patients with high myopia and glaucoma (mean [SD] spherical equivalent, -8.3 [1.9] D) were included for evaluation of specificity and sensitivity. The 95th and 99th percentiles of the mean and clock-hour circumpapillary RNFL thicknesses and the individual superpixel thicknesses of the RNFL thickness map measured by spectral-domain optical coherence tomography were calculated from the 180 eyes with high myopia. Participants were recruited from January 2, 2013, to December 30, 2015. The following 6 criteria of RNFL abnormalities were examined: (1) mean circumpapillary RNFL thickness below the lower 95th or (2) the lower 99th percentile; (3) one clock-hour or more for RNFL thickness below the lower 95th or (4) the lower 99th percentile; and (5) twenty contiguous superpixels or more of RNFL thickness in the RNFL thickness map below the lower 95th or (6) the lower 99th percentile. Specificities and sensitivities for detection of RNFL abnormalities. Of the 46 healthy eyes and 74 eyes with glaucoma studied (from 39 men and 38 women), the myopic normative database showed a higher specificity (63.0%-100%) than did the built-in normative database of the optical coherence tomography instrument (8.7%-87.0%) for detection of RNFL abnormalities across all the criteria examined (differences in specificities between 13.0% [95% CI, 1.1%-24.9%; P = .01] and 54.3% [95% CI, 37.8%-70.9%; P < .001]) except for the criterion of mean RNFL thickness below the lower 99th percentile, in which both normative databases had the same specificities (100%) but the myopic normative database exhibited a higher sensitivity (71.6% vs 86.5%; difference in sensitivities, 14.9% [95% CI, 4.6%-25.1%; P = .002]). The application of a myopic normative database improved the specificity without compromising the sensitivity compared with the optical coherence tomography instrument's built-in normative database for detection of RNFL abnormalities in eyes with high myopia. Inclusion of myopic normative databases should be considered in optical coherence tomography instruments.

A Retrospective Assessment of Four Antigen Assays for the Detection of Invasive Candidiasis Among High-Risk Hospitalized Patients.

PubMed

Hartl, Barbara; Zeller, Iris; Manhart, Angelika; Selitsch, Brigitte; Lass-Flörl, Cornelia; Willinger, Birgit

2018-06-01

Because of their high mortality rates and non-specific symptoms, invasive Candida infections pose a huge diagnostic and therapeutic challenge. In this study, we evaluated the three mannan antigen assays Platelia, Platelia Plus and Serion, and the (1-3)-β-D-glucan assay Fungitell in a group of high-risk (hematological and surgical) patients. Test results of 305 patients hospitalized at the Vienna General Hospital and the University Hospital of Innsbruck were retrospectively analyzed. We assessed the test accuracy by means of descriptive statistics. Nine (2.95%) patients were affected by invasive candidiasis (IC), and 25 (8.2%) patients had a probable/possible infection. The majority of patients (271; 88.9%) showed no signs of infection. The Platelia and Serion mannan assays had a low sensitivity (65% and 52%, respectively), but high specificity (98% for both tests). The newer version of the Platelia assay, the Platelia Plus, had a higher sensitivity (85%) but a lower specificity (89%). The sensitivity of the Fungitell assay was high (100%), while its specificity was low (58%). The positive predictive values were 0.48 for the Platelia and 0.41 for the Serion assay, 0.26 for the Platelia Plus and 0.09 for the Fungitell assay. Our limited, retrospective study suggests the efficacy of mannan assays as screening (Platelia Plus) and confirmatory (Serion) tests, while the Fungitell assay can be used to exclude invasive Candida infections.

A PRELIMINARY assessment of BCG vacination in India.

PubMed

1955-01-01

A NEW ASSESSMENT ACTIVITY IN RELATION TO THE WHO/UNICEF BCG VACCINATION PROGRAMME IS DESCRIBED IN THIS REPORT: according to a detailed plan special field teams collect data on tuberculin sensitivity to determine how efficiently children are being selected for vaccination and to appraise the allergy produced by the mass vaccinations. Results of nine months' work in India have important implications for the practical BCG work.Testing of unvaccinated groups of schoolchildren shows that the pattern of tuberculin sensitivity differs in different parts of India. Specific tuberculin sensitivity is found in all areas, as evidenced by strong reactions to the 5 TU test. Many children had a low-grade non-specific sensitivity, evidenced by small reactions to 5 TU and large reactions to 100 TU. This non-specific tuberculin sensitivity was less frequent at high altitudes, and most common in low-lying humid areas: in all areas it was more prevalent than specific sensitivity.In some areas non-specific tuberculin sensitivity is so strong that it cannot be effectively distinguished from specific sensitivity: consequently, many children not infected with tuberculosis are undoubtedly being excluded from vaccination.Sample retesting of children vaccinated in the mass campaign revealed variable levels of allergy, in many instances much lower than had been expected. These results cannot be explained by a native incapacity of the Indian children to develop strong allergy-nor presumably by the vaccine used. Impairment of the vaccine by exposure to light could be no more than a contributory factor. The marked variability of the campaign results suggests that some factor connected with the handling or application of the vaccine (or possibly of the tuberculin) is involved.

Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment.

PubMed

Cabañas, R; Calderón, O; Ramírez, E; Fiandor, A; Caballero, T; Heredia, R; Herranz, P; Madero, R; Quirce, S; Bellón, T

2018-03-01

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed hypersensitivity reaction. The determination of drug causality is complex. The lymphocyte transformation test (LTT) has been reported positive in more than 50% of DRESS cases. Nevertheless, the sensitivity and specificity of LTT specifically in DRESS have not yet been established. Rechallenge with the culprit drug is contraindicated and cannot be used as gold standard for sensitivity and specificity determination. To estimate the sensitivity and specificity of LTT in a clinically defined series of patients with DRESS. Some 41 patients diagnosed with DRESS were included in the study. The results of the algorithm of the Spanish Pharmacovigilance System were used as the standard for a correct diagnosis of drug causality. A standard LTT was performed with involved drugs in acute or recovery samples. A stimulation index (SI) ≥2 in at least one concentration except for beta-lactams (SI ≥3) and contrast media (SI ≥4) was considered positive. Contingency tables and ROC curves were used for analysis. Sensitivity and specificity of LTT in the recovery phase of DRESS were 73% and 82%, respectively, whereas in the acute phase, they were only 40% and 30%, respectively. Comparison of skin tests and LTT confirmed a higher sensitivity and specificity of LTT in DRESS. LTT showed high sensitivity (S) and specificity (Sp) for anticonvulsants (S 100%, Sp 100%; P = .008), anti-TB drugs (S 87.5%, Sp 100%; P = .004), and beta-lactams (S 73%, Sp 100%; P = .001). ROC curves revealed that the best criteria for LTT positivity for all drugs are SI ≥2 in at least one concentration, increasing overall sensitivity to 80%, and for beta-lactams from 73% to 92%. LTT is a good diagnostic tool for drug causality in DRESS, mainly when performed in the recovery phase. © 2017 John Wiley & Sons Ltd.

Diagnostic accuracy of the MMSE in detecting probable and possible Alzheimer's disease in ethnically diverse highly educated individuals: an analysis of the NACC database.

PubMed

Spering, Cynthia C; Hobson, Valerie; Lucas, John A; Menon, Chloe V; Hall, James R; O'Bryant, Sid E

2012-08-01

To validate and extend the findings of a raised cut score of O'Bryant and colleagues (O'Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963-967.) for the Mini-Mental State Examination in detecting cognitive dysfunction in a bilingual sample of highly educated ethnically diverse individuals. Archival data were reviewed from participants enrolled in the National Alzheimer's Coordinating Center minimum data set. Data on 7,093 individuals with 16 or more years of education were analyzed, including 2,337 cases with probable and possible Alzheimer's disease, 1,418 mild cognitive impairment patients, and 3,088 nondemented controls. Ethnic composition was characterized as follows: 6,296 Caucasians, 581 African Americans, 4 American Indians or Alaska natives, 2 native Hawaiians or Pacific Islanders, 149 Asians, 43 "Other," and 18 of unknown origin. Diagnostic accuracy estimates (sensitivity, specificity, and likelihood ratio) of Mini-Mental State Examination cut scores in detecting probable and possible Alzheimer's disease were examined. A standard Mini-Mental State Examination cut score of 24 (≤23) yielded a sensitivity of 0.58 and a specificity of 0.98 in detecting probable and possible Alzheimer's disease across ethnicities. A cut score of 27 (≤26) resulted in an improved balance of sensitivity and specificity (0.79 and 0.90, respectively). In the cognitively impaired group (mild cognitive impairment and probable and possible Alzheimer's disease), the standard cut score yielded a sensitivity of 0.38 and a specificity of 1.00 while raising the cut score to 27 resulted in an improved balance of 0.59 and 0.96 of sensitivity and specificity, respectively. These findings cross-validate our previous work and extend them to an ethnically diverse cohort. A higher cut score is needed to maximize diagnostic accuracy of the Mini-Mental State Examination in individuals with college degrees.

Identifying substance misuse in primary care: TAPS Tool compared to the WHO ASSIST.

PubMed

Schwartz, R P; McNeely, J; Wu, L T; Sharma, G; Wahle, A; Cushing, C; Nordeck, C D; Sharma, A; O'Grady, K E; Gryczynski, J; Mitchell, S G; Ali, R L; Marsden, J; Subramaniam, G A

2017-05-01

There is a need for screening and brief assessment instruments to identify primary care patients with substance use problems. This study's aim was to examine the performance of a two-step screening and brief assessment instrument, the TAPS Tool, compared to the WHO ASSIST. Two thousand adult primary care patients recruited from five primary care clinics in four Eastern US states completed the TAPS Tool followed by the ASSIST. The ability of the TAPS Tool to identify moderate- and high-risk use scores on the ASSIST was examined using sensitivity and specificity analyses. The interviewer and self-administered computer tablet versions of the TAPS Tool generated similar results. The interviewer-administered version (at cut-off of 2), had acceptable sensitivity and specificity for high-risk tobacco (0.90 and 0.77) and alcohol (0.87 and 0.80) use. For illicit drugs, sensitivities were >0.82 and specificities >0.92. The TAPS (at a cut-off of 1) had good sensitivity and specificity for moderate-risk tobacco use (0.83 and 0.97) and alcohol (0.83 and 0.74). Among illicit drugs, sensitivity was acceptable for moderate-risk of marijuana (0.71), while it was low for all other illicit drugs and non-medical use of prescription medications. Specificities were 0.97 or higher for all illicit drugs and prescription medications. The TAPS Tool identified adult primary care patients with high-risk ASSIST scores for all substances as well moderate-risk users of tobacco, alcohol, and marijuana, although it did not perform well in identifying patients with moderate-risk use of other drugs or non-medical use of prescription medications. The advantages of the TAPS Tool over the ASSIST are its more limited number of items and focus solely on substance use in the past 3months. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and optimization of an efficient qPCR system for olive authentication in edible oils.

PubMed

Alonso-Rebollo, Alba; Ramos-Gómez, Sonia; Busto, María D; Ortega, Natividad

2017-10-01

The applicability of qPCR in olive-oil authentication depends on the DNA obtained from the oils and the amplification primers. Therefore, four olive-specific amplification systems based on the trnL gene were designed (A-, B-, C- and D-trnL systems). The qPCR conditions, primer concentration and annealing temperature, were optimized. The systems were tested for efficiency and sensitivity to select the most suitable for olive oil authentication. The selected system (D-trnL) demonstrated specificity toward olive in contrast to other oleaginous species (canola, soybean, sunflower, maize, peanut and coconut) and showed high sensitivity in a broad linear dynamic range (LOD and LOQ: 500ng - 0.0625pg). This qPCR system enabled detection, with high sensitivity and specificity, of olive DNA isolated from oils processed in different ways, establishing it as an efficient method for the authentication of olive oil regardless of its category. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas.

PubMed

Lin, Fan; Shi, Jianhui; Wang, Hanlin L; Ma, Xiao-Jun; Monroe, Robert; Luo, Yuling; Chen, Zongming; Liu, Haiyan

2018-05-09

Inconsistent data on detection of albumin expression by ribonucleic acid (RNA) in situ hybridization have been reported. We investigated the utility of RNAscope (Advanced Cell Diagnostics, Hayward, CA) in detection of albumin in hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (ICCs), and carcinomas from various organs using manual and automated staining. RNAscope for albumin detection was performed on 482 cases on tissue microarray sections and on 22 cases of ICC, including 14 surgical resection and eight core biopsy specimens. Thirty-six of 37 (97%) HCCs had detectable mRNA, whereas all non-HCC and non-ICC cases, except one lung adenocarcinoma, were negative for albumin. Fourteen of 22 ICCs (64%) were positive for albumin. RNAscope for albumin is highly sensitive and specific for identifying HCCs and is highly specific and moderately sensitive for detection of ICCs; however, rare carcinomas (non-HCC, non-ICC, and those with no hepatoid histomorphology) can also have aberrant expression of albumin.

Field Demonstration of a Multiplexed Point-of-Care Diagnostic Platform for Plant Pathogens.

PubMed

Lau, Han Yih; Wang, Yuling; Wee, Eugene J H; Botella, Jose R; Trau, Matt

2016-08-16

Effective disease management strategies to prevent catastrophic crop losses require rapid, sensitive, and multiplexed detection methods for timely decision making. To address this need, a rapid, highly specific and sensitive point-of-care method for multiplex detection of plant pathogens was developed by taking advantage of surface-enhanced Raman scattering (SERS) labeled nanotags and recombinase polymerase amplification (RPA), which is a rapid isothermal amplification method with high specificity. In this study, three agriculturally important plant pathogens (Botrytis cinerea, Pseudomonas syringae, and Fusarium oxysporum) were used to demonstrate potential translation into the field. The RPA-SERS method was faster, more sensitive than polymerase chain reaction, and could detect as little as 2 copies of B. cinerea DNA. Furthermore, multiplex detection of the three pathogens was demonstrated for complex systems such as the Arabidopsis thaliana plant and commercial tomato crops. To demonstrate the potential for on-site field applications, a rapid single-tube RPA/SERS assay was further developed and successfully performed for a specific target outside of a laboratory setting.

Sonicated Diagnostic Immunoblot for Bartonellosis

PubMed Central

Mallqui, Vania; Speelmon, Emily C.; Verástegui, Manuela; Maguiña-Vargas, Ciro; Pinell-Salles, Paula; Lavarello, Rosa; Delgado, Jose; Kosek, Margaret; Romero, Sofia; Arana, Yanina; Gilman, Robert H.

2000-01-01

Two simple Bartonella bacilliformis immunoblot preparation methods were developed. Antigen was prepared by two different methods: sonication of whole organisms or glycine extraction. Both methods were then tested for sensitivity and specificity. Well-defined control sera were utilized in the development of these diagnostic immunoblots, and possible cross-reactions were thoroughly examined. Sera investigated for cross-reaction with these diagnostic antigens were drawn from patients with brucellosis, chlamydiosis, Q fever, and cat scratch disease, all of whom were from regions where bartonellosis is not endemic. While both immunoblots yielded reasonable sensitivity and high specificity, we recommend the use of the sonicated immunoblot, which has a higher sensitivity when used to detect acute disease and produces fewer cross-reactions. The sonicated immunoblot reported here is 94% sensitive to chronic bartonellosis and 70% sensitive to acute bartonellosis. In a healthy group, it is 100% specific. This immunoblot preparation requires a simple sonication protocol for the harvesting of B. bacilliformis antigens and is well suited for use in regions of endemicity. PMID:10618267

Sensitivity and specificity of CT colonography for the detection of colonic neoplasia after positive faecal occult blood testing: systematic review and meta-analysis.

PubMed

Plumb, Andrew A; Halligan, Steve; Pendsé, Douglas A; Taylor, Stuart A; Mallett, Susan

2014-05-01

CT colonography (CTC) is recommended after positive faecal occult blood testing (FOBt) when colonoscopy is incomplete or infeasible. We aimed to estimate the sensitivity and specificity of CTC for colorectal cancer and adenomatous polyps following positive FOBt via systematic review. The MEDLINE, EMBASE, AMED and Cochrane Library databases were searched for CTC studies reporting sensitivity and specificity for colorectal cancer and adenomatous polyps. Included subjects had tested FOBt-positive by guaiac or immunochemical methods. Per-patient detection rates were summarized via forest plots. Meta-analysis of sensitivity and specificity was conducted using a bivariate random effects model and the average operating point calculated. Of 538 articles considered, 5 met inclusion criteria, describing results from 622 patients. Research study quality was good. CTC had a high per-patient average sensitivity of 88.8 % (95 % CI 83.6 to 92.5 %) for ≥6 mm adenomas or colorectal cancer, with low between-study heterogeneity. Specificity was both more heterogeneous and lower, at an average of 75.4 % (95 % CI 58.6 to 86.8 %). Few studies have investigated CTC in FOBt-positive individuals. CTC is sensitive at a ≥6 mm threshold but specificity is lower and variable. Despite the limited data, these results suggest that CTC may adequately substitute for colonoscopy when the latter is undesirable. • FOBt is the most common mass screening test for colorectal cancer. • Few studies evaluate CT colonography after positive FOBt. • CTC is approximately 89 % sensitive for ≥6 mm adenomas/cancer in this setting. • Specificity is lower, at approximately 75 %, and more variable. • CT colonography is a good alternative when colonoscopy is undesirable.

Detection of Bacteriuria by Canine Olfaction

PubMed Central

Maurer, Maureen; McCulloch, Michael; Willey, Angel M.; Hirsch, Wendi; Dewey, Danielle

2016-01-01

Background. Urinary tract infections (UTIs) are a significant medical problem , particularly for patients with neurological conditions and the elderly. Detection is often difficult in these patients, resulting in delayed diagnoses and more serious infections such as pyelonephritis and life-threatening sepsis. Many patients have a higher risk of UTIs because of impaired bladder function, catheterization, and lack of symptoms. Urinary tract infections are the most common nosocomial infection; however, better strategies are needed to improve early detection of the disease. Methods. In this double-blinded, case-control, validation study, we obtained fresh urine samples daily in a consecutive case series over a period of 16 weeks. Dogs were trained to distinguish urine samples that were culture-positive for bacteriuria from those of culture-negative controls, using reward-based clicker and treat methods. Results. Samples were obtained from 687 individuals (from 3 months to 92 years of age; 86% female and 14% male; 34% culture-positive and 66% culture-negative controls). Dogs detected urine samples positive for 100 000 colony-forming units/mL Escherichia coli (N = 250 trials; sensitivity 99.6%, specificity 91.5%). Dilution of E coli urine with distilled water did not affect accuracy at 1% (sensitivity 100%, specificity 91.1%) or 0.1% (sensitivity 100%, specificity 93.6%) concentration. Diagnostic accuracy was similar to Enterococcus (n = 50; sensitivity 100%, specificity 93.9%), Klebsiella (n = 50; sensitivity 100%, specificity 95.1%), and Staphylococcus aureus (n = 50; sensitivity 100%, specificity 96.3%). All dogs performed with similarly high accuracy: overall sensitivity was at or near 100%, and specificity was above 90%. Conclusions. Canine scent detection is an accurate and feasible method for detection of bacteriuria. PMID:27186578

Combining parasite lactate dehydrogenase-based and histidine-rich protein 2-based rapid tests to improve specificity for diagnosis of malaria Due to Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia.

PubMed

Grigg, Matthew J; William, Timothy; Barber, Bridget E; Parameswaran, Uma; Bird, Elspeth; Piera, Kim; Aziz, Ammar; Dhanaraj, Prabakaran; Yeo, Tsin W; Anstey, Nicholas M

2014-06-01

Plasmodium knowlesi causes severe and fatal malaria in Malaysia. Microscopic misdiagnosis is common and may delay appropriate treatment. P. knowlesi can cross-react with "species-specific" parasite lactate dehydrogenase (pLDH) monoclonal antibodies used in rapid diagnostic tests (RDTs) to detect P. falciparum and P. vivax. At one tertiary-care hospital and two district hospitals in Sabah, we prospectively evaluated two combination RDTs for malaria diagnosis by using both a pan-Plasmodium-pLDH (pan-pLDH)/P. falciparum-specific-pLDH (Pf-pLDH) RDT (OptiMAL-IT) and a non-P. falciparum VOM-pLDH/Pf-HRP2 RDT (CareStart). Differential cross-reactivity among these combinations was hypothesized to differentiate P. knowlesi from other Plasmodium monoinfections. Among 323 patients with PCR-confirmed P. knowlesi (n = 193), P. falciparum (n = 93), and P. vivax (n = 37) monoinfections, the VOM-pLDH individual component had the highest sensitivity for nonsevere (35%; 95% confidence interval [CI], 27 to 43%) and severe (92%; CI, 81 to 100%) P. knowlesi malaria. CareStart demonstrated a P. knowlesi sensitivity of 42% (CI, 34 to 49%) and specificity of 74% (CI, 65 to 82%), a P. vivax sensitivity of 83% (CI, 66 to 93%) and specificity of 71% (CI, 65 to 76%), and a P. falciparum sensitivity of 97% (CI, 90 to 99%) and specificity of 99% (CI, 97 to 100%). OptiMAL-IT demonstrated a P. knowlesi sensitivity of 32% (CI, 25 to 39%) and specificity of 21% (CI, 15 to 29%), a P. vivax sensitivity of 60% (CI, 42 to 75%) and specificity of 97% (CI, 94 to 99%), and a P. falciparum sensitivity of 82% (CI, 72 to 89%) and specificity of 39% (CI, 33 to 46%). The combination of CareStart plus OptiMAL-IT for P. knowlesi using predefined criteria gave a sensitivity of 25% (CI, 19 to 32%) and specificity of 97% (CI, 92 to 99%). Combining two RDT combinations was highly specific for P. knowlesi malaria diagnosis; however, sensitivity was poor. The specificity of pLDH RDTs was decreased for P. vivax and P. falciparum because of P. knowlesi cross-reactivity and cautions against their use alone in areas where P. knowlesi malaria is endemic. Sensitive P. knowlesi-specific RDTs and/or alternative molecular diagnostic tools are needed in areas where P. knowlesi malaria is endemic. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Aptamer-Immobilized Surface Plasmon Resonance Biosensor for Rapid and Sensitive Determination of Virulence Determinant.

PubMed

Song, Myeong-Sub; Sekhon, Simranjeet Singh; Shin, Woo-Ri; Rhee, Sung-Keun; Ko, Jung Ho; Kim, Sang Yong; Min, Jiho; Ahn, Ji-Young; Kim, Yang-Hoon

2018-05-01

Shigella sonnei isolate invasion plasmid antigen protein, IpaH, was successfully expressed in recombinant overexpression bacterial system. The soluble expression IpaH was enhanced with molecular chaperon co-expressed environment. Specific aptamer IpaH17 was isolated through the SELEX process and showed fM binding affinity. IpaH17-SPR biosensor platform was involved to verify the binding sensitivity and specificity. The IpaH concentration dependent IpaH17-SPR sensor response was highly linear with a linear regression constant of 99.4% in the range between 0 and 100 ng/mL. In addition, S. sonnei revealed the specific RU value and detected in a real-time manner within 1 hour. Our study indicated that IpaH17-SPR sensor can allow for rapid, sensitive and specific determination of Shigella sonnei virulent factor.

Detection of Entamoeba histolytica by Recombinase Polymerase Amplification.

PubMed

Nair, Gayatri; Rebolledo, Mauricio; White, A Clinton; Crannell, Zachary; Richards-Kortum, R Rebecca; Pinilla, A Elizabeth; Ramírez, Juan David; López, M Consuelo; Castellanos-Gonzalez, Alejandro

2015-09-01

Amebiasis is an important cause of diarrheal disease worldwide and has been associated with childhood malnutrition. Traditional microscopy approaches are neither sensitive nor specific for Entamoeba histolytica. Antigen assays are more specific, but many cases are missed unless tested by molecular methods. Although polymerase chain reaction (PCR) is effective, the need for sophisticated, expensive equipment, infrastructure, and trained personnel limits its usefulness, especially in the resource-limited, endemic areas. Here, we report development of a recombinase polymerase amplification (RPA) method to detect E. histolytica specifically. Using visual detection by lateral flow (LF), the test was highly sensitive and specific and could be performed without additional equipment. The availability of this inexpensive, sensitive, and field-applicable diagnostic test could facilitate rapid diagnosis and treatment of amebiasis in endemic regions. © The American Society of Tropical Medicine and Hygiene.

Optical coherence tomography in the diagnosis of dysplasia and adenocarcinoma in Barret's esophagus

NASA Astrophysics Data System (ADS)

Gladkova, N. D.; Zagaynova, E. V.; Zuccaro, G.; Kareta, M. V.; Feldchtein, F. I.; Balalaeva, I. V.; Balandina, E. B.

2007-02-01

Statistical analysis of endoscopic optical coherence tomography (EOCT) surveillance of 78 patients with Barrett's esophagus (BE) is presented in this study. The sensitivity of OCT device in retrospective open detection of early malignancy (including high grade dysplasia and intramucosal adenocarcinoma (IMAC)) was 75%, specificity 82%, diagnostic accuracy - 80%, positive predictive value- 60%, negative predictive value- 87%. In the open recognition of IMAC sensitivity was 81% and specificity were 85% each. Results of a blind recognition with the same material were similar: sensitivity - 77%, specificity 85%, diagnostic accuracy - 82%, positive predictive value- 70%, negative predictive value- 87%. As the endoscopic detection of early malignancy is problematic, OCT holds great promise in enhancing the diagnostic capability of clinical GI endoscopy.

Sensitivity of different Trypanosoma vivax specific primers for the diagnosis of livestock trypanosomosis using different DNA extraction methods.

PubMed

Gonzales, J L; Loza, A; Chacon, E

2006-03-15

There are several T. vivax specific primers developed for PCR diagnosis. Most of these primers were validated under different DNA extraction methods and study designs leading to heterogeneity of results. The objective of the present study was to validate PCR as a diagnostic test for T. vivax trypanosomosis by means of determining the test sensitivity of different published specific primers with different sample preparations. Four different DNA extraction methods were used to test the sensitivity of PCR with four different primer sets. DNA was extracted directly from whole blood samples, blood dried on filter papers or blood dried on FTA cards. The results showed that the sensitivity of PCR with each primer set was highly dependant of the sample preparation and DNA extraction method. The highest sensitivities for all the primers tested were determined using DNA extracted from whole blood samples, while the lowest sensitivities were obtained when DNA was extracted from filter paper preparations. To conclude, the obtained results are discussed and a protocol for diagnosis and surveillance for T. vivax trypanosomosis is recommended.

Diagnostic Validity of High-Density Barium Sulfate in Gastric Cancer Screening: Follow-up of Screenees by Record Linkage with the Osaka Cancer Registry

PubMed Central

Yamamoto, Kenyu; Yamazaki, Hideo; Kuroda, Chikazumi; Kubo, Tsugio; Oshima, Akira; Katsuda, Toshizo; Kuwano, Tadao; Takeda, Yoshihiro

2010-01-01

Background The use of high-density barium sulfate was recommended by the Japan Society of Gastroenterological Cancer Screening (JSGCS) in 2004. We evaluated the diagnostic validity of gastric cancer screening that used high-density barium sulfate. Methods The study subjects were 171 833 residents of Osaka, Japan who underwent gastric cancer screening tests at the Osaka Cancer Prevention and Detection Center during the period from 1 January 2000 through 31 December 2001. Screening was conducted using either high-density barium sulfate (n = 48 336) or moderate-density barium sulfate (n = 123 497). The subjects were followed up and their medical records were linked to those of the Osaka Cancer Registry through 31 December 2002. The results of follow-up during 1 year were defined as the gold standard, and test performance values were calculated. Results The sensitivity and specificity of the screening test using moderate-density barium sulfate were 92.3% and 91.0%, respectively, while the sensitivity and specificity of the high-density barium test were 91.8% and 91.4%, respectively. The results of area under receiver-operating-characteristic (ROC) curve analysis revealed no significant difference between the 2 screening tests. Conclusions Screening tests using high- and moderate-density barium sulfate had similar validity, as determined by sensitivity, specificity, and ROC curve analysis. PMID:20551581

Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin resistance in county-level laboratories in Hunan province, China.

PubMed

Hu, Peilei; Bai, Liqiong; Liu, Fengping; Ou, Xichao; Zhang, Zhiying; Yi, Songlin; Chen, Zhongnan; Gong, Daofang; Liu, Binbin; Guo, Jingwei; Tan, Yunhong

2014-01-01

The Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis (TB) countries. However, there were little data obtained by validation or demonstration study of the assay in China. In this study, the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province, China. Consecutive patients with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant tuberculosis (MDR-TB) were enrolled. For each patient suspected to have PTB, three sputum specimens (one spot sputum, one night sputum, and one morning sputum) were collected and each sputum was tested with smear microscopy, Löwenstein-Jensen (LJ) culture, and Xpert MTB/RIF test. For comparison across subgroups and testing methods, 95% confidence intervals were calculated. All analyses were done with SPSS 16.0, and P < 0.05 was regarded as significant. For case detection, the sensitivity of Xpert MTB/RIF was 100% for smear- and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the overall sensitivity was 94.5% for all culture-positive patients. The specificity was 99.8%. The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB patients and the specificity reached 100.0% in the group of patients who are infected with nontuberculous mycobacteria. For the detection of rifampin resistance, the sensitivity of MTB/RIF RIF-resistance detection was 92.9%, and the specificity was 98.7%. Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests, 20 (76.9%) patients were infected by MDR-TB. The Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance, which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB control in China. Further evaluations in county-level laboratories for implementing the assay are still required.

Touch-down reverse transcriptase-PCR detection of IgV(H) rearrangement and Sybr-Green-based real-time RT-PCR quantitation of minimal residual disease in patients with chronic lymphocytic leukemia.

PubMed

Peková, Sona; Marková, Jana; Pajer, Petr; Dvorák, Michal; Cetkovský, Petr; Schwarz, Jirí

2005-01-01

Patients with chronic lymphocytic leukemia (CLL) can relapse even after aggressive therapy and autografts. It is commonly assumed that to prevent relapse the level of minimal residual disease (MRD) should be as low as possible. To evaluate MRD, highly sensitive quantitative assays are needed. The aim of the study was to develop a robust and sensitive method for detection of the clonal immunoglobulin heavy-chain variable (IgV(H)) rearrangement in CLL and to introduce a highly sensitive and specific methodology for MRD monitoring in patients with CLL who undergo intensive treatment. As a prerequisite for MRD detection, touch-down reverse transcriptase (RT)-PCR using degenerate primers were used for the diagnostic identification of (H) gene rearrangement(s). For quantitative MRD detection in 18 patients, we employed a real-time RT-PCR assay (RQ-PCR) making use of patient-specific primers and the cost-saving Sybr-Green reporter dye (SG). For precise calibration of RQ-PCR, patient-specific IgV(H) sequences were cloned. Touch-down RT-PCR with degenerate primers allowed the successful detection of IgV(H) clonal rearrangement(s) in 252 of 257 (98.1%) diagnostic samples. Biallelic rearrangements were found in 27 of 252 (10.7%) cases. Degenerate primers used for the identification of clonal expansion at diagnosis were not sensitive enough for MRD detection. In contrast, our RQ-PCR assay using patient-specific primers and SG reached the sensitivity of 10(-)(6). We demonstrated MRD in each patient tested, including four of four patients in complete remission following autologous hematopoietic stem cell transplantation (HSCT) and three of three following allogeneic 'mini'-HSCT. Increments in MRD might herald relapse; aggressive chemotherapy could induce molecular remission. Our touch-down RT-PCR has higher efficiency to detect clonal IgV(H) rearrangements including the biallelic ones. MRD quantitation of IgV(H) expression using SG-based RQ-PCR represents a highly specific, sensitive, and economic alternative to the current quantitative methods.

Computer aided detection of surgical retained foreign object for prevention

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

Hadjiiski, Lubomir, E-mail: lhadjisk@umich.edu; Marentis, Theodore C.; Rondon, Lucas

2015-03-15

Purpose: Surgical retained foreign objects (RFOs) have significant morbidity and mortality. They are associated with approximately $1.5 × 10{sup 9} annually in preventable medical costs. The detection accuracy of radiographs for RFOs is a mediocre 59%. The authors address the RFO problem with two complementary technologies: a three-dimensional (3D) gossypiboma micro tag, the μTag that improves the visibility of RFOs on radiographs, and a computer aided detection (CAD) system that detects the μTag. It is desirable for the CAD system to operate in a high specificity mode in the operating room (OR) and function as a first reader for themore » surgeon. This allows for fast point of care results and seamless workflow integration. The CAD system can also operate in a high sensitivity mode as a second reader for the radiologist to ensure the highest possible detection accuracy. Methods: The 3D geometry of the μTag produces a similar two dimensional (2D) depiction on radiographs regardless of its orientation in the human body and ensures accurate detection by a radiologist and the CAD. The authors created a data set of 1800 cadaver images with the 3D μTag and other common man-made surgical objects positioned randomly. A total of 1061 cadaver images contained a single μTag and the remaining 739 were without μTag. A radiologist marked the location of the μTag using an in-house developed graphical user interface. The data set was partitioned into three independent subsets: a training set, a validation set, and a test set, consisting of 540, 560, and 700 images, respectively. A CAD system with modules that included preprocessing μTag enhancement, labeling, segmentation, feature analysis, classification, and detection was developed. The CAD system was developed using the training and the validation sets. Results: On the training set, the CAD achieved 81.5% sensitivity with 0.014 false positives (FPs) per image in a high specificity mode for the surgeons in the OR and 96.1% sensitivity with 0.81 FPs per image in a high sensitivity mode for the radiologists. On the independent test set, the CAD achieved 79.5% sensitivity with 0.003 FPs per image in a high specificity mode for the surgeons and 90.2% sensitivity with 0.23 FPs per image in a high sensitivity mode for the radiologists. Conclusions: To the best of the authors’ knowledge, this is the first time a 3D μTag is used to produce a recognizable, substantially similar 2D projection on radiographs regardless of orientation in space. It is the first time a CAD system is used to search for man-made objects over anatomic background. The CAD system for the μTags achieved reasonable performance in both the high specificity and the high sensitivity modes.« less

Sensitivity and Specificity of Human Immunodeficiency Virus Rapid Serologic Assays and Testing Algorithms in an Antenatal Clinic in Abidjan, Ivory Coast

PubMed Central

Koblavi-Dème, Stéphania; Maurice, Chantal; Yavo, Daniel; Sibailly, Toussaint S.; N′guessan, Kabran; Kamelan-Tano, Yvonne; Wiktor, Stefan Z.; Roels, Thierry H.; Chorba, Terence; Nkengasong, John N.

2001-01-01

To evaluate serologic testing algorithms for human immunodeficiency virus (HIV) based on a combination of rapid assays among persons with HIV-1 (non-B subtypes) infection, HIV-2 infection, and HIV-1–HIV-2 dual infections in Abidjan, Ivory Coast, a total of 1,216 sera with known HIV serologic status were used to evaluate the sensitivity and specificity of four rapid assays: Determine HIV-1/2, Capillus HIV-1/HIV-2, HIV-SPOT, and Genie II HIV-1/HIV-2. Two serum panels obtained from patients recently infected with HIV-1 subtypes B and non-B were also included. Based on sensitivity and specificity, three of the four rapid assays were evaluated prospectively in parallel (serum samples tested by two simultaneous rapid assays) and serial (serum samples tested by two consecutive rapid assays) testing algorithms. All assays were 100% sensitive, and specificities ranged from 99.4 to 100%. In the prospective evaluation, both the parallel and serial algorithms were 100% sensitive and specific. Our results suggest that rapid assays have high sensitivity and specificity and, when used in parallel or serial testing algorithms, yield results similar to those of enzyme-linked immunosorbent assay-based testing strategies. HIV serodiagnosis based on rapid assays may be a valuable alternative in implementing HIV prevention and surveillance programs in areas where sophisticated laboratories are difficult to establish. PMID:11325995

Sensitivity and specificity of the online version of ImPACT in high school and collegiate athletes.

PubMed

Schatz, Philip; Sandel, Natalie

2013-02-01

The utility of postconcussion neurocognitive testing versus symptom data has been debated. The sensitivity of the desktop version of the Immediate Post-concussion assessment and cognitive testing (ImPACT) tool has been documented, but psychometric properties of the recently released online version of ImPACT have yet to be fully established. To document the sensitivity of the online ImPACT version in samples of (1) symptomatic concussed (high school and collegiate) athletes, and (2) asymptomatic concussed (high school and collegiate) athletes suspected of hiding their concussions. Cohort study; level of evidence, 3. A total of 81 athletes observed to sustain a concussion by a certified athletic trainer or team physician, a finding that was confirmed with reported postconcussion symptoms, completed the ImPACT test within 3 days of injury. Data were compared with an independent sample of 81 athletes who completed preseason baseline cognitive assessments using ImPACT and who were matched (with concussed athletes) on the basis of sex, age, sport, concussion history, and absence of attention deficit hyperactivity disorder and learning disability. An independent group of 37 athletes who were also observed to sustain a concussion completed ImPACT within 3 days of injury. These athletes reported no postconcussion symptoms but were noted for suspected invalid response patterns on ImPACT (impulse control index >30 and verbal memory index <69%). The subscale data from the assessments (excluding those contributing to the aforementioned indices) were compared with a matched sample of 37 athletes who completed preseason baseline cognitive assessments in ImPACT (using the same criteria described above). Data from the ImPACT online version yielded 91.4% sensitivity and 69.1% specificity. For asymptomatic athletes suspected of hiding their concussion, data from ImPACT yielded 94.6% sensitivity and 97.3% specificity. The online version of the ImPACT tool is a valid measure of neurocognitive performance at the acute stages of concussion, with high levels of sensitivity and specificity, even when athletes appear to be denying postconcussion symptoms.

Comparison of Abbott RealTime High-Risk HPV and Hybrid Capture 2 Assays for Detection of HPV Infection.

PubMed

Ko, Kiwoong; Yu, Shinae; Lee, Eun Hee; Park, Hyosoon; Woo, Hee-Yeon; Kwon, Min-Jung

2016-09-01

Various assays for detecting high-risk human papillomavirus (HR HPV) have been introduced recently, including the Abbott RealTime High-Risk HPV assay. We sought to compare the performance of Abbott PCR to Hybrid Capture 2 for the detection of HR HPV. A total of 941 cervical swab specimens were obtained. We submitted all specimens for HR HPV detection with HC2 and Abbott PCR, and then additionally analyzed discordant and concordant positive results using restriction fragment mass polymorphism (RFMP) genotyping analysis. HC2 detected one of 13 HR HPV types in 12.3% (116/941) of cases, while Abbott PCR detected one of 14 detectable HR HPV types in 12.9% (121/941) of cases. The overall agreement rate was 97.3% with a kappa coefficient of 0.879. Discordant results between these two assays were observed in 25 cases. HC2 showed a sensitivity of 90.0% and specificity of 95.9%, while Abbott PCR showed a sensitivity of 98.0% and specificity of 96.8% when using RFMP results as the gold standard. For HPV 16/18 detection, Abbott PCR showed 95.8%/88.9% sensitivity and 99.2%/99.8% specificity, respectively. The overall coinfection rate between HPV 16, 18 and non-16/18 was 9.9% (12/121) in Abbott PCR analysis. Considering its high agreement rate with HC2, higher sensitivity/specificity compared to HC2, and ability to differentiate HPV 16/18 from other HPV types, Abbott PCR could be a reliable laboratory testing method for the screening of HPV infections. © 2016 by the Association of Clinical Scientists, Inc.

