Population and High-Risk Group Screening for Glaucoma: The Los Angeles Latino Eye Study

PubMed Central

Francis, Brian A.; Vigen, Cheryl; Lai, Mei-Ying; Winarko, Jonathan; Nguyen, Betsy; Azen, Stanley

2011-01-01

Purpose. To evaluate the ability of various screening tests, both individually and in combination, to detect glaucoma in the general Latino population and high-risk subgroups. Methods. The Los Angeles Latino Eye Study is a population-based study of eye disease in Latinos 40 years of age and older. Participants (n = 6082) underwent Humphrey visual field testing (HVF), frequency doubling technology (FDT) perimetry, measurement of intraocular pressure (IOP) and central corneal thickness (CCT), and independent assessment of optic nerve vertical cup disc (C/D) ratio. Screening parameters were evaluated for three definitions of glaucoma based on optic disc, visual field, and a combination of both. Analyses were also conducted for high-risk subgroups (family history of glaucoma, diabetes mellitus, and age ≥65 years). Sensitivity, specificity, and receiver operating characteristic curves were calculated for those continuous parameters independently associated with glaucoma. Classification and regression tree (CART) analysis was used to develop a multivariate algorithm for glaucoma screening. Results. Preset cutoffs for screening parameters yielded a generally poor balance of sensitivity and specificity (sensitivity/specificity for IOP ≥21 mm Hg and C/D ≥0.8 was 0.24/0.97 and 0.60/0.98, respectively). Assessment of high-risk subgroups did not improve the sensitivity/specificity of individual screening parameters. A CART analysis using multiple screening parameters—C/D, HVF, and IOP—substantially improved the balance of sensitivity and specificity (sensitivity/specificity 0.92/0.92). Conclusions. No single screening parameter is useful for glaucoma screening. However, a combination of vertical C/D ratio, HVF, and IOP provides the best balance of sensitivity/specificity and is likely to provide the highest yield in glaucoma screening programs. PMID:21245400

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.

Support Vector Machines to improve physiologic hot flash measures: application to the ambulatory setting.

PubMed

Thurston, Rebecca C; Hernandez, Javier; Del Rio, Jose M; De La Torre, Fernando

2011-07-01

Most midlife women have hot flashes. The conventional criterion (≥2 μmho rise/30 s) for classifying hot flashes physiologically has shown poor performance. We improved this performance in the laboratory with Support Vector Machines (SVMs), a pattern classification method. We aimed to compare conventional to SVM methods to classify hot flashes in the ambulatory setting. Thirty-one women with hot flashes underwent 24 h of ambulatory sternal skin conductance monitoring. Hot flashes were quantified with conventional (≥2 μmho/30 s) and SVM methods. Conventional methods had low sensitivity (sensitivity=.57, specificity=.98, positive predictive value (PPV)=.91, negative predictive value (NPV)=.90, F1=.60), with performance lower with higher body mass index (BMI). SVMs improved this performance (sensitivity=.87, specificity=.97, PPV=.90, NPV=.96, F1=.88) and reduced BMI variation. SVMs can improve ambulatory physiologic hot flash measures. Copyright © 2010 Society for Psychophysiological Research.

An improved Abbott ARCHITECT assay for the detection of hepatitis B virus surface antigen (HBsAg).

PubMed

Lou, Sheng C; Pearce, Sandra K; Lukaszewska, Teresa X; Taylor, Russell E; Williams, Gregg T; Leary, Thomas P

2011-05-01

The sensitive and accurate detection of hepatitis B virus surface antigen (HBsAg) is critical to the identification of infection and the prevention of transfusion transmitted disease. Improvement in HBsAg assay sensitivity is essential to reduce the window to detect an acute HBV infection. Additionally, the sensitive detection of HBsAg mutants that continue to evolve due to vaccine escape, immune selection and an error prone reverse transcriptase is a necessity. A fully automated HBsAg prototype assay on the Abbott ARCHITECT instrument was developed to improve sensitivity and mutant detection. This magnetic microparticle-based assay utilizes anti-HBsAg monoclonal antibodies to capture antigen present in serum or plasma. Captured antigen is then detected using anti-HBsAg antibody conjugated with the chemiluminescent compound, acridinium. The sensitivity of the ARCHITECT HBsAg prototype assay was improved as compared to the current ARCHITECT, PRISM, and competitor HBsAg assays. The enhancement in assay sensitivity was demonstrated by the use of commercially available HBV seroconversion panels. The prototype assay detected more panel members (185 of 383) vs. the current ARCHITECT (171), PRISM (181), or competitor HBsAg assays (73/140 vs. 62/140, respectively). The ARCHITECT prototype assay also efficiently detected all mutants evaluated. Finally, the sensitivity improvement did not compromise the specificity of the assay (99.94%). An improved Abbott ARCHITECT HBsAg prototype assay with enhanced detection of HBsAg and HBsAg mutants, as well as equivalent specificity was developed for the detection, diagnosis, and management of HBV infection. Copyright © 2011 Elsevier B.V. All rights reserved.

Improved Detection of Botulinum Neurotoxin Serotype A by Endopep-MS through Peptide Substrate Modification

PubMed Central

Wang, Dongxia; Baudys, Jakub; Ye, Yiming; Rees, Jon C.; Barr, John R.; Pirkle, James L.; Kalb, Suzanne R.

2015-01-01

Botulinum neurotoxins (BoNTs) are a family of seven toxin serotypes that are the most toxic substances known to man. Intoxication with BoNT causes flaccid paralysis and can lead to death if untreated with serotype specific antibodies. Supportive care, including ventilation, may be necessary. Rapid and sensitive detection of BoNT is necessary for timely clinical confirmation of clinical botulism. Previously, our laboratory developed a fast and sensitive mass spectrometry (MS) method termed the Endopep-MS assay. The BoNT serotypes are rapidly detected and differentiated by extracting the toxin with serotype specific antibodies and detecting the unique and serotype specific cleavage products of peptide substrates that mimic the sequence of the BoNT native targets. To further improve the sensitivity of the Endopep-MS assay, we report here the optimization of the substrate peptide for the detection of BoNT/A. Modifications on the terminal groups of the original peptide substrate with acetylation and amidation significantly improved the detection of BoNT/A cleavage products. The replacement of some internal amino acid residues with single or multiple substitutions led to further improvement. An optimized peptide increased assay sensitivity five fold with toxin spiked into buffer solution or different biological matrices. PMID:23017875

Underreporting of Fall Injuries of Older Adults: Implications for Wellness Visit Fall Risk Screening.

PubMed

Hoffman, Geoffrey J; Ha, Jinkyung; Alexander, Neil B; Langa, Kenneth M; Tinetti, Mary; Min, Lillian C

2018-04-17

To compare the accuracy of and factors affecting the accuracy of self-reported fall-related injuries (SFRIs) with those of administratively obtained FRIs (AFRIs). Retrospective observational study SETTING: United States PARTICIPANTS: Fee-for-service Medicare beneficiaries aged 65 and older (N=47,215). We used 24-month self-report recall data from 2000-2012 Health and Retirement Study data to identify SFRIs and linked inpatient, outpatient, and ambulatory Medicare data to identify AFRIs. Sensitivity and specificity were assessed, with AFRIs defined using the University of California at Los Angeles/RAND algorithm as the criterion standard. Logistic regression models were used to identify sociodemographic and health predictors of sensitivity. Overall sensitivity and specificity were 28% and 92%. Sensitivity was greater for the oldest adults (38%), women (34%), those with more functional limitations (47%), and those with a prior fall (38%). In adjusted results, several participant factors (being female, being white, poor functional status, depression, prior falls) were modestly associated with better sensitivity and specificity. Injury severity (requiring hospital care) most substantively improved SFRI sensitivity (73%). An overwhelming 72% of individuals who received Medicare-reimbursed health care for FRIs failed to report a fall injury when asked. Future efforts to address underreporting in primary care of nonwhite and healthier older adults are critical to improve preventive efforts. Redesigned questions-for example, that address stigma of attributing injury to falling-may improve sensitivity. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

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

PubMed

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

2015-03-01

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

Whole-animal imaging of bacterial infection using endoscopic excitation of β-lactamase (BlaC)-specific fluorogenic probe

NASA Astrophysics Data System (ADS)

Nooshabadi, Fatemeh; Yang, Hee-Jeong; Cheng, Yunfeng; Xie, Hexin; Rao, Jianghong; Cirillo, Jeffrey D.; Maitland, Kristen C.

2016-03-01

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the most frequent causes of death worldwide. The slow growth rate of Mtb limits progress toward understanding tuberculosis including diagnosis of infections and evaluating therapeutic efficacy. Development of near-infrared (NIR) β-lactamase (BlaC)-specific fluorogenic substrate has made a significant breakthrough in the whole-animal imaging to detect Mtb infection. The reporter enzyme fluorescence (REF) system using a BlaC-specific fluorogenic substrate has improved the detection sensitivity in whole-animal optical imaging down to ~104 colony forming units (CFU) of bacteria, about 100-fold improvement over recombinant strains. However, improvement of detection sensitivity is strongly needed for clinical diagnosis of early stage infection at greater tissue depth. In order to improve detection sensitivity, we have integrated a fiber-based microendoscpe into a whole-animal imaging system to transmit the excitation light from the fiber bundle to the fluorescent target directly and measure fluorescent level using BlaC-specific REF substrate in the mouse lung. REF substrate, CNIR800, was delivered via aerosol route to the pulmonary infected mice with M. bovis BCG strain at 24 hours post-infection and groups of mice were imaged at 1-4 hours post-administration of the substrate using the integrated imaging system. In this study we evaluated the kinetics of CNIR800 substrate using REF technology using the integrated imaging system. Integration of these technologies has great promise for improved detection sensitivity allowing pre-clinical imaging for evaluation of new therapeutic agents.

Artificial neural network techniques to improve the ability of optical coherence tomography to detect optic neuritis.

PubMed

Garcia-Martin, Elena; Herrero, Raquel; Bambo, Maria P; Ara, Jose R; Martin, Jesus; Polo, Vicente; Larrosa, Jose M; Garcia-Feijoo, Julian; Pablo, Luis E

2015-01-01

To analyze the ability of Spectralis optical coherence tomography (OCT) to detect multiple sclerosis (MS) and to distinguish MS eyes with antecedent optic neuritis (ON). To analyze the capability of artificial neural network (ANN) techniques to improve the diagnostic precision. MS patients and controls were enrolled (n = 217). OCT was used to determine the 768 retinal nerve fiber layer thicknesses. Sensitivity and specificity were evaluated to test the ability of OCT to discriminate between MS and healthy eyes, and between MS with and without antecedent ON using ANN. Using ANN technique multilayer perceptrons, OCT could detect MS with a sensitivity of 89.3%, a specificity of 87.6%, and a diagnostic precision of 88.5%. Compared with the OCT-provided parameters, the ANN had a better sensitivity-specificity balance. ANN technique improves the capability of Spectralis OCT to detect MS disease and to distinguish MS eyes with or without antecedent ON.

’Coxiella Burnetii’ Vaccine Development: Lipopolysaccharide Structural Analysis

DTIC Science & Technology

1991-02-20

Analytical instrumentation and methodology is presented for the determination of endotoxin -related structures at much improved sensitivity and... ENDOTOXIN CHARACTERIZATION BY SFC .......................... 10 III. COXIELLA BURNETII LPS CHARACTERIZATION A. EXPERIMENTAL...period for the determination of endotoxin -related structures at much improved sensitivity and specificity. Reports, and their applications, are listed in

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

pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

PubMed

Wang, Xue-Qing; Zhang, Qiang

2012-10-01

pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Improving detection of HIV-associated cognitive impairment: Comparison of the International HIV Dementia Scale and a Brief Screening Battery

PubMed Central

de Almeida, Sergio Monteiro; Kamat, Rujvi; Cherner, Mariana; Umlauf, Anya; Ribeiro, Clea Elisa; de Pereira, Ana Paula; Franklin, Donald; Heaton, Robert K.; Ellis, Ronald J.

2016-01-01

Objectives The International HIV Dementia Scale (IHDS) was developed to screen for HIV-associated dementia (HAD), but it has been used more generally for HIV-associated neurocognitive disorder (HAND). This study sought to examine the accuracy of the IHDS in a cohort of Brazilian HIV-infected individuals and compare its performance to an alternative screening battery for detecting HAND. Methods 108 participants (including 60 HIV-infected persons), completed the IHDS and a gold standard neuropsychological (NP) battery of 17 tests. As alternative screening method, all possible three-test combinations from the NP battery were examined and a superiority index (a marker of specificity and sensitivity) was calculated. Results Sensitivity and specificity to HAND using the standard IHDS cutpoint of 10 were 36% and 75% respectively. The best balance between sensitivity and specificity was accomplished with a modified cutpoint of 11.5, which yielded sensitivity of 72% and specificity of 58%. The top two most sensitive test combinations, compared to the gold standard NP battery, were Trail Making Test A, WAIS-III Digit Symbol (DS) and HVLT-R Total Recall (sensitivity 91%, specificity 96%), and DS, BVMT-R Total Recall and Grooved Pegboard Test-Dominant Hand (sensitivity 94%, specificity 91%). Conclusions Both test combinations can be administered in under 10 minutes and were more accurate than the IHDS in classifying HIV+ participants as NP impaired or unimpaired. These data suggest that demographically corrected T-scores from commonly used NP measures with modest time and material demands can improve identification of patients with HAND who may benefit from a more extensive NP examination. PMID:27828876

Improving Detection of HIV-Associated Cognitive Impairment: Comparison of the International HIV Dementia Scale and a Brief Screening Battery.

PubMed

de Almeida, Sérgio Monteiro; Kamat, Rujvi; Cherner, Mariana; Umlauf, Anya; Ribeiro, Clea E; de Pereira, Ana Paula; Franklin, Donald; Heaton, Robert K; Ellis, Ronald J

2017-03-01

The International HIV Dementia Scale (IHDS) was developed to screen for HIV-associated dementia, but it has been used more generally for HIV-associated neurocognitive disorder (HAND). This study sought to examine the accuracy of the IHDS in a cohort of Brazilian HIV-infected individuals and compare its performance to an alternative screening battery for detecting HAND. A total of 108 participants (including 60 HIV-infected persons) completed the IHDS and a gold standard neuropsychological (NP) battery of 17 tests. As alternative screening method, all possible 3-test combinations from the NP battery were examined and a superiority index (a marker of specificity and sensitivity) was calculated. Sensitivity and specificity to HAND using the standard IHDS cutpoint of 10 were 36% and 75%, respectively. The best balance between sensitivity and specificity was accomplished with a modified cutpoint of 11.5, which yielded sensitivity of 72% and specificity of 58%. The top two most sensitive test combinations, compared with the gold standard NP battery, were Trail Making Test A, Wechsler Adult Intelligence Scale III Digit Symbol and Hopkins Verbal Learning Test-Revised Total Recall (sensitivity 91%, specificity 96%), and Digit Symbol, Brief Visuospatial Memory Test-Revised Total Recall and Grooved Pegboard Test-dominant hand (sensitivity 94%, specificity 91%). Both test combinations can be administered in less than 10 minutes and were more accurate than the IHDS in classifying HIV+ participants as NP impaired or unimpaired. These data suggest that demographically corrected T-scores from commonly used NP measures with modest time and material demands can improve identification of patients with HAND who may benefit from a more extensive NP examination.

[The role of endotracheal aspirate culture in the diagnosis of ventilator-associated pneumonia: a meta analysis].

PubMed

Wang, Fei; He, Bei

2013-01-01

To investigate the role of endotracheal aspirate (EA) culture in the diagnosis and antibiotic management in ventilator-associated pneumonia (VAP). We searched CNKI, Wanfang, PUBMED and EMBASE databases published from January 1990 to December 2011, to find relevant literatures on VAP microbiological diagnostic techniques including EA and bronchoalveolar lavage (BALF). The following key words were used: ventilator associated pneumonia, diagnosis and adult. Meta-analysis was performed and the sensitivity and specificity of EA on VAP diagnosis were calculated. Our literature search identified 1665 potential articles, 8 of which fulfilled our selection criteria including 561 patients with paired cultures. Using BALF quantitative culture as reference standard, the sensitivity and specificity of EA were 72% and 71%. When considering quantitative culture of EA only, the sensitivity and specificity improved to 90% and 65%, while the positive and the negative predictive values were 68% and 89% respectively. However, the sensitivity and specificity of semi-quantitative culture of EA were only 50% and 80%, with a positive predictive value of 77% and a negative predictive value of 58% respectively. EA culture had relatively poor sensitivity and specificity, although quantitative culture of EA only could improve the sensitivity. Initiating therapy on the basis of EA quantitative culture may still result in excessive antibiotic usage. Our data suggested that EA could provide some information for clinical decision but could not replace the role of BALF quantitative culture in VAP diagnosis.

Use of Ancillary Carbapenemase Tests To Improve Specificity of Phenotypic Definitions for Carbapenemase-Producing Enterobacteriaceae.

PubMed

Miller, Shelley A; Hindler, Janet A; Chengcuenca, Angelo; Humphries, Romney M

2017-06-01

Carbapenemase-producing Enterobacteriaceae (CPE) are a significant threat to public health. In 2015, CDC revised the surveillance definition for CPE to include all Enterobacteriaceae resistant to any carbapenem tested. However, this definition is associated with poor specificity. We evaluated the performance of this definition, compared to carbapenemase PCR, for a collection of 125 Enterobacteriaceae We also investigated the impact of ancillary testing for carbapenemase of isolates that met the CDC CPE surveillance definition. The two ancillary tests evaluated were the Xpert Carba-R assay, a molecular test, and the carbapenem inactivation method (CIM). Two variables were evaluated for the CIM: suspension of organisms in double-distilled water (ddH 2 O) versus tryptic soy broth (TSB) to incubate disks, and incubation of plates for 6 h versus 18 to 20 h. The sensitivity and specificity of the Carba-R assay were 100% compared to the results of in-house PCR. The sensitivities of the CIM performed with TSB were 94.6% when read at 6 h and 97.7% when read at 18 to 20 h; the sensitivities with ddH 2 O were 88.0% when read at 6 h and 93.0% when incubated for 18 to 20 h. The specificity was 100% for all variables tested. Without ancillary testing, the sensitivity of the CDC definition was 98.9% for CPE, and the specificity was 6.1%. Testing isolates that screened positive by the CDC definition with the Xpert Carba-R did not change the sensitivity, and it improved the specificity to 100%. Similarly, the use of the CIM (TSB and 18 to 20 h of incubation) to confirm screen-positive isolates resulted in a sensitivity of 95.6% and specificity of 100%. Copyright © 2017 American Society for Microbiology.

Validation of Case Finding Algorithms for Hepatocellular Cancer from Administrative Data and Electronic Health Records using Natural Language Processing

PubMed Central

Sada, Yvonne; Hou, Jason; Richardson, Peter; El-Serag, Hashem; Davila, Jessica

2013-01-01

Background Accurate identification of hepatocellular cancer (HCC) cases from automated data is needed for efficient and valid quality improvement initiatives and research. We validated HCC ICD-9 codes, and evaluated whether natural language processing (NLP) by the Automated Retrieval Console (ARC) for document classification improves HCC identification. Methods We identified a cohort of patients with ICD-9 codes for HCC during 2005–2010 from Veterans Affairs administrative data. Pathology and radiology reports were reviewed to confirm HCC. The positive predictive value (PPV), sensitivity, and specificity of ICD-9 codes were calculated. A split validation study of pathology and radiology reports was performed to develop and validate ARC algorithms. Reports were manually classified as diagnostic of HCC or not. ARC generated document classification algorithms using the Clinical Text Analysis and Knowledge Extraction System. ARC performance was compared to manual classification. PPV, sensitivity, and specificity of ARC were calculated. Results 1138 patients with HCC were identified by ICD-9 codes. Based on manual review, 773 had HCC. The HCC ICD-9 code algorithm had a PPV of 0.67, sensitivity of 0.95, and specificity of 0.93. For a random subset of 619 patients, we identified 471 pathology reports for 323 patients and 943 radiology reports for 557 patients. The pathology ARC algorithm had PPV of 0.96, sensitivity of 0.96, and specificity of 0.97. The radiology ARC algorithm had PPV of 0.75, sensitivity of 0.94, and specificity of 0.68. Conclusion A combined approach of ICD-9 codes and NLP of pathology and radiology reports improves HCC case identification in automated data. PMID:23929403

Validation of Case Finding Algorithms for Hepatocellular Cancer From Administrative Data and Electronic Health Records Using Natural Language Processing.

PubMed

Sada, Yvonne; Hou, Jason; Richardson, Peter; El-Serag, Hashem; Davila, Jessica

2016-02-01

Accurate identification of hepatocellular cancer (HCC) cases from automated data is needed for efficient and valid quality improvement initiatives and research. We validated HCC International Classification of Diseases, 9th Revision (ICD-9) codes, and evaluated whether natural language processing by the Automated Retrieval Console (ARC) for document classification improves HCC identification. We identified a cohort of patients with ICD-9 codes for HCC during 2005-2010 from Veterans Affairs administrative data. Pathology and radiology reports were reviewed to confirm HCC. The positive predictive value (PPV), sensitivity, and specificity of ICD-9 codes were calculated. A split validation study of pathology and radiology reports was performed to develop and validate ARC algorithms. Reports were manually classified as diagnostic of HCC or not. ARC generated document classification algorithms using the Clinical Text Analysis and Knowledge Extraction System. ARC performance was compared with manual classification. PPV, sensitivity, and specificity of ARC were calculated. A total of 1138 patients with HCC were identified by ICD-9 codes. On the basis of manual review, 773 had HCC. The HCC ICD-9 code algorithm had a PPV of 0.67, sensitivity of 0.95, and specificity of 0.93. For a random subset of 619 patients, we identified 471 pathology reports for 323 patients and 943 radiology reports for 557 patients. The pathology ARC algorithm had PPV of 0.96, sensitivity of 0.96, and specificity of 0.97. The radiology ARC algorithm had PPV of 0.75, sensitivity of 0.94, and specificity of 0.68. A combined approach of ICD-9 codes and natural language processing of pathology and radiology reports improves HCC case identification in automated data.

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.

Improving EEG-Based Driver Fatigue Classification Using Sparse-Deep Belief Networks.

PubMed

Chai, Rifai; Ling, Sai Ho; San, Phyo Phyo; Naik, Ganesh R; Nguyen, Tuan N; Tran, Yvonne; Craig, Ashley; Nguyen, Hung T

2017-01-01

This paper presents an improvement of classification performance for electroencephalography (EEG)-based driver fatigue classification between fatigue and alert states with the data collected from 43 participants. The system employs autoregressive (AR) modeling as the features extraction algorithm, and sparse-deep belief networks (sparse-DBN) as the classification algorithm. Compared to other classifiers, sparse-DBN is a semi supervised learning method which combines unsupervised learning for modeling features in the pre-training layer and supervised learning for classification in the following layer. The sparsity in sparse-DBN is achieved with a regularization term that penalizes a deviation of the expected activation of hidden units from a fixed low-level prevents the network from overfitting and is able to learn low-level structures as well as high-level structures. For comparison, the artificial neural networks (ANN), Bayesian neural networks (BNN), and original deep belief networks (DBN) classifiers are used. The classification results show that using AR feature extractor and DBN classifiers, the classification performance achieves an improved classification performance with a of sensitivity of 90.8%, a specificity of 90.4%, an accuracy of 90.6%, and an area under the receiver operating curve (AUROC) of 0.94 compared to ANN (sensitivity at 80.8%, specificity at 77.8%, accuracy at 79.3% with AUC-ROC of 0.83) and BNN classifiers (sensitivity at 84.3%, specificity at 83%, accuracy at 83.6% with AUROC of 0.87). Using the sparse-DBN classifier, the classification performance improved further with sensitivity of 93.9%, a specificity of 92.3%, and an accuracy of 93.1% with AUROC of 0.96. Overall, the sparse-DBN classifier improved accuracy by 13.8, 9.5, and 2.5% over ANN, BNN, and DBN classifiers, respectively.

Improving EEG-Based Driver Fatigue Classification Using Sparse-Deep Belief Networks

PubMed Central

Chai, Rifai; Ling, Sai Ho; San, Phyo Phyo; Naik, Ganesh R.; Nguyen, Tuan N.; Tran, Yvonne; Craig, Ashley; Nguyen, Hung T.

2017-01-01

This paper presents an improvement of classification performance for electroencephalography (EEG)-based driver fatigue classification between fatigue and alert states with the data collected from 43 participants. The system employs autoregressive (AR) modeling as the features extraction algorithm, and sparse-deep belief networks (sparse-DBN) as the classification algorithm. Compared to other classifiers, sparse-DBN is a semi supervised learning method which combines unsupervised learning for modeling features in the pre-training layer and supervised learning for classification in the following layer. The sparsity in sparse-DBN is achieved with a regularization term that penalizes a deviation of the expected activation of hidden units from a fixed low-level prevents the network from overfitting and is able to learn low-level structures as well as high-level structures. For comparison, the artificial neural networks (ANN), Bayesian neural networks (BNN), and original deep belief networks (DBN) classifiers are used. The classification results show that using AR feature extractor and DBN classifiers, the classification performance achieves an improved classification performance with a of sensitivity of 90.8%, a specificity of 90.4%, an accuracy of 90.6%, and an area under the receiver operating curve (AUROC) of 0.94 compared to ANN (sensitivity at 80.8%, specificity at 77.8%, accuracy at 79.3% with AUC-ROC of 0.83) and BNN classifiers (sensitivity at 84.3%, specificity at 83%, accuracy at 83.6% with AUROC of 0.87). Using the sparse-DBN classifier, the classification performance improved further with sensitivity of 93.9%, a specificity of 92.3%, and an accuracy of 93.1% with AUROC of 0.96. Overall, the sparse-DBN classifier improved accuracy by 13.8, 9.5, and 2.5% over ANN, BNN, and DBN classifiers, respectively. PMID:28326009

Improved artificial neural networks in prediction of malignancy of lesions in contrast-enhanced MR-mammography.

PubMed

Vomweg, T W; Buscema, M; Kauczor, H U; Teifke, A; Intraligi, M; Terzi, S; Heussel, C P; Achenbach, T; Rieker, O; Mayer, D; Thelen, M

2003-09-01

The aim of this study was to evaluate the capability of improved artificial neural networks (ANN) and additional novel training methods in distinguishing between benign and malignant breast lesions in contrast-enhanced magnetic resonance-mammography (MRM). A total of 604 histologically proven cases of contrast-enhanced lesions of the female breast at MRI were analyzed. Morphological, dynamic and clinical parameters were collected and stored in a database. The data set was divided into several groups using random or experimental methods [Training & Testing (T&T) algorithm] to train and test different ANNs. An additional novel computer program for input variable selection was applied. Sensitivity and specificity were calculated and compared with a statistical method and an expert radiologist. After optimization of the distribution of cases among the training and testing sets by the T & T algorithm and the reduction of input variables by the Input Selection procedure a highly sophisticated ANN achieved a sensitivity of 93.6% and a specificity of 91.9% in predicting malignancy of lesions within an independent prediction sample set. The best statistical method reached a sensitivity of 90.5% and a specificity of 68.9%. An expert radiologist performed better than the statistical method but worse than the ANN (sensitivity 92.1%, specificity 85.6%). Features extracted out of dynamic contrast-enhanced MRM and additional clinical data can be successfully analyzed by advanced ANNs. The quality of the resulting network strongly depends on the training methods, which are improved by the use of novel training tools. The best results of an improved ANN outperform expert radiologists.

A New Approach for Detection Improvement of the Creutzfeldt-Jakob Disorder through a Specific Surface Chemistry Applied onto Titration Well

PubMed Central

Mille, Caroline; Debarnot, Dominique; Zorzi, Willy; Moualij, Benaissa El; Quadrio, Isabelle; Perret-Liaudet, Armand; Coudreuse, Arnaud; Legeay, Gilbert; Poncin-Epaillard, Fabienne

2012-01-01

This work illustrates the enhancement of the sensitivity of the ELISA titration for recombinant human and native prion proteins, while reducing other non-specific adsorptions that could increase the background signal and lead to a low sensitivity and false positives. It is achieved thanks to the association of plasma chemistry and coating with different amphiphilic molecules bearing either ionic charges and/or long hydrocarbon chains. The treated support by 3-butenylamine hydrochloride improves the signal detection of recombinant protein, while surface modification with the 3,7-dimethylocta-2,6-dien-1-diamine (geranylamine) enhances the sensitivity of the native protein. Beside the surface chemistry effect, these different results are associated with protein conformation. PMID:25586034

Sensitivity and Specificity of Suspected Case Definition Used during West Africa Ebola Epidemic

PubMed Central

Champaloux, Steven W.; Keïta, Sakoba; Martel, Lise; Bilivogui, Pepe; Knust, Barbara; McCollum, Andrea M.

2018-01-01

Rapid early detection and control of Ebola virus disease (EVD) is contingent on accurate case definitions. Using an epidemic surveillance dataset from Guinea, we analyzed an EVD case definition developed by the World Health Organization (WHO) and used in Guinea. We used the surveillance dataset (March–October 2014; n = 2,847 persons) to identify patients who satisfied or did not satisfy case definition criteria. Laboratory confirmation determined cases from noncases, and we calculated sensitivity, specificity and predictive values. The sensitivity of the defintion was 68.9%, and the specificity of the definition was 49.6%. The presence of epidemiologic risk factors (i.e., recent contact with a known or suspected EVD case-patient) had the highest sensitivity (74.7%), and unexplained deaths had the highest specificity (92.8%). Results for case definition analyses were statistically significant (p<0.05 by χ2 test). Multiple components of the EVD case definition used in Guinea contributed to improved overall sensitivity and specificity. PMID:29260687

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.

Sensitivity and Specificity of OCT Angiography to Detect Choroidal Neovascularization.

PubMed

Faridi, Ambar; Jia, Yali; Gao, Simon S; Huang, David; Bhavsar, Kavita V; Wilson, David J; Sill, Andrew; Flaxel, Christina J; Hwang, Thomas S; Lauer, Andreas K; Bailey, Steven T

2017-01-01

To determine the sensitivity and specificity of optical coherence tomography angiography (OCTA) in the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Prospective case series. Prospective series of seventy-two eyes were studied, which included eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal controls. All eyes underwent OCTA with a spectral domain (SD) OCT (Optovue, Inc.). The 3D angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram, and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence of CNV. The sensitivity and specificity of CNV detection compared to the gold standard of fluorescein angiography (FA) and OCT was determined for structural SD-OCT alone, en face OCTA alone, and with en face OCTA combined with cross-sectional OCTA. Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage (SRH) and sensitivity improved to 94% for both graders if eyes with SRH were excluded. The addition of cross-sectional OCTA along with en face OCTA improved the sensitivity to 100% for both graders. Structural OCT alone also had a sensitivity of 100%. The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader B. The specificity of structural OCT alone was 97.5% for grader A and 85% for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5% for grader A and 100% for grader B. Sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approaches that of the gold standard of FA with OCT, and it is better than en face OCTA alone. Structural OCT alone has excellent sensitivity for CNV detection. False positives from structural OCT can be mitigated with the addition of flow information with OCTA.

Connectome sensitivity or specificity: which is more important?

PubMed

Zalesky, Andrew; Fornito, Alex; Cocchi, Luca; Gollo, Leonardo L; van den Heuvel, Martijn P; Breakspear, Michael

2016-11-15

Connectomes with high sensitivity and high specificity are unattainable with current axonal fiber reconstruction methods, particularly at the macro-scale afforded by magnetic resonance imaging. Tensor-guided deterministic tractography yields sparse connectomes that are incomplete and contain false negatives (FNs), whereas probabilistic methods steered by crossing-fiber models yield dense connectomes, often with low specificity due to false positives (FPs). Densely reconstructed probabilistic connectomes are typically thresholded to improve specificity at the cost of a reduction in sensitivity. What is the optimal tradeoff between connectome sensitivity and specificity? We show empirically and theoretically that specificity is paramount. Our evaluations of the impact of FPs and FNs on empirical connectomes indicate that specificity is at least twice as important as sensitivity when estimating key properties of brain networks, including topological measures of network clustering, network efficiency and network modularity. Our asymptotic analysis of small-world networks with idealized modular structure reveals that as the number of nodes grows, specificity becomes exactly twice as important as sensitivity to the estimation of the clustering coefficient. For the estimation of network efficiency, the relative importance of specificity grows linearly with the number of nodes. The greater importance of specificity is due to FPs occurring more prevalently between network modules rather than within them. These spurious inter-modular connections have a dramatic impact on network topology. We argue that efforts to maximize the sensitivity of connectome reconstruction should be realigned with the need to map brain networks with high specificity. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

Specificity and Sensitivity of Claims-Based Algorithms for Identifying Members of Medicare+Choice Health Plans That Have Chronic Medical Conditions

PubMed Central

Rector, Thomas S; Wickstrom, Steven L; Shah, Mona; Thomas Greeenlee, N; Rheault, Paula; Rogowski, Jeannette; Freedman, Vicki; Adams, John; Escarce, José J

2004-01-01

Objective To examine the effects of varying diagnostic and pharmaceutical criteria on the performance of claims-based algorithms for identifying beneficiaries with hypertension, heart failure, chronic lung disease, arthritis, glaucoma, and diabetes. Study Setting Secondary 1999–2000 data from two Medicare+Choice health plans. Study Design Retrospective analysis of algorithm specificity and sensitivity. Data Collection Physician, facility, and pharmacy claims data were extracted from electronic records for a sample of 3,633 continuously enrolled beneficiaries who responded to an independent survey that included questions about chronic diseases. Principal Findings Compared to an algorithm that required a single medical claim in a one-year period that listed the diagnosis, either requiring that the diagnosis be listed on two separate claims or that the diagnosis to be listed on one claim for a face-to-face encounter with a health care provider significantly increased specificity for the conditions studied by 0.03 to 0.11. Specificity of algorithms was significantly improved by 0.03 to 0.17 when both a medical claim with a diagnosis and a pharmacy claim for a medication commonly used to treat the condition were required. Sensitivity improved significantly by 0.01 to 0.20 when the algorithm relied on a medical claim with a diagnosis or a pharmacy claim, and by 0.05 to 0.17 when two years rather than one year of claims data were analyzed. Algorithms that had specificity more than 0.95 were found for all six conditions. Sensitivity above 0.90 was not achieved all conditions. Conclusions Varying claims criteria improved the performance of case-finding algorithms for six chronic conditions. Highly specific, and sometimes sensitive, algorithms for identifying members of health plans with several chronic conditions can be developed using claims data. PMID:15533190

Diagnosis of glenoid labral tears using 3-tesla MRI vs. 3-tesla MRA: a systematic review and meta-analysis.

PubMed

Ajuied, Adil; McGarvey, Ciaran P; Harb, Ziad; Smith, Christian C; Houghton, Russell P; Corbett, Steven A

2018-05-01

Various protocols exist for magnetic resonance arthrogram (MRA) of the shoulder, including 3D isotropic scanning and positioning in neutral (2D neutral MRA), or abduction-external-rotation (ABER). MRA does not improve diagnostic accuracy for labral tears when compared to magnetic resonance imaging (MRI) performed using 3-Tesla (3T) magnets. Systematic review of the Cochrane, MEDLINE, and PubMed databases according to PRISMA guidelines. Included studies compared 3T MRI or 3T MRA (index tests) to arthroscopic findings (reference test). Methodological appraisal performed using QUADAS-2. Pooled sensitivity and specificity were calculated. Ten studies including 929 patients were included. Index test bias and applicability were a concern in the majority of studies. The use of arthroscopy as the reference test raised concern of verification bias in all studies. For anterior labral lesions, 3T MRI was less sensitive (0.83 vs. 0.87 p = 0.083) than 3T 2D neutral MRA. Compared to 3T 2D neutral MRA, both 3T 3D Isotropic MRA and 3T ABER MRA significantly improved sensitivity (0.87 vs. 0.95 vs. 0.94). For SLAP lesions, 3T 2D neutral MRA was of similar sensitivity to 3T MRI (0.84 vs. 0.83, p = 0.575), but less specific (0.99 vs. 0.92 p < 0.0001). For posterior labral lesions, 3T 2D neutral MRA had greater sensitivity than 3T 3D Isotropic MRA and 3T MRI (0.90 vs. 0.83 vs. 0.83). At 3-T, MRA improved sensitivity for diagnosis of anterior and posterior labral lesions, but reduced specificity in diagnosis of SLAP tears. 3T MRA with ABER positioning further improved sensitivity in diagnosis of anterior labral tears. IV.

Erysipelothrix rhusiopathiae and Mycoplasma hyopneumoniae: the sensitivities of enzyme-linked immunosorbent assays for detecting vaccinated sows of unknown disease status using serum and colostrum, and the correlation of the results for sow serum, colostrum, and piglet serum.

PubMed

Jenvey, Caitlin J; Reichel, Michael P; Cockcroft, Peter D

2015-03-01

Due to relatively high concentrations of immunoglobulins, colostrum has the potential to improve the sensitivity of diagnostic tests for diseases in pigs when compared with serum. It is possible that colostrum could improve the sensitivity of the antibody enzyme-linked immunosorbent assay (ELISA) compared with serum. Colostrum is also essential for piglets, providing protection against infections in the first few weeks and months of life. The sensitivity of 2 commercially available ELISAs, one for the detection of Erysipelothrix rhusiopathiae and the second for Mycoplasma hyopneumoniae antibodies, when used with sow colostrum in comparison with serum was investigated. The correlation of maternal E. rhusiopathiae- and M. hyopneumoniae-specific antibody levels with specific-antibody serum levels in the piglet was also determined. The sensitivity was defined as the proportion of vaccinated sows that were correctly identified as vaccinated at a given cutoff point. The true disease status of the sows with regard to the 2 infections was unknown. Blood and colostrum samples were collected from 20 sows, 10 primiparous and 10 multiparous, and blood samples were also collected from the piglets of each sow, 48-72 hr post-farrowing. The sensitivities of both ELISAs were significantly improved when using colostrum compared with serum. Sow serum and colostrum optical density (OD) values were significantly correlated. The mean sow OD values for serum for E. rhusiopathiae and M. hyopneumoniae and colostrum for E. rhusiopathiae were significantly correlated with piglet serum OD levels. If the improved sensitivity of colostrum can be demonstrated in infected animals, this will increase the ability of the test to identify infected animals using both individual and pooled colostrum. Testing serum and/or colostrum using ELISA can be useful predictors of piglet disease-specific OD values. © 2015 The Author(s).

Hierarchical Nanogold Labels to Improve the Sensitivity of Lateral Flow Immunoassay

NASA Astrophysics Data System (ADS)

Serebrennikova, Kseniya; Samsonova, Jeanne; Osipov, Alexander

2018-06-01

Lateral flow immunoassay (LFIA) is a widely used express method and offers advantages such as a short analysis time, simplicity of testing and result evaluation. However, an LFIA based on gold nanospheres lacks the desired sensitivity, thereby limiting its wide applications. In this study, spherical nanogold labels along with new types of nanogold labels such as gold nanopopcorns and nanostars were prepared, characterized, and applied for LFIA of model protein antigen procalcitonin. It was found that the label with a structure close to spherical provided more uniform distribution of specific antibodies on its surface, indicative of its suitability for this type of analysis. LFIA using gold nanopopcorns as a label allowed procalcitonin detection over a linear range of 0.5-10 ng mL-1 with the limit of detection of 0.1 ng mL-1, which was fivefold higher than the sensitivity of the assay with gold nanospheres. Another approach to improve the sensitivity of the assay included the silver enhancement method, which was used to compare the amplification of LFIA for procalcitonin detection. The sensitivity of procalcitonin determination by this method was 10 times better the sensitivity of the conventional LFIA with gold nanosphere as a label. The proposed approach of LFIA based on gold nanopopcorns improved the detection sensitivity without additional steps and prevented the increased consumption of specific reagents (antibodies).

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.

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

The sensitivity and specificity of subjective memory complaints and the subjective memory rating scale, deterioration cognitive observee, mini-mental state examination, six-item screener and clock drawing test in dementia screening.

PubMed

Ramlall, S; Chipps, J; Bhigjee, A I; Pillay, B J

2013-01-01

The effectiveness of dementia screening depends on the availability of suitable screening tools with good sensitivity and specificity to confidently distinguish normal age-related cognitive decline from dementia. The aim of this study was to evaluate the discriminant validity of 7 screening measures for dementia. A sample of 140 participants aged ≥60 years living in a residential facility for the aged were assessed clinically and assigned caseness for dementia using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised diagnostic criteria. Sensitivity and specificity of a selection of the following screening measures were tested using receiver operating characteristic (ROC) analysis for individual and combined tests: the Mini-Mental State Examination (MMSE), Six-Item Screener (SIS), Subjective Memory Complaint, Subjective Memory Complaint Clinical (SMCC), Subjective Memory Rating Scale (SMRS), Deterioration Cognitive Observee (DECO) and the Clock Drawing Test (CDT). Using ROC analyses, the SMCC, MMSE and CDT were found to be 'moderately accurate' in screening for dementia with an area under the curve (AUC) >0.70. The AUCs for the SIS (0.526), SMRS (0.661) and DECO (0.687) classified these measures as being 'less accurate'. At recommended cutoff scores, the SMCC had a sensitivity of 90.9% and specificity of 45.7%; the MMSE had a sensitivity of 63.6% and a specificity of 76.0%, and the CDT had a sensitivity of 44.4% and a specificity of 88.9%. Combining the SMCC and MMSE did not improve their predictive power except for a modest increase when using the sequential rule. The SMCC is composed of valid screening questions that have high sensitivity, are simple to administer and ideal for administration at the community or primary health care level as a first level of 'rule-out' screening. The MMSE can be included at a second stage of screening at the general hospital level and the CDT in specialist clinical settings. Sequential use of the SMCC and MMSE will improve the specificity of the former and the sensitivity of the latter. Copyright © 2013 S. Karger AG, Basel.

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.

Estimating sensitivity and specificity for technology assessment based on observer studies.

PubMed

Nishikawa, Robert M; Pesce, Lorenzo L

2013-07-01

The goal of this study was to determine the accuracy and precision of using scores from a receiver operating characteristic rating scale to estimate sensitivity and specificity. We used data collected in a previous study that measured the improvements in radiologists' ability to classify mammographic microcalcification clusters as benign or malignant with and without the use of a computer-aided diagnosis scheme. Sensitivity and specificity were estimated from the rating data from a question that directly asked the radiologists their biopsy recommendations, which was used as the "truth," because it is the actual recall decision, thus it is their subjective truth. By thresholding the rating data, sensitivity and specificity were estimated for different threshold values. Because of interreader and intrareader variability, estimated sensitivity and specificity values for individual readers could be as much as 100% in error when using rating data compared to using the biopsy recommendation data. When pooled together, the estimates using thresholding the rating data were in good agreement with sensitivity and specificity estimated from the recommendation data. However, the statistical power of the rating data estimates was lower. By simply asking the observer his or her explicit recommendation (eg, biopsy or no biopsy), sensitivity and specificity can be measured directly, giving a more accurate description of empirical variability and the power of the study can be maximized. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy.

PubMed

Yoshida, Naruo; Hirata, Hirokuni; Watanabe, Mineaki; Sugiyama, Kumiya; Arima, Masafumi; Fukushima, Yasutsugu; Ishii, Yoshiki

2015-07-01

Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P < 0.01) between hornet (R = 0.92) or paper wasp venom (R = 0.78) in improvement testing and conventional testing. To determine specificity, 20 volunteers who had never experienced a Hymenoptera sting were all negative for sIgE against these venoms in both improvement and conventional testing. Improved sensitivity was seen in 8 patients negative for sIgE against both venoms in conventional testing, while improvement testing revealed sIgE against hornet or paper wasp venom in 5 (total 38 (92.7%)) patients. The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Multivalent Binding and Biomimetic Cell Rolling Improves the Sensitivity and Specificity of Circulating Tumor Cell Capture.

PubMed

Myung, Ja Hye; Eblan, Michael J; Caster, Joseph M; Park, Sin-Jung; Poellmann, Michael J; Wang, Kyle; Tam, Kevin A; Miller, Seth M; Shen, Colette; Chen, Ronald C; Zhang, Tian; Tepper, Joel E; Chera, Bhishamjit S; Wang, Andrew Z; Hong, Seungpyo

2018-06-01

Purpose: We aimed to examine the effects of multivalent binding and biomimetic cell rolling on the sensitivity and specificity of circulating tumor cell (CTC) capture. We also investigated the clinical significance of CTCs and their kinetic profiles in patients with cancer undergoing radiotherapy treatment. Experimental Design: Patients with histologically confirmed primary carcinoma undergoing radiotherapy, with or without chemotherapy, were eligible for enrollment. Peripheral blood was collected prospectively at up to five time points, including before radiotherapy, at the first week, mid-point and final week of treatment, as well as 4 to 12 weeks after completion of radiotherapy. CTC capture was accomplished using a nanotechnology-based assay (CapioCyte) functionalized with aEpCAM, aHER-2, and aEGFR. Results: CapioCyte was able to detect CTCs in all 24 cancer patients enrolled. Multivalent binding via poly(amidoamine) dendrimers further improved capture sensitivity. We also showed that cell rolling effect can improve CTC capture specificity (% of captured cells that are CK + /CD45 - /DAPI + ) up to 38%. Among the 18 patients with sequential CTC measurements, the median CTC decreased from 113 CTCs/mL before radiotherapy to 32 CTCs/mL at completion of radiotherapy ( P = 0.001). CTCs declined throughout radiotherapy in patients with complete clinical and/or radiographic response, in contrast with an elevation in CTCs at mid or post-radiotherapy in the two patients with known pathologic residual disease. Conclusions: Our study demonstrated that multivalent binding and cell rolling can improve the sensitivity and specificity of CTC capture compared with multivalent binding alone, allowing reliable monitoring of CTC changes during and after treatment. Clin Cancer Res; 24(11); 2539-47. ©2018 AACR . ©2018 American Association for Cancer Research.

Application of adaptive boosting to EP-derived multilayer feed-forward neural networks (MLFN) to improve benign/malignant breast cancer classification

NASA Astrophysics Data System (ADS)

Land, Walker H., Jr.; Masters, Timothy D.; Lo, Joseph Y.; McKee, Dan

2001-07-01

A new neural network technology was developed for improving the benign/malignant diagnosis of breast cancer using mammogram findings. A new paradigm, Adaptive Boosting (AB), uses a markedly different theory in solutioning Computational Intelligence (CI) problems. AB, a new machine learning paradigm, focuses on finding weak learning algorithm(s) that initially need to provide slightly better than random performance (i.e., approximately 55%) when processing a mammogram training set. Then, by successive development of additional architectures (using the mammogram training set), the adaptive boosting process improves the performance of the basic Evolutionary Programming derived neural network architectures. The results of these several EP-derived hybrid architectures are then intelligently combined and tested using a similar validation mammogram data set. Optimization focused on improving specificity and positive predictive value at very high sensitivities, where an analysis of the performance of the hybrid would be most meaningful. Using the DUKE mammogram database of 500 biopsy proven samples, on average this hybrid was able to achieve (under statistical 5-fold cross-validation) a specificity of 48.3% and a positive predictive value (PPV) of 51.8% while maintaining 100% sensitivity. At 97% sensitivity, a specificity of 56.6% and a PPV of 55.8% were obtained.

Genetic influence on contrast sensitivity in middle-aged male twins.

PubMed

Cronin-Golomb, Alice; Panizzon, Matthew S; Lyons, Michael J; Franz, Carol E; Grant, Michael D; Jacobson, Kristen C; Eisen, Seth A; Laudate, Thomas M; Kremen, William S

2007-07-01

Contrast sensitivity is strongly associated with daily functioning among older adults, but the genetic and environmental contributions to this ability are unknown. Using the classical twin method, we addressed this issue by examining contrast sensitivity at five spatial frequencies (1.5-18 cycles per degree) in 718 middle-aged male twins from the Vietnam Era Twin Study of Aging (VETSA). Heritability estimates were modest (14-38%), whereas individual-specific environmental influences accounted for 62-86% of the variance. Identifying the types of individual-specific events that impact contrast sensitivity may suggest interventions to modulate this ability and thereby improve overall quality of life as adults age.

Development and Validation of Search Filters to Identify Articles on Family Medicine in Online Medical Databases

PubMed Central

Pols, David H.J.; Bramer, Wichor M.; Bindels, Patrick J.E.; van de Laar, Floris A.; Bohnen, Arthur M.

2015-01-01

Physicians and researchers in the field of family medicine often need to find relevant articles in online medical databases for a variety of reasons. Because a search filter may help improve the efficiency and quality of such searches, we aimed to develop and validate search filters to identify research studies of relevance to family medicine. Using a new and objective method for search filter development, we developed and validated 2 search filters for family medicine. The sensitive filter had a sensitivity of 96.8% and a specificity of 74.9%. The specific filter had a specificity of 97.4% and a sensitivity of 90.3%. Our new filters should aid literature searches in the family medicine field. The sensitive filter may help researchers conducting systematic reviews, whereas the specific filter may help family physicians find answers to clinical questions at the point of care when time is limited. PMID:26195683

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.

Evaluation and optimization of a commercial blocking ELISA for detecting antibodies to influenza A virus for research and surveillance of mallards.

PubMed

Shriner, Susan A; VanDalen, Kaci K; Root, J Jeffrey; Sullivan, Heather J

2016-02-01

The availability of a validated commercial assay is an asset for any wildlife investigation. However, commercial products are often developed for use in livestock and are not optimized for wildlife. Consequently, it is incumbent upon researchers and managers to apply commercial products appropriately to optimize program outcomes. We tested more than 800 serum samples from mallards for antibodies to influenza A virus with the IDEXX AI MultiS-Screen Ab test to evaluate assay performance. Applying the test per manufacturer's recommendations resulted in good performance with 84% sensitivity and 100% specificity. However, performance was improved to 98% sensitivity and 98% specificity by increasing the recommended cut-off. Using this alternative threshold for identifying positive and negative samples would greatly improve sample classification, especially for field samples collected months after infection when antibody titers have waned from the initial primary immune response. Furthermore, a threshold that balances sensitivity and specificity reduces estimation bias in seroprevalence estimates. Published by Elsevier B.V.

An improved method for detecting circulating microRNAs with S-Poly(T) Plus real-time PCR

PubMed Central

Niu, Yanqin; Zhang, Limin; Qiu, Huiling; Wu, Yike; Wang, Zhiwei; Zai, Yujia; Liu, Lin; Qu, Junle; Kang, Kang; Gou, Deming

2015-01-01

We herein describe a simple, sensitive and specific method for analysis of circulating microRNAs (miRNA), termed S-Poly(T) Plus real-time PCR assay. This new method is based on our previously developed S-Poly(T) method, in which a unique S-Poly(T) primer is used during reverse-transcription to increase sensitivity and specificity. Further increased sensitivity and simplicity of S-Poly(T) Plus, in comparison with the S-Poly(T) method, were achieved by a single-step, multiple-stage reaction, where RNAs were polyadenylated and reverse-transcribed at the same time. The sensitivity of circulating miRNA detection was further improved by a modified method of total RNA isolation from serum/plasma, S/P miRsol, in which glycogen was used to increase the RNA yield. We validated our methods by quantifying miRNA expression profiles in the sera of the patients with pulmonary arterial hypertension associated with congenital heart disease. In conclusion, we developed a simple, sensitive, and specific method for detecting circulating miRNAs that allows the measurement of 266 miRNAs from 100 μl of serum or plasma. This method presents a promising tool for basic miRNA research and clinical diagnosis of human diseases based on miRNA biomarkers. PMID:26459910

Improved spatial regression analysis of diffusion tensor imaging for lesion detection during longitudinal progression of multiple sclerosis in individual subjects

NASA Astrophysics Data System (ADS)

Liu, Bilan; Qiu, Xing; Zhu, Tong; Tian, Wei; Hu, Rui; Ekholm, Sven; Schifitto, Giovanni; Zhong, Jianhui

2016-03-01

Subject-specific longitudinal DTI study is vital for investigation of pathological changes of lesions and disease evolution. Spatial Regression Analysis of Diffusion tensor imaging (SPREAD) is a non-parametric permutation-based statistical framework that combines spatial regression and resampling techniques to achieve effective detection of localized longitudinal diffusion changes within the whole brain at individual level without a priori hypotheses. However, boundary blurring and dislocation limit its sensitivity, especially towards detecting lesions of irregular shapes. In the present study, we propose an improved SPREAD (dubbed improved SPREAD, or iSPREAD) method by incorporating a three-dimensional (3D) nonlinear anisotropic diffusion filtering method, which provides edge-preserving image smoothing through a nonlinear scale space approach. The statistical inference based on iSPREAD was evaluated and compared with the original SPREAD method using both simulated and in vivo human brain data. Results demonstrated that the sensitivity and accuracy of the SPREAD method has been improved substantially by adapting nonlinear anisotropic filtering. iSPREAD identifies subject-specific longitudinal changes in the brain with improved sensitivity, accuracy, and enhanced statistical power, especially when the spatial correlation is heterogeneous among neighboring image pixels in DTI.

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.

Repeat Cytology and Human Papillomavirus Screening Strategies in Detecting Preinvasive Cervical Lesions

PubMed Central

Li, Kemin; Yin, Rutie

2015-01-01

Abstract The aim of the present study was to determine the value of human papillomavirus (HPV) testing in screening patients with preinvasive cervical lesions. Seven hundred thirty-four women diagnosed with atypical squamous cells of undetermined significance (ASCUS+) cervical cytology during routine screening had additional cytologic testing and HPV DNA testing within 6 months of their diagnosis, after which all women who tested positive were referred for colposcopy and biopsy. The test findings were then used to determine the screening value of HPV for diagnosing preinvasive cervical lesions. Cytology and HPV testing were compared by conventional cytology. The odds ratio (OR) of sensitivity using ASCUS+ or low-grade squamous intraepithelial neoplasia (LSIL+) as a cutoff for detecting cervical intraepithelial neoplasia (CIN) II+ was, respectively, 0.78 (0.72, 0.85) and 0.82 (0.70, 0.95) (P < 0.01). The cytology for triage and conventional cytology had different sensitivities using ASCUS+ or LSIL+ as the cutoff (P < 0.01). The cytology or HPV testing and conventional cytology had a difference in sensitivity using ASCUS+, LSIL+, or high-grade squamous intraepithelial neoplasia (HSIL+) as the cutoff (P < 0.01). Cytology and HPV testing were also compared with conventional cytology. The OR of specificity using ASCUS+ or LSIL+ as the cutoff for the detection of CIN II+ was 1.97 (1.68, 2.31) and 1.10 (1.02, 1.18), respectively (P < 0.01). The cytology for triage and conventional cytology had a difference in specificity when ASCUS+ or LSIL+ was used as the cutoff (P < 0.01). Finally, the cytology or HPV testing and conventional cytology had a difference in specificity when ASCUS+, LSIL+, or HSIL+ was used as the cutoff (P < 0.01). Cytology and HPV testing and cytology for triage improved the specificity of detecting CIN II+, but this did not improve the sensitivity. Additionally, cytology or HPV testing improved the sensitivity of detecting CIN II+ but not the specificity. PMID:25654377

Diagnostic value of serum galactomannan, (1-3)-β-D-glucan, and Aspergillus fumigatus-specific IgA and IgG assays for invasive pulmonary aspergillosis in non-neutropenic patients.

PubMed

Dobias, R; Jaworska, P; Tomaskova, H; Kanova, M; Lyskova, P; Vrba, Z; Holub, C; Svobodová, L; Hamal, P; Raska, M

2018-03-25

Detection of serum galactomannan (GM) and (1-3)-β-D-glucan (BG) is considered useful for non-culture diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Only few studies evaluated these seromarkers in non-neutropenic patients suspected of having IPA. The aim of this study was to evaluate both tests together with the Aspergillus fumigatus-specific serum IgG and IgA (IgAG) test for serological IPA diagnosis in non-neutropenic patients.Sera from 87 patients suspected of having IPA were retrospectively analyzed. Patients were categorized into groups of proven IPA (n=10), putative IPA (n=31), and non-IPA colonization (n=46). When the GM, BG, and IgAG assays were used for patients included in the study, the sensitivity/specificity / positive predictive value (PPV) / negative predictive value (NPV) were 48.8%/91.3%/83.3%/66.7%, 82.9%/73.9%/73.9%/82.9%, and 75.6%/95.7%/93.9%/81.5%, respectively. Thus, the highest specificity and PPV were confirmed for the IgAG assay. Improvements in the sensitivity and NPV were achieved by "at least one positive" analysis with the GM and BG assays, with the sensitivity/specificity/PPV/NPV values being 85.0%/69.6%/71.4%/84.2%. Nevertheless, the highest sensitivity and NPV were achieved by the "at least one positive" analysis combining the GM, BG, and IgAG tests (97.6% and 96.8%, respectively).The involvement of the IgAG assay could improve IPA diagnosis in non-neutropenic patients by increasing the sensitivity and NPV when combined with the GM or BG assays. Further improvement was achieved by combining the GM, BG, and IgAG assays using the "at least one positive test" strategy, especially if doubt exists. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The power of timing: Adding a time-to-completion cutoff to the Word Choice Test and Recognition Memory Test improves classification accuracy.

PubMed

Erdodi, Laszlo A; Tyson, Bradley T; Shahein, Ayman G; Lichtenstein, Jonathan D; Abeare, Christopher A; Pelletier, Chantalle L; Zuccato, Brandon G; Kucharski, Brittany; Roth, Robert M

2017-05-01

The Recognition Memory Test (RMT) and Word Choice Test (WCT) are structurally similar, but psychometrically different. Previous research demonstrated that adding a time-to-completion cutoff improved the classification accuracy of the RMT. However, the contribution of WCT time-cutoffs to improve the detection of invalid responding has not been investigated. The present study was designed to evaluate the classification accuracy of time-to-completion on the WCT compared to the accuracy score and the RMT. Both tests were administered to 202 adults (M age  = 45.3 years, SD = 16.8; 54.5% female) clinically referred for neuropsychological assessment in counterbalanced order as part of a larger battery of cognitive tests. Participants obtained lower and more variable scores on the RMT (M = 44.1, SD = 7.6) than on the WCT (M = 46.9, SD = 5.7). Similarly, they took longer to complete the recognition trial on the RMT (M = 157.2 s,SD = 71.8) than the WCT (M = 137.2 s, SD = 75.7). The optimal cutoff on the RMT (≤43) produced .60 sensitivity at .87 specificity. The optimal cutoff on the WCT (≤47) produced .57 sensitivity at .87 specificity. Time-cutoffs produced comparable classification accuracies for both RMT (≥192 s; .48 sensitivity at .88 specificity) and WCT (≥171 s; .49 sensitivity at .91 specificity). They also identified an additional 6-10% of the invalid profiles missed by accuracy score cutoffs, while maintaining good specificity (.93-.95). Functional equivalence was reached at accuracy scores ≤43 (RMT) and ≤47 (WCT) or time-to-completion ≥192 s (RMT) and ≥171 s (WCT). Time-to-completion cutoffs are valuable additions to both tests. They can function as independent validity indicators or enhance the sensitivity of accuracy scores without requiring additional measures or extending standard administration time.

Development and first evaluation of a novel multiplex real-time PCR on whole blood samples for rapid pathogen identification in critically ill patients with sepsis.

PubMed

van de Groep, Kirsten; Bos, Martine P; Savelkoul, Paul H M; Rubenjan, Anna; Gazenbeek, Christel; Melchers, Willem J G; van der Poll, Tom; Juffermans, Nicole P; Ong, David S Y; Bonten, Marc J M; Cremer, Olaf L

2018-04-26

Molecular tests may enable early adjustment of antimicrobial therapy and be complementary to blood culture (BC) which has imperfect sensitivity in critically ill patients. We evaluated a novel multiplex real-time PCR assay to diagnose bloodstream pathogens directly in whole blood samples (BSI-PCR). BSI-PCR included 11 species- and four genus-specific PCRs, a molecular Gram-stain PCR, and two antibiotic resistance markers. We collected 5 mL blood from critically ill patients simultaneously with clinically indicated BC. Microbial DNA was isolated using the Polaris method followed by automated DNA extraction. Sensitivity and specificity were calculated using BC as reference. BSI-PCR was evaluated in 347 BC-positive samples (representing up to 50 instances of each pathogen covered by the test) and 200 BC-negative samples. Bacterial species-specific PCR sensitivities ranged from 65 to 100%. Sensitivity was 26% for the Gram-positive PCR, 32% for the Gram-negative PCR, and ranged 0 to 7% for yeast PCRs. Yeast detection was improved to 40% in a smaller set-up. There was no overall association between BSI-PCR sensitivity and time-to-positivity of BC (which was highly variable), yet Ct-values were lower for true-positive versus false-positive PCR results. False-positive results were observed in 84 (4%) of the 2200 species-specific PCRs in 200 culture-negative samples, and ranged from 0 to 6% for generic PCRs. Sensitivity of BSI-PCR was promising for individual bacterial pathogens, but still insufficient for yeasts and generic PCRs. Further development of BSI-PCR will focus on improving sensitivity by increasing input volumes and on subsequent implementation as a bedside test.

The use of breast ultrasound color Doppler vascular pattern morphology improves diagnostic sensitivity with minimal change in specificity.

PubMed

Svensson, W E; Pandian, A J; Hashimoto, H

2010-10-01

The aim of this study was to evaluate the use of vascular morphology, around and within the B-mode region of abnormality, for improving the diagnostic accuracy of two of the most common solid breast pathologies. The B-mode and Doppler images of 117 breast cancers and 366 fibroadenomas and lesions with a fibroadenoma-like appearance were reviewed retrospectively and the morphology of the vascular pattern was evaluated. The ratio of external to internal color Doppler, the external vascular pattern and the connecting vessels to internal vessels were assessed and differentiated into benign and malignant vascular patterns. These patterns were correlated with the histological diagnosis. Vascularity was demonstrated in 95 % of cancers and in 46 % of benign lesions with a trend to increasing vascularity in cancers. This provided poor specificity for excluding cancer in fibroadenomas. Variations in vascular pattern were recorded. The observed benign vascular patterns were avascularity, vascularity in the periphery and peripheral marginal vessels connecting with internal vascularity. The observed malignant vascular patterns were radially aligned external vessels with internal vessels being more numerous than external vessels which connected to radial vessels. (Fisher exact test p < 0.0001). Analysis of the vascular morphology improved the sensitivity for identifying cancers from 97 % (B-mode) to 99 % (B-mode and color Doppler) with a minimal reduction in specificity (93.7 to 92.6 %) or accuracy (94.6 to 94.2 %). The presence of vascularity within a lesion, by itself, is no longer a good predictor of malignancy because of the increase in Doppler sensitivity associated with improvements in ultrasound technology. The color Doppler ultrasound vascular pattern morphology improves the accuracy and sensitivity of B-mode image diagnosis, breast cancers and fibroadenomas with a minimal loss of specificity. Any breast lesion with radial rather than marginal connecting vessels should be regarded with suspicion. © Georg Thieme Verlag KG Stuttgart · New York.

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.

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.

Overcoming the errors of in-house PCR used in the clinical laboratory for the diagnosis of extrapulmonary tuberculosis.

PubMed

Kunakorn, M; Raksakai, K; Pracharktam, R; Sattaudom, C

1999-03-01

Our experiences from 1993 to 1997 in the development and use of IS6110 base PCR for the diagnosis of extrapulmonary tuberculosis in a routine clinical setting revealed that error-correcting processes can improve existing diagnostic methodology. The reamplification method initially used had a sensitivity of 90.91% and a specificity of 93.75%. The concern was focused on the false positive results of this method caused by product-carryover contamination. This method was changed to single round PCR with carryover prevention by uracil DNA glycosylase (UDG), resulting in a 100% specificity but only 63% sensitivity. Dot blot hybridization was added after the single round PCR, increasing the sensitivity to 87.50%. However, false positivity resulted from the nonspecific dot blot hybridization signal, reducing the specificity to 89.47%. The hybridization of PCR was changed to a Southern blot with a new oligonucleotide probe giving the sensitivity of 85.71% and raising the specificity to 99.52%. We conclude that the PCR protocol for routine clinical use should include UDG for carryover prevention and hybridization with specific probes to optimize diagnostic sensitivity and specificity in extrapulmonary tuberculosis testing.

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

PubMed

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

2017-06-01

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

Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening

PubMed Central

Phillips, Michael; Bauer, Thomas L.; Cataneo, Renee N.; Lebauer, Cassie; Mundada, Mayur; Pass, Harvey I.; Ramakrishna, Naren; Rom, William N.; Vallières, Eric

2015-01-01

Background Breath volatile organic compounds (VOCs) have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening. Methods Model-building phase (unblinded): Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation): We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively). The algorithm predicted discriminant function (DF) values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B). Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening. Results Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88). In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel. Conclusions Breath VOC mass ion biomarkers identified lung cancer in a separate independent cohort, in a blinded replicated study. Combining breath biomarkers with chest CT could potentially improve the sensitivity and specificity of lung cancer screening. Trial Registration ClinicalTrials.gov NCT00639067 PMID:26698306

[Application of a continual improvement approach to selecting diagnostic markers for acute pancreatitis in an emergency department].

PubMed

Salinas, María; Flores, Emilio; López-Garrigós, Maite; Díaz, Elena; Esteban, Patricia; Leiva-Salinas, Carlos

2017-01-01

To apply a continual improvement model to develop an algorithm for ordering laboratory tests to diagnose acute pancreatitis in a hospital emergency department. Quasi-experimental study using the continual improvement model (plan, do, check, adjust cycles) in 2 consecutive phases in emergency patients: amylase and lipase results were used to diagnose acute pancreatitis in the first phase; in the second, only lipase level was first determined; amylase testing was then ordered only if the lipase level fell within a certain range. We collected demographic data, number amylase and lipase tests ordered and the findings, final diagnosis, and the results of a questionnaire to evaluate satisfaction with emergency care. The first phase included 517 patients, of whom 20 had acute pancreatitis. For amylase testing sensitivity was 0.70; specificity, 0.85; positive predictive value (PPV), 17; and negative predictive value (NPV), 0.31. For lipase testing these values were sensitivity, 0.85; specificity, 0.96; PPV, 21, and NPV, 0.16. When both tests were done, sensitivity was 0.85; specificity 0.99; PPV, 85; and NPV, 0.15. The second phase included data for 4815 patients, 118 of whom had acute pancreatitis. The measures of diagnostic yield for the new algorithm were sensitivity, 0.92; specificity, 0.98; PPV, 46; and NPV, 0.08]. This study demonstrates a process for developing a protocol to guide laboratory testing in acute pancreatitis in the hospital emergency department. The proposed sequence of testing for pancreatic enzyme levels can be effective for diagnosing acute pancreatitis in patients with abdominal pain.

Fractal and twin SVM-based handgrip recognition for healthy subjects and trans-radial amputees using myoelectric signal.

PubMed

Arjunan, Sridhar Poosapadi; Kumar, Dinesh Kant; Jayadeva J

2016-02-01

Identifying functional handgrip patterns using surface electromygram (sEMG) signal recorded from amputee residual muscle is required for controlling the myoelectric prosthetic hand. In this study, we have computed the signal fractal dimension (FD) and maximum fractal length (MFL) during different grip patterns performed by healthy and transradial amputee subjects. The FD and MFL of the sEMG, referred to as the fractal features, were classified using twin support vector machines (TSVM) to recognize the handgrips. TSVM requires fewer support vectors, is suitable for data sets with unbalanced distributions, and can simultaneously be trained for improving both sensitivity and specificity. When compared with other methods, this technique resulted in improved grip recognition accuracy, sensitivity, and specificity, and this improvement was significant (κ=0.91).

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.

Genetic Influence on Contrast Sensitivity in Middle-Aged Male Twins

PubMed Central

Cronin-Golomb, Alice; Panizzon, Matthew S.; Lyons, Michael J.; Franz, Carol E.; Grant, Michael D.; Jacobson, Kristen C.; Eisen, Seth A.; Laudate, Thomas M.; Kremen, William S.

2007-01-01

Contrast sensitivity is strongly associated with daily functioning among older adults, but the genetic and environmental contributions to this ability are unknown. Using the classical twin method, we addressed this issue by examining contrast sensitivity at five spatial frequencies (1.5–18 cycles per degree) in 718 middle-aged male twins from the Vietnam Era Twin Study of Aging (VETSA). Heritability estimates were modest (14%–38%), whereas individual-specific environmental influences accounted for 62%–86% of the variance. Identifying the types of individual-specific events that impact contrast sensitivity may suggest interventions to modulate this ability and thereby improve overall quality of life as adults age. PMID:17604073

Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas.

PubMed

Youland, Ryan S; Pafundi, Deanna H; Brinkmann, Debra H; Lowe, Val J; Morris, Jonathan M; Kemp, Bradley J; Hunt, Christopher H; Giannini, Caterina; Parney, Ian F; Laack, Nadia N

2018-05-01

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%, M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

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

MRI in multiple sclerosis: current status and future prospects

PubMed Central

Bakshi, Rohit; Thompson, Alan J; Rocca, Maria A; Pelletier, Daniel; Dousset, Vincent; Barkhof, Frederik; Inglese, Matilde; Guttmann, Charles R G; Horsfield, Mark A; Filippi, Massimo

2008-01-01

Many promising MRI approaches for research or clinical management of multiple sclerosis (MS) have recently emerged, or are under development or refinement. Advanced MRI methods need to be assessed to determine whether they allow earlier diagnosis or better identification of phenotypes. Improved post-processing should allow more efficient and complete extraction of information from images. Magnetic resonance spectroscopy should improve in sensitivity and specificity with higher field strengths and should enable the detection of a wider array of metabolites. Diffusion imaging is moving closer to the goal of defining structural connectivity and, thereby, determining the functional significance of lesions at specific locations. Cell-specific imaging now seems feasible with new magnetic resonance contrast agents. The imaging of myelin water fraction brings the hope of providing a specific measure of myelin content. Ultra-high-field MRI increases sensitivity, but also presents new technical challenges. Here, we review these recent developments in MRI for MS, and also look forward to refinements in spinal-cord imaging, optic-nerve imaging, perfusion MRI, and functional MRI. Advances in MRI should improve our ability to diagnose, monitor, and understand the pathophysiology of MS. PMID:18565455

Establishing a malaria diagnostics centre of excellence in Kisumu, Kenya.

PubMed

Ohrt, Colin; Obare, Peter; Nanakorn, Ampon; Adhiambo, Christine; Awuondo, Ken; O'Meara, Wendy Prudhomme; Remich, Shon; Martin, Kurt; Cook, Earnest; Chretien, Jean-Paul; Lucas, Carmen; Osoga, Joseph; McEvoy, Peter; Owaga, Martin Lucas; Odera, James Sande; Ogutu, Bernhards

2007-06-12

Malaria microscopy, while the gold standard for malaria diagnosis, has limitations. Efficacy estimates in drug and vaccine malaria trials are very sensitive to small errors in microscopy endpoints. This fact led to the establishment of a Malaria Diagnostics Centre of Excellence in Kisumu, Kenya. The primary objective was to ensure valid clinical trial and diagnostic test evaluations. Key secondary objectives were technology transfer to host countries, establishment of partnerships, and training of clinical microscopists. A twelve-day "long" and a four-day "short" training course consisting of supervised laboratory practicals, lectures, group discussions, demonstrations, and take home assignments were developed. Well characterized slides were developed and training materials iteratively improved. Objective pre- and post-course evaluations consisted of 30 slides (19 negative, 11 positive) with a density range of 50-660 parasites/mul, a written examination (65 questions), a photographic image examination (30 images of artifacts and species specific characteristics), and a parasite counting examination. To date, 209 microscopists have participated from 11 countries. Seventy-seven experienced microscopists participated in the "long" courses, including 47 research microscopists. Sensitivity improved by a mean of 14% (CI 9-19%) from 77% baseline (CI 73-81 %), while specificity improved by a mean of 17% (CI 11-23%) from 76% (CI 70-82%) baseline. Twenty-three microscopists who had been selected for a four-day refresher course showed continued improvement with a mean final sensitivity of 95% (CI 91-98%) and specificity of 97% (CI 95-100%). Only 9% of those taking the pre-test in the "long" course achieved a 90% sensitivity and 95% specificity, which increased to 61% of those completing the "short" course. All measures of performance improved substantially across each of the five organization types and in each course offered. The data clearly illustrated that false positive and negative malaria smears are a serious problem, even with research microscopists. Training dramatically improved performance. Quality microscopy can be provided by the Centre of Excellence concept. This concept can be extended to other diagnostics of public health importance, and comprehensive disease control strategies.

Establishing a malaria diagnostics centre of excellence in Kisumu, Kenya

PubMed Central

Ohrt, Colin; Obare, Peter; Nanakorn, Ampon; Adhiambo, Christine; Awuondo, Ken; O'Meara, Wendy Prudhomme; Remich, Shon; Martin, Kurt; Cook, Earnest; Chretien, Jean-Paul; Lucas, Carmen; Osoga, Joseph; McEvoy, Peter; Owaga, Martin Lucas; Odera, James Sande; Ogutu, Bernhards

2007-01-01

Background Malaria microscopy, while the gold standard for malaria diagnosis, has limitations. Efficacy estimates in drug and vaccine malaria trials are very sensitive to small errors in microscopy endpoints. This fact led to the establishment of a Malaria Diagnostics Centre of Excellence in Kisumu, Kenya. The primary objective was to ensure valid clinical trial and diagnostic test evaluations. Key secondary objectives were technology transfer to host countries, establishment of partnerships, and training of clinical microscopists. Case description A twelve-day "long" and a four-day "short" training course consisting of supervised laboratory practicals, lectures, group discussions, demonstrations, and take home assignments were developed. Well characterized slides were developed and training materials iteratively improved. Objective pre- and post-course evaluations consisted of 30 slides (19 negative, 11 positive) with a density range of 50–660 parasites/μl, a written examination (65 questions), a photographic image examination (30 images of artifacts and species specific characteristics), and a parasite counting examination. Discussion and Evaluation To date, 209 microscopists have participated from 11 countries. Seventy-seven experienced microscopists participated in the "long" courses, including 47 research microscopists. Sensitivity improved by a mean of 14% (CI 9–19%) from 77% baseline (CI 73–81 %), while specificity improved by a mean of 17% (CI 11–23%) from 76% (CI 70–82%) baseline. Twenty-three microscopists who had been selected for a four-day refresher course showed continued improvement with a mean final sensitivity of 95% (CI 91–98%) and specificity of 97% (CI 95–100%). Only 9% of those taking the pre-test in the "long" course achieved a 90% sensitivity and 95% specificity, which increased to 61% of those completing the "short" course. All measures of performance improved substantially across each of the five organization types and in each course offered. Conclusion The data clearly illustrated that false positive and negative malaria smears are a serious problem, even with research microscopists. Training dramatically improved performance. Quality microscopy can be provided by the Centre of Excellence concept. This concept can be extended to other diagnostics of public health importance, and comprehensive disease control strategies. PMID:17565676

Improved Sensitivity of Spectroscopic Quantification of Stable Isotope Content Using Capillary Absorption Spectroscopy

NASA Astrophysics Data System (ADS)

Moran, J.; Wilcox Freeburg, E.; Kriesel, J.; Linley, T. J.; Kelly, J.; Coleman, M. L.; Christensen, L. E.; Vance, S.

2016-12-01

Spectroscopy-based platforms have recently risen to the forefront for making stable isotope measurements of methane, carbon dioxide, water, or other analytes. These spectroscopy systems can be relatively straightforward to operate (versus a mass spectrometry platform), largely relieve the analyst of mass interference artifacts, and many can be used in the field. Despite these significant advantages, however, existing spectroscopy techniques suffer from a lack of measurement sensitivity that can ultimately limit select applications including spatially resolved and compound-specific measurements. Here we present a capillary absorption spectroscopy (CAS) system that is designed to mitigate sensitivity issues in spectroscopy-based stable isotope evaluation. The system uses mid-wave infrared excitation generated from a continuous wave quantum cascade laser. Importantly, the sample `chamber' is a flexible capillary with a total volume of less than one cc. Proprietary coatings on the internal surface of the fiber improve optical performance, guiding the light to a detector and facilitating high levels of interaction between the laser beam and gaseous analytes. We present data demonstrating that a tapered hollow fiber cell, with an internal diameter that broadens toward the detector, reduces optical feedback to further improve measurement sensitivity. Sensitivity of current hollow fiber / CAS systems enable measurements of only 10's of picomoles CO2 while theoretical improvements should enable measurements of as little as 10's of femtomoles. Continued optimization of sample introduction and improvements to optical feedback are being explored. Software is being designed to provide rapid integration of data and generation of processed isotope measurements using a graphical user interface. Taken together, the sensitivity improvements of the CAS system under development could, when coupled to a laser ablation sampling device, enable up to 2 µm spatial resolution (roughly the size of a eukaryotic cell or multiple prokaryotic cells) or provide a basis for compounds specific stable isotope analysis of trace biomarkers. The small size and low weight of the system holds future potential for field and / or remote deployment.

“Global” visual training and extent of transfer in amblyopic macaque monkeys

PubMed Central

Kiorpes, Lynne; Mangal, Paul

2015-01-01

Perceptual learning is gaining acceptance as a potential treatment for amblyopia in adults and children beyond the critical period. Many perceptual learning paradigms result in very specific improvement that does not generalize beyond the training stimulus, closely related stimuli, or visual field location. To be of use in amblyopia, a less specific effect is needed. To address this problem, we designed a more general training paradigm intended to effect improvement in visual sensitivity across tasks and domains. We used a “global” visual stimulus, random dot motion direction discrimination with 6 training conditions, and tested for posttraining improvement on a motion detection task and 3 spatial domain tasks (contrast sensitivity, Vernier acuity, Glass pattern detection). Four amblyopic macaques practiced the motion discrimination with their amblyopic eye for at least 20,000 trials. All showed improvement, defined as a change of at least a factor of 2, on the trained task. In addition, all animals showed improvements in sensitivity on at least some of the transfer test conditions, mainly the motion detection task; transfer to the spatial domain was inconsistent but best at fine spatial scales. However, the improvement on the transfer tasks was largely not retained at long-term follow-up. Our generalized training approach is promising for amblyopia treatment, but sustaining improved performance may require additional intervention. PMID:26505868

Genomic testing to determine drug response: measuring preferences of the public and patients using Discrete Choice Experiment (DCE)

PubMed Central

2013-01-01

Background The extent to which a genomic test will be used in practice is affected by factors such as ability of the test to correctly predict response to treatment (i.e. sensitivity and specificity of the test), invasiveness of the testing procedure, test cost, and the probability and severity of side effects associated with treatment. Methods Using discrete choice experimentation (DCE), we elicited preferences of the public (Sample 1, N = 533 and Sample 2, N = 525) and cancer patients (Sample 3, N = 38) for different attributes of a hypothetical genomic test for guiding cancer treatment. Samples 1 and 3 considered the test/treatment in the context of an aggressive curable cancer (scenario A) while the scenario for sample 2 was based on a non-aggressive incurable cancer (scenario B). Results In aggressive curable cancer (scenario A), everything else being equal, the odds ratio (OR) of choosing a test with 95% sensitivity was 1.41 (versus a test with 50% sensitivity) and willingness to pay (WTP) was $1331, on average, for this amount of improvement in test sensitivity. In this scenario, the OR of choosing a test with 95% specificity was 1.24 times that of a test with 50% specificity (WTP = $827). In non-aggressive incurable cancer (scenario B), the OR of choosing a test with 95% sensitivity was 1.65 (WTP = $1344), and the OR of choosing a test with 95% specificity was 1.50 (WTP = $1080). Reducing severity of treatment side effects from severe to mild was associated with large ORs in both scenarios (OR = 2.10 and 2.24 in scenario A and B, respectively). In contrast, patients had a very large preference for 95% sensitivity of the test (OR = 5.23). Conclusion The type and prognosis of cancer affected preferences for genomically-guided treatment. In aggressive curable cancer, individuals emphasized more on the sensitivity rather than the specificity of the test. In contrast, for a non-aggressive incurable cancer, individuals put similar emphasis on sensitivity and specificity of the test. While the public expressed strong preference toward lowering severity of side effects, improving sensitivity of the test had by far the largest influence on patients’ decision to use genomic testing. PMID:24176050

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.

The Autism Diagnostic Observation Schedule, Module 4: Application of the Revised Algorithms in an Independent, Well-Defined, Dutch Sample (n = 93).

PubMed

de Bildt, Annelies; Sytema, Sjoerd; Meffert, Harma; Bastiaansen, Jojanneke A C J

2016-01-01

This study examined the discriminative ability of the revised Autism Diagnostic Observation Schedule module 4 algorithm (Hus and Lord in J Autism Dev Disord 44(8):1996-2012, 2014) in 93 Dutch males with Autism Spectrum Disorder (ASD), schizophrenia, psychopathy or controls. Discriminative ability of the revised algorithm ASD cut-off resembled the original algorithm ASD cut-off: highly specific for psychopathy and controls, lower sensitivity than Hus and Lord (2014; i.e. ASD .61, AD .53). The revised algorithm AD cut-off improved sensitivity over the original algorithm. Discriminating ASD from schizophrenia was still challenging, but the better-balanced sensitivity (.53) and specificity (.78) of the revised algorithm AD cut-off may aide clinicians' differential diagnosis. Findings support using the revised algorithm, being conceptually conform the other modules, thus improving comparability across the lifespan.

Development and Validation of Search Filters to Identify Articles on Family Medicine in Online Medical Databases.

PubMed

Pols, David H J; Bramer, Wichor M; Bindels, Patrick J E; van de Laar, Floris A; Bohnen, Arthur M

2015-01-01

Physicians and researchers in the field of family medicine often need to find relevant articles in online medical databases for a variety of reasons. Because a search filter may help improve the efficiency and quality of such searches, we aimed to develop and validate search filters to identify research studies of relevance to family medicine. Using a new and objective method for search filter development, we developed and validated 2 search filters for family medicine. The sensitive filter had a sensitivity of 96.8% and a specificity of 74.9%. The specific filter had a specificity of 97.4% and a sensitivity of 90.3%. Our new filters should aid literature searches in the family medicine field. The sensitive filter may help researchers conducting systematic reviews, whereas the specific filter may help family physicians find answers to clinical questions at the point of care when time is limited. © 2015 Annals of Family Medicine, Inc.

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.

Sensitivity, specificity, and predictive values of pediatric metabolic syndrome components in relation to adult metabolic syndrome: the Princeton LRC follow-up study.

PubMed

Huang, Terry T-K; Nansel, Tonja R; Belsheim, Allen R; Morrison, John A

2008-02-01

To estimate the sensitivity, specificity, and predictive values of pediatric metabolic syndrome (MetS) components (obesity, fasting glucose, triglycerides, high-density lipoprotein, and blood pressure) at various cutoff points in relation to adult MetS. Data from the National Heart, Lung, and Blood Institute Lipid Research Clinics Princeton Prevalence Study (1973-1976) and the Princeton Follow-up Study (2000-2004) were used to calculate sensitivity, specificity, and positive and negative predictive values for each component at a given cutoff point and for aggregates of components. Individual pediatric components alone showed low to moderate sensitivity, high specificity, and moderate predictive values in relation to adult MetS. When all 5 pediatric MetS components were considered, the presence of at least 1 abnormality had higher sensitivity for adult MetS than individual components alone. When multiple abnormalities were mandatory for MetS, positive predictive value was high and sensitivity was low. Childhood body mass alone showed neither high sensitivity nor high positive predictive value for adult MetS. Considering multiple metabolic variables in childhood can improve the predictive usefulness for adult MetS, compared with each component or body mass alone. MetS variables may be useful for identifying some children who are at risk for prevention interventions.

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.

Impact of Image Filters and Observations Parameters in CBCT for Identification of Mandibular Osteolytic Lesions

PubMed Central

Monteiro, Bruna Moraes; Nobrega Filho, Denys Silveira; Lopes, Patrícia de Medeiros Loureiro; de Sales, Marcelo Augusto Oliveira

2012-01-01

The aim of this study was to analyze the influence of filters (algorithms) to improve the image of Cone Beam Computed Tomography (CBCT) in diagnosis of osteolytic lesions of the mandible, in order to establish the protocols for viewing images more suitable for CBCT diagnostics. 15 dry mandibles in which perforations were performed, simulating lesions, were submitted to CBCT examination. Two examiners analyzed the images, using filters to improve image Hard, Normal, and Very Sharp, contained in the iCAT Vision software, and protocols for assessment: axial; sagittal and coronal; and axial, sagittal and coronal planes simultaneously (MPR), on two occasions. The sensitivity and specificity (validity) of the cone beam computed tomography (CBCT) have been demonstrated as the values achieved were above 75% for sensitivity and above 85% for specificity, reaching around 95.5% of sensitivity and 99% of specificity when we used the appropriate observation protocol. It was concluded that the use of filters (algorithms) to improve the CBCT image influences the diagnosis, due to the fact that all measured values were correspondingly higher when it was used the filter Very Sharp, which justifies its use for clinical activities, followed by Hard and Normal filters, in order of decreasing values. PMID:22956955

Impact of Image Filters and Observations Parameters in CBCT for Identification of Mandibular Osteolytic Lesions.

PubMed

Monteiro, Bruna Moraes; Nobrega Filho, Denys Silveira; Lopes, Patrícia de Medeiros Loureiro; de Sales, Marcelo Augusto Oliveira

2012-01-01

The aim of this study was to analyze the influence of filters (algorithms) to improve the image of Cone Beam Computed Tomography (CBCT) in diagnosis of osteolytic lesions of the mandible, in order to establish the protocols for viewing images more suitable for CBCT diagnostics. 15 dry mandibles in which perforations were performed, simulating lesions, were submitted to CBCT examination. Two examiners analyzed the images, using filters to improve image Hard, Normal, and Very Sharp, contained in the iCAT Vision software, and protocols for assessment: axial; sagittal and coronal; and axial, sagittal and coronal planes simultaneously (MPR), on two occasions. The sensitivity and specificity (validity) of the cone beam computed tomography (CBCT) have been demonstrated as the values achieved were above 75% for sensitivity and above 85% for specificity, reaching around 95.5% of sensitivity and 99% of specificity when we used the appropriate observation protocol. It was concluded that the use of filters (algorithms) to improve the CBCT image influences the diagnosis, due to the fact that all measured values were correspondingly higher when it was used the filter Very Sharp, which justifies its use for clinical activities, followed by Hard and Normal filters, in order of decreasing values.

Polymerase chain reaction in the detection of tumor cells: new approaches in diagnosis and follow-up of patients with thyroid cancer.

PubMed

Bojunga, Jörg; Kusterer, Klaus; Schumm-Draeger, Petra-Maria; Usadel, Klaus-Henning

2002-12-01

Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increasing frequency. In addition to other measures, diagnosis is based on fine-needle aspiration cytology examination. Recently, new assays using reverse transcription-polymerase chain reaction (PCR) are being tested to improve sensitivity and specificity of primary diagnosis and detection of recurrent thyroid cancer. In the preoperative diagnosis of thyroid cancer, several tissue- and/or tumor-specific mRNA have been described and in several cases, a higher sensitivity and specificity could be achieved using molecular techniques compared to conventional methods. In the postoperative follow-up of patients with thyroid cancer, conflicting data have been published and the use of PCR techniques revealed several problems of the molecular approach, which are based on some technical as well as biologic limitations. Despite these problems, which are discussed in detail in this review, molecular techniques may nevertheless improve the sensitivity and accuracy of fine-needle aspiration of thyroid nodules, fine-needle aspiration of metastases, and detection of recurrent disease in peripheral blood samples.

B-mode Ultrasound Versus Color Doppler Twinkling Artifact in Detecting Kidney Stones

PubMed Central

Harper, Jonathan D.; Hsi, Ryan S.; Shah, Anup R.; Dighe, Manjiri K.; Carter, Stephen J.; Moshiri, Mariam; Paun, Marla; Lu, Wei; Bailey, Michael R.

2013-01-01

Abstract Purpose To compare color Doppler twinkling artifact and B-mode ultrasonography in detecting kidney stones. Patients and Methods Nine patients with recent CT scans prospectively underwent B-mode and twinkling artifact color Doppler ultrasonography on a commercial ultrasound machine. Video segments of the upper pole, interpolar area, and lower pole were created, randomized, and independently reviewed by three radiologists. Receiver operator characteristics were determined. Results There were 32 stones in 18 kidneys with a mean stone size of 8.9±7.5 mm. B-mode ultrasonography had 71% sensitivity, 48% specificity, 52% positive predictive value, and 68% negative predictive value, while twinkling artifact Doppler ultrasonography had 56% sensitivity, 74% specificity, 62% positive predictive value, and 68% negative predictive value. Conclusions When used alone, B-mode is more sensitive, but twinkling artifact is more specific in detecting kidney stones. This information may help users employ twinkling and B-mode to identify stones and developers to improve signal processing to harness the fundamental acoustic differences to ultimately improve stone detection. PMID:23067207

Brief group training of medical students in focused cardiac ultrasound may improve diagnostic accuracy of physical examination.

PubMed

Stokke, Thomas M; Ruddox, Vidar; Sarvari, Sebastian I; Otterstad, Jan E; Aune, Erlend; Edvardsen, Thor

2014-11-01

Physical examination and auscultation can be challenging for medical students. The aim of this study was to investigate whether a brief session of group training in focused cardiac ultrasound (FCU) with a pocket-sized device would allow medical students to improve their ability to detect clinically relevant cardiac lesions at the bedside. Twenty-one medical students in their clinical curriculum completed 4 hours of FCU training in groups. The students examined patients referred for echocardiography with emphasis on auscultation, followed by FCU. Findings from physical examination and FCU were compared with those from standard echocardiography performed and analyzed by cardiologists. In total, 72 patients were included in the study, and 110 examinations were performed. With a stethoscope, sensitivity to detect clinically relevant (moderate or greater) valvular disease was 29% for mitral regurgitation, 33% for aortic regurgitation, and 67% for aortic stenosis. FCU improved sensitivity to detect mitral regurgitation (69%, P < .001). However, sensitivity to detect aortic regurgitation (43%) and aortic stenosis (70%) did not improve significantly. Specificity was ≥89% for all valvular diagnoses by both methods. For nonvalvular diagnoses, FCU's sensitivity to detect moderate or greater left ventricular dysfunction (90%) was excellent, detection of right ventricular dysfunction (79%) was good, while detection of dilated left atrium (53%), dilated right atrium (49%), pericardial effusion (40%), and dilated aortic root (25%) was less accurate. Specificity varied from 57% to 94%. After brief group training in FCU, medical students could detect mitral regurgitation significantly better compared with physical examination, whereas detection of aortic regurgitation and aortic stenosis did not improve. Left ventricular dysfunction was detected with high sensitivity. More extensive training is advised. Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Is improved contrast sensitivity a natural consequence of visual training?

PubMed Central

Levi, Aaron; Shaked, Danielle; Tadin, Duje; Huxlin, Krystel R.

2015-01-01

Many studies have shown that training and testing conditions modulate specificity of visual learning to trained stimuli and tasks. In visually impaired populations, generalizability of visual learning to untrained stimuli/tasks is almost always reported, with contrast sensitivity (CS) featuring prominently among these collaterally-improved functions. To understand factors underlying this difference, we measured CS for direction and orientation discrimination in the visual periphery of three groups of visually-intact subjects. Group 1 trained on an orientation discrimination task with static Gabors whose luminance contrast was decreased as performance improved. Group 2 trained on a global direction discrimination task using high-contrast random dot stimuli previously used to recover motion perception in cortically blind patients. Group 3 underwent no training. Both forms of training improved CS with some degree of specificity for basic attributes of the trained stimulus/task. Group 1's largest enhancement was in CS around the trained spatial/temporal frequencies; similarly, Group 2's largest improvements occurred in CS for discriminating moving and flickering stimuli. Group 3 saw no significant CS changes. These results indicate that CS improvements may be a natural consequence of multiple forms of visual training in visually intact humans, albeit with some specificity to the trained visual domain(s). PMID:26305736

Evaluation of the articular cartilage of the knee joint: value of adding a T2 mapping sequence to a routine MR imaging protocol.

PubMed

Kijowski, Richard; Blankenbaker, Donna G; Munoz Del Rio, Alejandro; Baer, Geoffrey S; Graf, Ben K

2013-05-01

To determine whether the addition of a T2 mapping sequence to a routine magnetic resonance (MR) imaging protocol could improve diagnostic performance in the detection of surgically confirmed cartilage lesions within the knee joint at 3.0 T. This prospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. The study group consisted of 150 patients (76 male and 74 female patients with an average age of 41.2 and 41.5 years, respectively) who underwent MR imaging and arthroscopy of the knee joint. MR imaging was performed at 3.0 T by using a routine protocol with the addition of a sagittal T2 mapping sequence. Images from all MR examinations were reviewed in consensus by two radiologists before surgery to determine the presence or absence of cartilage lesions on each articular surface, first by using the routine MR protocol alone and then by using the routine MR protocol with T2 maps. Each articular surface was then evaluated at arthroscopy. Generalized estimating equation models were used to compare the sensitivity and specificity of the routine MR imaging protocol with and without T2 maps in the detection of surgically confirmed cartilage lesions. The sensitivity and specificity in the detection of 351 cartilage lesions were 74.6% and 97.8%, respectively, for the routine MR protocol alone and 88.9% and 93.1% for the routine MR protocol with T2 maps. Differences in sensitivity and specificity were statistically significant (P < .001). The addition of T2 maps to the routine MR imaging protocol significantly improved the sensitivity in the detection of 24 areas of cartilage softening (from 4.2% to 62%, P < .001), 41 areas of cartilage fibrillation (from 20% to 66%, P < .001), and 96 superficial partial-thickness cartilage defects (from 71% to 88%, P = .004). The addition of a T2 mapping sequence to a routine MR protocol at 3.0 T improved sensitivity in the detection of cartilage lesions within the knee joint from 74.6% to 88.9%, with only a small reduction in specificity. The greatest improvement in sensitivity with use of the T2 maps was in the identification of early cartilage degeneration. © RSNA, 2013.

Immunophenotyping in systemic mastocytosis diagnosis: 'CD25 positive' alone is more informative than the 'CD25 and/or CD2' WHO criterion.

PubMed

Morgado, José Mário T; Sánchez-Muñoz, Laura; Teodósio, Cristina G; Jara-Acevedo, Maria; Alvarez-Twose, Iván; Matito, Almudena; Fernández-Nuñez, Elisa; García-Montero, Andrés; Orfao, Alberto; Escribano, Luís

2012-04-01

Aberrant expression of CD2 and/or CD25 by bone marrow, peripheral blood or other extracutaneous tissue mast cells is currently used as a minor World Health Organization diagnostic criterion for systemic mastocytosis. However, the diagnostic utility of CD2 versus CD25 expression by mast cells has not been prospectively evaluated in a large series of systemic mastocytosis. Here we evaluate the sensitivity and specificity of CD2 versus CD25 expression in the diagnosis of systemic mastocytosis. Mast cells from a total of 886 bone marrow and 153 other non-bone marrow extracutaneous tissue samples were analysed by multiparameter flow cytometry following the guidelines of the Spanish Network on Mastocytosis at two different laboratories. The 'CD25+ and/or CD2+ bone marrow mast cells' World Health Organization criterion showed an overall sensitivity of 100% with 99.0% specificity for the diagnosis of systemic mastocytosis whereas CD25 expression alone presented a similar sensitivity (100%) with a slightly higher specificity (99.2%). Inclusion of CD2 did not improve the sensitivity of the test and it decreased its specificity. In tissues other than bone marrow, the mast cell phenotypic criterion revealed to be less sensitive. In summary, CD2 expression does not contribute to improve the diagnosis of systemic mastocytosis when compared with aberrant CD25 expression alone, which supports the need to update and replace the minor World Health Organization 'CD25+ and/or CD2+' mast cell phenotypic diagnostic criterion by a major criterion based exclusively on CD25 expression.

Sensitizers in EUV chemically amplified resist: mechanism of sensitivity improvement

NASA Astrophysics Data System (ADS)

Vesters, Yannick; Jiang, Jing; Yamamoto, Hiroki; De Simone, Danilo; Kozawa, Takahiro; De Gendt, Stefan; Vandenberghe, Geert

2018-03-01

EUV lithography utilizes photons with 91.6 eV energy to ionize resists, generate secondary electrons, and enable electron driven reactions that produce acid in chemically amplified photoresist. Efficiently using the available photons is of key importance. Unlike DUV lithography, where photons are selectively utilized by photoactive compounds, photons at 13.5nm wavelength ionize almost all materials. Nevertheless, specific elements have a significantly higher atomic photon-absorption cross section at 91.6 eV. To increase photon absorption, sensitizer molecules, containing highly absorbing elements, can be added to photoresist formulations. These sensitizers have gained growing attention in recent years, showing significant sensitivity improvement. But there are few experimental evidences that the sensitivity improvement is due to the higher absorption only, as adding metals salts into the resist formulation can induce other mechanisms, like modification of the dissolution rate, potentially affecting patterning performance. In this work, we used different sensitizers in chemically amplified resist. We measured experimentally the absorption of EUV light, the acid yield, the dissolution rate and the patterning performance of the resists. Surprisingly, the absorption of EUV resist was decreased with addition of metal salt sensitizers. Nevertheless, the resist with sensitizer showed a higher acid yield. Sensitizer helps achieving higher PAG conversion to acid, notably due to an increase of the secondary electron generation. Patterning data confirm a significant sensitivity improvement, but at the cost of roughness degradation at high sensitizer loading. This can be explained by the chemical distribution of the sensitizer in the resist combined with a modification of the dissolution contrast, as observed by Dissolution Rate Monitor.

Determination of the optimal case definition for the diagnosis of end-stage renal disease from administrative claims data in Manitoba, Canada.

PubMed

Komenda, Paul; Yu, Nancy; Leung, Stella; Bernstein, Keevin; Blanchard, James; Sood, Manish; Rigatto, Claudio; Tangri, Navdeep

2015-01-01

End-stage renal disease (ESRD) is a major public health problem with increasing prevalence and costs. An understanding of the long-term trends in dialysis rates and outcomes can help inform health policy. We determined the optimal case definition for the diagnosis of ESRD using administrative claims data in the province of Manitoba over a 7-year period. We determined the sensitivity, specificity, predictive value and overall accuracy of 4 administrative case definitions for the diagnosis of ESRD requiring chronic dialysis over different time horizons from Jan. 1, 2004, to Mar. 31, 2011. The Manitoba Renal Program Database served as the gold standard for confirming dialysis status. During the study period, 2562 patients were registered as recipients of chronic dialysis in the Manitoba Renal Program Database. Over a 1-year period (2010), the optimal case definition was any 2 claims for outpatient dialysis, and it was 74.6% sensitive (95% confidence interval [CI] 72.3%-76.9%) and 94.4% specific (95% CI 93.6%-95.2%) for the diagnosis of ESRD. In contrast, a case definition of at least 2 claims for dialysis treatment more than 90 days apart was 64.8% sensitive (95% CI 62.2%-67.3%) and 97.1% specific (95% CI 96.5%-97.7%). Extending the period to 5 years greatly improved sensitivity for all case definitions, with minimal change to specificity; for example, for the optimal case definition of any 2 claims for dialysis treatment, sensitivity increased to 86.0% (95% CI 84.7%-87.4%) at 5 years. Accurate case definitions for the diagnosis of ESRD requiring dialysis can be derived from administrative claims data. The optimal definition required any 2 claims for outpatient dialysis. Extending the claims period to 5 years greatly improved sensitivity with minimal effects on specificity for all case definitions.

Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

PubMed

Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S

2006-08-01

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Comparing performance of mothers using simplified mid-upper arm circumference (MUAC) classification devices with an improved MUAC insertion tape in Isiolo County, Kenya.

PubMed

Grant, Angeline; Njiru, James; Okoth, Edgar; Awino, Imelda; Briend, André; Murage, Samuel; Abdirahman, Saida; Myatt, Mark

2018-01-01

A novel approach for improving community case-detection of acute malnutrition involves mothers/caregivers screening their children for acute malnutrition using a mid-upper arm circumference (MUAC) insertion tape. The objective of this study was to test three simple MUAC classification devices to determine whether they improved the sensitivity of mothers/caregivers at detecting acute malnutrition. Prospective, non-randomised, partially-blinded, clinical diagnostic trial describing and comparing the performance of three "Click-MUAC" devices and a MUAC insertion tape. The study took place in twenty-one health facilities providing integrated management of acute malnutrition (IMAM) services in Isiolo County, Kenya. Mothers/caregivers classified their child ( n =1040), aged 6-59 months, using the "Click-MUAC" devices and a MUAC insertion tape. These classifications were compared to a "gold standard" classification (the mean of three measurements taken by a research assistant using the MUAC insertion tape). The sensitivity of mother/caregiver classifications was high for all devices (>93% for severe acute malnutrition (SAM), defined by MUAC < 115 mm, and > 90% for global acute malnutrition (GAM), defined by MUAC < 125 mm). Mother/caregiver sensitivity for SAM and GAM classification was higher using the MUAC insertion tape (100% sensitivity for SAM and 99% sensitivity for GAM) than using "Click-MUAC" devices. Younden's J for SAM classification, and sensitivity for GAM classification, were significantly higher for the MUAC insertion tape (99% and 99% respectively). Specificity was high for all devices (>96%) with no significant difference between the "Click-MUAC" devices and the MUAC insertion tape. The results of this study indicate that, although the "Click-MUAC" devices performed well, the MUAC insertion tape performed best. The results for sensitivity are higher than found in previous studies. The high sensitivity for both SAM and GAM classification by mothers/caregivers with the MUAC insertion tape could be due to the use of an improved MUAC tape design which has a number of new design features. The one-on-one demonstration provided to mothers/caregivers on the use of the devices may also have helped improve sensitivity. The results of this study provide evidence that mothers/caregivers can perform sensitive and specific classifications of their child's nutritional status using MUAC. Clinical trials registration number: NCT02833740.

Ten Basic Suggestions to Social Studies Students for Improving Your Writing

ERIC Educational Resources Information Center

Roselle, Daniel

1977-01-01

Ten guidelines to help students improve their writing include clear expression, specificity, originality, avoiding stereotyping, linking paragraphs, setting time by parallel events, linking past and present, use of primary sources, giving evidence for generalizations, and reading to increase sensitivity. (AV)

Effect of light intensity adjusted for species-specific spectral sensitivity on live performance and processing yield of male broiler chickens

USDA-ARS?s Scientific Manuscript database

Adoption of alternative lighting systems to replace traditional incandescent light sources offers the opportunity to tailor lighting systems according to spectral sensitivity needs of different species. Providing a lighting environment that accounts for poultry vision may improve bird welfare and p...

DSM-IV and Culturally Sensitive Diagnosis: Some Observations for Counselors.

ERIC Educational Resources Information Center

Smart, David W.; Smart, Julie F.

1997-01-01

Describes the evolution of cultural sensitivity in the third and fourth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Discusses five improvements in the DSM-IV: (1) descriptions of specific cultural features; (2) glossary of culture-bound syndromes; (3) outline of cultural formulation; (4) broader definition of Axis…

Assessment of simple colorimetric procedures to determine smoking status of diabetic subjects.

PubMed

Smith, R F; Mather, H M; Ellard, G A

1998-02-01

The performance of a simple colorimetric assay for urinary nicotine metabolites to assess smoking status in diabetic subjects (n = 251) was investigated. Several variations of the colorimetric assay and a qualitative extraction procedure were evaluated in comparison with a cotinine immunoassay as the "gold standard." Among these, the best overall performance was achieved with the qualitative test (sensitivity 95%; specificity 100%). The quantitative measurement of total nicotine metabolites performed less well (sensitivity 92%; specificity 97%) but could be improved by incorporating a blank extraction (sensitivity 98%; specificity 98%). Allowance for diuresis appeared to offer no advantage over the other methods. These results support previous findings regarding the use of these colorimetric procedures in nondiabetic subjects and, contrary to other recent observations, their performance was not impaired in diabetic patients.

Artificial neural network retrained to detect myocardial ischemia using a Japanese multicenter database.

PubMed

Nakajima, Kenichi; Okuda, Koichi; Watanabe, Satoru; Matsuo, Shinro; Kinuya, Seigo; Toth, Karin; Edenbrandt, Lars

2018-03-07

An artificial neural network (ANN) has been applied to detect myocardial perfusion defects and ischemia. The present study compares the diagnostic accuracy of a more recent ANN version (1.1) with the initial version 1.0. We examined 106 patients (age, 77 ± 10 years) with coronary angiographic findings, comprising multi-vessel disease (≥ 50% stenosis) (52%) or old myocardial infarction (27%), or who had undergone coronary revascularization (30%). The ANN versions 1.0 and 1.1 were trained in Sweden (n = 1051) and Japan (n = 1001), respectively, using 99m Tc-methoxyisobutylisonitrile myocardial perfusion images. The ANN probabilities (from 0.0 to 1.0) of stress defects and ischemia were calculated in candidate regions of abnormalities. The diagnostic accuracy was compared using receiver-operating characteristics (ROC) analysis and the calculated area under the ROC curve (AUC) using expert interpretation as the gold standard. Although the AUC for stress defects was 0.95 and 0.93 (p = 0.27) for versions 1.1 and 1.0, respectively, that for detecting ischemia was significantly improved in version 1.1 (p = 0.0055): AUC 0.96 for version 1.1 (sensitivity 87%, specificity 96%) vs. 0.89 for version 1.0 (sensitivity 78%, specificity 97%). The improvement in the AUC shown by version 1.1 was also significant for patients with neither coronary revascularization nor old myocardial infarction (p = 0.0093): AUC = 0.98 for version 1.1 (sensitivity 88%, specificity 100%) and 0.88 for version 1.0 (sensitivity 76%, specificity 100%). Intermediate ANN probability between 0.1 and 0.7 was more often calculated by version 1.1 compared with version 1.0, which contributed to the improved diagnostic accuracy. The diagnostic accuracy of the new version was also improved in patients with either single-vessel disease or no stenosis (n = 47; AUC, 0.81 vs. 0.66 vs. p = 0.0060) when coronary stenosis was used as a gold standard. The diagnostic ability of the ANN version 1.1 was improved by retraining using the Japanese database, particularly for identifying ischemia.

Contrast-enhanced spectral mammography improves diagnostic accuracy in the symptomatic setting.

PubMed

Tennant, S L; James, J J; Cornford, E J; Chen, Y; Burrell, H C; Hamilton, L J; Girio-Fragkoulakis, C

2016-11-01

To assess the diagnostic accuracy of contrast-enhanced spectral mammography (CESM), and gauge its "added value" in the symptomatic setting. A retrospective multi-reader review of 100 consecutive CESM examinations was performed. Anonymised low-energy (LE) images were reviewed and given a score for malignancy. At least 3 weeks later, the entire examination (LE and recombined images) was reviewed. Histopathology data were obtained for all cases. Differences in performance were assessed using receiver operator characteristic (ROC) analysis. Sensitivity, specificity, and lesion size (versus MRI or histopathology) differences were calculated. Seventy-three percent of cases were malignant at final histology, 27% were benign following standard triple assessment. ROC analysis showed improved overall performance of CESM over LE alone, with area under the curve of 0.93 versus 0.83 (p<0.025). CESM showed increased sensitivity (95% versus 84%, p<0.025) and specificity (81% versus 63%, p<0.025) compared to LE alone, with all five readers showing improved accuracy. Tumour size estimation at CESM was significantly more accurate than LE alone, the latter tending to undersize lesions. In 75% of cases, CESM was deemed a useful or significant aid to diagnosis. CESM provides immediately available, clinically useful information in the symptomatic clinic in patients with suspicious palpable abnormalities. Radiologist sensitivity, specificity, and size accuracy for breast cancer detection and staging are all improved using CESM as the primary mammographic investigation. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Temperature sensitive surfaces and methods of making same

DOEpatents

Liang, Liang [Richland, WA; Rieke, Peter C [Pasco, WA; Alford, Kentin L [Pasco, WA

2002-09-10

Poly-n-isopropylacrylamide surface coatings demonstrate the useful property of being able to switch charateristics depending upon temperature. More specifically, these coatings switch from being hydrophilic at low temperature to hydrophobic at high temperature. Research has been conducted for many years to better characterize and control the properties of temperature sensitive coatings. The present invention provides novel temperature sensitive coatings on articles and novel methods of making temperature sensitive coatings that are disposed on the surfaces of various articles. These novel coatings contain the reaction products of n-isopropylacrylamide and are characterized by their properties such as advancing contact angles. Numerous other characteristics such as coating thickness, surface roughness, and hydrophilic-to-hydrophobic transition temperatures are also described. The present invention includes articles having temperature-sensitve coatings with improved properties as well as improved methods for forming temperature sensitive coatings.