Screening for prenatal substance use: development of the Substance Use Risk Profile-Pregnancy scale.

PubMed

Yonkers, Kimberly A; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B; Rounsaville, Bruce J

2010-10-01

To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into "training" (n=1,610) and "validation" (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike's Information Criterion=579.75, Nagelkerke R=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. III.

A systematic review of the diagnostic accuracy of provocative tests of the neck for diagnosing cervical radiculopathy

PubMed Central

Pool, Jan J. M.; van Tulder, Maurits W.; Riphagen, Ingrid I.; de Vet, Henrica C. W.

2006-01-01

Clinical provocative tests of the neck, which position the neck and arm inorder to aggravate or relieve arm symptoms, are commonly used in clinical practice in patients with a suspected cervical radiculopathy. Their diagnostic accuracy, however, has never been examined in a systematic review. A comprehensive search was conducted in order to identify all possible studies fulfilling the inclusion criteria. A study was included if: (1) any provocative test of the neck for diagnosing cervical radiculopathy was identified; (2) any reference standard was used; (3) sensitivity and specificity were reported or could be (re-)calculated; and, (4) the publication was a full report. Two reviewers independently selected studies, and assessed methodological quality. Only six studies met the inclusion criteria, which evaluated five provocative tests. In general, Spurling’s test demonstrated low to moderate sensitivity and high specificity, as did traction/neck distraction, and Valsalva’s maneuver. The upper limb tension test (ULTT) demonstrated high sensitivity and low specificity, while the shoulder abduction test demonstrated low to moderate sensitivity and moderate to high specificity. Common methodological flaws included lack of an optimal reference standard, disease progression bias, spectrum bias, and review bias. Limitations include few primary studies, substantial heterogeneity, and numerous methodological flaws among the studies; therefore, a meta-analysis was not conducted. This review suggests that, when consistent with the history and other physical findings, a positive Spurling’s, traction/neck distraction, and Valsalva’s might be indicative of a cervical radiculopathy, while a negative ULTT might be used to rule it out. However, the lack of evidence precludes any firm conclusions regarding their diagnostic value, especially when used in primary care. More high quality studies are necessary in order to resolve this issue. PMID:17013656

Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX.

PubMed

Koizumi, N; Harada, Y; Beika, M; Minamikawa, T; Yamaoka, Y; Dai, P; Murayama, Y; Yanagisawa, A; Otsuji, E; Tanaka, H; Takamatsu, T

2016-08-01

The establishment of a precise and rapid method to detect metastatic lymph nodes (LNs) is essential to perform less invasive surgery with reduced gastrectomy along with reduced lymph node dissection. We herein describe a novel imaging strategy to detect 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence in excised LNs specifically with reduced effects of tissue autofluorescence based on photo-oxidation of PpIX. We applied the method in a clinical setting, and evaluated its feasibility. To reduce the unfavorable effect of autofluorescence, we focused on photo-oxidation of PpIX: Following light irradiation, PpIX changes into another substance, photo-protoporphyrin, via an oxidative process, which has a different spectral peak, at 675 nm, whereas PpIX has its spectral peak at 635 nm. Based on the unique spectral alteration, fluorescence spectral imaging before and after light irradiation and subsequent originally-developed image processing was performed. Following in vitro study, we applied this method to a total of 662 excised LNs obtained from 30 gastric cancer patients administered 5-ALA preoperatively. Specific visualization of PpIX was achieved in in vitro study. The method allowed highly sensitive detection of metastatic LNs, with sensitivity of 91.9% and specificity of 90.8% in the in vivo clinical trial. Receiver operating characteristic analysis indicated high diagnostic accuracy, with the area under the curve of 0.926. We established a highly sensitive and specific 5-ALA-induced fluorescence imaging method applicable in clinical settings. The novel method has a potential to become a useful tool for intraoperative rapid diagnosis of LN metastasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Screening for Prenatal Substance Use

PubMed Central

Yonkers, Kimberly A.; Gotman, Nathan; Kershaw, Trace; Forray, Ariadna; Howell, Heather B.; Rounsaville, Bruce J.

2011-01-01

OBJECTIVE To report on the development of a questionnaire to screen for hazardous substance use in pregnant women and to compare the performance of the questionnaire with other drug and alcohol measures. METHODS Pregnant women were administered a modified TWEAK (Tolerance, Worried, Eye-openers, Amnesia, K[C] Cut Down) questionnaire, the 4Ps Plus questionnaire, items from the Addiction Severity Index, and two questions about domestic violence (N=2,684). The sample was divided into “training” (n=1,610) and “validation” (n=1,074) subsamples. We applied recursive partitioning class analysis to the responses from individuals in the training subsample that resulted in a three-item Substance Use Risk Profile-Pregnancy scale. We examined sensitivity, specificity, and the fit of logistic regression models in the validation subsample to compare the performance of the Substance Use Risk Profile-Pregnancy scale with the modified TWEAK and various scoring algorithms of the 4Ps. RESULTS The Substance Use Risk Profile-Pregnancy scale is comprised of three informative questions that can be scored for high- or low-risk populations. The Substance Use Risk Profile-Pregnancy scale algorithm for low-risk populations was mostly highly predictive of substance use in the validation subsample (Akaike’s Information Criterion=579.75, Nagelkerke R2=0.27) with high sensitivity (91%) and adequate specificity (67%). The high-risk algorithm had lower sensitivity (57%) but higher specificity (88%). CONCLUSION The Substance Use Risk Profile-Pregnancy scale is simple and flexible with good sensitivity and specificity. The Substance Use Risk Profile-Pregnancy scale can potentially detect a range of substances that may be abused. Clinicians need to further assess women with a positive screen to identify those who require treatment for alcohol or illicit substance use in pregnancy. PMID:20859145

Performance of a Novel Algorithm Using Automated Digital Microscopy for Diagnosing Tuberculosis.

PubMed

Ismail, Nazir A; Omar, Shaheed V; Lewis, James J; Dowdy, David W; Dreyer, Andries W; van der Meulen, Hermina; Nconjana, George; Clark, David A; Churchyard, Gavin J

2015-06-15

TBDx automated microscopy is a novel technology that processes digital microscopic images to identify acid-fast bacilli (AFB). Use of TBDx as part of a diagnostic algorithm could improve the diagnosis of tuberculosis (TB), but its performance characteristics have not yet been formally tested. To evaluate the performance of the TBDx automated microscopy system in algorithms for diagnosis of TB. Prospective samples from patients with presumed TB were processed in parallel with conventional smear microscopy, TBDx microscopy, and liquid culture. All TBDx-positive specimens were also tested with the Xpert MTB/RIF (GXP) assay. We evaluated the sensitivity and specificity of two algorithms-(1) TBDx-GXP (TBDx with positive specimens tested by Xpert MTB/RIF) and (2) TBDx alone-against the gold standard liquid media culture. Of 1,210 samples, 1,009 were eligible for evaluation, of which 109 were culture positive for Mycobacterium tuberculosis. The TBDx system identified 70 specimens (68 culture positive) as having 10 or more putative AFB (high positive) and 207 (19 culture positive) as having 1-9 putative AFB (low positive). An algorithm in which "low-positive" results on TBDx were confirmed by GXP had 78% sensitivity (85 of 109) and 99.8% specificity (889 of 900), requiring 21% (207 of 1,009) specimens to be processed by GXP. As a stand-alone test, a "high-positive" result on TBDx had 62% sensitivity and 99.7% specificity. TBDx used in diagnostic algorithms with GXP provided reasonable sensitivity and high specificity for active TB while dramatically reducing the number GXP tests performed. As a stand-alone microscopy system, its performance was equivalent to that of a highly experienced TB microscopist.

Performance of FDG-PET/CT in solitary pulmonary nodule based on pre-test likelihood of malignancy: results from the ITALIAN retrospective multicenter trial.

PubMed

Evangelista, Laura; Cuocolo, Alberto; Pace, Leonardo; Mansi, Luigi; Del Vecchio, Silvana; Miletto, Paolo; Sanfilippo, Silvia; Pellegrino, Sara; Guerra, Luca; Pepe, Giovanna; Peluso, Giuseppina; Salvatore, Marco; Galicchio, Rosj; Zuffante, Michele; Annunziata, Salvatore; Farsad, Mohsen; Chiaravalloti, Agostino; Spadafora, Marco

2018-05-07

The aim of this study was to determine the performance of 18 F-FDG-PET/CT in patients with solitary pulmonary nodule (SPN), stratifying the risk according to the likelihood of pulmonary malignancy. FDG-PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. FDG uptake in SPN was assessed by a 4-point scoring system and semiquantitative analysis using the ratio between SUVmax in SPN and SUVmean in mediastinal blood pool (BP) and between SUVmax in SPN and SUVmean in liver (L). Histopathology and/or follow-up data were used as standard of reference. SPN was malignant in 180 (36%) patients, benign in 175 (35%), and indeterminate in 147 (29%). The 355 patients with a definitive SPN nature (malignant or benign) were considered for the analysis. Considering FDG uptake ≥ 2, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy were 85.6%, 85.7%, 86%, 85.2%, and 85.6% respectively. Sensitivity and PPV were higher (P < 0.05) in intermediate and high-risk patients, while specificity and NPV were higher (P < 0.05) in low-risk patients. On receiver operating characteristic curve analysis, the cut-offs for better discrimination between benign and malignant SPN were 1.56 (sensitivity 81% and specificity 87%) and 1.12 (sensitivity 81% and specificity 86%) for SUVmax/SUVmeanBP and SUVmax/SUVmeanL respectively. In intermediate and high-risk patients, including the SUVmax/SUVmeanBP, the specificity shifted from 85% and 50% to 100%. Visual FDG-PET/CT has an acceptable performance in patients with SPN, but accuracy improves when SUVratios are considered, particularly in patients with intermediate and high risk of malignancy.

Efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability.

PubMed

Nakagawa, Hitoshi; Nagasaka, Takeshi; Cullings, Harry M; Notohara, Kenji; Hoshijima, Naoko; Young, Joanne; Lynch, Henry T; Tanaka, Noriaki; Matsubara, Nagahide

2009-06-01

It is sometimes difficult to diagnose Lynch syndrome by the simple but strict clinical criteria, or even by the definitive genetic testing for causative germline mutation of mismatch repair genes. Thus, some practical and efficient screening strategy to select highly possible Lynch syndrome patients is exceedingly desirable. We performed a comprehensive study to evaluate the methylation status of whole MLH1 promoter region by direct bisulfite sequencing of the entire MLH1 promoter regions on Lynch and non-Lynch colorectal cancers (CRCs). Then, we established a convenient assay to detect methylation in key CpG islands responsible for the silencing of MLH1 expression. We studied the methylation status of MLH1 as well as the CpG island methylator phenotype (CIMP) and immunohistochemical analysis of mismatch repair proteins on 16 cases of Lynch CRC and 19 cases of sporadic CRCs with high-frequency microsatellite instability (MSI-H). Sensitivity to detect Lynch syndrome by MLH1 (CCAAT) methylation was 88% and the specificity was 84%. Positive likelihood ratio (PLR) was 5.5 and negative likelihood ratio (NLR) was 0.15. Sensitivity by mutational analysis of BRAF was 100%, specificity was 84%, PLR was 6.3 and NLR was zero. By CIMP analysis; sensitivity was 88%, specificity was 79%, PLR was 4.2, and NLR was 0.16. BRAF mutation or MLH1 methylation analysis combined with MSI testing could be a good alternative to screen Lynch syndrome patients in a cost effective manner. Although the assay for CIMP status also showed acceptable sensitivity and specificity, it may not be practical because of its rather complicated assay.

IRAS: High-Throughput Identification of Novel Alternative Splicing Regulators.

PubMed

Zheng, S

2016-01-01

Alternative splicing is a fundamental regulatory process of gene expression. Defects in alternative splicing can lead to various diseases, and modification of disease-causing splicing events presents great therapeutic promise. Splicing outcome is commonly affected by extracellular stimuli and signaling cascades that converge on RNA-binding splicing regulators. These trans-acting factors recognize cis-elements in pre-mRNA transcripts to affect spliceosome assembly and splice site choices. Identification of these splicing regulators and/or upstream modulators has been difficult and traditionally done by piecemeal. High-throughput screening strategies to find multiple regulators of exon splicing have great potential to accelerate the discovery process, but typically confront low sensitivity and low specificity of screening assays. Here we describe a unique screening strategy, IRAS (identifying regulators of alternative splicing), using a pair of dual-output minigene reporters to allow for sensitive detection of exon splicing changes. Each dual-output reporter produces green fluorescent protein (GFP) and red fluorescent protein (RFP) fluorescent signals to assay the two spliced isoforms exclusively. The two complementary minigene reporters alter GFP/RFP output ratios in the opposite direction in response to splicing change. Applying IRAS in cell-based high-throughput screens allows sensitive and specific identification of splicing regulators and modulators for any alternative exons of interest. In comparison to previous high-throughput screening methods, IRAS substantially enhances the specificity of the screening assay. This strategy significantly eliminates false positives without sacrificing sensitive identification of true regulators of splicing. © 2016 Elsevier Inc. All rights reserved.

A virus-MIPs fluorescent sensor based on FRET for highly sensitive detection of JEV.

PubMed

Liang, Caishuang; Wang, Huan; He, Kui; Chen, Chunyan; Chen, Xiaoming; Gong, Hang; Cai, Changqun

2016-11-01

Major stumbling blocks in the recognition and detection of virus are the unstable biological recognition element or the complex detection means. Here a fluorescent sensor based on virus-molecular imprinted polymers (virus-MIPs) was designed for specific recognition and highly sensitive detection of Japanese encephalitis virus (JEV). The virus-MIPs were anchored on the surface of silica microspheres modified by fluorescent dye, pyrene-1-carboxaldehyde (PC). The fluorescence intensity of PC can be enhanced by the principle of fluorescence resonance energy transfer (FRET), where virus acted as energy donor and PC acted as energy acceptor. The enhanced fluorescence intensity was proportional to the concentration of virus in the range of 24-960pM, with a limit of detection (LOD, 3σ) of 9.6pM, and the relative standard deviation was 1.99%. In additional, the specificity study confirmed the resultant MIPs has high-selectivity for JEV. This sensor would become a new key for the detection of virus because of its high sensitive, simple operation, high stability and low cost. Copyright © 2016. Published by Elsevier B.V.

Rhabdomyolysis and acute kidney injury: creatine kinase as a prognostic marker and validation of the McMahon Score in a 10-year cohort: A retrospective observational evaluation.

PubMed

Simpson, Joanna P; Taylor, Andrew; Sudhan, Nazneen; Menon, David K; Lavinio, Andrea

2016-12-01

High-volume fluid resuscitation and the administration of sodium bicarbonate and diuretics have a theoretical renoprotective role in patients at high risk of acute kidney injury (AKI) following rhabdomyolysis. Abnormally elevated creatine kinase has previously been used as a biological marker for the identification of patients at high risk of AKI following rhabdomyolysis. To assess the sensitivity and specificity of plasma creatine kinase (admission and peak values) for the prediction of AKI requiring renal replacement therapy (RRT) or of death in patients with confirmed rhabdomyolysis. To compare the diagnostic performance of creatine kinase with the McMahon score. Retrospective observational study. Data collection included McMahon and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores; daily creatine kinase; daily creatinine and electrolytes; ICU length of stay and mortality. Neurosciences and Trauma Critical Care Unit (Cambridge, UK). In total, 232 adults with confirmed rhabdomyolysis (creatine kinase > 1000 Ul) admitted to Neurosciences and Trauma Critical Care Unit between 2002 and 2012. AKI, RRT and mortality. Forty-five (19%) patients developed AKI and 29 (12.5%) patients required RRT. Mortality was significantly higher in patients who developed AKI (62 vs. 18%, P < 0.001). Average creatine kinase on admission was 5009 (range 69-157 860) Ul. Creatine kinase peaked between the day of admission and day 3 in 91% of cases. PEAK creatine kinase of at least 5000 Ul is 55% specific and 83% sensitive for the prediction of AKI requiring RRT. A McMahon Score of at least 6 calculated on admission is 68% specific and 86% sensitive for RRT. Creatine kinase is not a specific or early predictor of AKI in patients with rhabdomyolysis. Although a PEAK creatine kinase of at least 5000 Ul has sensitivity acceptable for screening purposes, this is often a delayed finding. A McMahon score of at least 6 calculated on admission allows for a more sensitive, specific and timely identification of patients who may benefit from high-volume fluid resuscitation.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in the screening of diabetes and impaired glucose tolerance.

PubMed

Hu, Yaomin; Liu, Wei; Chen, Yawen; Zhang, Ming; Wang, Lihua; Zhou, Huan; Wu, Peihong; Teng, Xiangyu; Dong, Ying; Zhou, Jia wen; Xu, Hua; Zheng, Jun; Li, Shengxian; Tao, Tao; Hu, Yumei; Jia, Yun

2010-09-01

The aim of this study is to assess the validity of combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298 subjects were included. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve) analysis was used to examine the sensitivity and specificity of FPG and HbA1c for detecting diabetes and IGT, which was defined according to the 1999 World Health Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was associated with a sensitivity and specificity of 81.0 and 81.0%, respectively; The screening model using FPG > or = 6.1 mmol/l or HbA1c > or = 6.1% had sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model using FPG > or = 6.1 mmol/l and HbA1c > or = 6.1% had specificity of 96.3% for detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening model using FPG > or = 5.6 mmol/l or HbA1c > or = 5.6% had sensitivity of 87.9% for detecting undiagnosed IGT; The screening model using FPG > or = 5.6 mmol/l and HbA1c > or = 5.6% had specificity of 82.4% for detecting undiagnosed IGT. Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c (FPG and/or HbA1C) might be a more sensitive and specific screening tool for identifying high-risk individuals with diabetes and IGT at an early stage.

Detection of CIN by naked eye visualization after application of acetic acid.

PubMed

Londhe, M; George, S S; Seshadri, L

1997-06-01

A prospective study was undertaken to determine the sensitivity and specificity of acetic application to the cervix followed by naked eye visualization as a screening test for detection of cervical intraepithelial neoplasia. Three hundred and seventy two sexually active woman in the reproductive age group were studied. All the women underwent Papanicolaou test, acetic acid test and colposcopy. One hundred and seventy five woman were acetic acid test negative, 197 women were acetic acid test positive. The sensitivity of acetic acid test was 72.4%, specificity 54% and false negative rate 15.2%, as compared to papanicolaou test which had a sensitivity of 13.2%, specificity of 96.3% and false negative rate of 24.4%. The advantage of the acetic acid test lies in its easy technique, low cost and high sensitivity which are important factors for determining the efficacy of any screening programme in developing countries.

A preliminary study of screening for risk of autism in children with fragile X syndrome: testing two risk cut-offs for the Checklist for Autism in Toddlers.

PubMed

Scambler, D J; Hepburn, S L; Hagerman, R J; Rogers, S J

2007-04-01

Risk criteria for the Checklist for Autism in Toddlers (CHAT) and modified risk criteria (i.e. the Denver Criteria) were compared in a group of children with fragile X syndrome (FXS) and autism. Participants were 17 children aged 2-4 years with DNA confirmation of FXS. Four children had autism and 13 children did not. Preliminary findings regarding the sensitivity and specificity of the CHAT for detecting risk for autism in children with FXS are as follows: using the original CHAT risk criteria, sensitivity and specificity were 50% and 100%, respectively; and using the Denver Criteria, sensitivity and specificity were 75% and 92%, respectively. The CHAT and the Denver Criteria resulted in preliminary findings suggesting high levels of sensitivity to autism in children with FXS.

Sensitivity and specificity of real-time PCR and bacteriological culture for francisellosis in farm-raised Nile tilapia (Oreochromis niloticus L.).

PubMed

Assis, G B N; de Oliveira, T F; Gardner, I A; Figueiredo, H C P; Leal, C A G

2017-06-01

Despite the worldwide occurrence of Francisella noatunensis subsp. orientalis (Fno) infection in farmed tilapia, sensitivity and specificity estimates of commonly used diagnostic tests have not been reported. This study aimed to estimate the sensitivity and specificity of bacteriological culture and qPCR to detect Fno infection. We tested 559 fish, sampled from four farms with different epidemiological scenarios: (i) healthy fish in a hatchery free of Fno; (ii) targeted sampling of diseased fish with suggestive external clinical signs of francisellosis during an outbreak; (iii) convenience sampling of diseased and clinically healthy fish during an outbreak; and (iv) sampling of healthy fish in a cage farm without a history of outbreaks, but with francisellosis reported in other farms in the same reservoir. The qPCR had higher median sensitivity (range, 48.8-99.5%) than culture (range, 1.6-74.4%). Culture had a substantially lower median sensitivity (1.6%) than qPCR (48.8%) to detect Fno in carrier tilapia (farm 4). Median specificity estimates for both tests were >99.2%. The qPCR is the superior test for use in surveillance and monitoring programmes for francisellosis in farmed Nile tilapia, but both tests have high sensitivity and specificity which make them fit for use in the diagnosis of Fno outbreaks. © 2016 John Wiley & Sons Ltd.

Anthropometric indicators of obesity as screening tools for high blood pressure in the elderly.

PubMed

Leal Neto, João de Souza; Coqueiro, Raildo da Silva; Freitas, Roberta Souza; Fernandes, Marcos Henrique; Oliveira, Daniela Sousa; Barbosa, Aline Rodrigues

2013-08-01

The study objectives were to investigate the indicators of obesity most associated with high blood pressure in community-dwelling elderly and identify among these which one best discriminates high blood pressure. This is an epidemiological, population, cross-sectional and home-based study of elderly people (≥ 60 years, n = 316) residing in northeastern Brazil. The results showed that the body mass index and the body adiposity index were the indicators more closely associated with high blood pressure in both sexes. Both in female and male genders, body mass index showed high values of specificity and low sensitivity values for discriminating high blood pressure, whereas the body adiposity index showed high sensitivity and moderate specificity values. In clinical practice and health surveillance, it is suggested that both indicators be used as screening tools for hypertension in the elderly. © 2013 Wiley Publishing Asia Pty Ltd.

All-carbon suspended nanowire sensors as a rapid highly-sensitive label-free chemiresistive biosensing platform.

PubMed

Thiha, Aung; Ibrahim, Fatimah; Muniandy, Shalini; Dinshaw, Ignatius Julian; Teh, Swe Jyan; Thong, Kwai Lin; Leo, Bey Fen; Madou, Marc

2018-06-01

Nanowire sensors offer great potential as highly sensitive electrochemical and electronic biosensors because of their small size, high aspect ratios, and electronic properties. Nevertheless, the available methods to fabricate carbon nanowires in a controlled manner remain limited to expensive techniques. This paper presents a simple fabrication technique for sub-100 nm suspended carbon nanowire sensors by integrating electrospinning and photolithography techniques. Carbon Microelectromechanical Systems (C-MEMS) fabrication techniques allow fabrication of high aspect ratio carbon structures by patterning photoresist polymers into desired shapes and subsequent carbonization of resultant structures by pyrolysis. In our sensor platform, suspended nanowires were deposited by electrospinning while photolithography was used to fabricate support structures. We have achieved suspended carbon nanowires with sub-100 nm diameters in this study. The sensor platform was then integrated with a microfluidic chip to form a lab-on-chip device for label-free chemiresistive biosensing. We have investigated this nanoelectronics label-free biosensor's performance towards bacterial sensing by functionalization with Salmonella-specific aptamer probes. The device was tested with varying concentrations of Salmonella Typhimurium to evaluate sensitivity and various other bacteria to investigate specificity. The results showed that the sensor is highly specific and sensitive in detection of Salmonella with a detection limit of 10 CFU mL -1 . Moreover, this proposed chemiresistive assay has a reduced turnaround time of 5 min and sample volume requirement of 5 µL which are much less than reported in the literature. Copyright © 2018 Elsevier B.V. All rights reserved.

Digital-Direct-RT-PCR: a sensitive and specific method for quantification of CTC in patients with cervical carcinoma.

PubMed

Pfitzner, Claudia; Schröder, Isabel; Scheungraber, Cornelia; Dogan, Askin; Runnebaum, Ingo Bernhard; Dürst, Matthias; Häfner, Norman

2014-02-05

The detection of circulating tumour cells (CTC) in cancer patients may be useful for therapy monitoring and prediction of relapse. A sensitive assay based on HPV-oncogene transcripts which are highly specific for cervical cancer cells was established. The Digital-Direct-RT-PCR (DD-RT-PCR) combines Ficoll-separation, ThinPrep-fixation and one-step RT-PCR in a low-throughput digital-PCR format enabling the direct analysis and detection of individual CTC without RNA isolation. Experimental samples demonstrated a sensitivity of one HPV-positive cell in 500,000 HPV-negative cells. Spike-in experiments with down to 5 HPV-positive cells per millilitre EDTA-blood resulted in concordant positive results by PCR and immunocytochemistry. Blood samples from 3 of 10 CxCa patients each contained a single HPV-oncogene transcript expressing CTC among 5 to 15*10(5) MNBC. Only 1 of 7 patients with local but 2 of 3 women with systemic disease had CTC. This highly sensitive DD-RT-PCR for the detection of CTC may also be applied to other tumour entities which express tumour-specific transcripts.

Development of a highly specific enzyme immunoassay for oxytocin and its use in plasma samples.

PubMed

Haraya, Shiomi; Karasawa, Koji; Sano, Yoshihiro; Ozawa, Kimiko; Kato, Nobumasa; Arakawa, Hidetoshi

2017-01-01

Background The peptide hormone oxytocin acts in the central nervous system and plays an important role in various complex social behaviours. We report the production of a high affinity and specificity antibody for oxytocin and its use in a highly sensitive enzyme immunoassay. Biotin that was chemically bound to oxytocin derivative containing zero to six lysines as bridge was the labelled antigen. Seven labelled antigens were used to develop a highly sensitive enzyme immunoassay. Methods Antioxytocin antiserum was obtained by immunization of oxytocin-bovine thyrogloblin conjugate to rabbit. Oxytocin sample was added to the second antibody-coated microtitre plate and allowed to react overnight at 4℃, then biotinylated oxytocin was added 1 h at 4℃, and horseradish peroxidase-labelled avidin was added and incubated for 1 h at room temperature. The plate was then washed. Horseradish peroxidase activity was measured by a colorimetric method using o-phenylenediamine (490 nm). Results The sensitivity of the enzyme immunoassay improved as the number of lysine residues increased; consequently, biotinylated oxytocin bridged with five lysines was used. A standard curve for oxytocin ranged from 1.0 to 1000 pg/assay. The detection limit of the assay was 2.36 pg, and the reproducibility was 3.6% as CV% ( n = 6). Cross-reactivity with vasopressin and vasotocin was less than 0.01%. Conclusion The sensitivity of the enzyme immunoassay could be improved by increasing the number of lysine residues on the biotin-labelled antigen. The proposed method is sensitive and more specific than conventional immunoassays for oxytocin and can be used to determine plasma oxytocin concentrations.

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography

PubMed Central

Ernst, Marielle; Romero, Javier M.; Buhk, Jan-Hendrik; Cheng, Bastian; Herrmann, Jochen; Fiehler, Jens; Groth, Michael

2015-01-01

Purpose The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO. Materials and Methods 102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio. Results Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%). Conclusion In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT. PMID:26479718

Rapid concentration and sensitive detection of hookworm ova from wastewater matrices using a real-time PCR method.

PubMed

Gyawali, P; Sidhu, J P S; Ahmed, W; Jagals, P; Toze, S

2015-12-01

The risk of human hookworm infections from land application of wastewater matrices could be high in regions with high hookworm prevalence. A rapid, sensitive and specific hookworm detection method from wastewater matrices is required in order to assess human health risks. Currently available methods used to identify hookworm ova to the species level are time consuming and lack accuracy. In this study, a real-time PCR method was developed for the rapid, sensitive and specific detection of canine hookworm (Ancylostoma caninum) ova from wastewater matrices. A. caninum was chosen because of its morphological similarity to the human hookworm (Ancylostoma duodenale and Necator americanus). The newly developed PCR method has high detection sensitivity with the ability to detect less than one A. caninum ova from 1 L of secondary treated wastewater at the mean threshold cycle (CT) values ranging from 30.1 to 34.3. The method is also able to detect four A. caninum ova from 1 L of raw wastewater and from ∼4 g of treated sludge with mean CT values ranging from 35.6 to 39.8 and 39.8 to 39.9, respectively. The better detection sensitivity obtained for secondary treated wastewater compared to raw wastewater and sludge samples could be attributed to sample turbidity. The proposed method appears to be rapid, sensitive and specific compared to traditional methods and has potential to aid in the public health risk assessment associated with land application of wastewater matrices. Furthermore, the method can be adapted to detect other helminth ova of interest from wastewater matrices. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Highly labeled methylene blue-ds DNA silica nanoparticles for signal enhancement of immunoassays: application to the sensitive detection of bacteria in human platelet concentrates.

PubMed

Bonnet, Romaric; Farre, Carole; Valera, Lionel; Vossier, Ludivine; Léon, Fanny; Dagland, Typhaine; Pouzet, Agnès; Jaffrézic-Renault, Nicole; Fareh, Jeannette; Fournier-Wirth, Chantal; Chaix, Carole

2018-05-15

A nanoparticle-based electrochemical sandwich immunoassay was developed for bacteria detection in platelet concentrates. For the assay, magnetic beads were functionalized with antibodies to allow the specific capture of bacteria from the complex matrix, and innovative methylene blue-DNA/nanoparticle assemblies provided the electrochemical response for amplified detection. This nanoparticular system was designed as a temperature-sensitive nano-tool for electrochemical detection. First, oligonucleotide-functionalized nanoparticles were obtained by direct synthesis of the DNA strands on the nanoparticle surface using an automated oligonucleotide synthesizer. Densely packed DNA coverage was thus obtained. Then, DNA duplexes were constructed on the NP surface with a complementary strand bearing a 3 methylene blue tag. This strategy ultimately produced highly functionalized nanoparticles with electrochemical markers. These assemblies enabled amplification of the electrochemical signal, resulting in a very good sensitivity. A proof-of-concept was carried out for E. coli detection in human platelet concentrates. Bacterial contamination of this complex biological matrix is the highest residual infectious risk in blood transfusion. The development of a rapid assay that could reach 10-102 CFU mL-1 sensitivity is a great challenge. The nanoparticle-based electrochemical sandwich immunoassay carried out on a boron doped diamond electrode proved to be sensitive for E. coli detection in human platelets. Two antibody pairs were used to develop either a generic assay against certain Gram negative strains or a specific assay for E. coli. The methylene blue-DNA/nanoparticles amplify sensitivity ×1000 compared with the assay run without NPs for electrochemical detection. A limit of detection of 10 CFU mL-1 in a biological matrix was achieved for E. coli using the highly specific antibody pair.

Simultaneous ultramicroanalysis of both 17-keto-and 17beta-hydroxy androgens in biological fluids.

PubMed

Ganjam, V K

1976-11-01

Sensitive methods for quantifying androgens were lacking. Therefore, a relatively simple procedure for separating steroids was combined with highly specific assay methods so that eight androgens could be measured with high accuracy, precision and sensitivity. Semi-automated separations on Sephadex LH-20 columns used heptane:methylene chloride:ethanol:water (50:50:1:0.12) and a flow rate of 17.0 min/ml. The six peaks eluted contained androstenedine; androsterone, epiandrosterone and dihydrotestosterone; testosterone and dehydroepiandrosterone; 3alpha-androstanediol; 3beta-androstanediol; and androstenediol. Androstenedione, dehydroepiandrosterone and androstenediol were quantified using specific antisera (sensitivity less than or equal to 75 pg). Testosterone and dihydrotestosterone were measured by competitive protein-binding assays using rabbit TeBG (sensitivity less than or equal to 150 pg). 3alpha- and 3beta-androstanediol were similarly assayed using human TeBG (sensitivity approximately 150 pg). Androsterone was reduced with NaBH4 and the resulting 3alpha-androstanediol was assayed using human TeBG (sensitivity approximately 200 pg). Inter- and intra-assay variations were less than 10% for radioimmunoassays and less than 16% for competitive protein-binding assays over the entire dose response curve.

Diagnostic Performance of CT for Diagnosis of Fat-Poor Angiomyolipoma in Patients With Renal Masses: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Cho, Jeong Yeon; Kim, Sang Youn; Kim, Seung Hyup

2017-11-01

The purpose of this article is to systematically review and perform a meta-analysis of the diagnostic performance of CT for diagnosis of fat-poor angiomyolipoma (AML) in patients with renal masses. MEDLINE and EMBASE were systematically searched up to February 2, 2017. We included diagnostic accuracy studies that used CT for diagnosis of fat-poor AML in patients with renal masses, using pathologic examination as the reference standard. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity of included studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Sensitivity analyses using several clinically relevant covariates were performed to explore heterogeneity. Fifteen studies (2258 patients) were included. Pooled sensitivity and specificity were 0.67 (95% CI, 0.48-0.81) and 0.97 (95% CI, 0.89-0.99), respectively. Substantial and considerable heterogeneity was present with regard to sensitivity and specificity (I 2 = 91.21% and 78.53%, respectively). At sensitivity analyses, the specificity estimates were comparable and consistently high across all subgroups (0.93-1.00), but sensitivity estimates showed significant variation (0.14-0.82). Studies using pixel distribution analysis (n = 3) showed substantially lower sensitivity estimates (0.14; 95% CI, 0.04-0.40) compared with the remaining 12 studies (0.81; 95% CI, 0.76-0.85). CT shows moderate sensitivity and excellent specificity for diagnosis of fat-poor AML in patients with renal masses. When methods other than pixel distribution analysis are used, better sensitivity can be achieved.

Combining Parasite Lactate Dehydrogenase-Based and Histidine-Rich Protein 2-Based Rapid Tests To Improve Specificity for Diagnosis of Malaria Due to Plasmodium knowlesi and Other Plasmodium Species in Sabah, Malaysia

PubMed Central

William, Timothy; Barber, Bridget E.; Parameswaran, Uma; Bird, Elspeth; Piera, Kim; Aziz, Ammar; Dhanaraj, Prabakaran; Yeo, Tsin W.; Anstey, Nicholas M.

2014-01-01

Plasmodium knowlesi causes severe and fatal malaria in Malaysia. Microscopic misdiagnosis is common and may delay appropriate treatment. P. knowlesi can cross-react with “species-specific” parasite lactate dehydrogenase (pLDH) monoclonal antibodies used in rapid diagnostic tests (RDTs) to detect P. falciparum and P. vivax. At one tertiary-care hospital and two district hospitals in Sabah, we prospectively evaluated two combination RDTs for malaria diagnosis by using both a pan-Plasmodium-pLDH (pan-pLDH)/P. falciparum-specific-pLDH (Pf-pLDH) RDT (OptiMAL-IT) and a non-P. falciparum VOM-pLDH/Pf-HRP2 RDT (CareStart). Differential cross-reactivity among these combinations was hypothesized to differentiate P. knowlesi from other Plasmodium monoinfections. Among 323 patients with PCR-confirmed P. knowlesi (n = 193), P. falciparum (n = 93), and P. vivax (n = 37) monoinfections, the VOM-pLDH individual component had the highest sensitivity for nonsevere (35%; 95% confidence interval [CI], 27 to 43%) and severe (92%; CI, 81 to 100%) P. knowlesi malaria. CareStart demonstrated a P. knowlesi sensitivity of 42% (CI, 34 to 49%) and specificity of 74% (CI, 65 to 82%), a P. vivax sensitivity of 83% (CI, 66 to 93%) and specificity of 71% (CI, 65 to 76%), and a P. falciparum sensitivity of 97% (CI, 90 to 99%) and specificity of 99% (CI, 97 to 100%). OptiMAL-IT demonstrated a P. knowlesi sensitivity of 32% (CI, 25 to 39%) and specificity of 21% (CI, 15 to 29%), a P. vivax sensitivity of 60% (CI, 42 to 75%) and specificity of 97% (CI, 94 to 99%), and a P. falciparum sensitivity of 82% (CI, 72 to 89%) and specificity of 39% (CI, 33 to 46%). The combination of CareStart plus OptiMAL-IT for P. knowlesi using predefined criteria gave a sensitivity of 25% (CI, 19 to 32%) and specificity of 97% (CI, 92 to 99%). Combining two RDT combinations was highly specific for P. knowlesi malaria diagnosis; however, sensitivity was poor. The specificity of pLDH RDTs was decreased for P. vivax and P. falciparum because of P. knowlesi cross-reactivity and cautions against their use alone in areas where P. knowlesi malaria is endemic. Sensitive P. knowlesi-specific RDTs and/or alternative molecular diagnostic tools are needed in areas where P. knowlesi malaria is endemic. PMID:24696029

Robust Detection of Rare Species Using Environmental DNA: The Importance of Primer Specificity

PubMed Central

Wilcox, Taylor M.; McKelvey, Kevin S.; Young, Michael K.; Jane, Stephen F.; Lowe, Winsor H.; Whiteley, Andrew R.; Schwartz, Michael K.

2013-01-01

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method’s sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design. PMID:23555689

Robust detection of rare species using environmental DNA: the importance of primer specificity.

PubMed

Wilcox, Taylor M; McKelvey, Kevin S; Young, Michael K; Jane, Stephen F; Lowe, Winsor H; Whiteley, Andrew R; Schwartz, Michael K

2013-01-01

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method's sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design.

Derivation of data-driven triggers for palliative care consultation in critically ill patients.

PubMed

Hua, May S; Ma, Xiaoyue; Li, Guohua; Wunsch, Hannah

2018-04-30

To examine the ability of existing triggers for intensive care unit (ICU) palliative care consultation to predict 6-month mortality, and derive new triggers for consultation based on risk factors for 6-month mortality. Retrospective cohort study of NY state residents who received intensive care, 2008-2013. We examined sensitivity and specificity of existing triggers for predicting 6-month mortality and used logistic regression to generate patient subgroups at high-risk for 6-month mortality as potential novel triggers for ICU palliative care consultation. Of 1,019,849 patients, 195,847 (19.2%) died within 6 months of admission. Existing triggers were specific but not sensitive for predicting 6-month mortality, (sensitivity 0.3%-11.1%, specificity 96.5-99.9% for individual triggers). Using logistic regression, patient subgroups with the highest predicted probability of 6-month mortality were older patients admitted with sepsis (age 70-79 probability 49.7%, [49.5-50.0]) or cancer (non-metastatic cancer, age 70-79 probability 51.5%, [51.1-51.9]; metastatic cancer, age 70-79 probability 60.3%, [59.9-60.6]). Sensitivity and specificity of novel triggers ranged from 0.05% to 9.2% and 98.6% to 99.9%, respectively. Existing triggers for palliative care consultation are specific, but insensitive for 6-month mortality. Using a data-driven approach to derive novel triggers may identify subgroups of patients at high-risk of 6-month mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Diagnostic performance of serological tests to detect antibodies against acute scrub typhus infection in central India.

PubMed

Pote, Kiran; Narang, Rahul; Deshmukh, Pradeep

2018-01-01

Differentiating scrub typhus from other acute febrile illness is difficult due to non specificity of clinical symptoms and relative absence of eschar in Indian population. The diagnosis thus relies mainly on laboratory tests. Antibody based serological tests are mainstay of scrub typhus diagnosis. Here, we evaluated the diagnostic performance of IgM ELISA, IgM IFA and ICT to detect antibodies against O. tsutsugamushi in acute serum of febrile patients. The serum samples from 600 randomly selected patients suffering from acute undifferentiated fever were tested by all the three tests mentioned above. We used latent class analysis to generate unbiased results as all the tests for scrub typhus diagnosis are imperfect and none of them can be considered as reference standard. We found that IgM ELISA with cutoff titer 0.5 OD has high diagnostic accuracy (sensitivity 99.9% and specificity 99.15) than IgM IFA (sensitivity 96.8% and specificity 99.7%) for scrub typhus diagnosis. ICT used in our study had very high specificity 100% but low sensitivity (38%) which would limit its use for acute serum samples. ICT being a screening or point of care test, has to be more sensitive while some compromise with specificity is affordable. Hence, optimal cutoff for ICT should be evaluated under different settings. IgM ELISA being simple and affordable could be an alternative diagnostic test to IgM IFA which is subjective and costly.

Identification of prostate cancer biomarkers in urinary exosomes

PubMed Central

Øverbye, Anders; Skotland, Tore; Koehler, Christian J.; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2015-01-01

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer. PMID:26196085

Identification of prostate cancer biomarkers in urinary exosomes.

PubMed

Øverbye, Anders; Skotland, Tore; Koehler, Christian J; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

2015-10-06

Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.

A 3-Year Study of Predictive Factors for Positive and Negative Appendicectomies.

PubMed

Chang, Dwayne T S; Maluda, Melissa; Lee, Lisa; Premaratne, Chandrasiri; Khamhing, Srisongham

2018-03-06

Early and accurate identification or exclusion of acute appendicitis is the key to avoid the morbidity of delayed treatment for true appendicitis or unnecessary appendicectomy, respectively. We aim (i) to identify potential predictive factors for positive and negative appendicectomies; and (ii) to analyse the use of ultrasound scans (US) and computed tomography (CT) scans for acute appendicitis. All appendicectomies that took place at our hospital from the 1st of January 2013 to the 31st of December 2015 were retrospectively recorded. Test results of potential predictive factors of acute appendicitis were recorded. Statistical analysis was performed using Fisher exact test, logistic regression analysis, sensitivity, specificity, and positive and negative predictive values calculation. 208 patients were included in this study. 184 patients had histologically proven acute appendicitis. The other 24 patients had either nonappendicitis pathology or normal appendix. Logistic regression analysis showed statistically significant associations between appendicitis and white cell count, neutrophil count, C-reactive protein, and bilirubin. Neutrophil count was the test with the highest sensitivity and negative predictive values, whereas bilirubin was the test with the highest specificity and positive predictive values (PPV). US and CT scans had high sensitivity and PPV for diagnosing appendicitis. No single test was sufficient to diagnose or exclude acute appendicitis by itself. Combining tests with high sensitivity (abnormal neutrophil count, and US and CT scans) and high specificity (raised bilirubin) may predict acute appendicitis more accurately.

Quantitative Analysis of Swallowing Function Between Dysphagia Patients and Healthy Subjects Using High-Resolution Manometry

PubMed Central

2017-01-01

Objective To compare swallowing function between healthy subjects and patients with pharyngeal dysphagia using high resolution manometry (HRM) and to evaluate the usefulness of HRM for detecting pharyngeal dysphagia. Methods Seventy-five patients with dysphagia and 28 healthy subjects were included in this study. Diagnosis of dysphagia was confirmed by a videofluoroscopy. HRM was performed to measure pressure and timing information at the velopharynx (VP), tongue base (TB), and upper esophageal sphincter (UES). HRM parameters were compared between dysphagia and healthy groups. Optimal threshold values of significant HRM parameters for dysphagia were determined. Results VP maximal pressure, TB maximal pressure, UES relaxation duration, and UES resting pressure were lower in the dysphagia group than those in healthy group. UES minimal pressure was higher in dysphagia group than in the healthy group. Receiver operating characteristic (ROC) analyses were conducted to validate optimal threshold values for significant HRM parameters to identify patients with pharyngeal dysphagia. With maximal VP pressure at a threshold value of 144.0 mmHg, dysphagia was identified with 96.4% sensitivity and 74.7% specificity. With maximal TB pressure at a threshold value of 158.0 mmHg, dysphagia was identified with 96.4% sensitivity and 77.3% specificity. At a threshold value of 2.0 mmHg for UES minimal pressure, dysphagia was diagnosed at 74.7% sensitivity and 60.7% specificity. Lastly, UES relaxation duration of <0.58 seconds had 85.7% sensitivity and 65.3% specificity, and UES resting pressure of <75.0 mmHg had 89.3% sensitivity and 90.7% specificity for identifying dysphagia. Conclusion We present evidence that HRM could be a useful evaluation tool for detecting pharyngeal dysphagia. PMID:29201816

Assessment of algorithms to identify patients with thrombophilia following venous thromboembolism.

PubMed

Delate, Thomas; Hsiao, Wendy; Kim, Benjamin; Witt, Daniel M; Meyer, Melissa R; Go, Alan S; Fang, Margaret C

2016-01-01

Routine testing for thrombophilia following venous thromboembolism (VTE) is controversial. The use of large datasets to study the clinical impact of thrombophilia testing on patterns of care and patient outcomes may enable more efficient analysis of this practice in a wide range of settings. We set out to examine how accurately algorithms using International Classification of Diseases 9th Revision (ICD-9) codes and/or pharmacy data reflect laboratory-confirmed thrombophilia diagnoses. A random sample of adult Kaiser Permanente Colorado patients diagnosed with unprovoked VTE between 1/2004 and 12/2010 underwent medical record abstraction of thrombophilia test results. Algorithms using "ICD-9" (positive if a thrombophilia ICD-9 code was present), "Extended anticoagulation (AC)" (positive if AC therapy duration was >6 months), and "ICD-9 & Extended AC" (positive for both) criteria to identify possible thrombophilia cases were tested. Using positive thrombophilia laboratory results as the gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value of each algorithm were calculated, along with 95% confidence intervals (CIs). In our cohort of 636 patients, sensitivities were low (<50%) for each algorithm. "ICD-9" yielded the highest PPV (41.5%, 95% CI 26.3-57.9%) and a high specificity (95.9%, 95% CI 94.0-97.4%). "Extended AC" had the highest sensitivity but lowest specificity, and "ICD-9 & Extended AC" had the highest specificity but lowest sensitivity. ICD-9 codes for thrombophilia are highly specific for laboratory-confirmed cases, but all algorithms had low sensitivities. Further development of methods to identify thrombophilia patients in large datasets is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantitative Analysis of Swallowing Function Between Dysphagia Patients and Healthy Subjects Using High-Resolution Manometry.

PubMed

Park, Chul-Hyun; Kim, Don-Kyu; Lee, Yong-Taek; Yi, Youbin; Lee, Jung-Sang; Kim, Kunwoo; Park, Jung Ho; Yoon, Kyung Jae

2017-10-01

To compare swallowing function between healthy subjects and patients with pharyngeal dysphagia using high resolution manometry (HRM) and to evaluate the usefulness of HRM for detecting pharyngeal dysphagia. Seventy-five patients with dysphagia and 28 healthy subjects were included in this study. Diagnosis of dysphagia was confirmed by a videofluoroscopy. HRM was performed to measure pressure and timing information at the velopharynx (VP), tongue base (TB), and upper esophageal sphincter (UES). HRM parameters were compared between dysphagia and healthy groups. Optimal threshold values of significant HRM parameters for dysphagia were determined. VP maximal pressure, TB maximal pressure, UES relaxation duration, and UES resting pressure were lower in the dysphagia group than those in healthy group. UES minimal pressure was higher in dysphagia group than in the healthy group. Receiver operating characteristic (ROC) analyses were conducted to validate optimal threshold values for significant HRM parameters to identify patients with pharyngeal dysphagia. With maximal VP pressure at a threshold value of 144.0 mmHg, dysphagia was identified with 96.4% sensitivity and 74.7% specificity. With maximal TB pressure at a threshold value of 158.0 mmHg, dysphagia was identified with 96.4% sensitivity and 77.3% specificity. At a threshold value of 2.0 mmHg for UES minimal pressure, dysphagia was diagnosed at 74.7% sensitivity and 60.7% specificity. Lastly, UES relaxation duration of <0.58 seconds had 85.7% sensitivity and 65.3% specificity, and UES resting pressure of <75.0 mmHg had 89.3% sensitivity and 90.7% specificity for identifying dysphagia. We present evidence that HRM could be a useful evaluation tool for detecting pharyngeal dysphagia.

Diagnosing periprosthetic infection: false-positive intraoperative Gram stains.

PubMed

Oethinger, Margret; Warner, Debra K; Schindler, Susan A; Kobayashi, Hideo; Bauer, Thomas W

2011-04-01

Intraoperative Gram stains have a reported low sensitivity but high specificity when used to help diagnose periprosthetic infections. In early 2008, we recognized an unexpectedly high frequency of apparent false-positive Gram stains from revision arthroplasties. The purpose of this report is to describe the cause of these false-positive test results. We calculated the sensitivity and specificity of all intraoperative Gram stains submitted from revision arthroplasty cases during a 3-month interval using microbiologic cultures of the same samples as the gold standard. Methods of specimen harvesting, handling, transport, distribution, specimen processing including tissue grinding/macerating, Gram staining, and interpretation were studied. After a test modification, results of specimens were prospectively collected for a second 3-month interval, and the sensitivity and specificity of intraoperative Gram stains were calculated. The retrospective review of 269 Gram stains submitted from revision arthroplasties indicated historic sensitivity and specificity values of 23% and 92%, respectively. Systematic analysis of all steps of the procedure identified Gram-stained but nonviable bacteria in commercial broth reagents used as diluents for maceration of periprosthetic membranes before Gram staining and culture. Polymerase chain reaction and sequencing showed mixed bacterial DNA. Evaluation of 390 specimens after initiating standardized Millipore filtering of diluent fluid revealed a reduced number of positive Gram stains, yielding 9% sensitivity and 99% specificity. Clusters of false-positive Gram stains have been reported in other clinical conditions. They are apparently rare related to diagnosing periprosthetic infections but have severe consequences if used to guide treatment. Even occasional false-positive Gram stains should prompt review of laboratory methods. Our observations implicate dead bacteria in microbiologic reagents as potential sources of false-positive Gram stains.

Oxidative status in different settings and with different methodological approaches compared by Receiver Operating Characteristic curve analysis.

PubMed

Cighetti, Giuliana; Bamonti, Fabrizia; Aman, Caroline S; Gregori, Dario; De Giuseppe, Rachele; Novembrino, Cristina; de Liso, Federica; Maiavacca, Rita; Paroni, Rita

2015-01-01

To test the performance of different analytical approaches in highlighting the occurrence of deregulated redox status in various physio-pathological situations. 35 light and 61 heavy smokers, 19 chronic renal failure, 59 kidney transplanted patients, and 87 healthy controls were retrospectively considered for the study. Serum oxidative stress and antioxidant status, assessed by spectrophotometric Reactive Oxygen Metabolites (d-ROMs) and Total Antioxidant Capacity (TAC) tests, respectively, were compared with plasma free (F-MDA) and total (T-MDA) malondialdehyde, both quantified by isotope-dilution-gas chromatography-mass spectrometry (ID-GC-MS). Sensitivity, specificity and cut-off points of T-MDA, F-MDA, d-ROMs and TAC were evaluated by both Receiver Operating Characteristic (ROC) analyses and area under the ROC curve (AUC). Only T-MDA assay showed a clear absence of oxidative stress in controls and significant increase in all patients (AUC 1.00, sensitivity and specificity 100%). Accuracy was good for d-ROMs (AUC 0.87, sensitivity 72.8%, specificity 100%) and F-MDA (AUC 0.82, sensitivity 74.7%, specificity 83.9%), but not high enough for TAC to show in patients impaired antioxidant defense (AUC 0.66, sensitivity 52.0%, specificity 92.9%). This study reveals T-MDA as the best marker to detect oxidative stress, shows the ability of d-ROMs to identify modified oxidative status particularly in the presence of high damages, and evidences the poor TAC performance. d-ROMs and TAC assays could be useful for routine purposes; however, for an accurate clinical data evaluation, their comparison versus a "gold standard method" is required. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Artificial neural networks: Predicting head CT findings in elderly patients presenting with minor head injury after a fall.

PubMed

Dusenberry, Michael W; Brown, Charles K; Brewer, Kori L

2017-02-01

To construct an artificial neural network (ANN) model that can predict the presence of acute CT findings with both high sensitivity and high specificity when applied to the population of patients≥age 65years who have incurred minor head injury after a fall. An ANN was created in the Python programming language using a population of 514 patients ≥ age 65 years presenting to the ED with minor head injury after a fall. The patient dataset was divided into three parts: 60% for "training", 20% for "cross validation", and 20% for "testing". Sensitivity, specificity, positive and negative predictive values, and accuracy were determined by comparing the model's predictions to the actual correct answers for each patient. On the "cross validation" data, the model attained a sensitivity ("recall") of 100.00%, specificity of 78.95%, PPV ("precision") of 78.95%, NPV of 100.00%, and accuracy of 88.24% in detecting the presence of positive head CTs. On the "test" data, the model attained a sensitivity of 97.78%, specificity of 89.47%, PPV of 88.00%, NPV of 98.08%, and accuracy of 93.14% in detecting the presence of positive head CTs. ANNs show great potential for predicting CT findings in the population of patients ≥ 65 years of age presenting with minor head injury after a fall. As a good first step, the ANN showed comparable sensitivity, predictive values, and accuracy, with a much higher specificity than the existing decision rules in clinical usage for predicting head CTs with acute intracranial findings. Copyright © 2016 Elsevier Inc. All rights reserved.

Sensitivity and Specificity of Laser-Scanning In Vivo Confocal Microscopy for Filamentous Fungal Keratitis: Role of Observer Experience.

PubMed

Kheirkhah, Ahmad; Syed, Zeba A; Satitpitakul, Vannarut; Goyal, Sunali; Müller, Rodrigo; Tu, Elmer Y; Dana, Reza

2017-07-01

To determine sensitivity and specificity of laser-scanning in vivo confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with microbial keratitis and to evaluate the effect of observer's imaging experience on these parameters. Retrospective reliability study. This study included 21 patients with filamentous fungal keratitis and 24 patients with bacterial keratitis (as controls). The etiology of infection was confirmed based on the response to specific therapy regardless of culture results. All patients had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany). The images were evaluated for the presence of fungal filaments by 2 experienced observers and 2 inexperienced observers. All observers were masked to the clinical and microbiologic data. The mean number of images obtained per eye was 917 ± 353. The average sensitivity of LS-IVCM for detecting fungal filaments was 71.4% ± 0% for the experienced observers and 42.9% ± 6.7% for the inexperienced observers. The average specificity was 89.6% ± 3.0% and 87.5% ± 17.7% for these 2 groups of observers, respectively. Although there was a good agreement between the 2 experienced observers (κ = 0.77), the inexperienced observers showed only a moderate interobserver agreement (κ = 0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who had positive culture or longer duration of the disease. Although LS-IVCM has a high specificity for diagnosing filamentous fungal keratitis, its sensitivity is moderate and highly dependent on the level of the observer's experience and training with this imaging modality. Copyright © 2017 Elsevier Inc. All rights reserved.

Deciphering the Sensitivity and Specificity of the Implantable Doppler in Free Flap Monitoring.

PubMed

Chang, Edward I; Ibrahim, Amir; Zhang, Hong; Liu, Jun; Nguyen, Alexander T; Reece, Gregory P; Yu, Peirong

2015-11-19

The efficacy of implantable Dopplers (iD) remains an area of considerable debate. Our study aims to decipher the sensitivity and specificity of the iD for free flap monitoring. A retrospective review of all free flaps with an iD was performed between 2000-2012. A Cook-Swartz iD was used in 439 patients (head and neck: n=364, breast: n=53, and extremity: n=22), and demonstrated equivalent sensitivity and specificity between flap types. The overall sensitivity and specificity was 77.8% and 88.4% respectively. The iD was placed on the artery in 267 patients, the vein in 101 patients, and 71 patients had a Doppler placed on both the artery and vein with significantly greater specificity for monitoring the artery than the vein (94.2% vs. 74.0%, p<0.001), but no difference between monitoring both the artery and the vein. Venous monitoring was significantly associated with a takeback (OR: 3.17, CI: 1.70-5.91; p=0.0003). There were 284 flaps that also had a monitoring segment in addition to the iD which significantly increased specificity for microvascular complications (OR: 17.71, CI: 3.39-92.23; p=0.0006). The specificity (90.5% vs. 84.8%) and sensitivity (80.0% vs. 66.7%) were significantly higher for clinically monitored flaps. The takeback rate was 13.0%, with positive findings in 59.6%, and 5.2% total flap loss. The use of implantable Dopplers has high sensitivity and specificity for buried free flap despite positive findings in less than 60% of take backs. Monitoring the artery is preferable to the vein, but clinical exam remains the gold standard for flap monitoring.

Deciphering the Sensitivity and Specificity of the Implantable Doppler Probe in Free Flap Monitoring.

PubMed

Chang, Edward I; Ibrahim, Amir; Zhang, Hong; Liu, Jun; Nguyen, Alexander T; Reece, Gregory P; Yu, Peirong

2016-03-01

The efficacy of implantable Doppler probes remains an area of considerable debate. This study aims to decipher its sensitivity and specificity for free flap monitoring. A retrospective review of all free flaps with an implantable Doppler probe was performed between 2000 and 2012. A Cook-Swartz implantable Doppler probe was used in 439 patients (head and neck, n = 364; breast, n = 53; extremity, n = 22), and demonstrated equivalent sensitivity and specificity between flap types. The overall sensitivity and specificity were 77.8 percent and 88.4 percent, respectively. The artery was monitored in 267 patients, compared to venous monitoring in 101 patients, and in 71 patients both the artery and vein were monitored. Arterial monitoring had significantly greater specificity than venous monitoring, (94.2 percent versus 74.0 percent; p < 0.001), but no benefit was found in monitoring both the artery and the vein. Venous monitoring was significantly associated with reoperation (OR, 3.17; 95 percent CI, 1.70 to 5.91; p = 0.0003). There were 284 flaps that had a monitoring segment in addition to the implantable Doppler probe that significantly increased overall specificity for microvascular complications (OR, 17.71; 95 percent CI, 3.39 to 92.23; p = 0.0006). The specificity (90.5 percent versus 84.8 percent) and sensitivity (80.0 percent versus 66.7 percent) were significantly higher for clinically monitored flaps. The take-back rate was 13.0 percent, with positive findings in 59.6 percent, and 5.2 percent total flap loss. The use of implantable Doppler probes has high sensitivity and specificity for buried free flaps despite positive findings in less than 60 percent of take-backs. Monitoring the artery is recommended, but clinical examination remains the gold standard for flap monitoring. Diagnostic, IV.

The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

PubMed

Guerrero-Romero, Fernando; Simental-Mendía, Luis E; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Ramos-Zavala, María G; Hernández-González, Sandra O; Jacques-Camarena, Omar; Rodríguez-Morán, Martha

2010-07-01

To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. We performed a euglycemic-hyperinsulinemic clamp test. Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P < 0.005). Correlation between the TyG index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

Posturography and locomotor tests of dynamic balance after long-duration spaceflight.

PubMed

Cohen, Helen S; Kimball, Kay T; Mulavara, Ajitkumar P; Bloomberg, Jacob J; Paloski, William H

2012-01-01

The currently approved objective clinical measure of standing balance in astronauts after space flight is the Sensory Organization Test battery of computerized dynamic posturography. No tests of walking balance are currently approved for standard clinical testing of astronauts. This study determined the sensitivity and specificity of standing and walking balance tests for astronauts before and after long-duration space flight. Astronauts were tested on an obstacle avoidance test known as the Functional Mobility Test (FMT) and on the Sensory Organization Test using sway-referenced support surface motion with eyes closed (SOT 5) before and six months after (n=15) space flight on the International Space Station. They were tested two to seven days after landing. Scores on SOT tests decreased and scores on FMT increased significantly from pre- to post-flight. In other words, post-flight scores were worse than pre-flight scores. SOT and FMT scores were not significantly related. ROC analyses indicated supra-clinical cut-points for SOT 5 and for FMT. The standard clinical cut-point for SOT 5 had low sensitivity to post-flight astronauts. Higher cut-points increased sensitivity to post-flight astronauts but decreased specificity to pre-flight astronauts. Using an FMT cut-point that was moderately highly sensitive and highly specific plus SOT 5 at the standard clinical cut-point was no more sensitive than SOT 5, alone. FMT plus SOT 5 at higher cut-points was more specific and more sensitive. The total correctly classified was highest for FMT, alone, and for FMT plus SOT 5 at the highest cut-point. These findings indicate that standard clinical comparisons are not useful for identifying problems. Testing both standing and walking balance will be more likely to identify balance deficits.

Can magnetic resonance imaging at 3.0-Tesla reliably detect patients with endometriosis? Initial results.

PubMed

Thomeer, Maarten G; Steensma, Anneke B; van Santbrink, Evert J; Willemssen, Francois E; Wielopolski, Piotr A; Hunink, Myriam G; Spronk, Sandra; Laven, Joop S; Krestin, Gabriel P

2014-04-01

The aim of this study was to determine whether an optimized 3.0-Tesla magnetic resonance imaging (MRI) protocol is sensitive and specific enough to detect patients with endometriosis. This was a prospective cohort study with consecutive patients. Forty consecutive patients with clinical suspicion of endometriosis underwent 3.0-Tesla MRI, including a T2-weighted high-resolution fast spin echo sequence (spatial resolution=0.75 ×1.2 ×1.5 mm³) and a 3D T1-weighted high-resolution gradient echo sequence (spatial resolution=0.75 ×1.2 × 2.0 mm³). Two radiologists reviewed the dataset with consensus reading. During laparoscopy, which was used as reference standard, all lesions were characterized according to the revised criteria of the American Fertility Society. Patient-level and region-level sensitivities and specificities and lesion-level sensitivities were calculated. Patient-level sensitivity was 42% for stage I (5/12) and 100% for stages II, III and IV (25/25). Patient-level specificity for all stages was 100% (3/3). The region-level sensitivity and specificity was 63% and 97%, respectively. The sensitivity per lesion was 61% (90% for deep lesions, 48% for superficial lesions and 100% for endometriomata). The detection rate of obliteration of the cul-the-sac was 100% (10/10) with no false positive findings. The interreader agreement was substantial to perfect (kappa=1 per patient, 0.65 per lesion and 0.71 for obliteration of the cul-the-sac). An optimized 3.0-Tesla MRI protocol is accurate in detecting stage II to stage IV endometriosis. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Diagnostic markers for the detection of ovarian cancer in BRCA1 mutation carriers

PubMed Central

Weingartshofer, Sigrid; Rappaport-Fürhauser, Christine; Zeilinger, Robert; Pils, Dietmar; Muhr, Daniela; Braicu, Elena I.; Kastner, Marie-Therese; Tan, Yen Y.; Semmler, Lorenz; Sehouli, Jalid; Singer, Christian F.

2017-01-01

Background Screening for ovarian cancer (OC) in women at high risk consists of a combination of carbohydrate antigen 125 (CA125) and transvaginal ultrasound, despite their low sensitivity and specificity. This could be improved by the combination of several biomarkers, which has been shown in average risk patients but has not been investigated until now in female BRCA mutation carriers. Methods Using a multiplex, bead-based, immunoassay system, we analyzed the concentrations of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, CA125 and human epididymis antigen 4 in 26 healthy wild type women, 26 healthy BRCA1 mutation carriers, 28 wildtype OC patients and 26 OC patients with BRCA1 mutation. Results Using the ROC analysis, we found a high overall sensitivity of 94.3% in differentiating healthy controls from OC patients with comparable results in the wildtype subgroup (sensitivity 92.8%, AUC = 0.988; p = 5.2e-14) as well as in BRCA1 mutation carriers (sensitivity 95.2%, AUC = 0.978; p = 1.7e-15) at an overall specificity of 92.3%. The used algorithm also allowed to identify healthy BRCA1 mutation carriers when compared to healthy wildtype women (sensitivity 88.4%, specificity 80.7%, AUC = 0.895; p = 6e-08), while this was less pronounced in patients with OC (sensitivity 66.7%, specificity 67.8%, AUC = 0.724; p = 0.00065). Conclusion We have developed an algorithm, which can differentiate between healthy women and OC patients and have for the first time shown, that such an algorithm can also be used in BRCA mutation carriers. To clarify a suggested benefit to the existing early detection program, large prospective trials with mainly early stage OC cases are warranted. PMID:29244844

Sensitivity of frozen section histology for identifying Propionibacterium acnes infections in revision shoulder arthroplasty.

PubMed

Grosso, Matthew J; Frangiamore, Salvatore J; Ricchetti, Eric T; Bauer, Thomas W; Iannotti, Joseph P

2014-03-19

Propionibacterium acnes is a clinically relevant pathogen with total shoulder arthroplasty. The purpose of this study was to determine the sensitivity of frozen section histology in identifying patients with Propionibacterium acnes infection during revision total shoulder arthroplasty and investigate various diagnostic thresholds of acute inflammation that may improve frozen section performance. We reviewed the results of forty-five patients who underwent revision total shoulder arthroplasty. Patients were divided into the non-infection group (n = 15), the Propionibacterium acnes infection group (n = 18), and the other infection group (n = 12). Routine preoperative testing was performed and intraoperative tissue culture and frozen section histology were collected for each patient. The histologic diagnosis was determined by one pathologist for each of the four different thresholds. The absolute maximum polymorphonuclear leukocyte concentration was used to construct a receiver operating characteristics curve to determine a new potential optimal threshold. Using the current thresholds for grading frozen section histology, the sensitivity was lower for the Propionibacterium acnes infection group (50%) compared with the other infection group (67%). The specificity of frozen section was 100%. Using a receiver operating characteristics curve, an optimized threshold was found at a total of ten polymorphonuclear leukocytes in five high-power fields (400×). Using this threshold, the sensitivity of frozen section for Propionibacterium acnes was increased to 72%, and the specificity remained at 100%. Using current histopathology grading systems, frozen sections were specific but showed low sensitivity with respect to the Propionibacterium acnes infection. A new threshold value of a total of ten or more polymorphonuclear leukocytes in five high-power fields may increase the sensitivity of frozen section, with minimal impact on specificity.

Development of a Fluorescent Based Immunosensor for the Serodiagnosis of Canine Leishmaniasis Combining Immunomagnetic Separation and Flow Cytometry

PubMed Central

Sousa, Susana; Cardoso, Luís; Reed, Steven G.; Reis, Alexandre B.; Martins-Filho, Olindo A.; Silvestre, Ricardo; Cordeiro da Silva, Anabela

2013-01-01

Background An accurate diagnosis is essential for the control of infectious diseases. In the search for effective and efficient tests, biosensors have increasingly been exploited for the development of new and highly sensitive diagnostic methods. Here, we describe a new fluorescent based immunosensor comprising magnetic polymer microspheres coated with recombinant antigens to improve the detection of specific antibodies generated during an infectious disease. As a challenging model, we used canine leishmaniasis due to the unsatisfactory sensitivity associated with the detection of infection in asymptomatic animals where the levels of pathogen-specific antibodies are scarce. Methodology Ni-NTA magnetic microspheres with 1,7 µm and 8,07 µm were coated with the Leishmania recombinant proteins LicTXNPx and rK39, respectively. A mixture of equal proportions of both recombinant protein-coated microspheres was used to recognize and specifically bind anti-rK39 and anti-LicTNXPx antibodies present in serum samples of infected dogs. The microspheres were recovered by magnetic separation and the percentage of fluorescent positive microspheres was quantified by flow cytometry. Principal Findings A clinical evaluation carried out with 129 dog serum samples using the antigen combination demonstrated a sensitivity of 98,8% with a specificity of 94,4%. rK39 antigen alone demonstrated a higher sensitivity for symptomatic dogs (96,9%), while LicTXNPx antigen showed a higher sensitivity for asymptomatic (94,4%). Conclusions Overall, our results demonstrated the potential of a magnetic microsphere associated flow cytometry methodology as a viable tool for highly sensitive laboratorial serodiagnosis of both clinical and subclinical forms of canine leishmaniasis. PMID:23991232

The use of intrathecal analgesia and contrast radiography as preoperative diagnostic methods for digital flexor tendon sheath pathology.

PubMed

Fiske-Jackson, A R; Barker, W H J; Eliashar, E; Foy, K; Smith, R K W

2013-01-01

The sensitivity of ultrasonography for the diagnosis of manica flexoria (MF) tears within the digital flexor tendon sheath (DFTS) is lower than for diagnosis of marginal tears of the deep digital flexor tendon (DDFT). Additional diagnostic tools would assist in appropriate decision making for either conservative or surgical management. To evaluate the improvement in lameness of horses with MF or DDFT tears following intrathecal analgesia and to assess the sensitivity and specificity of contrast radiography for the diagnosis of these tears. The case records of horses presented to a referral clinic over a 7-year period that underwent intrathecal diagnostic analgesia, or intrathecal analgesia and contrast radiography, of the DFTS with subsequent tenoscopy were examined. Fifty-three limbs had intrathecal diagnostic analgesia performed and 23 contrast tenograms were assessed in horses undergoing DFTS tenoscopy. Horses with DDFT tears were significantly more likely to respond positively to intrathecal diagnostic analgesia than those with MF tears (P = 0.02). Using contrast radiography, tears of the MF were predicted with an overall sensitivity of 96% and specificity of 80%; marginal tears of the DDFT were predicted with an overall sensitivity of 57% and specificity of 84%. The results of intrathecal analgesia of the DFTS in combination with contrast radiography have a high sensitivity for predicting MF tears. The sensitivity of contrast radiography for predicting tears of the DDFT is lower but the specificity remains high. Contrast radiography performed at the same time as intrathecal analgesia provides useful information regarding the presence of MF tears and DDFT tears, which can assist in the decision of whether to manage the lameness conservatively or with tenoscopic evaluation. © 2012 EVJ Ltd.

Uroplakin II (UPII), GATA3, and p40 are Highly Sensitive Markers for the Differential Diagnosis of Invasive Urothelial Carcinoma.

PubMed

Hoang, Laura L; Tacha, David; Bremer, Ryan E; Haas, Thomas S; Cheng, Liang

2015-01-01

Distinguishing between invasive urothelial carcinoma from other genitourinary lesions such as prostatic and renal carcinomas can be difficult, and may require highly sensitive immunohistochemical markers. GATA-binding protein 3 (GATA3) has been reported in a high percentage of urothelial and breast carcinomas. Mouse monoclonal uroplakin II (UPII) and p40 antibodies have recently been developed and demonstrated high specificity in urothelial carcinoma. This study evaluated the immunohistochemical staining sensitivities of UPII, GATA3, p40, and p63 in the detection of invasive urothelial carcinoma. UPII, GATA3, and p40 were further tested for specificity in lung, breast, colon, kidney, and prostate cancers. In all invasive urothelial carcinoma cases, UPII, GATA3, p40, and p63 exhibited sensitivities of 77.7%, 83.5%, 85.4%, and 80.6%, respectively. The combination of UPII, GATA3, and p40 antibodies stained 94.2% (97/103) of all invasive urothelial carcinoma cases, including 92.2% (71/77) of grade 2-3 urothelial carcinomas. In addition, GATA3 and UPII showed negative staining in lung squamous cell carcinomas and p40 showed negative staining in breast infiltrating ductal carcinomas. The combination of UPII, GATA3, and p40 showed negative staining in lung adenocarcinoma, colon adenocarcinoma, and renal carcinomas. In conclusion, UPII, GATA3, and p40, when used in combination, are highly sensitive in the differential diagnosis of invasive urothelial carcinoma.

Point of care diagnosis of multiple schistosome parasites: Species-specific DNA detection in urine by loop-mediated isothermal amplification (LAMP).

PubMed

Lodh, Nilanjan; Mikita, Kei; Bosompem, Kwabena M; Anyan, William K; Quartey, Joseph K; Otchere, Joseph; Shiff, Clive J

2017-09-01

Schistosomes are easily transmitted and high chance of repeat infection, so if control strategies based on targeted mass drug administration (MDA) are to succeed it is essential to have a test that is sensitive, accurate and simple to use. It is known and regularly demonstrated that praziquantel does not always eliminate an infection so in spite of the successes of control programs a residual of the reservoir survives to re-infect snails. The issue of diagnostic sensitivity becomes more critical in the assessment of program effectiveness. While serology, such as antigen capture tests might improve sensitivity, it has been shown that the presence of species-specific DNA fragments will indicate, most effectively, the presence of active parasites. Polymerase chain reaction (PCR) can amplify and detect DNA from urine residue captured on Whatman No. 3 filter paper that is dried after filtration. Previously we have detected S. mansoni and S. haematobium parasite-specific small repeat DNA fragment from filtered urine on filter paper by PCR. In the current study, we assessed the efficacy of detection of 86 urine samples for either or both schistosome parasites by PCR and loop-mediated isothermal amplification (LAMP) that were collected from a low to moderate transmission area in Ghana. Two different DNA extraction methods, standard extraction kit and field usable LAMP-PURE kit were also evaluated by PCR and LAMP amplification. With S. haematobium LAMP amplification for both extractions showed similar sensitivity and specificity when compared with PCR amplification (100%) verified by gel electrophoresis. For S. mansoni sensitivity was highest for LAMP amplification (100%) for standard extraction than PCR and LAMP with LAMP-PURE (99% and 94%). The LAMP-PURE extraction produced false negatives, which require further investigation for this field usable extraction kit. Overall high positive and negative predictive values (90% - 100%) for both species demonstrated a highly robust approach. The LAMP approach is close to point of care use and equally sensitive and specific to detection of species-specific DNA by PCR. LAMP can be an effective means to detect low intensity infection due to its simplicity and minimal DNA extraction requirement. This will enhance the effectiveness of surveillance and MDA control programs of schistosomiasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive models of lameness in dairy cows achieve high sensitivity and specificity with force measurements in three dimensions.

PubMed

Dunthorn, Jason; Dyer, Robert M; Neerchal, Nagaraj K; McHenry, Jonathan S; Rajkondawar, Parimal G; Steingraber, Gary; Tasch, Uri

2015-11-01

Lameness remains a significant cause of production losses, a growing welfare concern and may be a greater economic burden than clinical mastitis . A growing need for accurate, continuous automated detection systems continues because US prevalence of lameness is 12.5% while individual herds may experience prevalence's of 27.8-50.8%. To that end the first force-plate system restricted to the vertical dimension identified lame cows with 85% specificity and 52% sensitivity. These results lead to the hypothesis that addition of transverse and longitudinal dimensions could improve sensitivity of lameness detection. To address the hypothesis we upgraded the original force plate system to measure ground reaction forces (GRFs) across three directions. GRFs and locomotion scores were generated from randomly selected cows and logistic regression was used to develop a model that characterised relationships of locomotion scores to the GRFs. This preliminary study showed 76 variables across 3 dimensions produced a model with greater than 90% sensitivity, specificity, and area under the receiver operating curve (AUC). The result was a marked improvement on the 52% sensitivity, and 85% specificity previously observed with the 1 dimensional model or the 45% sensitivities reported with visual observations. Validation of model accuracy continues with the goal to finalise accurate automated methods of lameness detection.

75 FR 29763 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-27

... commercialization of results of federally-funded research and development. Foreign patent applications are filed on... patent applications. Simple, Quantitative and Highly Specific Antibody Detection of Lyme Disease... markedly out-performed the C6 ELISA test (currently the most sensitive test available, with 76% sensitivity...

Immune biosensors based on the SPR and TIRE: efficiency of their application for bacteria determination

NASA Astrophysics Data System (ADS)

Starodub, N. F.; Ogorodniichuk, J.; Lebedeva, T.; Shpylovyy, P.

2013-11-01

In this work we have designed high-specific biosensors for Salmonella typhimurium detection based on the surface plasmon resonance (SPR) and total internal reflection ellipsometry (TIRE). It has been demonstrated high selectivity and sensitivity of analysis. As a registering part for our experiments the Spreeta (USA) and "Plasmonotest" (Ukraine) with flowing cell have been applied among of SPR device. Previous researches confirmed an efficiency of SPR biosensors using for detecting of specific antigen-antibody interactions therefore this type of reactions with some previous preparations of surface binding layer was used as reactive part. It has been defined that in case with Spreeta sensitivity was on the level 103 - 107 cells/ml. Another biosensor based on the SPR has shown the sensitivity within 101 - 106 cells/ml. Maximal sensitivity was on the level of several cells in 10 ml (up to the fact that less than 5 cells) which has been obtained using the biosensor based on TIRE.

A new highly sensitive and specific real-time PCR assay targeting the malate dehydrogenase gene of Kingella kingae and application to 201 pediatric clinical specimens.

PubMed

Houmami, Nawal El; Durand, Guillaume André; Bzdrenga, Janek; Darmon, Anne; Minodier, Philippe; Seligmann, Hervé; Raoult, Didier; Fournier, Pierre-Edouard

2018-06-06

Kingella kingae is a significant pediatric pathogen responsible for bone and joint infections, occult bacteremia, and endocarditis in early childhood. Past efforts to detect this bacterium by culture and broad-range 16S rRNA gene polymerase chain reaction (PCR) assays from clinical specimens have proven unsatisfactory and were gradually let out for the benefit of specific real-time PCR tests targeting the groEL gene and RTX locus of K. kingae by the late 2000s. However, recent studies showed that real-time PCR (RT-PCR) assays targeting the Kingella sp. RTX locus that are currently available for the diagnosis of K. kingae infection lack of specificity because they could not distinguish between K. kingae and the recently described K. negevensis species. Furthermore, in silico analysis of the groEL gene from a large collection of 45 K. kingae strains showed that primers and probes from K. kingae groEL -based RT-PCR assays display a few mismatches with K. kingae groEL variations that may result in a decreased detection sensitivity, especially in paucibacillary clinical specimens. In order to provide an alternative to groEL - and RTX-targeting RT-PCR assays that may suffer from suboptimal specificity and sensitivity, a K. kingae -specific RT-PCR assay targeting the malate dehydrogenase ( mdh ) gene was developed for predicting no mismatch against 18 variants of the K. kingae mdh gene from 20 distinct sequences types of K. kingae This novel K. kingae -specific RT-PCR assay demonstrated a high specificity and sensitivity and was successfully used to diagnose K. kingae infections and carriage in 104 clinical specimens from children aged between 7 months and 7 years old. Copyright © 2018 American Society for Microbiology.