Unsupervised machine-learning method for improving the performance of ambulatory fall-detection systems

PubMed Central

2012-01-01

Background Falls can cause trauma, disability and death among older people. Ambulatory accelerometer devices are currently capable of detecting falls in a controlled environment. However, research suggests that most current approaches can tend to have insufficient sensitivity and specificity in non-laboratory environments, in part because impacts can be experienced as part of ordinary daily living activities. Method We used a waist-worn wireless tri-axial accelerometer combined with digital signal processing, clustering and neural network classifiers. The method includes the application of Discrete Wavelet Transform, Regrouping Particle Swarm Optimization, Gaussian Distribution of Clustered Knowledge and an ensemble of classifiers including a multilayer perceptron and Augmented Radial Basis Function (ARBF) neural networks. Results Preliminary testing with 8 healthy individuals in a home environment yields 98.6% sensitivity to falls and 99.6% specificity for routine Activities of Daily Living (ADL) data. Single ARB and MLP classifiers were compared with a combined classifier. The combined classifier offers the greatest sensitivity, with a slight reduction in specificity for routine ADL and an increased specificity for exercise activities. In preliminary tests, the approach achieves 100% sensitivity on in-group falls, 97.65% on out-group falls, 99.33% specificity on routine ADL, and 96.59% specificity on exercise ADL. Conclusion The pre-processing and feature-extraction steps appear to simplify the signal while successfully extracting the essential features that are required to characterize a fall. The results suggest this combination of classifiers can perform better than MLP alone. Preliminary testing suggests these methods may be useful for researchers who are attempting to improve the performance of ambulatory fall-detection systems. PMID:22336100

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

PubMed

Kleine-Tebbe, Jörg; Jakob, Thilo

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

Effectiveness of the CANRISK tool in the identification of dysglycemia in First Nations and Métis in Canada

PubMed Central

Gina, Agarwal; Ying, Jiang; Susan, Rogers Van Katwyk; Chantal, Lemieux; Heather, Orpana; Yang, Mao; Brandan, Hanley; Karen, Davis; Laurel, Leuschen; Howard, Morrison

2018-01-01

Abstract Introduction: First Nations/Métis populations develop diabetes earlier and at higher rates than other Canadians. The Canadian diabetes risk questionnaire (CANRISK) was developed as a diabetes screening tool for Canadians aged 40 years or over. The primary aim of this paper is to assess the effectiveness of the existing CANRISK tool and risk scores in detecting dysglycemia in First Nations/Métis participants, including among those under the age of 40. A secondary aim was to determine whether alternative waist circumference (WC) and body mass index (BMI) cut-off points improved the predictive ability of logistic regression models using CANRISK variables to predict dysglycemia. Methods: Information from a self-administered CANRISK questionnaire, anthropometric measurements, and results of a standard oral glucose tolerance test (OGTT) were collected from First Nations and Métis participants (n = 1479). Sensitivity and specificity of CANRISK scores using published risk score cut-off points were calculated. Logistic regression was conducted with alternative ethnicity-specific BMI and WC cut-off points to predict dysglycemia using CANRISK variables. Results: Compared with OGTT results, using a CANRISK score cut-off point of 33, the sensitivity and specificity of CANRISK was 68% and 63% among individuals aged 40 or over; it was 27% and 87%, respectively among those under 40. Using a lower cut-off point of 21, the sensitivity for individuals under 40 improved to 77% with a specificity of 44%. Though specificity at this threshold was low, the higher level of sensitivity reflects the importance of the identification of high risk individuals in this population. Despite altered cut-off points of BMI and WC, logistic regression models demonstrated similar predictive ability. Conclusion: CANRISK functioned well as a preliminary step for diabetes screening in a broad age range of First Nations and Métis in Canada, with an adjusted CANRISK cutoff point for individuals under 40, and with no incremental improvement from using alternative BMI/WC cut-off points. PMID:29443485

Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts.

PubMed

Calabrese, Emma; Maaser, Christian; Zorzi, Francesca; Kannengiesser, Klaus; Hanauer, Stephen B; Bruining, David H; Iacucci, Marietta; Maconi, Giovanni; Novak, Kerri L; Panaccione, Remo; Strobel, Deike; Wilson, Stephanie R; Watanabe, Mamoru; Pallone, Francesco; Ghosh, Subrata

2016-05-01

Bowel ultrasonography (US) is considered a useful technique for assessing mural inflammation and complications in Crohn's disease (CD). The aim of this review is to appraise the evidence on the accuracy of bowel US for CD. In addition, we aim to provide recommendations for its optimal use. Publications were identified by literature search from 1992 to 2014 and selected based on predefined criteria: 15 or more patients; bowel US for diagnosing CD, complications, postoperative recurrence, activity; adequate reference standards; prospective study design; data reported to allow calculation of sensitivity, specificity, agreement, or correlation values; articles published in English. The search yielded 655 articles, of which 63 were found to be eligible and retrieved as full-text articles for analysis. Bowel US showed 79.7% sensitivity and 96.7% specificity for the diagnosis of suspected CD, and 89% sensitivity and 94.3% specificity for initial assessment in established patients with CD. Bowel US identified ileal CD with 92.7% sensitivity, 88.2% specificity, and colon CD with 81.8% sensitivity, 95.3% specificity, with lower accuracy for detecting proximal lesions. The oral contrast agent improves the sensitivity and specificity in determining CD lesions and in assessing sites and extent. Bowel US is a tool for evaluation of CD lesions in terms of complications, postoperative recurrence, and monitoring response to medical therapy; it reliably detects postoperative recurrence and complications, as well as offers the possibility of monitoring disease progression.

Geriatric-specific triage criteria are more sensitive than standard adult criteria in identifying need for trauma center care in injured older adults.

PubMed

Ichwan, Brian; Darbha, Subrahmanyam; Shah, Manish N; Thompson, Laura; Evans, David C; Boulger, Creagh T; Caterino, Jeffrey M

2015-01-01

We evaluate the sensitivity of Ohio's 2009 emergency medical services (EMS) geriatric trauma triage criteria compared with the previous adult triage criteria in identifying need for trauma center care among older adults. We studied a retrospective cohort of injured patients aged 16 years or older in the 2006 to 2011 Ohio Trauma Registry. Patients aged 70 years or older were considered geriatric. We identified whether each patient met the geriatric and the adult triage criteria. The outcome measure was need for trauma center care, defined by surrogate markers: Injury Severity Score greater than 15, operating room in fewer than 48 hours, any ICU stay, and inhospital mortality. We calculated sensitivity and specificity of both triage criteria for both age groups. We included 101,577 patients; 33,379 (33%) were geriatric. Overall, 57% of patients met adult criteria and 68% met geriatric criteria. Using Injury Severity Score, for older adults geriatric criteria were more sensitive for need for trauma center care (93%; 95% confidence interval [CI] 92% to 93%) than adult criteria (61%; 95% CI 60% to 62%). Geriatric criteria decreased specificity in older adults from 61% (95% CI 61% to 62%) to 49% (95% CI 48% to 49%). Geriatric criteria in older adults (93% sensitivity, 49% specificity) performed similarly to the adult criteria in younger adults (sensitivity 87% and specificity 44%). Similar patterns were observed for other outcomes. Standard adult EMS triage guidelines provide poor sensitivity in older adults. Ohio's geriatric trauma triage guidelines significantly improve sensitivity in identifying Injury Severity Score and other surrogate markers of the need for trauma center care, with modest decreases in specificity for older adults. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Evaluation of clinical sensitivity and specificity of hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency Virus-1 by cobas MPX: Detection of occult HBV infection in an HBV-endemic area.

PubMed

Ha, Jihye; Park, Younhee; Kim, Hyon-Suk

2017-11-01

Transfusion-transmitted infectious diseases remain a major concern for blood safety, particularly with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Nucleic acid testing (NAT) in donor screening shortens the serologically negative window period and reduces virus transmission. The cobas MPX (Roche Molecular Systems, Inc., Branchburg, New Jersey) is a recently developed multiplex qualitative PCR system that enables the simultaneous detection of HBV, HCV, and HIV with improved sensitivity and throughput using cobas 6800 and 8800 instruments. The aim of this study was to conduct an evaluation of the clinical sensitivity and specificity of cobas MPX detection of HBV, HCV, and HIV in clinical specimens. Among samples referred for HBV, HCV, and HIV-1 quantification at Severance Hospital, Yonsei University College of Medicine, positive samples were selected to evaluate sensitivity. A total of 843 samples was tested using both cobas MPX and COBAS AmpliPrep/COBAS TaqMan Tests for HBV, HCV, and HIV-1 using the cobas 8800 system and a COBAS TaqMan 96 analyzer, respectively. Samples that showed discrepancies were confirmed by nested PCR. The cobas MPX achieved excellent sensitivity and specificity for the detection of HBV, HCV, and HIV-1 in clinical samples. We found that the lower limit of detection (LOD) of blood screening by NAT actually improves clinical sensitivity, and occult HBV infection prevalence among healthy employees of the hospital was rather high. Copyright © 2017 Elsevier B.V. All rights reserved.

Research Diagnostic Criteria for Temporomandibular Disorders: Validity of Axis I Diagnoses

PubMed Central

Truelove, Edmond; Pan, Wei; Look, John O.; Mancl, Lloyd A.; Ohrbach, Richard K.; Velly, Ana; Huggins, Kimberly; Lenton, Patricia; Schiffman, Eric L.

2011-01-01

AIMS To estimate the criterion validity of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I TMD diagnoses. METHODS A combined total of 614 TMD community and clinic cases and 91 controls were examined at 3 study sites. RDC/TMD Axis I diagnoses were algorithmically derived from an examination performed by calibrated dental hygienists. Reference standards (Gold Standards) were established by means of consensus diagnoses rendered by 2 TMD experts using all available clinical data, including imaging studies. Validity of the RDC/TMD Axis I TMD diagnoses was estimated relative to reference-standard diagnoses (gold standard diagnoses). Target sensitivity and specificity were set a priori at ≥ 0.70 and ≥ 0.95, respectively. RESULTS Target sensitivity and specificity were not observed for any of the 8 RDC/TMD diagnoses. The highest validity was achieved for Group Ia myofascial pain (sensitivity 0.65, specificity 0.92) and Group Ib myofascial pain with limited opening (sensitivity 0.79, specificity 0.92). Target sensitivity and specificity were observed only when both Group I diagnoses were combined (0.87 and 0.98, respectively). For Group II (disc displacements) and Group III (arthralgia, arthritis, arthrosis) diagnoses, all estimates for sensitivity were below target (0.03 to 0.53), and specificity ranged from below to on target (0.86 to 0.99). CONCLUSION The RDC/TMD Axis I TMD diagnoses did not reach the targets set at sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Target validity was obtained only for myofascial pain without differentiation between normal and limited opening. Revision of the current Axis I TMD diagnostic algorithms is warranted to improve their validity. PMID:20213030

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia.

PubMed

Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

2014-09-01

Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. © 2014 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

Sensitivity and specificity of the Eating Assessment Tool and the Volume-Viscosity Swallow Test for clinical evaluation of oropharyngeal dysphagia

PubMed Central

Rofes, L; Arreola, V; Mukherjee, R; Clavé, P

2014-01-01

Background Oropharyngeal dysphagia (OD) is an underdiagnosed digestive disorder that causes severe nutritional and respiratory complications. Our aim was to determine the accuracy of the Eating Assessment Tool (EAT-10) and the Volume-Viscosity Swallow Test (V-VST) for clinical evaluation of OD. Methods We studied 120 patients with swallowing difficulties and 14 healthy subjects. OD was evaluated by the 10-item screening questionnaire EAT-10 and the bedside method V-VST, videofluoroscopy (VFS) being the reference standard. The V-VST is an effort test that uses boluses of different volumes and viscosities to identify clinical signs of impaired efficacy (impaired labial seal, piecemeal deglutition, and residue) and impaired safety of swallow (cough, voice changes, and oxygen desaturation ≥3%). Discriminating ability was assessed by the AUC of the ROC curve and sensitivity and specificity values. Key Results According to VFS, prevalence of OD was 87%, 75.6% with impaired efficacy and 80.9% with impaired safety of swallow including 17.6% aspirations. The EAT-10 showed a ROC AUC of 0.89 for OD with an optimal cut-off at 2 (0.89 sensitivity and 0.82 specificity). The V-VST showed 0.94 sensitivity and 0.88 specificity for OD, 0.79 sensitivity and 0.75 specificity for impaired efficacy, 0.87 sensitivity and 0.81 specificity for impaired safety, and 0.91 sensitivity and 0.28 specificity for aspirations. Conclusions & Inferences Clinical methods for screening (EAT-10) and assessment (V-VST) of OD offer excellent psychometric proprieties that allow adequate management of OD. Their universal application among at-risk populations will improve the identification of patients with OD at risk for malnutrition and aspiration pneumonia. PMID:24909661

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

Improving the sensitivity and specificity of a bioanalytical assay for the measurement of certolizumab pegol.

PubMed

Smeraglia, John; Silva, John-Paul; Jones, Kieran

2017-08-01

In order to evaluate placental transfer of certolizumab pegol (CZP), a more sensitive and selective bioanalytical assay was required to accurately measure low CZP concentrations in infant and umbilical cord blood. Results & methodology: A new electrochemiluminescence immunoassay was developed to measure CZP levels in human plasma. Validation experiments demonstrated improved selectivity (no matrix interference observed) and a detection range of 0.032-5.0 μg/ml. Accuracy and precision met acceptance criteria (mean total error ≤20.8%). Dilution linearity and sample stability were acceptable and sufficient to support the method. The electrochemiluminescence immunoassay was validated for measuring low CZP concentrations in human plasma. The method demonstrated a more than tenfold increase in sensitivity compared with previous assays, and improved selectivity for intact CZP.

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.

Preparation and Characterization of Cyclotrimethylenetrinitramine (RDX) with Reduced Sensitivity

PubMed Central

Wang, Yuqiao; Li, Xin; Chen, Shusen; Ma, Xiao; Yu, Ziyang; Jin, Shaohua; Li, Lijie; Chen, Yu

2017-01-01

The internal defects and shape of cyclotrimethylenetrinitramine (RDX) crystal are critical parameters for the preparation of reduced sensitivity RDX (RS-RDX). In the current study, RDX was re-crystallized and spheroidized to form the high-quality RDX that was further characterized by purity, apparent density, size distribution, specific surface area, impact sensitivity, and shock sensitivity. The effects of re-crystallization solvent on the growth morphology of RDX crystal were investigated by both theoretical simulation and experiment test, and consistent results were obtained. The high-quality RDX exhibited a high purity (≥99.90%), high apparent density (≥1.811 g/cm3), spherical shape, and relatively low impact sensitivity (6%). Its specific surface area was reduced more than 30%. Compared with conventional RDXs, the high-quality RDX reduced the shock sensitivities of PBXN-109 and PBXW-115 by more than 30%, indicating that it was a RS-RDX. The reduced sensitivity and good processability of the high-quality RDX would be significant in improving the performances of RDX-based PBXs. PMID:28825661

A new D-dimer cutoff in bedridden hospitalized elderly patients.

PubMed

Granziera, Serena; Rechichi, Alfonsina; De Rui, Marina; De Carlo, Paola; Bertozzo, Giulia; Marigo, Lucia; Nante, Giovanni; Manzato, Enzo

2013-03-01

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ± 6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 μg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 μg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.

[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.

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

Sensitivity, Specificity, and Predictive Values of Pediatric Metabolic Syndrome Components in Relation to Adult Metabolic Syndrome: The Princeton LRC Follow-up Study

PubMed Central

Huang, Terry T-K; Nansel, Tonja R.; Belsheim, Allen R.; Morrison, John A.

2008-01-01

Objective To estimate the sensitivity, specificity, and predictive values of pediatric metabolic syndrome (MetS) components (obesity, fasting glucose, triglycerides, high-density lipoprotein, and blood pressure) at various cutoffs in relation to adult MetS. Study design Data from the NHLBI Lipid Research Clinics (LRC) Princeton Prevalence Study (1973–76) and the Princeton Follow-up Study (PFS, 2000-4) were used to calculate sensitivity, specificity, and positive and negative predictive values for each component at a given cutoff, as well as for aggregates of components. Results Individual pediatric components alone showed low to moderate sensitivity, high specificity, and moderate predictive values in relation to adult MetS. When all five pediatric MetS components were considered, the presence of at least one abnormality had higher sensitivity for adult MetS than individual components alone. When multiple abnormalities were mandatory for MetS, positive predictive value was high and sensitivity was low. Childhood body mass alone showed neither high sensitivity nor high positive predictive value for adult MetS. Conclusions Considering multiple metabolic variables in childhood can improve the predictive utility for adult MetS, compared to each component or body mass alone. MetS variables may be useful for identifying some at risk children for prevention interventions. PMID:18206687

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.

Combination of STOP-Bang Score with Mallampati Score fails to improve specificity in the prediction of sleep-disordered breathing.

PubMed

Dette, Frank G; Graf, Juergen; Cassel, Werner; Lloyd-Jones, Carla; Boehm, Stefan; Zoremba, Martin; Schramm, Patrick; Pestel, Gunther; Thal, Serge C

2016-06-01

Sleep-disordered breathing (SDB) is closely associated with perioperative complications. STOP-Bang score was validated for preoperative screening of SDB. However, STOP-Bang Score lacks adequately high specificity. We aimed to improve it by combining it with the Mallampati Score. The study included 347 patients, in which we assessed both STOP-Bang and Mallampati scores. Overnight oxygen saturation was measured to calculate ODI4%. We calculated the sensitivity and specificity for AHI and ODI4% of both scores separately and in combination. We found that STOP-Bang Score ≥3 was present in 71%, ODI≥5/h (AHI ≥5/h) in 42.6% (39.3%) and ODI≥15/h (AHI ≥15/h) in 13.5% (17.8%). For ODI4%≥5/h (AHI ≥5/h) we observed in men a response rate for sensitivity and specificity of STOP-Bang of 94.5% and 17.1% (90.9% and 12.5%) and in women 66% and 51% (57.8% and 46.9%). For ODI4%≥15/h (AHI≥15/h) it was 92% and 12% (84.6% and 10.3%) and 93% and 49% (75% and 49.2%). For ODI4%≥5 (AHI≥5) sensitivity and specificity of Mallampati score were in men 38.4% and 78.6% (27.3% and 68.2%) and in women 25% and 82.7% (21.9% and 81.3%), for ODI≥15 (AHI ≥15/h) 38.5% and 71.8% (26.9% and 69.2%) and 33.3% and 81.4% (17.9% and 79.6%). In combination, for ODI4%≥15/h, we found sensitivity in men to be 92.3% and in women 93.3%, specificity 10.3% and 41.4%. STOP-Bang Score combined with Mallampati Score fails to increase specificity. Low specificity should be considered when using both scores for preoperative screening of SDB.

Do race-specific definitions of short long bones improve the detection of down syndrome on second-trimester genetic sonograms?

PubMed

Harper, Lorie M; Gray, Diana; Dicke, Jeffrey; Stamilio, David M; Macones, George A; Odibo, Anthony O

2010-02-01

The purpose of this study was to determine whether the use of race-specific definitions of short femur and humerus lengths improves Down syndrome detection. This was a retrospective cohort study over 16 years. For each self-reported maternal race (white, African American, Hispanic, and Asian), we evaluated the efficiency of Down syndrome detection using published race-specific formulas compared with a standard formula for short femur and humerus lengths (observed versus expected lengths < or =0.91 and < or =0.89, respectively). The sensitivity, specificity, and 95% confidence intervals for each parameter were compared. Screening performance was compared by areas under the receiver operating characteristic curves. Of 58,710 women, 209 (0.3%) had a diagnosis of a fetus with Down syndrome. Although the race-based formula increased sensitivity in each population, the increase was statistically significant only in the white population, whereas a decrease in specificity was statistically significant in all 4 populations, as denoted by nonoverlapping confidence intervals. The area under the receiver operating characteristic curve for the model using the race-specific definition of short femur length was 0.67 versus 0.65 compared with the standard definition, and for humerus length it was 0.70 versus 0.71. The use of race-based formulas for the determination of short femur and humerus lengths did not significantly improve the detection rates for Down syndrome.

MR imaging of silicone breast implants: evaluation of prospective and retrospective interpretations and interobserver agreement.

PubMed

Quinn, S F; Neubauer, N M; Sheley, R C; Demlow, T A; Szumowski, J

1996-01-01

MR imaging was used to evaluate the integrity of silicone breast implants in 54 women with 108 implants. MR images were interpreted by relatively inexperienced readers who tried to reproduce the experiences reported in the literature. The study examines the interobserver agreement using different diagnostic signs and the influence of experience on interpretation errors. Prospective and retrospective interpretations were compared with surgical findings at the time of explanation. Diagnostic indicators, including the linguine sign, the inverted tear drop sign, the C sign, water droplets mixed with silicone, and extracapsular globules of silicone, were evaluated for diagnostic efficacy and interobserver agreement. The prospective sensitivity and specificity were 87% and 78%, respectively. With the retrospective interpretations, the sensitivity and specificity increased to 93% and 92%, respectively. Most of the prospective false-positive interpretations were due to misinterpreting radial folds as signs of implant rupture. Six implants interpreted retrospectively as false positives had gross amounts of silicone around the implants at surgery but there were no obvious rents in the implant shells. There was fair to excellent interobserver agreement with the individual diagnostic signs except for extracapsular globules of silicone. All of the signs had specificities of greater than 90%. The sensitivities of the individual signs were less than the overall retrospective sensitivity. With experience, the sensitivity improved from 87% to 93% and the specificity improved from 78% to 92%. This study helps substantiate the use of diagnostic signs used by other authors to detect silicone loss from breast implants by MR imaging; however, questions remain as to the clinical role of MR imaging in evaluating implants for silicone loss.

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Measuring the impact of cataract surgery on generic and vision-specific quality of life.

PubMed

Groessl, Erik J; Liu, Lin; Sklar, Marisa; Tally, Steven R; Kaplan, Robert M; Ganiats, Theodore G

2013-08-01

Cataracts are the leading cause of blindness worldwide and cause visual impairment for millions of adults in the United States. We compared the sensitivity of a vision-specific health-related quality of life (HRQOL) measure to that of multiple generic measures of HRQOL before and at 2 time points after cataract surgery. Participants completed 1 vision-specific and 5 generic quality of life measures before cataract surgery, and again 1 and 6 months after surgery. Random effects modeling was used to measure changes over the three assessment points. The NEI-VFQ25 total score and all 11 subscales showed significant improvements during the first interval (baseline and 1 month). During the second interval (1-6 months post-surgery), significant improvements were observed on the total score and 5 of 11 NEI-VFQ25 subscales. There were significant increases in HRQOL during the first interval on some preference-based generic HRQOL measures, though changes during the second interval were mostly non-significant. None of the SF-36v2™ or SF6D scales changed significantly between any of the assessment periods. The NEI-VFQ25 was sensitive to changes in vision-specific domains of QOL. Some preference-based generic HRQOL measures were also sensitive to change and showed convergence with the NEI-VFQ25, but the effects were small. The SF-36v2™ and SF-6D did not change in a similar manner, possibly reflecting a lack of vision-related content. Studies seeking to document both the vision-specific and generic HRQOL improvements of cataract surgery should consider these results when selecting measures.

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.

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.

Data transformation methods for multiplexed assays

DOEpatents

Tammero, Lance F. Bentley; Dzenitis, John M; Hindson, Benjamin J

2013-07-23

Methods to improve the performance of an array assay are described. A correlation between fluorescence intensity-related parameters and negative control values of the assay is determined. The parameters are then adjusted as a function of the correlation. As a result, sensitivity of the assay is improved without changes in its specificity.

The use of hippocampal volumetric measurements to improve diagnostic accuracy in pediatric patients with mesial temporal sclerosis.

PubMed

Guzmán Pérez-Carrillo, Gloria J; Owen, Christopher; Schwetye, Katherine E; McFarlane, Spencer; Vellimana, Ananth K; Mar, Soe; Miller-Thomas, Michelle M; Shimony, Joshua S; Smyth, Matthew D; Benzinger, Tammie L S

2017-06-01

OBJECTIVE Many patients with medically intractable epilepsy have mesial temporal sclerosis (MTS), which significantly affects their quality of life. The surgical excision of MTS lesions can result in marked improvement or even complete resolution of the epileptic episodes. Reliable radiological diagnosis of MTS is a clinical challenge. The purpose of this study was to evaluate the utility of volumetric mapping of the hippocampi for the identification of MTS in a case-controlled series of pediatric patients who underwent resection for medically refractory epilepsy, using pathology as a gold standard. METHODS A cohort of 57 pediatric patients who underwent resection for medically intractable epilepsy between 2005 and 2015 was evaluated. On pathological investigation, this group included 24 patients with MTS and 33 patients with non-MTS findings. Retrospective quantitative volumetric measurements of the hippocampi were acquired for 37 of these 57 patients. Two neuroradiologists with more than 10 years of experience who were blinded to the patients' MTS status performed the retrospective review of MR images. To produce the volumetric data, MR scans were parcellated and segmented using the FreeSurfer software suite. Hippocampal regions of interest were compared against an age-weighted local regression curve generated with data from the pediatric normal cohort. Standard deviations and percentiles of specific subjects were calculated. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for the original clinical read and the expert readers. Receiver operating characteristic curves were generated for the methods of classification to compare results from the readers with the authors' results, and an optimal threshold was determined. From that threshold the sensitivity, specificity, PPV, and NPV were calculated for the volumetric analysis. RESULTS With the use of quantitative volumetry, a sensitivity of 72%, a specificity of 95%, a PPV of 93%, an NPV of 78%, and an area under the curve of 0.84 were obtained using a percentage difference of normalized hippocampal volume. The resulting specificity (95%) and PPV (93%) are superior to the original clinical read and to Reader A and Reader B's findings (range for specificity 74%-86% and for PPV 64%-71%). The sensitivity (72%) and NPV (78%) are comparable to Reader A's findings (73% and 81%, respectively) and are better than those of the original clinical read and of Reader B (sensitivity 45% and 63% and NPV 71% and 70%, respectively). CONCLUSIONS Volumetric measurement of the hippocampi outperforms expert readers in specificity and PPV, and it demonstrates comparable to superior sensitivity and NPV. Volumetric measurements can complement anatomical imaging for the identification of MTS, much like a computer-aided detection tool would. The implementation of this approach in the daily clinical workflow could significantly improve diagnostic accuracy.

An evaluation of the SD Bioline HIV/syphilis duo test.

PubMed

Holden, Jeffrey; Goheen, Joshua; Jett-Goheen, Mary; Barnes, Mathilda; Hsieh, Yu-Hsiang; Gaydos, Charlotte A

2018-01-01

Many health agencies now recommend routine HIV and syphilis testing for pregnant women and most-at-risk populations such as men who have sex with men. With the increased availability of highly sensitive, low cost rapid point-of-care tests, the ability to meet those recommendations has increased, granting wider access to quick and accurate diagnoses. Using blood specimens collected from a Baltimore City Health Department (BCHD) sexually transmitted infection clinic, we evaluated the SD Bioline HIV/Syphilis Duo, a rapid test that simultaneously detects antibodies to HIV and syphilis and has the potential to further benefit clinics and patients by reducing costs, testing complexity, and patient wait times. SD DUO HIV sensitivity and specificity, when compared to BCHD results, were 91.7 and 99.5%, respectively. SD DUO syphilis sensitivity and specificity, when compared to rapid plasma reagin, were 85.7 and 96.8%, respectively, and 69.7 and 99.7%, respectively, when compared to Treponema pallidum particle agglutination (TPPA). SD DUO syphilis sensitivity and specificity, when compared to a traditional screening algorithm, improved to 92.3 and 100%, respectively, and improved to 72.9 and 99.7%, respectively, when compared to a reverse screening algorithm. The HIV component of the SD DUO performed moderately well. However, results for the SD DUO syphilis component, when compared to TPPA, support the need for further testing and assessment.

Vision in the common bed bug Cimex lectularius L. (Hemiptera: Cimicidae): eye morphology and spectral sensitivity.

PubMed

McNeill, C A; Allan, S A; Koehler, P G; Pereira, R M; Weeks, E N I

2016-12-01

Bed bugs as pests of public health importance recently experienced a resurgence in populations throughout the U.S. and other countries. Consequently, recent research efforts have focused on improving understanding of bed bug physiology and behaviour to improve management. While few studies have investigated the visual capabilities of bed bugs, the present study focused specifically on eye morphology and spectral sensitivity. A 3-D imaging technique was used to document bed bug eye morphology from the first instar through adult and revealed morphological characteristics that differentiate the common bed bug from the tropical bed bug as well as sex-specific differences. Electrophysiological measurements were used to evaluate the spectral sensitivity of adult bed bugs. Male bed bugs were more responsive than females at some wavelengths. Electrophysiological studies provided evidence for at least one photoreceptor with a spectral sensitivity curve peak in the green (λ max 520 nm) region of the spectrum. The broadened long wavelength portion of the spectral sensitivity curve may potentially indicate another photoreceptor in the yellow-green (λ max 550 nm) portion of the spectrum or screening pigments. Understanding more about bed bug visual biology is vital for designing traps, which are an important component of integrated bed bug management. © 2016 The Royal Entomological Society.

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).

Improved sensitivity high-definition interline CCD using the KODAK TRUESENSE color filter pattern

NASA Astrophysics Data System (ADS)

DiBella, James; Andreghetti, Marco; Enge, Amy; Chen, William; Stanka, Timothy; Kaser, Robert

2010-01-01

The KODAK TRUESENSE Color Filter Pattern has technology that for the first time is applied to a commercially available interline CCD. This 2/3" true-HD sensor will be described along with its performance attributes, including sensitivity improvement as compared to the Bayer CFA version of the same sensor. In addition, an overview of the system developed for demonstration and evaluation will be provided. Examples of the benefits of the new technology in specific applications including surveillance and intelligent traffic systems will be discussed.

Quantum Error Correction for Metrology

NASA Astrophysics Data System (ADS)

Sushkov, Alex; Kessler, Eric; Lovchinsky, Igor; Lukin, Mikhail

2014-05-01

The question of the best achievable sensitivity in a quantum measurement is of great experimental relevance, and has seen a lot of attention in recent years. Recent studies [e.g., Nat. Phys. 7, 406 (2011), Nat. Comms. 3, 1063 (2012)] suggest that in most generic scenarios any potential quantum gain (e.g. through the use of entangled states) vanishes in the presence of environmental noise. To overcome these limitations, we propose and analyze a new approach to improve quantum metrology based on quantum error correction (QEC). We identify the conditions under which QEC allows one to improve the signal-to-noise ratio in quantum-limited measurements, and we demonstrate that it enables, in certain situations, Heisenberg-limited sensitivity. We discuss specific applications to nanoscale sensing using nitrogen-vacancy centers in diamond in which QEC can significantly improve the measurement sensitivity and bandwidth under realistic experimental conditions.

Diagnostic performance of an automated analysis software for the diagnosis of Alzheimer’s dementia with 18F FDG PET

PubMed Central

Partovi, Sasan; Yuh, Roger; Pirozzi, Sara; Lu, Ziang; Couturier, Spencer; Grosse, Ulrich; Schluchter, Mark D; Nelson, Aaron; Jones, Robert; O’Donnell, James K; Faulhaber, Peter

2017-01-01

The objective of this study was to assess the ability of a quantitative software-aided approach to improve the diagnostic accuracy of 18F FDG PET for Alzheimer’s dementia over visual analysis alone. Twenty normal subjects (M:F-12:8; mean age 80.6 years) and twenty mild AD subjects (M:F-12:8; mean age 70.6 years) with 18F FDG PET scans were obtained from the ADNI database. Three blinded readers interpreted these PET images first using a visual qualitative approach and then using a quantitative software-aided approach. Images were classified on two five-point scales based on normal/abnormal (1-definitely normal; 5-definitely abnormal) and presence of AD (1-definitely not AD; 5-definitely AD). Diagnostic sensitivity, specificity, and accuracy for both approaches were compared based on the aforementioned scales. The sensitivity, specificity, and accuracy for the normal vs. abnormal readings of all readers combined were higher when comparing the software-aided vs. visual approach (sensitivity 0.93 vs. 0.83 P = 0.0466; specificity 0.85 vs. 0.60 P = 0.0005; accuracy 0.89 vs. 0.72 P<0.0001). The specificity and accuracy for absence vs. presence of AD of all readers combined were higher when comparing the software-aided vs. visual approach (specificity 0.90 vs. 0.70 P = 0.0008; accuracy 0.81 vs. 0.72 P = 0.0356). Sensitivities of the software-aided and visual approaches did not differ significantly (0.72 vs. 0.73 P = 0.74). The quantitative software-aided approach appears to improve the performance of 18F FDG PET for the diagnosis of mild AD. It may be helpful for experienced 18F FDG PET readers analyzing challenging cases. PMID:28123864

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials.

PubMed

Verma, Nishant; Beretvas, S Natasha; Pascual, Belen; Masdeu, Joseph C; Markey, Mia K

2018-03-14

Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

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

A novel approach to enhance antibody sensitivity and specificity by peptide cross-linking

PubMed Central

Namiki, Takeshi; Valencia, Julio C.; Hall, Matthew D.; Hearing, Vincent J.

2008-01-01

Most current techniques employed to improve antigen-antibody signals in western blotting and in immunohistochemistry rely on sample processing prior to staining (e.g. microwaving) or using a more robust reporter (e.g. a secondary antibody with biotin-streptavidin). We have developed and optimized a new approach intended to stabilize the complexes formed between antigens and their respective primary antibodies by cupric ions at high pH. This technique improves the affinity and lowers cross-reactivity with non-specific bands of ∼20% of antibodies tested (5/25). Here we report that this method can enhance antigen-antibody specificity and can improve the utility of some poorly reactive primary antibodies. PMID:18801330

Autoantibody Approach for Serum-Based Detection of Head and Neck Cancer — EDRN Public Portal

Cancer.gov

Our long term goal is to improve survival of patients with head and neck squamous cell carcinoma (HNSCC) through early detection using simple noninvasive serum assays in an ELISA-like platform. The objective of this proposal is to improve and confirm the validity of a diagnostic serum assay based on a panel of cancer-specific biomarkers for early cancer detection in patients with HNSCC. Our central hypothesis is that the detection of antibody responses to HNSCC-specific antigens, using a panel of biomarkers, can provide sufficient sensitivity and specificity suitable for clinical testing in the primary setting to screen and diagnose HNSCC in high risk populations to improve early detection.

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.

Likelihood ratio-based differentiation of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in patients with sonographically evident diffuse hashimoto thyroiditis: preliminary study.

PubMed

Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi

2012-11-01

To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for discrimination of nodular Hashimoto thyroiditis from papillary thyroid carcinoma; therefore, it is a promising risk index for thyroid nodules and warrants further investigation.

Clinical Validation of Multiplex Real-Time PCR Assays for Detection of Bacterial Meningitis Pathogens

PubMed Central

Theodore, M. Jordan; Mair, Raydel; Trujillo-Lopez, Elizabeth; du Plessis, Mignon; Wolter, Nicole; Baughman, Andrew L.; Hatcher, Cynthia; Vuong, Jeni; Lott, Lisa; von Gottberg, Anne; Sacchi, Claudio; McDonald, J. Matthew; Messonnier, Nancy E.; Mayer, Leonard W.

2012-01-01

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA and serogroup-specific genes in the cap locus for N. meningitidis serogroups A, B, C, W135, X, and Y. However, the assay sensitivity for serogroups B, W135, and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays for serogroup B synD, W135 synG, and Y synF showed 100% specificity for detecting N. meningitidis species, with high sensitivity (serogroup B synD, 99% [75/76]; W135 synG, 97% [38/39]; and Y synF, 100% [66/66]). The lower limits of detection (LLD) were 9, 43, and 10 copies/reaction for serogroup B synD, W135 synG, and Y synF assays, respectively, a significant improvement compared to results for the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of (i) N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA (NHS assay); (ii) N. meningitidis serogroups A, W135, and X (AWX assay); and (iii) N. meningitidis serogroups B, C, and Y (BCY assay). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for the singleplex assay. Pairwise comparison of real-time PCR between multiplex and singleplex assays showed that cycle threshold values of the multiplex assay were similar to those for the singleplex assay. There were no substantial differences in sensitivity and specificity between these multiplex and singleplex real-time PCR assays. PMID:22170919

Sensitivity and specificity of a new automated system for the detection of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus nucleic acid in blood and plasma donations.

PubMed

Galel, Susan A; Simon, Toby L; Williamson, Phillip C; AuBuchon, James P; Waxman, Dan A; Erickson, Yasuko; Bertuzis, Rasa; Duncan, John R; Malhotra, Khushbeer; Vaks, Jeffrey; Huynh, Nancy; Pate, Lisa Lee

2018-03-01

Use of nucleic acid testing (NAT) in donor infectious disease screening improves transfusion safety. Advances in NAT technology include improvements in assay sensitivity and system automation, and real-time viral target discrimination in multiplex assays. This article describes the sensitivity and specificity of cobas MPX, a multiplex assay for detection of human immunodeficiency virus (HIV)-1 Group M, HIV-2 and HIV-1 Group O RNA, HCV RNA, and HBV DNA, for use on the cobas 6800/8800 Systems. The specificity of cobas MPX was evaluated in samples from donors of blood and source plasma in the United States. Analytic sensitivity was determined with reference standards. Infectious window periods (WPs) before NAT detectability were calculated for current donor screening assays. The specificity of cobas MPX was 99.946% (99.883%-99.980%) in 11,203 blood donor samples tested individually (IDT), 100% (99.994%-100%) in 63,012 donor samples tested in pools of 6, and 99.994% (99.988%-99.998%) in 108,306 source plasma donations tested in pools of 96. Seven HCV NAT-yield donations and one seronegative occult HBV infection were detected. Ninety-five percent and 50% detection limits in plasma (IU/mL) were 25.7 and 3.8 for HIV-1M, 7.0 and 1.3 for HCV, and 1.4 and 0.3 for HBV. The HBV WP was 1 to 4 days shorter than other donor screening assays by IDT. cobas MPX demonstrated high specificity in blood and source plasma donations tested individually and in pools. High sensitivity, in particular for HBV, shortens the WP and may enhance detection of occult HBV. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Clinical validation of multiplex real-time PCR assays for detection of bacterial meningitis pathogens.

PubMed

Wang, Xin; Theodore, M Jordan; Mair, Raydel; Trujillo-Lopez, Elizabeth; du Plessis, Mignon; Wolter, Nicole; Baughman, Andrew L; Hatcher, Cynthia; Vuong, Jeni; Lott, Lisa; von Gottberg, Anne; Sacchi, Claudio; McDonald, J Matthew; Messonnier, Nancy E; Mayer, Leonard W

2012-03-01

Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA and serogroup-specific genes in the cap locus for N. meningitidis serogroups A, B, C, W135, X, and Y. However, the assay sensitivity for serogroups B, W135, and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays for serogroup B synD, W135 synG, and Y synF showed 100% specificity for detecting N. meningitidis species, with high sensitivity (serogroup B synD, 99% [75/76]; W135 synG, 97% [38/39]; and Y synF, 100% [66/66]). The lower limits of detection (LLD) were 9, 43, and 10 copies/reaction for serogroup B synD, W135 synG, and Y synF assays, respectively, a significant improvement compared to results for the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of (i) N. meningitidis ctrA, H. influenzae hpd, and S. pneumoniae lytA (NHS assay); (ii) N. meningitidis serogroups A, W135, and X (AWX assay); and (iii) N. meningitidis serogroups B, C, and Y (BCY assay). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for the singleplex assay. Pairwise comparison of real-time PCR between multiplex and singleplex assays showed that cycle threshold values of the multiplex assay were similar to those for the singleplex assay. There were no substantial differences in sensitivity and specificity between these multiplex and singleplex real-time PCR assays.

Validity of self-assessment in a quality improvement collaborative in Ecuador.

PubMed

Hermida, Jorge; Broughton, Edward I; Miller Franco, Lynne

2011-12-01

Health care quality improvement (QI) efforts commonly use self-assessment to measure compliance with quality standards. This study investigates the validity of self-assessment of quality indicators. Cross sectional. A maternal and newborn care improvement collaborative intervention conducted in health facilities in Ecuador in 2005. Four external evaluators were trained in abstracting medical records to calculate six indicators reflecting compliance with treatment standards. About 30 medical records per month were examined at 12 participating health facilities for a total of 1875 records. The same records had already been reviewed by QI teams at these facilities (self-assessment). Overall compliance, agreement (using the Kappa statistic), sensitivity and specificity were analyzed. We also examined patterns of disagreement and the effect of facility characteristics on levels of agreement. External evaluators reported compliance of 69-90%, while self-assessors reported 71-92%, with raw agreement of 71-95% and Kappa statistics ranging from fair to almost perfect agreement. Considering external evaluators as the gold standard, sensitivity of self-assessment ranged from 90 to 99% and specificity from 48 to 86%. Simpler indicators had fewer disagreements. When disagreements occurred between self-assessment and external valuators, the former tended to report more positive findings in five of six indicators, but this tendency was not of a magnitude to change program actions. Team leadership, understanding of the tools and facility size had no overall impact on the level of agreement. When compared with external evaluation (gold standard), self-assessment was found to be sufficiently valid for tracking QI team performance. Sensitivity was generally higher than specificity. Simplifying indicators may improve validity.

Validation of a second-generation multivariate index assay for malignancy risk of adnexal masses.

PubMed

Coleman, Robert L; Herzog, Thomas J; Chan, Daniel W; Munroe, Donald G; Pappas, Todd C; Smith, Alan; Zhang, Zhen; Wolf, Judith

2016-07-01

Women with adnexal mass suspected of ovarian malignancy are likely to benefit from consultation with a gynecologic oncologist, but imaging and biomarker tools to ensure this referral show low sensitivity and may miss cancer at critical stages. The multivariate index assay (MIA) was designed to improve the detection of ovarian cancer among women undergoing surgery for a pelvic mass. To improve the prediction of benign masses, we undertook the redesign and validation of a second-generation MIA (MIA2G). MIA2G was developed using banked serum samples from a previously published prospective, multisite registry of patients who underwent surgery to remove an adnexal mass. Clinical validity was then established using banked serum samples from the OVA500 trial, a second prospective cohort of adnexal surgery patients. Based on the final pathology results of the OVA500 trial, this intended-use population for MIA2G testing was high risk, with an observed cancer prevalence of 18.7% (92/493). Coded samples were assayed for MIA2G biomarkers by an external clinical laboratory. Then MIA2G results were calculated and submitted to a clinical statistics contract organization for decoding and comparison to MIA results for each subject. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, among other measures, and stratified by menopausal status, stage, and histologic subtype. Three MIA markers (cancer antigen 125, transferrin, and apolipoprotein A-1) and 2 new biomarkers (follicle-stimulating hormone and human epididymis protein 4) were included in MIA2G. A single cut-off separated high and low risk of malignancy regardless of patient menopausal status, eliminating potential for confusion or error. MIA2G specificity (69%, 277/401 [n/N]; 95% confidence interval [CI], 64.4-73.4%) and PPV (40%, 84/208; 95% CI, 33.9-47.2%) were significantly improved over MIA (specificity, 54%, 215/401; 95% CI, 48.7-58.4%, and PPV, 31%, 85/271; 95% CI, 26.1-37.1%, respectively) in this cohort. Sensitivity and NPV were not significantly different between the 2 tests. When combined with physician assessment, MIA2G correctly identified 75% of the malignancies missed by physician assessment alone. MIA2G specificity and PPV were significantly improved compared with MIA, while sensitivity and NPV were unchanged. The second-generation test significantly improved the predicted efficiency of triage vs MIA without sacrificing high sensitivity and NPV, which are essential for effectiveness. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

Making perceptual learning practical to improve visual functions.

PubMed

Polat, Uri

2009-10-01

Task-specific improvement in performance after training is well established. The finding that learning is stimulus-specific and does not transfer well between different stimuli, between stimulus locations in the visual field, or between the two eyes has been used to support the notion that neurons or assemblies of neurons are modified at the earliest stage of cortical processing. However, a debate regarding the proposed mechanism underlying perceptual learning is an ongoing issue. Nevertheless, generalization of a trained task to other functions is an important key, for both understanding the neural mechanisms and the practical value of the training. This manuscript describes a structured perceptual learning method that previously used (amblyopia, myopia) and a novel technique and results that were applied for presbyopia. In general, subjects were trained for contrast detection of Gabor targets under lateral masking conditions. Training improved contrast sensitivity and diminished the lateral suppression when it existed (amblyopia). The improvement was transferred to unrelated functions such as visual acuity. The new results of presbyopia show substantial improvement of the spatial and temporal contrast sensitivity, leading to improved processing speed of target detection as well as reaction time. Consequently, the subjects, who were able to eliminate the need for reading glasses, benefited. Thus, here we show that the transfer of functions indicates that the specificity of improvement in the trained task can be generalized by repetitive practice of target detection, covering a sufficient range of spatial frequencies and orientations, leading to an improvement in unrelated visual functions. Thus, perceptual learning can be a practical method to improve visual functions in people with impaired or blurred vision.

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.

Assessing the effectiveness of combining evaluation methods for the early identification of students with inadequate knowledge during a clerkship.

PubMed

Hemmer, Paul A.; Grau, Thomas; Pangaro, Louis N.

2001-10-01

This study examined the predictive validity of in-clerkship evaluation methods to identify medical students who have insufficient knowledge. Study subjects were 124 third-year medical students at the Uniformed Services University. Insufficient knowledge was defined by: (1) a clerkship 'pre-test' score one standard deviation below the mean or lower; or (2) any teacher verbally rating a student's general knowledge as 'marginal' or less; or (3) a student did not pass Step One of the United States Medical Licensing Examination (USMLE). We determined sensitivity and specificity using a standard score of 90%. Using USMLE Step One pass-fail performance did not improve sensitivity. Combining a 'pre-test' and instructors' formal evaluation session comments improves the early identification of students with insufficient knowledge, allowing for formative feedback and remediation during the clerkship.

The MG Composite

PubMed Central

Burns, Ted M.; Conaway, Mark; Sanders, Donald B.

2010-01-01

Objective: To study the concurrent and construct validity and test-retest reliability in the practice setting of an outcome measure for myasthenia gravis (MG). Methods: Eleven centers participated in the validation study of the Myasthenia Gravis Composite (MGC) scale. Patients with MG were evaluated at 2 consecutive visits. Concurrent and construct validities of the MGC were assessed by evaluating MGC scores in the context of other MG-specific outcome measures. We used numerous potential indicators of clinical improvement to assess the sensitivity and specificity of the MGC for detecting clinical improvement. Test-retest reliability was performed on patients at the University of Virginia. Results: A total of 175 patients with MG were enrolled at 11 sites from July 1, 2008, to January 31, 2009. A total of 151 patients were seen in follow-up. Total MGC scores showed excellent concurrent validity with other MG-specific scales. Analyses of sensitivities and specificities of the MGC revealed that a 3-point improvement in total MGC score was optimal for signifying clinical improvement. A 3-point improvement in the MGC also appears to represent a meaningful improvement to most patients, as indicated by improved 15-item myasthenia gravis quality of life scale (MG-QOL15) scores. The psychometric properties were no better for an individualized subscore made up of the 2 functional domains that the patient identified as most important to treat. The test-retest reliability coefficient of the MGC was 98%, with a lower 95% confidence interval of 97%, indicating excellent test-retest reliability. Conclusions: The Myasthenia Gravis Composite is a reliable and valid instrument for measuring clinical status of patients with myasthenia gravis in the practice setting and in clinical trials. PMID:20439845

Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma

PubMed Central

Tang, Lin-Quan; Zhang, Hua; Li, Yan; Liu, Wan-Li; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

2016-01-01

To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC. PMID:27093005

SYMPOSIUM ON MULTIMODALITY CARDIOVASCULAR MOLECULAR IMAGING IMAGING TECHNOLOGY - PART 2

PubMed Central

de Kemp, Robert A.; Epstein, Frederick H.; Catana, Ciprian; Tsui, Benjamin M.W.; Ritman, Erik L.

2013-01-01

Rationale The ability to trace or identify specific molecules within a specific anatomic location provides insight into metabolic pathways, tissue components and tracing of solute transport mechanisms. With the increasing use of small animals for research such imaging must have sufficiently high spatial resolution to allow anatomic localization as well as sufficient specificity and sensitivity to provide an accurate description of the molecular distribution and concentration. Methods Imaging methods based on electromagnetic radiation, such as PET, SPECT, MRI and CT, are increasingly applicable due to recent advances in novel scanner hardware, image reconstruction software and availability of novel molecules which have enhanced sensitivity in these methodologies. Results Micro-PET has been advanced by development of detector arrays that provide higher resolution and positron emitting elements that allow new molecular tracers to be labeled. Micro-MRI has been improved in terms of spatial resolution and sensitivity by increased magnet field strength and development of special purpose coils and associated scan protocols. Of particular interest is the associated ability to image local mechanical function and solute transport processes which can be directly related to the molecular information. This is further strengthened by the synergistic integration of the PET with MRI. Micro-SPECT has been improved by use of coded aperture imaging approaches as well as image reconstruction algorithms which can better deal with the photon limited scan data. The limited spatial resolution can be partially overcome by integrating the SPECT with CT. Micro-CT by itself provides exquisite spatial resolution of anatomy, but recent developments of high spatial resolution photon counting and spectrally-sensitive imaging arrays, combined with x-ray optical devices, have promise for actual molecular identification by virtue of the chemical bond lengths of molecules, especially of bio-polymers. Conclusion With the increasing use of small animals for evaluating new clinical imaging techniques as well as providing increased insights into patho-physiological phenomena, the availability of improved detection systems, scanning protocols and associated software, the repertoire of molecular imaging is greatly increased in sensitivity and specificity. PMID:20457793

Neurolysin Knockout Mice Generation and Initial Phenotype Characterization*

PubMed Central

Cavalcanti, Diogo M. L. P.; Castro, Leandro M.; Rosa Neto, José C.; Seelaender, Marilia; Neves, Rodrigo X.; Oliveira, Vitor; Forti, Fábio L.; Iwai, Leo K.; Gozzo, Fabio C.; Todiras, Mihail; Schadock, Ines; Barros, Carlos C.; Bader, Michael; Ferro, Emer S.

2014-01-01

The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity. PMID:24719317

Emerging enhanced imaging technologies of the esophagus: spectroscopy, confocal laser endomicroscopy, and optical coherence tomography.

PubMed

Robles, Lourdes Y; Singh, Satish; Fisichella, Piero Marco

2015-05-15

Despite advances in diagnoses and therapy, esophageal adenocarcinoma remains a highly lethal neoplasm. Hence, a great interest has been placed in detecting early lesions and in the detection of Barrett esophagus (BE). Advanced imaging technologies of the esophagus have then been developed with the aim of improving biopsy sensitivity and detection of preplastic and neoplastic cells. The purpose of this article was to review emerging imaging technologies for esophageal pathology, spectroscopy, confocal laser endomicroscopy (CLE), and optical coherence tomography (OCT). We conducted a PubMed search using the search string "esophagus or esophageal or oesophageal or oesophagus" and "Barrett or esophageal neoplasm" and "spectroscopy or optical spectroscopy" and "confocal laser endomicroscopy" and "confocal microscopy" and "optical coherence tomography." The first and senior author separately reviewed all articles. Our search identified: 19 in vivo studies with spectroscopy that accounted for 1021 patients and 4 ex vivo studies; 14 clinical CLE in vivo studies that accounted for 941 patients and 1 ex vivo study with 13 patients; and 17 clinical OCT in vivo studies that accounted for 773 patients and 2 ex vivo studies. Human studies using spectroscopy had a very high sensitivity and specificity for the detection of BE. CLE showed a high interobserver agreement in diagnosing esophageal pathology and an accuracy of predicting neoplasia. We also found several clinical studies that reported excellent diagnostic sensitivity and specificity for the detection of BE using OCT. Advanced imaging technology for the detection of esophageal lesions is a promising field that aims to improve the detection of early esophageal lesions. Although advancing imaging techniques improve diagnostic sensitivities and specificities, their integration into diagnostic protocols has yet to be perfected. Copyright © 2015 Elsevier Inc. All rights reserved.

Reformatted images improve the detection rate of acute traumatic subdural hematomas on brain CT compared with axial images alone.

PubMed

Amrhein, Timothy J; Mostertz, William; Matheus, Maria Gisele; Maass-Bolles, Genevieve; Sharma, Komal; Collins, Heather R; Kranz, Peter G

2017-02-01

Subdural hematomas (SDHs) comprise a significant percentage of missed intracranial hemorrhage on axial brain CT. SDH detection rates could be improved with the addition of reformatted images. Though performed at some centers, the potential additional diagnostic sensitivity of reformatted images has not yet been investigated. The purpose of our study is to determine if the addition of coronal and sagittal reformatted images to an axial brain CT increases the sensitivity and specificity for detection of acute traumatic SDH. We retrospectively reviewed consecutive brain CTs acquired for acute trauma that contained new SDHs. An equivalent number of normal brain CTs served as control. Paired sets of images were created for each case: (1) axial images only ("axial only") and (2) axial, coronal, sagittal images ("reformat added"). Three readers interpreted both the axial only and companion reformat added for each case, separated by 1 month. Reading times and SDH detection rates were compared. One hundred SDH and 100 negative examinations were collected. Sensitivity and specificity for the axial-only scans were 75.7 and 94.3 %, respectively, compared with 88.3 and 98.3 % for reformat added. There was a 24.3 % false negative (missed SDH) rate with axial-only scans versus 11.7 % with reformat added (p = <0.001). Median reader interpretation times were longer with the addition of reformatted images (125 versus 89 s), but this difference was not significant (p = 0.23). The addition of coronal and sagittal images in trauma brain CT resulted in improved sensitivity and specificity as well as a reduction in SDH false negatives by greater than 50 %. Reformatted images substantially reduce the number of missed SDHs compared with axial images alone.

Detection of pericardial effusion by chest roentgenography and electrocardiography versus echocardiography.

PubMed Central

Manyari, D. E.; Milliken, J. A.; Colwell, B. T.; Burggraf, G. W.