Highly specific preoperative selection of solitary parathyroid adenoma cases in primary hyperparathyroidism by quantitative image analysis of the early-phase Technetium-99m sestamibi scan.

PubMed

Kim, DaeHee; Rhodes, Jeffrey A; Hashim, Jeffrey A; Rickabaugh, Lawrence; Brams, David M; Pinkus, Edward; Dou, Yamin

2018-06-07

Highly specific preoperative localizing test is required to select patients for minimally invasive parathyroidectomy (MIP) in lieu of traditional four-gland exploration. We hypothesized that Tc-99m sestamibi scan interpretation incorporating numerical measurements on the degree of asymmetrical activity from bilateral thyroid beds can be useful in localizing single adenoma for MIP. We devised a quantitative interpretation method for Tc-99m sestamibi scan based on the numerically graded asymmetrical activity on early phase. The numerical ratio value of each scan was obtained by dividing the number of counts from symmetrically drawn regions of interest (ROI) over bilateral thyroid beds. The final pathology and clinical outcome of 109 patients were used to perform receiver operating curve (ROC) analysis. Receiver operating curve analysis revealed the area under the curve (AUC) was calculated to be 0.71 (P = 0.0032), validating this method as a diagnostic tool. The optimal cut-off point for the ratio value with maximal combined sensitivity and specificity was found with corresponding sensitivity of 67.9% (56.5-77.2%, 95% CI) and specificity of 75.0% (52.8-91.8%, 95% CI). An additional higher cut-off with higher specificity with minimal possible sacrifice on sensitivity was also selected, yielding sensitivity of 28.6% (18.8-38.6%, 95% CI) and specificity of 90.0% (69.6-98.8%, 95% CI). Our results demonstrated that the more asymmetrical activity on the initial phase, the more successful it is to localize a single parathyroid adenoma on sestamibi scans. Using early-phase Tc-99m sestamibi scan only, we were able to select patients for minimally invasive parathyroidectomy with 90% specificity. © 2018 The Royal Australian and New Zealand College of Radiologists.

An investigation of new toxicity test method performance in validation studies: 1. Toxicity test methods that have predictive capacity no greater than chance.

PubMed

Bruner, L H; Carr, G J; Harbell, J W; Curren, R D

2002-06-01

An approach commonly used to measure new toxicity test method (NTM) performance in validation studies is to divide toxicity results into positive and negative classifications, and the identify true positive (TP), true negative (TN), false positive (FP) and false negative (FN) results. After this step is completed, the contingent probability statistics (CPS), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are calculated. Although these statistics are widely used and often the only statistics used to assess the performance of toxicity test methods, there is little specific guidance in the validation literature on what values for these statistics indicate adequate performance. The purpose of this study was to begin developing data-based answers to this question by characterizing the CPS obtained from an NTM whose data have a completely random association with a reference test method (RTM). Determining the CPS of this worst-case scenario is useful because it provides a lower baseline from which the performance of an NTM can be judged in future validation studies. It also provides an indication of relationships in the CPS that help identify random or near-random relationships in the data. The results from this study of randomly associated tests show that the values obtained for the statistics vary significantly depending on the cut-offs chosen, that high values can be obtained for individual statistics, and that the different measures cannot be considered independently when evaluating the performance of an NTM. When the association between results of an NTM and RTM is random the sum of the complementary pairs of statistics (sensitivity + specificity, NPV + PPV) is approximately 1, and the prevalence (i.e., the proportion of toxic chemicals in the population of chemicals) and PPV are equal. Given that combinations of high sensitivity-low specificity or low specificity-high sensitivity (i.e., the sum of the sensitivity and specificity equal to approximately 1) indicate lack of predictive capacity, an NTM having these performance characteristics should be considered no better for predicting toxicity than by chance alone.

Development of a highly sensitive lateral immunochromatographic assay for rapid detection of Vibrio parahaemolyticus.

PubMed

Liu, Xinfeng; Guan, Yuyao; Cheng, Shiliang; Huang, Yidan; Yan, Qin; Zhang, Jun; Huang, Guanjun; Zheng, Jian; Liu, Tianqiang

2016-12-01

Vibrio parahaemolyticus is widely present in brackish water all over the world, causing infections in certain aquatic animals. It is also a foodborne pathogen that causes diarrhea in humans. The aim of this study is to develop an immunochromatographic lateral flow assay (LFA) for rapid detection of V. parahaemolyticus in both aquatic products and human feces of diarrheal patients. Two monoclonal antibody (MAb) pairs, GA1a-IC9 and IC9-KB4c, were developed and proven to be highly specific and sensitive to V. parahaemolyticus. Based on the two MAb pairs, two types of LFA strips were prepared. Their testing limits for V. parahaemolyticus culture were both 1.2×10 3 CFU/ml. The diagnostic sensitivities and specificities were both 100% for the 32 tested microbial species, including 6 Vibrio species. Subsequently, the LFA strips were used to test Whiteleg shrimps and human feces. The type II strip showed a higher diagnostic sensitivity. Its sensitivity and specificity for hepatopancreas and fecal samples from 13 Whiteleg shrimps and fecal samples from 146 human diarrheal patients were all 100%. In conclusion, our homemade type II LFA is a very promising testing device for rapid and convenient detection of V. parahaemolyticus infection not only in aquatic animals, but also in human diarrheal patients. This sensitive immunochromtographic LFA allows rapid detection of V. parahaemolyticus without requirement of culture enrichment. Copyright © 2016. Published by Elsevier B.V.

Novel Designs for Application Specific MEMS Pressure Sensors

PubMed Central

Fragiacomo, Giulio; Reck, Kasper; Lorenzen, Lasse; Thomsen, Erik V.

2010-01-01

In the framework of developing innovative microfabricated pressure sensors, we present here three designs based on different readout principles, each one tailored for a specific application. A touch mode capacitive pressure sensor with high sensitivity (14 pF/bar), low temperature dependence and high capacitive output signal (more than 100 pF) is depicted. An optical pressure sensor intrinsically immune to electromagnetic interference, with large pressure range (0–350 bar) and a sensitivity of 1 pm/bar is presented. Finally, a resonating wireless pressure sensor power source free with a sensitivity of 650 KHz/mmHg is described. These sensors will be related with their applications in harsh environment, distributed systems and medical environment, respectively. For many aspects, commercially available sensors, which in vast majority are piezoresistive, are not suited for the applications proposed. PMID:22163425

Discrimination of Influenza Infection (A/2009 H1N1) from Prior Exposure by Antibody Protein Microarray Analysis

PubMed Central

te Beest, Dennis; de Bruin, Erwin; Imholz, Sandra; Wallinga, Jacco; Teunis, Peter; Koopmans, Marion; van Boven, Michiel

2014-01-01

Reliable discrimination of recent influenza A infection from previous exposure using hemagglutination inhibition (HI) or virus neutralization tests is currently not feasible. This is due to low sensitivity of the tests and the interference of antibody responses generated by previous infections. Here we investigate the diagnostic characteristics of a newly developed antibody (HA1) protein microarray using data from cross-sectional serological studies carried out before and after the pandemic of 2009. The data are analysed by mixture models, providing a probabilistic classification of sera (susceptible, prior-exposed, recently infected). Estimated sensitivity and specificity for identifying A/2009 infections are low using HI (66% and 51%), and high when using A/2009 microarray data alone or together with A/1918 microarray data (96% and 95%). As a heuristic, a high A/2009 to A/1918 antibody ratio (>1.05) is indicative of recent infection, while a low ratio is indicative of a pre-existing response, even if the A/2009 titer is high. We conclude that highly sensitive and specific classification of individual sera is possible using the protein microarray, thereby enabling precise estimation of age-specific infection attack rates in the population even if sample sizes are small. PMID:25405997

Screening of depression in adolescents through the Internet : sensitivity and specificity of two screening questionnaires.

PubMed

Cuijpers, Pim; Boluijt, Petra; van Straten, Annemieke

2008-02-01

The Internet may offer new opportunities for treating depressed adolescents. However, before such treatments are possible, well-validated screening instruments are needed. In the current study, we validate two Internet-based screening instruments for depression among adolescents, the major depression inventory (MDI), and the Center for Epidemiological Studies-Depression scale (CES-D). A total of 1,392 adolescents, recruited through high schools and the Internet, filled in the online questionnaires. Of these, 243 (17%) were interviewed with the MINI diagnostic interview to assess the presence of a mood disorder. Cronbach's alpha was high for both the CES-D (0.93) and the MDI (0.88), and both correlated highly with each other (0.88; P < .001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CES-D (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening.

Polymerase chain reaction-hybridization method using urease gene sequences for high-throughput Ureaplasma urealyticum and Ureaplasma parvum detection and differentiation.

PubMed

Xu, Chen; Zhang, Nan; Huo, Qianyu; Chen, Minghui; Wang, Rengfeng; Liu, Zhili; Li, Xue; Liu, Yunde; Bao, Huijing

2016-04-15

In this article, we discuss the polymerase chain reaction (PCR)-hybridization assay that we developed for high-throughput simultaneous detection and differentiation of Ureaplasma urealyticum and Ureaplasma parvum using one set of primers and two specific DNA probes based on urease gene nucleotide sequence differences. First, U. urealyticum and U. parvum DNA samples were specifically amplified using one set of biotin-labeled primers. Furthermore, amine-modified DNA probes, which can specifically react with U. urealyticum or U. parvum DNA, were covalently immobilized to a DNA-BIND plate surface. The plate was then incubated with the PCR products to facilitate sequence-specific DNA binding. Horseradish peroxidase-streptavidin conjugation and a colorimetric assay were used. Based on the results, the PCR-hybridization assay we developed can specifically differentiate U. urealyticum and U. parvum with high sensitivity (95%) compared with cultivation (72.5%). Hence, this study demonstrates a new method for high-throughput simultaneous differentiation and detection of U. urealyticum and U. parvum with high sensitivity. Based on these observations, the PCR-hybridization assay developed in this study is ideal for detecting and discriminating U. urealyticum and U. parvum in clinical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Glycan-functionalized graphene-FETs toward selective detection of human-infectious avian influenza virus

NASA Astrophysics Data System (ADS)

Ono, Takao; Oe, Takeshi; Kanai, Yasushi; Ikuta, Takashi; Ohno, Yasuhide; Maehashi, Kenzo; Inoue, Koichi; Watanabe, Yohei; Nakakita, Shin-ichi; Suzuki, Yasuo; Kawahara, Toshio; Matsumoto, Kazuhiko

2017-03-01

There are global concerns about threat of pandemic caused by the human-infectious avian influenza virus. To prevent the oncoming pandemic, it is crucial to analyze the viral affinity to human-type or avian-type sialoglycans with high sensitivity at high speed. Graphene-FET (G-FET) realizes such high-sensitive electrical detection of the targets, owing to graphene’s high carrier mobility. In the present study, G-FET was functionalized using sialoglycans and employed for the selective detection of lectins from Sambucus sieboldiana and Maackia amurensis as alternatives of the human and avian influenza viruses. Glycan-functionalized G-FET selectively monitored the sialoglycan-specific binding reactions at subnanomolar sensitivity.

Comparison of glaucoma diagnostic accuracy of macular ganglion cell complex thickness based on nonhighly myopic and highly myopic normative database

PubMed Central

Chen, Henry Shen-Lih; Liu, Chun-Hsiu; Lu, Da-Wen

2016-01-01

Background/Purpose: To evaluate and compare the diagnostic discriminative ability for detecting glaucoma in highly myopic eyes from a normative database of macular ganglion cell complex (mGCC) thickness based on nonhighly myopic and highly myopic normal eyes. Methods: Forty-nine eyes of 49 participants with high myopia (axial length ≥ 26.0 mm) were enrolled. Spectral-domain optical coherence tomography scans were done using RS-3000, and the mGCC thickness/significance maps within a 9-mm diameter circle were generated using built-in software. We compared the difference of sensitivity, specificity, and diagnostic accuracy between the nonhighly myopic database and the highly myopic database for differentiating the early glaucomatous eyes from the nonglaucomatous eyes. Results: This study enrolled 15 normal eyes and 34 eyes with glaucoma. The mean mGCC thickness of the glaucoma group was significantly less than that of the normal group (p < 0.001). Sensitivity was 96.3%, and the specificity was 50.0% when using the nonhighly myopic normative database. When the highly myopic normative database was used, the sensitivity was 88.9%, and the specificity was 90.0%. The false positive rate was significantly lower when using the highly myopic normative database (p < 0.05). Conclusion: The evaluations of glaucoma in eyes with high myopia using a nonhighly myopic normative database may lead to a frequent misdiagnosis. When evaluating glaucoma in high myopic eyes, the mGCC thickness determined by the long axial length high myopic normative database should be applied. PMID:29018704

Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis.

PubMed

Kim, Hae Young; Park, Ji Hoon; Lee, Yoon Jin; Lee, Sung Soo; Jeon, Jong-June; Lee, Kyoung Ho

2018-04-01

Purpose To perform a systematic review and meta-analysis to identify computed tomographic (CT) features for differentiating complicated appendicitis in patients suspected of having appendicitis and to summarize their diagnostic accuracy. Materials and Methods Studies on diagnostic accuracy of CT features for differentiating complicated appendicitis (perforated or gangrenous appendicitis) in patients suspected of having appendicitis were searched in Ovid-MEDLINE, EMBASE, and the Cochrane Library. Overlapping descriptors used in different studies to denote the same image finding were subsumed under a single CT feature. Pooled diagnostic accuracy of the CT features was calculated by using a bivariate random effects model. CT features with pooled diagnostic odds ratios with 95% confidence intervals not including 1 were considered as informative. Results Twenty-three studies were included, and 184 overlapping descriptors for various CT findings were subsumed under 14 features. Of these, 10 features were informative for complicated appendicitis. There was a general tendency for these features to show relatively high specificity but low sensitivity. Extraluminal appendicolith, abscess, appendiceal wall enhancement defect, extraluminal air, ileus, periappendiceal fluid collection, ascites, intraluminal air, and intraluminal appendicolith showed pooled specificity greater than 70% (range, 74%-100%), but sensitivity was limited (range, 14%-59%). Periappendiceal fat stranding was the only feature that showed high sensitivity (94%; 95% confidence interval: 86%, 98%) but low specificity (40%; 95% confidence interval, 23%, 60%). Conclusion Ten informative CT features for differentiating complicated appendicitis were identified in this study, nine of which showed high specificity, but low sensitivity. © RSNA, 2017 Online supplemental material is available for this article.

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

NASA Technical Reports Server (NTRS)

2004-01-01

Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P less than 0.00l). Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

NASA Technical Reports Server (NTRS)

Rahman, Atiar

2006-01-01

Background: Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). Methods and Results: 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P<0.001). Conclusions: Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

Reversal of apomorphine locomotor sensitization by a single post-conditioning trial treatment with a low autoreceptor dose of apomorphine: a memory re-consolidation approach.

PubMed

Carrera, Marinete Pinheiro; Carey, Robert J; Dias, Flávia Regina Cruz; de Matos, Liana Wermelinger

2011-07-01

Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of apomorphine (2.0mg/kg). Two days following a 5 session sensitization induction phase, a brief 5min non-drug test for conditioning was conducted. Only the paired groups exhibited locomotor stimulant conditioned response effects. Immediately following this brief test for conditioning, the paired and the unpaired groups received injections of 0.05mg/kg apomorphine, 2.0mg/kg apomorphine or vehicle designed to differentially impact memory re-consolidation of the conditioning. Two days later, all groups received a sensitization challenge test with 2.0mg/kg apomorphine. The 2.0mg/kg apomorphine post-trial treatment potentiated sensitization while the 0.05mg/kg eliminated sensitization. These effects were only observed in the paired groups. The activation of dopaminergic systems by the high dose of apomorphine strengthened the drug/environment association whereas the inhibition of dopamine activity by the low auto-receptor dose eliminated this association. The results point to the importance of conditioning to context specific sensitization and targeting memory re-consolidation of conditioning as a paradigm to modify sensitization. Copyright © 2011 Elsevier Inc. All rights reserved.

Portable SERS sensor for malachite green and other small dye molecules

NASA Astrophysics Data System (ADS)

Qiu, Suyan; Zhao, Fusheng; Li, Jingting; Shih, Wei-Chuan

2017-02-01

Sensitive detection of specific chemicals on site can be extremely powerful in many fields. Owing to its molecular fingerprinting capability, surface-enhanced Raman scattering has been one of the technological contenders. In this paper, we describe the novel use of DNA topological nanostructure on nanoporous gold nanoparticle (NPG-NP) array chip for chemical sensing. NPG-NP features large surface area and high-density plasmonic field enhancement known as "hotspots". Hence, NPG-NP array chip has found many applications in nanoplasmonic sensor development. This technique can provide novel label-free molecular sensing capability and enables high sensitivity and specificity detection using a portable Raman spectrometer.

[COMPARATIVE SENSITIVITY OF CHOLINESTERASES IN VERTEBRATES AND INVERTEBRATES TO HIGHLY SPECIFIC ORGANOPHOSPHORUS INHIBITORS DIISOPROPYL FLUOROPHOSPHATE (DFP) AND (2-ETHOXYMETHYL PHOSPHORYL THIOETHYL) ETHYL (METHYL) SULPHONIUM SULPHOMETHYLAT (GD-42)].

PubMed

Basova, N E; Kormilitsyn, B N; Perchenok, A Yu; Rozengart, E V; Saakov, V S; Suvorov, A A

2015-01-01

The review presents data on comparative reactivity of 68 cholinesterase preparation from various organs and tissues in a number of vertebrates and invertebrates based on sensitivity to two highly specific and most studied organophosphorus inhibitors--diisopropyl fluorophosphates (DFP) and (2-ethoxymethyl phosphoryl thioethyl) ethyl (methyl) sulphonium sulphomethylat (GD-42). Analysis of these data suggests a great diversity in enzymologic characteristics of cholinesterase preparation in representatives of vertebrates and invertebrates, this variety observed even for closely related enzymes in animals of almost the same level of development.

Genotyping of high-risk anal human papillomavirus (HPV): ion torrent-next generation sequencing vs. linear array.

PubMed

Nowak, Rebecca G; Ambulos, Nicholas P; Schumaker, Lisa M; Mathias, Trevor J; White, Ruth A; Troyer, Jennifer; Wells, David; Charurat, Manhattan E; Bentzen, Søren M; Cullen, Kevin J

2017-06-13

Our next generation sequencing (NGS)-based human papillomavirus (HPV) genotyping assay showed a high degree of concordance with the Roche Linear Array (LA) with as little as 1.25 ng formalin-fixed paraffin-embedded-derived genomic DNA in head and neck and cervical cancer samples. This sensitive genotyping assay uses barcoded HPV PCR broad-spectrum general primers 5+/6+ (BSGP)5+/6+ applicable to population studies, but it's diagnostic performance has not been tested in cases with multiple concurrent HPV infections. We conducted a cross-sectional study to compare the positive and negative predictive value (PPV and NPV), sensitivity and specificity of the NGS assay to detect HPV genotype infections as compared to the LA. DNA was previously extracted from ten anal swab samples from men who have sex with men in Nigeria enrolled on the TRUST/RV368 cohort study. Two-sample tests of proportions were used to examine differences in the diagnostic performance of the NGS assay to detect high vs. low-risk HPV type-specific infections. In total there were 94 type-specific infections detected in 10 samples with a median of 9.5, range (9 to 10) per sample. Using the LA as the gold standard, 84.4% (95% CI: 75.2-91.2) of the same anal type-specific infections detected on the NGS assay had been detected by LA. The PPV and sensitivity differed significantly for high risk (PPV: 90%, 95% CI: 79.5-96.2; sensitivity: 93.1%, 95% CI: 83.3-98.1) as compared to low risk HPV (PPV: 73%, 95% CI: 54.1-87.7; sensitivity: 61.1, 95% CI: 43.5-76.9) (all p < 0.05). The NPV for all types was 92.5% (95% CI: 88.4-95.4). The NPV and specificity were similar for high and low risk HPVs (all p > 0.05). The NGS assay detected 10 HPV genotypes that were not among the 37 genotypes found on LA (30, 32, 43, 44, 74, 86, 87, 90, 91, 114). The NGS assay accurately detects multiple HPV infections in individual clinical specimens with limited sample volume and has extended coverage compared to LA.

Usefulness of the volume-viscosity swallow test for screening dysphagia in subacute stroke patients in rehabilitation income.

PubMed

Guillén-Solà, Anna; Marco, Ester; Martínez-Orfila, Joan; Donaire Mejías, M Fernanda; Depolo Passalacqua, Marina; Duarte, Esther; Escalada, Ferran

2013-01-01

Swallowing disorders affect up to 35-85% of patients with stroke. Dysphagia complications can lead to malnutrition, dehydration, bronchoaspirative pneumonia and death, and have impact on health care costs. To evaluate the clinical screening capacity of the Volume Viscosity Swallow Test (V-VST) for oropharyngeal dysphagia and aspiration in a homogeneous stroke patient sample. Cohort study of 52 stroke patients in a subacute phase. Piecemeal deglutition and oropharyngeal residue were considered signs of impaired efficacy and cough, fall in oxygen saturation and voice changes, signs of impaired safety. Sensitivity, specificity, positive and negative predictive values, accuracy and likelihood ratios were calculated for V-VST results and compared with those of videofluoroscopy (VFS), the gold standard for studies on swallowing disorders. The V-VST is a highly sensitive and specific test to detect aspiration with sensitivity of 88.2% and specificity of 71.4%; negative predictive value was 92.6%; accuracy index was 0.74. Sensitivity and specificity for penetration were 34.3% and 70.6%, respectively; accuracy was 32%. The V-VST is low in cost, easy to use and very sensitive, meeting the requirements of oropharyngeal dysphagia and aspiration screening test in subacute stroke patients.

[Sensitivity and specificity of the breast screening program in the Isere region based on positive results between 1991 and 1999].

PubMed

Garnier, A; Poncet, F; Billette De Villemeur, A; Exbrayat, C; Bon, M F; Chevalier, A; Salicru, B; Tournegros, J M

2009-06-01

The screening program guidelines specify that the call back rate of women for additional imaging (positive mammogram) should not exceed 7% at initial screening, and 5% at subsequent screening. Materials and methods. Results in the Isere region (12%) have prompted a review of the correlation between the call back rate and indicators of quality (detection rate, sensitivity, specificity, positive predictive value) for the radiologists providing interpretations during that time period. Three groups of radiologists were identified: the group with call back rate of 10% achieved the best results (sensitivity: 92%, detection rate: 0.53%, specificity: 90%). The group with lowest call back rate (7.7%) showed insufficient sensitivity (58%). The last group with call back rate of 18.3%, showed no improvement in sensitivity (82%) and detection rate (0.53%), but showed reduced specificity (82%). The protocol update in 2001 does not resolve this problematic situation and national results continue to demonstrate a high percentage of positive screening mammograms. A significant increase in the number of positive screening examinations compared to recommended guidelines is not advantageous and leads to an overall decrease in the quality of the screening.

Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) processing speed scores as measures of noncredible responding: The third generation of embedded performance validity indicators.

PubMed

Erdodi, Laszlo A; Abeare, Christopher A; Lichtenstein, Jonathan D; Tyson, Bradley T; Kucharski, Brittany; Zuccato, Brandon G; Roth, Robert M

2017-02-01

Research suggests that select processing speed measures can also serve as embedded validity indicators (EVIs). The present study examined the diagnostic utility of Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests as EVIs in a mixed clinical sample of 205 patients medically referred for neuropsychological assessment (53.3% female, mean age = 45.1). Classification accuracy was calculated against 3 composite measures of performance validity as criterion variables. A PSI ≤79 produced a good combination of sensitivity (.23-.56) and specificity (.92-.98). A Coding scaled score ≤5 resulted in good specificity (.94-1.00), but low and variable sensitivity (.04-.28). A Symbol Search scaled score ≤6 achieved a good balance between sensitivity (.38-.64) and specificity (.88-.93). A Coding-Symbol Search scaled score difference ≥5 produced adequate specificity (.89-.91) but consistently low sensitivity (.08-.12). A 2-tailed cutoff on the Coding/Symbol Search raw score ratio (≤1.41 or ≥3.57) produced acceptable specificity (.87-.93), but low sensitivity (.15-.24). Failing ≥2 of these EVIs produced variable specificity (.81-.93) and sensitivity (.31-.59). Failing ≥3 of these EVIs stabilized specificity (.89-.94) at a small cost to sensitivity (.23-.53). Results suggest that processing speed based EVIs have the potential to provide a cost-effective and expedient method for evaluating the validity of cognitive data. Given their generally low and variable sensitivity, however, they should not be used in isolation to determine the credibility of a given response set. They also produced unacceptably high rates of false positive errors in patients with moderate-to-severe head injury. Combining evidence from multiple EVIs has the potential to improve overall classification accuracy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Evaluation of the BinaxNOW® Streptococcus pneumoniae antigen test on fresh, frozen and concentrated urine samples in elderly patients with and without community-acquired pneumonia.

PubMed

Saukkoriipi, Annika; Pascal, Thierry; Palmu, Arto A

2016-02-01

We evaluated the BinaxNOW® urine antigen test in elderly. For fresh un-concentrated urine samples, the sensitivity for pneumococcal pneumonia was 63% and specificity 97%. After freezing and concentration, the results comparable to positive control line in intensity at 60 min gave high sensitivity (81%) with no loss in specificity (96%). Copyright © 2015 Elsevier B.V. All rights reserved.

Reflective type objective based spectral-domain phase-sensitive optical coherence tomography for high-sensitive structural and functional imaging of cochlear microstructures through intact bone of an excised guinea pig cochlea

NASA Astrophysics Data System (ADS)

Subhash, Hrebesh M.; Wang, Ruikang K.; Chen, Fangyi; Nuttall, Alfred L.

2013-03-01

Most of the optical coherence tomographic (OCT) systems for high resolution imaging of biological specimens are based on refractive type microscope objectives, which are optimized for specific wave length of the optical source. In this study, we present the feasibility of using commercially available reflective type objective for high sensitive and high resolution structural and functional imaging of cochlear microstructures of an excised guinea pig through intact temporal bone. Unlike conventional refractive type microscopic objective, reflective objective are free from chromatic aberrations due to their all-reflecting nature and can support a broadband of spectrum with very high light collection efficiency.

Detection of Francisella tularensis-Specific Antibodies in Patients with Tularemia by a Novel Competitive Enzyme-Linked Immunosorbent Assay

PubMed Central

Sharma, Neekun; Hotta, Akitoyo; Yamamoto, Yoshie; Fujita, Osamu; Uda, Akihiko; Morikawa, Shigeru; Yamada, Akio

2013-01-01

A novel competitive enzyme-linked immunosorbent assay (cELISA) was developed and evaluated for detection of antibodies against Francisella tularensis in humans. The assay is based on the ability of serum antibodies to inhibit the binding of monoclonal antibodies (MAbs) directed against F. tularensis lipopolysaccharide antigens. The assay was evaluated using serum samples of tularemia patients, inactivated F. tularensis-immunized rabbits, and F. tularensis-infected mice. Antibodies against F. tularensis were successfully detected in serum samples of tularemia patients as well as the immunized and infected animals. The cELISA method was compared to indirect ELISA (iELISA) and the commonly used microagglutination test (MA) using serum samples of 19 tularemia patients and 50 healthy individuals. The sensitivity and specificity of cELISA were 93.9 and 96.1%, respectively, in comparison to the iELISA. MA was less sensitive than cELISA with a sensitivity and specificity of only 81.8 and 98.0%, respectively. A high degree of correlation (R2 = 0.8226) was observed between cELISA and iELISA results. The novel cELISA developed in this study appears to be highly sensitive and specific for serodiagnosis of human tularemia. The potential of the MAb-based cELISA to be used in both human and animal samples emphasizes its usefulness for serological survey of tularemia among multiple animal species. PMID:23114700

Graphene oxide-based optical biosensor functionalized with peptides for explosive detection.

PubMed

Zhang, Qian; Zhang, Diming; Lu, Yanli; Yao, Yao; Li, Shuang; Liu, Qingjun

2015-06-15

A label-free optical biosensor was constructed with biofunctionalized graphene oxide (GO) for specific detection of 2,4,6-trinitrotoluene (TNT). By chemically binding TNT-specific peptides with GO, the biosensor gained unique optoelectronic properties and high biological sensitivity, with transducing bimolecular bonding into optical signals. Through UV absorption detection, increasing absorbance responses could be observed in presence of TNT at different concentrations, as low as 4.40×10(-9) mM, and showed dose-dependence and stable behavior. Specific responses of the biosensor were verified with the corporation of 2,6-dinitrotoluene (DNT), which had similar molecular structure to TNT. Thus, with high sensitivity and selectivity, the biosensor provided a convenient approach for detection of explosives as miniaturizing and integrating devices. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiplexed Simultaneous High Sensitivity Sensors with High-Order Mode Based on the Integration of Photonic Crystal 1 × 3 Beam Splitter and Three Different Single-Slot PCNCs.

PubMed

Zhou, Jian; Huang, Lijun; Fu, Zhongyuan; Sun, Fujun; Tian, Huiping

2016-07-07

We simulated an efficient method for the sensor array of high-sensitivity single-slot photonic crystal nanobeam cavities (PCNCs) on a silicon platform. With the combination of a well-designed photonic crystal waveguide (PhCW) filter and an elaborate single-slot PCNC, a specific high-order resonant mode was filtered for sensing. A 1 × 3 beam splitter carefully established was implemented to split channels and integrate three sensors to realize microarrays. By applying the three-dimensional finite-difference-time-domain (3D-FDTD) method, the sensitivities calculated were S₁ = 492 nm/RIU, S₂ = 244 nm/RIU, and S₃ = 552 nm/RIU, respectively. To the best of our knowledge, this is the first multiplexing design in which each sensor cite features such a high sensitivity simultaneously.

Multiplexed Simultaneous High Sensitivity Sensors with High-Order Mode Based on the Integration of Photonic Crystal 1 × 3 Beam Splitter and Three Different Single-Slot PCNCs

PubMed Central

Zhou, Jian; Huang, Lijun; Fu, Zhongyuan; Sun, Fujun; Tian, Huiping

2016-01-01

We simulated an efficient method for the sensor array of high-sensitivity single-slot photonic crystal nanobeam cavities (PCNCs) on a silicon platform. With the combination of a well-designed photonic crystal waveguide (PhCW) filter and an elaborate single-slot PCNC, a specific high-order resonant mode was filtered for sensing. A 1 × 3 beam splitter carefully established was implemented to split channels and integrate three sensors to realize microarrays. By applying the three-dimensional finite-difference-time-domain (3D-FDTD) method, the sensitivities calculated were S1 = 492 nm/RIU, S2 = 244 nm/RIU, and S3 = 552 nm/RIU, respectively. To the best of our knowledge, this is the first multiplexing design in which each sensor cite features such a high sensitivity simultaneously. PMID:27399712

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

PubMed

Dreizin, David; Boscak, Alexis R; Anstadt, Michael J; Tirada, Nikki; Chiu, William C; Munera, Felipe; Bodanapally, Uttam K; Hornick, Michael; Stein, Deborah M

2016-12-01

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. © RSNA, 2016.

Claims-Based Definition of Death in Japanese Claims Database: Validity and Implications

PubMed Central

Ooba, Nobuhiro; Setoguchi, Soko; Ando, Takashi; Sato, Tsugumichi; Yamaguchi, Takuhiro; Mochizuki, Mayumi; Kubota, Kiyoshi

2013-01-01

Background For the pending National Claims Database in Japan, researchers will not have access to death information in the enrollment files. We developed and evaluated a claims-based definition of death. Methodology/Principal Findings We used healthcare claims and enrollment data between January 2005 and August 2009 for 195,193 beneficiaries aged 20 to 74 in 3 private health insurance unions. We developed claims-based definitions of death using discharge or disease status and Charlson comorbidity index (CCI). We calculated sensitivity, specificity and positive predictive values (PPVs) using the enrollment data as a gold standard in the overall population and subgroups divided by demographic and other factors. We also assessed bias and precision in two example studies where an outcome was death. The definition based on the combination of discharge/disease status and CCI provided moderate sensitivity (around 60%) and high specificity (99.99%) and high PPVs (94.8%). In most subgroups, sensitivity of the preferred definition was also around 60% but varied from 28 to 91%. In an example study comparing death rates between two anticancer drug classes, the claims-based definition provided valid and precise hazard ratios (HRs). In another example study comparing two classes of anti-depressants, the HR with the claims-based definition was biased and had lower precision than that with the gold standard definition. Conclusions/Significance The claims-based definitions of death developed in this study had high specificity and PPVs while sensitivity was around 60%. The definitions will be useful in future studies when used with attention to the possible fluctuation of sensitivity in some subpopulations. PMID:23741526

Evaluation of lateral flow devices for identification of infected poultry by testing swab and feather specimens during H5N1 highly pathogenic avian influenza outbreaks in Vietnam.

PubMed

Slomka, Marek J; To, Thanh L; Tong, Hien H; Coward, Vivien J; Mawhinney, Ian C; Banks, Jill; Brown, Ian H

2012-09-01

Evaluation of two commercial lateral flow devices (LFDs) for avian influenza (AI) detection in H5N1 highly pathogenic AI infected poultry in Vietnam. Determine sensitivity and specificity of the LFDs relative to a validated highly sensitive H5 RRT PCR. Swabs (cloacal and tracheal) and feathers were collected from 46 chickens and 48 ducks (282 clinical specimens) and tested by both LFDs and H5 RRT PCR. A subset of 59 chicken and 34 duck specimens was also tested by virus isolation (VI), the 'gold standard'. Twenty-six chickens and 15 ducks were shown to be infected by at least one RRT PCR positive clinical specimen per bird. Bird-level sensitivity for the Anigen LFD was 84·6% for chickens and 53·3% for ducks, and for the Quickvue LFD 65·4% for chickens and 33·3% for ducks. Comparison of the three clinical specimens revealed that chicken feathers were the most sensitive with 84% and 56% sensitivities for Anigen and Quickvue respectively. All 21 RRT PCR positive swabs from ducks were negative by both LFDs. However, duck feather testing gave sensitivities of 53·3% and 33·3% for Anigen and Quickvue respectively. Specificity was 100% for both LFDs in all investigations. Although LFDs were less sensitive than AI RRT PCR and VI, high titre viral shedding in H5N1 highly pathogenic avian influenza (HPAI) infected and diseased chickens is sufficient for a proportion of birds to be identified as AI infected by LFDs. Feathers were the optimal specimen for LFD testing in such diseased HPAI scenarios, particularly for ducks where swab testing by LFDs failed to identify any infected birds. However, specimens should be forwarded to the laboratory for confirmation by more sensitive diagnostic techniques. © 2011 Blackwell Publishing Ltd.

Diagnosis accuracy of two vision screeners for visual health surveillance of workers who use video display terminals

PubMed Central

Molina-Torres, María-José; Crespo, María-del-Mar Seguí; Francés, Ana Tauste; Lacarra, Blanca Lumbreras; Ronda-Pérez, Elena

2016-01-01

Objective: To compare the diagnostic accuracy of two vision screeners by a visual examination performed by an optometrist (gold standard) and to evaluate the concordance between both screeners and between each screener and the gold standard. Methods: This was a cross-sectional study that included computer workers who attended a routine yearly health examination. The study included administrative office workers (n=91) aged 50.2±7.9 years (mean±standard deviation), 69.2% of whom were women and 68.1% of whom used video display terminals (VDT) for >4 h/day. The routine visual examination included monocular and binocular distance visual acuity (VA), distance and near lateral phoria (LP), stereo acuity (SA), and color vision. Tests were repeated with Optec 6500 (by Stereo Optical) and Visiotest (by Essilor) screeners. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and false positive and negative rates were calculated. Kappa coefficient (κ) was used to measure the concordance of the screeners and the gold standard. Results: The sensitivity and specificity for monocular VA were over 80% for both vision screeners; PPV was below 25%. Sensitivity and specificity were lower for SA (55%-70%), PPV was 50%, and NPV was 75% for both screeners. For distance LP, sensitivity and PPV were <10% in both cases. The screeners differed in their values for near LP: Optec 6500 had higher sensitivity (43.5%), PPV (37.0%), and NPV (79.7%); whereas the Visiotest had higher specificity (83.8%). For color vision, Visiotest showed low sensitivity, low PPV, and high specificity. Visiotest obtained false positive rates that were lower or similar to Optec 6500, and both screeners obtained false negative rates below 50%. Both screeners showed poor concordance (κ<0.40). Conclusions: A high value for NPV would qualify both screeners as acceptable alternatives for visual health surveillance when used as a screening tool; patients with positive test results should be referred to a specialist. PMID:27488039

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis.

PubMed

van't Hoog, Anna H; Cobelens, Frank; Vassall, Anna; van Kampen, Sanne; Dorman, Susan E; Alland, David; Ellner, Jerrold

2013-01-01

High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

Quantifying the effect of side branches in endothelial shear stress estimates

PubMed Central

Giannopoulos, Andreas A.; Chatzizisis, Yiannis S.; Maurovich-Horvat, Pal; Antoniadis, Antonios P.; Hoffmann, Udo; Steigner, Michael L.; Rybicki, Frank J.; Mitsouras, Dimitrios

2016-01-01

Background and aims Low and high endothelial shear stress (ESS) is associated with coronary atherosclerosis progression and high-risk plaque features. Coronary ESS is currently assessed via computational fluid dynamic (CFD) simulation in the lumen geometry determined from invasive imaging such as intravascular ultrasound and optical coherence tomography. This process typically omits side branches of the target vessel in the CFD model as invasive imaging of those vessels is not clinically-indicated. The purpose of this study was to determine the extent to which this simplification affects the determination of those regions of the coronary endothelium subjected to pathologic ESS. Methods We determined the diagnostic accuracy of ESS profiling without side branches to detect pathologic ESS in the major coronary arteries of 5 hearts imaged ex vivo with CT angiography. ESS of the three major coronary arteries was calculated both without (test model), and with (reference model) inclusion of all side branches >1.5 mm in diameter, using previously-validated CFD approaches. Diagnostic test characteristics (accuracy, sensitivity, specificity and negative and positive predictive value [NPV/PPV]) with respect to the reference model were assessed for both the entire length as well as only the proximal portion of each major coronary artery, where the majority of high-risk plaques occur. Results Using the model without side branches overall accuracy, sensitivity, specificity, NPV and PPV were 83.4%, 54.0%, 96%, 95.9% and 55.1%, respectively to detect low ESS, and 87.0%, 67.7%, 90.7%, 93.7% and 57.5%, respectively to detect high ESS. When considering only the proximal arteries, test characteristics differed for low and high ESS, with low sensitivity (67.7%) and high specificity (90.7%) to detect low ESS, and low sensitivity (44.7%) and high specificity (95.5%) to detect high ESS. Conclusions The exclusion of side branches in ESS vascular profiling studies greatly reduces the ability to detect regions of the major coronary arteries subjected to pathologic ESS. Single-conduit models can in general only be used to rule out pathologic ESS. PMID:27372207

Quantifying the effect of side branches in endothelial shear stress estimates.

PubMed

Giannopoulos, Andreas A; Chatzizisis, Yiannis S; Maurovich-Horvat, Pal; Antoniadis, Antonios P; Hoffmann, Udo; Steigner, Michael L; Rybicki, Frank J; Mitsouras, Dimitrios

2016-08-01

Low and high endothelial shear stress (ESS) is associated with coronary atherosclerosis progression and high-risk plaque features. Coronary ESS is currently assessed via computational fluid dynamic (CFD) simulation of coronary blood flow in the lumen geometry determined from invasive imaging such as intravascular ultrasound and optical coherence tomography. This process typically omits side branches of the target vessel in the CFD model as invasive imaging of those vessels is not usually clinically-indicated. The purpose of this study was to determine the extent to which this simplification affects the determination of those regions of the coronary endothelium subjected to pathologic ESS. We determined the diagnostic accuracy of ESS profiling without side branches to detect pathologic ESS in the major coronary arteries of 5 hearts imaged ex vivo with computed tomography angiography (CTA). ESS of the three major coronary arteries was calculated both without (test model), and with (reference model) inclusion of all side branches >1.5 mm in diameter, using previously-validated CFD approaches. Diagnostic test characteristics (accuracy, sensitivity, specificity and negative and positive predictive value [NPV/PPV]) with respect to the reference model were assessed for both the entire length as well as only the proximal portion of each major coronary artery, where the majority of high-risk plaques occur. Using the model without side branches overall accuracy, sensitivity, specificity, NPV and PPV were 83.4%, 54.0%, 96%, 95.9% and 55.1%, respectively to detect low ESS, and 87.0%, 67.7%, 90.7%, 93.7% and 57.5%, respectively to detect high ESS. When considering only the proximal arteries, test characteristics differed for low and high ESS, with low sensitivity (67.7%) and high specificity (90.7%) to detect low ESS, and low sensitivity (44.7%) and high specificity (95.5%) to detect high ESS. The exclusion of side branches in ESS vascular profiling studies greatly reduces the ability to detect regions of the major coronary arteries subjected to pathologic ESS. Single-conduit models can in general only be used to rule out pathologic ESS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Mutation-Associated Neoantigen Functional Expansion of Specific T cells (MANAFEST) assay: a sensitive platform for monitoring antitumor immunity.

PubMed

Danilova, Ludmila; Anagnostou, Valsamo; Caushi, Justina X; Sidhom, John-William; Guo, Haidan; Chan, Hok Yee; Suri, Prerna; Tam, Ada J; Zhang, Jiajia; El Asmar, Margueritta; Marrone, Kristen A; Naidoo, Jarushka; Brahmer, Julie R; Forde, Patrick M; Baras, Alexander S; Cope, Leslie; Velculescu, Victor E; Pardoll, Drew; Housseau, Franck; Smith, Kellie N

2018-06-12

Mutation-associated neoantigens (MANAs) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology. Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining (ICS) have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires. The FEST (Functional Expansion of Specific T cells) assay described herein integrates TCR sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications. This assay can be adapted for all types of antigens, including mutation associated neoantigens (MANAs) via tumor exome-guided prediction of MANAs. Following in vitro identification by the MANAFEST assay, the MANA-specific CDR3 sequence can be used as a molecular barcode to detect and monitor the dynamics of these clonotypes in blood, tumor, and normal tissue of patients receiving immunotherapy. MANAFEST is compatible with high-throughput routine clinical and lab practices. Copyright ©2018, American Association for Cancer Research.

Development of an immunomagnetic separation-polymerase chain reaction (IMS-PCR) assay specific for Enterocytozoon bieneusi in water samples.

PubMed

Sorel, N; Guillot, E; Thellier, M; Accoceberry, I; Datry, A; Mesnard-Rouiller, L; Miégeville, M

2003-01-01

Microsporidia have become widely recognized as important human pathogens. Among Microsporidia, Enterocytozoon bieneusi is responsible for severe gastrointestinal disease. To date, no current therapy has been proven effective. Their mode of transmission and environmental occurrence are poorly documented because of the lack of detection methods that are both species-specific and sensitive. In this study, we developed a sensitive and specific molecular method to detect E. bieneusi spores in water samples. The molecular assay combined immunomagnetic separation (IMS) and polymerase chain reaction (PCR) amplification to detect E. bieneusi spores. A comparison was made of IMS magnetic beads coated with two different monoclonal antibodies, one specific for the Encephalitozoon genus that cross-reacts with E. bieneusi and the other specific only for the E. bieneusi species itself. Immunotech beads coated with the antibody specific for E. bieneusi were found to be the most effective combination. The highly specific IMS-PCR assay developed in this study provides a rapid and sensitive means of screening water samples for the presence of E. bieneusi spores.

Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet in obese women.

PubMed

Gray, Dona L; O'Brien, Kevin D; D'Alessio, David A; Brehm, Bonnie J; Deeg, Mark A

2008-04-01

Although circulating glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor high-density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of weight loss or changes in insulin sensitivity on circulating GPI-PLD levels. The objective of the study was to determine the effect of weight loss and changes in insulin sensitivity on plasma GPI-PLD levels. Forty-two nondiabetic obese women were included in the study, which involved a 3-month dietary intervention randomizing patients to a low-fat or a low-carbohydrate diet. The study's main outcome measures were plasma GPI-PLD levels and insulin sensitivity as estimated by the homeostasis model assessment. The very low carbohydrate diet group lost more weight after 3 months (-7.6 +/- 3.2 vs -4.2 +/- 3.5 kg, P < .01), although the decrease in insulin resistance was similar between groups. Weight loss with either diet did not alter plasma GPI-PLD levels. However, baseline GPI-PLD levels correlated with the change in insulin sensitivity in response to the low-fat diet, whereas baseline insulin sensitivity correlated with the change in insulin sensitivity in response to the low-carbohydrate diet. Plasma GPI-PLD may serve as a clinical tool to determine the effect of a low-fat diet on insulin sensitivity.

Highly sensitive and quantitative detection of rare pathogens through agarose droplet microfluidic emulsion PCR at the single-cell level.

PubMed

Zhu, Zhi; Zhang, Wenhua; Leng, Xuefei; Zhang, Mingxia; Guan, Zhichao; Lu, Jiangquan; Yang, Chaoyong James

2012-10-21

Genetic alternations can serve as highly specific biomarkers to distinguish fatal bacteria or cancer cells from their normal counterparts. However, these mutations normally exist in very rare amount in the presence of a large excess of non-mutated analogs. Taking the notorious pathogen E. coli O157:H7 as the target analyte, we have developed an agarose droplet-based microfluidic ePCR method for highly sensitive, specific and quantitative detection of rare pathogens in the high background of normal bacteria. Massively parallel singleplex and multiplex PCR at the single-cell level in agarose droplets have been successfully established. Moreover, we challenged the system with rare pathogen detection and realized the sensitive and quantitative analysis of a single E. coli O157:H7 cell in the high background of 100,000 excess normal K12 cells. For the first time, we demonstrated rare pathogen detection through agarose droplet microfluidic ePCR. Such a multiplex single-cell agarose droplet amplification method enables ultra-high throughput and multi-parameter genetic analysis of large population of cells at the single-cell level to uncover the stochastic variations in biological systems.

Risk of Acute Liver Failure in Patients With Drug-Induced Liver Injury: Evaluation of Hy's Law and a New Prognostic Model.

PubMed

Lo Re, Vincent; Haynes, Kevin; Forde, Kimberly A; Goldberg, David S; Lewis, James D; Carbonari, Dena M; Leidl, Kimberly B F; Reddy, K Rajender; Nezamzadeh, Melissa S; Roy, Jason; Sha, Daohang; Marks, Amy R; De Boer, Jolanda; Schneider, Jennifer L; Strom, Brian L; Corley, Douglas A

2015-12-01

Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Hy's Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76-0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71-0.99) and a specificity value of 0.76 (95% CI, 0.75-0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52-1.00) in the validation analysis. Hy's Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Detectability and anatomical correlation of middle ear cholesteatoma using fused thin slice non-echo planar imaging diffusion-weighted image and magnetic resonance cisternography (FTS-nEPID).

PubMed

Kanoto, Masafumi; Sugai, Yukio; Hosoya, Takaaki; Toyoguchi, Yuuki; Konno, Yoshihiro; Watarai, Fumika; Ito, Tsukasa; Watanabe, Tomoo; Kakehata, Seiji

2015-12-01

Cholesteatomas show high intensity in diffusion-weighted imaging (DWI). We performed fused thin slice non-echo planar imaging (EPI) DWI and magnetic resonance cisternography (FTS-nEPID) for cholesteatoma patients to increase the detectability of FTS-nEPID for cholesteatoma. The subjects are 77 consecutive patients who underwent FTS-nEPID as a preoperative study (mean age: 53.3±21.8, 47 men and 30 women). Otorhinolaryngologists performed the operations. We anatomically classified the middle ear into four portions. A radiologist evaluated the images for cholesteatoma and assessed the anatomical invasive range in four portions using only FTS-nEPID. We classified large cholesteatomas that invaded more than three portions and small ones that invaded less than two portions based on the results obtained from surgery, and calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). For all cholesteatomas with an existing diagnosis, the sensitivity, specificity, PPV, and NPV were 71%, 70%, 94%, and 27%, respectively. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 49%, 85%, 77%, and 64%, respectively. For large cholesteatomas with an existing diagnosis, the sensitivity was 86%. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 51%, 57%, 88%, and 18%, respectively. For small cholesteatomas with an existing diagnosis, the sensitivity, specificity, PPV, and NPV were 59%, 78%, 92%, and 30%, respectively. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 40%, 85%, 60%, and 71%, respectively. FTS-nEPID may be useful for diagnosing cholesteatomas. Further research is needed for anatomical evaluation because there were many false-negative results. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiplexed lateral flow microarray assay for detection of citrus pathogens Xylella fastidiosa and Xanthomonas axonopodis pv citri

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

Cary,; Bruce, R; Stubben, Christopher J

The invention provides highly sensitive and specific assays for the major citrus pathogens Xylella fastidiosa and Xanthomonas axonopodis, including a field deployable multiplexed assay capable of rapidly assaying for both pathogens simultaneously. The assays are directed at particular gene targets derived from pathogenic strains that specifically cause the major citrus diseases of citrus variegated chlorosis (Xylella fastidiosa 9a5c) and citrus canker (Xanthomonas axonopodis pv citri). The citrus pathogen assays of the invention offer femtomole sensitivity, excellent linear dynamic range, and rapid and specific detection.

Parasites under the Spotlight: Applications of Vibrational Spectroscopy to Malaria Research.

PubMed

Perez-Guaita, David; Marzec, Katarzyna M; Hudson, Andrew; Evans, Corey; Chernenko, Tatyana; Matthäus, Christian; Miljkovic, Milos; Diem, Max; Heraud, Philip; Richards, Jack S; Andrew, Dean; Anderson, David A; Doerig, Christian; Garcia-Bustos, Jose; McNaughton, Don; Wood, Bayden R

2018-04-20

New technologies to diagnose malaria at high sensitivity and specificity are urgently needed in the developing world where the disease continues to pose a huge burden on society. Infrared and Raman spectroscopy-based diagnostic methods have a number of advantages compared with other diagnostic tests currently on the market. These include high sensitivity and specificity for detecting low levels of parasitemia along with ease of use and portability. Here, we review the application of vibrational spectroscopic techniques for monitoring and detecting malaria infection. We discuss the role of vibrational (infrared and Raman) spectroscopy in understanding the processes of parasite biology and its application to the study of interactions with antimalarial drugs. The distinct molecular phenotype that characterizes malaria infection and the high sensitivity enabling detection of low parasite densities provides a genuine opportunity for vibrational spectroscopy to become a front-line tool in the elimination of this deadly disease and provide molecular insights into the chemistry of this unique organism.

High Throughput Multiplex PCR and Probe-based Detection with Luminex Beads for Seven Intestinal Parasites

PubMed Central

Taniuchi, Mami; Verweij, Jaco J.; Noor, Zannatun; Sobuz, Shihab U.; van Lieshout, Lisette; Petri, William A.; Haque, Rashidul; Houpt, Eric R.

2011-01-01

Polymerase chain reaction (PCR) assays for intestinal parasites are increasingly being used on fecal DNA samples for enhanced specificity and sensitivity of detection. Comparison of these tests against microscopy and copro-antigen detection has been favorable, and substitution of PCR-based assays for the ova and parasite stool examination is a foreseeable goal for the near future. One challenge is the diverse list of protozoan and helminth parasites. Several existing real-time PCR assays for the major intestinal parasites—Cryptosporidium spp., Giardia intestinalis, Entamoeba histolytica, Ancylostoma duodenale, Ascaris lumbricoides, Necator americanus, and Strongyloides stercoralis—were adapted into a high throughput protocol. The assay involves two multiplex PCR reactions, one with specific primers for the protozoa and one with specific primers for the helminths, after which PCR products are hybridized to beads linked to internal oligonucleotide probes and detected on a Luminex platform. When compared with the parent multiplex real-time PCR assays, this multiplex PCR-bead assay afforded between 83% and 100% sensitivity and specificity on a total of 319 clinical specimens. In conclusion, this multiplex PCR-bead protocol provides a sensitive diagnostic screen for a large panel of intestinal parasites. PMID:21292910

Interpreting IgE sensitization tests in food allergy.

PubMed

Chokshi, Niti Y; Sicherer, Scott H

2016-01-01

Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.

Establishment of the cross-clade antigen detection system for H5 subtype influenza viruses using peptide monoclonal antibodies specific for influenza virus H5 hemagglutinin.

PubMed

Takahashi, Hitoshi; Nagata, Shiho; Odagiri, Takato; Kageyama, Tsutomu

2018-04-15

The H5 subtype of highly pathogenic avian influenza (H5 HPAI) viruses is a threat to both animal and human public health and has the potential to cause a serious future pandemic in humans. Thus, specific and rapid detection of H5 HPAI viruses is required for infection control in humans. To develop a simple and rapid diagnostic system to detect H5 HPAI viruses with high specificity and sensitivity, we attempted to prepare monoclonal antibodies (mAbs) that specifically recognize linear epitopes in hemagglutinin (HA) of H5 subtype viruses. Nine mAb clones were obtained from mice immunized with a synthetic partial peptide of H5 HA molecules conserved among various H5 HPAI viruses. The antigen-capture enzyme-linked immunosorbent assay using the most suitable combination of these mAbs, which bound specifically to lysed H5 HA under an optimized detergent condition, was specific for H5 viruses and could broadly detect H5 viruses in multiple different clades. Taken together, these peptide mAbs, which recognize linear epitopes in a highly conserved region of H5 HA, may be useful for specific and highly sensitive detection of H5 HPAI viruses and can help in the rapid diagnosis of human, avian, and animal H5 virus infections. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison of digital mammography and digital breast tomosynthesis in the detection of architectural distortion.

PubMed

Dibble, Elizabeth H; Lourenco, Ana P; Baird, Grayson L; Ward, Robert C; Maynard, A Stanley; Mainiero, Martha B

2018-01-01

To compare interobserver variability (IOV), reader confidence, and sensitivity/specificity in detecting architectural distortion (AD) on digital mammography (DM) versus digital breast tomosynthesis (DBT). This IRB-approved, HIPAA-compliant reader study used a counterbalanced experimental design. We searched radiology reports for AD on screening mammograms from 5 March 2012-27 November 2013. Cases were consensus-reviewed. Controls were selected from demographically matched non-AD examinations. Two radiologists and two fellows blinded to outcomes independently reviewed images from two patient groups in two sessions. Readers recorded presence/absence of AD and confidence level. Agreement and differences in confidence and sensitivity/specificity between DBT versus DM and attendings versus fellows were examined using weighted Kappa and generalised mixed modeling, respectively. There were 59 AD patients and 59 controls for 1,888 observations (59 × 2 (cases and controls) × 2 breasts × 2 imaging techniques × 4 readers). For all readers, agreement improved with DBT versus DM (0.61 vs. 0.37). Confidence was higher with DBT, p = .001. DBT achieved higher sensitivity (.59 vs. .32), p < .001; specificity remained high (>.90). DBT achieved higher positive likelihood ratio values, smaller negative likelihood ratio values, and larger ROC values. DBT decreases IOV, increases confidence, and improves sensitivity while maintaining high specificity in detecting AD. • Digital breast tomosynthesis decreases interobserver variability in the detection of architectural distortion. • Digital breast tomosynthesis increases reader confidence in the detection of architectural distortion. • Digital breast tomosynthesis improves sensitivity in the detection of architectural distortion.

Comparison of fifteen commercial assays for detecting Varicella Zoster virus IgG with reference to a time resolved fluorescence immunoassay (TRFIA) and the performance of two commercial assays for screening sera from immunocompromised individuals.

PubMed

Chris Maple, P A; Gunn, Annabel; Sellwood, Jane; Brown, David W G; Gray, Jim J

2009-02-01

The performance of fifteen, commercially available, VZV IgG assays and an "in house" indirect immunofluorescence (IF) assay has been compared to a reference VZV IgG time resolved immunofluorescence assay (VZV TRFIA). A panel of 273 VZV TRFIA IgG positive serum samples and 136 VZV TRFIA IgG susceptible sera, collected from a number of UK hospitals was used. Irrespective of the interpretation of equivocal results the most sensitive assays were Dade Behring EIA (97.4%), "in house" IF (95.2%), Human EIA (92.3%) and Becton Dickinson latex agglutination (94.1%). The least sensitive assays were Virion EIA (69.6%), Diesse EIA (68.9%) and Diasys EIA (68.5%). The least sensitive (<70%) assays all had >99.0% specificity whereas the most sensitive assays had lower specificities; for example, Dade Behring EIA had a specificity of 69.9% when equivocals were treated as VZV IgG negative. For some assays e.g. Dade Behring EIA there were major discrepancies between our findings and those reported by the manufacturer which may reflect the constitution of the panel(s) of sera used for evaluation or the reference method adopted or the choice of cut-off criteria (particularly relevant to our findings for the Behring EIA). Care must be taken to choose an assay with high specificity in order to accurately assess the need for vaccination or immunoprophylaxis; however, high sensitivity is preferable to prevent inappropriate and expensive treatment.

The role of cone-beam breast-CT for breast cancer detection relative to breast density.

PubMed

Wienbeck, Susanne; Uhlig, Johannes; Luftner-Nagel, Susanne; Zapf, Antonia; Surov, Alexey; von Fintel, Eva; Stahnke, Vera; Lotz, Joachim; Fischer, Uwe

2017-12-01

To evaluate the impact of breast density on the diagnostic accuracy of non-contrast cone-beam breast computed tomography (CBBCT) in comparison to mammography for the detection of breast masses. A retrospective study was conducted from August 2015 to July 2016. Fifty-nine patients (65 breasts, 112 lesions) with BI-RADS, 5th edition 4 or 5 assessment in mammography and/or ultrasound of the breast received an additional non-contrast CBBCT. Independent double blind reading by two radiologists was performed for mammography and CBBCT imaging. Sensitivity, specificity and AUC were compared between the modalities. Breast lesions were histologically examined in 85 of 112 lesions (76%). The overall sensitivity for CBBCT (reader 1: 91%, reader 2: 88%) was higher than in mammography (both: 68%, p<0.001), and also for the high-density group (p<0.05). The specificity and AUC was higher for mammography in comparison to CBBCT (p<0.05 and p<0.001). The interobserver agreement (ICC) between the readers was 90% (95% CI: 86-93%) for mammography and 87% (95% CI: 82-91%) for CBBCT. Compared with two-view mammography, non-contrast CBBCT has higher sensitivity, lower specificity, and lower AUC for breast mass detection in both high and low density breasts. • Overall sensitivity for non-contrast CBBCT ranged between 88%-91%. • Sensitivity was higher for CBBCT than mammography in both density types (p<0.001). • Specificity was higher for mammography than CBBCT in both density types (p<0.05). • AUC was larger for mammography than CBBCT in both density types (p<0.001).

Improved oxygenation 24 hours after transition to airway pressure release ventilation or high-frequency oscillatory ventilation accurately discriminates survival in immunocompromised pediatric patients with acute respiratory distress syndrome*.

PubMed

Yehya, Nadir; Topjian, Alexis A; Thomas, Neal J; Friess, Stuart H

2014-05-01

Children with an immunocompromised condition and requiring invasive mechanical ventilation have high risk of death. Such patients are commonly transitioned to rescue modes of nonconventional ventilation, including airway pressure release ventilation and high-frequency oscillatory ventilation, for acute respiratory distress syndrome refractory to conventional ventilation. Our aim was to describe our experience with airway pressure release ventilation and high-frequency oscillatory ventilation in children with an immunocompromised condition and acute respiratory distress syndrome refractory to conventional ventilation and to identify factors associated with survival. Retrospective cohort study. Tertiary care, university-affiliated PICU. Sixty pediatric patients with an immunocompromised condition and acute respiratory distress syndrome refractory to conventional ventilation transitioned to either airway pressure release ventilation or high-frequency oscillatory ventilation. None. Demographic data, ventilator settings, arterial blood gases, oxygenation index, and PaO(2)/FIO(2) were recorded before transition to either mode of nonconventional ventilation and at predetermined intervals after transition for up to 5 days. Mortality in the entire cohort was 63% and did not differ between patients transitioned to airway pressure release ventilation and high-frequency oscillatory ventilation. For both airway pressure release ventilation and high-frequency oscillatory ventilation, improvements in oxygenation index and PaO(2)/FIO(2) at 24 hours expressed as a fraction of pretransition values (oxygenation index(24)/oxygenation index(pre) and PaO(2)/FIO(224)/PaO(2)/FIO(2pre)) reliably discriminated nonsurvivors from survivors, with receiver operating characteristic areas under the curves between 0.89 and 0.95 (p for all curves < 0.001). Sensitivity-specificity analysis suggested that less than 15% reduction in oxygenation index (90% sensitive, 75% specific) or less than 90% increase in PaO(2)/FIO(2) (80% sensitive, 94% specific) 24 hours after transition to airway pressure release ventilation were the optimal cutoffs to identify nonsurvivors. The comparable values 24 hours after transition to high-frequency oscillatory ventilation were less than 5% reduction in oxygenation index (100% sensitive, 83% specific) or less than 80% increase in PaO(2)/FIO(2) (91% sensitive, 89% specific) to identify nonsurvivors. In this single-center retrospective study of pediatric patients with an immunocompromised condition and acute respiratory distress syndrome failing conventional ventilation transitioned to either airway pressure release ventilation or high-frequency oscillatory ventilation, improved oxygenation at 24 hours expressed as PaO(2)/FIO(224)/PaO(2)/FIO(2pre) or oxygenation index(24)/oxygenation indexpre reliably discriminates nonsurvivors from survivors. These findings should be prospectively verified.

Detection of knockdown resistance (kdr) mutations in Anopheles gambiae: a comparison of two new high-throughput assays with existing methods

PubMed Central

Bass, Chris; Nikou, Dimitra; Donnelly, Martin J; Williamson, Martin S; Ranson, Hilary; Ball, Amanda; Vontas, John; Field, Linda M

2007-01-01

Background Knockdown resistance (kdr) is a well-characterized mechanism of resistance to pyrethroid insecticides in many insect species and is caused by point mutations of the pyrethroid target site the para-type sodium channel. The presence of kdr mutations in Anopheles gambiae, the most important malaria vector in Africa, has been monitored using a variety of molecular techniques. However, there are few reports comparing the performance of these different assays. In this study, two new high-throughput assays were developed and compared with four established techniques. Methods Fluorescence-based assays based on 1) TaqMan probes and 2) high resolution melt (HRM) analysis were developed to detect kdr alleles in An. gambiae. Four previously reported techniques for kdr detection, Allele Specific Polymerase Chain Reaction (AS-PCR), Heated Oligonucleotide Ligation Assay (HOLA), Sequence Specific Oligonucleotide Probe – Enzyme-Linked ImmunoSorbent Assay (SSOP-ELISA) and PCR-Dot Blot were also optimized. The sensitivity and specificity of all six assays was then compared in a blind genotyping trial of 96 single insect samples that included a variety of kdr genotypes and African Anopheline species. The relative merits of each assay was assessed based on the performance in the genotyping trial, the length/difficulty of each protocol, cost (both capital outlay and consumable cost), and safety (requirement for hazardous chemicals). Results The real-time TaqMan assay was both the most sensitive (with the lowest number of failed reactions) and the most specific (with the lowest number of incorrect scores). Adapting the TaqMan assay to use a PCR machine and endpoint measurement with a fluorimeter showed a slight reduction in sensitivity and specificity. HRM initially gave promising results but was more sensitive to both DNA quality and quantity and consequently showed a higher rate of failure and incorrect scores. The sensitivity and specificity of AS-PCR, SSOP-ELISA, PCR Dot Blot and HOLA was fairly similar with a small number of failures and incorrect scores. Conclusion The results of blind genotyping trials of each assay indicate that where maximum sensitivity and specificity are required the TaqMan real-time assay is the preferred method. However, the cost of this assay, particularly in terms of initial capital outlay, is higher than that of some of the other methods. TaqMan assays using a PCR machine and fluorimeter are nearly as sensitive as real-time assays and provide a cost saving in capital expenditure. If price is a primary factor in assay choice then the AS-PCR, SSOP-ELISA, and HOLA are all reasonable alternatives with the SSOP-ELISA approach having the highest throughput. PMID:17697325

A highly sensitive and selective aptamer-based colorimetric sensor for the rapid detection of PCB 77.

PubMed

Cheng, Ruojie; Liu, Siyao; Shi, Huijie; Zhao, Guohua

2018-01-05

A highly sensitive, specific and simple colorimetric sensor based on aptamer was established for the detection of polychlorinated biphenyls (PCB 77). The use of unmodified gold nanoparticles as a colorimetric probe for aptamer sensors enabled the highly sensitive and selective detection of polychlorinated biphenyls (PCB 77). A linear range of 0.5nM to 900nM was obtained for the colorimetric assay with a minimum detection limit of 0.05nM. In addition, by the methods of circular dichroism, UV and naked eyes, we found that the 35 base fragments retained after cutting 5 bases from the 5 'end of aptamer plays the most significant role in the PCB 77 specific recognition process. We found a novel way to truncated nucleotides to optimize the detection of PCB 77, and the selected nucleotides also could achieve high affinity with PCB 77. At the same time, the efficient detection of the PCB 77 by our colorimetric sensor in the complex environmental water samples was realized, which shows a good application prospect. Copyright © 2017 Elsevier B.V. All rights reserved.

Necrotizing Soft Tissue Infection: Diagnostic Accuracy of Physical Examination, Imaging, and LRINEC Score: A Systematic Review and Meta-Analysis.

PubMed

Fernando, Shannon M; Tran, Alexandre; Cheng, Wei; Rochwerg, Bram; Kyeremanteng, Kwadwo; Seely, Andrew J E; Inaba, Kenji; Perry, Jeffrey J

2018-04-18

We sought to summarize accuracy of physical examination, imaging, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score in diagnosis of necrotizing soft tissue infection (NSTI) in adults with a soft tissue infection clinically concerning for NSTI. NSTI is a life-threatening diagnosis. Delay to diagnosis and surgical management is associated with increased mortality. We searched 6 databases from inception through November 2017. We included English-language studies reporting diagnostic accuracy of testing or LRINEC Score. Outcome was NSTI confirmed by surgery or histopathology. Two reviewers screened all citations and extracted data independently. Summary measures were obtained from the Hierarchical Summary Receiver Operating Characteristic model. From 2,290 citations, we included 23 studies (n = 5982). Of physical examination signs, pooled sensitivity and specificity for fever was 46.0% and 77.0% respectively, for hemorrhagic bullae 25.2% and 95.8%, and for hypotension 21.0% and 97.7%. Computed tomography (CT) had sensitivity of 88.5% and specificity of 93.3%, while plain radiography had sensitivity of 48.9% and specificity of 94.0%. Finally, LRINEC ≥ 6 had sensitivity of 68.2% and specificity of 84.8%, while LRINEC ≥ 8 had sensitivity of 40.8% and specificity of 94.9%. Absence of any 1 physical examination feature (eg, fever or hypotension) is not sufficient to rule-out NSTI. CT is superior to plain radiography. LRINEC had poor sensitivity, and should not be used to rule-out NSTI. Given the poor sensitivity of these tests, a high clinical suspicion warrants early surgical consultation for definitive diagnosis and management.

Reliability, validity, sensitivity and specificity of Guajarati version of the Roland-Morris Disability Questionnaire.

PubMed

Nambi, S Gopal

2013-01-01

The most common instruments developed to assess the functional status of patients with Non specific low back pain is the Roland-Morris Disability Questionnaire (RMDQ). Clinical and epidemiological research related to low back pain in the Gujarati population would be facilitated by the availability of well-established outcome measures. To find the reliability, validity, sensitivity and specificity of the Gujarati version of the RMDQ for use in Non Specific Chronic low back pain. A reliability, validity, sensitivity and specificity study of Gujarati version of the Roland-Morris Disability Questionnaire (RMDQ). Thirty out patients with Non Specific Chronic low back pain were assessed by the RMDQ. Reliability is assessed by using internal consistency and the intra-class correlation coefficient (ICC). Internal construct validity is assessed by RASCH Analysis and external construct validity is assessed by association with pain and spinal movement. Clinical calculator was used to determine the sensitivity and specificity. Internal consistency of the RMDQ is found to be adequate (> 0.65) at both times, with high ICC's also at both time points. Internal construct validity of the scale is good, indicating a single underlying construct. Expected associations with pain and spinal movement confirm external construct validity. The Sensitivity and Specificity at cut off point of 0.5 was 80% and 84% with respectively positive predictive value (PPV) of 83.33% and negative predictive value (NPV) of 80.76%. The Questionnaire is at the ordinal level. The RMDQ is a one-dimensional, ordinal measure, which works well in the Gujarati population.

Determining sensitivity/specificity of virtual reality-based neuropsychological tool for detecting residual abnormalities following sport-related concussion.

PubMed

Teel, Elizabeth; Gay, Michael; Johnson, Brian; Slobounov, Semyon

2016-05-01

Computer-based neuropsychological (NP) evaluation is an effective clinical tool used to assess cognitive function which complements the clinical diagnosis of a concussion. However, some researchers and clinicians argue its lack of ecological validity places limitations on externalizing results to a sensory rich athletic environment. Virtual reality-based NP assessment offers clinical advantages using an immersive environment and evaluating domains not typically assessed by traditional NP assessments. The sensitivity and specificity of detecting lingering cognitive abnormalities was examined on components of a virtual reality-based NP assessment battery to cohort affiliation (concussed vs. controls). Data were retrospectively gathered on 128 controls (no concussion) and 24 concussed college-age athletes on measures of spatial navigation, whole body reaction, attention, and balance in a virtual environment. Concussed athletes were tested within 10 days (M = 8.33, SD = 1.06) of concussion and were clinically asymptomatic at the time of testing. A priori alpha level was set at 0.05 for all tests. Spatial navigation (sensitivity 95.8%/specificity 91.4%, d = 1.89), whole body reaction time (sensitivity 95.2%/specificity 89.1%, d = 1.50) and combined virtual reality modules (sensitivity 95.8%,/specificity 96.1%, d = 3.59) produced high sensitivity/specificity values when determining performance-based variability between groups. Use of a virtual reality-based NP platform can detect lingering cognitive abnormalities resulting from concussion in clinically asymptomatic participants. Virtual reality NP platforms may compliment the traditional concussion assessment battery by providing novel information. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Accuracy of dementia diagnosis: a direct comparison between radiologists and a computerized method.

PubMed

Klöppel, Stefan; Stonnington, Cynthia M; Barnes, Josephine; Chen, Frederick; Chu, Carlton; Good, Catriona D; Mader, Irina; Mitchell, L Anne; Patel, Ameet C; Roberts, Catherine C; Fox, Nick C; Jack, Clifford R; Ashburner, John; Frackowiak, Richard S J

2008-11-01

There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimer's disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimer's disease and controls into their respective groups. Radiologists correctly classified 65-95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimer's disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimer's disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimer's disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice.

Accuracy of dementia diagnosis—a direct comparison between radiologists and a computerized method

PubMed Central

Stonnington, Cynthia M.; Barnes, Josephine; Chen, Frederick; Chu, Carlton; Good, Catriona D.; Mader, Irina; Mitchell, L. Anne; Patel, Ameet C.; Roberts, Catherine C.; Fox, Nick C.; Jack, Clifford R.; Ashburner, John; Frackowiak, Richard S. J.

2008-01-01

There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimer's disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimer's disease and controls into their respective groups. Radiologists correctly classified 65–95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimer's disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimer's disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimer's disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice. PMID:18835868

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.

Estimation of sensitivity and specificity of brain magnetic resonance imaging and single photon emission computed tomography in the diagnosis of olfactory dysfunction after head traumas.

PubMed

Atighechi, Saeid; Zolfaghari, Aliasghar; Baradaranfar, Mohammadhossein; Dadgarnia, Mohammadhossein

2013-01-01

Olfactory dysfunction has an incidence of 5-10% after head injury. Several objective and subjective tests had been proposed. Recent studies showed that brain single photon emission computed tomography (SPECT) and brain magnetic resonance imaging (MRI) have good diagnostic value in this era in which the most common sites of involvement were olfactory bulb and olfactory nerve in MRI and frontal lobe in SPECT. This study aimed to estimate the sensitivity and specificity of brain MRI and brain SPECT in the diagnosis of traumatic hyposmia and anosmia. From February 2009 to March 2011, 63 patients with head injury and smell complaint were selected for this study. Using an identification test and a threshold smell test, 28 were anosmic and 27 had hyposmia and the remaining 8 were normosmic. All of them underwent brain MRI and SPECT. The sensitivity of SPECT was 81.5 and 85.7% in hyposmia and anosmia, respectively. Its specificity was 87.5% in anosmia and 87.7% in anosmia. MRI sensitivity was 66.7% in hyposmia but 82.1% in anosmia. Its specificity was 85.7% in anosmia and 87.7% in anosmia. If MRI and SPECT were considered together, the sensitivity was 92.3% in hyposmia and 92% in anosmia, but the specificity was 87% in both cases. According to our study, both brain MRI and SPECT have high sensitivity and specificity in the diagnosis of traumatic anosmia, although brain SPECT is slightly superior to MRI. If the two techniques are applied together, the accuracy will be increased.

Antibody conjugated glycine doped polyaniline nanofilms as efficient biosensor for atrazine

NASA Astrophysics Data System (ADS)

Bhardwaj, Sanjeev K.; Sharma, Amit L.; Kim, Ki-Hyun; Deep, Akash

2017-12-01

Atrazine is an important member of triazine family of pesticides. The development of its detection methods gained great attention due to the potential health risks associated with its contamination in various media including water, soil, and food. The contamination of atrazine in drinking water beyond the legal permissible limit of EPA (e.g. 3 ng ml-1) may cause various damages to living organisms (e.g. heart, urinary, and limb defects). In this research, we discuss the potential significance of a highly sensitive conductometric immunosensor for sensing the atrazine pesticide. To this end, electrochemical assembly of glycine doped polyaniline (PAni) nanofilms on silicon (Si) substrate was built and modified further with anti-atrazine antibodies. The herein developed immunosensor offered highly sensitive detection of atrazine with a low detection limit of 0.07 ng ml-1. The proposed biosensor was simple in design with excellent performance in terms of its sensitivity, stability and specificity. Highlights •Glycine doped PAni nanofilms have been electropolymerized on Silicon substrates. •Functionality of the above thin films provides opportunity to develop an immunosensing platform. •Highly sensitive and specific detection of atrazine has been realized over a wide concentration range with a LOD of 0.07 ng ml-1. Novelty statement Atrazine is a widely used pesticide in the agriculture sector. It is highly recommended to develop simple biosensing systems for enabling the prospect of routine monitoring. The present research for the first time proposes the design of a glycine doped PAni based simple and highly effective biosensor for the atrazine pesticide. The doping of glycine has easily generated functional groups on the nano-PAni material for further convenient immobilization of anti-atrazine antibodies. The proposed sensor can be highlighted with advantages like ease of fabrication, use of environment friendly functionalization agent, specificity, wide linearity, and good sensitivity with enhanced viability.

Circulation of Crimean-Congo Hemorrhagic Fever Virus in the Former Yugoslav Republic of Macedonia Revealed by Screening of Cattle Sera Using a Novel Enzyme-linked Immunosorbent Assay

PubMed Central

Mertens, Marc; Vatansever, Zati; Mrenoshki, Slavcho; Krstevski, Kiril; Stefanovska, Jovana; Djadjovski, Igor; Cvetkovikj, Iskra; Farkas, Robert; Schuster, Isolde; Donnet, Fabien; Comtet, Loic; Tordo, Noël; Ben Mechlia, Mohamed; Balkema-Buschmann, Anne; Mitrov, Dine; Groschup, Martin H.

2015-01-01

Background There are only few assays available for the detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)-specific antibodies in animals, and data about diagnostic sensitivity and specificity are incompletely documented for most of these tests. This is unfortunate since CCHFV antibodies in animals can be used as indicator for virus circulation in a geographic area and therewith potential risk of human exposure. This paper therefore reports on a novel ELISA for the detection of CCHFV-specific antibodies in cattle and on its application for testing ruminant sera from the Former Yugoslav Republic of Macedonia. Principal Findings A highly sensitive and specific ELISA was developed to detect CCHFV-specific IgG antibodies in cattle. The assay was validated by using 503 negative serum samples from a country where CCHFV has never been detected until now, and by using 54 positive serum samples. The positive sera were verified by using two commercially available assays (for testing human serum) which we have adapted for use in animals. The sensitivity of the novel ELISA was 98% and its specificity 99%. The presence of Hyalomma ticks was demonstrated in the Former Yugoslav Republic of Macedonia and depending on the region antibody prevalence rates up to 80% were detected in the cattle population. Conclusion This article describes a fully validated, highly sensitive and specific ELISA for the detection of CCHFV-specific IgG antibodies in cattle. Using this assay, CCHFV-specific antibodies were detected for the first time in cattle in the Former Yugoslav Republic of Macedonia, giving evidence for an active circulation of this virus in the country. Supporting this conclusion, the occurrence of the main vector of CCHFV was demonstrated in the present work for the first time in Former Yugoslav Republic of Macedonia. PMID:25742017

High-sensitivity explosives detection using dual-excitation-wavelength resonance-Raman detector

NASA Astrophysics Data System (ADS)

Yellampalle, Balakishore; McCormick, William B.; Wu, Hai-Shan; Sluch, Mikhail; Martin, Robert; Ice, Robert V.; Lemoff, Brian

2014-05-01

A key challenge for standoff explosive sensors is to distinguish explosives, with high confidence, from a myriad of unknown background materials that may have interfering spectral peaks. To meet this challenge a sensor needs to exhibit high specificity and high sensitivity in detection at low signal-to-noise ratio levels. We had proposed a Dual-Excitation- Wavelength Resonance-Raman Detector (DEWRRED) to address this need. In our previous work, we discussed various components designed at WVHTCF for a DEWRRED sensor. In this work, we show a completely assembled laboratory prototype of a DEWRRED sensor and utilize it to detect explosives from two standoff distances. The sensor system includes two novel, compact CW deep-Ultraviolet (DUV) lasers, a compact dual-band high throughput DUV spectrometer, and a highly-sensitive detection algorithm. We choose DUV excitation because Raman intensities from explosive traces are enhanced and fluorescence and solar background are not present. The DEWRRED technique exploits the excitation wavelength dependence of Raman signal strength, arising from complex interplay of resonant enhancement, self-absorption and laser penetration depth. We show measurements from >10 explosives/pre-cursor materials at different standoff distances. The sensor showed high sensitivity in explosive detection even when the signalto- noise ratio was close to one (~1.6). We measured receiver-operating-characteristics, which show a clear benefit in using the dual-excitation-wavelength technique as compared to a single-excitation-wavelength technique. Our measurements also show improved specificity using the amplitude variation information in the dual-excitation spectra.