1978-01-01

To determine the sensitivity and specificity of chest roentgenography and electrocardiography in the detection of pericardial effusion, echocardiography was used as the diagnostic standard. Chest roentgenograms and electrocardiograms of 124 patients, 57 of whom had pericardial effusion, were read without knowledge of the echocardiographic interpretation. The sensitivity of roentgenographic diagnosis was low (20%), as was that of diagnosis from decreased voltage on the electrocardiogram (26%). The specificity of the chest roentgenogram was 89% and that of the low-voltage electrocardiogram 97%. The high specificity of the low-voltage electrocardiogram may have been due in part to the exclusion of obese and emphysematous subjects from the study. When cardiomegaly detected roentgenographically or a low-voltage electrocardiogram or both were considered as evidence of pericardial effusion, sensitivity improved to 82% but specificity declined to 29%. It is concluded the chest roentgenography and electrocardiography are unsatisfactory as screening investigations for the detection of pericardial effusion. Images FIG. 1 FIG. 2 FIG. 3 PMID:688146

The PHQ-PD as a Screening Tool for Panic Disorder in the Primary Care Setting in Spain

PubMed Central

Wood, Cristina Mae; Ruíz-Rodríguez, Paloma; Tomás-Tomás, Patricia; Gracia-Gracia, Irene; Dongil-Collado, Esperanza; Iruarrizaga, M. Iciar

2016-01-01

Introduction Panic disorder is a common anxiety disorder and is highly prevalent in Spanish primary care centres. The use of validated tools can improve the detection of panic disorder in primary care populations, thus enabling referral for specialized treatment. The aim of this study is to determine the accuracy of the Patient Health Questionnaire-Panic Disorder (PHQ-PD) as a screening and diagnostic tool for panic disorder in Spanish primary care centres. Method We compared the psychometric properties of the PHQ-PD to the reference standard, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview. General practitioners referred 178 patients who completed the entire PHQ test, including the PHQ-PD, to undergo the SCID-I. The sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of the PHQ-PD were assessed. Results The operating characteristics of the PHQ-PD are moderate. The best cut-off score was 5 (sensitivity .77, specificity .72). Modifications to the questionnaire's algorithms improved test characteristics (sensitivity .77, specificity .72) compared to the original algorithm. The screening question alone yielded the highest sensitivity score (.83). Conclusion Although the modified algorithm of the PHQ-PD only yielded moderate results as a diagnostic test for panic disorder, it was better than the original. Using only the first question of the PHQ-PD showed the best psychometric properties (sensitivity). Based on these findings, we suggest the use of the screening questions for screening purposes and the modified algorithm for diagnostic purposes. PMID:27525977

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

Broad-specificity immunoassay for O,O-diethyl organophosphorus pesticides: Application of molecular modeling to improve assay sensitivity and study antibody recognition

USDA-ARS?s Scientific Manuscript database

A monoclonal antibody (MAb) against 4-(diethoxyphosphorothioyloxy)benzoic acid (hapten 1) was raised and used to develop a broad-specificity competitive indirect enzyme-linked immunosorbent assay (ciELISA) for 14 O,O-diethyl organophosphorus pesticides (OPs). Computer-assisted molecular modeling was...

Improving sensitivity and specificity of capturing and detecting targeted cancer cells with anti-biofouling polymer coated magnetic iron oxide nanoparticles.

PubMed

Lin, Run; Li, Yuancheng; MacDonald, Tobey; Wu, Hui; Provenzale, James; Peng, Xingui; Huang, Jing; Wang, Liya; Wang, Andrew Y; Yang, Jianyong; Mao, Hui

2017-02-01

Detecting circulating tumor cells (CTCs) with high sensitivity and specificity is critical to management of metastatic cancers. Although immuno-magnetic technology for in vitro detection of CTCs has shown promising potential for clinical applications, the biofouling effect, i.e., non-specific adhesion of biomolecules and non-cancerous cells in complex biological samples to the surface of a device/probe, can reduce the sensitivity and specificity of cell detection. Reported herein is the application of anti-biofouling polyethylene glycol-block-allyl glycidyl ether copolymer (PEG-b-AGE) coated iron oxide nanoparticles (IONPs) to improve the separation of targeted tumor cells from aqueous phase in an external magnetic field. PEG-b-AGE coated IONPs conjugated with transferrin (Tf) exhibited significant anti-biofouling properties against non-specific protein adsorption and off-target cell uptake, thus substantially enhancing the ability to target and separate transferrin receptor (TfR) over-expressed D556 medulloblastoma cells. Tf conjugated PEG-b-AGE coated IONPs exhibited a high capture rate of targeted tumor cells (D556 medulloblastoma cell) in cell media (58.7±6.4%) when separating 100 targeted tumor cells from 1×10 5 non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads ® ). Copyright © 2016 Elsevier B.V. All rights reserved.

Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies

PubMed Central

Streeter, Jason E.; Gessner, Ryan; Miles, Iman; Dayton, Paul A.

2010-01-01

Molecular imaging with ultrasound relies on microbubble contrast agents (MCAs) selectively adhering to a ligand-specific target. Prior studies have shown that only small quantities of microbubbles are retained at their target sites, therefore, enhancing contrast sensitivity to low concentrations of microbubbles is essential to improve molecular imaging techniques. In order to assess the effect of MCA diameter on imaging sensitivity, perfusion and molecular imaging studies were performed with microbubbles of varying size distributions. To assess signal improvement and MCA circulation time as a function of size and concentration, blood perfusion was imaged in rat kidneys using nontargeted size-sorted MCAs with a Siemens Sequoia ultrasound system (Siemans, Mountain View, CA) in cadence pulse sequencing (CPS) mode. Molecular imaging sensitivity improvements were studied with size-sorted αvβ3-targeted bubbles in both fibrosarcoma and R3230 rat tumor models. In perfusion imaging studies, video intensity and contrast persistence was ≈8 times and ≈3 times greater respectively, for “sorted 3-micron” MCAs (diameter, 3.3 ± 1.95 μm) when compared to “unsorted” MCAs (diameter, 0.9 ± 0.45 μm) at low concentrations. In targeted experiments, application of sorted 3-micron MCAs resulted in a ≈20 times video intensity increase over unsorted populations. Tailoring size-distributions results in substantial imaging sensitivity improvement over unsorted populations, which is essential in maximizing sensitivity to small numbers of MCAs for molecular imaging. PMID:20236606

Near-infrared imaging for management of chronic maxillary sinusitis

NASA Astrophysics Data System (ADS)

You, Joon S.; Cerussi, Albert E.; Kim, James; Ison, Sean; Wong, Brian; Cui, Haotian; Bhandarkar, Naveen

2015-03-01

Efficient management of chronic sinusitis remains a great challenge for primary care physicians. Unlike ENT specialists using Computed Tomography scans, they lack an affordable and safe method to accurately screen and monitor sinus diseases in primary care settings. Lack of evidence-based sinusitis management leads to frequent under-treatments and unnecessary over-treatments (i.e. antibiotics). Previously, we reported low-cost optical imaging designs for oral illumination and facial optical imaging setup. It exploits the sensitivity of NIR transmission intensity and their unique patterns to the sinus structures and presence of fluid/mucous-buildup within the sinus cavities. Using the improved NIR system, we have obtained NIR sinus images of 45 subjects with varying degrees of sinusitis symptoms. We made diagnoses of these patients based on two types of evidence: symptoms alone or NIR images along. These diagnostic results were then compared to the gold standard diagnosis using computed tomography through sensitivity and specificity analysis. Our results indicate that diagnosis of mere presence of sinusitis that is, distinguishing between healthy individuals vs. diseased individuals did not improve much when using NIR imaging compared to the diagnosis based on symptoms alone (69% in sensitivity, 75% specificity). However, use of NIR imaging improved the differential diagnosis between mild and severe diseases significantly as the sensitivity improved from 75% for using diagnosis based on symptoms alone up to 95% for using diagnosis based on NIR images. Reported results demonstrate great promise for using NIR imaging system for management of chronic sinusitis patients in primary care settings without resorting to CT.

Vertical or horizontal orientation of foot radiographs does not affect image interpretation

PubMed Central

Ferran, Nicholas Antonio; Ball, Luke; Maffulli, Nicola

2012-01-01

Summary This study determined whether the orientation of dorsoplantar and oblique foot radiographs has an effect on radiograph interpretation. A test set of 50 consecutive foot radiographs were selected (25 with fractures, and 25 normal), and duplicated in the horizontal orientation. The images were randomly arranged, numbered 1 through 100, and analysed by six image interpreters. Vertical and horizontal area under the ROC curve, accuracy, sensitivity and specificity were calculated for each image interpreter. There was no significant difference in the area under the ROC curve, accuracy, sensitivity or specificity of image interpretation between images viewed in the vertical or horizontal orientation. While conventions for display of radiographs may help to improve the development of an efficient visual search strategy in trainees, and allow for standardisation of publication of radiographic images, variation from the convention in clinical practice does not appear to affect the sensitivity or specificity of image interpretation. PMID:23738310

HPV Genotyping of Modified General Primer-Amplicons Is More Analytically Sensitive and Specific by Sequencing than by Hybridization

PubMed Central

Meisal, Roger; Rounge, Trine Ballestad; Christiansen, Irene Kraus; Eieland, Alexander Kirkeby; Worren, Merete Molton; Molden, Tor Faksvaag; Kommedal, Øyvind; Hovig, Eivind; Leegaard, Truls Michael

2017-01-01

Sensitive and specific genotyping of human papillomaviruses (HPVs) is important for population-based surveillance of carcinogenic HPV types and for monitoring vaccine effectiveness. Here we compare HPV genotyping by Next Generation Sequencing (NGS) to an established DNA hybridization method. In DNA isolated from urine, the overall analytical sensitivity of NGS was found to be 22% higher than that of hybridization. NGS was also found to be the most specific method and expanded the detection repertoire beyond the 37 types of the DNA hybridization assay. Furthermore, NGS provided an increased resolution by identifying genetic variants of individual HPV types. The same Modified General Primers (MGP)-amplicon was used in both methods. The NGS method is described in detail to facilitate implementation in the clinical microbiology laboratory and includes suggestions for new standards for detection and calling of types and variants with improved resolution. PMID:28045981

HPV Genotyping of Modified General Primer-Amplicons Is More Analytically Sensitive and Specific by Sequencing than by Hybridization.

PubMed

Meisal, Roger; Rounge, Trine Ballestad; Christiansen, Irene Kraus; Eieland, Alexander Kirkeby; Worren, Merete Molton; Molden, Tor Faksvaag; Kommedal, Øyvind; Hovig, Eivind; Leegaard, Truls Michael; Ambur, Ole Herman

2017-01-01

Sensitive and specific genotyping of human papillomaviruses (HPVs) is important for population-based surveillance of carcinogenic HPV types and for monitoring vaccine effectiveness. Here we compare HPV genotyping by Next Generation Sequencing (NGS) to an established DNA hybridization method. In DNA isolated from urine, the overall analytical sensitivity of NGS was found to be 22% higher than that of hybridization. NGS was also found to be the most specific method and expanded the detection repertoire beyond the 37 types of the DNA hybridization assay. Furthermore, NGS provided an increased resolution by identifying genetic variants of individual HPV types. The same Modified General Primers (MGP)-amplicon was used in both methods. The NGS method is described in detail to facilitate implementation in the clinical microbiology laboratory and includes suggestions for new standards for detection and calling of types and variants with improved resolution.

Enzymatic signal amplification for sensitive detection of intracellular antigens by flow cytometry.

PubMed

Karkmann, U; Radbruch, A; Hölzel, V; Scheffold, A

1999-11-19

Flow cytometry is the method of choice for the analysis of single cells with respect to the expression of specific antigens. Antigens can be detected with specific antibodies either on the cell surface or within the cells, after fixation and permeabilization of the cell membrane. Using conventional fluorochrome-labeled antibodies several thousand antigens are required for clear-cut separation of positive and negative cells. More sensitive reagents, e.g., magnetofluorescent liposomes conjugated to specific antibodies permit the detection of less than 200 molecules per cell but cannot be used for the detection of intracellular antigens. Here, we describe an enzymatic amplification technique (intracellular tyramine-based signal amplification, ITSA) for the sensitive cytometric analysis of intracellular cytokines by immunofluorescence. This approach results in a 10 to 15-fold improvement of the signal-to-noise ratio compared to conventional fluorochrome labeled antibodies and permits the detection of as few as 300-400 intracellular antigens per cell.

Substrate-specific modifications on magnetic iron oxide nanoparticles as an artificial peroxidase for improving sensitivity in glucose detection.

PubMed

Liu, Yanping; Yu, Faquan

2011-04-08

Magnetic iron oxide nanoparticles (MION) were recently found to act as a peroxidase with intrinsic advantages over natural counterparts. Their limited affinity toward catalysis substrates, however, dramatically reduces their utility. In this paper, some effective groups were screened out and conjugated on MION as substrate-specific modifications for improving MION's affinity to substrates and hence utility. Nanoparticles of four different superficial structures were synthesized and characterized by TEM, size, zeta potential and SQUID, and assayed for peroxidase activity. Glucose detection was selected as an application model system to evaluate the bonus thereof. Catalysis was found to follow Michaelis-Menten kinetics. Sulfhydryl groups incorporated on MION (SH-MION) notably improve the affinity toward a substrate (hydrogen peroxide) and so do amino groups (NH₂-MION) toward another substrate, proved by variation in the determined kinetic parameters. A synergistically positive effect was observed and an apparently elevated detection sensitivity and a significantly lowered detection limit of glucose were achieved when integrated with both sulfhydryl and amino groups (SH-NH₂-MION). Our findings suggest that substrate-specific surface modifications are a straightforward and robust strategy to improve MION peroxidase-like activity. The high activity extends magnetic nanoparticles to wide applications other than glucose detection.

Optimisation of the zinc sulphate turbidity test for the determination of immune status.

PubMed

Hogan, I; Doherty, M; Fagan, J; Kennedy, E; Conneely, M; Crowe, B; Lorenz, I

2016-02-13

Failure of passive transfer of maternal immunity occurs in calves that fail to absorb sufficient immunoglobulins from ingested colostrum. The zinc sulphate turbidity test has been developed to test bovine neonates for this failure. The specificity of this test has been shown to be less than ideal. The objective was to examine how parameters of the zinc sulphate turbidity test may be manipulated in order to improve its diagnostic accuracy. One hundred and five blood samples were taken from calves of dairy cows receiving various rates of colostrum feeding. The zinc sulphate turbidity test was carried out multiple times on each sample, varying the solution strength, time of reaction and wavelength of light used and the results compared with those of a radial immunodiffusion test, which is the reference method for measuring immunoglobulin concentration in serum. Reducing the time over which the reaction occurs, or increasing the wavelength of light used to read the turbidity, resulted in decreased specificity without improving sensitivity. Increasing the concentration of the zinc sulphate solution used in the test was shown to improve the specificity without decreasing sensitivity. Examination of the cut-off points suggested that a lower cut-off point would improve the performance. British Veterinary Association.

A modified single-tube one-step product-enhanced reverse transcriptase (mSTOS-PERT) assay with heparin as DNA polymerase inhibitor for specific detection of RTase activity.

PubMed

Fan, Xiao-Yong; Lü, Guo-Zhen; Wu, Li-Na; Chen, Jing-Hua; Xu, Wen-Qing; Zhao, Chun-Nü; Guo, Sheng-Qi

2006-12-01

Current regulations and recommendations proposed for the production of vaccines in continuous cell lines of any origin demand that these be free of exogenous viruses, particularly retroviruses. Recently, the ultra-sensitive product-enhanced reverse transcriptase (PERT) assay can be used to detect minute of reverse transcriptase (RTase) in single retroviral particle and is 10(6) times more sensitive than the conventional RTase assays. However, coincidental with this increase in sensitivity is an increase in false-positive reactions derived from contaminating cellular DNA polymerases, which are known to have RTase-like activities. To develop a modified single-tube one-step PERT (mSTOS-PERT) assay with improvements on decreasing significantly the level of false-positive reactions, and to evaluate the mSTOS-PERT assay for sensitivity and specificity. Ampliwaxtrade mark was used to compartmentalize the reverse transcription (RT) and PCR step in the same micro-tube with more efficiency and reproducibility, while maintaining the high sensitivity. The DNA amplification products were separated by 2% agarose gel electrophoresis, and then analyzed by non-isotopic Southern blot hybridization. A wide variety of cell lines used in biologicals production were detected to validate the improved mSTOS-PERT assay. The detection limit for the mSTOS-PERT assay was at least 10(-9)U, when using AMV-RTase as a positive control. Furthermore, heparin involvement in the RT step can eliminate completely the false-positive PERT signals which are exhibited by cellular polymerases such as DNA-dependent DNA polymerase alpha, gamma released by cell death. Most mammalian cells (MRC-5, Vero, WISH, 2BS, RK-13, MDCK, etc.) are PERT-negative in cell supernatants. Some PERT-positive signals in cell lysates were found to be introduced by the cellular DNA polymerases and could be inhibited specifically by heparin. Chick cells derived from either chick embryo fibroblasts (CEF) or allantoic fluid from SPF embryonated eggs, murine hybridoma cell SP2/0, etc., contained authentic RTase activities, which could not be inactivated by heparin. The improved mSTOS-PERT assay described here may distinguish the genuine RTase activity from cellular polymerases with high sensitivity and specificity, and is rapid and easy to perform to screen for the possible contamination of minute retroviruses in the cell substrates used in vaccine production.

Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates.

PubMed

Low, Andrew J; Dong, Winnie; Chan, Dennison; Sing, Tobias; Swanstrom, Ronald; Jensen, Mark; Pillai, Satish; Good, Benjamin; Harrigan, P Richard

2007-09-12

Integrating CCR5 antagonists into clinical practice would benefit from accurate assays of co-receptor usage (CCR5 versus CXCR4) with fast turnaround and low cost. Published HIV V3-loop based predictors of co-receptor usage were compared with actual phenotypic tropism results in a large cohort of antiretroviral naive individuals to determine accuracy on clinical samples and identify areas for improvement. Aligned HIV envelope V3 loop sequences (n = 977), derived by bulk sequencing were analyzed by six methods: the 11/25 rule; a neural network (NN), two support vector machines, and two subtype-B position specific scoring matrices (PSSM). Co-receptor phenotype results (Trofile Co-receptor Phenotype Assay; Monogram Biosciences) were stratified by CXCR4 relative light unit (RLU) readout and CD4 cell count. Co-receptor phenotype was available for 920 clinical samples with V3 genotypes having fewer than seven amino acid mixtures (n = 769 R5; n = 151 X4-capable). Sensitivity and specificity for predicting X4 capacity were evaluated for the 11/25 rule (30% sensitivity/93% specificity), NN (44%/88%), PSSM(sinsi) (34%/96%), PSSM(x4r5) (24%/97%), SVMgenomiac (22%/90%) and SVMgeno2pheno (50%/89%). Quantitative increases in sensitivity could be obtained by optimizing the cut-off for methods with continuous output (PSSM methods), and/or integrating clinical data (CD4%). Sensitivity was directly proportional to strength of X4 signal in the phenotype assay (P < 0.05). Current default implementations of co-receptor prediction algorithms are inadequate for predicting HIV X4 co-receptor usage in clinical samples, particularly those X4 phenotypes with low CXCR4 RLU signals. Significant improvements can be made to genotypic predictors, including training on clinical samples, using additional data to improve predictions and optimizing cutoffs and increasing genotype sensitivity.

A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment

PubMed Central

Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

2015-01-01

Digital PCR has developed rapidly since it was first reported in the 1990s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products. PMID:26239916

A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

PubMed

Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

2015-08-04

Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

Strategies to improve the accuracy of vision measurement by teachers in rural Chinese secondary schoolchildren: Xichang Pediatric Refractive Error Study (X-PRES) report no. 6.

PubMed

Sharma, Abhishek; Li, Liping; Song, Yue; Choi, Kai; Lam, Dennis S C; Zhang, Mingzhi; Zheng, Mingwei; Zhou, Zhongxia; Liu, Xiaojian; Wu, Bin; Congdon, Nathan

2008-10-01

To assess and improve the accuracy of lay screeners compared with vision professionals in detecting visual impairment in secondary schoolchildren in rural China. After brief training, 32 teachers and a team of vision professionals independently measured vision in 1892 children in Xichang. The children also underwent vision measurement by health technicians in a concurrent government screening program. Of 32 teachers, 28 (87.5%) believed that teacher screening was worthwhile. Sensitivity (93.5%) and specificity (91.2%) of teachers detecting uncorrected presenting visual acuity of 20/40 or less were better than for presenting visual acuity (sensitivity, 85.2%; specificity, 84.8%). Failure of teachers to identify children owning but not wearing glasses and teacher bias toward better vision in children wearing glasses explain the worse results for initial vision. Wearing glasses was the student factor most strongly predictive of inaccurate teacher screening (P < .001). The sensitivity and specificity of the government screening program detecting low presenting visual acuity were 86.7% and 28.7%, respectively. Teacher vision screening after brief training can achieve accurate results in this setting, and there is support among teachers for screening. Screening of uncorrected rather than presenting visual acuity is recommended in settings with a high prevalence of corrected and uncorrected refractive error. Low specificity in the government program renders it ineffective.

Assessment of Mycobacterium tuberculosis OmpATb as a Novel Antigen for the Diagnosis of Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

In search for improved tools to control bovine tuberculosis, the development of diagnostic tests with improved specificity and sensitivity has a high priority. Such tests require the identification of enhanced immunodiagnostic reagents. In this study, we evaluated the potential of Rv0899 (Outer memb...

Ethanol production improvement driven by genome-scale metabolic modeling and sensitivity analysis in Scheffersomyces stipitis

PubMed Central

2017-01-01

The yeast Scheffersomyces stipitis naturally produces ethanol from xylose, however reaching high ethanol yields is strongly dependent on aeration conditions. It has been reported that changes in the availability of NAD(H/+) cofactors can improve fermentation in some microorganisms. In this work genome-scale metabolic modeling and phenotypic phase plane analysis were used to characterize metabolic response on a range of uptake rates. Sensitivity analysis was used to assess the effect of ARC on ethanol production indicating that modifying ARC by inhibiting the respiratory chain ethanol production can be improved. It was shown experimentally in batch culture using Rotenone as an inhibitor of the mitochondrial NADH dehydrogenase complex I (CINADH), increasing ethanol yield by 18%. Furthermore, trajectories for uptakes rates, specific productivity and specific growth rate were determined by modeling the batch culture, to calculate ARC associated to the addition of CINADH inhibitor. Results showed that the increment in ethanol production via respiratory inhibition is due to excess in ARC, which generates an increase in ethanol production. Thus ethanol production improvement could be predicted by a change in ARC. PMID:28658270

Ethanol production improvement driven by genome-scale metabolic modeling and sensitivity analysis in Scheffersomyces stipitis.

PubMed

Acevedo, Alejandro; Conejeros, Raúl; Aroca, Germán

2017-01-01

The yeast Scheffersomyces stipitis naturally produces ethanol from xylose, however reaching high ethanol yields is strongly dependent on aeration conditions. It has been reported that changes in the availability of NAD(H/+) cofactors can improve fermentation in some microorganisms. In this work genome-scale metabolic modeling and phenotypic phase plane analysis were used to characterize metabolic response on a range of uptake rates. Sensitivity analysis was used to assess the effect of ARC on ethanol production indicating that modifying ARC by inhibiting the respiratory chain ethanol production can be improved. It was shown experimentally in batch culture using Rotenone as an inhibitor of the mitochondrial NADH dehydrogenase complex I (CINADH), increasing ethanol yield by 18%. Furthermore, trajectories for uptakes rates, specific productivity and specific growth rate were determined by modeling the batch culture, to calculate ARC associated to the addition of CINADH inhibitor. Results showed that the increment in ethanol production via respiratory inhibition is due to excess in ARC, which generates an increase in ethanol production. Thus ethanol production improvement could be predicted by a change in ARC.

Immunophenotyping does not improve predictivity of the local lymph node assay in mice.

PubMed

Strauss, Volker; Kolle, Susanne N; Honarvar, Naveed; Dammann, Martina; Groeters, Sibylle; Faulhammer, Frank; Landsiedel, Robert; van Ravenzwaay, Bennard

2015-04-01

The local lymph node assay (LLNA) is a regulatory accepted test for the identification of skin sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. However, there is evidence that LLNA is overestimating the sensitization potential of certain substance classes in particular those exerting skin irritation. Some reports describe the additional use of flow cytometry-based immunophenotyping to better discriminate irritants from sensitizing irritants in LLNA. In the present study, the 22 performance standards plus 8 surfactants were assessed using the radioactive LLNA method. In addition, lymph node cells were immunophenotyped to evaluate the specificity of the lymph node response using cell surface markers such as B220 or CD19, CD3, CD4, CD8, I-A(κ) and CD69 with the aim to allow a better discrimination above all between irritants and sensitizers, but also non-irritating sensitizers and non-sensitizers. However, the markers assessed in this study do not sufficiently differentiate between irritants and irritant sensitizers and therefore did not improve the predictive capacity of the LLNA. Copyright © 2014 John Wiley & Sons, Ltd.

Sensitivity improvement of an electrical sensor achieved by control of biomolecules based on the negative dielectrophoretic force.

PubMed

Kim, Hye Jin; Kim, Jinsik; Yoo, Yong Kyoung; Lee, Jeong Hoon; Park, Jung Ho; Hwang, Kyo Seon

2016-11-15

Effective control of nano-scale biomolecules can enhance the sensitivity and limit of detection of an interdigitated microelectrode (IME) sensor. Manipulation of the biomolecules by dielectrophoresis (DEP), especially the negative DEP (nDEP) force, so that they are trapped between electrodes (sensing regions) was predicted to increase the binding efficiency of the antibody and target molecules, leading to a more effective reaction. To prove this concept, amyloid beta 42 (Aβ42) and prostate specific antigen (PSA) protein were respectively trapped between the sensing region owing to the nDEP force under 5V and 0.05V, which was verified with COMSOL simulation. Using the simulation value, the resistance change (ΔR/Rb) of the IME sensor from the specific antibody-antigen reaction of the two biomolecules and the change in fluorescence intensity were compared in the reference (pDEP) and nDEP conditions. The ΔR/Rb value improved by about 2-fold and 1.66-fold with nDEP compared to the reference condition with various protein concentrations, and these increases were confirmed with fluorescence imaging. Overall, nDEP enhanced the detection sensitivity for Aβ42 and PSA by 128% and 258%, respectively, and the limit of detection improved by up to 2-orders of magnitude. These results prove that DEP can improve the biosensor's performance. Copyright © 2016 Elsevier B.V. All rights reserved.

7 CFR 1468.4 - Establishing Conservation Farm Option (CFO) pilot project areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Conservation of soil, water, and related natural resources, (ii) Water quality protection or improvement, (iii... that can be geographically described and has specific environmental sensitivities or significant soil...

Extensor tendinopathy of the elbow assessed with sonoelastography: histologic correlation.

PubMed

Klauser, Andrea S; Pamminger, Mathias; Halpern, Ethan J; Abd Ellah, Mohamed M H; Moriggl, Bernhard; Taljanovic, Mihra S; Deml, Christian; Sztankay, Judit; Klima, Guenther; Jaschke, Werner R

2017-08-01

To compare agreement between conventional B-mode ultrasound (US) and compression sonoelastography (SEL) of the common extensor tendons of the elbow with histological evaluation. Twenty-six common extensor tendons were evaluated in 17 cadavers (11 females, median age 85 years and 6 males, median age 80 years). B-mode US was graded into: Grade 1, homogeneous fibrillar pattern; grade 2, hypoechoic areas and/or calcifications <30%; and grade 3 > 30%. SEL was graded into: Grade 1 indicated blue (hardest) to green (hard); grade 2 yellow (soft); and grade 3 red (softest). B-mode US, SEL, and a combined grading score incorporating both were compared to histological findings in 76 biopsies. Histological alterations were detected in 55/76 biopsies. Both modalities showed similar results (sensitivity, specificity, and accuracy 84%, 81%, and 83% for B-mode US versus 85%, 86%, and 86% for SEL, respectively, P > 0.3). However, a combination of both resulted in significant improvement in sensitivity (96%, P < 0.02) without significant change in specificity (81%, P < 0.3), yielding an improved overall accuracy (92%). Combined imaging of the extensor tendons with both modalities is superior to either modality alone for predicting the presence of pathologic findings on histology. • Combination of B-mode US and SEL proved efficiency in diagnosing lateral epicondylitis. • Combination of B-mode US and SEL in lateral epicondylitis correlates to histology. • Combination of both modalities provides improved sensitivity without loss of specificity.

Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

PubMed Central

Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

2014-01-01

Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

Sensitivity of predicted bioaerosol exposure from open windrow composting facilities to ADMS dispersion model parameters.

PubMed

Douglas, P; Tyrrel, S F; Kinnersley, R P; Whelan, M; Longhurst, P J; Walsh, K; Pollard, S J T; Drew, G H

2016-12-15

Bioaerosols are released in elevated quantities from composting facilities and are associated with negative health effects, although dose-response relationships are not well understood, and require improved exposure classification. Dispersion modelling has great potential to improve exposure classification, but has not yet been extensively used or validated in this context. We present a sensitivity analysis of the ADMS dispersion model specific to input parameter ranges relevant to bioaerosol emissions from open windrow composting. This analysis provides an aid for model calibration by prioritising parameter adjustment and targeting independent parameter estimation. Results showed that predicted exposure was most sensitive to the wet and dry deposition modules and the majority of parameters relating to emission source characteristics, including pollutant emission velocity, source geometry and source height. This research improves understanding of the accuracy of model input data required to provide more reliable exposure predictions. Copyright © 2016. Published by Elsevier Ltd.

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.

Use of the Air Force Post-Deployment Health Reassessment for the identification of depression and posttraumatic stress disorder: public health implications for suicide prevention.

PubMed

McCarthy, Michael D; Thompson, Sanna J; Knox, Kerry L

2012-03-01

Military members are required to complete the Post-Deployment Health Assessment on return from deployment and the Post-Deployment Health Reassessment (PHDRA) 90 to 180 days later, and we assessed the PDHRA's sensitivity and specificity in identifying posttraumatic stress disorder (PTSD) and depression after a military deployment among US Air Force personnel. We computed the PDHRA's sensitivity and specificity for depression and PTSD and developed a structural model to suggest possible improvements to it. For depression, sensitivity and specificity were 0.704 and 0.651, respectively; for PTSD, they were 0.774 and 0.650, respectively. Several variables produced significant direct effects on depression and trauma, suggesting that modifications could increase its sensitivity and specificity. The PDHRA was moderately effective in identifying airmen with depression and PTSD. It identified behavioral health concerns in many airmen who did not develop a diagnostic mental health condition. Its low level of specificity may result in reduced barriers to care and increased support services, key components of a public health approach to suicide prevention, for airmen experiencing subacute levels of distress after deployment, which may, in part, account for lower suicide rates among airmen after deployment.

Adaptive smoothing based on Gaussian processes regression increases the sensitivity and specificity of fMRI data.

PubMed

Strappini, Francesca; Gilboa, Elad; Pitzalis, Sabrina; Kay, Kendrick; McAvoy, Mark; Nehorai, Arye; Snyder, Abraham Z

2017-03-01

Temporal and spatial filtering of fMRI data is often used to improve statistical power. However, conventional methods, such as smoothing with fixed-width Gaussian filters, remove fine-scale structure in the data, necessitating a tradeoff between sensitivity and specificity. Specifically, smoothing may increase sensitivity (reduce noise and increase statistical power) but at the cost loss of specificity in that fine-scale structure in neural activity patterns is lost. Here, we propose an alternative smoothing method based on Gaussian processes (GP) regression for single subjects fMRI experiments. This method adapts the level of smoothing on a voxel by voxel basis according to the characteristics of the local neural activity patterns. GP-based fMRI analysis has been heretofore impractical owing to computational demands. Here, we demonstrate a new implementation of GP that makes it possible to handle the massive data dimensionality of the typical fMRI experiment. We demonstrate how GP can be used as a drop-in replacement to conventional preprocessing steps for temporal and spatial smoothing in a standard fMRI pipeline. We present simulated and experimental results that show the increased sensitivity and specificity compared to conventional smoothing strategies. Hum Brain Mapp 38:1438-1459, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Utility of Water Siphon Maneuver for Eliciting Gastroesophageal Reflux During Barium Esophagography: Correlation With Histologic Findings.

PubMed

Dane, B; Doshi, A; Khan, A; Megibow, A

2018-06-12

The objective of this study is to evaluate whether the water siphon maneuver improves detection of gastroesophageal (GE) reflux during barium esophagography compared with observation for spontaneous reflux only. Histopathologic analysis is the reference standard. This retrospective study assessed 87 outpatients who underwent both barium esophagography and upper endoscopy-guided biopsy within a 30-day interval. The water siphon maneuver was routinely performed when spontaneous GE reflux was not observed during the fluoroscopic study. Radiology reports were reviewed for mentions of the presence of reflux and the circumstances in which it was observed (as a spontaneous occurrence or as a result of the water siphon maneuver). Pathology reports from subsequent endoscopic biopsies were reviewed to identify histologic changes of reflux disease. The sensitivity, specificity, and accuracy of esophagography, observation for spontaneous reflux, and the water siphon maneuver were calculated and then compared using a McNemar test. Of the 87 patients, 57 (65.5%) had GE reflux diagnosed on the basis of histologic changes noted on endoscopy, and 30 (34.5%) did not. A total of 57 patients (65.5%) showed reflux during esophagography, 41 (71.9%) of whom had reflux diagnosed by the water siphon maneuver, and 16 (28.1%) had reflux diagnosed on the basis of observation of spontaneous reflux. Forty-four patients had reflux diagnosed on the basis of both a barium study and histologic findings; 13 patients had reflux noted on esophagography but had negative histologic findings. The overall sensitivity, specificity, and accuracy of esophagography for reflux were 77.2%, 56.7%, and 70.1%, respectively. Spontaneous reflux alone had a sensitivity, specificity, and accuracy of 21.1%, 86.7%, and 43.7%, respectively. The water siphon maneuver showed a sensitivity of 71.1%, a specificity of 65.4%, and accuracy of 69.0%. The differences in the sensitivity, specificity, and accuracy of the water siphon maneuver versus observation of spontaneous reflux were statistically significant (p ≤ 0.004). A properly performed and interpreted water siphon maneuver significantly increases the sensitivity and accuracy for GE reflux during esophagography, compared with observation for spontaneous reflux alone. The water siphon maneuver is a simple addition to barium esophagography that improves sensitivity and accuracy for the diagnosis of GE reflux compared with observation alone.

Shear-wave elastography improves the specificity of breast US: the BE1 multinational study of 939 masses.

PubMed

Berg, Wendie A; Cosgrove, David O; Doré, Caroline J; Schäfer, Fritz K W; Svensson, William E; Hooley, Regina J; Ohlinger, Ralf; Mendelson, Ellen B; Balu-Maestro, Catherine; Locatelli, Martina; Tourasse, Christophe; Cavanaugh, Barbara C; Juhan, Valérie; Stavros, A Thomas; Tardivon, Anne; Gay, Joel; Henry, Jean-Pierre; Cohen-Bacrie, Claude

2012-02-01

To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses. From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-approved, HIPAA-compliant protocol. B-mode Breast Imaging Reporting and Data System (BI-RADS) features and assessments were recorded. SW elastographic evaluation (mean, maximum, and minimum elasticity of stiffest portion of mass and surrounding tissue; lesion-to-fat elasticity ratio; ratio of SW elastographic-to-B-mode lesion diameter or area; SW elastographic lesion shape and homogeneity) was performed. Qualitative color SW elastographic stiffness was assessed independently. Nine hundred thirty-nine masses were analyzable; 102 BI-RADS category 2 masses were assumed to be benign; reference standard was available for 837 category 3 or higher lesions. Considering BI-RADS category 4a or higher as test positive for malignancy, effect of SW elastographic features on area under the receiver operating characteristic curve (AUC), sensitivity, and specificity after reclassifying category 3 and 4a masses was determined. Median participant age was 50 years; 289 of 939 (30.8%) masses were malignant (median mass size, 12 mm). B-mode BI-RADS AUC was 0.950; eight of 303 (2.6%) BI-RADS category 3 masses, 18 of 193 (9.3%) category 4a lesions, 41 of 97 (42%) category 4b lesions, 42 of 57 (74%) category 4c lesions, and 180 of 187 (96.3%) category 5 lesions were malignant. By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P<.001); AUC increased to 0.962 (P=.005). Oval shape on SW elastographic images and quantitative maximum elasticity of 80 kPa (5.2 m/sec) or less improved specificity (69.4% [451 of 650] and 77.4% [503 of 650], P<.001 for both), without significant improvement in sensitivity or AUC. Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity. © RSNA, 2012

Detecting DNA methylation of the BCL2, CDKN2A and NID2 genes in urine using a nested methylation specific polymerase chain reaction assay to predict bladder cancer.

PubMed

Scher, Michael B; Elbaum, Michael B; Mogilevkin, Yakov; Hilbert, David W; Mydlo, Jack H; Sidi, A Ami; Adelson, Martin E; Mordechai, Eli; Trama, Jason P

2012-12-01

Detection of methylated DNA has been shown to be a good biomarker for bladder cancer. Bladder cancer has the highest recurrence rate of any cancer and, as such, patients are regularly monitored using invasive diagnostic techniques. As urine is easily attainable, bladder cancer is an optimal cancer to detect using DNA methylation. DNA methylation is highly specific in cancer detection. However, it is difficult to detect because of the limited amount of DNA present in the urine of patients with bladder cancer. Therefore, an improved, sensitive and noninvasive diagnostic test is needed. We developed a highly specific and sensitive nested methylation specific polymerase chain reaction assay to detect the presence of bladder cancer in small volumes of patient urine. The genes assayed for DNA methylation are BCL2, CDKN2A and NID2. The regions surrounding the DNA methylation sites were amplified in a methylation independent first round polymerase chain reaction and the amplification product from the first polymerase chain reaction was used in a real-time methylation specific polymerase chain reaction. Urine samples were collected from patients receiving treatment at Wolfson Medical Center in Holon, Israel. In a pilot clinical study using patient urine samples we were able to differentiate bladder cancer from other urogenital malignancies and nonmalignant conditions with a sensitivity of 80.9% and a specificity of 86.4%. We developed a novel methylation specific polymerase chain reaction assay for the detection and monitoring of bladder cancer using DNA extracted from patient urine. The assay may also be combined with other diagnostic tests to improve accuracy. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Combining measurements from three anatomical areas for glaucoma diagnosis using Fourier-domain optical coherence tomography.

PubMed

Loewen, Nils A; Zhang, Xinbo; Tan, Ou; Francis, Brian A; Greenfield, David S; Schuman, Joel S; Varma, Rohit; Huang, David

2015-09-01

To improve the diagnostic power for glaucoma by combining measurements of peripapillary nerve fibre layer (NFL), macular ganglion cell complex (GCC) and disc variables obtained with Fourier-domain optical coherence tomography (FD-OCT) into the glaucoma structural diagnostic index (GSDI). In this observational, cross-sectional study of subjects from the Advanced Imaging of Glaucoma Study, GCC and NFL of healthy and perimetrical glaucoma subjects from four major academic referral centres of the Advanced Imaging of Glaucoma Study were mapped with the RTVue FD-OCT. Global loss volume and focal loss volume parameters were defined using NFL and GCC normative reference maps. Optimal weights for NFL, GCC and disc variables were combined using multivariate logistic regression to build the GSDI. Glaucoma severity was classified using the Enhanced Glaucoma Staging System (GSS2). Diagnostic accuracy was assessed by sensitivity, specificity and the area under the receiver operator characteristic curve (AUC). We analysed 118 normal eyes of 60 subjects, 236 matched eyes of 166 subjects with perimetrical glaucoma, and 105 eyes from a healthy reference group of 61 subjects. The GSDI included composite overall thickness and focal loss volume with weighted NFL and GCC components, as well as the vertical cup-to-disc ratio. The AUC of 0.922 from leave-one-out cross validation was better than the best component variable alone (p=0.047). The partial AUC in the high specificity region was also better (p=0.01), with a sensitivity of 69% at 99% specificity, and a sensitivity of 80.3% at 95% specificity. For GSS2 stages 3-5 the sensitivity was 98% at 99% specificity, and 100% at 95% specificity. Combining structural measurements of GCC, NFL and disc variables from FD-OCT created a GSDI that improved the accuracy for glaucoma diagnosis. NCT01314326. 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.

Clinical Effectiveness of Prospectively Reported Sonographic Twinkling Artifact for the Diagnosis of Renal Calculus in Patients Without Known Urolithiasis.

PubMed

Masch, William R; Cohan, Richard H; Ellis, James H; Dillman, Jonathan R; Rubin, Jonathan M; Davenport, Matthew S

2016-02-01

The purpose of this study was to determine the clinical effectiveness of prospectively reported sonographic twinkling artifact for the diagnosis of renal calculus in patients without known urolithiasis. All ultrasound reports finalized in one health system from June 15, 2011, to June 14, 2014, that contained the words "twinkle" or "twinkling" in reference to suspected renal calculus were identified. Patients with known urolithiasis or lack of a suitable reference standard (unenhanced abdominal CT with ≤ 2.5-mm slice thickness performed ≤ 30 days after ultrasound) were excluded. The sensitivity, specificity, and positive likelihood ratio of sonographic twinkling artifact for the diagnosis of renal calculus were calculated by renal unit and stratified by two additional diagnostic features for calcification (echogenic focus, posterior acoustic shadowing). Eighty-five patients formed the study population. Isolated sonographic twinkling artifact had sensitivity of 0.78 (82/105), specificity of 0.40 (26/65), and a positive likelihood ratio of 1.30 for the diagnosis of renal calculus. Specificity and positive likelihood ratio improved and sensitivity declined when the following additional diagnostic features were present: sonographic twinkling artifact and echogenic focus (sensitivity, 0.61 [64/105]; specificity, 0.65 [42/65]; positive likelihood ratio, 1.72); sonographic twinkling artifact and posterior acoustic shadowing (sensitivity, 0.31 [33/105]; specificity, 0.95 [62/65]; positive likelihood ratio, 6.81); all three features (sensitivity, 0.31 [33/105]; specificity, 0.95 [62/65]; positive likelihood ratio, 6.81). Isolated sonographic twinkling artifact has a high false-positive rate (60%) for the diagnosis of renal calculus in patients without known urolithiasis.

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.

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.

Rapid Molecular Microbiologic Diagnosis of Prosthetic Joint Infection

PubMed Central

Cazanave, Charles; Greenwood-Quaintance, Kerryl E.; Hanssen, Arlen D.; Karau, Melissa J.; Schmidt, Suzannah M.; Gomez Urena, Eric O.; Mandrekar, Jayawant N.; Osmon, Douglas R.; Lough, Lindsay E.; Pritt, Bobbi S.; Steckelberg, James M.

2013-01-01

We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee (n = 272) or hip (n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture (P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure. PMID:23658273

Effect of Sport Related Concussion on Clinically Measured Simple Reaction Time

PubMed Central

Eckner, James T.; Kutcher, Jeffrey S.; Broglio, Steven P.; Richardson, James K.

2013-01-01

Background Reaction time (RT) is a valuable component of the sport concussion assessment battery. RT is typically measured using computers running specialized software, which limits its applicability in some athletic settings and populations. To address this, we developed a simple clinical test of RT (RTclin) that involves grasping a falling measuring stick. Purpose To determine the effect of concussion on RTclin and its sensitivity and specificity for concussion. Materials and methods Concussed athletes (n=28) and non-concussed control teammates (n=28) completed RTclin assessments at baseline and within 48 hours of injury. Repeated measures ANOVA compared mean baseline and follow-up RTclin values between groups. Sensitivity and specificity were calculated over a range of reliable change confidence levels. Results RTclin differed significantly between groups (p < .001): there was significant prolongation from baseline to post-injury in the concussed group (p= .003), with a trend toward improvement in the control group (p = .058). Sensitivity and specificity were maximized when a critical change value of 0 ms was applied (i.e., any increase in RTclin from baseline was interpreted as abnormal), which corresponded to a sensitivity of 75%, specificity of 68%, and a 65% reliable change confidence level. Conclusions RTclin appears sensitive to the effects of concussion and distinguished concussed and non-concussed athletes with similar sensitivity and specificity to other commonly used concussion assessment tools. Given its simplicity, low cost, and minimal time requirement, RTclin should be considered a viable component of the sports medicine provider’s multifaceted concussion assessment battery. PMID:23314889

SISGR: Room Temperature Single-Molecule Detection and Imaging by Stimulated Emission Microscopy

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

Xie, Xiaoliang Sunney

Single-molecule spectroscopy has made considerable impact on many disciplines including chemistry, physics, and biology. To date, most single-molecule spectroscopy work is accomplished by detecting fluorescence. On the other hand, many naturally occurring chromophores, such as retinal, hemoglobin and cytochromes, do not have detectable fluorescence. There is an emerging need for single-molecule spectroscopy techniques that do not require fluorescence. In the last proposal period, we have successfully demonstrated stimulated emission microscopy, single molecule absorption, and stimulated Raman microscopy based on a high-frequency modulation transfer technique. These first-of-a- kind new spectroscopy/microscopy methods tremendously improved our ability to observe molecules that fluorescence weakly,more » even to the limit of single molecule detection for absorption measurement. All of these methods employ two laser beams: one (pump beam) excites a single molecule to a real or virtual excited state, and the other (probe beam) monitors the absorption/emission property of the single. We extract the intensity change of the probe beam with high sensitivity by implementing a high-frequency phase-sensitive detection scheme, which offers orders of magnitude improvement in detection sensitivity over direct absorption/emission measurement. However, single molecule detection based on fluorescence or absorption is fundamentally limited due to their broad spectral response. It is important to explore other avenues in single molecule detection and imaging which provides higher molecular specificity for studying a wide variety of heterogeneous chemical and biological systems. This proposal aimed to achieve single-molecule detection sensitivity with near resonance stimulated Raman scattering (SRS) microscopy. SRS microscopy was developed in our lab as a powerful technique for imaging heterogeneous samples based on their intrinsic vibrational contrasts, which provides much higher molecular specificity than absorption and fluorescence. Current sensitivity limit of SRS microscopy has not yet reached single molecule detection. We proposed to capitalize on our state-of-the-art SRS microscopy and develop near-resonance enhanced SRS for single molecule detection of carotenoids and heme proteins. The specific aims we pursued are: (1) building the next SRS generation microscope that utilizes near resonance enhancement to allow detection and imaging of single molecules with undetectable fluorescence, such as -carotene. (2) using near-resonance SRS as a contrast mechanism to study dye-sensitize semiconductor interface, elucidating the heterogeneous electron ejection kinetics with high spatial and temporal resolution. (3) studying the binding and unbinding of oxygen in single hemoglobin molecules in order to gain molecular level understanding of the long-standing issue of cooperativity. The new methods developed in the fund period of this grant have advanced the detection sensitivity in many aspects. Near-resonance SRS improved the signal by using shorter wavelengths for SRS microscopy. Frequency modulation and multi-color SRS target the reduction of background to improve the chemical specificity of SRS while maintaining the high imaging speed. Time-domain coherent Raman scattering microscopy targets to reduce the noise floor of coherent Raman microscopy. These methods have already demonstrated first-of-a-kind new applications in biology and medical research. However, we are still one order of magnitude away from single molecule limit. It is important to continue to improve the laser specification and develop new imaging methods to finally achieve label-free single molecule microscopy.« less

Impact of transition from microscopy to molecular screening for detection of intestinal protozoa in Dutch patients.

PubMed

Svraka-Latifovic, S; Bouter, S; Naus, H; Bakker, L J; Timmerman, C P; Dorigo-Zetsma, J W

2014-11-01

Detection of intestinal protozoa by PCR methods has been described as being sensitive and specific, and as improving the diagnostic yield. Here we present the outcome of the transition from microscopy to molecular screening for detection of a select group of intestinal protozoa in faeces in our laboratory. Introduction of molecular screening for intestinal protozoa resulted in higher sensitivity, reduced hands-on-time, reduced time-to-results, leading to improved diagnostic efficiency. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

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.

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

MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar.

PubMed

Jørstad, Melissa Davidsen; Marijani, Msafiri; Dyrhol-Riise, Anne Ma; Sviland, Lisbet; Mustafa, Tehmina

2018-01-01

Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

Accuracy of the volume-viscosity swallow test for clinical screening of oropharyngeal dysphagia and aspiration.

PubMed

Clavé, Pere; Arreola, Viridiana; Romea, Maise; Medina, Lucía; Palomera, Elisabet; Serra-Prat, Mateu

2008-12-01

To determine the accuracy of the bedside volume-viscosity swallow test (V-VST) for clinical screening of impaired safety and efficacy of deglutition. We studied 85 patients with dysphagia and 12 healthy subjects. Series of 5-20 mL nectar (295.02 mPa.s), liquid (21.61 mPa.s) and pudding (3682.21 mPa.s) bolus were administered during the V-VST and videofluoroscopy. Cough, fall in oxygen saturation > or =3%, and voice changes were considered signs of impaired safety, and piecemeal deglutition and oropharyngeal residue, signs of impaired efficacy. Videofluoroscopy showed patients had prolonged swallow response (> or =1064 ms); 52.1% had safe swallow at nectar, 32.9%, at liquid (p<0.05), and 80.6% at pudding viscosity (p<0.05); 29.4% had aspirations, and 45.8% oropharyngeal residue. The V-VST showed 83.7% sensitivity and 64.7% specificity for bolus penetration into the larynx and 100% sensitivity and 28.8% specificity for aspiration. Sensitivity of V-VST was 69.2% for residue, 88.4% for piecemeal deglutition, and 84.6% for identifying patients whose deglutition improved by enhancing bolus viscosity. Specificity was 80.6%, 87.5%, and 73.7%, respectively. The V-VST is a sensitive clinical method to identify patients with dysphagia at risk for respiratory and nutritional complications, and patients whose deglutition could be improved by enhancing bolus viscosity. Patients with a positive test should undergo videofluoroscopy.

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

PTP1B and SHP2 in POMC neurons reciprocally regulate energy balance in mice

PubMed Central

Banno, Ryoichi; Zimmer, Derek; De Jonghe, Bart C.; Atienza, Marybless; Rak, Kimberly; Yang, Wentian; Bence, Kendra K.

2010-01-01

Protein tyrosine phosphatase 1B (PTP1B) and SH2 domain–containing protein tyrosine phosphatase–2 (SHP2) have been shown in mice to regulate metabolism via the central nervous system, but the specific neurons mediating these effects are unknown. Here, we have shown that proopiomelanocortin (POMC) neuron–specific deficiency in PTP1B or SHP2 in mice results in reciprocal effects on weight gain, adiposity, and energy balance induced by high-fat diet. Mice with POMC neuron–specific deletion of the gene encoding PTP1B (referred to herein as POMC-Ptp1b–/– mice) had reduced adiposity, improved leptin sensitivity, and increased energy expenditure compared with wild-type mice, whereas mice with POMC neuron–specific deletion of the gene encoding SHP2 (referred to herein as POMC-Shp2–/– mice) had elevated adiposity, decreased leptin sensitivity, and reduced energy expenditure. POMC-Ptp1b–/– mice showed substantially improved glucose homeostasis on a high-fat diet, and hyperinsulinemic-euglycemic clamp studies revealed that insulin sensitivity in these mice was improved on a standard chow diet in the absence of any weight difference. In contrast, POMC-Shp2–/– mice displayed impaired glucose tolerance only secondary to their increased weight gain. Interestingly, hypothalamic Pomc mRNA and α–melanocyte-stimulating hormone (αMSH) peptide levels were markedly reduced in POMC-Shp2–/– mice. These studies implicate PTP1B and SHP2 as important components of POMC neuron regulation of energy balance and point to what we believe to be a novel role for SHP2 in the normal function of the melanocortin system. PMID:20160350

Highly sensitive detection of human papillomavirus type 16 DNA using time-resolved fluorescence microscopy and long lifetime probes

NASA Astrophysics Data System (ADS)

Wang, Xue F.; Periasamy, Ammasi; Wodnicki, Pawel; Siadat-Pajouh, M.; Herman, Brian

1995-04-01

We have been interested in the role of Human Papillomavirus (HPV) in cervical cancer and its diagnosis; to that end we have been developing microscopic imaging and fluorescent in situ hybridization (FISH) techniques to genotype and quantitate the amount of HPV present at a single cell level in cervical PAP smears. However, we have found that low levels of HPV DNA are difficult to detect accurately because theoretically obtainable sensitivity is never achieved due to nonspecific autofluorescence, fixative induced fluorescence of cells and tissues, and autofluorescence of the optical components in the microscopic system. In addition, the absorption stains used for PAP smears are intensely autofluorescent. Autofluorescence is a rapidly decaying process with lifetimes in the range of 1-100 nsec, whereas phosphorescence and delayed fluorescence have lifetimes in the range of 1 microsecond(s) ec-10 msec. The ability to discriminate between specific fluorescence and autofluorescence in the time-domain has improved the sensitivity of diagnostic test such that they perform comparably to, or even more sensitive than radioisotopic assays. We have developed a novel time-resolved fluorescence microscope to improve the sensitivity of detection of specific molecules of interest in slide based specimens. This time-resolved fluorescence microscope is based on our recently developed fluorescence lifetime imaging microscopy (FILM) in conjunction with the use of long lifetime fluorescent labels. By using fluorescence in situ hybridization and the long lifetime probe (europium), we have demonstrated the utility of this technique for detection of HPV DNA in cervicovaginal cells. Our results indicate that the use of time-resolved fluorescence microscopy and long lifetime probes increases the sensitivity of detection by removing autofluorescence and will thus lead to improved early diagnosis of cervical cancer. Since the highly sensitive detection of DNA in clinical samples using fluorescence in situ hybridization image is useful for the diagnosis of many other type of diseases, the system we have developed should find numerous applications for the diagnosis of disease states.

Development and deployment of a rapid recombinase polymerase amplification Ebola virus detection assay in Guinea in 2015.