Receiver operating characteristic analysis of prediction for gastric cancer development using serum pepsinogen and Helicobacter pylori antibody tests.

PubMed

Hamashima, Chisato; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

2017-03-09

Chronic Helicobacter pylori infection plays a central role in the development of gastric cancer as shown by biological and epidemiological studies. The H. pylori antibody and serum pepsinogen (PG) tests have been anticipated to predict gastric cancer development. We determined the predictive sensitivity and specificity of gastric cancer development using these tests. Receiver operating characteristic analysis was performed, and areas under the curve were estimated. The predictive sensitivity and specificity of gastric cancer development were compared among single tests and combined methods using serum pepsinogen and H. pylori antibody tests. From a large-scale population-based cohort of over 100,000 subjects followed between 1990 and 2004, 497 gastric cancer subjects and 497 matched healthy controls were chosen. The predictive sensitivity and specificity were low in all single tests and combination methods. The highest predictive sensitivity and specificity were obtained for the serum PG I/II ratio. The optimal PG I/II cut-off values were 2.5 and 3.0. At a PG I/II cut-off value of 3.0, the sensitivity was 86.9% and the specificity was 39.8%. Even if three biomarkers were combined, the sensitivity was 97.2% and the specificity was 21.1% when the cut-off values were 3.0 for PG I/II, 70 ng/mL for PG I, and 10.0 U/mL for H. pylori antibody. The predictive accuracy of gastric cancer development was low with the serum pepsinogen and H. pylori antibody tests even if these tests were combined. To adopt these biomarkers for gastric cancer screening, a high specificity is required. When these tests are adopted for gastric cancer screening, they should be carefully interpreted with a clear understanding of their limitations.

Promoter methylation of MCAM, ERα and ERβ in serum of early stage prostate cancer patients.

PubMed

Brait, Mariana; Banerjee, Mithu; Maldonado, Leonel; Ooki, Akira; Loyo, Myriam; Guida, Elisa; Izumchenko, Evgeny; Mangold, Leslie; Humphreys, Elizabeth; Rosenbaum, Eli; Partin, Alan; Sidransky, David; Hoque, Mohammad Obaidul

2017-02-28

Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.8 % and specificity is 41.1%. As a result, the serum PSA test leads to numerous unneeded biopsies. Therefore, a rigorous search for biomarkers for early detection of PC is ongoing. In this study, we aim to assess a panel of epigenetic markers in an intend to develop an early detection test for PC. The sensitivity and specificity of hypermethylation of MCAM was 66% and 73% respectively which is an improvement from the sensitivity and specificity of PSA. Considering a combination marker panel of MCAM, ERα and ERβ increased the sensitivity to 75% and the specificity became 70% for the minimally invasive early detection test of PC. Sixteen primary matched tumor and serum were analyzed by quantitative methylation specific PCR (QMSP) to determine analytical and clinical sensitivity of the genes tested (SSBP2, MCAM, ERα, ERβ, APC, CCND2, MGMT, GSTP1, p16 and RARβ2). Additionally, serum samples from eighty four cases of PC, thirty controls and seven cases diagnosed as high grade Prostatic Intraepithelial Neoplasia (HGPIN) were analyzed. Promoter methylation of MCAM, ERα and ERβ have a potential to be utilized as biomarker for the early detection of prostate PC as their sensitivity and specificity seem to be better than serum PSA in our cohort of samples. After robust validation in a larger prospective cohort, our findings may reduce the numbers of unwarranted prostate biopsies.

Clinical applicability of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases with Raynaud's phenomenon.

PubMed

Wu, Po-Chang; Huang, Min-Nung; Kuo, Yu-Min; Hsieh, Song-Chou; Yu, Chia-Li

2013-08-01

Nailfold capillaroscopy is a useful tool to distinguish primary from secondary Raynaud's phenomenon (RP) by examining the morphology of nailfold capillaries but its role in disease diagnosis is not clearly established. The purpose of this study was to evaluate the roles of quantitative nailfold capillaroscopy in differential diagnosis of connective tissue diseases (CTDs) with RP. The data between the year 2005 and 2009 were retrieved from the nailfold capillaroscopic database of National Taiwan University Hospital (NTUH). Only the data from the patients with RP were analyzed. The criteria for interpretation of capillaroscopic findings were predefined. The final diagnoses of the patients were based on the American College of Rheumatology classification criteria for individual diseases, independent of nailfold capillaroscopic findings. The sensitivity and the specificity of each capillaroscopic pattern to the diseases were determined. The data from a total of 67 patients were qualified for the current study. We found the sensitivity and specificity of scleroderma pattern for systemic sclerosis (SSc) were 89.47% and 80%, and the specificity of the early, active, and late scleroderma patterns for SSc reached 87.5%, 97.5%, and 95%, respectively. The sensitivity/specificity of systemic lupus erythematosus (SLE) pattern for SLE and polymyositis/dermatomyositis (PM/DM) pattern for PM/DM were 33.33%/95.45% and 60%/96.3%, respectively. The sensitivity/specificity of mixed connective tissue disease (MCTD) pattern for MCTD were 20%/100%. The nailfold capillaroscopic (NC) patterns may be useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD patterns exhibit high specificity but relatively low sensitivity. Copyright © 2012. Published by Elsevier B.V.

The oblique effect has an optical component: Orientation-specific contrast thresholds after correction of high-order aberrations

PubMed Central

Murray, Ian J.; Elliott, Sarah L.; Pallikaris, Aris; Werner, John S.; Choi, Stacey; Tahir, Humza J.

2010-01-01

Most of the high-order aberrations of the eye are not circularly symmetric. Hence, while it is well known that human vision is subject to cortically based orientation preference in cell tuning, the optics of the eye might also introduce some orientational anisotropy. We tested this idea by measuring contrast sensitivity at different orientations of sine-wave gratings when viewing through a closed-loop adaptive optics phoropter. Under aberration-corrected conditions, mean contrast sensitivity improved for all observers by a factor of 1.8× to 5×. The detectability of some orientations improved more than others. As expected, this orientation-specific effect varied between individuals. The sensitivity benefits were accurately predicted from MTF model simulations, demonstrating that the observed effects reflected the individual's pattern of high-order aberrations. In one observer, the orientation-specific effects were substantial: an improvement of 8× at one orientation and 2× in another orientation. The experiments confirm that, for conditions that are not diffraction limited, the optics of the eye introduce rotational asymmetry to the luminance distribution on the retina and that this impacts vision, inducing orientational anisotropy. These results suggest that the traditional view of meridional anisotropy having an entirely neural origin may be true for diffraction-limited pupils but that viewing through larger pupils introduces an additional orientation-specific optical component to this phenomenon. PMID:20884505

Chemokines additional to IFN-γ can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype.

PubMed

Nonghanphithak, Ditthawat; Reechaipichitkul, Wipa; Namwat, Wises; Naranbhai, Vivek; Faksri, Kiatichai

2017-07-01

Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON ® -TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16.7% sensitivity; CCL2 showed moderate sensitivity (70.8%) and specificity (74.4%); CXCL10 showed high sensitivity (87.5%) and specificity (78.9%). Compared to IFN-γ alone, IFN-γ combined with CXCL10 significantly improved (p < 0.001) the sensitivity and specificity to discriminate between ATB and HC (97.9% sensitivity and 94.9% specificity) and between ATB and LTBI (89.6% sensitivity and 71.1% specificity). Levels of CCL2 were very significantly lower (p < 0.0001) in EC compared to HC groups and hence CCL2 is a useful marker for EC. This study demonstrated the potential application of profiling using multiple chemokines for differentiating among the various M. tuberculosis infection possibilities. We also present evidence to support the EC phenomenon based on the decrease of CCL2 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accidental falls in hospital inpatients: evaluation of sensitivity and specificity of two risk assessment tools.

PubMed

Lovallo, Carmela; Rolandi, Stefano; Rossetti, Anna Maria; Lusignani, Maura

2010-03-01

This paper is a report of a study comparing the effectiveness of two falls risk assessment tools (Conley Scale and Hendrich Risk Model) by using them simultaneously with the same sample of hospital inpatients. Different risk assessment tools are available in literature. However, neither recent critical reviews nor international guidelines on fall prevention have identified tools that can be generalized to all categories of hospitalized patients. A prospective observational study was carried out in acute medical, surgical wards and rehabilitation units. From October 2007 to January 2008, 1148 patients were assessed with both instruments, subsequently noting the occurrence of falls. The sensitivity, specificity, positive and negative predictive values, and Receiver Operating Characteristics curves were calculated. The number of patients correctly identified with the Conley Scale (n = 41) was higher than with the Hendrich Model (n = 27). The Conley Scale gave sensitivity and specificity values of 69.49% and 61% respectively. The Hendrich Model gave a sensitivity value of 45.76% and a specificity value of 71%. Positive and negative predictive values were comparable. The Conley Scale is indicated for use in the medical sector, on the strength of its high sensitivity. However, since its specificity is very low, it is deemed useful to submit individual patients giving positive results to more in-depth clinical evaluation in order to decide whether preventive measures need to be taken. In surgical sectors, the low sensitivity values given by both scales suggest that further studies are warranted.

3D fluid-attenuated inversion recovery imaging: reduced CSF artifacts and enhanced sensitivity and specificity for subarachnoid hemorrhage.

PubMed

Lummel, N; Schoepf, V; Burke, M; Brueckmann, H; Linn, J

2011-12-01

FLAIR images are highly sensitive for SAH. However, CSF flow artifacts caused by conventional FLAIR can produce false-positive results. Here, we compare 3D and 3D FLAIR sequences, focusing on their potential for containing these artifacts and their sensitivity and specificity for detection of SAHs. We evaluated the following 4 FLAIR sequences: 1) 2D FLAIR at 1.5T, 2) 2D FLAIR, 3) 2D PROPELLER-FLAIR, and 4) 3D Cube-FLAIR at 3T. All sequences were performed in 5 healthy volunteers; sequences 2 and 4 were also performed under routine conditions in 10 patients with focal epilepsy and in 10 patients with SAH. Two neuroradiologists independently conducted the analysis. The presence of flow artifacts in the ventricles and cisterns of healthy volunteers and patients with epilepsy was evaluated and scored on a 4-point scale. Mean values were calculated and compared by using paired t tests. Sensitivity and specificity for SAH detection in sequences 2 and 4 were determined. Cube-FLAIR showed almost no CSF artifacts in the volunteers and the patients with epilepsy; therefore, it was superior to any other FLAIR (P < .001). Sensitivity and specificity of SAH detection by 3T FLAIR were 58.3% and 89.4%, respectively, whereas Cube-FLAIR had a sensitivity of 95% and a specificity of 100%. Cube-FLAIR allows FLAIR imaging with almost no CSF artifacts and is, thus, particularly useful for SAH detection.

Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection.

PubMed

Fortner, Renée Turzanski; Damms-Machado, Antje; Kaaks, Rudolf

2017-11-01

Tumor-associated autoantibodies (AAbs), produced as an immune response to tumor-associated antigens (TAAs), are a novel pathway of early detection markers. We conducted a systematic review on AAbs and ovarian cancer to summarize the diagnostic performance of individual AAbs and AAb panels. A total of 29 studies including 85 AAbs were included; 27 of the studies were conducted in prevalent cases and cancer-free controls and 2 investigations included pre-diagnosis samples. The majority of studies were hypothesis-driven, evaluating AAbs to target TAAs; 10 studies used screening approaches such as serological expression cloning (SEREX) and nucleic acid-programmable protein arrays (NAPPA). The highest sensitivities for individual AAbs were reported for RhoGDI-AAbs (89.5%) and TUBA1C-AAbs (89%); however, specificity levels were relatively low (80% and 75%, respectively). High sensitivities at high specificities were reported for HOXA7-AAbs for detection of moderately differentiated ovarian tumors (66.7% sensitivity at 100% specificity) and IL8-AAbs in stage I-II ovarian cancer (65.5% sensitivity at 98% specificity). A panel of 11 AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) provided 45% sensitivity at 98% specificity for serous ovarian cancer, when at least 2 AAbs were above a threshold of 95% specificity. Twelve of the AAbs identified in this review were investigated in more than one study. Data on diagnostic discrimination by tumor histology and stage at diagnosis are sparse. Limited data suggest select AAb markers improve diagnostic discrimination when combined with markers such as CA125 and HE4. AAbs for ovarian cancer early detection is an emerging area, and large-scale, prospective investigations considering histology and stage are required for discovery and validation. However, data to date suggests panels of AAbs may eventually reach sufficient diagnostic discrimination to allow earlier detection of disease as a complement to existing markers and transvaginal ultrasound. Copyright © 2017. Published by Elsevier Inc.

Highly sensitive detection of dipicolinic acid with a water-dispersible terbium-metal organic framework.

PubMed

Bhardwaj, Neha; Bhardwaj, Sanjeev; Mehta, Jyotsana; Kim, Ki-Hyun; Deep, Akash

2016-12-15

The sensitive detection of dipicolinic acid (DPA) is strongly associated with the sensing of bacterial organisms in food and many types of environmental samples. To date, the demand for a sensitive detection method for bacterial toxicity has increased remarkably. Herein, we investigated the DPA detection potential of a water-dispersible terbium-metal organic framework (Tb-MOF) based on the fluorescence quenching mechanism. The Tb-MOF showed a highly sensitive ability to detect DPA at a limit of detection of 0.04nM (linear range of detection: 1nM to 5µM) and also offered enhanced selectivity from other commonly associated organic molecules. The present study provides a basis for the application of Tb-MOF for direct, convenient, highly sensitive, and specific detection of DPA in the actual samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Mass Spectrometry-based Assay for High Throughput and High Sensitivity Biomarker Verification

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

Guo, Xuejiang; Tang, Keqi

Searching for disease specific biomarkers has become a major undertaking in the biomedical research field as the effective diagnosis, prognosis and treatment of many complex human diseases are largely determined by the availability and the quality of the biomarkers. A successful biomarker as an indicator to a specific biological or pathological process is usually selected from a large group of candidates by a strict verification and validation process. To be clinically useful, the validated biomarkers must be detectable and quantifiable by the selected testing techniques in their related tissues or body fluids. Due to its easy accessibility, protein biomarkers wouldmore » ideally be identified in blood plasma or serum. However, most disease related protein biomarkers in blood exist at very low concentrations (<1ng/mL) and are “masked” by many none significant species at orders of magnitude higher concentrations. The extreme requirements of measurement sensitivity, dynamic range and specificity make the method development extremely challenging. The current clinical protein biomarker measurement primarily relies on antibody based immunoassays, such as ELISA. Although the technique is sensitive and highly specific, the development of high quality protein antibody is both expensive and time consuming. The limited capability of assay multiplexing also makes the measurement an extremely low throughput one rendering it impractical when hundreds to thousands potential biomarkers need to be quantitatively measured across multiple samples. Mass spectrometry (MS)-based assays have recently shown to be a viable alternative for high throughput and quantitative candidate protein biomarker verification. Among them, the triple quadrupole MS based assay is the most promising one. When it is coupled with liquid chromatography (LC) separation and electrospray ionization (ESI) source, a triple quadrupole mass spectrometer operating in a special selected reaction monitoring (SRM) mode, also known as multiple reaction monitoring (MRM), is capable of quantitatively measuring hundreds of candidate protein biomarkers from a relevant clinical sample in a single analysis. The specificity, reproducibility and sensitivity could be as good as ELISA. Furthermore, SRM MS can also quantify protein isoforms and post-translational modifications, for which traditional antibody-based immunoassays often don’t exist.« less

Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis.

PubMed

Hyun, Dong-Wook; Min, Hyun Jin; Kim, Min-Soo; Whon, Tae Woong; Shin, Na-Ri; Kim, Pil Soo; Kim, Hyun Sik; Lee, June Young; Kang, Woorim; Choi, Augustine M K; Yoon, Joo-Heon; Bae, Jin-Woo

2018-04-01

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis ( n = 20) and healthy controls ( n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgE low ), low microbial biodiversity with a high relative abundance of Firmicutes phylum ( Staphylococcus aureus ) and a low relative abundance of Actinobacteria phylum ( Propionibacterium acnes ) was observed in individuals with high total serum IgE levels (group IgE high ). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgE high as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes , is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology. Copyright © 2018 American Society for Microbiology.

High Sensitivity and High Detection Specificity of Gold-Nanoparticle-Grafted Nanostructured Silicon Mass Spectrometry for Glucose Analysis.

PubMed

Tsao, Chia-Wen; Yang, Zhi-Jie

2015-10-14

Desorption/ionization on silicon (DIOS) is a high-performance matrix-free mass spectrometry (MS) analysis method that involves using silicon nanostructures as a matrix for MS desorption/ionization. In this study, gold nanoparticles grafted onto a nanostructured silicon (AuNPs-nSi) surface were demonstrated as a DIOS-MS analysis approach with high sensitivity and high detection specificity for glucose detection. A glucose sample deposited on the AuNPs-nSi surface was directly catalyzed to negatively charged gluconic acid molecules on a single AuNPs-nSi chip for MS analysis. The AuNPs-nSi surface was fabricated using two electroless deposition steps and one electroless etching step. The effects of the electroless fabrication parameters on the glucose detection efficiency were evaluated. Practical application of AuNPs-nSi MS glucose analysis in urine samples was also demonstrated in this study.

A Heat Vulnerability Index: Spatial Patterns of Exposure, Sensitivity and Adaptive Capacity for Santiago de Chile.

PubMed

Inostroza, Luis; Palme, Massimo; de la Barrera, Francisco

2016-01-01

Climate change will worsen the high levels of urban vulnerability in Latin American cities due to specific environmental stressors. Some impacts of climate change, such as high temperatures in urban environments, have not yet been addressed through adaptation strategies, which are based on poorly supported data. These impacts remain outside the scope of urban planning. New spatially explicit approaches that identify highly vulnerable urban areas and include specific adaptation requirements are needed in current urban planning practices to cope with heat hazards. In this paper, a heat vulnerability index is proposed for Santiago, Chile. The index was created using a GIS-based spatial information system and was constructed from spatially explicit indexes for exposure, sensitivity and adaptive capacity levels derived from remote sensing data and socio-economic information assessed via principal component analysis (PCA). The objective of this study is to determine the levels of heat vulnerability at local scales by providing insights into these indexes at the intra city scale. The results reveal a spatial pattern of heat vulnerability with strong variations among individual spatial indexes. While exposure and adaptive capacities depict a clear spatial pattern, sensitivity follows a complex spatial distribution. These conditions change when examining PCA results, showing that sensitivity is more robust than exposure and adaptive capacity. These indexes can be used both for urban planning purposes and for proposing specific policies and measures that can help minimize heat hazards in highly dynamic urban areas. The proposed methodology can be applied to other Latin American cities to support policy making.

A Heat Vulnerability Index: Spatial Patterns of Exposure, Sensitivity and Adaptive Capacity for Santiago de Chile

PubMed Central

Palme, Massimo; de la Barrera, Francisco

2016-01-01

Climate change will worsen the high levels of urban vulnerability in Latin American cities due to specific environmental stressors. Some impacts of climate change, such as high temperatures in urban environments, have not yet been addressed through adaptation strategies, which are based on poorly supported data. These impacts remain outside the scope of urban planning. New spatially explicit approaches that identify highly vulnerable urban areas and include specific adaptation requirements are needed in current urban planning practices to cope with heat hazards. In this paper, a heat vulnerability index is proposed for Santiago, Chile. The index was created using a GIS-based spatial information system and was constructed from spatially explicit indexes for exposure, sensitivity and adaptive capacity levels derived from remote sensing data and socio-economic information assessed via principal component analysis (PCA). The objective of this study is to determine the levels of heat vulnerability at local scales by providing insights into these indexes at the intra city scale. The results reveal a spatial pattern of heat vulnerability with strong variations among individual spatial indexes. While exposure and adaptive capacities depict a clear spatial pattern, sensitivity follows a complex spatial distribution. These conditions change when examining PCA results, showing that sensitivity is more robust than exposure and adaptive capacity. These indexes can be used both for urban planning purposes and for proposing specific policies and measures that can help minimize heat hazards in highly dynamic urban areas. The proposed methodology can be applied to other Latin American cities to support policy making. PMID:27606592

Dual channel sensitive detection of hsa-miR-21 based on rolling circle amplification and quantum dots tagging.

PubMed

Wangt, Dan-Chen; Hu, Li-Hui; Zhou, Yu-Hui; Huang, Yu-Ting; Li, Xinhua; Zhu, Jun-Jie

2014-04-01

An isothermal, highly sensitive and specific assay for the detection of hsa-miR-21 with the integration of QDs tagging and rolling circle amplification was offered. In addition, a dual channel strategy for miRNA detection was proposed: anodic stripping voltammetry (ASV) and fluorescent method were both performed for the final Cd2+ signal readout. The designed strategy exhibited good specificity to hsa-miR-21 and presented comparable detection results by detection methods.

Measurement of neutralizing serum antibodies of patients vaccinated with human papillomavirus L1 or L2-based immunogens using furin-cleaved HPV Pseudovirions.

PubMed

Wang, Joshua W; Jagu, Subhashini; Wang, Chenguang; Kitchener, Henry C; Daayana, Sai; Stern, Peter L; Pang, Susana; Day, Patricia M; Huh, Warner K; Roden, Richard B S

2014-01-01

Antibodies specific for neutralizing epitopes in either Human papillomavirus (HPV) capsid protein L1 or L2 can mediate protection from viral challenge and thus their accurate and sensitive measurement at high throughput is likely informative for monitoring response to prophylactic vaccination. Here we compare measurement of L1 and L2-specific neutralizing antibodies in human sera using the standard Pseudovirion-Based Neutralization Assay (L1-PBNA) with the newer Furin-Cleaved Pseudovirion-Based Neutralization Assay (FC-PBNA), a modification of the L1-PBNA intended to improve sensitivity towards L2-specific neutralizing antibodies without compromising assay of L1-specific responses. For detection of L1-specific neutralizing antibodies in human sera, the FC- PBNA and L1-PBNA assays showed similar sensitivity and a high level of correlation using WHO standard sera (n = 2), and sera from patients vaccinated with Gardasil (n = 30) or an experimental human papillomavirus type 16 (HPV16) L1 VLP vaccine (n = 70). The detection of L1-specific cross-neutralizing antibodies in these sera using pseudovirions of types phylogenetically-related to those targeted by the L1 virus-like particle (VLP) vaccines was also consistent between the two assays. However, for sera from patients (n = 17) vaccinated with an L2-based immunogen (TA-CIN), the FC-PBNA was more sensitive than the L1-PBNA in detecting L2-specific neutralizing antibodies. Further, the neutralizing antibody titers measured with the FC-PBNA correlated with those determined with the L2-PBNA, another modification of the L1-PBNA that spacio-temporally separates primary and secondary receptor engagement, as well as the protective titers measured using passive transfer studies in the murine genital-challenge model. In sum, the FC-PBNA provided sensitive measurement for both L1 VLP and L2-specific neutralizing antibody in human sera. Vaccination with TA-CIN elicits weak cross-protective antibody in a subset of patients, suggesting the need for an adjuvant.

Introduction of a hydrolysis probe PCR assay for high-throughput screening of methicillin-resistant Staphylococcus aureus with the ability to include or exclude detection of Staphylococcus argenteus.

PubMed

Bogestam, Katja; Vondracek, Martin; Karlsson, Mattias; Fang, Hong; Giske, Christian G

2018-01-01

Many countries using sensitive screening methods for detection of carriage of methicillin-resistant Staphylococcus aureus (MRSA) have a sustained low incidence of MRSA infections. For diagnostic laboratories with high sample volumes, MRSA screening requires stability, low maintenance and high performance at a low cost. Herein we designed oligonucleotides for a new nuc targeted hydrolysis probe PCR to replace the standard in-house nuc SybrGreen PCR assay. This new, more time-efficient, PCR assay resulted in a 40% increase in daily sample capacity, with maintained high specificity and sensitivity. The assay was also able to detect Staphylococcus aureus clonal cluster 75 (CC75) lineage strains, recently re-classified as Staphylococcus argenteus, with a sensitivity considerably increased compared to our previous assay. While awaiting consensus if the CC75 lineage of S. aureus should be considered as S. argenteus, and whether methicillin-resistant S. argenteus should be included in the MRSA definition, many diagnostic laboratories need to update their MRSA assay sensitivity/specificity towards this lineage/species. The MRSA screening assay presented in this manuscript is comprised of nuc oligonucleotides separately targeting S. aureus and CC75 lineage strains/S. argenteus, thus providing high user flexibility for the detection of CC75 lineage strains/S. argenteus.

ECG Criteria to Differentiate Between Takotsubo (Stress) Cardiomyopathy and Myocardial Infarction.

PubMed

Frangieh, Antonio H; Obeid, Slayman; Ghadri, Jelena-Rima; Imori, Yoichi; D'Ascenzo, Fabrizio; Kovac, Marc; Ruschitzka, Frank; Lüscher, Thomas F; Duru, Firat; Templin, Christian

2016-06-13

ECG criteria differentiating Takotsubo cardiomyopathy (TTC) from mainly anterior myocardial infarction (MI) have been suggested; however, this was in small patient populations. Twelve-lead admission ECGs of consecutive 200 TTC and 200 MI patients were compared in dichotomized groups based on the presence or absence of ST-elevation MI (STEMI versus STE-TTC and non-ST elevation MI versus non ST-elevation-TTC). When comparing STEMI and STE-TTC, ST-elevation in -aVR was characteristic of STE-TTC with a sensitivity/specificity of 43% and 95%, positive predictive value (PPV) 91%, and a negative predictive value (NPV) 62% (P<0.001); when ST-elevation in -aVR is accompanied by ST-elevation in inferior leads, sensitivity/specificity were 14% and 98% (PPV was 89% and NPV 52%) (P=0.001), and 12% and 100% when associated with ST-elevation in anteroseptal leads (PPV 100%, NPV 52%) (P<0.001). On the other hand, STEMI was characterized by ST-elevation in aVR (sensitivity/specificity of 31% and 95% P<0.001, PPV 85% and NPV 59%) and ST-depression in V2-V3-V4 (sensitivity/specificity of 24% and 100% P<0.001, PPV 100% and NPV 76%). When comparing non-ST elevation MI and non ST-elevation-TTC, T-inversion in leads I-aVL-V5-V6 had a sensitivity/specificity of 17% and 97% for non ST-elevation-TTC (PPV 83% and NPV 55%) (P<0.001), and ST-elevation in -aVR with T-inversion in any lead was also specific for non ST-elevation-TTC (sensitivity/specificity of 8% and 100%, PPV 100% and NPV 53%) (P=0.006). In non-ST elevation MI patients, the presence of ST-depression in V2-V3 was specific (sensitivity/specificity of 11% and 99%, PPV 91% and NPV 51%) (P=0.01). ECG on admission can differentiate between TTC and acute MI, with high specificity and positive predictive value. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01947621. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Can paediatric early warning scores (PEWS) be used to guide the need for hospital admission and predict significant illness in children presenting to the emergency department? An assessment of PEWS diagnostic accuracy using sensitivity and specificity.

PubMed

Lillitos, Peter J; Hadley, Graeme; Maconochie, Ian

2016-05-01

Designed to detect early deterioration of the hospitalised child, paediatric early warning scores (PEWS) validity in the emergency department (ED) is less validated. We aimed to evaluate sensitivity and specificity of two commonly used PEWS (Brighton and COAST) in predicting hospital admission and, for the first time, significant illness. Retrospective analysis of PEWS data for paediatric ED attendances at St Mary's Hospital, London, UK, in November 2012. Patients with missing data were excluded. Diagnoses were grouped: medical and surgical. To classify diagnoses as significant, established guidelines were used and, where not available, common agreement between three acute paediatricians. 1921 patients were analysed. There were 211 admissions (11%). 1630 attendances were medical (86%) and 273 (14%) surgical. Brighton and COAST PEWS performed similarly. hospital admission: PEWS of ≥3 was specific (93%) but poorly sensitive (32%). The area under the receiver operating curve (AUC) was low at 0.690. Significant illness: for medical illness, PEWS ≥3 was highly specific (96%) but poorly sensitive (44%). The AUC was 0.754 and 0.755 for Brighton and COAST PEWS, respectively. Both scores performed poorly for predicting significant surgical illness (AUC 0.642). PEWS ≥3 performed well in predicting significant respiratory illness: sensitivity 75%, specificity 91%. Both Brighton and COAST PEWS scores performed similarly. A score of ≥3 has good specificity but poor sensitivity for predicting hospital admission and significant illness. Therefore, a high PEWS should be taken seriously but a low score is poor at ruling out the requirement for admission or serious underlying illness. PEWS was better at detecting significant medical illness compared with detecting the need for admission. PEWS performed poorly in detecting significant surgical illness. PEWS may be particularly useful in evaluating respiratory illness in a paediatric ED. 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/

Molecular Tools for the Detection of Nitrogen Cycling Archaea

PubMed Central

Rusch, Antje

2013-01-01

Archaea are widespread in extreme and temperate environments, and cultured representatives cover a broad spectrum of metabolic capacities, which sets them up for potentially major roles in the biogeochemistry of their ecosystems. The detection, characterization, and quantification of archaeal functions in mixed communities require Archaea-specific primers or probes for the corresponding metabolic genes. Five pairs of degenerate primers were designed to target archaeal genes encoding key enzymes of nitrogen cycling: nitrite reductases NirA and NirB, nitrous oxide reductase (NosZ), nitrogenase reductase (NifH), and nitrate reductases NapA/NarG. Sensitivity towards their archaeal target gene, phylogenetic specificity, and gene specificity were evaluated in silico and in vitro. Owing to their moderate sensitivity/coverage, the novel nirB-targeted primers are suitable for pure culture studies only. The nirA-targeted primers showed sufficient sensitivity and phylogenetic specificity, but poor gene specificity. The primers designed for amplification of archaeal nosZ performed well in all 3 criteria; their discrimination against bacterial homologs appears to be weakened when Archaea are strongly outnumbered by bacteria in a mixed community. The novel nifH-targeted primers showed high sensitivity and gene specificity, but failed to discriminate against bacterial homologs. Despite limitations, 4 of the new primer pairs are suitable tools in several molecular methods applied in archaeal ecology. PMID:23365509

EUV lithography using water-developable resist material derived from biomass

NASA Astrophysics Data System (ADS)

Takei, Satoshi; Oshima, Akihiro; Oyama, Tomoko G.; Ichikawa, Takumi; Sekiguchi, Atsushi; Kashiwakura, Miki; Kozawa, Takahiro; Tagawa, Seiichi

2013-03-01

A water-developable resist material which had specific desired properties such as high sensitivity of 5.0 μC/cm2, thermal stability of 160 °C, suitable calculated linear absorption coefficients of 13.5 nm, and acceptable CF4 etch selectivity was proposed using EB lithography for EUV lithography. A water developable resist material derived from biomass is expected for non-petroleum resources, environmental affair, safety, easiness of handling, and health of the working people, instead of the common developable process of trimethylphenylammonium hydroxide. 100 nm line and 400 nm space patterning images with exposure dose of 5.0 μC/cm2 were provided by specific process conditions of EB lithography. The developed trehalose derivatives with hydroxyl groups and EB sensitive groups in the water-developable resist material derived from biomass were applicable to future development of high-sensitive and resolution negative type of water-developable resist material as a novel chemical design.

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma.

PubMed

Li, Yuping; Xu, Hanyan; Su, Shanshan; Ye, Junru; Chen, Junjie; Jin, Xuru; Lin, Quan; Zhang, Dongqing; Ye, Caier; Chen, Chengshui

2017-01-01

Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma. A total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples. EGFR mutation status in plasma samples were tested with ADx-SuperARMS EGFR assay and tumor tissue samples were tested with ADx-ARMS EGFR assay. The clinical sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) of ADx-SuperARMS EGFR assay were calculated by using EGFR mutation status in tumor tissue as standard reference. A receiver operating characteristic (ROC) analysis was implemented and an area under the curve (AUC) was calculated to evaluate sensitivity and specificity of exon 19 deletion (E19Del) and L858R mutation detection. The objective response rate (ORR) were calculated according to the EGFR mutation status determined by ADx-superARMS as well. 0.2% analytical sensitivity and 100% specificity of the ADx-SuperARMS EGFR assays for EGFR E19Del, L858R, and T790M mutants were confirmed by using a series of diluted cell line DNA. In the clinical study, EGFR mutations were detected in 45.9% (50/109) of the plasma samples and in 56.9% (62/109) of the matched tumor tissue samples. The sensitivity, specificity, PPV and NPV of the ADx-SuperARMS EGFR assay for plasma EGFR mutation detection were 82.0% (50/61), 100% (48/48), 100% (50/50), and 81.4% (48/59), respectively. In ROC analysis, ADx-SuperARMS achieved sensitivity and specificity of 88% and 99% in E19Dels as well as sensitivity and specificity of 89% and 100% in L858R, respectively. Among the 35 patients who were plasma EGFR mutation positive and treated with first generation of EGFR-tyrosine kinase inhibitors (TKIs), 23 (65.7%) achieved partial response, 11 (31.4%) sustained disease, and 1 (2.9%) progressive disease. The ORR and disease control rate (DCR) were 65.7% and 97.1%, respectively. ADx-SuperARMS EGFR assay is likely to be a highly sensitive and specific method to noninvasively detect plasma EGFR mutations of patients with advanced lung adenocarcinoma. The EGFR mutations detected by ADx-SuperARMS EGFR assay could predict the efficacy of the treatment with first generation of EGFR-TKIs. Hence, EGFR blood testing with ADx-SuperARMS could address the unmet clinical needs.

Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: a comparison using control sera obtained from healthy individuals and patients with multiple medical problems.

PubMed

Wichainun, Ramjai; Kasitanon, Nuntana; Wangkaew, Suparaporn; Hongsongkiat, Sith; Sukitawut, Waraporn; Louthrenoo, Worawit

2013-12-01

Antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) are often tested as a screening tool in patients with suspected systemic lupus erythematosus or connective tissue diseases. ANA can be seen in healthy controls (HC) and patients with multiple medical problems (MMP). To determine the sensitivity and specificity of ANA and anti-dsDNA in SLE patients, using sera from HC and MMP patients. Serum samples from HC, MMP and SLE patients, 100 in each group, were analyzed for the presence of ANA and anti-dsDNA, by indirect immunofluorescent assay, using a HEp-2 cell and Crithidia luciliae as substrates, respectively. The prevalence of ANA at a titer of ≥1:80 and ≥ 1:160 was 8% and 4%, respectively, in HC; and it was 12% and 6% respectively, in MMP patients. The prevalence of anti-dsDNA was 0% in HC and 3% in MMP patients. When using HC sera for the diagnosis of SLE, the sensitivity of ANA at a titer of ≥ 1:80 and ≥ 1:160 was 98% and 90%, respectively, with specificity of 92% and 96%, respectively. The specificity decreased to 88% and 94%, respectively, when using sera from MMP patients. The specificity of anti-dsDNA was 100% and 97%, when using sera from HC and MMP patients, respectively. ANA and anti-dsDNA gave high sensitivity and high specificity in patients with SLE, even when using MMP patient's sera as controls. Physicians should take care in interpreting ANA and anti-dsDNA results in MMP patients who do not have signs or symptoms of SLE or connective tissue diseases.

[Comparison of simple pooling and bivariate model used in meta-analyses of diagnostic test accuracy published in Chinese journals].

PubMed

Huang, Yuan-sheng; Yang, Zhi-rong; Zhan, Si-yan

2015-06-18

To investigate the use of simple pooling and bivariate model in meta-analyses of diagnostic test accuracy (DTA) published in Chinese journals (January to November, 2014), compare the differences of results from these two models, and explore the impact of between-study variability of sensitivity and specificity on the differences. DTA meta-analyses were searched through Chinese Biomedical Literature Database (January to November, 2014). Details in models and data for fourfold table were extracted. Descriptive analysis was conducted to investigate the prevalence of the use of simple pooling method and bivariate model in the included literature. Data were re-analyzed with the two models respectively. Differences in the results were examined by Wilcoxon signed rank test. How the results differences were affected by between-study variability of sensitivity and specificity, expressed by I2, was explored. The 55 systematic reviews, containing 58 DTA meta-analyses, were included and 25 DTA meta-analyses were eligible for re-analysis. Simple pooling was used in 50 (90.9%) systematic reviews and bivariate model in 1 (1.8%). The remaining 4 (7.3%) articles used other models pooling sensitivity and specificity or pooled neither of them. Of the reviews simply pooling sensitivity and specificity, 41(82.0%) were at the risk of wrongly using Meta-disc software. The differences in medians of sensitivity and specificity between two models were both 0.011 (P<0.001, P=0.031 respectively). Greater differences could be found as I2 of sensitivity or specificity became larger, especially when I2>75%. Most DTA meta-analyses published in Chinese journals(January to November, 2014) combine the sensitivity and specificity by simple pooling. Meta-disc software can pool the sensitivity and specificity only through fixed-effect model, but a high proportion of authors think it can implement random-effect model. Simple pooling tends to underestimate the results compared with bivariate model. The greater the between-study variance is, the more likely the simple pooling has larger deviation. It is necessary to increase the knowledge level of statistical methods and software for meta-analyses of DTA data.

Nanotechnology: a promising method for oral cancer detection and diagnosis.

PubMed

Chen, Xiao-Jie; Zhang, Xue-Qiong; Liu, Qi; Zhang, Jing; Zhou, Gang

2018-06-11

Oral cancer is a common and aggressive cancer with high morbidity, mortality, and recurrence rate globally. Early detection is of utmost importance for cancer prevention and disease management. Currently, tissue biopsy remains the gold standard for oral cancer diagnosis, but it is invasive, which may cause patient discomfort. The application of traditional noninvasive methods-such as vital staining, exfoliative cytology, and molecular imaging-is limited by insufficient sensitivity and specificity. Thus, there is an urgent need for exploring noninvasive, highly sensitive, and specific diagnostic techniques. Nano detection systems are known as new emerging noninvasive strategies that bring the detection sensitivity of biomarkers to nano-scale. Moreover, compared to current imaging contrast agents, nanoparticles are more biocompatible, easier to synthesize, and able to target specific surface molecules. Nanoparticles generate localized surface plasmon resonances at near-infrared wavelengths, providing higher image contrast and resolution. Therefore, using nano-based techniques can help clinicians to detect and better monitor diseases during different phases of oral malignancy. Here, we review the progress of nanotechnology-based methods in oral cancer detection and diagnosis.