PubMed

Faye, Oumar; Faye, Ousmane; Soropogui, Barré; Patel, Pranav; El Wahed, Ahmed Abd; Loucoubar, Cheikh; Fall, Gamou; Kiory, Davy; Magassouba, N'Faly; Keita, Sakoba; Kondé, Mandy Kader; Diallo, Alpha Amadou; Koivogui, Lamine; Karlberg, Helen; Mirazimi, Ali; Nentwich, Oliver; Piepenburg, Olaf; Niedrig, Matthias; Weidmann, Manfred; Sall, Amadou Alpha

2015-01-01

In the absence of a vaccine or specific treatments for Ebola virus disease (EVD), early identification of cases is crucial for the control of EVD epidemics. We evaluated a new extraction kit (SpeedXtract (SE), Qiagen) on sera and swabs in combination with an improved diagnostic reverse transcription recombinase polymerase amplification assay for the detection of Ebola virus (EBOV-RT-RPA). The performance of combined extraction and detection was best for swabs. Sensitivity and specificity of the combined SE and EBOV-RT-RPA were tested in a mobile laboratory consisting of a mobile glovebox and a Diagnostics-in-a-Suitcase powered by a battery and solar panel, deployed to Matoto Conakry, Guinea as part of the reinforced surveillance strategy in April 2015 to reach the goal of zero cases. The EBOV-RT-RPA was evaluated in comparison to two real-time PCR assays. Of 928 post-mortem swabs, 120 tested positive, and the combined SE and EBOV-RT-RPA yielded a sensitivity and specificity of 100% in reference to one real-time RT-PCR assay. Another widely used real-time RT-PCR was much less sensitive than expected. Results were provided very fast within 30 to 60 min, and the field deployment of the mobile laboratory helped improve burial management and community engagement.

Training improves interobserver reliability for the diagnosis of scaphoid fracture displacement.

PubMed

Buijze, Geert A; Guitton, Thierry G; van Dijk, C Niek; Ring, David

2012-07-01

The diagnosis of displacement in scaphoid fractures is notorious for poor interobserver reliability. We tested whether training can improve interobserver reliability and sensitivity, specificity, and accuracy for the diagnosis of scaphoid fracture displacement on radiographs and CT scans. Sixty-four orthopaedic surgeons rated a set of radiographs and CT scans of 10 displaced and 10 nondisplaced scaphoid fractures for the presence of displacement, using a web-based rating application. Before rating, observers were randomized to a training group (34 observers) and a nontraining group (30 observers). The training group received an online training module before the rating session, and the nontraining group did not. Interobserver reliability for training and nontraining was assessed by Siegel's multirater kappa and the Z-test was used to test for significance. There was a small, but significant difference in the interobserver reliability for displacement ratings in favor of the training group compared with the nontraining group. Ratings of radiographs and CT scans combined resulted in moderate agreement for both groups. The average sensitivity, specificity, and accuracy of diagnosing displacement of scaphoid fractures were, respectively, 83%, 85%, and 84% for the nontraining group and 87%, 86%, and 87% for the training group. Assuming a 5% prevalence of fracture displacement, the positive predictive value was 0.23 in the nontraining group and 0.25 in the training group. The negative predictive value was 0.99 in both groups. Our results suggest training can improve interobserver reliability and sensitivity, specificity and accuracy for the diagnosis of scaphoid fracture displacement, but the improvements are slight. These findings are encouraging for future research regarding interobserver variation and how to reduce it further.

Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis

PubMed Central

Bradley, Phelim; Gordon, N. Claire; Walker, Timothy M.; Dunn, Laura; Heys, Simon; Huang, Bill; Earle, Sarah; Pankhurst, Louise J.; Anson, Luke; de Cesare, Mariateresa; Piazza, Paolo; Votintseva, Antonina A.; Golubchik, Tanya; Wilson, Daniel J.; Wyllie, David H.; Diel, Roland; Niemann, Stefan; Feuerriegel, Silke; Kohl, Thomas A.; Ismail, Nazir; Omar, Shaheed V.; Smith, E. Grace; Buck, David; McVean, Gil; Walker, A. Sarah; Peto, Tim E. A.; Crook, Derrick W.; Iqbal, Zamin

2015-01-01

The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package (‘Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes. PMID:26686880

Evaluation of a novel chemical sensor system to detect clinical mastitis in bovine milk.

PubMed

Mottram, Toby; Rudnitskaya, Alisa; Legin, Andrey; Fitzpatrick, Julie L; Eckersall, P David

2007-05-15

Automatic detection of clinical mastitis is an essential part of high performance and robotic milking. Currently available technology (conductivity monitoring) is unable to achieve acceptable specificity or sensitivity of detection of clinical mastitis or other clinical diseases. Arrays of sensors with high cross-sensitivity have been successfully applied for recognition and quantitative analysis of other multicomponent liquids. An experiment was conducted to determine whether a multisensor system ("electronic tongue") based on an array of chemical sensors and suitable data processing could be used to discriminate between milk secretions from infected and healthy glands. Measurements were made with a multisensor system of milk samples from two different farms in two experiments. A total of 67 samples of milk from both mastitic and healthy glands were in two sets. It was demonstrated that the multisensor system could distinguish between control and clinically mastitic milk samples (p=0.05). The sensitivity and specificity of the sensor system (93 and 96% correspondingly) showed an improvement over conductivity (56 and 82% correspondingly). The multisensor system offers a novel method of improving mastitis detection.

Electronic Raman scattering as an ultra-sensitive probe of strain effects in semiconductors.

PubMed

Fluegel, Brian; Mialitsin, Aleksej V; Beaton, Daniel A; Reno, John L; Mascarenhas, Angelo

2015-05-28

Semiconductor strain engineering has become a critical feature of high-performance electronics because of the significant device performance enhancements that it enables. These improvements, which emerge from strain-induced modifications to the electronic band structure, necessitate new ultra-sensitive tools to probe the strain in semiconductors. Here, we demonstrate that minute amounts of strain in thin semiconductor epilayers can be measured using electronic Raman scattering. We applied this strain measurement technique to two different semiconductor alloy systems using coherently strained epitaxial thin films specifically designed to produce lattice-mismatch strains as small as 10(-4). Comparing our strain sensitivity and signal strength in Al(x)Ga(1-x)As with those obtained using the industry-standard technique of phonon Raman scattering, we found that there was a sensitivity improvement of 200-fold and a signal enhancement of 4 × 10(3), thus obviating key constraints in semiconductor strain metrology.

Electronic Raman scattering as an ultra-sensitive probe of strain effects in semiconductors

PubMed Central

Fluegel, Brian; Mialitsin, Aleksej V.; Beaton, Daniel A.; Reno, John L.; Mascarenhas, Angelo

2015-01-01

Semiconductor strain engineering has become a critical feature of high-performance electronics because of the significant device performance enhancements that it enables. These improvements, which emerge from strain-induced modifications to the electronic band structure, necessitate new ultra-sensitive tools to probe the strain in semiconductors. Here, we demonstrate that minute amounts of strain in thin semiconductor epilayers can be measured using electronic Raman scattering. We applied this strain measurement technique to two different semiconductor alloy systems using coherently strained epitaxial thin films specifically designed to produce lattice-mismatch strains as small as 10−4. Comparing our strain sensitivity and signal strength in AlxGa1−xAs with those obtained using the industry-standard technique of phonon Raman scattering, we found that there was a sensitivity improvement of 200-fold and a signal enhancement of 4 × 103, thus obviating key constraints in semiconductor strain metrology. PMID:26017853

Riboswitch-based sensor in low optical background

NASA Astrophysics Data System (ADS)

Harbaugh, Svetlana V.; Davidson, Molly E.; Chushak, Yaroslav G.; Kelley-Loughnane, Nancy; Stone, Morley O.

2008-08-01

Riboswitches are a type of natural genetic control element that use untranslated sequence in the RNA to recognize and bind to small molecules that regulate expression of that gene. Creation of synthetic riboswitches to novel ligands depends on the ability to screen for analyte binding sensitivity and specificity. In our work, we have coupled a synthetic riboswitch to an optical reporter assay based on fluorescence resonance energy transfer (FRET) between two genetically-coded fluorescent proteins. Specifically, a theophylline-sensitive riboswitch was placed upstream of the Tobacco Etch Virus (TEV) protease coding sequence, and a FRET-based construct, BFP-eGFP or eGFP-REACh, was linked by a peptide encoding the recognition sequence for TEV protease. Cells expressing the riboswitch showed a marked optical difference in fluorescence emission in the presence of theophylline. However, the BFP-eGFP FRET pair posses significant optical background that reduces the sensitivity of a FRET-based assay. To improve the optical assay, we designed a nonfluorescent yellow fluorescent protein (YFP) mutant called REACh (for Resonance Energy-Accepting Chromoprotein) as the FRET acceptor for eGFP. The advantage of using an eGFP-REACh pair is the elimination of acceptor fluorescence which leads to an improved detection of FRET via better signal-to-noise ratio. The EGFP-REACh fusion protein was constructed with the TEV protease cleavage site; thus upon TEV translation, cleavage occurs diminishing REACh quenching and increasing eGFP emission resulting in a 4.5-fold improvement in assay sensitivity.

Development and characterization of serotype-specific monoclonal antibodies against the dengue virus-4 (DENV-4) non-structural protein (NS1).

PubMed

Gelanew, Tesfaye; Hunsperger, Elizabeth

2018-02-06

Dengue, caused by one of the four serologically distinct dengue viruses (DENV-1 to - 4), is a mosquito-borne disease of serious global health significance. Reliable and cost-effective diagnostic tests, along with effective vaccines and vector-control strategies, are highly required to reduce dengue morbidity and mortality. Evaluation studies revealed that many commercially available NS1 antigen (Ag) tests have limited sensitivity to DENV-4 serotype compared to the other three serotypes. These studies indicated the need for development of new NS1 Ag detection test with improved sensitivity to DENV-4. An NS1 capture enzyme linked immunoassay (ELISA) specific to DENV-4 may improve the detection of DENV-4 cases worldwide. In addition, a serotype-specific NS1 Ag test identifies both DENV and the infecting serotype. In this study, we used a small-ubiquitin-like modifier (SUMO*) cloning vector to express a SUMO*-DENV-4 rNS1 fusion protein to develop NS1 DENV-4 specific monoclonal antibodies (MAbs). These newly developed MAbs were then optimized for use in an anti-NS1 DENV-4 capture ELISA. The serotype specificity and sensitivity of this ELISA was evaluated using (i) supernatants from DENV (1-4)-infected Vero cell cultures, (ii) rNS1s from all the four DENV (1-4) and, (iii) rNS1s of related flaviviruses (yellow fever virus; YFV and West Nile virus; WNV). From the evaluation studies of the newly developed MAbs, we identified three DENV-4 specific anti-NS1 MAbs: 3H7A9, 8A6F2 and 6D4B10. Two of these MAbs were optimal for use in a DENV-4 serotype-specific NS1 capture ELISA: MAb 8A6F2 as the capture antibody and 6D4B10 as a detection antibody. This ELISA was sensitive and specific to DENV-4 with no cross-reactivity to other three DENV (1-3) serotypes and other heterologous flaviviruses. Taken together these data indicated that our MAbs are useful reagents for the development of DENV-4 immunodiagnostic tests.

Prostate Specific Membrane Antigen Positron Emission Tomography May Improve the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging in Localized Prostate Cancer.

PubMed

Rhee, H; Thomas, P; Shepherd, B; Gustafson, S; Vela, I; Russell, P J; Nelson, C; Chung, E; Wood, G; Malone, G; Wood, S; Heathcote, P

2016-10-01

Positron emission tomography using ligands targeting prostate specific membrane antigen has recently been introduced. Positron emission tomography imaging with (68)Ga-PSMA-HBED-CC has been shown to detect metastatic prostate cancer lesions at a high rate. In this study we compare multiparametric magnetic resonance imaging and prostate specific membrane antigen positron emission tomography of the prostate with whole mount ex vivo prostate histopathology to determine the true sensitivity and specificity of these imaging modalities for detecting and locating tumor foci within the prostate. In a prospective clinical trial setting 20 patients with localized prostate cancer and a planned radical prostatectomy were recruited. All patients underwent multiparametric magnetic resonance imaging and positron emission tomography before surgery, and whole mount histopathology slides were directly compared to the images. European Society of Urogenital Radiology guidelines for reporting magnetic resonance imaging were used as a template for regional units of analysis. The uropathologist and radiologists were blinded to individual components of the study, and the final correlation was performed by visual and deformable registration analysis. A total of 50 clinically significant lesions were identified from the whole mount histopathological analysis. Based on regional analysis the sensitivity, specificity, positive predictive value and negative predictive value for multiparametric magnetic resonance imaging were 44%, 94%, 81% and 76%, respectively. With prostate specific membrane antigen positron emission tomography the sensitivity, specificity, positive predictive value and negative predictive value were 49%, 95%, 85% and 88%, respectively. Prostate specific membrane antigen positron emission tomography yielded a higher specificity and positive predictive value. A significant proportion of cancers are potentially missed and underestimated by both imaging modalities. Prostate specific membrane antigen positron emission tomography may be used in addition to multiparametric magnetic resonance imaging to help improve local staging in those patients undergoing retropubic radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity.

PubMed

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-29

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity

NASA Astrophysics Data System (ADS)

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-01

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Multi-test cervical cancer diagnosis with missing data estimation

NASA Astrophysics Data System (ADS)

Xu, Tao; Huang, Xiaolei; Kim, Edward; Long, L. Rodney; Antani, Sameer

2015-03-01

Cervical cancer is a leading most common type of cancer for women worldwide. Existing screening programs for cervical cancer suffer from low sensitivity. Using images of the cervix (cervigrams) as an aid in detecting pre-cancerous changes to the cervix has good potential to improve sensitivity and help reduce the number of cervical cancer cases. In this paper, we present a method that utilizes multi-modality information extracted from multiple tests of a patient's visit to classify the patient visit to be either low-risk or high-risk. Our algorithm integrates image features and text features to make a diagnosis. We also present two strategies to estimate the missing values in text features: Image Classifier Supervised Mean Imputation (ICSMI) and Image Classifier Supervised Linear Interpolation (ICSLI). We evaluate our method on a large medical dataset and compare it with several alternative approaches. The results show that the proposed method with ICSLI strategy achieves the best result of 83.03% specificity and 76.36% sensitivity. When higher specificity is desired, our method can achieve 90% specificity with 62.12% sensitivity.

MOF-Sensitized Solar Cells Enabled by a Pillared Porphyrin Framework

DOE PAGES

Spoerke, Erik D.; Small, Leo J.; Foster, Michael E.; ...

2017-03-01

Metal–organic frameworks (MOFs) are highly ordered, functionally tunable supramolecular materials with the potential to improve dye-sensitized solar cells (DSSCs). Several recent reports have indicated that photocurrent can be generated in Grätzel-type DSSC devices when MOFs are used as the sensitizer. However, the specific role(s) of the incorporated MOFs and the potential influence of residual MOF precursor species on device performance are unclear. Herein, we describe the assembly and characterization of a simplified DSSC platform in which isolated MOF crystals are used as the sensitizer in a planar device architecture. We selected a pillared porphyrin framework (PPF) as the MOF sensitizer,more » taking particular care to avoid contamination from light-absorbing MOF precursors. Photovoltaic and electrochemical characterization under simulated 1-sun and wavelength-selective illumination revealed photocurrent generation that is clearly ascribable to the PPF MOF. In conclusion, continued refinement of highly versatile MOF structure and chemistry holds promise for dramatic improvements in emerging photovoltaic technologies.« less

Mechanical design optimization of a single-axis MOEMS accelerometer based on a grating interferometry cavity for ultrahigh sensitivity

NASA Astrophysics Data System (ADS)

Lu, Qianbo; Bai, Jian; Wang, Kaiwei; Lou, Shuqi; Jiao, Xufen; Han, Dandan; Yang, Guoguang

2016-08-01

The ultrahigh static displacement-acceleration sensitivity of a mechanical sensing chip is essential primarily for an ultrasensitive accelerometer. In this paper, an optimal design to implement to a single-axis MOEMS accelerometer consisting of a grating interferometry cavity and a micromachined sensing chip is presented. The micromachined sensing chip is composed of a proof mass along with its mechanical cantilever suspension and substrate. The dimensional parameters of the sensing chip, including the length, width, thickness and position of the cantilevers are evaluated and optimized both analytically and by finite-element-method (FEM) simulation to yield an unprecedented acceleration-displacement sensitivity. Compared with one of the most sensitive single-axis MOEMS accelerometers reported in the literature, the optimal mechanical design can yield a profound sensitivity improvement with an equal footprint area, specifically, 200% improvement in displacement-acceleration sensitivity with moderate resonant frequency and dynamic range. The modified design was microfabricated, packaged with the grating interferometry cavity and tested. The experimental results demonstrate that the MOEMS accelerometer with modified design can achieve the acceleration-displacement sensitivity of about 150μm/g and acceleration sensitivity of greater than 1500V/g, which validates the effectiveness of the optimal design.

Refining the Assessment of Hopelessness: An Improved Way to Look to the Future

ERIC Educational Resources Information Center

Fisher, Lauren B.; Overholser, James C.

2013-01-01

Despite its high sensitivity, the Beck Hopelessness Scale (BHS) has demonstrated low specificity, has an ambiguous factor structure, and includes inadequate items. The current study examined the psychometric properties of a modified BHS (mBHS) using a Likert scale format that would allow for improved reliability, validity, and clinical utility.…

Rotator cuff crepitus: could Codman really feel a cuff tear?

PubMed

Ponce, Brent A; Kundukulam, Joseph A; Sheppard, Evan D; Determann, Jason R; McGwin, Gerald; Narducci, Carl A; Crowther, Marshall J

2014-07-01

The objective of this study was to assess the accuracy of palpating crepitus to diagnose rotator cuff tears. Seventy consecutive consenting patients who presented with shoulder pain and no previous imaging or surgery on the affected shoulder were prospectively enrolled during a 10-month period. A standardized patient history and examination, including the crepitus test, were recorded in addition to obtaining standard radiographs. Additional imaging after initial evaluation was performed with magnetic resonance imaging and interpreted by a musculoskeletal radiologist blinded to the examination findings. Statistical analysis was used to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the crepitus test in the clinical diagnosis of a rotator cuff tear. Sixty-three patients had histories, examinations, and imaging studies available for analysis. The crepitus test had a sensitivity of 67%, specificity of 80%, PPV of 91%, and NPV of 43% for all types of rotator cuff tears. The sensitivity and specificity for full-thickness or high-grade partial tears was 82% and 73%, respectively; the PPV and NPV were 77% and 79%. Increasing age improved accuracy as the presence of crepitus in patients older than 55 years had a sensitivity of 76%, specificity of 100%, PPV of 100%, and NPV of 38%. The crepitus test has a favorable sensitivity, specificity, PPV, and NPV to assess the integrity of the rotator cuff and may be a useful examination in the clinical diagnosis of a rotator cuff tear. Published by Mosby, Inc.

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.

Cognitive Screening in Brain Tumors: Short but Sensitive Enough?

PubMed Central

Robinson, Gail A.; Biggs, Vivien; Walker, David G.

2015-01-01

Cognitive deficits in brain tumors are generally thought to be relatively mild and non-specific, although recent evidence challenges this notion. One possibility is that cognitive screening tools are being used to assess cognitive functions but their sensitivity to detect cognitive impairment may be limited. For improved sensitivity to recognize mild and/or focal cognitive deficits in brain tumors, neuropsychological evaluation tailored to detect specific impairments has been thought crucial. This study investigates the sensitivity of a cognitive screening tool, the Montreal Cognitive Assessment (MoCA), compared to a brief but tailored cognitive assessment (CA) for identifying cognitive deficits in an unselected primary brain tumor sample (i.e., low/high-grade gliomas, meningiomas). Performance is compared on broad measures of impairment: (a) number of patients impaired on the global screening measure or in any cognitive domain; and (b) number of cognitive domains impaired and specific analyses of MoCA-Intact and MoCA-Impaired patients on specific cognitive tests. The MoCA-Impaired group obtained lower naming and word fluency scores than the MoCA-Intact group, but otherwise performed comparably on cognitive tests. Overall, based on our results from patients with brain tumor, the MoCA has extremely poor sensitivity for detecting cognitive impairments and a brief but tailored CA is necessary. These findings will be discussed in relation to broader issues for clinical management and planning, as well as specific considerations for neuropsychological assessment of brain tumor patients. PMID:25815273

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

PubMed

Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

2012-09-01

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Evaluation of SYBR green I based visual loop-mediated isothermal amplification (LAMP) assay for genus and species-specific diagnosis of malaria in P. vivax and P. falciparum endemic regions.

PubMed

Singh, Ruchi; Singh, Dhirendra Pratap; Savargaonkar, Deepali; Singh, Om P; Bhatt, Rajendra M; Valecha, Neena

2017-01-01

Loop-mediated isothermal amplification (LAMP) is an emerging nucleic acid based diag- nostic approach that is easily adaptable to the field settings with limited technical resources. This study was aimed to evaluate the LAMP assay for the detection and identification of Plasmodium falciparum and P. vivax infection in malaria suspected cases using genus and species-specific assay. The 18S rRNA-based LAMP assay was evaluated for diagnosis of genus Plasmodium, and species- specific diagnosis of P. falciparum and P. vivax, infection employing 317 malaria suspected cases, and the results were compared with those obtained by 18S nested PCR (n-PCR). All the samples were confirmed by microscopy for the presence of Plasmodium parasite. The n-PCR was positive in all Plasmodium-infected cases (n=257; P. falciparum=133; P. vivax=124) and negative in microscopy negative cases (n=58) except for two cases which were positive for P. vivax, giving a sen- sitivity of 100% (95% CI: 97.04-100%) and a specificity of 100% (95% CI: 88.45-99.5%). Genus-specific LAMP assay missed 11 (3.2%) microscopy and n-PCR confirmed vivax malaria cases. Considering PCR results as a refer- ence, LAMP was 100% sensitive and specific for P. falciparum, whereas it exhibited 95.16% sensitivity and 96.7% specificity for P. vivax. The n-PCR assay detected 10 mixed infection cases while species-specific LAMP detected five mixed infection cases of P. vivax and P. falciparum, which were not detected by microscopy. Genus-specific LAMP assay displayed low sensitivity. Falciparum specific LAMP assay displayed high sensitivity whereas vivax specific LAMP assay displayed low sensitivity. Failed detection of vivax cases otherwise confirmed by the n-PCR assay indicates exploitation of new targets and improved detection methods to attain 100% results for P. vivax detection.

Molecular Detection and Species-Specific Identification of Medically Important Aspergillus Species by Real-Time PCR in Experimental Invasive Pulmonary Aspergillosis ▿

PubMed Central

Walsh, Thomas J.; Wissel, Mark C.; Grantham, Kevin J.; Petraitiene, Ruta; Petraitis, Vidmantas; Kasai, Miki; Francesconi, Andrea; Cotton, Margaret P.; Hughes, Johanna E.; Greene, Lora; Bacher, John D.; Manna, Pradip; Salomoni, Martin; Kleiboeker, Steven B.; Reddy, Sushruth K.

2011-01-01

Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species. A set of real-time qPCR primers and probes was developed by utilizing unique ITS1 regions for genus- and species-specific detection of the four most common medically important Aspergillus species (Aspergillus fumigatus, A. flavus, A. niger, and A. terreus). Pan-Aspergillus and species-specific qPCRs with BAL fluid were more sensitive than culture for detection of IPA caused by A. fumigatus in untreated (P < 0.0007) and treated (P ≤ 0.008) animals, respectively. For infections caused by A. terreus and A. niger, culture and PCR amplification from BAL fluid yielded similar sensitivities for untreated and treated animals. Pan-Aspergillus PCR was more sensitive than culture for detection of A. flavus in treated animals (P = 0.002). BAL fluid pan-Aspergillus and species-specific PCRs were comparable in sensitivity to BAL fluid galactomannan (GM) assay. The copy numbers from the qPCR assays correlated with quantitative cultures to determine the pulmonary residual fungal burdens in lung tissue. Pan-Aspergillus and species-specific qPCR assays may improve the rapid and accurate identification of IPA in immunocompromised patients. PMID:21976757

Grading Dysphagia as a Toxicity of Head and Neck Cancer: Differences in Severity Classification Based on MBS DIGEST and Clinical CTCAE Grades.

PubMed

Goepfert, Ryan P; Lewin, Jan S; Barrow, Martha P; Warneke, Carla L; Fuller, Clifton D; Lai, Stephen Y; Weber, Randal S; Hutcheson, Katherine A

2018-04-01

Clinician-reported toxicity grading through common terminology criteria for adverse events (CTCAE) stages dysphagia based on symptoms, diet, and tube dependence. The new dynamic imaging grade of swallowing toxicity (DIGEST) tool offers a similarly scaled five-point ordinal summary grade of pharyngeal swallowing as determined through results of a modified barium swallow (MBS) study. This study aims to inform clinicians on the similarities and differences between dysphagia severity according to clinical CTCAE and MBS-derived DIGEST grading. A cross-sectional sample of 95 MBS studies was randomly selected from a prospectively-acquired MBS database among patients treated with organ preservation strategies for head and neck cancer. MBS DIGEST and clinical CTCAE dysphagia grades were compared. DIGEST and CTCAE dysphagia grades had "fair" agreement per weighted κ of 0.358 (95% CI .231-.485). Using a threshold of DIGEST ≥ 3 as reference, CTCAE had an overall sensitivity of 0.50, specificity of 0.84, and area under the curve (AUC) of 0.67 to identify severe MBS-detected dysphagia. At less than 6 months, sensitivity was 0.72, specificity was 0.76, and AUC was 0.75 while at greater than 6 months, sensitivity was 0.22, specificity was 0.90, and AUC was 0.56 for CTCAE to detect dysphagia as determined by DIGEST. Classification of pharyngeal dysphagia on MBS using DIGEST augments our understanding of dysphagia severity according to the clinically-derived CTCAE while maintaining the simplicity of an ordinal scale. DIGEST likely complements CTCAE toxicity grading through improved specificity for physiologic dysphagia in the acute phase and improved sensitivity for dysphagia in the late-phase.

Improved Automated Detection of Diabetic Retinopathy on a Publicly Available Dataset Through Integration of Deep Learning.

PubMed

Abràmoff, Michael David; Lou, Yiyue; Erginay, Ali; Clarida, Warren; Amelon, Ryan; Folk, James C; Niemeijer, Meindert

2016-10-01

To compare performance of a deep-learning enhanced algorithm for automated detection of diabetic retinopathy (DR), to the previously published performance of that algorithm, the Iowa Detection Program (IDP)-without deep learning components-on the same publicly available set of fundus images and previously reported consensus reference standard set, by three US Board certified retinal specialists. We used the previously reported consensus reference standard of referable DR (rDR), defined as International Clinical Classification of Diabetic Retinopathy moderate, severe nonproliferative (NPDR), proliferative DR, and/or macular edema (ME). Neither Messidor-2 images, nor the three retinal specialists setting the Messidor-2 reference standard were used for training IDx-DR version X2.1. Sensitivity, specificity, negative predictive value, area under the curve (AUC), and their confidence intervals (CIs) were calculated. Sensitivity was 96.8% (95% CI: 93.3%-98.8%), specificity was 87.0% (95% CI: 84.2%-89.4%), with 6/874 false negatives, resulting in a negative predictive value of 99.0% (95% CI: 97.8%-99.6%). No cases of severe NPDR, PDR, or ME were missed. The AUC was 0.980 (95% CI: 0.968-0.992). Sensitivity was not statistically different from published IDP sensitivity, which had a CI of 94.4% to 99.3%, but specificity was significantly better than the published IDP specificity CI of 55.7% to 63.0%. A deep-learning enhanced algorithm for the automated detection of DR, achieves significantly better performance than a previously reported, otherwise essentially identical, algorithm that does not employ deep learning. Deep learning enhanced algorithms have the potential to improve the efficiency of DR screening, and thereby to prevent visual loss and blindness from this devastating disease.

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.

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

Nielsen, Yousef W., E-mail: yujwni01@heh.regionh.d; Eiberg, Jonas P.; Logager, Vibeke B.

The purpose of this investigation was to determine if addition of infragenicular steady-state (SS) magnetic resonance angiography (MRA) to first-pass imaging improves diagnostic performance compared with first-pass imaging alone in patients with peripheral arterial disease (PAD) undergoing whole-body (WB) MRA. Twenty consecutive patients with PAD referred to digital-subtraction angiography (DSA) underwent WB-MRA. Using a bolus-chase technique, first-pass WB-MRA was performed from the supra-aortic vessels to the ankles. The blood-pool contrast agent gadofosveset trisodium was used at a dose of 0.03 mmol/kg body weight. Ten minutes after injection of the contrast agent, high-resolution (0.7-mm isotropic voxels) SS-MRA of the infragenicular arteriesmore » was performed. Using DSA as the 'gold standard,' sensitivities and specificities for detecting significant arterial stenoses ({>=}50% luminal narrowing) with first-pass WB-MRA, SS-MRA, and combined first-pass and SS-MRA were calculated. Kappa statistics were used to determine intermodality agreement between MRA and DSA. Overall sensitivity and specificity for detecting significant arterial stenoses with first-pass WB-MRA was 0.70 (95% confidence interval 0.61 to 0.78) and 0.97 (0.94 to 0.99), respectively. In first-pass WB-MRA, the lowest sensitivity was in the infragenicular region, with a value of 0.42 (0.23 to 0.63). Combined analysis of first-pass WB-MRA and SS-MRA increased sensitivity to 0.81 (0.60 to 0.93) in the infragenicular region, with specificity of 0.94 (0.88 to 0.97). Sensitivity and specificity for detecting significant arterial stenoses with isolated infragenicular SS-MRA was 0.47 (0.27 to 0.69) and 0.86 (0.78 to 0.91), respectively. Intermodality agreement between MRA and DSA in the infragenicular region was moderate for first-pass WB-MRA ({kappa} = 0.49), fair for SS-MRA ({kappa} = 0.31), and good for combined first-pass/SS-MRA ({kappa} = 0.71). Addition of infragenicular SS-MRA to first-pass WB MRA improves diagnostic performance.« less

Reliable change of the sensory organization test.

PubMed

Broglio, Steven P; Ferrara, Michael S; Sopiarz, Kay; Kelly, Michael S

2008-03-01

To establish the sensitivity and specificity of the NeuroCom Sensory Organization Test (SOT) and provide practitioners with cut-scores for clinical decision making using estimates of reliable change. Retrospective cohort study. Research laboratory. Healthy (n = 66) and concussed (n = 63) young adult participants. Postural control assessments on the NeuroCom SOT were completed twice (baseline and follow-up) for both groups. Postconcussion assessments were administered within 24 hours of injury diagnosis. The reliable change technique was used to calculated cut-scores for each SOT variable (composite balance; somatosensory, visual, and vestibular ratios) at the 95%, 90%, 85%, 80%, 75%, and 70% confidence interval levels. When cut-scores were applied to the post-concussion evaluations, sensitivity and specificity varied with SOT variable and confidence interval. An evaluation for change on one or more SOT variable resulted in the highest combined sensitivity (57%) and specificity (80%) at the 75% confidence interval. Use of reliable change scores to detect significant changes in performance on the SOT resulted in decreased sensitivity and improved specificity compared to a previous report. These findings indicate that some concussed athletes may not show large changes in postconcussion postural control and this postural control evaluation should not be used in exclusion of other assessment techniques. The postural control assessment should be combined with other evaluative measures to gain the highest sensitivity to concussive injuries.

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.

Sensitivity enhancement in swept-source optical coherence tomography by parametric balanced detector and amplifier

PubMed Central

Kang, Jiqiang; Wei, Xiaoming; Li, Bowen; Wang, Xie; Yu, Luoqin; Tan, Sisi; Jinata, Chandra; Wong, Kenneth K. Y.

2016-01-01

We proposed a sensitivity enhancement method of the interference-based signal detection approach and applied it on a swept-source optical coherence tomography (SS-OCT) system through all-fiber optical parametric amplifier (FOPA) and parametric balanced detector (BD). The parametric BD was realized by combining the signal and phase conjugated idler band that was newly-generated through FOPA, and specifically by superimposing these two bands at a photodetector. The sensitivity enhancement by FOPA and parametric BD in SS-OCT were demonstrated experimentally. The results show that SS-OCT with FOPA and SS-OCT with parametric BD can provide more than 9 dB and 12 dB sensitivity improvement, respectively, when compared with the conventional SS-OCT in a spectral bandwidth spanning over 76 nm. To further verify and elaborate their sensitivity enhancement, a bio-sample imaging experiment was conducted on loach eyes by conventional SS-OCT setup, SS-OCT with FOPA and parametric BD at different illumination power levels. All these results proved that using FOPA and parametric BD could improve the sensitivity significantly in SS-OCT systems. PMID:27446655

Combination Testing Using a Single MSH5 Variant alongside HLA Haplotypes Improves the Sensitivity of Predicting Coeliac Disease Risk in the Polish Population.

PubMed

Paziewska, Agnieszka; Cukrowska, Bozena; Dabrowska, Michalina; Goryca, Krzysztof; Piatkowska, Magdalena; Kluska, Anna; Mikula, Michal; Karczmarski, Jakub; Oralewska, Beata; Rybak, Anna; Socha, Jerzy; Balabas, Aneta; Zeber-Lubecka, Natalia; Ambrozkiewicz, Filip; Konopka, Ewa; Trojanowska, Ilona; Zagroba, Malgorzata; Szperl, Malgorzata; Ostrowski, Jerzy

2015-01-01

Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing.

Design of a Physiology-Sensitive VR-Based Social Communication Platform for Children With Autism.

PubMed

Kuriakose, Selvia; Lahiri, Uttama

2017-08-01

Individuals with autism are often characterized by impairments in communication, reciprocal social interaction and explicit expression of their affective states. In conventional techniques, a therapist adjusts the intervention paradigm by monitoring the affective state e.g., anxiety of these individuals for effective floor-time-therapy. Conventional techniques, though powerful, are observation-based and face resource limitations. Technology-assisted systems can provide a quantitative, individualized rehabilitation platform. Presently-available systems are designed primarily to chain learning via aspects of one's performance alone restricting individualization. Specifically, these systems are not sensitive to one's anxiety. Our presented work seeks to bridge this gap by developing a novel VR-based interactive system with Anxiety-Sensitive adaptive technology. Specifically, such a system is capable of objectively identifying and quantifying one's anxiety level from real-time biomarkers, along with performance metrics. In turn it can adaptively respond in an individualized manner to foster improved social communication skills. In our present research, we have used Virtual Reality (VR) to design a proof-of-concept application that exposes participants to social tasks of varying challenges. Results of a preliminary usability study indicate the potential of our VR-based Anxiety-Sensitive system to foster improved task performance, thereby serving as a potent complementary tool in the hands of therapist.

HPAEC-PAD for oligosaccharide analysis-novel insights into analyte sensitivity and response stability.

PubMed

Mechelke, Matthias; Herlet, Jonathan; Benz, J Philipp; Schwarz, Wolfgang H; Zverlov, Vladimir V; Liebl, Wolfgang; Kornberger, Petra

2017-12-01

The rising importance of accurately detecting oligosaccharides in biomass hydrolyzates or as ingredients in food, such as in beverages and infant milk products, demands for the availability of tools to sensitively analyze the broad range of available oligosaccharides. Over the last decades, HPAEC-PAD has been developed into one of the major technologies for this task and represents a popular alternative to state-of-the-art LC-MS oligosaccharide analysis. This work presents the first comprehensive study which gives an overview of the separation of 38 analytes as well as enzymatic hydrolyzates of six different polysaccharides focusing on oligosaccharides. The high sensitivity of the PAD comes at cost of its stability due to recession of the gold electrode. By an in-depth analysis of the sensitivity drop over time for 35 analytes, including xylo- (XOS), arabinoxylo- (AXOS), laminari- (LOS), manno- (MOS), glucomanno- (GMOS), and cellooligosaccharides (COS), we developed an analyte-specific one-phase decay model for this effect over time. Using this model resulted in significantly improved data normalization when using an internal standard. Our results thereby allow a quantification approach which takes the inevitable and analyte-specific PAD response drop into account. Graphical abstract HPAEC-PAD analysis of oligosaccharides and determination of PAD response drop leading to an improved data normalization.

Improvement of the cost-benefit analysis algorithm for high-rise construction projects

NASA Astrophysics Data System (ADS)

Gafurov, Andrey; Skotarenko, Oksana; Plotnikov, Vladimir

2018-03-01

The specific nature of high-rise investment projects entailing long-term construction, high risks, etc. implies a need to improve the standard algorithm of cost-benefit analysis. An improved algorithm is described in the article. For development of the improved algorithm of cost-benefit analysis for high-rise construction projects, the following methods were used: weighted average cost of capital, dynamic cost-benefit analysis of investment projects, risk mapping, scenario analysis, sensitivity analysis of critical ratios, etc. This comprehensive approach helped to adapt the original algorithm to feasibility objectives in high-rise construction. The authors put together the algorithm of cost-benefit analysis for high-rise construction projects on the basis of risk mapping and sensitivity analysis of critical ratios. The suggested project risk management algorithms greatly expand the standard algorithm of cost-benefit analysis in investment projects, namely: the "Project analysis scenario" flowchart, improving quality and reliability of forecasting reports in investment projects; the main stages of cash flow adjustment based on risk mapping for better cost-benefit project analysis provided the broad range of risks in high-rise construction; analysis of dynamic cost-benefit values considering project sensitivity to crucial variables, improving flexibility in implementation of high-rise projects.

Sensitivity and specificity of mammographic screening as practised in Vermont and Norway

PubMed Central

Hofvind, S; Geller, B M; Skelly, J; Vacek, P M

2012-01-01

Objective The aim of this study was to examine the sensitivity and specificity of screening mammography as performed in Vermont, USA, and Norway. Methods Incident screening data from 1997 to 2003 for female patients aged 50–69 years from the Vermont Breast Cancer Surveillance System (116 996 subsequent screening examinations) and the Norwegian Breast Cancer Screening Program (360 872 subsequent screening examinations) were compared. Sensitivity and specificity estimates for the initial (based on screening mammogram only) and final (screening mammogram plus any further diagnostic imaging) interpretations were directly adjusted for age using 5-year age intervals for the combined Vermont and Norway population, and computed for 1 and 2 years of follow-up, which ended at the time of the next screening mammogram. Results For the 1-year follow-up, sensitivities for initial assessments were 82.0%, 88.2% and 92.5% for 1-, 2- and >2-year screening intervals, respectively, in Vermont (p=0.022). For final assessments, the values were 73.6%, 83.3% and 81.2% (p=0.047), respectively. For Norway, sensitivities for initial assessments were 91.0% and 91.3% (p=0.529) for 2- and >2-year intervals, and 90.7% and 91.3%, respectively, for final assessments (p=0.630). Specificity was lower in Vermont than in Norway for each screening interval and for all screening intervals combined, for both initial (90.6% vs 97.8% for all intervals; p<0.001) and final (98.8% vs 99.5% for all intervals; p<0.001) assessments. Conclusion Our study showed higher sensitivity and specificity in a biennial screening programme with an independent double reading than in a predominantly annual screening program with a single reading. Advances in knowledge This study demonstrates that higher recall rates and lower specificity are not always associated with higher sensitivity of screening mammography. Differences in the screening processes in Norway and Vermont suggest potential areas for improvement in the latter. PMID:22993383

Organic electrochemical transistor based immunosensor for prostate specific antigen (PSA) detection using gold nanoparticles for signal amplification.

PubMed

Kim, Duck-Jin; Lee, Nae-Eung; Park, Joon-Shik; Park, In-Jun; Kim, Jung-Gu; Cho, Hyoung J

2010-07-15

We demonstrated a highly sensitive organic electrochemical transistor (OECT) based immunosensor with a low detection limit for prostate specific antigen/alpha1-antichymotrypsin (PSA-ACT) complex. The poly(styrenesulfonate) doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) based OECT with secondary antibody conjugated gold nanoparticles (AuNPs) provided a detection limit of the PSA-ACT complex as low as 1pg/ml, as well as improved sensitivity and a dynamic range, due to the role of AuNPs in the signal amplification. The sensor performances were particularly improved in the lower concentration range where the detection is clinically important for the preoperative diagnosis and screening of prostate cancer. This result shows that the OECT-based immunosensor can be used as a transducer platform acceptable to the point-of-care (POC) diagnostic systems and demonstrates adaptability of organic electronics to clinical applications. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Green light may improve diagnostic accuracy of nailfold capillaroscopy with a simple digital videomicroscope.

PubMed

Weekenstroo, Harm H A; Cornelissen, Bart M W; Bernelot Moens, Hein J

2015-06-01

Nailfold capillaroscopy is a non-invasive and safe technique for the analysis of microangiopathologies. Imaging quality of widely used simple videomicroscopes is poor. The use of green illumination instead of the commonly used white light may improve contrast. The aim of the study was to compare the effect of green illumination with white illumination, regarding capillary density, the number of microangiopathologies, and sensitivity and specificity for systemic sclerosis. Five rheumatologists have evaluated 80 images; 40 images acquired with green light, and 40 images acquired with white light. A larger number of microangiopathologies were found in images acquired with green light than in images acquired with white light. This results in slightly higher sensitivity with green light in comparison with white light, without reducing the specificity. These findings suggest that green instead of white illumination may facilitate evaluation of capillaroscopic images obtained with a low-cost digital videomicroscope.

Tiered application of the neutral red release and EpiOcular™ assays for evaluating the eye irritation potential of agrochemical formulations.

PubMed

Settivari, Raja S; Amado, Ricardo Acosta; Corvaro, Marco; Visconti, Nicolo R; Kan, Lynn; Carney, Edward W; Boverhof, Darrell R; Gehen, Sean C

2016-11-01

Agrochemical formulations have been underrepresented in validation efforts for implementing alternative eye irritation approaches but represent a significant opportunity to reduce animal testing. This study assesses the utility of the neutral red release assay (NRR) and EpiOcular™ assay (EO) for predicting the eye irritation potential of 64 agrochemical formulations relative to Draize data. In the NRR, formulations with an NRR50 value ≤ 50 mg/mL were categorized as UN GHS Cat 1 and those >250 mg/mL were classified as UN GHS Non Classified (NC). The accuracy, sensitivity, and specificity were 78, 85 and 76% and 73, 85 and 61% for identifying UN GHS 1 and NC formulations, respectively. Specificity was poor for formulations with NRR50 > 50 to ≤250 mg/mL. The EO (ET-40 method) was explored to differentiate formulations that were UN GHS 1/2 and UN GHS NC. The EO resulted in accuracy, sensitivity, and specificity of 65%, 58% and 75% for identifying UN GHS NC formulations. To improve the overall performance, the assays were implemented using a tiered-approach where the NRR was run as a first-tier followed by the EO. The tiered-approach resulted in improved accuracy (75%) and balanced sensitivity (73%) and specificity (77%) for distinguishing between irritating and non-irritating agrochemical formulations. Copyright © 2016 Elsevier Inc. All rights reserved.

Post-Servicing Mission 4 Flux Calibration of the STIS Echelle Modes

NASA Astrophysics Data System (ADS)

Azalee Bostroem, K.; Aloisi, A.; Proffitt, C.; Osten, R.; Bohlin, R.

2011-01-01

STIS echelle modes show a wavelength-dependent decline in sensitivity with time. While this trend is observed in all STIS spectroscopic modes, the echelle sensitivity is further affected by a time-dependent shift in the blaze function. To improve the echelle flux calibration, new baselines for the echelle sensitivities are derived from post-Servicing Mission 4 (SM4) observations of the Hubble Space Telescope standard star G191-B2B. We present how these baseline sensitivities compare to pre-failure trends. Specifically, where the new results differ from expectations and discuss anomalous results found in E140H monitoring observations are highlighted.

Adaptive controller for volumetric display of neuroimaging studies

NASA Astrophysics Data System (ADS)

Bleiberg, Ben; Senseney, Justin; Caban, Jesus

2014-03-01

Volumetric display of medical images is an increasingly relevant method for examining an imaging acquisition as the prevalence of thin-slice imaging increases in clinical studies. Current mouse and keyboard implementations for volumetric control provide neither the sensitivity nor specificity required to manipulate a volumetric display for efficient reading in a clinical setting. Solutions to efficient volumetric manipulation provide more sensitivity by removing the binary nature of actions controlled by keyboard clicks, but specificity is lost because a single action may change display in several directions. When specificity is then further addressed by re-implementing hardware binary functions through the introduction of mode control, the result is a cumbersome interface that fails to achieve the revolutionary benefit required for adoption of a new technology. We address the specificity versus sensitivity problem of volumetric interfaces by providing adaptive positional awareness to the volumetric control device by manipulating communication between hardware driver and existing software methods for volumetric display of medical images. This creates a tethered effect for volumetric display, providing a smooth interface that improves on existing hardware approaches to volumetric scene manipulation.

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.

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

Definition of improvement in juvenile idiopathic arthritis using the juvenile arthritis disease activity score.

PubMed

Horneff, Gerd; Becker, Ingrid

2014-07-01

The aim of this study was to define improvement thresholds for the Juvenile Arthritis Disease Activity Score (JADAS). Physicians' and parents' judgements on treatment efficacy, the ACR paediatric response measure (PedACR) and JADAS were extracted from BIKER. Patients were categorized by baseline classes in the 10-joint JADAS (JADAS10) as low (5 to <15), moderate (15 to <25) and high (25 to ≤40). Cut-offs for defining improvement following treatment with biologics or MTX were chosen by calculating the interquartile ranges (IQRs) of the judgement groups and considering the accuracy, sensitivity and specificity of the resulting model. Differences in the change of JADAS10 by JIA category were also analysed by analysis of variance (ANOVA). Sensitivity, specificity and accuracy were calculated. A total of 1315 treatment courses were analysed. The ANOVA of the JIA categories showed no significant differences of the mean JADAS10 in all baseline classes and IQRs also showed good overall limits. Therefore all JIA categories were combined for a collective cut-off. Analysis by baseline class revealed clear cut-off points. Improvement could be defined by the minimal decrease in the JADAS10 in baseline class low by 4 (41%), moderate by 10 (53%) and high by 17 (57%). The model shows values for accuracy from 75.6 to 85.5% and comparable values for sensitivity and specificity. Improvement after 3 months can be defined efficiently by the decrease of the JADAS10, depending on the baseline JADAS10 score, which specifies low, moderate or high disease activity. Our model demonstrates clear cut-off values. The JADAS10 may be used in addition to ACR criteria in clinical trials. Also, since the JADAS10 can easily be calculated at each patient visit, it also can be used for clinical decisions. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Noninvasive detection of intracerebral hemorrhage using near-infrared spectroscopy (NIRS)

NASA Astrophysics Data System (ADS)

Hennes, Hans-Juergen; Lott, Carsten; Windirsch, Michael; Hanley, Daniel F.; Boor, Stephan; Brambrink, Ansgar; Dick, Wolfgang

1998-01-01

Intracerebral Hemorrhage (IH) is an important cause of secondary brain injury in neurosurgical patients. Early identification and treatment improve neurologic outcome. We have tested Near Infrared Spectroscopy (NIRS) as an alternative noninvasive diagnostic tool compared to CT-Scans to detect IH. We prospectively studied 212 patients with neurologic symptoms associated with intracranial pathology before performing a CT-scan. NIRS signals indicated pathologies in 181 cases (sensitivity 0.96; specificity 0.29). In a subgroup of subdural hematomas NIRS detected 45 of 46 hematomas (sensitivity 0.96; specificity 0.79). Identification of intracerebral hemorrhage using NIRS has the potential to allow early treatment, thus possibly avoiding further injury.

Noninvasive detection of intracerebral hemorrhage using near-infrared spectroscopy (NIRS)

NASA Astrophysics Data System (ADS)

Hennes, Hans J.; Lott, C.; Windirsch, Michael; Hanley, Daniel F.; Boor, Stephan; Brambrink, Ansgar; Dick, Wolfgang

1997-12-01

Intracerebral Hemorrhage (IH) is an important cause of secondary brain injury in neurosurgical patients. Early identification and treatment improve neurologic outcome. We have tested Near Infrared Spectroscopy (NIRS) as an alternative noninvasive diagnostic tool compared to CT-Scans to detect IH. We prospectively studied 212 patients with neurologic symptoms associated with intracranial pathology before performing a CT-scan. NIRS signals indicated pathologies in 181 cases (sensitivity 0.96; specificity 0.29). In a subgroup of subdural hematomas NIRS detected 45 of 46 hematomas (sensitivity 0.96; specificity 0.79). Identification of intracerebral hemorrhage using NIRS has the potential to allow early treatment, thus possibly avoiding further injury.

Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography.

PubMed

Paul, Shashi B; Das, Prasenjit; Mahanta, Mousumi; Sreenivas, Vishnubhatla; Kedia, Saurabh; Kalra, Nancy; Kaur, Harpreet; Vijayvargiya, Maneesh; Ghosh, Shouriyo; Gamanagatti, Shivanand R; Shalimar; Gupta, Siddhartha Dutta; Acharya, Subrat K

2017-12-01

To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. CH patients (n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed (r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity.

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.

Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of the knee.

PubMed

Van Dyck, Pieter; Kenis, Christoph; Vanhoenacker, Filip M; Lambrecht, Valérie; Wouters, Kristien; Gielen, Jan L; Dossche, Lieven; Parizel, Paul M

2014-06-01

The aim of this prospective study was to compare routine MRI scans of the knee at 1.5 and 3 T obtained in the same individuals in terms of their performance in the diagnosis of cartilage lesions. One hundred patients underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR examinations consisted of multiplanar 2D turbo spin-echo sequences. Three radiologists independently graded all articular surfaces of the knee joint seen at MRI. With arthroscopy as the reference standard, the sensitivity, specificity, and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the proportion of correctly graded cartilage lesions within the knee joint were determined and compared using resampling statistics. For all readers and surfaces combined, the respective sensitivity, specificity, and accuracy for detecting all grades of cartilage lesions in the knee joint using MRI were 60, 96, and 87% at 1.5 T and 69, 96, and 90% at 3 T. There was a statistically significant improvement in sensitivity (p < 0.05), but not specificity or accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a statistically significant (p < 0.05) improvement in the proportion of correctly graded cartilage lesions at 3 T as compared to 1.5 T. A 3-T MR protocol significantly improves diagnostic performance for the purpose of detecting cartilage lesions within the knee joint, when compared with a similar protocol performed at 1.5 T. III.

Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

PubMed Central

Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, Jose G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Aucott, John N.

2015-01-01

The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. PMID:26447113

Evaluation of clinical methods for diagnosing bacterial vaginosis.

PubMed

Gutman, Robert E; Peipert, Jeffrey F; Weitzen, Sherry; Blume, Jeffrey

2005-03-01

To determine whether the current clinical criteria for diagnosing bacterial vaginosis can be simplified by using 2 clinical criteria rather than the standard 3 of 4 criteria (Amsel's criteria). This was a prospective observational study of 269 women undergoing a vaginal examination in the Women's Primary Care Center, Division of Research, or Colposcopy Clinic at Women & Infants Hospital. All 4 clinical criteria for diagnosing bacterial vaginosis were collected, and Gram stain was used as the gold standard. Sensitivity and specificity were calculated for each individual criterion, combinations of criteria, and a colorimetric pH and amine card. Receiver operating characteristic curve was generated to estimate the preferred pH and percentage of clue cells for diagnosing bacterial vaginosis. The prevalence of bacterial vaginosis in our study population was 38.7%. Vaginal pH was the most sensitive of all the criteria, at 89%, and a positive amine odor was the individual criteria with the highest specificity, at 93%. Similar specificity was seen with combinations of 2 criteria and Amsel's criteria. Receiver operating characteristic curve analysis yielded a preferred pH and percentage of clue cells of 5.0 and 20%, respectively. However, a pH of 4.5 or greater improves sensitivity with minimal loss of specificity. The clinical criteria for diagnosing bacterial vaginosis can be simplified to 2 clinical criteria without loss of sensitivity and specificity.

[Optimization and assessment of a reverse hybridization system for the detection of HBV drug-resistant mutations].

PubMed

Liu, Yan-chen; Huang, Ai-long; Hu, Yuan; Hu, Jie-li; Lai, Guo-qi; Zhang, Wen-lu

2011-12-01

To establish a detection method for HBV drug-resistant mutations related to lamivudine, adefovir and entecavir by optimization and assessment of reverse hybridization system. 26 degenerated probes covering 10 drug-resistant hotspots of 3 drugs were synthesized and immobilized on the same positively charged nylon membrane. PCR products labeled with digoxigenin were hybridized with corresponding probes. To improve the sensitivity and specificity, 4 reaction steps of reverse hybridization were optimized including the number of labeled digoxigenin, the energy intensity of UV cross-linking, hybridization and stringency wash conditions. To prove the feasibility, the specificity, sensitivity and accuracy of this system were assessed respectively. Sensitive and specific results are obtained by the optimization of the following 4 reaction steps: the primers labeled with 3 digoxigenin, energy intensity of UV cross-linking for 1500 x 0.1 mJ/cm², hybridization at 42 degrees C and stringency wash with 0.5 x SSC and 0.1% SDS solution at 44 degrees C for 30 min. In the assessment of system, the majority of probes have high specificity. The quantity of PCR product with a concentration of 10 ng/μl or above can be detected by this method. The concordant rate between reverse hybridization and direct sequencing is 93.9% in the clinical sample test. Though the specificity of several probes needs to be improved further, it is a simple, rapid and sensitive method which can detect HBV resistant mutations related to lamivudine, adefovir and entecavir simultaneously. Due to the short distance between 180 and 181, likewise 202 and 204, the sequence of the same probe covers two codon positions, and hybridization will be interfered by each other. To avoid such interference, the possible solution is that probes are designed by arranging and combining various forms of two near codons.

Molecular diagnostics for human leptospirosis.

PubMed

Waggoner, Jesse J; Pinsky, Benjamin A

2016-10-01

The definitive diagnosis of leptospirosis, which results from infection with spirochetes of the genus Leptospira, currently relies on the use of culture, serological testing (microscopic agglutination testing), and molecular detection. The purpose of this review is to describe new molecular diagnostics for Leptospira and discuss advancements in the use of available methods. Efforts have been focused on improving the clinical sensitivity of Leptospira detection using molecular methods. In this review, we describe a reoptimized pathogenic species-specific real-time PCR (targeting lipL32) that has demonstrated improved sensitivity, findings by two groups that real-time reverse-transcription PCR assays targeting the 16S rrs gene can improve detection, and two new loop-mediated amplification techniques. Quantitation of leptospiremia, detection in different specimen types, and the complementary roles played by molecular detection and microscopic agglutination testing will be discussed. Finally, a protocol for Leptospira strain subtyping using variable number tandem repeat targets and high-resolution melting will be described. Molecular diagnostics have an established role for the diagnosis of leptospirosis and provide an actionable diagnosis in the acute setting. The use of real-time reverse-transcription PCR for testing serum/plasma and cerebrospinal fluid, when available, may improve the detection of Leptospira without decreasing clinical specificity.

Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis.

PubMed

Daly, Michael J; Finlay, Dewar D; Guldenring, Daniel; Bond, Raymond R; McCann, Aaron J; Scott, Peter J; Adgey, Jennifer A; Harbinson, Mark T

2017-12-01

Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI). Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L. Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m 2 . Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM ( n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used. Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Nanoparticle-mediated knockdown of DNA repair sensitizes cells to radiotherapy and extends survival in a genetic mouse model of glioblastoma.

PubMed

Kievit, Forrest M; Wang, Kui; Ozawa, Tatsuya; Tarudji, Aria W; Silber, John R; Holland, Eric C; Ellenbogen, Richard G; Zhang, Miqin

2017-10-01

Glioblastoma (GBM) remains incurable, and recurrent tumors rarely respond to standard-of-care radiation and chemo-therapies. Therefore, strategies that enhance the effects of these therapies should provide significant benefits to GBM patients. We have developed a nanoparticle delivery vehicle that can stably bind and protect nucleic acids for specific delivery into brain tumor cells. These nanoparticles can deliver therapeutic siRNAs to sensitize GBM cells to radiotherapy and improve GBM treatment via systemic administration. We show that nanoparticle-mediated knockdown of the DNA repair protein apurinic endonuclease 1 (Ape1) sensitizes GBM cells to radiotherapy and extend survival in a genetic mouse model of GBM. Specific knockdown of Ape1 activity by 30% in brain tumor tissue doubled the extended survival achieved with radiotherapy alone. Ape1 is a promising target for increasing the effectiveness of radiotherapy, and nanoparticle-mediated delivery of siRNA is a promising strategy for tumor specific knockdown of Ape1. Copyright © 2017. Published by Elsevier Inc.

Advanced yellow fever virus genome detection in point-of-care facilities and reference laboratories.

PubMed

Domingo, Cristina; Patel, Pranav; Yillah, Jasmin; Weidmann, Manfred; Méndez, Jairo A; Nakouné, Emmanuel Rivalyn; Niedrig, Matthias

2012-12-01

Reported methods for the detection of the yellow fever viral genome are beset by limitations in sensitivity, specificity, strain detection spectra, and suitability to laboratories with simple infrastructure in areas of endemicity. We describe the development of two different approaches affording sensitive and specific detection of the yellow fever genome: a real-time reverse transcription-quantitative PCR (RT-qPCR) and an isothermal protocol employing the same primer-probe set but based on helicase-dependent amplification technology (RT-tHDA). Both assays were evaluated using yellow fever cell culture supernatants as well as spiked and clinical samples. We demonstrate reliable detection by both assays of different strains of yellow fever virus with improved sensitivity and specificity. The RT-qPCR assay is a powerful tool for reference or diagnostic laboratories with real-time PCR capability, while the isothermal RT-tHDA assay represents a useful alternative to earlier amplification techniques for the molecular diagnosis of yellow fever by field or point-of-care laboratories.

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

PubMed Central

Bacconi, Andrea; Richmond, Gregory S.; Baroldi, Michelle A.; Laffler, Thomas G.; Blyn, Lawrence B.; Carolan, Heather E.; Frinder, Mark R.; Toleno, Donna M.; Metzgar, David; Gutierrez, Jose R.; Massire, Christian; Rounds, Megan; Kennel, Natalie J.; Rothman, Richard E.; Peterson, Stephen; Carroll, Karen C.; Wakefield, Teresa; Ecker, David J.

2014-01-01

The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml whole-blood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections. PMID:24951806

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.

Perceptual Learning Improves Contrast Sensitivity of V1 Neurons in Cats

PubMed Central

Hua, Tianmiao; Bao, Pinglei; Huang, Chang-Bing; Wang, Zhenhua; Xu, Jinwang

2010-01-01

Summary Background Perceptual learning has been documented in adult humans over a wide range of tasks. Although the often observed specificity of learning is generally interpreted as evidence for training-induced plasticity in early cortical areas, physiological evidence for training-induced changes in early visual cortical areas is modest, despite reports of learning-induced changes of cortical activities in fMRI studies. To reveal the physiological bases of perceptual learning, we combined psychophysical measurements with extracellular single-unit recording under anesthetized preparations, and examined the effects of training in grating orientation identification on both perceptual and neuronal contrast sensitivity functions of cats. Results We have found that training significantly improved perceptual contrast sensitivity of the cats to gratings with the spatial frequencies near the ‘trained’ spatial frequency, with stronger effects in the trained eye. Consistent with behavioral assessments, the mean contrast sensitivity of neurons recorded from V1 of the trained cats was significantly higher than that of neurons recorded from the untrained cats. Furthermore, in the trained cats, the contrast sensitivity of V1 neurons responding preferentially to stimuli presented via the trained eyes was significantly greater than that of neurons responding preferentially to stimuli presented via the ‘untrained’ eyes. The effect was confined to the trained spatial frequencies. In both trained and untrained cats, the neuronal contrast sensitivity functions derived from the contrast sensitivity of the individual neurons were highly correlated with behaviorally determined perceptual contrast sensitivity functions. Conclusions We suggest that training-induced neuronal contrast-gain in area V1 underlies behaviorally determined perceptual contrast sensitivity improvements. PMID:20451388

Evaluation of acute knee pain in primary care.

PubMed

Jackson, Jeffrey L; O'Malley, Patrick G; Kroenke, Kurt

2003-10-07

The evaluation of acute knee pain often includes radiography of the knee. To synthesize the literature to determine the role of radiologic procedures in evaluating common causes of acute knee pain: fractures, meniscal or ligamentous injuries, osteoarthritis, and pseudogout. MEDLINE search from 1966 to October 2002. We included all published, peer-reviewed studies of decision rules for fractures. We included studies that used arthroscopy as the gold standard for measuring the accuracy of the physical examination and magnetic resonance imaging (MRI) for meniscal and ligamentous knee damage. We included all studies on the use of radiographs in pseudogout. We extracted all data in duplicate and abstracted physical examination and MRI results into 2 x 2 tables. Among the 5 decision rules for deciding when to use plain films in knee fractures, the Ottawa knee rules (injury due to trauma and age >55 years, tenderness at the head of the fibula or the patella, inability to bear weight for 4 steps, or inability to flex the knee to 90 degrees) have the strongest supporting evidence. When the history suggests a potential meniscal or ligamentous injury, the physical examination is moderately sensitive (meniscus, 87%; anterior cruciate ligament, 74%; and posterior cruciate ligament, 81%) and specific (meniscus, 92%; anterior cruciate ligament, 95%; and posterior cruciate ligament, 95%). The Lachman test is more sensitive and specific for ligamentous tears than is the drawer sign. For meniscal tears, joint line tenderness is sensitive (75%) but not specific (27%), while the McMurray test is specific (97%) but not sensitive (52%). Compared with the physical examination, MRI is more sensitive for ligamentous and meniscal damage but less specific. When the differential diagnosis for acute knee pain includes an exacerbation of osteoarthritis, clinical features (age >50 years, morning stiffness <30 minutes, crepitus, or bony enlargement) are 89% sensitive and 88% specific for underlying chronic arthritis. Adding plain films improves sensitivity slightly but not specificity. Plain films for pseudogout are not sensitive or specific, according to limited-quality studies. We recommend the Ottawa knee rules to decide when to obtain plain films for suspected knee fracture. A careful physical examination should be sufficient to decide whether to refer patients with potential meniscal and ligament injuries, and we prefer clinical criteria rather than plain films for evaluating osteoarthritis. We do not recommend using plain films to diagnose pseudogout.

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations

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

Kirman, C.R., E-mail: ckirman@summittoxicology.com

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sourcesmore » of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. - Highlights: • An improved version of the PBPK model for Cr(VI) toxicokinetics was developed. • The model incorporates data collected to fill important data gaps. • Model predictions for specific age groups and sensitive subpopulations are provided. • Implications to human health risk assessment are discussed.« less

Exercise testing after beta-blockade: improved specificity and predictive value in detecting coronary heart disease.

PubMed Central

Marcomichelakis, J; Donaldson, R; Green, J; Joseph, S; Kelly, H B; Taggart, P; Somerville, W

1980-01-01

The value of exercise testing in detecting myocardial ischaemia resulting from coronary atheroma remains controversial. In order to increase the reliability of exercise testing, all its components (asymptomatic, haemodynamic, and electrocardiographic) have been scrutinised. In this study, concerned only with the electrocardiographic response to exercise, the incorporation of beta-blockade into the standard exercise procedure has improved specificity and predictive value without affecting sensitivity. Fifty patients with anginal pain and 50 asymptomatic subjects with an abnormal electrocardiogram were investigated by exercise testing before and after beta-blockade (oxprenolol). All subjects had coronary arteriograms and left ventriculograms, and the results of exercise testing were related to the presence or absence of obstructive coronary artery disease. Possible causes of false positive exercise tests were eliminated by echocardiography. Though beta-blockade was unreliable in distinguishing ischaemic from non-ischaemic resting electrocardiograms, it eliminated all the false positive electrocardiographic responses to exercise in both groups and did not abolish any of the true positive electrocardiographic responses. Thus, specificity and predictive value were improved without reduction in sensitivity. This technique may not necessarily be applicable to other groups of patients or to a random population, but the results of this study suggest it will be a useful additional routine procedure in the investigation of coronary heart disease. PMID:7437172

Educational interventions to improve screening mammography interpretation: a randomized, controlled trial

PubMed Central

BM, Geller; A, Bogart; PA, Carney; EA, Sickles; RA, Smith; B, Monsees; LW, Bassett; DM, Buist; K, Kerlikowske; T, Onega; B, Yankaskas; S, Haneuse; DA, Hill; M, Wallis; DL, Miglioretti

2014-01-01

Purpose Conduct a randomized controlled trial of educational interventions to improve performance of screening mammography interpretation. Materials and Methods We randomly assigned physicians who interpret mammography to one of three groups: (1) self-paced DVD; (2) live, expert-led educational session; or (3) control. The DVD and live interventions used mammography cases of varying difficulty and associated teaching points. Interpretive performance was compared using a pre-/post-test design. Sensitivity, specificity, and positive predictive value (PPV) were calculated relative to two outcomes: cancer status and consensus of three experts about recall, and each were compared using logistic regression adjusting for pre-test performance. Results 102 radiologists completed all aspects of the trial. After adjustment for pre-intervention performance, the odds of improved sensitivity for correctly identifying a lesion relative to expert recall were 1.34 times higher for DVD participants than controls (95% confidence interval [CI]: 1.00, 1.81; P=0.050). The odds of improved PPV for correctly identifying a lesion relative to both expert recall (odds ratio [OR]=1.94, 95% CI: 1.24, 3.05; P=0.004) and cancer status (OR=1.81, 95% CI: 1.01, 3.23; P=0.045) were significantly improved for DVD participants compared to controls with no significant change in specificity. For the live-intervention group, specificity was significantly lower than the control group (OR relative to expert recall=0.80; 95% CI: 0.64, 1.00; P=0.048; OR relative to cancer=0.79; 95% CI: 0.65, 0.95; P=0.015). Conclusion In this randomized controlled trial, the DVD educational intervention resulted in a significant improvement in mammography interpretive screening performance on a test-set, which could translate into improved clinical interpretative performance. PMID:24848854

Educational interventions to improve screening mammography interpretation: a randomized controlled trial.

PubMed

Geller, Berta M; Bogart, Andy; Carney, Patricia A; Sickles, Edward A; Smith, Robert; Monsees, Barbara; Bassett, Lawrence W; Buist, Diana M; Kerlikowske, Karla; Onega, Tracy; Yankaskas, Bonnie C; Haneuse, Sebastien; Hill, Deirdre; Wallis, Matthew G; Miglioretti, Diana

2014-06-01

The objective of our study was to conduct a randomized controlled trial of educational interventions that were created to improve performance of screening mammography interpretation. We randomly assigned physicians who interpret mammography to one of three groups: self-paced DVD, live expert-led educational seminar, or control. The DVD and seminar interventions used mammography cases of varying difficulty and provided associated teaching points. Interpretive performance was compared using a pretest-posttest design. Sensitivity, specificity, and positive predictive value (PPV) were calculated relative to two outcomes: cancer status and consensus of three experts about recall. The performance measures for each group were compared using logistic regression adjusting for pretest performance. One hundred two radiologists completed all aspects of the trial. After adjustment for preintervention performance, the odds of improved sensitivity for correctly identifying a lesion relative to expert recall were 1.34 times higher for DVD participants than for control subjects (95% CI, 1.00-1.81; p = 0.050). The odds of an improved PPV for correctly identifying a lesion relative to both expert recall (odds ratio [OR] = 1.94; 95% CI, 1.24-3.05; p = 0.004) and cancer status (OR = 1.81; 95% CI, 1.01-3.23; p = 0.045) were significantly improved for DVD participants compared with control subjects, with no significant change in specificity. For the seminar group, specificity was significantly lower than the control group (OR relative to expert recall = 0.80; 95% CI, 0.64-1.00; p = 0.048; OR relative to cancer status = 0.79; 95% CI, 0.65-0.95; p = 0.015). In this randomized controlled trial, the DVD educational intervention resulted in a significant improvement in screening mammography interpretive performance on a test set, which could translate into improved interpretative performance in clinical practice.

The ERα-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice

PubMed Central

Zhu, Liangru; Xu, Pingwen; Cao, Xuehong; Yang, Yongjie; Hinton, Antentor Othrell; Xia, Yan; Saito, Kenji; Yan, Xiaofeng; Zou, Fang; Ding, Hongfang; Wang, Chunmei; Yan, Chunling; Saha, Pradip; Khan, Sohaib A.; Zhao, Jean; Fukuda, Makoto; Tong, Qingchun; Clegg, Deborah J.; Chan, Lawrence

2015-01-01

Estrogens act upon estrogen receptor (ER)α to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ERα specifically in proopiomelanocortin (POMC) progenitor neurons. These mutant mice also develop insulin resistance and are insensitive to the glucose-regulatory effects of estrogens. Moreover, we showed that propyl pyrazole triol (an ERα agonist) stimulates the phosphatidyl inositol 3-kinase (PI3K) pathway specifically in POMC progenitor neurons, and that blockade of PI3K attenuates propyl pyrazole triol-induced activation of POMC neurons. Finally, we show that effects of estrogens to inhibit food intake and to improve insulin sensitivity are significantly attenuated in female mice with PI3K genetically inhibited in POMC progenitor neurons. Together, our results indicate that an ERα-PI3K cascade in POMC progenitor neurons mediates estrogenic actions to suppress food intake and improve insulin sensitivity. PMID:26375425

The ERα-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice.

PubMed

Zhu, Liangru; Xu, Pingwen; Cao, Xuehong; Yang, Yongjie; Hinton, Antentor Othrell; Xia, Yan; Saito, Kenji; Yan, Xiaofeng; Zou, Fang; Ding, Hongfang; Wang, Chunmei; Yan, Chunling; Saha, Pradip; Khan, Sohaib A; Zhao, Jean; Fukuda, Makoto; Tong, Qingchun; Clegg, Deborah J; Chan, Lawrence; Xu, Yong

2015-12-01

Estrogens act upon estrogen receptor (ER)α to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ERα specifically in proopiomelanocortin (POMC) progenitor neurons. These mutant mice also develop insulin resistance and are insensitive to the glucose-regulatory effects of estrogens. Moreover, we showed that propyl pyrazole triol (an ERα agonist) stimulates the phosphatidyl inositol 3-kinase (PI3K) pathway specifically in POMC progenitor neurons, and that blockade of PI3K attenuates propyl pyrazole triol-induced activation of POMC neurons. Finally, we show that effects of estrogens to inhibit food intake and to improve insulin sensitivity are significantly attenuated in female mice with PI3K genetically inhibited in POMC progenitor neurons. Together, our results indicate that an ERα-PI3K cascade in POMC progenitor neurons mediates estrogenic actions to suppress food intake and improve insulin sensitivity.

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.

PubMed

Clarke, Charlotte H; Yip, Christine; Badgwell, Donna; Fung, Eric T; Coombes, Kevin R; Zhang, Zhen; Lu, Karen H; Bast, Robert C

2011-09-01

The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P=0.015, McNemar's test). Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. Copyright © 2011. Published by Elsevier Inc.

Proteomic Biomarkers Apolipoprotein A1, Truncated Transthyretin and Connective Tissue Activating Protein III Enhance the Sensitivity of CA125 for Detecting Early Stage Epithelial Ovarian Cancer

PubMed Central

Clarke, Charlotte H.; Yip, Christine; Badgwell, Donna; Fung, Eric T.; Coombes, Kevin R.; Zhang, Zhen; Lu, Karen H.; Bast, Robert C.

2011-01-01

Objective The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Methods Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. Results In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P= 0.015, McNemar's test). Conclusion Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. PMID:21708402

Improved scintimammography using a high-resolution camera mounted on an upright mammography gantry

NASA Astrophysics Data System (ADS)

Itti, Emmanuel; Patt, Bradley E.; Diggles, Linda E.; MacDonald, Lawrence; Iwanczyk, Jan S.; Mishkin, Fred S.; Khalkhali, Iraj

2003-01-01

99mTc-sestamibi scintimammography (SMM) is a useful adjunct to conventional X-ray mammography (XMM) for the assessment of breast cancer. An increasing number of studies has emphasized fair sensitivity values for the detection of tumors >1 cm, compared to XMM, particularly in situations where high glandular breast densities make mammographic interpretation difficult. In addition, SMM has demonstrated high specificity for cancer, compared to various functional and anatomic imaging modalities. However, large field-of-view (FOV) gamma cameras are difficult to position close to the breasts, which decreases spatial resolution and subsequently, the sensitivity of detection for tumors <1 cm. New dedicated detectors featuring small FOV and increased spatial resolution have recently been developed. In this setting, improvement in tumor detection sensitivity, particularly with regard to small cancers is expected. At Division of Nuclear Medicine, Harbor-UCLA Medical Center, we have performed over 2000 SMM within the last 9 years. We have recently used a dedicated breast camera (LumaGEM™) featuring a 12.8×12.8 cm 2 FOV and an array of 2×2×6 mm 3 discrete crystals coupled to a photon-sensitive photomultiplier tube readout. This camera is mounted on a mammography gantry allowing upright imaging, medial positioning and use of breast compression. Preliminary data indicates significant enhancement of spatial resolution by comparison with standard imaging in the first 10 patients. Larger series will be needed to conclude on sensitivity/specificity issues.

Dedicated training program for shoulder sonography: the results of a quality program reverberate with everyone.

PubMed

Delzell, Patricia B; Boyle, Alex; Schneider, Erika

2015-06-01

The purpose of this study was to define and report on the effect of a comprehensive musculoskeletal sonography training program to improve accuracy (sensitivity and specificity) for the diagnosis of rotator cuff tears in relatively inexperienced operators. Before the training program was implemented, radiologists (n = 12) had a mean of 2 years (range, <1-12 years) of experience performing and interpreting musculoskeletal sonography. Pre- and post-training shoulder sonographic results were compared to surgical reports or, in their absence, to shoulder magnetic resonance imaging or computed tomographic arthrographic results if within 2 months of the sonographic examination. A total of 82 patients were included in the pre-training group (January 2010-December 2011), and 50 patients were included in the post-training group (January 2012-June 2013). The accuracy, sensitivity, specificity, and positive and negative predictive values were determined for the presence or absence of supraspinatus and infraspinatus tendon tears. After implementation of the training program, the sensitivity of sonography for detecting full-thickness rotator cuff tears increased by 14%, and the sensitivity for detecting partial-thickness rotator cuff tears increased by 3%. Quality improvement programs and acquisition standardization along with ongoing, focused case conferences for the entire care team increased the sensitivity of shoulder sonography for diagnosing both full- and partial-thickness rotator cuff tears, independent of the years of operator experience. © 2015 by the American Institute of Ultrasound in Medicine.

Evaluation of echocardiography in the management of elderly patients with heart failure.

PubMed

Hendry, A; Hacking, L; Langhorne, P; Vallance, R; MacDonald, J

1999-09-01

To determine the validity of a clinical diagnosis of systolic dysfunction in elderly patients with heart failure and assess the contribution of echocardiography to their management. 61 elderly patients with a diagnosis of heart failure in a geriatric assessment unit setting. Prospective study determining sensitivity, specificity and predictive values of a clinical and radiological diagnosis compared with echocardiographic standard. Proposed management was compared before and after echocardiography. Clinical assessment was highly sensitive (93%) but lacked specificity (32%). Combining radiological and clinical diagnoses increased specificity to 58%. Echocardiography revised the lead cardiac diagnosis for 28% of patients and influenced patient management plans for 41%. For elderly patients with heart failure, echocardiography improves diagnostic accuracy and identifies those patients with potential to benefit from angiotensin-converting enzyme inhibitors.

Sensitivity and specificity of two different automated external defibrillators.

PubMed

Israelsson, Johan; Wangenheim, Burkard von; Årestedt, Kristofer; Semark, Birgitta; Schildmeijer, Kristina; Carlsson, Jörg

2017-11-01

The aim was to investigate the clinical performance of two different types of automated external defibrillators (AEDs). Three investigators reviewed 2938 rhythm analyses performed by AEDs in 240 consecutive patients (median age 72, q1-q3=62-83) who had suffered cardiac arrest between January 2011 and March 2015. Two different AEDs were used (AED A n=105, AED B n=135) in-hospital (n=91) and out-of-hospital (n=149). Among 194 shockable rhythms, 17 (8.8%) were not recognized by AED A, while AED B recognized 100% (n=135) of shockable episodes (sensitivity 91.2 vs 100%, p<0.01). In AED A, 8 (47.1%) of these episodes were judged to be algorithm errors while 9 (52.9%) were caused by external artifacts. Among 1039 non-shockable rhythms, AED A recommended shock in 11 (1.0%), while AED B recommended shock in 63 (4.1%) of 1523 episodes (specificity 98.9 vs 95.9, p<0.001). In AED A, 2 (18.2%) of these episodes were judged to be algorithm errors (AED B, n=40, 63.5%), while 9 (81.8%) were caused by external artifacts (AED B, n=23, 36.5%). There were significant differences in sensitivity and specificity between the two different AEDs. A higher sensitivity of AED B was associated with a lower specificity while a higher specificity of AED A was associated with a lower sensitivity. AED manufacturers should work to improve the algorithms. In addition, AED use should always be reviewed with a routine for giving feedback, and medical personnel should be aware of the specific strengths and shortcomings of the device they are using. Copyright © 2017 Elsevier B.V. All rights reserved.

Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis.

PubMed

Hengartner, M P; Heekeren, K; Dvorsky, D; Walitza, S; Rössler, W; Theodoridou, A

2017-09-01

The aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics. A total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). Altogether n=24 persons developed manifest psychosis within three years and according to Kaplan-Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC]=0.65, P<.05), whereas BS did not predict psychosis beyond mere chance (AUC=0.52, P=.730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC=0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC=0.62 (sensitivity=0.42; specificity=0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC=0.85; sensitivity=0.86; specificity=0.85; positive predictive value=0.54; negative predictive value=0.97). We showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Correcting the anion gap for hypoalbuminaemia does not improve detection of hyperlactataemia

PubMed Central

Dinh, C H; Ng, R; Grandinetti, A; Joffe, A; Chow, D C

2006-01-01

Background An elevated lactate level reflects impaired tissue oxygenation and is a predictor of mortality. Studies have shown that the anion gap is inadequate as a screen for hyperlactataemia, particularly in critically ill and trauma patients. A proposed explanation for the anion gap's poor sensitivity and specificity in detecting hyperlactataemia is that the serum albumin is frequently low. This study therefore, sought to compare the predictive values of the anion gap and the anion gap corrected for albumin (cAG) as an indicator of hyperlactataemia as defined by a lactate ⩾2.5 mmol/l. Methods A retrospective review of 639 sets of laboratory values from a tertiary care hospital. Patients' laboratory results were included in the study if serum chemistries and lactate were drawn consecutively. The sensitivity, specificity, and predictive values were obtained. A receiver operator characteristics curve (ROC) was drawn and the area under the curve (AUC) was calculated. Results An anion gap ⩾12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 79%, and 58%, respectively, and a cAG ⩾12 provided a sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 59%, 66%, and 69%, respectively. The ROC curves between anion gap and cAG as a predictor of hyperlactataemia were almost identical. The AUC was 0.757 and 0.750, respectively. Conclusions The sensitivities, specificities, and predictive values of the anion gap and cAG were inadequate in predicting the presence of hyperlactataemia. The cAG provides no additional advantage over the anion gap in the detection of hyperlactataemia. PMID:16858097

Digital Rectal Examination and Balloon Expulsion Test in the Study of Defecatory Disorders: Are They Suitable as Screening or Excluding Tests?

PubMed

Caetano, Ana C; Santa-Cruz, André; Rolanda, Carla

2016-01-01

Background . Rome III criteria add physiological criteria to symptom-based criteria of chronic constipation (CC) for the diagnosis of defecatory disorders (DD). However, a gold-standard test is still lacking and physiological examination is expensive and time-consuming. Aim . Evaluate the usefulness of two low-cost tests-digital rectal examination (DRE) and balloon expulsion test (BET)-as screening or excluding tests of DD. Methods . We performed a systematic search in PUBMED and MEDLINE. We selected studies where constipated patients were evaluated by DRE or BET. Heterogeneity was assessed and random effect models were used to calculate the sensitivity, specificity, and negative predictive value (NPV) of the DRE and the BET. Results . Thirteen studies evaluating BET and four studies evaluating DRE (2329 patients) were selected. High heterogeneity ( I 2 > 80%) among studies was demonstrated. The studies evaluating the BET showed a sensitivity and specificity of 67% and 80%, respectively. Regarding the DRE, a sensitivity of 80% and specificity of 84% were calculated. NPV of 72% for the BET and NPV of 64% for the DRE were estimated. The sensitivity and specificity were similar when we restrict the analysis to studies using Rome criteria to define CC. The BET seems to perform better when a cut-off time of 2 minutes is used and when it is compared with a combination of physiological tests. Considering the DRE, strict criteria seem to improve the sensitivity but not the specificity of the test. Conclusion . Neither of the low-cost tests seems suitable for screening or excluding DD.

Sensitivity of subject-specific models to errors in musculo-skeletal geometry.

PubMed

Carbone, V; van der Krogt, M M; Koopman, H F J M; Verdonschot, N

2012-09-21

Subject-specific musculo-skeletal models of the lower extremity are an important tool for investigating various biomechanical problems, for instance the results of surgery such as joint replacements and tendon transfers. The aim of this study was to assess the potential effects of errors in musculo-skeletal geometry on subject-specific model results. We performed an extensive sensitivity analysis to quantify the effect of the perturbation of origin, insertion and via points of each of the 56 musculo-tendon parts contained in the model. We used two metrics, namely a Local Sensitivity Index (LSI) and an Overall Sensitivity Index (OSI), to distinguish the effect of the perturbation on the predicted force produced by only the perturbed musculo-tendon parts and by all the remaining musculo-tendon parts, respectively, during a simulated gait cycle. Results indicated that, for each musculo-tendon part, only two points show a significant sensitivity: its origin, or pseudo-origin, point and its insertion, or pseudo-insertion, point. The most sensitive points belong to those musculo-tendon parts that act as prime movers in the walking movement (insertion point of the Achilles Tendon: LSI=15.56%, OSI=7.17%; origin points of the Rectus Femoris: LSI=13.89%, OSI=2.44%) and as hip stabilizers (insertion points of the Gluteus Medius Anterior: LSI=17.92%, OSI=2.79%; insertion point of the Gluteus Minimus: LSI=21.71%, OSI=2.41%). The proposed priority list provides quantitative information to improve the predictive accuracy of subject-specific musculo-skeletal models. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sensitivity and specificity of Norwegian optometrists' evaluation of diabetic retinopathy in single-field retinal images - a cross-sectional experimental study.

PubMed

Sundling, Vibeke; Gulbrandsen, Pål; Straand, Jørund

2013-01-10

In the working age group, diabetic retinopathy is a leading cause of visual impairment. Regular eye examinations and early treatment of retinopathy can prevent visual loss, so screening for diabetic retinopathy is cost-effective. Dilated retinal digital photography with the additional use of ophthalmoscopy is the most effective and robust method of diabetic retinopathy screening. The aim of this study was to estimate the sensitivity and specificity of diabetic retinopathy screening when performed by Norwegian optometrists. This study employed a cross-sectional experimental design. Seventy-four optometrists working in private optometric practice were asked to screen 14 single-field retinal images for possible diabetic retinopathy. The screening was undertaken using a web-based visual identification and management of ophthalmological conditions (VIMOC) examination. The images used in the VIMOC examination were selected from a population survey and had been previously examined by two independent ophthalmologists. In order to establish a "gold standard", images were only chosen for use in the VIMOC examination if they had elicited diagnostic agreement between the two independent ophthalmologists. To reduce the possibility of falsely high specificity occurring by chance, half the presented images were of retinas that were not affected by diabetic retinopathy. Sensitivity and specificity for diabetic retinopathy was calculated with 95% confidence intervals (CIs). The mean (95%CI) sensitivity for identifying eyes with any diabetic retinopathy was 67% (62% to 72%). The mean (95%CI) specificity for identifying eyes without diabetic retinopathy was 84% (80% to 89%). The mean (95%CI) sensitivity for identifying eyes with mild non-proliferative diabetic retinopathy or moderate non-proliferative diabetes was 54% (47% to 61%) and 100%, respectively. Only four optometrists (5%) met the required standard of at least 80% sensitivity and 95% specificity that has been previously set for diabetic retinopathy screening programmes. The evaluation of retinal images for diabetic retinopathy by Norwegian optometrists does not meet the required screening standard of at least 80% sensitivity and 95% specificity. The introduction of measures to improve this situation could have implications for both formal optometric training and continuing optometric professional education.

Sensitivity and specificity of Norwegian optometrists’ evaluation of diabetic retinopathy in single-field retinal images – a cross-sectional experimental study

PubMed Central

2013-01-01

Background In the working age group, diabetic retinopathy is a leading cause of visual impairment. Regular eye examinations and early treatment of retinopathy can prevent visual loss, so screening for diabetic retinopathy is cost-effective. Dilated retinal digital photography with the additional use of ophthalmoscopy is the most effective and robust method of diabetic retinopathy screening. The aim of this study was to estimate the sensitivity and specificity of diabetic retinopathy screening when performed by Norwegian optometrists. Methods This study employed a cross-sectional experimental design. Seventy-four optometrists working in private optometric practice were asked to screen 14 single-field retinal images for possible diabetic retinopathy. The screening was undertaken using a web-based visual identification and management of ophthalmological conditions (VIMOC) examination. The images used in the VIMOC examination were selected from a population survey and had been previously examined by two independent ophthalmologists. In order to establish a “gold standard”, images were only chosen for use in the VIMOC examination if they had elicited diagnostic agreement between the two independent ophthalmologists. To reduce the possibility of falsely high specificity occurring by chance, half the presented images were of retinas that were not affected by diabetic retinopathy. Sensitivity and specificity for diabetic retinopathy was calculated with 95% confidence intervals (CIs). Results The mean (95%CI) sensitivity for identifying eyes with any diabetic retinopathy was 67% (62% to 72%). The mean (95%CI) specificity for identifying eyes without diabetic retinopathy was 84% (80% to 89%). The mean (95%CI) sensitivity for identifying eyes with mild non-proliferative diabetic retinopathy or moderate non-proliferative diabetes was 54% (47% to 61%) and 100%, respectively. Only four optometrists (5%) met the required standard of at least 80% sensitivity and 95% specificity that has been previously set for diabetic retinopathy screening programmes. Conclusions The evaluation of retinal images for diabetic retinopathy by Norwegian optometrists does not meet the required screening standard of at least 80% sensitivity and 95% specificity. The introduction of measures to improve this situation could have implications for both formal optometric training and continuing optometric professional education. PMID:23305337

Targeted drug delivery and enhanced intracellular release using functionalized liposomes

NASA Astrophysics Data System (ADS)

Garg, Ashish

The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving the overall quality of life, post cancer survival. Integrin alpha5beta1 is expressed on several types of cancer cells, including colon cancer and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin alpha 5beta1 using an appropriate drug delivery nano-vector can significantly help in inhibiting tumor growth and reducing tumor metastasis. The work in this thesis focuses on designing and optimizing, functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin alpha5beta1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, PR_b peptide specifically recognizes and binds to integrin alpha5beta1 expressing cells. The work demonstrates that by optimizing the amount of PEG and PR_b on the liposomal interface, nano-vectors can be engineered that bind to CT26.WT colon cancer cells in a specific manner and internalize through alpha 5beta1-mediated endocytosis. To further improve the efficacy of the system, PR_b functionalized pH-sensitive stealth liposomes that exhibit triggered release under mild acidic conditions present in endocytotic vesicles were designed. The study showed that PR_b functionalized pH-sensitive stealth liposomes, undergo destabilization under mildly acidic conditions and incorporation of the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b functionalized pH-sensitive stealth liposomes bind to CT26.WT colon carcinoma cells that express integrin alpha5beta 1, undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. PR_b-targeted pH-sensitive stealth liposomes encapsulating 5-fluorouracil (5-FU) show significantly higher cytotoxicity than the PR_b-targeted inert stealth liposomes and the non-targeted stealth liposomes (both pH-sensitive and inert). The studies demonstrated that optimized PR_b functionalized pH sensitive liposomes have the potential to deliver a payload, such as chemotherapeutic agents, directly to colon cancer cells in an efficient and specific manner.

Accurate Detection of Streptococcus pyogenes at the Point of Care Using the cobas Liat Strep A Nucleic Acid Test.

PubMed

Wang, Fangnian; Tian, Yu; Chen, Lingjun; Luo, Robert; Sickler, Joanna; Liesenfeld, Oliver; Chen, Shuqi

2017-10-01

The performance of a polymerase chain reaction-based point-of-care assay, the cobas Strep A Nucleic Acid Test for use on the cobas Liat System (cobas Liat Strep A assay), for the detection of group A Streptococcus bacteria was evaluated in primary care settings. Throat swab specimens from 427 patients were tested with the cobas Liat Strep A assay and a rapid antigen detection test (RADT) by existing medical staff at 5 primary care clinics, and results were compared with bacterial culture. The cobas Liat Strep A assay demonstrated equivalent sensitivity (97.7%) and specificity (93.3%) to reference culture with a 15-minute turnaround time. In comparison to RADTs, the cobas Liat Strep A assay showed improved sensitivity (97.7% Liat vs 84.5% RADT). The Clinical Laboratory Improvement Amendments-waived cobas Liat Strep A assay demonstrated the ease of use and improved turnaround time of RADTs along with the sensitivity of culture.

Development and Validation of Osteoporosis Risk-Assessment Model for Korean Men

PubMed Central

Oh, Sun Min; Song, Bo Mi; Nam, Byung-Ho; Rhee, Yumie; Moon, Seong-Hwan; Kim, Deog Young; Kang, Dae Ryong

2016-01-01

Purpose The aim of the present study was to develop an osteoporosis risk-assessment model to identify high-risk individuals among Korean men. Materials and Methods The study used data from 1340 and 1110 men ≥50 years who participated in the 2009 and 2010 Korean National Health and Nutrition Examination Survey, respectively, for development and validation of an osteoporosis risk-assessment model. Osteoporosis was defined as T score ≤-2.5 at either the femoral neck or lumbar spine. Performance of the candidate models and the Osteoporosis Self-assessment Tool for Asian (OSTA) was compared with sensitivity, specificity, and area under the receiver operating characteristics curve (AUC). A net reclassification improvement was further calculated to compare the developed Korean Osteoporosis Risk-Assessment Model for Men (KORAM-M) with OSTA. Results In the development dataset, the prevalence of osteoporosis was 8.1%. KORAM-M, consisting of age and body weight, had a sensitivity of 90.8%, a specificity of 42.4%, and an AUC of 0.666 with a cut-off score of -9. In the validation dataset, similar results were shown: sensitivity 87.9%, specificity 39.7%, and AUC 0.638. Additionally, risk categorization with KORAM-M showed improved reclassification over that of OSTA up to 22.8%. Conclusion KORAM-M can be simply used as a pre-screening tool to identify candidates for dual energy X-ray absorptiometry tests. PMID:26632400

Validity of the language development survey in infants born preterm.

PubMed

Beaulieu-Poulin, Camille; Simard, Marie-Noëlle; Babakissa, Hélène; Lefebvre, Francine; Luu, Thuy Mai

2016-07-01

Preterm infants are at greater risk of language delay. Early identification of language delay is essential to improve functional outcome in these children. To examine the concurrent validity of Rescorla's Language Development Survey and the Bayley Scales of Infant and Toddler Development (Bayley-III) at 18months corrected age in preterm infants. Test accuracy study. 189 preterm infants born <29weeks were assessed at 18months. The Language Development Survey, a parent-reported screening instrument, was administered in French concurrently with the Language Scales of the Bayley-III. Receiver-Operating-Characteristics curves were used to determine optimal cut-off score on the Language Development Survey to identify Bayley-III score <85. Sensitivity, specificity, positive and negative predictive values, and κ coefficient were calculated. Using Rescorla's original cut-off scores of ≤10 words for boys and ≤24 for girls, sensitivity was 76% and 88% for boys and girls, respectively, and specificity was 73% and 52% for boys and girls, respectively, in identifying language delay as per the Bayley-III. The optimal threshold was ≤10 words for both boys and girls. In girls, lowering the cut-off score decreased sensitivity (79%), but improved specificity (82%), thus lowering the number of false-positives. Our findings support using the Language Development Survey as an expressive language screener in preterm infants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Validity of Race, Ethnicity, and National Origin in Population-based Cancer Registries and Rapid Case Ascertainment Enhanced With a Spanish Surname List.

PubMed

Clarke, Lisa C; Rull, Rudolph P; Ayanian, John Z; Boer, Robert; Deapen, Dennis; West, Dee W; Kahn, Katherine L

2016-01-01

Accurate information regarding race, ethnicity, and national origins is critical for identifying disparities in the cancer burden. To examine the use of a Spanish surname list to improve the quality of race-related information obtained from rapid case ascertainment (RCA) and to estimate the accuracy of race-related information obtained from cancer registry records collected by routine reporting. Self-reported survey responses of 3954 participants from California enrolled in the Cancer Care Outcomes Research and Surveillance Consortium. Sensitivity, specificity, positive predictive value, and percent agreement. We used logistic regression to identify predictors of underreporting and overreporting of a race/ethnicity. Use of the Spanish surname list increased the sensitivity of RCA for Latino ethnicity from 37% to 83%. Sensitivity for cancer registry records collected by routine reporting was ≥95% for whites, blacks, and Asians, and specificity was high for all groups (86%-100%). However, patterns of misclassification by race/ethnicity were found that could lead to biased cancer statistics for specific race/ethnicities. Discordance between self-reported and registry-reported race/ethnicity was more likely for women, Latinos, and Asians. Methods to improve race and ethnicity data, such as using Spanish surnames in RCA and instituting data collection guidelines for hospitals, are needed to ensure minorities are accurately represented in clinical and epidemiological research.

Improved removal of blood contamination from ThinPrep cervical cytology samples for Raman spectroscopic analysis.

PubMed

Traynor, Damien; Duraipandian, Shiyamala; Martin, Cara M; O'Leary, John J; Lyng, Fiona M

2018-05-01

There is an unmet need for methods to help in the early detection of cervical precancer. Optical spectroscopy-based techniques, such as Raman spectroscopy, have shown great potential for diagnosis of different cancers, including cervical cancer. However, relatively few studies have been carried out on liquid-based cytology (LBC) pap test specimens and confounding factors, such as blood contamination, have been identified. Previous work reported a method to remove blood contamination before Raman spectroscopy by pretreatment of the slides with hydrogen peroxide. The aim of the present study was to extend this work to excessively bloody samples to see if these could be rendered suitable for Raman spectroscopy. LBC ThinPrep specimens were treated by adding hydrogen peroxide directly to the vial before slide preparation. Good quality Raman spectra were recorded from negative and high grade (HG) cytology samples with no blood contamination and with heavy blood contamination. Good classification between negative and HG cytology could be achieved for samples with no blood contamination (sensitivity 92%, specificity 93%) and heavy blood contamination (sensitivity 89%, specificity 88%) with poorer classification when samples were combined (sensitivity 82%, specificity 87%). This study demonstrates for the first time the improved potential of Raman spectroscopy for analysis of ThinPrep specimens regardless of blood contamination. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Improving Recognition of Pediatric Severe Sepsis in the Emergency Department: Contributions of a Vital Sign-Based Electronic Alert and Bedside Clinician Identification.

PubMed

Balamuth, Fran; Alpern, Elizabeth R; Abbadessa, Mary Kate; Hayes, Katie; Schast, Aileen; Lavelle, Jane; Fitzgerald, Julie C; Weiss, Scott L; Zorc, Joseph J

2017-12-01

Recognition of pediatric sepsis is a key clinical challenge. We evaluate the performance of a sepsis recognition process including an electronic sepsis alert and bedside assessment in a pediatric emergency department (ED). This was a cohort study with quality improvement intervention in a pediatric ED. Exposure was a positive electronic sepsis alert, defined as elevated pulse rate or hypotension, concern for infection, and at least one of the following: abnormal capillary refill, abnormal mental status, or high-risk condition. A positive electronic sepsis alert prompted team assessment or huddle to determine need for sepsis protocol. Clinicians could initiate team assessment or huddle according to clinical concern without positive electronic sepsis alert. Severe sepsis outcome defined as activation of the sepsis protocol in the ED or development of severe sepsis requiring ICU admission within 24 hours. There were 182,509 ED visits during the study period, with 86,037 before electronic sepsis alert implementation and 96,472 afterward, and 1,112 (1.2%) positive electronic sepsis alerts. Overall, 326 patients (0.3%) were treated for severe sepsis within 24 hours. Test characteristics of the electronic sepsis alert alone to detect severe sepsis were sensitivity 86.2% (95% confidence interval [CI] 82.0% to 89.5%), specificity 99.1% (95% CI 99.0% to 99.2%), positive predictive value 25.4% (95% CI 22.8% to 28.0%), and negative predictive value 100% (95% CI 99.9% to 100%). Inclusion of the clinician screen identified 43 additional electronic sepsis alert-negative children, with severe sepsis sensitivity 99.4% (95% CI 97.8% to 99.8%) and specificity 99.1% (95% CI 99.1% to 99.2%). Electronic sepsis alert implementation increased ED sepsis detection from 83% to 96%. Electronic sepsis alert for severe sepsis demonstrated good sensitivity and high specificity. Addition of clinician identification of electronic sepsis alert-negative patients further improved sensitivity. Implementation of the electronic sepsis alert was associated with improved recognition of severe sepsis. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions

PubMed Central

Sharp, Tyler M.; Lalita, Paul; Tikomaidraubuta, Kini; Cardoso, Yolanda Rebello; Naivalu, Taina; Khan, Aalisha Sahu; Marfel, Maria; Hancock, W. Thane; Tomashek, Kay M.; Margolis, Harold S.

2016-01-01

Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable. PMID:27225409

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

None

The overall objective of the proposed Phase II project is to demonstrate the feasibility of a commercially practicable method of detecting the identified molecules with sufficient sensitivity and specificity so as to provide economic improvements in storage health management practices that exceed the cost of implementing the method.

Broadband plasmonic-enhanced forward and backward multiplex coherent anti-Stokes Raman scattering microscopy

NASA Astrophysics Data System (ADS)

Guo, Baoshan; Jiang, Lan; Hua, Yanhong; Li, Xin; Cui, Tianhong; Lu, Yongfeng

2018-03-01

Coherent anti-Stokes Raman scattering (CARS) microscopy is an attractive technique for label-free biochemical-specific characterization of biological specimens. However, it has very low sensitivity in monitoring and imaging molecules present in extremely low concentrations or at fast speeds. To improve this sensitivity, especially for multiplex CARS, the intensity of the pump beam and broadband Stokes beam should be enhanced simultaneously. Therefore, the gold shell particle and gold surface are demonstrated to enhance the forward and backward CARS, respectively. Results show that a signal enhancement factor of ˜25,000 can be achieved for the gold surface and an even higher enhancement factor can be achieved for the gold shell particles. Thus, we can obtain an enhanced CARS signal in a broad spectral range, which will substantially improve the detection sensitivity of hyperspectral CARS spectroscopy and imaging.

pH-Sensitive nanoparticles as smart carriers for selective intracellular drug delivery to tumor.

PubMed

Li, Xin-Xin; Chen, Jing; Shen, Jian-Min; Zhuang, Ran; Zhang, Shi-Qi; Zhu, Zi-Yun; Ma, Jing-Bo

2018-05-05

Herein, a smart pH-sensitive nanoparticle (DGL-PEG-Tat-KK-DMA-DOX) was prepared to achieve the selective intracellular drug delivery. In this nanoparticle, a PEG-grafted cell penetrating peptide (PEG-Tat-KK) was designed and acted as the cell penetrating segment. By introducing the pH-sensitive amide bonds between the peptide and blocking agent (2,3-dimethylmaleic anhydride, DMA), the controllable moiety (PEG-Tat-KK-DMA) endowed the nanoparticle with a charge-switchable shell and temporarily blocked penetrating function, thus improving the specific internalization. Besides, dendrigraft poly-L-lysine (DGL) used as the skeleton can greatly improve the drug loading because of the highly dendritic framework. Under the stimuli of acidic pH, this nanoparticle exhibited a remarkable charge-switchable property. The drug release showed an expected behavior with little release in the neutral pH media but relatively fast release in the acidic media. The in vitro experiments revealed that the cellular uptake and cytotoxicity were significantly enhanced after the pH was decreased. In vivo biodistribution and antitumor research indicated that the nanoparticle had noteworthy specificity and antitumor efficacy with a tumor inhibition rate of 79.7%. These results verified this nanoparticle could efficiently improve the selective intracellular delivery and possessed a great potential in tumor treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Thermosensitive liposomes for localized delivery and triggered release of chemotherapy

PubMed Central

Ta, Terence; Porter, Tyrone M.

2016-01-01

Liposomes are a promising class of nanomedicine with the potential to provide site-specific chemotherapy, thus improving the quality of cancer patient care. First-generation liposomes have emerged as one of the first nanomedicines used clinically for localized delivery of chemotherapy. Second-generation liposomes, i.e. stimuli-responsive liposomes, have the potential to not only provide site-specific chemotherapy, but also triggered drug release and thus greater spatial and temporal control of therapy. Temperature-sensitive liposomes are an especially attractive option, as tumors can be heated in a controlled and predictable manner with external energy sources. Traditional thermosensitive liposomes are composed of lipids that undergo a gel-to-liquid phase transition at several degrees above physiological temperature. More recently, temperature-sensitization of liposomes has been demonstrated with the use of lysolipids and synthetic temperature-sensitive polymers. The design, drug release behavior, and clinical potential of various temperature-sensitive liposomes, as well as the various heating modalities used to trigger release, are discussed in this review. PMID:23583706

Performance of a histidine-rich protein 2 rapid diagnostic test, Paracheck Pf®, for detection of malaria infections in Ugandan pregnant women.

PubMed

Dhorda, Mehul; Piola, Patrice; Nyehangane, Dan; Tumwebaze, Benon; Nalusaji, Aisha; Nabasumba, Carolyn; Turyakira, Eleanor; McGready, Rose; Ashley, Elizabeth; Guerin, Philippe J; Snounou, Georges

2012-01-01

Improved laboratory diagnosis is critical to reduce the burden of malaria in pregnancy. Peripheral blood smears appear less sensitive than Plasmodium falciparum histidine-rich protein 2-based rapid diagnostic tests (RDTs) for placental malaria infections in studies conducted at delivery. In this study, 81 women in Uganda in the second or third trimester of pregnancy were followed-up until delivery. At each visit, peripheral blood was tested by blood smear, RDT, and nested species-specific polymerase chain reaction (PCR). Sensitivity and specificity of the tests was calculated with PCR, which detected 22 infections of P. falciparum, as the gold standard. The sensitivity and specificity of blood smears were 36.4% (95% confidence interval [CI] = 18.0-59.2%) and 99.6% (95% CI = 97.7-100%), respectively. The corresponding values for RDT were 31.8% (95% CI = 14.7-54.9%) and 100% (95% CI = 98.3-100%). The RDTs could replace blood smears for diagnosis of malaria in pregnancy by virtue of their relative ease of use. Field-based sensitive tests for malaria in pregnancy are urgently needed.

Screening for attention-deficit/hyperactivity disorder in borderline personality disorder.

PubMed

Weibel, Sébastien; Nicastro, Rosetta; Prada, Paco; Cole, Pierre; Rüfenacht, Eva; Pham, Eléonore; Dayer, Alexandre; Perroud, Nader

2018-01-15

A valid screening instrument is needed to detect attention-deficit/hyperactivity disorder (ADHD) in treatment-seeking borderline personality disorder (BPD) patients. We aimed to test the performance of the widely-used Adult ADHD Self-Report Scale v1.1 screener (ASRS-v1.1). 317 BPD subjects were systematically assessed for comorbid ADHD and completed the ASRS-v1.1. 79 BPD patients also completed the Wender Utah Rating Scale (WURS-25). The prevalence of adult ADHD was of 32.4%. The overall positive predictive value of the ASRS-v1.1 was of 38.5%, the negative predictive value 77.0%, the sensitivity 72.8%, and the specificity 43.9%. Combining WURS-25 and ASRS-v1.1 improved sensitivity to 81.8% and specificity to 59.6%. Cross-sectional study on treatment-seeking patients. We found a high prevalence of ADHD using structured interviews. The ASRS-v1.1 was not a sensitive screener for identifying possible ADHD cases in a BPD population, with a high number of false positives. When combined with the WURS-25, it offered improved screening. Copyright © 2017 Elsevier B.V. All rights reserved.

Label-Enhanced Surface Plasmon Resonance: A New Concept for Improved Performance in Optical Biosensor Analysis

PubMed Central

Granqvist, Niko; Hanning, Anders; Eng, Lars; Tuppurainen, Jussi; Viitala, Tapani

2013-01-01

Surface plasmon resonance (SPR) is a well-established optical biosensor technology with many proven applications in the study of molecular interactions as well as in surface and material science. SPR is usually applied in the label-free mode which may be advantageous in cases where the presence of a label may potentially interfere with the studied interactions per se. However, the fundamental challenges of label-free SPR in terms of limited sensitivity and specificity are well known. Here we present a new concept called label-enhanced SPR, which is based on utilizing strongly absorbing dye molecules in combination with the evaluation of the full shape of the SPR curve, whereby the sensitivity as well as the specificity of SPR is significantly improved. The performance of the new label-enhanced SPR method was demonstrated by two simple model assays: a small molecule assay and a DNA hybridization assay. The small molecule assay was used to demonstrate the sensitivity enhancement of the method, and how competitive assays can be used for relative affinity determination. The DNA assay was used to demonstrate the selectivity of the assay, and the capabilities in eliminating noise from bulk liquid composition variations. PMID:24217357

GaAs Coupled Micro Resonators with Enhanced Sensitive Mass Detection

PubMed Central

Chopard, Tony; Lacour, Vivien; Leblois, Therese

2014-01-01

This work demonstrates the improvement of mass detection sensitivity and time response using a simple sensor structure. Indeed, complicated technological processes leading to very brittle sensing structures are often required to reach high sensitivity when we want to detect specific molecules in biological fields. These developments constitute an obstacle to the early diagnosis of diseases. An alternative is the design of coupled structures. In this study, the device is based on the piezoelectric excitation and detection of two GaAs microstructures vibrating in antisymmetric modes. GaAs is a crystal which has the advantage to be micromachined easily using typical clean room processes. Moreover, we showed its high potential in direct biofunctionalisation for use in the biological field. A specific design of the device was performed to improve the detection at low mass and an original detection method has been developed. The principle is to exploit the variation in amplitude at the initial resonance frequency which has in the vicinity of weak added mass the greatest slope. Therefore, we get a very good resolution for an infinitely weak mass: relative voltage variation of 8%/1 fg. The analysis is based on results obtained by finite element simulation. PMID:25474375

Combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes (COMPARE-MS) for the rapid, sensitive and quantitative detection of DNA methylation.

PubMed

Yegnasubramanian, Srinivasan; Lin, Xiaohui; Haffner, Michael C; DeMarzo, Angelo M; Nelson, William G

2006-02-09

Hypermethylation of CpG island (CGI) sequences is a nearly universal somatic genome alteration in cancer. Rapid and sensitive detection of DNA hypermethylation would aid in cancer diagnosis and risk stratification. We present a novel technique, called COMPARE-MS, that can rapidly and quantitatively detect CGI hypermethylation with high sensitivity and specificity in hundreds of samples simultaneously. To quantitate CGI hypermethylation, COMPARE-MS uses real-time PCR of DNA that was first digested by methylation-sensitive restriction enzymes and then precipitated by methyl-binding domain polypeptides immobilized on a magnetic solid matrix. We show that COMPARE-MS could detect five genome equivalents of methylated CGIs in a 1000- to 10,000-fold excess of unmethylated DNA. COMPARE-MS was used to rapidly quantitate hypermethylation at multiple CGIs in >155 prostate tissues, including benign and malignant prostate specimens, and prostate cell lines. This analysis showed that GSTP1, MDR1 and PTGS2 CGI hypermethylation as determined by COMPARE-MS could differentiate between malignant and benign prostate with sensitivities >95% and specificities approaching 100%. This novel technology could significantly improve our ability to detect CGI hypermethylation.

Diagnostic accuracy of three monoclonal stool tests in a large series of untreated Helicobacter pylori infected patients.

PubMed

Lario, Sergio; Ramírez-Lázaro, María José; Montserrat, Antònia; Quílez, María Elisa; Junquera, Félix; Martínez-Bauer, Eva; Sanfeliu, Isabel; Brullet, Enric; Campo, Rafael; Segura, Ferran; Calvet, Xavier

2016-06-01

Immunochromatographic tests need to be improved in order to enhance their reliability. Recently, several new kits have appeared on the market. The objective was to evaluate the diagnostic accuracy of three monoclonal rapid stool tests - the new Uni-Gold™ H.pylori Antigen (Trinity Biotech, Ireland), the RAPID Hp StAR (Oxoid Ltd., UK) and the ImmunoCard STAT! HpSA (Meridian Diagnostics, USA) - for detecting H. pylori infection prior to eradication treatment. Diagnostic accuracy (sensitivity and specificity) and reliability (concordance between observers) were evaluated in 250 untreated consecutive dyspeptic patients. The gold standard for diagnosing H. pylori infection was defined as the concordance of two or more of rapid urease test (RUT), histopathology and urease breath test (UBT) or positive culture in isolation. Readings of immunochromatographic tests were performed by two different observers. Sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated. Sensitivity and specificity were compared using the McNemar test. The three tests showed a good correlation, with Kappa values>0.9. RAPID Hp StAR had a sensitivity of 91%-92% and a specificity ranging from 77% to 85%. Its sensitivity was higher than that of Uni-Gold™ H.pylori Antigen and ImmunoCard STAT! HpSA (p<0.01). Uni-Gold™ H.pylori Antigen kit showed a sensitivity of 83%, similar to ImmunoCard STAT! HpSA. Specificity of Uni-Gold™ H.pylori Antigen approached 90% (87-89%) and was superior to that of RAPID Hp StAR (p<0.01). Uni-Gold™ H.pylori Antigen and ImmunoCard STAT! HpSA present similar levels of diagnostic accuracy. RAPID Hp StAR was the most sensitive but less reliable of the three immunochromatographic stool tests. None are as accurate and reliable as UBT, RUT and histology. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Automated analysis of retinal images for detection of referable diabetic retinopathy.

PubMed

Abràmoff, Michael D; Folk, James C; Han, Dennis P; Walker, Jonathan D; Williams, David F; Russell, Stephen R; Massin, Pascale; Cochener, Beatrice; Gain, Philippe; Tang, Li; Lamard, Mathieu; Moga, Daniela C; Quellec, Gwénolé; Niemeijer, Meindert

2013-03-01

The diagnostic accuracy of computer detection programs has been reported to be comparable to that of specialists and expert readers, but no computer detection programs have been validated in an independent cohort using an internationally recognized diabetic retinopathy (DR) standard. To determine the sensitivity and specificity of the Iowa Detection Program (IDP) to detect referable diabetic retinopathy (RDR). In primary care DR clinics in France, from January 1, 2005, through December 31, 2010, patients were photographed consecutively, and retinal color images were graded for retinopathy severity according to the International Clinical Diabetic Retinopathy scale and macular edema by 3 masked independent retinal specialists and regraded with adjudication until consensus. The IDP analyzed the same images at a predetermined and fixed set point. We defined RDR as more than mild nonproliferative retinopathy and/or macular edema. A total of 874 people with diabetes at risk for DR. Sensitivity and specificity of the IDP to detect RDR, area under the receiver operating characteristic curve, sensitivity and specificity of the retinal specialists' readings, and mean interobserver difference (κ). The RDR prevalence was 21.7% (95% CI, 19.0%-24.5%). The IDP sensitivity was 96.8% (95% CI, 94.4%-99.3%) and specificity was 59.4% (95% CI, 55.7%-63.0%), corresponding to 6 of 874 false-negative results (none met treatment criteria). The area under the receiver operating characteristic curve was 0.937 (95% CI, 0.916-0.959). Before adjudication and consensus, the sensitivity/specificity of the retinal specialists were 0.80/0.98, 0.71/1.00, and 0.91/0.95, and the mean intergrader κ was 0.822. The IDP has high sensitivity and specificity to detect RDR. Computer analysis of retinal photographs for DR and automated detection of RDR can be implemented safely into the DR screening pipeline, potentially improving access to screening and health care productivity and reducing visual loss through early treatment.

Demand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal Immunochemical Test and Age/Sex-Specific Thresholds for Test Positivity.

PubMed

Chen, Sam Li-Sheng; Hsu, Chen-Yang; Yen, Amy Ming-Fang; Young, Graeme P; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Lee, Yi-Chia; Chiu, Han-Mo; Chiou, Shu-Ti; Chen, Hsiu-Hsi

2018-06-01

Background: Despite age and sex differences in fecal hemoglobin (f-Hb) concentrations, most fecal immunochemical test (FIT) screening programs use population-average cut-points for test positivity. The impact of age/sex-specific threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening are unknown. Methods: Using data from 723,113 participants enrolled in a Taiwanese population-based colorectal cancer screening with single FIT between 2004 and 2009, sensitivity and specificity were estimated for various f-Hb thresholds for test positivity. This included estimates based on a "universal" threshold, receiver-operating-characteristic curve-derived threshold, targeted sensitivity, targeted false-positive rate, and a colonoscopy-capacity-adjusted method integrating colonoscopy workload with and without age/sex adjustments. Results: Optimal age/sex-specific thresholds were found to be equal to or lower than the universal 20 μg Hb/g threshold. For older males, a higher threshold (24 μg Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear relationship was observed between sensitivity and colonoscopy workload with workload rising disproportionately to sensitivity at 16 μg Hb/g. At this "colonoscopy-capacity-adjusted" threshold, the test positivity (colonoscopy workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0% workload and a lower 78.7% sensitivity using 20 μg Hb/g. When constrained on capacity, age/sex-adjusted estimates were generally lower. However, optimizing age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or greater compared with a universal threshold. Conclusions: Age/sex-specific thresholds improve FIT accuracy with modest increases in colonoscopy demand. Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds may be useful in optimizing individual screening programs based on detection accuracy, population characteristics, and clinical capacity. Cancer Epidemiol Biomarkers Prev; 27(6); 704-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Electronic Raman scattering as an ultra-sensitive probe of strain effects in semiconductors

DOE PAGES

Fluegel., Brian; Mialitsin, Aleksej V.; Beaton, Daniel A.; ...

2015-05-28

In this study, the semiconductor strain engineering has become a critical feature of high-performance electronics because of the significant device performance enhancements that it enables. These improvements, which emerge from strain-induced modifications to the electronic band structure, necessitate new ultra-sensitive tools to probe the strain in semiconductors. Here, we demonstrate that minute amounts of strain in thin semiconductor epilayers can be measured using electronic Raman scattering. We applied this strain measurement technique to two different semiconductor alloy systems using coherently strained epitaxial thin films specifically designed to produce lattice-mismatch strains as small as 10 –4. Comparing our strain sensitivity andmore » signal strength in Al xGa 1–xAs with those obtained using the industry-standard technique of phonon Raman scattering, we found that there was a sensitivity improvement of 200-fold and a signal enhancement of 4 × 10 3, thus obviating key constraints in semiconductor strain metrology.« less

Improving the depth sensitivity of time-resolved measurements by extracting the distribution of times-of-flight

PubMed Central

Diop, Mamadou; St. Lawrence, Keith

2013-01-01

Time-resolved (TR) techniques provide a means of discriminating photons based on their time-of-flight. Since early arriving photons have a lower probability of probing deeper tissue than photons with long time-of-flight, time-windowing has been suggested as a method for improving depth sensitivity. However, TR measurements also contain instrument contributions (instrument-response-function, IRF), which cause temporal broadening of the measured temporal point-spread function (TPSF) compared to the true distribution of times-of-flight (DTOF). The purpose of this study was to investigate the influence of the IRF on the depth sensitivity of TR measurements. TPSFs were acquired on homogeneous and two-layer tissue-mimicking phantoms with varying optical properties. The measured IRF and TPSFs were deconvolved using a stable algorithm to recover the DTOFs. The microscopic Beer-Lambert law was applied to the TPSFs and DTOFs to obtain depth-resolved absorption changes. In contrast to the DTOF, the latest part of the TPSF was not the most sensitive to absorption changes in the lower layer, which was confirmed by computer simulations. The improved depth sensitivity of the DTOF was illustrated in a pig model of the adult human head. Specifically, it was shown that dynamic absorption changes obtained from the late part of the DTOFs recovered from TPSFs acquired by probes positioned on the scalp were similar to absorption changes measured directly on the brain. These results collectively demonstrate that this method improves the depth sensitivity of TR measurements by removing the effects of the IRF. PMID:23504445

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

PubMed

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

2018-06-01

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

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.

House-dust mite allergy: mapping of Dermatophagoides pteronyssinus allergens for dogs by two-dimensional immunoblotting.

PubMed

Martins, Luís Miguel Lourenço; Marques, Andreia Grilo; Pereira, Luísa Maria Dotti Silva; Goicoa, Ana; Semião-Santos, Saul José; Bento, Ofélia Pereira

2015-04-01

Specific immunotherapy has shown to be very useful for allergy control in dogs, with a common success rate ranging from 65% to 70%. However, this efficacy could probably be improved and the identification of individual allergomes, with the choice of more adequate molecular allergen pools for specific immunotherapy, being the strategy. To map Dermatophagoides pteronyssinus (Der p) allergens for mite-sensitized atopic dogs, for better understanding how individual allergograms may influence the response to house-dust mite immunotherapy. To identify the Der p mite allergome for dogs, 20 individuals allergic to dust-mites and sensitized to Der p, were selected. The extract from Der p was submitted to isoelectric focusing (IEF), one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were blotted onto polyvinylidene difluoride (PVDF) membranes and immunoblottings were performed with patient sera. Allergen-bound specific IgE was detected. Eleven allergens were identified from isoelectric focusing (IEF), as well as from 1-D SDS PAGE. From 2-D SDS-PAGE, 24 spots were identified. Several similarities were found between dog and human allergograms and no absolute correlation between sensitization and allergy was observed either. As in humans, different individual allergograms do not seem to implicate different clinical patterns, but may influence the response to specific immunotherapy. The molecular epidemiology approach in veterinary allergy management, by the characterization of individual patients' allergoms and by choosing the best molecular allergen pool for each patient could also improve the efficacy of allergy immunotherapy.

Choosing a design to fit the situation: how to improve specificity and positive predictive values using Bayesian lot quality assurance sampling.

PubMed

Olives, Casey; Pagano, Marcello

2013-02-01

Lot Quality Assurance Sampling (LQAS) is a provably useful tool for monitoring health programmes. Although LQAS ensures acceptable Producer and Consumer risks, the literature alleges that the method suffers from poor specificity and positive predictive values (PPVs). We suggest that poor LQAS performance is due, in part, to variation in the true underlying distribution. However, until now the role of the underlying distribution in expected performance has not been adequately examined. We present Bayesian-LQAS (B-LQAS), an approach to incorporating prior information into the choice of the LQAS sample size and decision rule, and explore its properties through a numerical study. Additionally, we analyse vaccination coverage data from UNICEF's State of the World's Children in 1968-1989 and 2008 to exemplify the performance of LQAS and B-LQAS. Results of our numerical study show that the choice of LQAS sample size and decision rule is sensitive to the distribution of prior information, as well as to individual beliefs about the importance of correct classification. Application of the B-LQAS approach to the UNICEF data improves specificity and PPV in both time periods (1968-1989 and 2008) with minimal reductions in sensitivity and negative predictive value. LQAS is shown to be a robust tool that is not necessarily prone to poor specificity and PPV as previously alleged. In situations where prior or historical data are available, B-LQAS can lead to improvements in expected performance.

Performance of the high-sensitivity troponin assay in diagnosing acute myocardial infarction: systematic review and meta-analysis

PubMed Central

Al-Saleh, Ayman; Alazzoni, Ashraf; Al Shalash, Saleh; Ye, Chenglin; Mbuagbaw, Lawrence; Thabane, Lehana; Jolly, Sanjit S.

2014-01-01

Background High-sensitivity cardiac troponin assays have been adopted by many clinical centres worldwide; however, clinicians are uncertain how to interpret the results. We sought to assess the utility of these assays in diagnosing acute myocardial infarction (MI). Methods We carried out a systematic review and meta-analysis of studies comparing high-sensitivity with conventional assays of cardiac troponin levels among adults with suspected acute MI in the emergency department. We searched MEDLINE, EMBASE and Cochrane databases up to April 2013 and used bivariable random-effects modelling to obtain summary parameters for diagnostic accuracy. Results We identified 9 studies that assessed the use of high-sensitivity troponin T assays (n = 9186 patients). The summary sensitivity of these tests in diagnosing acute MI at presentation to the emergency department was estimated to be 0.94 (95% confidence interval [CI] 0.89–0.97); for conventional tests, it was 0.72 (95% CI 0.63–0.79). The summary specificity was 0.73 (95% CI 0.64–0.81) for the high-sensitivity assay compared with 0.95 (95% CI 0.93–0.97) for the conventional assay. The differences in estimates of the summary sensitivity and specificity between the high-sensitivity and conventional assays were statistically significant (p < 0.01). The area under the curve was similar for both tests carried out 3–6 hours after presentation. Three studies assessed the use of high-sensitivity troponin I assays and showed similar results. Interpretation Used at presentation to the emergency department, the high-sensitivity cardiac troponin assay has improved sensitivity, but reduced specificity, compared with the conventional troponin assay. With repeated measurements over 6 hours, the area under the curve is similar for both tests, indicating that the major advantage of the high-sensitivity test is early diagnosis. PMID:25295240

Audit of cytology of upper urinary tract.

PubMed

Malta, F; Lenos, M; Leotsakos, I; Katafigiotis, I; Gakiopoulou, H; Constantinides, C; Mikou, P

2016-10-01

Cytology is an essential tool for the investigation of urinary tract malignancy. In this audit, we aimed to assess our laboratory performance in the diagnosis of upper urinary tract malignancy and to use the information provided to improve our service. We retrieved cytology reports of upper urinary tract specimens from two periods, re-evaluated the cases, compared the reports with histology data and estimated the sensitivity, specificity and positive predictive value (PPV). In the time interval between the two periods, we adopted new terminology, established better communication with clinicians and gained experience in the field. Finally, the data from the two periods were compared. In phase A, we estimated a sensitivity of 73%, specificity of 86% and PPV of 84.6%. As a result of the cytological re-evaluation, correlation with histology and clinical follow-up, plus communication with the clinicians during the audit, we established new terminology and a new request form. A three tiered grading system of atypia (mild, moderate and severe) was replaced by a two tiered grading system. The first category "atypia probably benign" corresponded to "mild atypia" while the second category "atypia, not otherwise specified" corresponded to "moderate atypia". The cases diagnosed as "severe atypia" were reclassified as "suspicious for malignancy". In phase B, the sensitivity, specificity and PPV were 75%, 89% and 90%, respectively. Our laboratory performance is in concordance with reported data and has been improved through this study. The audit process is extremely valuable for the identification of problems, for taking action and, finally, for the improvement of the clinical cytology service in the field of upper urinary tract malignancy. © 2016 John Wiley & Sons Ltd.

A technique to improve diagnostic information from fine-needle aspirations: immunohistochemistry on cytoscrape.

PubMed

Skov, Birgit Guldhammer; Kiss, Katalin; Ramsted, Julie; Linnemann, Dorte

2009-04-25

Cytologic examination of fine-needle aspiration (FNA) material is being used increasingly for the diagnosis of pulmonary lesions. Accurate distinction between nonsmall cell lung cancer (NSCLC), including subgroups, and small cell lung cancer and between primary lung cancer and metastases has therapeutic impact. However, the distinction between these groups may be difficult on smears. In this report, the authors describe a simple method, called cytoscrape (CS), which can be used on virtually any smear to produce material useful for ancillary methods, including immunohistochemistry. Aspirates from 47 patients who had possible malignant infiltrates identified on computed tomography scans of the chest were included. Smears were stained by May-Grunwald-Giemsa and Diff-Quick for diagnostic purposes. CS material was obtained by gently scraping cells off the slides. Clots were made, and the sections were stained for thyroid transcription factor-1 (TTF-1) and mucin. The utility of the CS technique was evaluated by assessing the sensitivity and specificity of the method and by quantifying the extra diagnostic information obtained by the method relative to smears alone. Malignant tumor cells in the CS material were identified in 43 aspirates (91%). Both the sensitivity and the specificity for TTF-1 were 100%. The sensitivity for mucin was 60%, and the specificity for mucin was 100%. The diagnoses made on smears were improved by CS in 31 patients (72%), in that more precise separation of subgroups of NSCLC was possible or information on primary tumors was obtained. The CS technique improved the diagnostic information from FNA in a clinically relevant way. The method is simple, quick, and inexpensive. (c) 2009 American Cancer Society.

Abbreviated breast magnetic resonance protocol: Value of high-resolution temporal dynamic sequence to improve lesion characterization.

PubMed

Oldrini, Guillaume; Fedida, Benjamin; Poujol, Julie; Felblinger, Jacques; Trop, Isabelle; Henrot, Philippe; Darai, Emile; Thomassin-Naggara, Isabelle

2017-10-01

To evaluate the added value of ULTRAFAST-MR sequence to an abbreviated FAST protocol in comparison with FULL protocol to distinguish benign from malignant lesions in a population of women, regardless of breast MR imaging indication. From March 10th to September 22th, 2014, we retrospectively included a total of 70 consecutive patients with 106 histologically proven lesions (58 malignant and 48 benign) who underwent breast MR imaging for preoperative breast staging (n=38), high-risk screening (n=7), problem solving (n=18), and nipple discharge (n=4) with 12 time resolved imaging of contrast kinetics (TRICKS) acquisitions during contrast inflow interleaved in a regular high-resolution dynamic MRI protocol (FULL protocol). Two readers scored MR exams as either positive or negative and described significant lesions according to Bi-RADS lexicon with a TRICKS images (ULTRAFAST), an abbreviated protocol (FAST) and all images (FULL protocol). Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for each protocol and compared with McNemar's test. For all readers, the combined FAST-ULTRAFAST protocol significantly improved the reading with a specificity of 83.3% and 70.8% in comparison with FAST protocol or FULL protocol, respectively, without change in sensitivity. By adding ULTRAFAST protocol to FAST protocol, readers 1 and 2 were able to correctly change the diagnosis in 22.9% (11/48) and 10.4% (5/48) of benign lesions, without missing any malignancy, respectively. Both interpretation and image acquisition times for combined FAST-ULTRAFAST protocol and FAST protocol were shorter compared to FULL protocol (p<0.001). Compared to FULL protocol, adding ULTRAFAST to FAST protocol improves specificity, mainly in correctly reclassifying benign masses and reducing interpretation and acquisition time, without decreasing sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface Plasmon Resonance kinetic analysis of the interaction between G-quadruplex nucleic acids and an anti-G-quadruplex monoclonal antibody.

PubMed

Lago, Sara; Nadai, Matteo; Rossetto, Monica; Richter, Sara N

2018-06-01

G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a highly sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody on the SPR sensor chip to optimize detection of binding antigens. SPR was employed to characterize the anti-G4 antibody interaction with G4 and non-G4 oligonucleotides. Dextran-functionalized sensor chips were used both in covalent coupling and capturing procedures. The use of two leading molecule for orienting the antibody of interest allowed to improve its activity from completely non-functional to 65% active. The specificity of the anti-G4 antobody for G4 structures could thus be assessed with high sensitivity and reliability. Optimization of the immobilization protocol for SPR biosensing, allowed us to determine the anti-G4 antibody affinity and specificity for G4 antigens with higher sensitivity with respect to other in vitro assays such as ELISA. Anti-G4 antibody specificity is a fundamental assumption for the future utilization of this kind of antibodies for monitoring G4s directly in cells. The heterogeneous orientation of amine-coupling immobilized ligands is a general problem that often leads to partial or complete inactivation of the molecules. Here we describe a new strategy for improving ligand orientation: driving it from two sides. This principle can be virtually applied to every molecule that loses its activity or is poorly immobilized after standard coupling to the SPR chip surface. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.

PubMed

Nankivell, Brian J; Renthawa, Jasveen; Jeoffreys, Neisha; Kable, Kathy; O'Connell, Philip J; Chapman, Jeremy R; Wong, Germaine; Sharma, Raghwa N

2015-08-01

Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction. We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients. The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results. Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

PubMed

Tran Vu Thieu, Nga; Trinh Van, Tan; Tran Tuan, Anh; Klemm, Elizabeth J; Nguyen Ngoc Minh, Chau; Voong Vinh, Phat; Pham Thanh, Duy; Ho Ngoc Dan, Thanh; Pham Duc, Trung; Langat, Pinky; Martin, Laura B; Galan, Jorge; Liang, Li; Felgner, Philip L; Davies, D Huw; de Jong, Hanna K; Maude, Rapeephan R; Fukushima, Masako; Wijedoru, Lalith; Ghose, Aniruddha; Samad, Rasheda; Dondorp, Arjen M; Faiz, Abul; Darton, Thomas C; Pollard, Andrew J; Thwaites, Guy E; Dougan, Gordon; Parry, Christopher M; Baker, Stephen

2017-08-01

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients. IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease. IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid. We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. 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.

Identifying Depressed Older Adults in Primary Care: A Secondary Analysis of a Multisite Randomized Controlled Trial

PubMed Central

Voils, Corrine I.; Olsen, Maren K.; Williams, John W.; for the IMPACT Study Investigators

2008-01-01

Objective: To determine whether a subset of depressive symptoms could be identified to facilitate diagnosis of depression in older adults in primary care. Method: Secondary analysis was conducted on 898 participants aged 60 years or older with major depressive disorder and/or dysthymic disorder (according to DSM-IV criteria) who participated in the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) study, a multisite, randomized trial of collaborative care for depression (recruitment from July 1999 to August 2001). Linear regression was used to identify a core subset of depressive symptoms associated with decreased social, physical, and mental functioning. The sensitivity and specificity, adjusting for selection bias, were evaluated for these symptoms. The sensitivity and specificity of a second subset of 4 depressive symptoms previously validated in a midlife sample was also evaluated. Results: Psychomotor changes, fatigue, and suicidal ideation were associated with decreased functioning and served as the core set of symptoms. Adjusting for selection bias, the sensitivity of these 3 symptoms was 0.012 and specificity 0.994. The sensitivity of the 4 symptoms previously validated in a midlife sample was 0.019 and specificity was 0.997. Conclusion: We identified 3 depression symptoms that were highly specific for major depressive disorder in older adults. However, these symptoms and a previously identified subset were too insensitive for accurate diagnosis. Therefore, we recommend a full assessment of DSM-IV depression criteria for accurate diagnosis. PMID:18311416

Effect of education and gender adjustment on the sensitivity and specificity of a cognitive screening battery for dementia: results from the MoVIES Project. Monongahela Valley Independent Elders Survey.

PubMed

Belle, S H; Seaberg, E C; Ganguli, M; Ratcliff, G; DeKosky, S; Kuller, L H

1996-01-01

The Monongahela Valley Independent Elders Survey (MoVIES) used a multiphase process to identify demented persons among 1,366 randomly selected noninstitutionalized individuals 65 years and older. Raw test scores from a cognitive screening battery were used to identify cognitively impaired individuals who were referred for a clinical evaluation. Subsequently, test scores were adjusted for education and gender within age strata. Adjusting test scores affected sensitivity for dementia only among the most educated, increasing sensitivity among younger subjects and decreasing among the older subjects. Specificity increased among the least educated and the oldest subjects. Overall, the adjusted criteria did not perform as well as the unadjusted criteria in this sample. Adjustment for education will not necessarily improve the ability of a screening battery for cognitive function to identify demented persons, particularly if unadjusted scores perform well.

Comparison of the genexpert enterovirus assay (GXEA) with real-time one step RT-PCR for the detection of enteroviral RNA in the cerebrospinal fluid of patients with meningitis.

PubMed

Hong, JiYoung; Kim, Ahyoun; Hwang, Seoyeon; Cheon, Doo-Sung; Kim, Jong-Hyen; Lee, June-Woo; Park, Jae-Hak; Kang, Byunghak

2015-02-13

Enteroviruses (EVs) are the leading cause of aseptic meningitis worldwide. Detection of enteroviral RNA in clinical specimens has been demonstrated to improve the management of patient care, especially that of neonates and young children. To establish a sensitive and reliable assay for routine laboratory diagnosis, we compared the sensitivity and specificity of the GeneXpert Enterovirus Assay (GXEA) with that of the reverse transcription polymerase chain reaction (RT-PCR) based assay referred to as real-time one step RT-PCR (RTo-PCR). The sensitivity/specificity produced by GXEA and RTo-PCR were 100%/100% and 65%/100%, respectively. Both methods evaluated in this article can be used for detection of enterovirus in clinical specimens and these nucleic acid amplification methods are useful assays for the diagnosis of enteroviral infection.

Cervical VEMP threshold response curve in the identification of Ménière's disease.

PubMed

Zhu, Yi; McPherson, James; Beatty, Charles; Driscoll, Colin; Neff, Brian; Eggers, Scott; Shepard, Neil T

2014-03-01

To investigate the sensitivity/specificity of a shift upward in the most sensitive frequency of the cervical vestibular evoked myogenic potential (cVEMP) threshold-response curve in the identification of Ménière's disease (MD). A secondary purpose was to investigate the clinical characteristics that had an impact on the sensitivity/specificity and to adjust the criteria for a positive shift upward in the cVEMP curve to maximize performance of the test. A retrospective review of patients diagnosed with MD and those without MD. Two hundred ninety-four patients met the inclusion criteria of symptom complaints of spontaneous events of vertigo and a full vestibular and balance evaluation with cVEMP threshold-response curve testing. Two hundred six of these patients were diagnosed with MD, and 88 patients were determined to be non-MD. Review of the patients' medical records was used to extract data on the results of the cVEMP curve, age, gender, duration from time of onset of spontaneous events, pure tone average from hearing test, and water caloric asymmetry. Student's t-test, χ² test, receiver operating characteristic (ROC) curve with area under the curve (AUC), Pearson correlation coefficient, and sensitivity/specificity from 2 × 2 tables were all used in the analysis. Basic sensitivity/specificity for a shift upward in the most sensitive frequency to 1000 Hz in the cVEMP threshold-response curve was 0.47/0.64 respectively. Clinical characteristics that were found to have a significant impact on the sensitivity/specificity were age equal to or above 60 yr and a caloric asymmetry ≥25%. Various combinations of age and caloric with the requirement of a shift upward in the cVEMP curve most sensitive frequency to 1000 Hz resulted in significant but modest improvements in sensitivity/specificity. However, the overall performance was not shown acceptable for routine clinical use with maximum sensitivity at 0.73. Therefore, placing an emphasis on specificity over sensitivity results showed specificity of 0.95 for those under 60 yr and 0.90 for those 60 yr of age or older with sensitivity at 0.20, but only in the context of a ≥25% caloric asymmetry. We recommend the use of the shift upward to 1000 Hz with a caloric asymmetry as the clinical protocol to maximize the use of the cVEMP threshold-response curve for assistance in the identification of MD, in the context of a ≥25% caloric asymmetry. This implies that if the test is negative no interpretation of identification of MD can be made. If the test is positive the results can be used to increase the argument for MD since the probability of the result being a false positive is only 5-10%. American Academy of Audiology.

Incremental Value (Bayesian Framework) of Thoracic Ultrasonography over Thoracic Auscultation for Diagnosis of Bronchopneumonia in Preweaned Dairy Calves.

PubMed

Buczinski, S; Ménard, J; Timsit, E

2016-07-01

Thoracic ultrasonography (TUS) is a specific and relatively sensitive method to diagnose bronchopneumonia (BP) in dairy calves. Unfortunately, as it requires specific training and equipment, veterinarians typically base their diagnosis on thoracic auscultation (AUSC), which is rapid and easy to perform. We hypothesized that the use of TUS, in addition to AUSC, can significantly increase accuracy of BP diagnosis. Therefore, the objectives were to (i) determine the incremental value of TUS over AUSC for diagnosis of BP in preweaned dairy calves and (ii) assess diagnostic accuracy of AUSC. Two hundred and nine dairy calves (<1 month of age) were enrolled in this cross-sectional study. Prospective cross-sectional study. All calves from a veal calves unit were examined (independent operators) using the Wisconsin Calf Respiratory Scoring Criteria (CRSC), AUSC, and TUS. A Bayesian latent class approach was used to estimate the incremental value of AUSC over TUS (integrated discrimination improvement [IDI]) and the diagnostic accuracy of AUSC. Abnormal CRSC, AUSC, and TUS were recorded in 3.3, 53.1, and 23.9% of calves, respectively. AUSC was sensitive (72.9%; 95% Bayesian credible interval [BCI]: 50.1-96.4%), but not specific (53.3%; 95% BCI: 43.3-64.0%) to diagnose BP. Compared to AUSC, TUS was more specific (92.9%; 95% BCI: 86.5-97.1%), but had similar sensitivity (76.5%; 95% BCI: 60.2-88.8%). The incremental value of TUS over AUSC was high (IDI = 43.7%; 5% BCI: 22.0-63.0%) significantly improving proportions of sick and healthy calves appropriately classified. The use of TUS over AUSC significantly improved accuracy of BP diagnosis in dairy calves. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria.

PubMed

2014-03-01

Behçet's disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical diagnostic criteria led to their reassessment. An International Team for the Revision of the International Criteria for BD (from 27 countries) submitted data from 2556 clinically diagnosed BD patients and 1163 controls with BD-mimicking diseases or presenting at least one major BD sign. These were randomly divided into training and validation sets. Logistic regression, 'leave-one-country-out' cross-validation and clinical judgement were employed to develop new International Criteria for BD (ICBD) with the training data. Existing and new criteria were tested for their performance in the validation set. For the ICBD, ocular lesions, oral aphthosis and genital aphthosis are each assigned 2 points, while skin lesions, central nervous system involvement and vascular manifestations 1 point each. The pathergy test, when used, was assigned 1 point. A patient scoring ≥4 points is classified as having BD. In the training set, 93.9% sensitivity and 92.1% specificity were assessed compared with 81.2% sensitivity and 95.9% specificity for the ISG criteria. In the validation set, ICBD demonstrated an unbiased estimate of sensitivity of 94.8% (95% CI: 93.4-95.9%), considerably higher than that of the ISG criteria (85.0%). Specificity (90.5%, 95% CI: 87.9-92.8%) was lower than that of the ISG-criteria (96.0%), yet still reasonably high. For countries with at least 90%-of-cases and controls having a pathergy test, adding 1 point for pathergy test increased the estimate of sensitivity from 95.5% to 98.5%, while barely reducing specificity from 92.1% to 91.6%. The new proposed criteria derived from multinational data exhibits much improved sensitivity over the ISG criteria while maintaining reasonable specificity. It is proposed that the ICBD criteria to be adopted both as a guide for diagnosis and classification of BD. © 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.

Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma.

PubMed

Mazurek, Agnieszka M; Fiszer-Kierzkowska, A; Rutkowski, T; Składowski, K; Pierzyna, M; Scieglińska, D; Woźniak, G; Głowacki, G; Kawczyński, R; Małusecka, E

2013-01-01

The precise analysis of tumour markers in blood such as circulating cell-free DNA (cfDNA) could have a significant impact in facilitating monitoring of patients after initial therapy. Although high levels of total cfDNA in plasma of cancer patients are consistently demonstrated, a low sensitivity of DNA alterations is reported. The major question regards the recovery of tumour-specific cfDNA such as KRAS mutated DNA and cancer-associated type 16 of human papillomavirus (HPV16). TaqMan technology was used for detection of KRAS mutation, HPV16 and to quantify cfDNA in blood plasma. Comparison of four different column-based commercial kits shows that the cfDNA purification carried out by the Genomic Mini AX Body Fluids kit and the QIAamp Circulating Nucleic Acid kit gave us the possibility to improve the sensitivity of detection of KRAS mutation and HPV16. The optimized method was used to follow the reduction in cancer-specific cfDNA after therapy. We found that large volume extractions with low volume of DNA eluate enabled trace amounts of tumour-specific cfDNA from cancer patients to be effectively identified. Data presented in this study facilitate detection of tumour-specific cfDNA and improve standards needed for the implementation of cfDNA technology into routine clinical practice.

Cardiovascular biomarkers and sex: the case for women.

PubMed

Daniels, Lori B; Maisel, Alan S

2015-10-01

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

On-site detection of stacked genetically modified soybean based on event-specific TM-LAMP and a DNAzyme-lateral flow biosensor.

PubMed

Cheng, Nan; Shang, Ying; Xu, Yuancong; Zhang, Li; Luo, Yunbo; Huang, Kunlun; Xu, Wentao

2017-05-15

Stacked genetically modified organisms (GMO) are becoming popular for their enhanced production efficiency and improved functional properties, and on-site detection of stacked GMO is an urgent challenge to be solved. In this study, we developed a cascade system combining event-specific tag-labeled multiplex LAMP with a DNAzyme-lateral flow biosensor for reliable detection of stacked events (DP305423× GTS 40-3-2). Three primer sets, both event-specific and soybean species-specific, were newly designed for the tag-labeled multiplex LAMP system. A trident-like lateral flow biosensor displayed amplified products simultaneously without cross contamination, and DNAzyme enhancement improved the sensitivity effectively. After optimization, the limit of detection was approximately 0.1% (w/w) for stacked GM soybean, which is sensitive enough to detect genetically modified content up to a threshold value established by several countries for regulatory compliance. The entire detection process could be shortened to 120min without any large-scale instrumentation. This method may be useful for the in-field detection of DP305423× GTS 40-3-2 soybean on a single kernel basis and on-site screening tests of stacked GM soybean lines and individual parent GM soybean lines in highly processed foods. Copyright © 2017 Elsevier B.V. All rights reserved.

An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

PubMed

Reinisch, S; Schweiger, K; Pablik, E; Collet-Fenetrier, B; Peyrin-Biroulet, L; Alfaro, I; Panés, J; Moayyedi, P; Reinisch, W

2016-09-01

The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC. © 2016 John Wiley & Sons Ltd.

Evaluating the diagnostic accuracy of the Xpert MTB/RIF assay on bronchoalveolar lavage fluid: A retrospective study.

PubMed

Lu, Yanjun; Zhu, Yaowu; Shen, Na; Tian, Lei; Sun, Ziyong

2018-02-08

Limited data on the diagnostic accuracy of the Xpert MTB/RIF assay using bronchoalveolar lavage fluid from patients with suspected pulmonary tuberculosis (PTB) have been reported in China. Therefore, a retrospective study was designed to evaluate the diagnostic accuracy of this assay. Clinical, radiological, and microbiological characteristics of 238 patients with suspected PTB were reviewed retrospectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of active PTB were calculated for the Xpert MTB/RIF assay using TB culture or final diagnosis based on clinical and radiological evaluation as the reference standard. The sensitivity and specificity of the Xpert MTB/RIF assay were 84.5% and 98.9%, respectively, and those for smear microscopy were 36.2% and 100%, respectively, when compared to the culture method. However, compared with the sensitivity and specificity of final diagnosis based on clinical and radiological evaluation, the sensitivity and specificity of the assay were 72.9% and 98.7%, respectively, which were significantly higher than those for smear microscopy. The Xpert MTB/RIF assay on bronchoalveolar lavage fluid could serve as an additional rapid diagnostic tool for PTB in a high TB-burden country and improve the time to TB treatment initiation in patients with PTB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Not all ultrasounds are created equal: general sonography versus musculoskeletal sonography in the detection of rotator cuff tears

PubMed Central

Cole, Brandi; Twibill, Kristen; Lam, Patrick; Hackett, Lisa

2016-01-01

Background This cross-sectional analytic diagnostic accuracy study was designed to compare the accuracy of ultrasound performed by general sonographers in local radiology practices with ultrasound performed by an experienced musculoskeletal sonographer for the detection of rotator cuff tears. Methods In total, 238 patients undergoing arthroscopy who had previously had an ultrasound performed by both a general sonographer and a specialist musculoskeletal sonographer made up the study cohort. Accuracy of diagnosis was compared with the findings at arthroscopy. Results When analyzed as all tears versus no tears, musculoskeletal sonography had an accuracy of 97%, a sensitivity of 97% and a specificity of 95%, whereas general sonography had an accuracy of 91%, a sensitivity of 91% and a specificity of 86%. When the partial tears were split with those ≥ 50% thickness in the tear group and those < 50% thickness in the no-tear group, musculoskeletal sonography had an accuracy of 97%, a sensitivity of 97% and a specificity of 100% and general sonography had an accuracy of 85%, a sensitivity of 84% and a specificity of 87%. Conclusions Ultrasound in the hands of an experienced musculoskeletal sonographer is highly accurate for the diagnosis of rotator cuff tears. General sonography has improved subsequent to earlier studies but remains inferior to an ultrasound performed by a musculoskeletal sonographer. PMID:27660657

A Comparative Observational Study of the Use of Saline Uterine Hydrosonography for the Diagnosis and Assessment of Uterine Cavity Lesions in Women

PubMed Central

2016-01-01

Aim of this study was to evaluate the performance of saline hydrosonography (HSGM) (also known as saline infusion sonography (SIS)) against transvaginal ultrasound scan (TVS) and hysteroscopy in the diagnosis of uterine cavity lesions. Diagnostic hysteroscopy with biopsy is considered as the “gold standard” to diagnose intrauterine abnormalities. The introduction of HSGM has improved the diagnostic capability of ultrasound. It is important to establish the efficacy and safety of HSGM before it is widely recommended for use. This retrospective observational data was collected from all 223 patients who underwent TVS, HSGM, and hysteroscopy as part of their gynaecological investigations from 1 January 2008 to 31 December 2010 at Central Middlesex Hospital, London. Endometrial Polyps. TVS: sensitivity 60.53%, specificity 97.06%, positive predictive value (PPV) 95.83%, and negative predictive value (NPV) 68.75% and HSGM: sensitivity 95%, specificity 97.14%, PPV 97.44%, and NPV 94.44%. Submucous Leiomyoma. TVS: sensitivity 57.14%, specificity 93.48%, PPV 84.21%, and NPV 78.18% and HSGM: sensitivity 96.55%, specificity 100.00%, PPV 100.00%, and NPV 97.92%. Diagnostic efficacy of HSGM is superior to TVS for the diagnosis of endometrial polyps and submucous fibroids. HSGM should be considered as an intermediate investigation after TVS to assess intracavity pathology and to confirm the diagnosis; hysteroscopy should become a therapeutic intervention. PMID:27597989

A prediction model based on an artificial intelligence system for moderate to severe obstructive sleep apnea.

PubMed

Sun, Lei Ming; Chiu, Hung-Wen; Chuang, Chih Yuan; Liu, Li

2011-09-01

Obstructive sleep apnea (OSA) is a major concern in modern medicine; however, it is difficult to diagnose. Screening questionnaires such as the Berlin questionnaire, Rome questionnaire, and BASH'IM score are used to identify patients with OSA. However, the sensitivity and specificity of these tools are not satisfactory. We aim to introduce an artificial intelligence method to screen moderate to severe OSA patients (apnea-hypopnea index ≧15). One hundred twenty patients were asked to complete a newly developed questionnaire before undergoing an overnight polysomnography (PSG) study. One hundred ten validated questionnaires were enrolled in this study. Genetic algorithm (GA) was used to build the five best models based on these questionnaires. The same data were analyzed with logistic regression (LR) for comparison. The sensitivity of the GA models varied from 81.8% to 88.0%, with a specificity of 95% to 97%. On the other hand, the sensitivity and specificity of the LR model were 55.6% and 57.9%, respectively. GA provides a good solution to build models for screening moderate to severe OSA patients, who require PSG evaluation and medical intervention. The questionnaire did not require any special biochemistry data and was easily self-administered. The sensitivity and specificity of the GA models are satisfactory and may improve when more patients are recruited.

Robustness Regions for Dichotomous Decisions.

ERIC Educational Resources Information Center

Vijn, Pieter; Molenaar, Ivo W.

1981-01-01

In the case of dichotomous decisions, the total set of all assumptions/specifications for which the decision would have been the same is the robustness region. Inspection of this (data-dependent) region is a form of sensitivity analysis which may lead to improved decision making. (Author/BW)

USRD type F63 transducer

NASA Astrophysics Data System (ADS)

Jevnager, M. D.; Tims, A. C.

1981-11-01

A small reversible audio frequency range transducer was developed. The type F63 transducer is designed to meet the specific needs of the user. It is sensitive and stable with temperature and moderate hydrostatic pressures as required by Naval Mine Engineering Facility to improve their mission capability.

A two-factor theory for concussion assessment using ImPACT: memory and speed.

PubMed

Schatz, Philip; Maerlender, Arthur

2013-12-01

We present the initial validation of a two-factor structure of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) using ImPACT composite scores and document the reliability and validity of this factor structure. Factor analyses were conducted for baseline (N = 21,537) and post-concussion (N = 560) data, yielding "Memory" (Verbal and Visual) and "Speed" (Visual Motor Speed and Reaction Time) Factors; inclusion of Total Symptom Scores resulted in a third discrete factor. Speed and Memory z-scores were calculated, and test-retest reliability (using intra-class correlation coefficients) at 1 month (0.88/0.81), 1 year (0.85/0.75), and 2 years (0.76/0.74) were higher than published data using Composite scores. Speed and Memory scores yielded 89% sensitivity and 70% specificity, which was higher than composites (80%/62%) and comparable with subscales (91%/69%). This emergent two-factor structure has improved test-retest reliability with no loss of sensitivity/specificity and may improve understanding and interpretability of ImPACT test results.

Hybrid ANN optimized artificial fish swarm algorithm based classifier for classification of suspicious lesions in breast DCE-MRI

NASA Astrophysics Data System (ADS)

Janaki Sathya, D.; Geetha, K.

2017-12-01

Automatic mass or lesion classification systems are developed to aid in distinguishing between malignant and benign lesions present in the breast DCE-MR images, the systems need to improve both the sensitivity and specificity of DCE-MR image interpretation in order to be successful for clinical use. A new classifier (a set of features together with a classification method) based on artificial neural networks trained using artificial fish swarm optimization (AFSO) algorithm is proposed in this paper. The basic idea behind the proposed classifier is to use AFSO algorithm for searching the best combination of synaptic weights for the neural network. An optimal set of features based on the statistical textural features is presented. The investigational outcomes of the proposed suspicious lesion classifier algorithm therefore confirm that the resulting classifier performs better than other such classifiers reported in the literature. Therefore this classifier demonstrates that the improvement in both the sensitivity and specificity are possible through automated image analysis.

Natural gas applications for hybrid vehicles. Final report, October 1992-July 1993

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

Bentley, J.M.

1993-08-01

Hybrid vehicle technology holds the potential for improved efficiency and emissions compared with internal combustion (IC) engines and improved range and refueling convenience over electric vehicles. This study evaluated the potential for using natural gas as a hybrid vehicle fuel. Potential regulatory and market drivers were evaluated for hybrids generally and natural gas hybrids in specific. Heat engine options and other configuration issues were investigated to determine efficiency, emissions or other benefits of light- and heavy-duty hybrids. Several hybrid vehicle configurations were evaluated to determine the specific packaging attributes of natural gas in a hybrid configuration. Generally, conventional IC enginesmore » appear adequate for most emissions-sensitive hybrid applications with no great advantage being gained from using turbines or other more advanced heat engines. The largest technology barrier to a near-term hybrid is the weight of available or near-term batteries. Smaller, light-duty hybrid vehicles will be more sensitive to this weight handicap than larger vehicles such as the urban transit bus.« less

Screening for Spiritual Struggle in an Adolescent Transgender Clinic: Feasibility and Acceptability.

PubMed

Grossoehme, Daniel H; Teeters, Alexis; Jelinek, Sue; Dimitriou, Sophia M; Conard, Lee Ann E

2016-01-01

Spiritual struggles are associated with poorer health outcomes, including depression, which has higher prevalence among transgender individuals than the general population. This study's objective was to improve the quality of care in an outpatient transgender clinic by screening patients and caregivers for spiritual struggle and future intervention. The quality improvement questions addressed were whether screening for spiritual struggle was feasible and acceptable; and whether the sensitivity and specificity of the Rush Protocol were acceptable. Revision of the screening was based on cognitive interviews with the 115 adolescents and caregivers who were screened. Prevalence of spiritual struggle was 38-47%. Compared to the Negative R-COPE, the Rush Protocol screener had sensitivities of 44-80% and specificities of 60-74%. The Rush Protocol was acceptable to adolescents seen in a transgender clinic, caregivers, and clinic staff; was feasible to deliver during outpatient clinic visits, and offers a straightforward means of identifying transgender persons and caregivers experiencing spiritual struggle.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2012-01-26

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

Diagnostic performance of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry in blood bacterial infections: a systematic review and meta-analysis.

PubMed

Scott, Jamie S; Sterling, Sarah A; To, Harrison; Seals, Samantha R; Jones, Alan E

2016-07-01

Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) has shown promise in decreasing time to identification of causative organisms compared to traditional methods; however, the utility of MALDI-TOF MS in a heterogeneous clinical setting is uncertain. To perform a systematic review on the operational performance of the Bruker MALDI-TOF MS system and evaluate published cut-off values compared to traditional blood cultures. A comprehensive literature search was performed. Studies were included if they performed direct MALDI-TOF MS analysis of blood culture specimens in human patients with suspected bacterial infections using the Bruker Biotyper software. Sensitivities and specificities of the combined studies were estimated using a hierarchical random effects linear model (REML) incorporating cut-off scores of ≥1.7 and ≥2.0. Fifty publications were identified, with 11 studies included after final review. The estimated sensitivity utilising a cut-off of ≥2.0 from the combined studies was 74.6% (95% CI = 67.9-89.3%), with an estimated specificity of 88.0% (95% CI = 74.8-94.7%). When assessing a cut-off of ≥1.7, the combined sensitivity increases to 92.8% (95% CI = 87.4-96.0%), but the estimated specificity decreased to 81.2% (95% CI = 61.9-96.6%). In this analysis, MALDI-TOF MS showed acceptable sensitivity and specificity in bacterial speciation with the current recommended cut-off point compared to blood cultures; however, lowering the cut-off point from ≥2.0 to ≥1.7 would increase the sensitivity of the test without significant detrimental effect on the specificity, which could improve clinician confidence in their results.

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors

PubMed Central

Kiss, Joseph E.; Steele, Whitney R.; Wright, David J.; Mast, Alan E.; Carey, Patricia M.; Murphy, Edward L.; Gottschall, Jerry L.; Simon, Toby L.; Cable, Ritchard G.

2014-01-01

BACKGROUND Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. STUDY DESIGN AND METHODS A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/ RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 µ.g/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. RESULTS HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 u.g/L was a good surrogate for assessing IDE. CONCLUSION RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency. PMID:23617531

Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.

PubMed

Aranda, G; Careaga, M; Hanzu, F A; Patrascioiu, I; Ríos, P; Mora, M; Morales-Romero, B; Jiménez, W; Halperin, I; Casals, G

2016-10-01

Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

Laboratory variables for assessing iron deficiency in REDS-II Iron Status Evaluation (RISE) blood donors.

PubMed

Kiss, Joseph E; Steele, Whitney R; Wright, David J; Mast, Alan E; Carey, Patricia M; Murphy, Edward L; Gottschall, Jerry L; Simon, Toby L; Cable, Ritchard G

2013-11-01

Iron deficiency is common in regular blood donors. We evaluated the diagnostic sensitivity and specificity of red blood cell (RBC) hematology analyzer indices to assess iron status as a part of donor management. A total of 1659 male and female donors from the Retrovirus Epidemiology Donor Study-II (REDS-II) Donor Iron Status Evaluation (RISE) study who were either first-time/reactivated (FT/RA; no donations for 2 years) or frequent donors were recruited into a longitudinal study of regular donation of RBCs. Of these, 1002 donors returned 15 to 24 months later for a final assessment. Absent iron stores (AIS) was defined as plasma ferritin level of less than 12 μg/L. Logarithm of the ratio of soluble transferrin receptor to ferritin of at least 2.07 (≥97.5% in FT/RA males) was used to define iron-deficient erythropoiesis (IDE). Receiver operating characteristics analysis was performed to assess selected RBC indices (e.g., percentage of hypochromic mature RBCs, proportion of hypochromic mature RBCs [HYPOm], and hemoglobin [Hb] content of reticulocytes [CHr]) in identifying AIS and IDE. HYPOm and CHr detected IDE with comparable sensitivity, 72% versus 69%, but differed in specificity: HYPOm 68% and CHr 53%. For detecting AIS, sensitivity was improved to 85% for HYPOm and 81% for CHr but specificity was reduced for both. Venous Hb had high specificity but poor sensitivity for IDE and AIS. A plasma ferritin level of less than 26.7 μg/L was a good surrogate for assessing IDE. RBC indices correlate with AIS and IDE and are more informative than Hb measurement, but lack sufficient sensitivity and specificity to be used as diagnostic tools in blood donors at risk for iron deficiency. © 2013 American Association of Blood Banks.

EEG, evoked potentials and pulsed Doppler in asphyxiated term infants.

PubMed

Julkunen, Mia K; Himanen, Sari-Leena; Eriksson, Kai; Janas, Martti; Luukkaala, Tiina; Tammela, Outi

2014-09-01

To evaluate electroencephalograms (EEG), evoked potentials (EPs) and Doppler findings in the cerebral arteries as predictors of a 1-year outcome in asphyxiated newborn infants. EEG and EPs (brain stem auditory (BAEP), somatosensory (SEP), visual (VEP) evoked potentials) were assessed in 30 asphyxiated and 30 healthy term infants during the first days (range 1-8). Cerebral blood flow velocities (CBFV) were measured from the cerebral arteries using pulsed Doppler at ∼24h of age. EEG, EPs, Doppler findings, symptoms of hypoxic ischemic encephalopathy (HIE) and their combination were evaluated in predicting a 1-year outcome. An abnormal EEG background predicted poor outcome in the asphyxia group with a sensitivity of 67% and 81% specificity, and an abnormal SEP with 75% and 79%, respectively. Combining increased systolic CBFV (mean+3SD) with abnormal EEG or SEP improved the specificity, but not the sensitivity. The predictive values of abnormal BAEP and VEP were poor. Normal EEG and SEP predicted good outcome in the asphyxia group with sensitivities from 79% to 81%. The combination of normal EEG, normal SEP and systolic CBFV<3SD predicted good outcome with a sensitivity of 74% and 100% specificity. Combining abnormal EEG or EPs findings with increased systolic CBFV did not improve prediction of a poor 1-year outcome of asphyxiated infants. Normal EEG and normal SEP combined with systolic CBFV<3SD at about 24 h can be valuable in the prediction of normal 1-year outcome. Combining systolic CBFV at 24 h with EEG and SEP examinations can be of use in the prediction of normal 1-year outcome among asphyxiated infants. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Detection of bacterial pathogens in Mongolia meningitis surveillance with a new real-time PCR assay to detect Haemophilus influenzae.

PubMed

Wang, Xin; Mair, Raydel; Hatcher, Cynthia; Theodore, M Jordan; Edmond, Karen; Wu, Henry M; Harcourt, Brian H; Carvalho, Maria da Gloria S; Pimenta, Fabiana; Nymadawa, Pagbajab; Altantsetseg, Dorjpurev; Kirsch, Mariah; Satola, Sarah W; Cohn, Amanda; Messonnier, Nancy E; Mayer, Leonard W

2011-04-01

Since the implementation of Haemophilus influenzae (Hi) serotype b vaccine, other serotypes and non-typeable strains have taken on greater importance as a cause of Hi diseases. A rapid and accurate method is needed to detect all Hi regardless of the encapsulation status. We developed 2 real-time PCR (rt-PCR) assays to detect specific regions of the protein D gene (hpd). Both hpd assays are very specific and sensitive for detection of Hi. Of the 63 non-Hi isolates representing 21 bacterial species, none was detected by the hpd #1 assay, and only one of 2 H. aphrophilus isolates was detected by the hpd #3 assay. The hpd #1 and #3 assays detected 97% (229/237) and 99% (234/237) of Hi isolates, respectively, and were superior for detection of both typeable and non-typeable Hi isolates, as compared to previously developed rt-PCR targeting ompP2 or bexA. The diagnostic sensitivity and specificity of these rt-PCR assays were assessed on cerebrospinal fluid specimens collected as part of meningitis surveillance in Ulaanbaatar, Mongolia. The etiology (Neisseria meningitidis, Hi, and Streptococcus pneumoniae) of 111 suspected meningitis cases was determined by conventional methods (culture and latex agglutination), previously developed rt-PCR assays, and the new hpd assays. The rt-PCR assays were more sensitive for detection of meningitis pathogens than other classical methods and improved detection from 50% (56/111) to 75% (83/111). The hpd #3 assay identified a non-b Hi that was missed by the bexA assay and other methods. A sensitive rt-PCR assay to detect both typeable and non-typeable Hi is a useful tool for improving Hi disease surveillance especially after Hib vaccine introduction. Published by Elsevier GmbH.

Digital multi-channel stabilization of four-mode phase-sensitive parametric multicasting.

PubMed

Liu, Lan; Tong, Zhi; Wiberg, Andreas O J; Kuo, Bill P P; Myslivets, Evgeny; Alic, Nikola; Radic, Stojan

2014-07-28

Stable four-mode phase-sensitive (4MPS) process was investigated as a means to enhance two-pump driven parametric multicasting conversion efficiency (CE) and signal to noise ratio (SNR). Instability of multi-beam, phase sensitive (PS) device that inherently behaves as an interferometer, with output subject to ambient induced fluctuations, was addressed theoretically and experimentally. A new stabilization technique that controls phases of three input waves of the 4MPS multicaster and maximizes CE was developed and described. Stabilization relies on digital phase-locked loop (DPLL) specifically was developed to control pump phases to guarantee stable 4MPS operation that is independent of environmental fluctuations. The technique also controls a single (signal) input phase to optimize the PS-induced improvement of the CE and SNR. The new, continuous-operation DPLL has allowed for fully stabilized PS parametric broadband multicasting, demonstrating CE improvement over 20 signal copies in excess of 10 dB.

Solar x ray astronomy rocket program

NASA Technical Reports Server (NTRS)

1990-01-01

The dynamics were studied of the solar corona through the imaging of large scale coronal structures with AS&E High Resolution Soft X ray Imaging Solar Sounding Rocket Payload. The proposal for this program outlined a plan of research based on the construction of a high sensitivity X ray telescope from the optical and electronic components of the previous flight of this payload (36.038CS). Specifically, the X ray sensitive CCD camera was to be placed in the prime focus of the grazing incidence X ray mirror. The improved quantum efficiency of the CCD detector (over the film which had previously been used) allows quantitative measurements of temperature and emission measure in regions of low x ray emission such as helmet streamers beyond 1.2 solar radii or coronal holes. Furthermore, the improved sensitivity of the CCD allows short exposures of bright objects to study unexplored temporal regimes of active region loop evolution.