Development of an Indirect ELISA for Serological Diagnosis of Bovine herpesvirus 5

PubMed Central

Campos, Fabrício S.; da Rosa, Matheus C.; Finger, Paula F.; de Oliveira, Patricia D.; Conceição, Fabricio R.; Fischer, Geferson; Roehe, Paulo M.; Leite, Fábio P. L.

2016-01-01

Bovine herpesviruses 1 and 5 (BoHV-1 and BoHV-5) are economically important pathogens, associated with a variety of clinical syndromes, including respiratory and genital disease, reproductive failure and meningoencephalitis. The standard serological assay to diagnose BoHV-1 and BoHV-5 infections is the virus neutralization test (VNT), a time consuming procedure that requires manipulation of infectious virus. In the present study a highly sensitive and specific single dilution indirect ELISA was developed using recombinant glycoprotein D from BoHV-5 as antigen (rgD5ELISA). Bovine serum samples (n = 450) were screened by VNT against BoHV-5a and by rgD5ELISA. Compared with the VNT, the rgD5ELISA demonstrated accuracy of 99.8%, with 100% sensitivity, 96.7% specificity and coefficient of agreement between the tests of 0.954. The rgD5ELISA described here shows excellent agreement with the VNT and is shown to be a simple, convenient, specific and highly sensitive virus-free assay for detection of serum antibodies to BoHV-5. PMID:26866923

Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

PubMed Central

Mbabazi, Phoebe; Hopkins, Heidi; Osilo, Emmanuel; Kalungu, Michael; Byakika-Kibwika, Pauline; Kamya, Moses R.

2015-01-01

Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high-transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria. PMID:25624399

A new signal amplification strategy of photoelectrochemical immunoassay for highly sensitive interleukin-6 detection based on TiO2/CdS/CdSe dual co-sensitized structure.

PubMed

Fan, Gao-Chao; Ren, Xiao-Lin; Zhu, Cheng; Zhang, Jian-Rong; Zhu, Jun-Jie

2014-09-15

Dual co-sensitized structure of TiO2/CdS/CdSe was designed to develop a novel photoelectrochemical immunoassay for highly sensitive detection of human interleukin-6 (IL-6). To construct a sensing electrode, TiO2/CdS hybrid was prepared by successive adsorption and reaction of Cd(2+) and S(2-) ions on the surface of TiO2 and then was employed as matrix for immobilization of anti-IL-6 antibody, whereas CdSe QDs linked to IL-6 were used for signal amplification via the specific antibody-antigen immunoreaction between anti-IL-6 and IL-6-CdSe bioconjugate. Greatly enhanced sensitivity for IL-6 detection was derived from the new co-sensitization signal amplification strategy. First, the TiO2/CdS/CdSe co-sensitized structure extended the absorption range to long wavelength of white light, which adequately utilized the light energy. Second, the TiO2/CdS/CdSe co-sensitized structure possessed stepwise band-edge levels favoring ultrafast transfer of photogenerated electrons and significantly prompted the photoelectrochemical performance. Besides, the introduction of CdSe effectively prevented the recombination of photogenerated electrons in the conduction band of CdS, further causing an enhanced photocurrent. Accordingly, upon the co-sensitization strategy, a novel immunoassay based on the competitive binding of anti-IL-6 antibody with IL-6 antigen and IL-6-CdSe bioconjugate was developed, and it exhibited a wide linear range from 1.0 pg/mL to 100 ng/mL with a low detection limit of 0.38 pg/mL for IL-6 detection. The proposed co-sensitization strategy presented high sensitivity, reproducibility, specificity and stability, and also opened up a new promising platform for detection of other biomarkers. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and validation of a highly sensitive urine-based test to identify patients with colonic adenomatous polyps.

PubMed

Wang, Haili; Tso, Victor; Wong, Clarence; Sadowski, Dan; Fedorak, Richard N

2014-03-20

Adenomatous polyps are precursors of colorectal cancer; their detection and removal is the goal of colon cancer screening programs. However, fecal-based methods identify patients with adenomatous polyps with low levels of sensitivity. The aim or this study was to develop a highly accurate, prototypic, proof-of-concept, spot urine-based diagnostic test using metabolomic technology to distinguish persons with adenomatous polyps from those without polyps. Prospective urine and stool samples were collected from 876 participants undergoing colonoscopy examination in a colon cancer screening program, from April 2008 to October 2009 at the University of Alberta. Colonoscopy reference standard identified 633 participants with no colonic polyps and 243 with colonic adenomatous polyps. One-dimensional nuclear magnetic resonance spectra of urine metabolites were analyzed to define a diagnostic metabolomic profile for colonic adenomas. A urine metabolomic diagnostic test for colonic adenomatous polyps was established using 67% of the samples (un-blinded training set) and validated using the other 33% of the samples (blinded testing set). The urine metabolomic diagnostic test's specificity and sensitivity were compared with those of fecal-based tests. Using a two-component, orthogonal, partial least-squares model of the metabolomic profile, the un-blinded training set identified patients with colonic adenomatous polyps with 88.9% sensitivity and 50.2% specificity. Validation using the blinded testing set confirmed sensitivity and specificity values of 82.7% and 51.2%, respectively. Sensitivities of fecal-based tests to identify colonic adenomas ranged from 2.5 to 11.9%. We describe a proof-of-concept spot urine-based metabolomic diagnostic test that identifies patients with colonic adenomatous polyps with a greater level of sensitivity (83%) than fecal-based tests.

Development of a highly specific HER2 monoclonal antibody for immunohistochemistry using protein microarray chips

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

Qi, Lili; Zhou, Lixin; Lu, Mingmin

HER2 is an orphan receptor tyrosine kinase of the EGFR families and is considered to be a key tumor driver gene [1]. Breast cancer and gastric cancer with HER2 amplification can be effectively treated by its neutralizing antibody, Herceptin. In clinic, Immunohistochemistry (IHC) was used as the primary screening method to diagnose HER2 amplification [2]. However, recent evidence suggested that the frequently used rabbit HER2 antibody 4B5 cross reacted with another family member HER4 [3]. IHC staining with 4B5 also indicated that there was strong non-specific cytoplasmic and nuclear signals in normal gastric mucosal cells and some gastric cancer samples.more » Using a protein lysate array which covers 85% of the human proteome, we have confirmed that the 4B5 bound to HER4 and a nuclear protein ZSCAN18 besides HER2. The non-specific binding accounts for the unexpected cytoplasmic and nuclear staining of 4B5 of normal gastric epithelium. Finally, we have developed a novel mouse HER2 monoclonal antibody UMAB36 with similar sensitivity to 4B5 but only reacted to HER2 across the 17,000 proteins on the protein chip. In 129 breast cancer and 158 gastric cancer samples, UMAB36 showed 100% sensitivity and specificity comparing to the HER2 FISH reference results with no unspecific staining in the gastric mucosa layer. Therefore, UMAB36 could provide as an alternative highly specific IHC reagent for testing HER2 amplification in gastric cancer populations. - Highlights: • HER2 antibody 4B5 cross-interacts with HER4 and ZSCAN18, which would interfere with the accuracy of IHC diagnosis of HER2. • A HER2 antibody UMAB36 has been developed with high sensitivity and specificity and can be utilized in HER2 diagnosis. • Protein lysate array is a novel strategy to screen for highly specific antibody.« less

Sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing.

PubMed

Anzala, O; Sanders, E J; Kamali, A; Katende, M; Mutua, G N; Ruzagira, E; Stevens, G; Simek, M; Price, M

2008-10-01

HIV rapid tests (RT) are a quick and non-technically demanding means to perform HIV voluntary counselling and testing (VCT) but understanding their limitations is vital to delivering quality VCT. To determine the sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing at four sites in East Africa. Cross-sectional study. Masaka District, Uganda; a sugar plantation in Kakira, Uganda; Coastal Villages in the Kilifi District of Kenya; and the Urban slum of Kangemi located West of Nairobi, Kenya. Six thousands two hundred and fifty five consenting volunteers were enrolled into the study, and 675 prevalent HIV infections were identified. The RT sensitivity tended to be high for all assays at all sites (97.63-100%) with the exception of the Uni-Gold assay (90.24% in Kangemi, 96.58% in Kilifi). Twenty four RT results were recorded as 'weak positives', 22 (92%) of which were negative by ELISA. There was a high rate of RT false positives in Uganda (positive predictive values ranging from 45.70% to 86.62%). The sensitivity and specificity of the RT varied significantly across sites. The rate of RT misclassification in Uganda suggests that a multiple test algorithm may be preferable to a single test as screener for HIV VCT.

Computed tomography findings of acute gastric volvulus.

PubMed

Millet, Ingrid; Orliac, Celine; Alili, Chakib; Guillon, Françoise; Taourel, Patrice

2014-12-01

To assess the diagnostic performance of CT signs of gastric volvulus in both confirmed cases and control subjects. We retrospectively reviewed CT findings in 10 patients with surgically confirmed acute gastric volvulus and 20 control subjects with gastric distension. Two radiologists independently evaluated CT images for risk factors of gastric volvulus, direct findings of gastric volvulus by assessing gastric dilatation, the presence of an antropyloric transition point, the respective position of the different stomach segments and of the greater and lesser curvatures, stenosis of the gastric segments through the oesophageal hiatus and for findings of gastric ischemia. The sensitivity and specificity of each finding were calculated. The most sensitive direct signs of gastric volvulus were an antropyloric transition point without any abnormality at the transition zone and the antrum at the same level or higher than the fundus. The presence of both these two findings as diagnostic criteria of gastric volvulus had 100% sensitivity and specificity for the diagnosis of gastric volvulus. There was no association between CT signs of ischemia and final bowel ischemia at pathology. CT is both highly sensitive and specific for diagnosing acute gastric volvulus. CT is highly reliable for diagnosing acute gastric volvulus with two findings. The two signs are gastropyloric transition zone and abnormal location of the antrum. This allows fast surgical management of this emergency.

Development of a genus-specific next generation sequencing approach for sensitive and quantitative determination of the Legionella microbiome in freshwater systems.

PubMed

Pereira, Rui P A; Peplies, Jörg; Brettar, Ingrid; Höfle, Manfred G

2017-03-31

Next Generation Sequencing (NGS) has revolutionized the analysis of natural and man-made microbial communities by using universal primers for bacteria in a PCR based approach targeting the 16S rRNA gene. In our study we narrowed primer specificity to a single, monophyletic genus because for many questions in microbiology only a specific part of the whole microbiome is of interest. We have chosen the genus Legionella, comprising more than 20 pathogenic species, due to its high relevance for water-based respiratory infections. A new NGS-based approach was designed by sequencing 16S rRNA gene amplicons specific for the genus Legionella using the Illumina MiSeq technology. This approach was validated and applied to a set of representative freshwater samples. Our results revealed that the generated libraries presented a low average raw error rate per base (<0.5%); and substantiated the use of high-fidelity enzymes, such as KAPA HiFi, for increased sequence accuracy and quality. The approach also showed high in situ specificity (>95%) and very good repeatability. Only in samples in which the gammabacterial clade SAR86 was present more than 1% non-Legionella sequences were observed. Next-generation sequencing read counts did not reveal considerable amplification/sequencing biases and showed a sensitive as well as precise quantification of L. pneumophila along a dilution range using a spiked-in, certified genome standard. The genome standard and a mock community consisting of six different Legionella species demonstrated that the developed NGS approach was quantitative and specific at the level of individual species, including L. pneumophila. The sensitivity of our genus-specific approach was at least one order of magnitude higher compared to the universal NGS approach. Comparison of quantification by real-time PCR showed consistency with the NGS data. Overall, our NGS approach can determine the quantitative abundances of Legionella species, i. e. the complete Legionella microbiome, without the need for species-specific primers. The developed NGS approach provides a new molecular surveillance tool to monitor all Legionella species in qualitative and quantitative terms if a spiked-in genome standard is used to calibrate the method. Overall, the genus-specific NGS approach opens up a new avenue to massive parallel diagnostics in a quantitative, specific and sensitive way.

The RclR Protein Is a Reactive Chlorine-specific Transcription Factor in Escherichia coli *

PubMed Central

Parker, Benjamin W.; Schwessinger, Emily A.; Jakob, Ursula; Gray, Michael J.

2013-01-01

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance. PMID:24078635

The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli.

PubMed

Parker, Benjamin W; Schwessinger, Emily A; Jakob, Ursula; Gray, Michael J

2013-11-08

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.

Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.

PubMed

Fällmar, David; Haller, Sven; Lilja, Johan; Danfors, Torsten; Kilander, Lena; Tolboom, Nelleke; Egger, Karl; Kellner, Elias; Croon, Philip M; Verfaillie, Sander C J; van Berckel, Bart N M; Ossenkoppele, Rik; Barkhof, Frederik; Larsson, Elna-Marie

2017-10-01

Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET. Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis. Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168). ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET. • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

An improved, rapid competitive ELISA using a novel conserved 3B epitope for the detection of serum antibodies to foot-and-mouth disease virus.

PubMed

Chung, Chungwon J; Clavijo, Alfonso; Bounpheng, Mangkey A; Uddowla, Sabena; Sayed, Abu; Dancho, Brooke; Olesen, Ian C; Pacheco, Juan; Kamicker, Barbara J; Brake, David A; Bandaranayaka-Mudiyanselage, Carey L; Lee, Stephen S; Rai, Devendra K; Rieder, Elizabeth

2018-06-01

The highly contagious foot-and-mouth disease virus (FMDV) afflicts cloven-hoofed animals, resulting in significant costs because of loss of trade and recovery from disease. We developed a sensitive, specific, and rapid competitive ELISA (cELISA) to detect serum antibodies to FMDV. The cELISA utilized a monoclonal blocking antibody specific for a highly conserved FMDV nonstructural 3B epitope, a recombinant mutant FMDV 3ABC coating protein, and optimized format variables including serum incubation for 90 min at 20-25°C. Samples from 16 animals experimentally infected with one FMDV serotype (A, O, Asia, or SAT-1) demonstrated early detection capacity beginning 7 d post-inoculation. All samples from 55 vesicular stomatitis virus antibody-positive cattle and 44 samples from cloven-hoofed animals affected by non-FMD vesicular diseases were negative in the cELISA, demonstrating 100% analytical specificity. The diagnostic sensitivity was 100% against sera from 128 cattle infected with isolates of all FMDV serotypes, emphasizing serotype-agnostic results. Diagnostic specificities of U.S. cattle ( n = 1135) and swine ( n = 207) sera were 99.4% and 100%, respectively. High repeatability and reproducibility were demonstrated with 3.1% coefficient of variation in percent inhibition data and 100% agreement using 2 kit lots and 400 negative control serum samples, with no difference between bench and biosafety cabinet operation. Negative results from vaccinated, uninfected cattle, pig, and sheep sera confirmed the DIVA (differentiate infected from vaccinated animals) capability. This rapid (<3 h), select agent-free assay with high sensitivity and specificity, DIVA capability, and room temperature processing capability will serve as a useful tool in FMDV surveillance, emergency preparedness, response, and outbreak recovery programs.

Development of a loop-mediated isothermal amplification assay for rapid detection of Burkholderia mallei.

PubMed

Mirzai, S; Safi, S; Mossavari, N; Afshar, D; Bolourchian, M

2016-08-31

The present study was conducted to establish a Loop-mediated isothermal amplification (LAMP) technique for the rapid detection of B. mallei the etiologic agent of glanders, a highly contagious disease of equines. A set of six specific primers targeting integrase gene cluster were designed for the LAMP test. The reaction was optimized using different temperatures and time intervals. The specificity of the assay was evaluated using DNA from B.pseudomallei and Pseudomonas aeruginosa. The LAMP products were analyzed both visually and under UV light after electrophoresis. The optimized conditions were found to be at 63ºC for 60 min. The assay showed high specificity and sensitivity. It was concluded that the established LAMP assay is a rapid, sensitive and practical tool for detection of B. mallei and early diagnosis of glanders.

Performance of the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria in Thai patients.

PubMed

Louthrenoo, Worawit; Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya

2017-05-01

To evaluate the sensitivity and specificity of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in Thai patients presenting with acute arthritis in a real-life setting. Data were analyzed on consecutive patients presenting with arthritis of less than 2 weeks duration. Sensitivity and specificity were calculated by using the presence of monosodium urate (MSU) crystals in the synovial fluid or tissue aspirate as gold standard for gout diagnosis. Subgroup analysis was performed in patients with early disease (≤2 years), established disease (>2 years), and those without tophus. Additional analysis also was performed in non-tophaceous gout patients, and patients with acute calcium pyrophosphate dihydrate crystal arthritis were used as controls. One hundred and nine gout and 74 non-gout patients participated in this study. Full ACR/EULAR classification criteria had sensitivity and specificity of 90.2 and 90.0%, respectively; and 90.2 and 85.0%, respectively, when synovial fluid microscopy was excluded. Clinical-only criteria yielded sensitivity and specificity of 79.8 and 87.8%, respectively. The criteria performed well among patients with early and non-tophaceous disease, but had lower specificity in patients with established disease. The variation of serum uric acid level was a major limitation of the classification criteria. The ACR/EULAR classification criteria had high sensitivity and specificity in Thai patients presenting with acute arthritis, even when clinical criteria alone were used.

Efficacy of functional movement screening for predicting injuries in coast guard cadets.

PubMed

Knapik, Joseph J; Cosio-Lima, Ludimila M; Reynolds, Katy L; Shumway, Richard S

2015-05-01

Functional movement screening (FMS) examines the ability of individuals to perform highly specific movements with the aim of identifying individuals who have functional limitations or asymmetries. It is assumed that individuals who can more effectively accomplish the required movements have a lower injury risk. This study determined the ability of FMS to predict injuries in the United States Coast Guard (USCG) cadets. Seven hundred seventy male and 275 female USCG freshman cadets were administered the 7 FMS tests before the physically intense 8-week Summer Warfare Annual Basic (SWAB) training. Physical training-related injuries were recorded during SWAB training. Cumulative injury incidence was calculated at various FMS cutpoint scores. The ability of the FMS total score to predict injuries was examined by calculating sensitivity and specificity. Determination of the FMS cutpoint that maximized specificity and sensitivity was determined from the Youden's index (sensitivity + specificity - 1). For men, FMS scores ≤ 12 were associated with higher injury risk than scores >12; for women, FMS scores ≤ 15 were associated with higher injury risk than scores >15. The Youden's Index indicated that the optimal FMS cutpoint was ≤ 11 for men (22% sensitivity, 87% specificity) and ≤ 14 for women (60% sensitivity, 61% specificity). Functional movement screening demonstrated moderate prognostic accuracy for determining injury risk among female Coast Guard cadets but relatively low accuracy among male cadets. Attempting to predict injury risk based on the FMS test seems to have some limited promise based on the present and past investigations.

Role of "Sural Sparing" Pattern (Absent/Abnormal Median and Ulnar with Present Sural SNAP) Compared to Absent/Abnormal Median or Ulnar with Normal Sural SNAP in Acute Inflammatory Demyelinating Polyneuropathy.

PubMed

Surpur, Spurthi Sunil; Govindarajan, Raghav

2017-01-01

Sural sparing defined as absent/abnormal median sensory nerve action potential (SNAP) amplitude or absent/abnormal ulnar SNAP amplitude with a normal sural SNAP amplitude is thought to be a marker for inflammatory demyelinating polyneuropathies. If sural sparing pattern specifically defined as absent/abnormal median and ulnar SNAP amplitude with normal sural SNAP amplitude (AMUNS) is sensitive and specific when compared with either absent/abnormal median and normal sural (AMNS) or absent/abnormal ulnar and normal sural (AUNS) for acute inflammatory demyelinating polyneuropathy (AIDP), chronic inflammatory demyelinating polyneuropathy (CIDP), select non-diabetic axonopathies (AXPs), and diabetic neuropathies (DNs). Retrospective analysis from 2001 to 2010 on all newly diagnosed AIDP, CIDP, select non-diabetic AXP, and DN. There were 20 AIDP and 23 CIDP. Twenty AXP and 50 DN patients between 2009 and 2010 were included as controls. AMUNS was seen in 65% of AIDP, 39% CIDP compared with 10% of AXP and 6% for DN with sensitivity of 51%, specificity of 92%, whereas the specificity of AMNS/AUNS was 73% and its sensitivity was 58%. If a patient has AMUNS they are >12 times more likely to have AIDP ( p  < 0.001). Sural sparing is highly specific but not sensitive when compared with either AMNS or AUNS in AIDP but does not add to sensitivity or specificity in CIDP.

Investigation of the feasibility of non-invasive optical sensors for the quantitative assessment of dehydration.

PubMed

Visser, Cobus; Kieser, Eduard; Dellimore, Kiran; van den Heever, Dawie; Smith, Johan

2017-10-01

This study explores the feasibility of prospectively assessing infant dehydration using four non-invasive, optical sensors based on the quantitative and objective measurement of various clinical markers of dehydration. The sensors were investigated to objectively and unobtrusively assess the hydration state of an infant based on the quantification of capillary refill time (CRT), skin recoil time (SRT), skin temperature profile (STP) and skin tissue hydration by means of infrared spectrometry (ISP). To evaluate the performance of the sensors a clinical study was conducted on a cohort of 10 infants (aged 6-36 months) with acute gastroenteritis. High sensitivity and specificity were exhibited by the sensors, in particular the STP and SRT sensors, when combined into a fusion regression model (sensitivity: 0.90, specificity: 0.78). The SRT and STP sensors and the fusion model all outperformed the commonly used "gold standard" clinical dehydration scales including the Gorelick scale (sensitivity: 0.56, specificity: 0.56), CDS scale (sensitivity: 1.0, specificity: 0.2) and WHO scale (sensitivity: 0.13, specificity: 0.79). These results suggest that objective and quantitative assessment of infant dehydration may be possible using the sensors investigated. However, further evaluation of the sensors on a larger sample population is needed before deploying them in a clinical setting. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Reliability of meat, fish, dairy, and egg intake over a 33-year interval in Adventist Health Study 2.

PubMed

Singh, Pramil N; Batech, Michael; Faed, Pegah; Jaceldo-Siegl, Karen; Martins, Marcia; Fraser, Gary E

2014-01-01

We studied Adventist Health Study 2 (AHS-2) cohort members to determine the reliability of long-term recall of adult dietary intake that occurred 33 years ago. Establishing the reliability of these measures supports studies of how dietary exposure across the life course affects risk of cancer and other noncommunicable disease outcomes. Among 1816 AHS-2 cohort members, we conducted a statistical comparison of long-term recall of meat, fish, dairy, and eggs at AHS-2 baseline with their report of current diet 33 years before AHS-2 baseline at an age of 30-60 years. Major findings are as follows: 1) a high correlation for frequency of red meat (R = 0.71), poultry (R = 0.67), and fish (R = 0.60); lower correlations for dairy (R = 0.19) and eggs (R = 0.28); 2) good concordance for dichotomous measures of red meat [sensitivity: 0.70; specificity: 0.92; positive predictive value (PPV): 0.91], poultry (sensitivity: 0.76; specificity: 0.87; PPV: 0.83), fish (sensitivity: 0.61; specificity: 0.93; PPV: 0.89), dairy (sensitivity: 0.95; specificity: 0.57; PPV: 0.99), and eggs (sensitivity: 0.95; specificity: 0.41; PPV: 0.96); negative predictive value for dairy and eggs was poor. Among older AHS-2 cohort members, we found good reliability of recall of red meat, poultry, and fish intake that occurred 33 years earlier.

Optical Coherence Tomography Angiography versus Dye Angiography in Age-Related Macular Degeneration: Sensitivity and Specificity Analysis.

PubMed

Nikolopoulou, Eleni; Lorusso, Massimo; Micelli Ferrari, Luisa; Cicinelli, Maria Vittoria; Bandello, Francesco; Querques, Giuseppe; Micelli Ferrari, Tommaso

2018-01-01

Optical coherence tomography angiography (OCTA) could be a valid tool to detect choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD), allowing the analysis of the type, the morphology, and the extension of CNV in most of the cases. To determine the sensitivity and specificity of OCTA in detecting CNV secondary to nAMD, compared to fluorescein angiography (FA) and indocyanine green angiography (ICGA). Prospective observational study. Patients with suspected nAMD were recruited between May and December 2016. Patients underwent FA, ICGA, spectral domain OCT, and OCTA (AngioVue, Optovue, Inc.). Sensitivity and specificity of FA, with or without ICGA, were assessed and compared with OCTA. Seventy eyes of 70 consecutive patients were included: 32 eyes (45.7%) with type I CNV, 8 eyes (11.4%) with type II CNV, 4 eyes (5.7%) with type III CNV, 6 eyes (8.6%) with mixed type I and type II CNV, and 20 eyes (28.6%) with no CNV. Sensitivity of OCTA was 88% and specificity was 90%. Concordance between FA/ICGA and OCTA was very good (0,91; range 0,81-1,00). OCTA showed high sensitivity and specificity for detection of CNV. Concordance between OCTA and gold-standard dye-based techniques was excellent. OCTA may represent a first-line noninvasive method for the diagnosis of nAMD.

Indication for Computed Tomography Scan in Shoulder Instability: Sensitivity and Specificity of Standard Radiographs to Predict Bone Defects After Traumatic Anterior Glenohumeral Instability.

PubMed

Delage Royle, Audrey; Balg, Frédéric; Bouliane, Martin J; Canet-Silvestri, Fanny; Garant-Saine, Laurianne; Sheps, David M; Lapner, Peter; Rouleau, Dominique M

2017-10-01

Quantifying glenohumeral bone loss is key in preoperative surgical planning for a successful Bankart repair. Simple radiographs can accurately measure bone defects in cases of recurrent shoulder instability. Cohort study (diagnosis); Level of evidence, 2. A true anteroposterior (AP) view, alone and in combination with an axillary view, was used to evaluate the diagnostic properties of radiographs compared with computed tomography (CT) scan, the current gold standard, to predict significant bone defects in 70 patients. Sensitivity, specificity, and positive and negative predictive values were evaluated and compared. Detection of glenoid bone loss on plain film radiographs, with and without axillary view, had a sensitivity of 86% for both views and a specificity of 73% and 64% with and without the axillary view, respectively. For detection of humeral bone loss, the sensitivity was 8% and 17% and the specificity was 98% and 91% with and without the axillary view, respectively. Regular radiographs would have missed 1 instance of significant bone loss on the glenoid side and 20 on the humeral side. Interobserver reliabilities were moderate for glenoid detection (κ = 0.473-0.503) and poor for the humeral side (κ = 0.278-0.336). Regular radiographs showed suboptimal sensitivity, specificity, and reliability. Therefore, CT scan should be considered in the treatment algorithm for accurate quantification of bone loss to prevent high rates of recurrent instability.

Sensitivity and Specificity of Long Wave Infrared Imaging for Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Coben, Robert; Myers, Thomas E.

2009-01-01

Objective: This study was the first to investigate the efficacy of long wave infrared (LWIR) imaging as a diagnostic tool for ADHD. Method: with ADHD and a high level of specificity (94%) in discriminating those with ADHD from those with other diagnoses. The overall classification rate was 73.16%. This was indicative of a high level of…

Examining the Sensitivity and Specificity of 2 Screening Instruments: Odontogenic or Temporomandibular Disorder Pain?

PubMed

Fonseca Alonso, Barbara; Nixdorf, Donald R; Shueb, Sarah S; John, Mike T; Law, Alan S; Durham, Justin

2017-01-01

Two groups of patients with orofacial pains that are clinically important to distinguish from each other are patients with odontogenic pain and temporomandibular disorder (TMD) pain. The aim of this study was to determine the sensitivity and specificity of 2 screening instruments in distinguishing between patients with these types of pain. A convenience sample of patients seeking care at an endodontic clinic and an orofacial pain clinic were recruited. The 14-item dental pain questionnaire (DePaQ) was used to screen for odontogenic pain and the 6-item TMD screener was used to screen for TMD pain. Sensitivity and specificity calculations with 95% confidence intervals (CIs) were performed for both instruments, and thresholds/acceptability/performance was assessed using published guidelines. Thirty-four patients with odontogenic pain and 37 patients with TMD pain were included in this study. The sensitivity of the DePaQ was 0.85 (95% CI, 0.69-0.95), and specificity was 0.11 (95% CI, 0.03-0.25). The sensitivity of the TMD screener was 0.92 (95% CI, 0.78-0.98), and specificity was 0.59 (95% CI, 0.41-0.75). The point estimates, a single value used to estimate the population parameter, for both the DePaQ and TMD screener were "acceptable" in identifying patients who had the pain condition in question (ie, sensitivity), whereas the point estimate for appropriately identifying patients who did not have the pain condition when they did not have it (ie, specificity) was "nonacceptable" for both. The DePaQ and the TMD screener lack diagnostic accuracy for differentiating TMD from odontogenic tooth pain without adjunctive (clinical) investigation(s) or examination. However, the TMD screener has high sensitivity for identifying true positives (ie, TMD pain) and would therefore be useful as a screening instrument when one can definitively exclude odontogenic etiology for pain on clinical and radiographic grounds, for instance in endodontic practices. In this study, the negative predictive value was also high in the TMD screener, and, therefore, we can trust a negative result (ie, when the TMD screener is negative, we can be fairly certain the pain diagnosis is not TMD and rule out TMD). Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Blindness and partial sight in an elderly population.

PubMed Central

Gibson, J M; Lavery, J R; Rosenthal, A R

1986-01-01

A cross sectional, prevalence survey of eye disease in the population over 75 years old of Melton Mowbray has been used to examine the accuracy and completeness of the Blind and Partially Sighted Registers. The Blind Register had high sensitivity and specificity but was found to underestimate the prevalence of blindness by a factor of 1.1. The Partially Sighted Register had high specificity, but the sensitivity was only 50% and it underestimated the prevalence of partial sight by a factor of 1.5. Seven persons eligible for registration, but previously not registered, were found, two as blind and five as partially sighted. This represented 21% of the registrable visually impaired population. PMID:3756128

Biomagnetic separation of Salmonella Typhimurium with high affine and specific ligand peptides isolated by phage display technique

NASA Astrophysics Data System (ADS)

Steingroewer, Juliane; Bley, Thomas; Bergemann, Christian; Boschke, Elke

2007-04-01

Analyses of food-borne pathogens are of great importance in order to minimize the health risk for customers. Thus, very sensitive and rapid detection methods are required. Current conventional culture techniques are very time consuming. Modern immunoassays and biochemical analysis also require pre-enrichment steps resulting in a turnaround time of at least 24 h. Biomagnetic separation (BMS) is a promising more rapid method. In this study we describe the isolation of high affine and specific peptides from a phage-peptide library, which combined with BMS allows the detection of Salmonella spp. with a similar sensitivity as that of immunomagnetic separation using antibodies.

Cost effectiveness analysis of screening for sight threatening diabetic eye disease

PubMed Central

James, Marilyn; Turner, David A; Broadbent, Deborah M; Vora, Jiten; Harding, Simon P

2000-01-01

Objective To measure the cost effectiveness of systematic photographic screening for sight threatening diabetic eye disease compared with existing practice. Design Cost effectiveness analysis Setting Liverpool. Subjects A target population of 5000 diabetic patients invited for screening. Main outcome measures Cost effectiveness (cost per true positive) of systematic and opportunistic programmes; incremental cost effectiveness of replacing opportunistic with systematic screening. Results Baseline prevalence of sight threatening eye disease was 14.1%. The cost effectiveness of the systematic programme was £209 (sensitivity 89%, specificity 86%, compliance 80%, annual cost £104 996) and of the opportunistic programme was £289 (combined sensitivity 63%, specificity 92%, compliance 78%, annual cost £99 981). The incremental cost effectiveness of completely replacing the opportunistic programme was £32. Absolute values of cost effectiveness were highly sensitive to varying prevalence, sensitivity and specificity, compliance, and programme size. Conclusion Replacing existing programmes with systematic screening for diabetic eye disease is justified. PMID:10856062

Accuracy of MRI for the diagnosis of metastatic cervical lymphadenopathy in patients with thyroid cancer.

PubMed

Chen, Qinghua; Raghavan, Prashant; Mukherjee, Sugoto; Jameson, Mark J; Patrie, James; Xin, Wenjun; Xian, Junfang; Wang, Zhenchang; Levine, Paul A; Wintermark, Max

2015-10-01

The aim of this study was to systematically compare a comprehensive array of magnetic resonance (MR) imaging features in terms of their sensitivity and specificity to diagnose cervical lymph node metastases in patients with thyroid cancer. The study included 41 patients with thyroid malignancy who underwent surgical excision of cervical lymph nodes and had preoperative MR imaging ≤4weeks prior to surgery. Three head and neck neuroradiologists independently evaluated all the MR images. Using the pathology results as reference, the sensitivity, specificity and interobserver agreement of each MR imaging characteristic were calculated. On multivariate analysis, no single imaging feature was significantly correlated with metastasis. In general, imaging features demonstrated high specificity, but poor sensitivity and moderate interobserver agreement at best. Commonly used MR imaging features have limited sensitivity at correctly identifying cervical lymph node metastases in patients with thyroid cancer. A negative neck MR scan should not dissuade a surgeon from performing a neck dissection in patients with thyroid carcinomas.

Rose Angina Questionnaire: Validation with cardiologists' diagnoses to detect coronary heart disease in Bangladesh

PubMed Central

Rahman, Muhammad Aziz; Spurrier, Nicola; Mahmood, Mohammad Afzal; Rahman, Mahmudur; Choudhury, Sohel Reza; Leeder, Stephen

2013-01-01

Aim/objectives The study aimed to validate the Rose Angina Questionnaire (RAQ) to detect coronary heart disease (CHD) by comparing with cardiologists' diagnoses in Bangladesh. Methods Patients aged 40–75 years attending to two cardiac hospitals were diagnosed as either CHD positive or CHD negative by cardiologists. The RAQ was used to reclassify them into CHD positive [RAQ] and CHD negative [RAQ]. Findings There were 302 CHD positive [cardiologists] and 302 CHD negative [cardiologists] individuals. The RAQ reclassified 194 individuals as CHD positive [RAQ] and 409 individuals as CHD negative [RAQ]. Therefore, the RAQ had 53% sensitivity and 89% specificity. There was no difference in sensitivity and specificity during subgroup analyzes by age and gender; the sensitivity was higher among people from lower socio-economic status. Conclusion The RAQ, having moderate sensitivity but high specificity to detect CHD, can be used to screen individuals at risk of CHD in large-scale epidemiological surveys. PMID:23438610

Rapid and sensitive detection of human astrovirus in water samples by loop-mediated isothermal amplification with hydroxynaphthol blue dye.

PubMed

Yang, Bo-Yun; Liu, Xiao-Lu; Wei, Yu-Mei; Wang, Jing-Qi; He, Xiao-Qing; Jin, Yi; Wang, Zi-Jian

2014-02-14

The aim of this paper was to develop a reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for rapid, sensitive and inexpensive detection of astrovirus. The detection limit of LAMP using in vitro RNA transcripts was 3.6 × 10 copies·μL⁻¹, which is as sensitive as the presently used PCR assays. However, the LAMP products could be identified as different colors with the naked eye following staining with hydroxynaphthol blue dye (HNB). No cross-reactivity with other gastroenteric viruses (rotavirus and norovirus) was observed, indicating the relatively high specificity of LAMP. The RT-LAMP method with HNB was used to effectively detect astrovirus in reclaimed water samples. The LAMP technique described in this study is a cheap, sensitive, specific and rapid method for the detection of astrovirus. The RT-LAMP method can be simply applied for the specific detection of astrovirus and has the potential to be utilized in the field as a screening test.

Immunodiagnosis of fascioliasis using sandwich enzyme-linked immunosorbent assay for detection of Fasciola gigantica paramyosin antigen

PubMed Central

Abou-Elhakam, Hany Mohamed Adel; Bauomy, Ibraheem Rabia; El Deeb, Somaya Osman; El Amir, Azza Mohamed

2013-01-01

Background: Many immunological techniques have been developed over years using the different Fasciola antigens for diagnosis of parasitic infection and to replace the parasitological techniques, which are time consuming and usually lack sensitivity and reproducibility. Materials and Methods: In this study, Fasciola gigantica paramyosin (Pmy) antigen was early detected in cattle sera using sandwich enzyme-linked immunosorbent assay (ELISA), to evaluate the Pmy antigen performance in diagnosis. This work was conducted on 135 cattle blood samples, which were classified according to parasitological investigation into, healthy control (30), fascioliasis (75), and other parasites (30) groups. Results: The sensitivity of Sandwich ELISA was 97.33%, and the specificity was 95%, in comparison with parasitological examination, which recorded 66.66% sensitivity and 100% specificity, respectively. Conclusions: It was clear that the native F. gigantica Pmy is considered as a powerful antigen in early immunodiagnosis of fascioliasis, using a highly sensitive and specific sandwich ELISA technique. PMID:23961441

Performance of Ultrasound in the Diagnosis of Gout in a Multicenter Study: Comparison With Monosodium Urate Monohydrate Crystal Analysis as the Gold Standard.

PubMed

Ogdie, Alexis; Taylor, William J; Neogi, Tuhina; Fransen, Jaap; Jansen, Tim L; Schumacher, H Ralph; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Cagnotto, Giovanni; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; Lima Gomes Ochtrop, Manuella; Janssen, Matthijs; Chen, Jiunn-Horng; Slot, Ole; Lazovskis, Juris; White, Douglas; Cimmino, Marco A; Uhlig, Till; Dalbeth, Nicola

2017-02-01

To examine the performance of ultrasound (US) for the diagnosis of gout using the presence of monosodium urate monohydrate (MSU) crystals as the gold standard. We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multicenter observational cross-sectional study of consecutive subjects with at least 1 swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with confirmed MSU crystals. Rheumatologists or radiologists who were blinded with regard to the results of the MSU crystal analysis performed US on 1 or more clinically affected joints. US findings of interest were double contour sign, tophus, and snowstorm appearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive US results among subjects with gout. US was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV, and NPV for the presence of any 1 of the features were 76.9%, 84.3%, 83.3%, and 78.2%, respectively. Sensitivity was higher among subjects with a disease duration of ≥2 years and among subjects with subcutaneous nodules on examination (suspected tophus). Associations with a positive US finding included suspected clinical tophus (odds ratio [OR] 4.77 [95% confidence interval (95% CI) 2.23-10.21]), any abnormality on plain radiography (OR 4.68 [95% CI 2.68-8.17]), and serum urate level (OR 1.31 [95% CI 1.06-1.62]). US features of MSU crystal deposition had high specificity and high PPV but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. © 2016, American College of Rheumatology.

Performance of Ultrasound in the Diagnosis of Gout in a Multi-Center Study: Comparison with Monosodium Urate Crystal Analysis as the Gold Standard

PubMed Central

Ogdie, Alexis; Taylor, William J; Neogi, Tuhina; Fransen, Jaap; Jansen, Tim L; Schumacher, H. Ralph; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K.; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Cagnotto, Giovanni; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; Ochtrop, Manuella Lima Gomes; Janssen, Matthijs; Chen, Jiunn-Horng; Slot, Ole; Lazovskis, Juris; White, Douglas; Cimmino, Marco A.; Uhlig, Till; Dalbeth, Nicola

2017-01-01

Objectives To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard. Methods We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional study of consecutive subjects with at least one swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with MSU crystal confirmation. Rheumatologists or radiologists, blinded to the results of the MSU crystal analysis, performed ultrasound on one or more clinically affected joints. Ultrasound findings of interest were: double contour sign (DCS), tophus, and ‘snowstorm’ appearance. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive ultrasound results among subjects with gout. Results Ultrasound was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV and NPV for the presence of any one of the features were 76.9%, 84.3%, 83.3% and 78.1% respectively. Sensitivity was higher among subjects with disease ≥2 years duration and among subjects with subcutaneous nodules on exam (suspected tophus). Associations with a positive ultrasound finding included suspected clinical tophus (odds ratio 4.77; 95% CI 2.23–10.21), any abnormal plain film radiograph (4.68; 2.68–8.17) and serum urate (1.31; 1.06–1.62). Conclusions Ultrasound features of MSU crystal deposition had high specificity and high positive predictive value but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi. PMID:27748084

Evaluation of a focussed protocol for hand-held echocardiography and computer-assisted auscultation in detecting latent rheumatic heart disease in scholars.

PubMed

Zühlke, Liesl J; Engel, Mark E; Nkepu, Simpiwe; Mayosi, Bongani M

2016-08-01

Introduction Echocardiography is the diagnostic test of choice for latent rheumatic heart disease. The utility of echocardiography for large-scale screening is limited by high cost, complex diagnostic protocols, and time to acquire multiple images. We evaluated the performance of a brief hand-held echocardiography protocol and computer-assisted auscultation in detecting latent rheumatic heart disease with or without pathological murmur. A total of 27 asymptomatic patients with latent rheumatic heart disease based on the World Heart Federation criteria and 66 healthy controls were examined by standard cardiac auscultation to detect pathological murmur. Hand-held echocardiography using a focussed protocol that utilises one view - that is, the parasternal long-axis view - and one measurement - that is, mitral regurgitant jet - and a computer-assisted auscultation utilising an automated decision tool were performed on all patients. The sensitivity and specificity of computer-assisted auscultation in latent rheumatic heart disease were 4% (95% CI 1.0-20.4%) and 93.7% (95% CI 84.5-98.3%), respectively. The sensitivity and specificity of the focussed hand-held echocardiography protocol for definite rheumatic heart disease were 92.3% (95% CI 63.9-99.8%) and 100%, respectively. The test reliability of hand-held echocardiography was 98.7% for definite and 94.7% for borderline disease, and the adjusted diagnostic odds ratios were 1041 and 263.9 for definite and borderline disease, respectively. Computer-assisted auscultation has extremely low sensitivity but high specificity for pathological murmur in latent rheumatic heart disease. Focussed hand-held echocardiography has fair sensitivity but high specificity and diagnostic utility for definite or borderline rheumatic heart disease in asymptomatic patients.

A novel line immunoassay based on recombinant virulence factors enables highly specific and sensitive serologic diagnosis of Helicobacter pylori infection.

PubMed

Formichella, Luca; Romberg, Laura; Bolz, Christian; Vieth, Michael; Geppert, Michael; Göttner, Gereon; Nölting, Christina; Walter, Dirk; Schepp, Wolfgang; Schneider, Arne; Ulm, Kurt; Wolf, Petra; Busch, Dirk H; Soutschek, Erwin; Gerhard, Markus

2013-11-01

Helicobacter pylori colonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome. H. pylori virulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to important H. pylori virulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed in Escherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) were H. pylori negative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), the recomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, the recomLine assay provides a valuable tool for the diagnosis of H. pylori infection.

Development of a highly sensitive three-dimensional gel electrophoresis method for characterization of monoclonal protein heterogeneity.

PubMed

Nakano, Keiichi; Tamura, Shogo; Otuka, Kohei; Niizeki, Noriyasu; Shigemura, Masahiko; Shimizu, Chikara; Matsuno, Kazuhiko; Kobayashi, Seiichi; Moriyama, Takanori

2013-07-15

Three-dimensional gel electrophoresis (3-DE), which combines agarose gel electrophoresis and isoelectric focusing/SDS-PAGE, was developed to characterize monoclonal proteins (M-proteins). However, the original 3-DE method has not been optimized and its specificity has not been demonstrated. The main goal of this study was to optimize the 3-DE procedure and then compare it with 2-DE. We developed a highly sensitive 3-DE method in which M-proteins are extracted from a first-dimension agarose gel, by diffusing into 150 mM NaCl, and the recovery of M-proteins was 90.6%. To validate the utility of the highly sensitive 3-DE, we compared it with the original 3-DE method. We found that highly sensitive 3-DE provided for greater M-protein recovery and was more effective in terms of detecting spots on SDS-PAGE gels than the original 3-DE. Moreover, highly sensitive 3-DE separates residual normal IgG from M-proteins, which could not be done by 2-DE. Applying the highly sensitive 3-DE to clinical samples, we found that the characteristics of M-proteins vary tremendously between individuals. We believe that our highly sensitive 3-DE method described here will prove useful in further studies of the heterogeneity of M-proteins. Copyright © 2013 Elsevier Inc. All rights reserved.

[Diagnostic advantages of the test system "DS-EIA-HBsAg-0.01" for detection of HBV surface antigen].

PubMed

Egorova, N I; Pyrenkova, I Iu; Igolkina, S N; Sharipova, I N; Puzyrev, V F; Obriadina, A P; Burkov, A N; Kornienko, N V; Fields, H A; Korovkin, A S; Shalunova, N V; Bektemirov, T A; Kuznetsov, K V; Koshcheeva, N A; Ulanova, T I

2009-01-01

The new highly sensitive test system "DS-EIA-HBsAg-0.01" (Priority Certificate No. 2006129019 of August 10, 2006) in detecting hepatitis B surface antigen (HBsAg) was assessed. The sensitivity of the test was estimated using the federal standards sample HBsAg 42-28-311-06, panels' samples Boston Biomedica Inc. (West Bridgewater, Mass, USA) and ZeptoMetrix Corp. (Buffalo, NY, USA). The findings have indicated that "DS-EIA-HBsAg-0.01" is equally effective in detecting different subtypes of HBsAg during a seroconversion period earlier than alternative assays. Along with its high analytical and diagnostic sensitivity, the system shows a high diagnostic specificity.

Nanotube antibody biosensor arrays for the detection of circulating breast cancer cells

NASA Astrophysics Data System (ADS)

Shao, Ning; Wickstrom, Eric; Panchapakesan, Balaji

2008-11-01

Recent reports have shown that nanoscale electronic devices can be used to detect a change in electrical properties when receptor proteins bind to their corresponding antibodies functionalized on the surface of the device, in extracts from as few as ten lysed tumor cells. We hypothesized that nanotube-antibody devices could sensitively and specifically detect entire live cancer cells. We report for the first time a single nanotube field effect transistor array, functionalized with IGF1R-specific and Her2-specific antibodies, which exhibits highly sensitive and selective sensing of live, intact MCF7 and BT474 human breast cancer cells in human blood. Those two cell lines both overexpress IGF1R and Her2, at different levels. Single or small bundle of nanotube devices that were functionalized with IGF1R-specific or Her2-specific antibodies showed 60% decreases in conductivity upon interaction with BT474 or MCF7 breast cancer cells in two µl drops of blood. Control experiments with non-specific antibodies or with MCF10A control breast cells produced a less than 5% decrease in electrical conductivity, illustrating the high sensitivity for whole cell binding by these single nanotube-antibody devices. We postulate that the free energy change due to multiple simultaneous cell-antibody binding events exerted stress along the nanotube surface, decreasing its electrical conductivity due to an increase in band gap. Because the free energy change upon cell-antibody binding, the stress exerted on the nanotube, and the change in conductivity are specific to a specific antigen-antibody interaction; these properties might be used as a fingerprint for the molecular sensing of circulating cancer cells. From optical microscopy observations during sensing, it appears that the binding of a single cell to a single nanotube field effect transistor produced the change in electrical conductivity. Thus we report a nanoscale oncometer with single cell sensitivity with a diameter 1000 times smaller than a cancer cell that functions in a drop of fresh blood.

Sensitivity and specificity of western blot testing of cerebrospinal fluid and serum for diagnosis of equine protozoal myeloencephalitis in horses with and without neurologic abnormalities.

PubMed

Daft, Barbara M; Barr, Bradd C; Gardner, Ian A; Read, Deryck; Bell, William; Peyser, Karen G; Ardans, Alex; Kinde, Hailu; Morrow, Jennifer K

2002-10-01

To determine sensitivity and specificity of western blot testing (WBT) of CSF and serum for diagnosis of equine protozoal myeloencephalitis (EPM) in horses with and without neurologic abnormalities. Prospective investigation. 65 horses with and 169 horses without neurologic abnormalities. CSF and serum from horses submitted for necropsy were tested for Sarcocystis neurona-specific antibody with a WBT. Results of postmortem examination were used as the gold standard against which results of the WBT were compared. Sensitivity of WBT of CSF was 87% for horses with and 88% for horses without neurologic abnormalities. Specificity of WBT of CSF was 44% for horses with and 60% for horses without neurologic abnormalities. Regardless of whether horses did or did not have neurologic abnormalities, sensitivity and specificity of WBT of serum were not significantly different from values for WBT of CSF. Ninety-four horses without EPM had histologic evidence of slight CNS inflammation. The low specificity of WBT of CSF indicated that it is inappropriate to diagnose EPM on the basis of a positive test result alone because of the possibility of false-positive test results. The high sensitivity, however, means that a negative result is useful in ruling out EPM. There was no advantage in testing CSF versus serum in horses without neurologic abnormalities. Slight CNS inflammation was common in horses with and without S neurona-specific antibodies in the CSF and should not be considered an indication of CNS infection with S neurona.

Evaluation of multiplex assay platforms for detection of influenza hemagglutinin subtype specific antibody responses.

PubMed

Li, Zhu-Nan; Weber, Kimberly M; Limmer, Rebecca A; Horne, Bobbi J; Stevens, James; Schwerzmann, Joy; Wrammert, Jens; McCausland, Megan; Phipps, Andrew J; Hancock, Kathy; Jernigan, Daniel B; Levine, Min; Katz, Jacqueline M; Miller, Joseph D

2017-05-01

Influenza hemagglutination inhibition (HI) and virus microneutralization assays (MN) are widely used for seroprevalence studies. However, these assays have limited field portability and are difficult to fully automate for high throughput laboratory testing. To address these issues, three multiplex influenza subtype-specific antibody detection assays were developed using recombinant hemagglutinin antigens in combination with Chembio, Luminex ® , and ForteBio ® platforms. Assay sensitivity, specificity, and subtype cross-reactivity were evaluated using a panel of well characterized human sera. Compared to the traditional HI, assay sensitivity ranged from 87% to 92% and assay specificity in sera collected from unexposed persons ranged from 65% to 100% across the platforms. High assay specificity (86-100%) for A(H5N1) rHA was achieved for sera from exposed or unexposed to hetorosubtype influenza HAs. In contrast, assay specificity for A(H1N1)pdm09 rHA using sera collected from A/Vietnam/1204/2004 (H5N1) vaccinees in 2008 was low (22-30%) in all platforms. Although cross-reactivity against rHA subtype proteins was observed in each assay platform, the correct subtype specific responses were identified 78%-94% of the time when paired samples were available for analysis. These results show that high throughput and portable multiplex assays that incorporate rHA can be used to identify influenza subtype specific infections. Published by Elsevier B.V.

Sensitive and Specific Target Sequences Selected from Retrotransposons of Schistosoma japonicum for the Diagnosis of Schistosomiasis

PubMed Central

Xu, Jing; Zhu, Xing-Quan; Wang, Sheng-Yue; Xia, Chao-Ming

2012-01-01

Background Schistosomiasis japonica is a serious debilitating and sometimes fatal disease. Accurate diagnostic tests play a key role in patient management and control of the disease. However, currently available diagnostic methods are not ideal, and the detection of the parasite DNA in blood samples has turned out to be one of the most promising tools for the diagnosis of schistosomiasis. In our previous investigations, a 230-bp sequence from the highly repetitive retrotransposon SjR2 was identified and it showed high sensitivity and specificity for detecting Schistosoma japonicum DNA in the sera of rabbit model and patients. Recently, 29 retrotransposons were found in S. japonicum genome by our group. The present study highlighted the key factors for selecting a new perspective sensitive target DNA sequence for the diagnosis of schistosomiasis, which can serve as example for other parasitic pathogens. Methodology/Principal Findings In this study, we demonstrated that the key factors based on the bioinformatic analysis for selecting target sequence are the higher genome proportion, repetitive complete copies and partial copies, and active ESTs than the others in the chromosome genome. New primers based on 25 novel retrotransposons and SjR2 were designed and their sensitivity and specificity for detecting S. japonicum DNA were compared. The results showed that a new 303-bp sequence from non-long terminal repeat (LTR) retrotransposon (SjCHGCS19) had high sensitivity and specificity. The 303-bp target sequence was amplified from the sera of rabbit model at 3 d post-infection by nested-PCR and it became negative at 17 weeks post-treatment. Furthermore, the percentage sensitivity of the nested-PCR was 97.67% in 43 serum samples of S. japonicum-infected patients. Conclusions/Significance Our findings highlighted the key factors based on the bioinformatic analysis for selecting target sequence from S. japonicum genome, which provide basis for establishing powerful molecular diagnostic techniques that can be used for monitoring early infection and therapy efficacy to support schistosomiasis control programs. PMID:22479661

Diagnostic Accuracy of the MMSE in Detecting Probable and Possible Alzheimer's Disease in Ethnically Diverse Highly Educated Individuals: An Analysis of the NACC Database

PubMed Central

Spering, Cynthia C.; Hobson, Valerie; Lucas, John A.; Menon, Chloe V.; Hall, James R.

2012-01-01

Background. To validate and extend the findings of a raised cut score of O’Bryant and colleagues (O’Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963–967.) for the Mini-Mental State Examination in detecting cognitive dysfunction in a bilingual sample of highly educated ethnically diverse individuals. Methods. Archival data were reviewed from participants enrolled in the National Alzheimer's Coordinating Center minimum data set. Data on 7,093 individuals with 16 or more years of education were analyzed, including 2,337 cases with probable and possible Alzheimer's disease, 1,418 mild cognitive impairment patients, and 3,088 nondemented controls. Ethnic composition was characterized as follows: 6,296 Caucasians, 581 African Americans, 4 American Indians or Alaska natives, 2 native Hawaiians or Pacific Islanders, 149 Asians, 43 “Other,” and 18 of unknown origin. Results. Diagnostic accuracy estimates (sensitivity, specificity, and likelihood ratio) of Mini-Mental State Examination cut scores in detecting probable and possible Alzheimer's disease were examined. A standard Mini-Mental State Examination cut score of 24 (≤23) yielded a sensitivity of 0.58 and a specificity of 0.98 in detecting probable and possible Alzheimer's disease across ethnicities. A cut score of 27 (≤26) resulted in an improved balance of sensitivity and specificity (0.79 and 0.90, respectively). In the cognitively impaired group (mild cognitive impairment and probable and possible Alzheimer's disease), the standard cut score yielded a sensitivity of 0.38 and a specificity of 1.00 while raising the cut score to 27 resulted in an improved balance of 0.59 and 0.96 of sensitivity and specificity, respectively. Conclusions. These findings cross-validate our previous work and extend them to an ethnically diverse cohort. A higher cut score is needed to maximize diagnostic accuracy of the Mini-Mental State Examination in individuals with college degrees. PMID:22396476

Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting

PubMed Central

Patel, Vinod B.; Singh, Ravesh; Connolly, Cathy; Kasprowicz, Victoria; Zumla, Allimudin; Ndungu, Thumbi; Dheda, Keertan

2010-01-01

Background/Objective The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). Methods Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. Results Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). Conclusions Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression. PMID:21203513

Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

PubMed

Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

2013-08-01

The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation markers.

What is the best way to diagnose and stage malignant pleural mesothelioma?

PubMed

Zahid, Imran; Sharif, Sumera; Routledge, Tom; Scarci, Marco

2011-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was which diagnostic modality [computed tomography (CT), positron emission tomography (PET), combination PET/CT and magnetic resonance imaging (MRI)] provides the best diagnostic and staging information in patients with malignant pleural mesothelioma (MPM). Overall, 61 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that fluorodeoxyglucose (FDG)-PET is superior to MRI and CT but inferior to PET-CT, in terms of diagnostic specificity, sensitivity and staging of MPM. Four studies reported outcomes using FDG-PET to diagnose MPM. PET diagnosed MPM with high sensitivity (92%) and specificity (87.9%). Mean standardised uptake value (SUV) was higher in malignant than benign disease (4.91 vs. 1.41, P<0.0001). Lymph node metastases were detected with higher accuracy (80% vs. 66.7%) compared to extrathoracic disease. Three studies assessed the utility of PET-CT to diagnose MPM. Mean SUV was higher in malignant than benign disease (6.5 vs. 0.8, P<0.001). MPM was diagnosed with high sensitivity (88.2%), specificity (92.9%) and accuracy (88.9%). PET-CT had low sensitivity for stage N2 (38%) and T4 (67%) disease. CT-guided needle biopsy definitively diagnosed MPM after just one biopsy (100% vs. 9%) much more often than a 'blind' approach. CT had a lower success rate (92% vs. 100%) than thoracoscopic pleural biopsy but was equivalent to MRI in terms of detection of lymph node metastases (P=0.85) and visceral pleural tumour (P=0.64). CT had a lower specificity for stage II (77% vs. 100%, P<0.01) and stage III (75% vs. 100%, P<0.01) disease compared to PET-CT. Overall, the high specificity and sensitivity rates seen with open pleural biopsy make it a superior diagnostic modality to CT, MRI or PET for diagnosing patients with MPM.

Identification and classification of genes required for tolerance to high-sucrose stress revealed by genome-wide screening of Saccharomyces cerevisiae.

PubMed

Ando, Akira; Tanaka, Fumiko; Murata, Yoshinori; Takagi, Hiroshi; Shima, Jun

2006-03-01

Yeasts used in bread making are exposed to high concentrations of sucrose during sweet dough fermentation. Despite its importance, tolerance to high-sucrose stress is poorly understood at the gene level. To clarify the genes required for tolerance to high-sucrose stress, genome-wide screening was undertaken using the complete deletion strain collection of diploid Saccharomyces cerevisiae. The screening identified 273 deletions that yielded high sucrose sensitivity, approximately 20 of which were previously uncharacterized. These 273 deleted genes were classified based on their cellular function and localization of their gene products. Cross-sensitivity of the high-sucrose-sensitive mutants to high concentrations of NaCl and sorbitol was studied. Among the 273 sucrose-sensitive deletion mutants, 269 showed cross-sensitivities to sorbitol or NaCl, and four (i.e. ade5,7, ade6, ade8, and pde2) were specifically sensitive to high sucrose. The general stress response pathways via high-osmolarity glycerol and stress response element pathways and the function of the invertase in the ade mutants were similar to those in the wild-type strain. In the presence of high-sucrose stress, intracellular contents of ATP in ade mutants were at least twofold lower than that of the wild-type cells, suggesting that depletion of ATP is a factor in sensitivity to high-sucrose stress. The genes identified in this study might be important for tolerance to high-sucrose stress, and therefore should be target genes in future research into molecular modification for breeding of yeast tolerant to high-sucrose stress.

Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children.

PubMed

Jenmalm, M C; Van Snick, J; Cormont, F; Salman, B

2001-10-01

Allergic diseases are believed to be due to T helper (Th)2-like immunity to allergens in affected tissues, and immune responses to allergens are characterized by a cross-regulation between Th1 and Th2 cells. Atopic individuals may develop IgE antibodies to only one or more allergens. However, the mechanisms behind sensitization to a specific allergen, e.g. why an individual develops IgE to cat but not birch, are not known. Our aim was to study birch- and cat-induced Th1 and Th2 cytokine secretion in children who were sensitized to birch but not to cat, and vice versa. The subjects in the study were 60 12-year-old children. Seventeen of the children were sensitized (skin prick test and circulating IgE positive) to birch but not cat, 13 were sensitized to cat but not birch, 11 were sensitized both to birch and cat, and 19 children were skin prick test and circulating IgE negative. Forty-six children had a history of atopic symptoms, and 42 of them had current symptoms. Peripheral blood mononuclear cells were separated from venous blood and stimulated with cat or birch allergen. The levels of IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma in the cell supernatants were analysed by ELISA. Sensitized children produced more of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 than non-sensitized atopic and non-atopic children in response to stimulation with the allergen they were sensitized to. High levels of the Th2 cytokines IL-4 and IL-5 and low levels of the anti-inflammatory cytokine IL-10 were associated with atopic symptoms, and high cat-induced IL-9 levels with asthma. The Th2 cytokines IL-4, IL-5, IL-9 and IL-13 were all commonly detected in sensitized children after stimulation with the specific, in contrast to an unrelated, allergen. Atopic symptoms were associated with increased levels of IL-4 and IL-5 and tended to be associated with low levels of IL-10, and asthma with high cat-induced IL-9 levels.

Salivary calculus diagnosis with 3-dimensional cone-beam computed tomography.

PubMed

Dreiseidler, Timo; Ritter, Lutz; Rothamel, Daniel; Neugebauer, Jörg; Scheer, Martin; Mischkowski, Robert A

2010-07-01

The objective of this study was to evaluate cone-beam CT (CBCT) diagnoses of sialoliths in the major salivary glands. Twenty-nine CBCT images containing salivary calculi were retrospectively evaluated for image quality and artifact influence. Additionally, the reproducibility of calculus measurement and the differences between CBCT measurements and ultrasonography (US) and histomorphometry (HM) measurements were determined. Diagnostic sensitivity and specificity calculations were based on the observations of 3 masked clinicians, who reviewed a total of 58 CBCT volumes. Salivary calculi were sufficiently visualized in all patients. Metal artifacts were detected in images of 7 patients, and movement artifacts in 2. CBCT calculi measurements were highly reproducible, with mean differences of less than 350 microm. Mean CBCT measurements of calculi diameters differed from mean US measurements by approximately 500 microm and differed from mean HM measurements by approximately 1 mm. For calculus diagnoses, the mean sensitivity and specificity were both 98.85%. Although poor image qualities and artifacts can reduce diagnostic information, salivary calculi can be evaluated adequately with CBCT. CBCT measurements of calculi are highly reproducible and differ little from measurements made with US and HM. Diagnostic sensitivity and specificity levels with CBCT are as high as or higher than those obtained with other diagnostic methods. Because of its high diagnostic-information-to-radiation-dose ratio, CBCT is the preferable imaging modality for salivary calculus diagnosis. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Determination of the diagnostic value of the Modified Mallampati Score, Upper Lip Bite Test and Facial Angle in predicting difficult intubation: A prospective descriptive study.

PubMed

Mahmoodpoor, Ata; Soleimanpour, Hassan; Golzari, Samad Ej; Nejabatian, Arezoo; Pourlak, Tannaz; Amani, Masoumeh; Hajmohammadi, Saeed; Hosseinzadeh, Hamzeh; Esfanjani, Robab Mehdizadeh

2017-02-01

Difficult intubation is a significant cause of mortality and morbidity related to anesthesia. We decided to evaluate the value of Modified Mallampati Score, Upper Lip Bite Test and Facial Angle in the prediction of difficult intubation. In a prospective descriptive study, data from 132 patients who were candidates for elective maxillofacial surgeries under general anesthesia were gathered. Facial Angles were measured by a maxillofacial surgeon according to cephalometry. The Modified Mallampati Score and Upper Lip Bite Test were first measured by an anesthesiologist and then another anesthesiologist was assigned to record the Cormack and Lehane score during the intubation. Grades 3 and 4 were considered as difficult intubation. Sensitivity, specificity, positive predictive value, negative predictive value and Youden index were calculated for all tests. Difficult intubation was reported in 12% of the patients. Facial Angle≤82.5° can predict difficult intubation with 87.5% sensitivity and 88.8% specificity. Among the three tests, a high Modified Mallampati Score had the highest specificity (94.5%) and a high Modified Mallampati Score and Facial Angle (FA≤82.5°) had the highest sensitivity (87.5%). The highest NPV, sensitivity and Youden index were observed when using Facial Angle with the Modified Mallampati Score or with Upper Lip Bite Test. Facial Angle has a high sensitivity, NPV and Youden index for the prediction of difficult intubation, but the best result is achieved when Facial Angle is used in combination with either the Modified Mallampati Score or Upper Lip Bit Test. Copyright © 2017 Elsevier Inc. All rights reserved.

Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue.

PubMed

Fritsch, Michael K; Bridge, Julia A; Schuster, Amy E; Perlman, Elizabeth J; Argani, Pedram

2003-01-01

Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we strongly suggest that the final interpretation of the results from this assay be viewed in light of the other features of the case, including clinical history, histology, and immunohistochemistry, by the diagnostic pathologist. Additional studies such as FISH may be useful in clarifying the nature of equivocal or unexpected results.

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm.

PubMed

Murungi, Moses; Fulton, Travis; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar; Nyehangane, Dan; Juliano, Jonathan J; Siedner, Mark J; Boum, Yap; Boyce, Ross M

2017-05-01

Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan -lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2 + )/pLDH-negative (pLDH - ) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2 + /pLDH + result, 94 (34.1%) with an HRP2 + /pLDH - result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2 + /pLDH - results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2 + /pLDH - results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting. Copyright © 2017 American Society for Microbiology.

Comparative Study of GeneXpert with ZN Stain and Culture in Samples of Suspected Pulmonary Tuberculosis

PubMed Central

Bajaj, Ashish; Bhatia, Vinay; Dutt, Sarjana

2016-01-01

Introduction Tuberculosis remains one of the deadliest communicable diseases. There are number of tests available for the diagnosis of tuberculosis but conventional microscopy has low sensitivity and culture although gold standard, but takes longer time for positivity. On the other side, Nucleic acid amplification techniques due to its rapidity and sensitivity not only help in early diagnosis and management of tuberculosis especially in patients with high clinical suspicion like immunocompromised patients, history of contact with active tuberculosis patient etc., but also curtail the transmission of the disease. Aim To evaluate the sensitivity, specificity, positive predictive value and negative predictive value of Nucleic acid amplification assay (GeneXpert) using respiratory samples in patients with suspected pulmonary tuberculosis and compare with AFB smear microscopy (Ziehl Neelsen stain) and Acid Fast Bacilli (AFB) culture. Materials and Methods We retrospectively reviewed the respiratory samples of suspected pulmonary tuberculosis (including Bronchoalveolar lavage and sputum) of 170 patients from Jan 2015 to Nov 2015 for ZN stain, culture and GeneXpert (Xpert® MTB/Rif assay). The sensitivity, specificity, PPV and NPV of GeneXpert and ZN microscopy were calculated using Liquid culture of Mycobacterium tuberculosis as gold standard. Results A total of 170 patient samples were evaluated in final analysis. Of these, 14 samples were positive by all three methods used in our study. The overall sensitivity, specificity, PPV and NPV of GeneXpert were 86.8%, 93.1%, 78.5% and 96% respectively and for BAL sample, 81.4%, 93.4%, 73.3% and 95.7% respectively. The overall sensitivity and specificity of AFB smear microscopy were 22.2%, % and 78.5% respectively and for BAL sample 22.2% and 100% respectively. For AFB negative samples sensitivity and specificity were 79.1% and 93.1% respectively. Conclusion GeneXpert has a higher sensitivity than AFB smear microscopy in respiratory samples. GeneXpert can be a useful tool for early diagnosis of patients with high clinical suspicion of pulmonary tuberculosis. Positive GeneXpert, but culture negative results should be read cautiously and be well correlated with clinical and treatment history of the patient. The other major advantage of Gene Xpert is that it simultaneously detects Rifampicin resistance and especially beneficial in patient with MDR and HIV associated tuberculosis and should be studied further. PMID:27437212

Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods.

PubMed

Garcia, J J; Blanca, M; Moreno, F; Vega, J M; Mayorga, C; Fernandez, J; Juarez, C; Romano, A; de Ramon, E

1997-01-01

The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects. Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity. In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared. Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP). Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values. Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated. Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis. Analysis of the areas defined by the ROC curves showed statistical differences among the three methods. When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays. Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods. We conclude that for quantitating IgE antibodies by RAST to the BPO determinant, BPO-SP or BPO-PLL conjugates offer advantages in sensitivity and specificity compared with BPO-HSA. These results support and extend previous in vitro studies by our group and highlight the importance of the carrier for RAST assays.

Immunohistochemical application of a highly sensitive and specific murine monoclonal antibody recognising the extracellular domain of the human hepatocyte growth factor receptor (MET).

PubMed

Gruver, Aaron M; Liu, Ling; Vaillancourt, Peter; Yan, Sau-Chi B; Cook, Joel D; Roseberry Baker, Jessica A; Felke, Erin M; Lacy, Megan E; Marchal, Christophe C; Szpurka, Hadrian; Holzer, Timothy R; Rhoads, Emily K; Zeng, Wei; Wortinger, Mark A; Lu, Jirong; Chow, Chi-kin; Denning, Irene J; Beuerlein, Gregory; Davies, Julian; Hanson, Jeff C; Credille, Kelly M; Wijayawardana, Sameera R; Schade, Andrew E

2014-12-01

Development of novel targeted therapies directed against hepatocyte growth factor (HGF) or its receptor (MET) necessitates the availability of quality diagnostics to facilitate their safe and effective use. Limitations of some commercially available anti-MET antibodies have prompted development of the highly sensitive and specific clone A2H2-3. Here we report its analytical properties when applied by an automated immunohistochemistry method. Excellent antibody specificity was demonstrated by immunoblot, ELISA, and IHC evaluation of characterised cell lines including NIH3T3 overexpressing the related kinase MST1R (RON). Sensitivity was confirmed by measurements of MET in cell lines or characterised tissues. IHC correlated well with FISH and quantitative RT-PCR assessments of MET (P < 0.001). Good total agreement (89%) was observed with the anti-MET antibody clone SP44 using whole-tissue sections, but poor positive agreement (21-47%) was seen in tissue microarray cores. Multiple lots displayed appropriate reproducibility (R(2)  > 0.9). Prevalence of MET positivity by IHC was higher in non-squamous cell NSCLC, MET or EGFR amplified cases, and in tumours harbouring abnormalities in EGFR exon 19 or 21. The anti-MET antibody clone A2H2-3 displays excellent specificity and sensitivity. These properties make it suitable for clinical trial investigations and development as a potential companion diagnostic. © 2014 The Authors. Histopathology Published by John Wiley & Sons Ltd.

Performance characteristics of the ARCHITECT anti-HCV assay.

PubMed

Jonas, Gesa; Pelzer, Claudia; Beckert, Christian; Hausmann, Michael; Kapprell, Hans-Peter

2005-10-01

The ARCHITECT Anti-HCV assay is a fully automated high throughput chemiluminescent microparticle immunoassay (CMIA) for the detection of antibodies to structural and nonstructural proteins of the hepatitis C virus (HCV). To further enhance the performance of this test, the assay was modified to improve the specificity for blood donor specimens. The specificity of the enhanced ARCHITECT Anti-HCV assay was evaluated by screening blood donor samples randomly collected from various German blood banks, as well as hospitalized patient samples derived from Germany and the US. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels and on a commercially available worldwide anti-HCV genotype performance panel. Apparent specificity of the modified ARCHITECT Anti-HCV assay in a blood donor population consisting of 3811 specimens was 99.92%, compared to 99.76% for the current on-market assay. Additionally, antibody sensitivity was determined on commercially available anti-HCV seroconversion panels. Seroconversion sensitivity equivalent to or better than the current on-market product was observed by testing 33 seroconversion panels. This study demonstrates that the modified version of the ARCHITECT Anti-HCV assay shows improved specificity for blood donor specimens compared to the current assay on market without compromising sensitivity. With the availability of the improved ARCHITECT Anti-HCV assay and the recent launch of the ARCHITECT HIV Ag/Ab Combo assay, the ARCHITECT system now offers a full hepatitis/retrovirus menu with excellent performance on a high throughput, random access, automated analyzer, ideally suited for blood screening and diagnostic applications.

A Comparative Study Between Smartphone-Based Microscopy and Conventional Light Microscopy in 1021 Dermatopathology Specimens.

PubMed

Jahan-Tigh, Richard R; Chinn, Garrett M; Rapini, Ronald P

2016-01-01

The incorporation of high-resolution cameras into smartphones has allowed for a variety of medical applications including the use of lens attachments that provide telescopic, macroscopic, and dermatoscopic data, but the feasibility and performance characteristics of such a platform for use in dermatopathology have not been described. To determine the diagnostic performance of a smartphone microscope compared to traditional light microscopy in dermatopathology specimens. A simple smartphone microscope constructed with a 3-mm ball lens was used to prospectively evaluate 1021 consecutive dermatopathology cases in a blinded fashion. Referred, consecutive specimens from the community were evaluated at a single university hospital. The performance characteristics of the smartphone platform were calculated by using conventional light microscopy as the gold standard. The sensitivity and specificity for the diagnosis of melanoma, nonmelanoma skin cancers, and other miscellaneous conditions by the phone microscopy platform, as compared with traditional light microscopy, were calculated. For basal cell carcinoma (n = 136), the sensitivity and specificity of smartphone microscopy were 95.6% and 98.1%, respectively. The sensitivity and specificity for squamous cell carcinoma (n = 94) were 89.4% and 97.3%, respectively. The lowest sensitivity was found in melanoma (n = 15) at 60%, although the specificity was high at 99.1%. The accuracy of diagnosis of inflammatory conditions and other neoplasms was variable. Mobile phone-based microscopy has excellent performance characteristics for the inexpensive diagnosis of nonmelanoma skin cancers in a setting where a traditional microscope is not available.

Highly sensitive and specific detection of Giardia duodenalis, Entamoeba histolytica, and Cryptosporidium spp. in human stool samples by the BD MAX™ Enteric Parasite Panel.

PubMed

Parčina, Marijo; Reiter-Owona, Ingrid; Mockenhaupt, Frank P; Vojvoda, Valerija; Gahutu, Jean Bosco; Hoerauf, Achim; Ignatius, Ralf

2018-02-01

Detection of intestinal protozoan parasites by light microscopy is cumbersome, needs experienced personnel, and may lack sensitivity and/or specificity as compared with molecular-based stool assays. Here, we evaluated the BD MAX™ Enteric Parasite Panel, i.e., a multiplex real-time PCR assay for simultaneous detection of Giardia duodenalis, Entamoeba histolytica, and cryptosporidia (Cryptosporidium parvum and C. hominis), by examining 200 positive human stool samples (138 × G. duodenalis, 27 × E. histolytica, 35 × Cryptosporidium spp.) and 119 controls including 18 samples with E. dispar. The majority of the samples, i.e., 153/200 (76.5%) positive samples and 66/119 (55.5%) controls, were confirmed by multiplex in-house PCR detecting the same parasites as the BD MAX™ Enteric Parasite Panel. The BD MAX™ assay did not yield false-positive results. Sensitivity and specificity were 97.8% (95% CI, 93.3-99.4%) and 100% (95% CI, 97.4-100%) for G. duodenalis, 100% (95% CI, 84.5-100%) and 100% (95% CI, 98.4-100%) for E. histolytica, and 100% (95% CI, 87.7-100%) and 100% (95% CI, 98.3-100%) for cryptosporidia, and similar data were obtained when only the 219 PCR-confirmed samples were analyzed. Thus, the BD MAX™ Enteric Parasite Panel provides a highly sensitive and specific tool for the laboratory diagnosis of three predominant protozoan parasites causing enteritis.

The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease.

PubMed

Aryan, Arvin; Azizi, Zahra; Teimouri, Azam; Ebrahimi Daryani, Nasser; Aletaha, Najme; Jahanbakhsh, Ali; Nouritaromlou, Mohammad Kazem; Alborzi, Forough; Mami, Masoud; Basirat, Vahid; Javid Anbardan, Sanam

2016-04-01

BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30±13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease.

Dynamic MR imaging of soft tissue tumors with assessment of the rate and character of lesion enhancement.

PubMed

Tacikowska, Małgorzata

2002-02-01

The aim of this study was to analyze the diagnostic usefulness of dynamic MRI with determination of the coefficient of enhancement rate and the character of tumor enhancement, and to assess both parameters in the differentiation of malignant lesions. The material consisted of 45 patients (30 sarcomas, 15 non-malignant lesions), age 16-64 years. MRI was done using an Elscint 2T unit, gradient echo techniques, apex angle 80 degrees. The repetition time (TR) was 80-200 ms, the echo time (TE) was 2-6 ms, 1 excitation; the acquisition time (TA) was 70-80 ms. The coefficient of tissue enhancement rate was calculated in the region of interest, and expressed as percent per second (erc%/s). The limit value of erc%/s was determined. The sensitivity and specificity of MRI were calculated in the differentiation of malignant tumors. The method of contrast filling of the tumors was assessed in successive phases after administration of gadolinium Gd-DTPA. Dynamic MRI with determination of the index of tumor enhancement rate is highly sensitive (93%) and specific (73%) in the differentiation of malignant and benign lesions. The usefulness of the assessment of tumor enhancement character was not confirmed, since the sensitivity and specificity were 73% and 33%. Dynamic MRI with determination of erc%/s and tumor enhancement character is highly sensitive (93%) and specific (87%). Dynamic MRI with determination of erc%/s and tumor enhancement character is the best method for differential diagnosis.

Evaluation of chromogenic media and seminested PCR in the identification of Candida species

PubMed Central

Daef, Enas; Moharram, Ahmed; Eldin, Salwa Seif; Elsherbiny, Nahla; Mohammed, Mona

2014-01-01

Identification of Candida cultured from various clinical specimens to the species level is increasingly necessary for clinical laboratories. Although sn PCR identifies the species within hours but its cost-effectiveness is to be considered. So there is always a need for media which help in the isolation and identification at the species level. The study aimed to evaluate the performance of different chromogenic media and to compare the effectiveness of the traditional phenotypic methods vs. seminested polymerase chain reaction (sn PCR) for identification of Candida species. One hundred and twenty seven Candida strains isolated from various clinical specimens were identified by conventional methods, four different chromogenic media and sn PCR. HiCrome Candida Differential and CHROMagar Candida media showed comparably high sensitivities and specificities in the identification of C. albicans, C. tropicalis, C. glabrata and C. krusei. CHROMagar Candida had an extra advantage of identifying all C. parapsilosis isolates. CHROMagar-Pal’s medium identified C. albicans, C. tropicalis and C. krusei with high sensitivities and specificities, but couldn’t identify C. glabrata or C. parapsilosis. It was the only medium that identified C. dubliniensis with a sensitivity and specificity of 100%. Biggy agar showed the least sensitivities and specificities. The overall concordance of the snPCR compared to the conventional tests including CHROMAgar Candida in the identification of Candida species was 97.5%. The use of CHROMAgar Candida medium is an easy and accurate method for presumptive identification of the most commonly encountered Candida spp. PMID:24948942