Perspective: Optical measurement of feature dimensions and shapes by scatterometry

NASA Astrophysics Data System (ADS)

Diebold, Alain C.; Antonelli, Andy; Keller, Nick

2018-05-01

The use of optical scattering to measure feature shape and dimensions, scatterometry, is now routine during semiconductor manufacturing. Scatterometry iteratively improves an optical model structure using simulations that are compared to experimental data from an ellipsometer. These simulations are done using the rigorous coupled wave analysis for solving Maxwell's equations. In this article, we describe the Mueller matrix spectroscopic ellipsometry based scatterometry. Next, the rigorous coupled wave analysis for Maxwell's equations is presented. Following this, several example measurements are described as they apply to specific process steps in the fabrication of gate-all-around (GAA) transistor structures. First, simulations of measurement sensitivity for the inner spacer etch back step of horizontal GAA transistor processing are described. Next, the simulated metrology sensitivity for sacrificial (dummy) amorphous silicon etch back step of vertical GAA transistor processing is discussed. Finally, we present the application of plasmonically active test structures for improving the sensitivity of the measurement of metal linewidths.

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.

Detection of Bone Marrow Edema in Nondisplaced Hip Fractures: Utility of a Virtual Noncalcium Dual-Energy CT Application.

PubMed

Kellock, Trenton T; Nicolaou, Savvas; Kim, Sandra S Y; Al-Busaidi, Sultan; Louis, Luck J; O'Connell, Tim W; Ouellette, Hugue A; McLaughlin, Patrick D

2017-09-01

Purpose To quantify the sensitivity and specificity of dual-energy computed tomographic (CT) virtual noncalcium images in the detection of nondisplaced hip fractures and to assess whether obtaining these images as a complement to bone reconstructions alters sensitivity, specificity, or diagnostic confidence. Materials and Methods The clinical research ethics board approved chart review, and the requirement to obtain informed consent was waived. The authors retrospectively identified 118 patients who presented to a level 1 trauma center emergency department and who underwent dual-energy CT for suspicion of a nondisplaced traumatic hip fracture. Clinical follow-up was the standard of reference. Three radiologists interpreted virtual noncalcium images for traumatic bone marrow edema. Bone reconstructions for the same cases were interpreted alone and then with virtual noncalcium images. Diagnostic confidence was rated on a scale of 1 to 10. McNemar, Fleiss κ, and Wilcoxon signed-rank tests were used for statistical analysis. Results Twenty-two patients had nondisplaced hip fractures and 96 did not have hip fractures. Sensitivity with virtual noncalcium images was 77% and 91% (17 and 20 of 22 patients), and specificity was 92%-99% (89-95 of 96 patients). Sensitivity increased by 4%-5% over that with bone reconstruction images alone for two of the three readers when both bone reconstruction and virtual noncalcium images were used. Specificity remained unchanged (99% and 100%). Diagnostic confidence in the exclusion of fracture was improved with combined bone reconstruction and virtual noncalcium images (median score: 10, 9, and 10 for readers 1, 2, and 3, respectively) compared with bone reconstruction images alone (median score: 9, 8, and 9). Conclusion When used as a supplement to standard bone reconstructions, dual-energy CT virtual noncalcium images increased sensitivity for the detection of nondisplaced traumatic hip fractures and improved diagnostic confidence in the exclusion of these fractures. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 17, 2017.

Effectiveness of Computer-Aided Detection in Community Mammography Practice

PubMed Central

Abraham, Linn; Taplin, Stephen H.; Geller, Berta M.; Carney, Patricia A.; D’Orsi, Carl; Elmore, Joann G.; Barlow, William E.

2011-01-01

Background Computer-aided detection (CAD) is applied during screening mammography for millions of US women annually, although it is uncertain whether CAD improves breast cancer detection when used by community radiologists. Methods We investigated the association between CAD use during film-screen screening mammography and specificity, sensitivity, positive predictive value, cancer detection rates, and prognostic characteristics of breast cancers (stage, size, and node involvement). Records from 684 956 women who received more than 1.6 million film-screen mammograms at Breast Cancer Surveillance Consortium facilities in seven states in the United States from 1998 to 2006 were analyzed. We used random-effects logistic regression to estimate associations between CAD and specificity (true-negative examinations among women without breast cancer), sensitivity (true-positive examinations among women with breast cancer diagnosed within 1 year of mammography), and positive predictive value (breast cancer diagnosed after positive mammograms) while adjusting for mammography registry, patient age, time since previous mammography, breast density, use of hormone replacement therapy, and year of examination (1998–2002 vs 2003–2006). All statistical tests were two-sided. Results Of 90 total facilities, 25 (27.8%) adopted CAD and used it for an average of 27.5 study months. In adjusted analyses, CAD use was associated with statistically significantly lower specificity (OR = 0.87, 95% confidence interval [CI] = 0.85 to 0.89, P < .001) and positive predictive value (OR = 0.89, 95% CI = 0.80 to 0.99, P = .03). A non-statistically significant increase in overall sensitivity with CAD (OR = 1.06, 95% CI = 0.84 to 1.33, P = .62) was attributed to increased sensitivity for ductal carcinoma in situ (OR = 1.55, 95% CI = 0.83 to 2.91; P = .17), although sensitivity for invasive cancer was similar with or without CAD (OR = 0.96, 95% CI = 0.75 to 1.24; P = .77). CAD was not associated with higher breast cancer detection rates or more favorable stage, size, or lymph node status of invasive breast cancer. Conclusion CAD use during film-screen screening mammography in the United States is associated with decreased specificity but not with improvement in the detection rate or prognostic characteristics of invasive breast cancer. PMID:21795668

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

PubMed

Xu, Li-Qian; Yang, Yun-Mei; Tong, Hong; Xu, Chang-Fu

2018-04-01

Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Evaluation of a Rapid Diagnostic Test for Yaws Infection in a Community Surveillance Setting

PubMed Central

Marks, Michael; Goncalves, Adriana; Vahi, Ventis; Sokana, Oliver; Puiahi, Elliot; Zhang, Zaixing; Dalipanda, Tenneth; Bottomley, Christian; Mabey, David; Solomon, Anthony W.

2014-01-01

Yaws is a non-venereal treponemal infection caused by Treponema pallidum ssp. pertenue. The WHO has launched a worldwide control programme, which aims to eradicate yaws by 2020. The development of a rapid diagnostic test (RDT) for serological diagnosis in the isolated communities affected by yaws is a key requirement for the successful implementation of the WHO strategy. We conducted a study to evaluate the utility of the DPP test in screening for yaws, utilizing samples collected as part of a community prevalence survey conducted in the Solomon Islands. 415 serum samples were tested using both traditional syphilis serology (TPPA and quantitative RPR) and the Chembio DPP Syphilis Screen and Confirm RDT. We calculated the sensitivity and specificity of the RDT as compared to gold standard serology. The sensitivity of the RDT against TPPA was 58.5% and the specificity was 97.6%. The sensitivity of the RDT against RPR was 41.7% and the specificity was 95.2%. The sensitivity of the DPP was strongly related to the RPR titre with a sensitivity of 92.0% for an RPR titre of >1/16. Wider access to DPP testing would improve our understanding of worldwide yaws case reporting and the test may play a key role in assessing patients presenting with yaws like lesions in a post-mass drug administration (MDA) setting. PMID:25211018

Evaluation of a rapid diagnostic test for yaws infection in a community surveillance setting.

PubMed

Marks, Michael; Goncalves, Adriana; Vahi, Ventis; Sokana, Oliver; Puiahi, Elliot; Zhang, Zaixing; Dalipanda, Tenneth; Bottomley, Christian; Mabey, David; Solomon, Anthony W

2014-09-01

Yaws is a non-venereal treponemal infection caused by Treponema pallidum ssp. pertenue. The WHO has launched a worldwide control programme, which aims to eradicate yaws by 2020. The development of a rapid diagnostic test (RDT) for serological diagnosis in the isolated communities affected by yaws is a key requirement for the successful implementation of the WHO strategy. We conducted a study to evaluate the utility of the DPP test in screening for yaws, utilizing samples collected as part of a community prevalence survey conducted in the Solomon Islands. 415 serum samples were tested using both traditional syphilis serology (TPPA and quantitative RPR) and the Chembio DPP Syphilis Screen and Confirm RDT. We calculated the sensitivity and specificity of the RDT as compared to gold standard serology. The sensitivity of the RDT against TPPA was 58.5% and the specificity was 97.6%. The sensitivity of the RDT against RPR was 41.7% and the specificity was 95.2%. The sensitivity of the DPP was strongly related to the RPR titre with a sensitivity of 92.0% for an RPR titre of >1/16. Wider access to DPP testing would improve our understanding of worldwide yaws case reporting and the test may play a key role in assessing patients presenting with yaws like lesions in a post-mass drug administration (MDA) setting.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab.

PubMed

Hattori, Yosuke; Kojima, Toshihisa; Kaneko, Atsushi; Kida, Daihei; Hirano, Yuji; Fujibayashi, Takayoshi; Yabe, Yuichiro; Oguchi, Takeshi; Kanayama, Yasuhide; Miyake, Hiroyuki; Kato, Takefumi; Takagi, Hideki; Hayashi, Masatoshi; Ito, Takayasu; Shioura, Tomone; Takahashi, Nobunori; Ishikawa, Hisato; Funahashi, Koji; Ishiguro, Naoki

2018-01-01

This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA). Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis. DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively. Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

[Quality of documentation of intraoperative and postoperative complications : improvement of documentation for a nationwide quality assurance program and comparison with routine data].

PubMed

Jakob, J; Marenda, D; Sold, M; Schlüter, M; Post, S; Kienle, P

2014-08-01

Complications after cholecystectomy are continuously documented in a nationwide database in Germany. Recent studies demonstrated a lack of reliability of these data. The aim of the study was to evaluate the impact of a control algorithm on documentation quality and the use of routine diagnosis coding as an additional validation instrument. Completeness and correctness of the documentation of complications after cholecystectomy was compared over a time interval of 12 months before and after implementation of an algorithm for faster and more accurate documentation. Furthermore, the coding of all diagnoses was screened to identify intraoperative and postoperative complications. The sensitivity of the documentation for complications improved from 46 % to 70 % (p = 0.05, specificity 98 % in both time intervals). A prolonged time interval of more than 6 weeks between patient discharge and documentation was associated with inferior data quality (incorrect documentation in 1.5 % versus 15 %, p < 0.05). The rate of case documentation within the 6 weeks after hospital discharge was clearly improved after implementation of the control algorithm. Sensitivity and specificity of screening for complications by evaluating routine diagnoses coding were 70 % and 85 %, respectively. The quality of documentation was improved by implementation of a simple memory algorithm.

Measurement of Glycosylated Alpha-Fetoprotein Improves Diagnostic Power over the Native Form in Hepatocellular Carcinoma

PubMed Central

Jin, Jonghwa; Park, Jiyoung; Yu, Su Jong; Yoon, Jung-Hwan; Kim, Youngsoo

2014-01-01

Serum alpha-fetoprotein (AFP) has long been used as a diagnostic marker for hepatocellular carcinoma (HCC), albeit controversially. Although it remains widely used in clinics, the value of AFP in HCC diagnosis has recently been challenged due to its significant rates of false positive and false negative findings. To improve the efficacy of AFP as HCC diagnostic marker, we developed a method of measuring total and glycosylated AFP by multiple reaction monitoring (MRM)-MS. In this study, we verified the total amount of AFP (nonglycopeptide levels) and the degree of glycosylated AFP (deglycopeptide levels) in 60 normal (41 men and 19 women; mean age 53 years; range 32–74 years), 35 LC (23 men and 12 women; mean age 56 years; range 43–78 years; HBV-related), and 60 HCC subjects (42 men and 18 women; mean age 58 years; range 38–76 years; HBV-related; 30 stage I, 15 stage II, and 10 stage III). By MRM-MS analysis, the nonglycopeptide had 56.7% sensitivity, 68.3% specificity, and an AUC of 0.687 [cutoff value: ≥0.02 (light/heavy ratio)], comparing the normal and HCC group, whereas the deglycopeptide had 93.3% sensitivity, 68.3% specificity, and an AUC of 0.859 [cutoff value: ≥0.02 (light/heavy ratio)]. In comparing the stage I HCC subgroup with the LC group, the nonglycopeptide had a sensitivity of 66.7%, specificity of 80.0%, and an AUC of 0.712 [cutoff value: ≥0.02 (light/heavy ratio)], whereas the deglycopeptide had a sensitivity of 96.7%, specificity of 80.0%, and an AUC of 0.918 [cutoff value: ≥0.02 (light/heavy ratio)]. These data demonstrate that the discriminatory power of the deglycopeptide is greater than that of the nonglycopeptide. We conclude that deglycopeptide can distinguish cancer status between normal subjects and HCC patients better than nonglycopeptide. PMID:25310463

Detection of artificial air space opacities with digital radiography: ex vivo study on enhanced latitude post-processing.

PubMed

Biederer, J; Bolte, H; Schmidt, T; Charalambous, N; Both, M; Kopp, U; Hoffmann, B; Freitag-Wolf, S; Van Metter, R; Heller, M

2010-03-01

To evaluate in a.-p. digital chest radiograms of an ex vivo system if increased latitude and enhanced image detail contrast (EVP) improve the accuracy of detecting artificial air space opacities in parts of the lung that are superimposed by the diaphragm. 19 porcine lungs were inflated inside a chest phantom, prepared with 20-50 ml gelatin-stabilized liquid to generate alveolar air space opacities, and examined with direct radiography (3.0 × 2.5 k detector/ 125 kVp/ 4 mAs). 276 a.-p. images with and without EVP of 1.0-3.0 were presented to 6 observers. 8 regions were read for opacities, the reference was defined by CT. Statistics included sensitivity/specificity, interobserver variability, and calculation of Az (area under ROC curve). Behind the diaphragm (opacities in 32/92 regions), the median sensitivity increased from 0.35 without EVP to 0.53-0.56 at EVP 1.5-3.0 (significant in 5/6 observers). The specificity decreased from 0.96 to 0.90 (significant in 6/6), and the Az value and interobserver correlation increased from 0.66 to 0.74 and 0.39 to 0.48, respectively. Above the diaphragm, the median sensitivity for artificial opacities (136/276 regions) increased from 0.71 to 0.77-0.82 with EVP (significant in 4/6 observers). The specificity and Az value decreased from 0.76 to 0.62 and 0.74 to 0.70, respectively, (significant in 3/6). In this ex vivo experiment, EVP improved the diagnostic accuracy for artificial air space opacities in the superimposed parts of the lung (area under the ROC curve). Above the diaphragm, the accuracy was not affected due to a tradeoff in sensitivity/specificity. © Georg Thieme Verlag KG Stuttgart · New York.

Context-specific effects of musical expertise on audiovisual integration

PubMed Central

Bishop, Laura; Goebl, Werner

2014-01-01

Ensemble musicians exchange auditory and visual signals that can facilitate interpersonal synchronization. Musical expertise improves how precisely auditory and visual signals are perceptually integrated and increases sensitivity to asynchrony between them. Whether expertise improves sensitivity to audiovisual asynchrony in all instrumental contexts or only in those using sound-producing gestures that are within an observer's own motor repertoire is unclear. This study tested the hypothesis that musicians are more sensitive to audiovisual asynchrony in performances featuring their own instrument than in performances featuring other instruments. Short clips were extracted from audio-video recordings of clarinet, piano, and violin performances and presented to highly-skilled clarinetists, pianists, and violinists. Clips either maintained the audiovisual synchrony present in the original recording or were modified so that the video led or lagged behind the audio. Participants indicated whether the audio and video channels in each clip were synchronized. The range of asynchronies most often endorsed as synchronized was assessed as a measure of participants' sensitivities to audiovisual asynchrony. A positive relationship was observed between musical training and sensitivity, with data pooled across stimuli. While participants across expertise groups detected asynchronies most readily in piano stimuli and least readily in violin stimuli, pianists showed significantly better performance for piano stimuli than for either clarinet or violin. These findings suggest that, to an extent, the effects of expertise on audiovisual integration can be instrument-specific; however, the nature of the sound-producing gestures that are observed has a substantial effect on how readily asynchrony is detected as well. PMID:25324819

Immuno-magnetic beads-based extraction-capillary zone electrophoresis-deep UV laser-induced fluorescence analysis of erythropoietin.

PubMed

Wang, Heye; Dou, Peng; Lü, Chenchen; Liu, Zhen

2012-07-13

Erythropoietin (EPO) is an important glycoprotein hormone. Recombinant human EPO (rhEPO) is an important therapeutic drug and can be also used as doping reagent in sports. The analysis of EPO glycoforms in pharmaceutical and sports areas greatly challenges analytical scientists from several aspects, among which sensitive detection and effective and facile sample preparation are two essential issues. Herein, we investigated new possibilities for these two aspects. Deep UV laser-induced fluorescence detection (deep UV-LIF) was established to detect the intrinsic fluorescence of EPO while an immuno-magnetic beads-based extraction (IMBE) was developed to specifically extract EPO glycoforms. Combined with capillary zone electrophoresis (CZE), CZE-deep UV-LIF allows high resolution glycoform profiling with improved sensitivity. The detection sensitivity was improved by one order of magnitude as compared with UV absorbance detection. An additional advantage is that the original glycoform distribution can be completely preserved because no fluorescent labeling is needed. By combining IMBE with CZE-deep UV-LIF, the overall detection sensitivity was 1.5 × 10⁻⁸ mol/L, which was enhanced by two orders of magnitude relative to conventional CZE with UV absorbance detection. It is applicable to the analysis of pharmaceutical preparations of EPO, but the sensitivity is insufficient for the anti-doping analysis of EPO in blood and urine. IMBE can be straightforward and effective approach for sample preparation. However, antibodies with high specificity were the key for application to urine samples because some urinary proteins can severely interfere the immuno-extraction. Copyright © 2012 Elsevier B.V. All rights reserved.

Sensitivity of Claims-Based Algorithms to Ascertain Smoking Status More Than Doubled with Meaningful Use.

PubMed

Huo, Jinhai; Yang, Ming; Tina Shih, Ya-Chen

2018-03-01

The "meaningful use of certified electronic health record" policy requires eligible professionals to record smoking status for more than 50% of all individuals aged 13 years or older in 2011 to 2012. To explore whether the coding to document smoking behavior has increased over time and to assess the accuracy of smoking-related diagnosis and procedure codes in identifying previous and current smokers. We conducted an observational study with 5,423,880 enrollees from the year 2009 to 2014 in the Truven Health Analytics database. Temporal trends of smoking coding, sensitivity, specificity, positive predictive value, and negative predictive value were measured. The rate of coding of smoking behavior improved significantly by the end of the study period. The proportion of patients in the claims data recorded as current smokers increased 2.3-fold and the proportion of patients recorded as previous smokers increased 4-fold during the 6-year period. The sensitivity of each International Classification of Diseases, Ninth Revision, Clinical Modification code was generally less than 10%. The diagnosis code of tobacco use disorder (305.1X) was the most sensitive code (9.3%) for identifying smokers. The specificities of these codes and the Current Procedural Terminology codes were all more than 98%. A large improvement in the coding of current and previous smoking behavior has occurred since the inception of the meaningful use policy. Nevertheless, the use of diagnosis and procedure codes to identify smoking behavior in administrative data is still unreliable. This suggests that quality improvements toward medical coding on smoking behavior are needed to enhance the capability of claims data for smoking-related outcomes research. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Improved detection of Burkholderia pseudomallei from non-blood clinical specimens using enrichment culture and PCR: narrowing diagnostic gap in resource-constrained settings.

PubMed

Tellapragada, Chaitanya; Shaw, Tushar; D'Souza, Annet; Eshwara, Vandana Kalwaje; Mukhopadhyay, Chiranjay

2017-07-01

To evaluate the diagnostic utility of enrichment culture and PCR for improved case detection rates of non-bacteraemic form of melioidosis in limited resource settings. Clinical specimens (n = 525) obtained from patients presenting at a tertiary care hospital of South India with clinical symptoms suggestive of community-acquired pneumonia, lower respiratory tract infections, superficial or internal abscesses, chronic skin ulcers and bone or joint infections were tested for the presence of Burkholderia pseudomallei using conventional culture (CC), enrichment culture (EC) and PCR. Sensitivity, specificity, positive and negative predictive values of CC and PCR were initially deduced using EC as the gold standard method. Further, diagnostic accuracies of all the three methods were analysed using Bayesian latent class modelling (BLCM). Detection rates of B. pseudomallei using CC, EC and PCR were 3.8%, 5.3% and 6%, respectively. Diagnostic sensitivities and specificities of CC and PCR were 71.4, 98.4% and 100 and 99.4%, respectively in comparison with EC as the gold standard test. With Bayesian latent class modelling, EC and PCR demonstrated sensitivities of 98.7 and 99.3%, respectively, while CC showed a sensitivity of 70.3% for detection of B. pseudomallei. An increase of 1.6% (95% CI: 1.08-4.32%) in the case detection rate of melioidosis was observed in the study population when EC and/or PCR were used in adjunct to the conventional culture technique. Our study findings underscore the diagnostic superiority of enrichment culture and/or PCR over conventional microbiological culture for improved case detection of melioidosis from non-blood clinical specimens. © 2017 John Wiley & Sons Ltd.

Determination of Caffeine in Beverages by Capillary Zone Electrophoresis: An Experiment for the Undergraduate Analytical Laboratory

NASA Astrophysics Data System (ADS)

Conte, Eric D.; Barry, Eugene F.; Rubinstein, Harry

1996-12-01

Certain individuals may be sensitive to specific compounds in comsumer products. It is important to quantify these analytes in food products in order to monitor their intake. Caffeine is one such compound. Determination of caffeine in beverages by spectrophotometric procedures requires an extraction procedure, which can prove time-consuming. Although the corresponding determination by HPLC allows for a direct injection, capillary zone electrophoresis provides several advantages such as extremely low solvent consumption, smaller sample volume requirements, and improved sensitivity.

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

PubMed Central

Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

2016-01-01

Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

MOBE-ChIP: Probing Cell Type-Specific Binding Through Large-Scale Chromatin Immunoprecipitation.

PubMed

Wang, Shenqi; Lau, On Sun

2018-01-01

In multicellular organisms, the initiation and maintenance of specific cell types often require the activity of cell type-specific transcriptional regulators. Understanding their roles in gene regulation is crucial but probing their DNA targets in vivo, especially in a genome-wide manner, remains a technical challenge with their limited expression. To improve the sensitivity of chromatin immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is performed at a substantially larger experimental scale and under low background conditions. Here, we describe the procedure in the study of transcription factors in the model plant Arabidopsis. However, with some modifications, the technique should also be implemented in other systems. Besides cell type-specific studies, MOBE-ChIP can also be used as a general strategy to improve ChIP signals.

Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer.

PubMed

Brawer, M K; Cheli, C D; Neaman, I E; Goldblatt, J; Smith, C; Schwartz, M K; Bruzek, D J; Morris, D L; Sokoll, L J; Chan, D W; Yeung, K K; Partin, A W; Allard, W J

2000-05-01

Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.

Boosted classification trees result in minor to modest improvement in the accuracy in classifying cardiovascular outcomes compared to conventional classification trees

PubMed Central

Austin, Peter C; Lee, Douglas S

2011-01-01

Purpose: Classification trees are increasingly being used to classifying patients according to the presence or absence of a disease or health outcome. A limitation of classification trees is their limited predictive accuracy. In the data-mining and machine learning literature, boosting has been developed to improve classification. Boosting with classification trees iteratively grows classification trees in a sequence of reweighted datasets. In a given iteration, subjects that were misclassified in the previous iteration are weighted more highly than subjects that were correctly classified. Classifications from each of the classification trees in the sequence are combined through a weighted majority vote to produce a final classification. The authors' objective was to examine whether boosting improved the accuracy of classification trees for predicting outcomes in cardiovascular patients. Methods: We examined the utility of boosting classification trees for classifying 30-day mortality outcomes in patients hospitalized with either acute myocardial infarction or congestive heart failure. Results: Improvements in the misclassification rate using boosted classification trees were at best minor compared to when conventional classification trees were used. Minor to modest improvements to sensitivity were observed, with only a negligible reduction in specificity. For predicting cardiovascular mortality, boosted classification trees had high specificity, but low sensitivity. Conclusions: Gains in predictive accuracy for predicting cardiovascular outcomes were less impressive than gains in performance observed in the data mining literature. PMID:22254181

Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia

NASA Astrophysics Data System (ADS)

Schwarz, Richard Alan

Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue specimens from 15 oral cancer patients. Improved contrast between neoplastic and healthy tissue was observed using 2-NBDG and EGF-Alexa 647.

Fabrication of an electrochemical sensor based on spiropyran for sensitive and selective detection of fluoride ion.

PubMed

Tao, Jia; Zhao, Peng; Li, Yinhui; Zhao, Wenjie; Xiao, Yue; Yang, Ronghua

2016-04-28

In the past decades, numerous electrochemical sensors based on exogenous electroactive substance have been reported. Due to non-specific interaction between the redox mediator and the target, the instability caused by false signal may not be avoided. To address this issue, in this paper, a new electrochemical sensor based on spiropyran skeleton, namely SPOSi, was designed for specific electrochemical response to fluoride ions (F(-)). The breakage of Si-O induced by F(-) based on the specific nucleophilic substitution reaction between F(-) and silica would directly produce a hydroquinone structure for electrochemical signal generation. To improve the sensitivity, SPOSi probe was assembled on the single-walled carbon nanotubes (SWCNTs) modified glassy carbon electrode (GCE) through the π-π conjugating interaction. This electrode was successfully applied to monitor F(-) with a detection limit of 8.3 × 10(-8) M. Compared with the conventional F(-) ion selected electrode (ISE) which utilized noncovalent interaction, this method displays higher stability and a comparable sensitivity in the urine samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Aspergillus PCR protocols for testing serum specimens.

PubMed

White, P Lewis; Mengoli, Carlo; Bretagne, Stéphane; Cuenca-Estrella, Manuel; Finnstrom, Niklas; Klingspor, Lena; Melchers, Willem J G; McCulloch, Elaine; Barnes, Rosemary A; Donnelly, J Peter; Loeffler, Juergen

2011-11-01

A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance.

Evaluation of Aspergillus PCR Protocols for Testing Serum Specimens▿†

PubMed Central

White, P. Lewis; Mengoli, Carlo; Bretagne, Stéphane; Cuenca-Estrella, Manuel; Finnstrom, Niklas; Klingspor, Lena; Melchers, Willem J. G.; McCulloch, Elaine; Barnes, Rosemary A.; Donnelly, J. Peter; Loeffler, Juergen

2011-01-01

A panel of human serum samples spiked with various amounts of Aspergillus fumigatus genomic DNA was distributed to 23 centers within the European Aspergillus PCR Initiative to determine analytical performance of PCR. Information regarding specific methodological components and PCR performance was requested. The information provided was made anonymous, and meta-regression analysis was performed to determine any procedural factors that significantly altered PCR performance. Ninety-seven percent of protocols were able to detect a threshold of 10 genomes/ml on at least one occasion, with 83% of protocols reproducibly detecting this concentration. Sensitivity and specificity were 86.1% and 93.6%, respectively. Positive associations between sensitivity and the use of larger sample volumes, an internal control PCR, and PCR targeting the internal transcribed spacer (ITS) region were shown. Negative associations between sensitivity and the use of larger elution volumes (≥100 μl) and PCR targeting the mitochondrial genes were demonstrated. Most Aspergillus PCR protocols used to test serum generate satisfactory analytical performance. Testing serum requires less standardization, and the specific recommendations shown in this article will only improve performance. PMID:21940479

A novel method for pair-matching using three-dimensional digital models of bone: mesh-to-mesh value comparison.

PubMed

Karell, Mara A; Langstaff, Helen K; Halazonetis, Demetrios J; Minghetti, Caterina; Frelat, Mélanie; Kranioti, Elena F

2016-09-01

The commingling of human remains often hinders forensic/physical anthropologists during the identification process, as there are limited methods to accurately sort these remains. This study investigates a new method for pair-matching, a common individualization technique, which uses digital three-dimensional models of bone: mesh-to-mesh value comparison (MVC). The MVC method digitally compares the entire three-dimensional geometry of two bones at once to produce a single value to indicate their similarity. Two different versions of this method, one manual and the other automated, were created and then tested for how well they accurately pair-matched humeri. Each version was assessed using sensitivity and specificity. The manual mesh-to-mesh value comparison method was 100 % sensitive and 100 % specific. The automated mesh-to-mesh value comparison method was 95 % sensitive and 60 % specific. Our results indicate that the mesh-to-mesh value comparison method overall is a powerful new tool for accurately pair-matching commingled skeletal elements, although the automated version still needs improvement.

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

Use of 3-nitrobenzonitrile as an additive for improved sensitivity in sonic-spray ionization mass spectrometry.

PubMed

Kanaki, Katerina; Pergantis, Spiros A

2014-12-15

Sonic-spray ionization (SSI) has been shown to produce gas-phase ions for a wide range of compounds, without the application of voltage or a laser. However, it remains to be shown that it can also provide similar sensitivities to those obtained by electrospray ionization mass spectrometry (ESI-MS). Here we report on an attempt to further improve the sensitivity of SSI-MS, more specifically a version of SSI that is referred to as Venturi easy ambient sonic-spray ionization (V-EASI) MS, by adding a signal-enhancing additive to the sample solution. The additive used is 3-nitrobenzonitrile (3-NBN), which has recently been used with success in a new ionization approach named matrix-assisted ionization vacuum. In order to conduct this study we have analyzed a range of compounds, including peptides, metalloproteins, and some organometalloids. During the V-EASI-MS analyses molecular ion and protonated molecule signal intensities as well as their corresponding signal-to-noise (S/N) ratios, obtained in the presence and absence of the 3-NBN, were compared. The 3-NBN-assisted V-EASI-MS approach developed here provides significant improvement in sensitivity relative to conventional V-EASI-MS for almost all compounds tested. More specifically, for peptides a 1.6- to 4-fold enhancement was realized, for proteins the enhancements were from 2- to 5-fold, and for some metalloid species enhancements reached up to 10-fold. However, optimum additive concentration and ion transfer capillary temperature were found to be compound-dependent and thus require optimization in order for maximum enhancements to be achieved. In most cases the 3-NBN-assisted V-EASI-MS approach provides comparable sensitivities and S/N ratios to ESI-MS on the same ion trap mass spectrometer. The use of 3-NBN with V-EASI-MS gives rise to a novel 3-NBN-assisted MS technique, which has demonstrated considerable signal enhancement for most of the compounds analyzed, thus improving its competitiveness towards the well-established and dominating ESI-MS technique. Copyright © 2014 John Wiley & Sons, Ltd.

Asymmetric exponential amplification reaction on a toehold/biotin featured template: an ultrasensitive and specific strategy for isothermal microRNAs analysis

PubMed Central

Chen, Jun; Zhou, Xueqing; Ma, Yingjun; Lin, Xiulian; Dai, Zong; Zou, Xiaoyong

2016-01-01

The sensitive and specific analysis of microRNAs (miRNAs) without using a thermal cycler instrument is significant and would greatly facilitate biological research and disease diagnostics. Although exponential amplification reaction (EXPAR) is the most attractive strategy for the isothermal analysis of miRNAs, its intrinsic limitations of detection efficiency and inevitable non-specific amplification critically restrict its use in analytical sensitivity and specificity. Here, we present a novel asymmetric EXPAR based on a new biotin/toehold featured template. A biotin tag was used to reduce the melting temperature of the primer/template duplex at the 5′ terminus of the template, and a toehold exchange structure acted as a filter to suppress the non-specific trigger of EXPAR. The asymmetric EXPAR exhibited great improvements in amplification efficiency and specificity as well as a dramatic extension of dynamic range. The limit of detection for the let-7a analysis was decreased to 6.02 copies (0.01 zmol), and the dynamic range was extended to 10 orders of magnitude. The strategy enabled the sensitive and accurate analysis of let-7a miRNA in human cancer tissues with clearly better precision than both standard EXPAR and RT-qPCR. Asymmetric EXPAR is expected to have an important impact on the development of simple and rapid molecular diagnostic applications for short oligonucleotides. PMID:27257058

Novel frontiers in ultra-structural and molecular MRI of the brain.

PubMed

Duyn, Jeff H; Koretsky, Alan P

2011-08-01

Recent developments in the MRI of the brain continue to expand its use in basic and clinical neuroscience. This review highlights some areas of recent progress. Higher magnetic field strengths and improved signal detectors have allowed improved visualization of the various properties of the brain, facilitating the anatomical definition of function-specific areas and their connections. For example, by sensitizing the MRI signal to the magnetic susceptibility of tissue, it is starting to become possible to reveal the laminar structure of the cortex and identify millimeter-scale fiber bundles. Using exogenous contrast agents, and innovative ways to manipulate contrast, it is becoming possible to highlight specific fiber tracts and cell populations. These techniques are bringing us closer to understanding the evolutionary blueprint of the brain, improving the detection and characterization of disease, and help to guide treatment. Recent MRI techniques are leading to more detailed and more specific contrast in the study of the brain.

Specificity of Disgust Vulnerability in the Distinction and Treatment of OCD

PubMed Central

Olatunji, Bunmi O.; Tart, Candyce D.; Ciesielski, Bethany G.; McGrath, Patrick B.; Smits, Jasper A. J.

2011-01-01

A growing body of research has implicated disgust as a potential risk factor for the development and maintenance of obsessive–compulsive disorder (OCD). The first aim of the present study was to determine whether related, yet distinct, disgust vulnerabilities are endorsed more strongly by individuals with OCD than by those with another anxiety disorder. The second aim was to examine the unique contributions of changes in disgust to symptom improvement observed with exposure-based treatment for OCD. In study 1, individuals with OCD, generalized anxiety disorder (GAD), and nonclinical controls (NCCs) completed a measure of disgust propensity and disgust sensitivity. Compared to NCCs and individuals with GAD, those with OCD more strongly endorsed disgust propensity. However, individuals with OCD did not significantly differ from individuals with GAD in disgust sensitivity, although both groups reported significantly higher disgust sensitivity levels compared to NCCs. Study 2 comprised mediation analyses of symptom improvement among individuals with OCD and revealed that decreases in disgust propensity over time mediated improvement in OCD symptoms, even after controlling for improvements in negative affect. The implications of these findings for conceptualizing the role of disgust in the nature and treatment of OCD are discussed. PMID:21353249

Differentiation chronic post traumatic stress disorder patients from healthy subjects using objective and subjective sleep-related parameters.

PubMed

Tahmasian, Masoud; Jamalabadi, Hamidreza; Abedini, Mina; Ghadami, Mohammad R; Sepehry, Amir A; Knight, David C; Khazaie, Habibolah

2017-05-22

Sleep disturbance is common in chronic post-traumatic stress disorder (PTSD). However, prior work has demonstrated that there are inconsistencies between subjective and objective assessments of sleep disturbance in PTSD. Therefore, we investigated whether subjective or objective sleep assessment has greater clinical utility to differentiate PTSD patients from healthy subjects. Further, we evaluated whether the combination of subjective and objective methods improves the accuracy of classification into patient versus healthy groups, which has important diagnostic implications. We recruited 32 chronic war-induced PTSD patients and 32 age- and gender-matched healthy subjects to participate in this study. Subjective (i.e. from three self-reported sleep questionnaires) and objective sleep-related data (i.e. from actigraphy scores) were collected from each participant. Subjective, objective, and combined (subjective and objective) sleep data were then analyzed using support vector machine classification. The classification accuracy, sensitivity, and specificity for subjective variables were 89.2%, 89.3%, and 89%, respectively. The classification accuracy, sensitivity, and specificity for objective variables were 65%, 62.3%, and 67.8%, respectively. The classification accuracy, sensitivity, and specificity for the aggregate variables (combination of subjective and objective variables) were 91.6%, 93.0%, and 90.3%, respectively. Our findings indicate that classification accuracy using subjective measurements is superior to objective measurements and the combination of both assessments appears to improve the classification accuracy for differentiating PTSD patients from healthy individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis.

PubMed

Chen, Xueping; Chen, Yongping; Wei, Qianqian; Ou, Ruwei; Cao, Bei; Zhao, Bi; Shang, Hui-Fang

2016-09-15

The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS). Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA. Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %. Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

A Web-Based Education Program for Colorectal Lesion Diagnosis with Narrow Band Imaging Classification.

PubMed

Aihara, Hiroyuki; Kumar, Nitin; Thompson, Christopher C

2018-04-19

An education system for narrow band imaging (NBI) interpretation requires sufficient exposure to key features. However, access to didactic lectures by experienced teachers is limited in the United States. To develop and assess the effectiveness of a colorectal lesion identification tutorial. In the image analysis pretest, subjects including 9 experts and 8 trainees interpreted 50 white light (WL) and 50 NBI images of colorectal lesions. Results were not reviewed with subjects. Trainees then participated in an online tutorial emphasizing NBI interpretation in colorectal lesion analysis. A post-test was administered and diagnostic yields were compared to pre-education diagnostic yields. Under the NBI mode, experts showed higher diagnostic yields (sensitivity 91.5% [87.3-94.4], specificity 90.6% [85.1-94.2], and accuracy 91.1% [88.5-93.7] with substantial interobserver agreement [κ value 0.71]) compared to trainees (sensitivity 89.6% [84.8-93.0], specificity 80.6% [73.5-86.3], and accuracy 86.0% [82.6-89.2], with substantial interobserver agreement [κ value 0.69]). The online tutorial improved the diagnostic yields of trainees to the equivalent level of experts (sensitivity 94.1% [90.0-96.6], specificity 89.0% [83.0-93.2], and accuracy 92.0% [89.3-94.7], p < 0.001 with substantial interobserver agreement [κ value 0.78]). This short, online tutorial improved diagnostic performance and interobserver agreement. © 2018 S. Karger AG, Basel.

Using the Bayesian Improved Surname Geocoding Method (BISG) to create a working classification of race and ethnicity in a diverse managed care population: a validation study.

PubMed

Adjaye-Gbewonyo, Dzifa; Bednarczyk, Robert A; Davis, Robert L; Omer, Saad B

2014-02-01

To validate classification of race/ethnicity based on the Bayesian Improved Surname Geocoding method (BISG) and assess variations in validity by gender and age. Secondary data on members of Kaiser Permanente Georgia, an integrated managed care organization, through 2010. For 191,494 members with self-reported race/ethnicity, probabilities for belonging to each of six race/ethnicity categories predicted from the BISG algorithm were used to assign individuals to a race/ethnicity category over a range of cutoffs greater than a probability of 0.50. Overall as well as gender- and age-stratified sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Receiver operating characteristic (ROC) curves were generated and used to identify optimal cutoffs for race/ethnicity assignment. The overall cutoffs for assignment that optimized sensitivity and specificity ranged from 0.50 to 0.57 for the four main racial/ethnic categories (White, Black, Asian/Pacific Islander, Hispanic). Corresponding sensitivity, specificity, PPV, and NPV ranged from 64.4 to 81.4 percent, 80.8 to 99.7 percent, 75.0 to 91.6 percent, and 79.4 to 98.0 percent, respectively. Accuracy of assignment was better among males and individuals of 65 years or older. BISG may be useful for classifying race/ethnicity of health plan members when needed for health care studies. © Health Research and Educational Trust.

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.

Improving digital breast tomosynthesis reading time: A pilot multi-reader, multi-case study using concurrent Computer-Aided Detection (CAD).

PubMed

Balleyguier, Corinne; Arfi-Rouche, Julia; Levy, Laurent; Toubiana, Patrick R; Cohen-Scali, Franck; Toledano, Alicia Y; Boyer, Bruno

2017-12-01

Evaluate concurrent Computer-Aided Detection (CAD) with Digital Breast Tomosynthesis (DBT) to determine impact on radiologist performance and reading time. The CAD system detects and extracts suspicious masses, architectural distortions and asymmetries from DBT planes that are blended into corresponding synthetic images to form CAD-enhanced synthetic images. Review of CAD-enhanced images and navigation to corresponding planes to confirm or dismiss potential lesions allows radiologists to more quickly review DBT planes. A retrospective, crossover study with and without CAD was conducted with six radiologists who read an enriched sample of 80 DBT cases including 23 malignant lesions in 21 women. Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) compared the readings with and without CAD to determine the effect of CAD on overall interpretation performance. Sensitivity, specificity, recall rate and reading time were also assessed. Multi-reader, multi-case (MRMC) methods accounting for correlation and requiring correct lesion localization were used to analyze all endpoints. AUCs were based on a 0-100% probability of malignancy (POM) score. Sensitivity and specificity were based on BI-RADS scores, where 3 or higher was positive. Average AUC across readers without CAD was 0.854 (range: 0.785-0.891, 95% confidence interval (CI): 0.769,0.939) and 0.850 (range: 0.746-0.905, 95% CI: 0.751,0.949) with CAD (95% CI for difference: -0.046,0.039), demonstrating non-inferiority of AUC. Average reduction in reading time with CAD was 23.5% (95% CI: 7.0-37.0% improvement), from an average 48.2 (95% CI: 39.1,59.6) seconds without CAD to 39.1 (95% CI: 26.2,54.5) seconds with CAD. Per-patient sensitivity was the same with and without CAD (0.865; 95% CI for difference: -0.070,0.070), and there was a small 0.022 improvement (95% CI for difference: -0.046,0.089) in per-lesion sensitivity from 0.790 without CAD to 0.812 with CAD. A slight reduction in specificity with a -0.014 difference (95% CI for difference: -0.079,0.050) and a small 0.025 increase (95% CI for difference: -0.036,0.087) in recall rate in non-cancer cases were observed with CAD. Concurrent CAD resulted in faster reading time with non-inferiority of radiologist interpretation performance. Radiologist sensitivity, specificity and recall rate were similar with and without CAD. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers

PubMed Central

Ronkainen, Niina J.; Okon, Stanley L.

2014-01-01

Nanotechnology has played a crucial role in the development of biosensors over the past decade. The development, testing, optimization, and validation of new biosensors has become a highly interdisciplinary effort involving experts in chemistry, biology, physics, engineering, and medicine. The sensitivity, the specificity and the reproducibility of biosensors have improved tremendously as a result of incorporating nanomaterials in their design. In general, nanomaterials-based electrochemical immunosensors amplify the sensitivity by facilitating greater loading of the larger sensing surface with biorecognition molecules as well as improving the electrochemical properties of the transducer. The most common types of nanomaterials and their properties will be described. In addition, the utilization of nanomaterials in immunosensors for biomarker detection will be discussed since these biosensors have enormous potential for a myriad of clinical uses. Electrochemical immunosensors provide a specific and simple analytical alternative as evidenced by their brief analysis times, inexpensive instrumentation, lower assay cost as well as good portability and amenability to miniaturization. The role nanomaterials play in biosensors, their ability to improve detection capabilities in low concentration analytes yielding clinically useful data and their impact on other biosensor performance properties will be discussed. Finally, the most common types of electroanalytical detection methods will be briefly touched upon. PMID:28788700

Use of a Rapid Test for Diagnosis of Dengue during Suspected Dengue Outbreaks in Resource-Limited Regions.

PubMed

Hunsperger, Elizabeth A; Sharp, Tyler M; Lalita, Paul; Tikomaidraubuta, Kini; Cardoso, Yolanda Rebello; Naivalu, Taina; Khan, Aalisha Sahu; Marfel, Maria; Hancock, W Thane; Tomashek, Kay M; Margolis, Harold S

2016-08-01

Dengue is major public health problem, globally. Timely verification of suspected dengue outbreaks allows for public health response, leading to the initiation of appropriate clinical care. Because the clinical presentation of dengue is nonspecific, dengue diagnosis would benefit from a sensitive rapid diagnostic test (RDT). We evaluated the diagnostic performance of an RDT that detects dengue virus (DENV) nonstructural protein 1 (NS1) and anti-DENV IgM during suspected acute febrile illness (AFI) outbreaks in four countries. Real-time reverse transcription-PCR and anti-DENV IgM enzyme-linked immunosorbent assay were used to verify RDT results. Anti-DENV IgM RDT sensitivity and specificity ranged from 55.3 to 91.7% and 85.3 to 98.5%, respectively, and NS1 sensitivity and specificity ranged from 49.7 to 92.9% and 22.2 to 89.0%, respectively. Sensitivity varied by timing of specimen collection and DENV serotype. Combined test results moderately improved the sensitivity. The use of RDTs identified dengue as the cause of AFI outbreaks where reference diagnostic testing was limited or unavailable. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Integrated digital error suppression for improved detection of circulating tumor DNA

PubMed Central

Kurtz, David M.; Chabon, Jacob J.; Scherer, Florian; Stehr, Henning; Liu, Chih Long; Bratman, Scott V.; Say, Carmen; Zhou, Li; Carter, Justin N.; West, Robert B.; Sledge, George W.; Shrager, Joseph B.; Loo, Billy W.; Neal, Joel W.; Wakelee, Heather A.; Diehn, Maximilian; Alizadeh, Ash A.

2016-01-01

High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method combines in silico elimination of highly stereotypical background artifacts with a molecular barcoding strategy for the efficient recovery of cfDNA molecules. Individually, these two methods each improve the sensitivity of cancer personalized profiling by deep sequencing (CAPP-Seq) by ~3 fold, and synergize when combined to yield ~15-fold improvements. As a result, iDES-enhanced CAPP-Seq facilitates noninvasive variant detection across hundreds of kilobases. Applied to clinical non-small cell lung cancer (NSCLC) samples, our method enabled biopsy-free profiling of EGFR kinase domain mutations with 92% sensitivity and 96% specificity and detection of ctDNA down to 4 in 105 cfDNA molecules. We anticipate that iDES will aid the noninvasive genotyping and detection of ctDNA in research and clinical settings. PMID:27018799

State-of-the-Art Fusion-Finder Algorithms Sensitivity and Specificity

PubMed Central

Carrara, Matteo; Beccuti, Marco; Lazzarato, Fulvio; Cavallo, Federica; Cordero, Francesca; Donatelli, Susanna; Calogero, Raffaele A.

2013-01-01

Background. Gene fusions arising from chromosomal translocations have been implicated in cancer. RNA-seq has the potential to discover such rearrangements generating functional proteins (chimera/fusion). Recently, many methods for chimeras detection have been published. However, specificity and sensitivity of those tools were not extensively investigated in a comparative way. Results. We tested eight fusion-detection tools (FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse, Bellerophontes, ChimeraScan, and TopHat-fusion) to detect fusion events using synthetic and real datasets encompassing chimeras. The comparison analysis run only on synthetic data could generate misleading results since we found no counterpart on real dataset. Furthermore, most tools report a very high number of false positive chimeras. In particular, the most sensitive tool, ChimeraScan, reports a large number of false positives that we were able to significantly reduce by devising and applying two filters to remove fusions not supported by fusion junction-spanning reads or encompassing large intronic regions. Conclusions. The discordant results obtained using synthetic and real datasets suggest that synthetic datasets encompassing fusion events may not fully catch the complexity of RNA-seq experiment. Moreover, fusion detection tools are still limited in sensitivity or specificity; thus, there is space for further improvement in the fusion-finder algorithms. PMID:23555082

The impact of alternative diagnoses on the utility of influenza-like illness case definition to detect the 2009 H1N1 pandemic.

PubMed

Rumoro, Dino P; Bayram, Jamil D; Silva, Julio C; Shah, Shital C; Hallock, Marilyn M; Gibbs, Gillian S; Waddell, Michael J

2012-01-01

To investigate the impact of excluding cases with alternative diagnoses on the sensitivity and specificity of the Centers for Disease Control and Prevention's (CDC) influenza-like illness (ILI) case definition in detecting the 2009 H1N1 influenza, using Geographic Utilization of Artificial Intelligence in Real-Time for Disease Identification and Alert Notification, a disease surveillance system. Retrospective cross-sectional study design. Emergency department of an urban tertiary care academic medical center. 1,233 ED cases, which were tested for respiratory viruses from September 5, 2009 to May 5, 2010. The main outcome measures were positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of the ILI case definition (both including and excluding alternative diagnoses) to detect H1N1. There was a significant decrease in sensitivity (chi2 = 9.09, p < 0.001) and significant improvement in specificity (chi2 = 179, p < 0.001), after excluding cases with alternative diagnoses. When early detection of an influenza epidemic is of prime importance, pursuing alternative diagnoses as part of CDC's ILI case definition may not be warranted for public health reporting due to the significant decrease in sensitivity, in addition to the resources required for detecting these alternative diagnoses.

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.

Rapid Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) by the Vitek MS Saramis system.

PubMed

Shan, Weiguang; Li, Jiaping; Fang, Ying; Wang, Xuan; Gu, Danxia; Zhang, Rong

2016-01-01

A rapid, sensitive, and accurate Vitek MS assay was developed to distinguish clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) from clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) by developing an in-house knowledgebase of SuperSpectra. Three unique peaks, including peaks at 2305.6 and 3007.3 Da specific to MRSA, and 6816.7 Da specific to MSSA, were selected for differentiating MRSA and MSSA. This assay accurately identified 84 and 91% of clinical MRSA and MSSA strains out of the total 142 clinically acquired S. aureus strains that were tested. This method will greatly improve the efficiency of single clinical sample identification of MRSA, thereby facilitating a reduction in the transmission of MRSA in clinical settings.

Occupancy Modeling for Improved Accuracy and Understanding of Pathogen Prevalence and Dynamics

PubMed Central

Colvin, Michael E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

2015-01-01

Most pathogen detection tests are imperfect, with a sensitivity < 100%, thereby resulting in the potential for a false negative, where a pathogen is present but not detected. False negatives in a sample inflate the number of non-detections, negatively biasing estimates of pathogen prevalence. Histological examination of tissues as a diagnostic test can be advantageous as multiple pathogens can be examined and providing important information on associated pathological changes to the host. However, it is usually less sensitive than molecular or microbiological tests for specific pathogens. Our study objectives were to 1) develop a hierarchical occupancy model to examine pathogen prevalence in spring Chinook salmon Oncorhynchus tshawytscha and their distribution among host tissues 2) use the model to estimate pathogen-specific test sensitivities and infection rates, and 3) illustrate the effect of using replicate within host sampling on sample sizes required to detect a pathogen. We examined histological sections of replicate tissue samples from spring Chinook salmon O. tshawytscha collected after spawning for common pathogens seen in this population: Apophallus/echinostome metacercariae, Parvicapsula minibicornis, Nanophyetus salmincola/ metacercariae, and Renibacterium salmoninarum. A hierarchical occupancy model was developed to estimate pathogen and tissue-specific test sensitivities and unbiased estimation of host- and organ-level infection rates. Model estimated sensitivities and host- and organ-level infections rates varied among pathogens and model estimated infection rate was higher than prevalence unadjusted for test sensitivity, confirming that prevalence unadjusted for test sensitivity was negatively biased. The modeling approach provided an analytical approach for using hierarchically structured pathogen detection data from lower sensitivity diagnostic tests, such as histology, to obtain unbiased pathogen prevalence estimates with associated uncertainties. Accounting for test sensitivity using within host replicate samples also required fewer individual fish to be sampled. This approach is useful for evaluating pathogen or microbe community dynamics when test sensitivity is <100%. PMID:25738709

Occupancy modeling for improved accuracy and understanding of pathogen prevalence and dynamics

USGS Publications Warehouse

Colvin, Michael E.; Peterson, James T.; Kent, Michael L.; Schreck, Carl B.

2015-01-01

Most pathogen detection tests are imperfect, with a sensitivity < 100%, thereby resulting in the potential for a false negative, where a pathogen is present but not detected. False negatives in a sample inflate the number of non-detections, negatively biasing estimates of pathogen prevalence. Histological examination of tissues as a diagnostic test can be advantageous as multiple pathogens can be examined and providing important information on associated pathological changes to the host. However, it is usually less sensitive than molecular or microbiological tests for specific pathogens. Our study objectives were to 1) develop a hierarchical occupancy model to examine pathogen prevalence in spring Chinook salmonOncorhynchus tshawytscha and their distribution among host tissues 2) use the model to estimate pathogen-specific test sensitivities and infection rates, and 3) illustrate the effect of using replicate within host sampling on sample sizes required to detect a pathogen. We examined histological sections of replicate tissue samples from spring Chinook salmon O. tshawytscha collected after spawning for common pathogens seen in this population:Apophallus/echinostome metacercariae, Parvicapsula minibicornis, Nanophyetus salmincola/metacercariae, and Renibacterium salmoninarum. A hierarchical occupancy model was developed to estimate pathogen and tissue-specific test sensitivities and unbiased estimation of host- and organ-level infection rates. Model estimated sensitivities and host- and organ-level infections rates varied among pathogens and model estimated infection rate was higher than prevalence unadjusted for test sensitivity, confirming that prevalence unadjusted for test sensitivity was negatively biased. The modeling approach provided an analytical approach for using hierarchically structured pathogen detection data from lower sensitivity diagnostic tests, such as histology, to obtain unbiased pathogen prevalence estimates with associated uncertainties. Accounting for test sensitivity using within host replicate samples also required fewer individual fish to be sampled. This approach is useful for evaluating pathogen or microbe community dynamics when test sensitivity is <100%.

Direct Detection of Nucleic Acid with Minimizing Background and Improving Sensitivity Based on a Conformation-Discriminating Indicator.

PubMed

Zhu, Lixuan; Qing, Zhihe; Hou, Lina; Yang, Sheng; Zou, Zhen; Cao, Zhong; Yang, Ronghua

2017-08-25

As is well-known, the nucleic acid indicator-based strategy is one of the major approaches to monitor the nucleic acid hybridization-mediated recognition events in biochemical analysis, displaying obvious advantages including simplicity, low cost, convenience, and generality. However, conventional indicators either hold strong self-fluorescence or can be lighted by both ssDNA and dsDNA, lacking absolute selectivity for a certain conformation, always with high background interference and low sensitivity in sensing; and additional processing (e.g., nanomaterial-mediated background suppression, and enzyme-catalyzed signal amplification) is generally required to improve the detection performance. In this work, a carbazole derivative, EBCB, has been synthesized and screened as a dsDNA-specific fluorescent indicator. Compared with conventional indicators under the same conditions, EBCB displayed a much higher selective coefficient for dsDNA, with little self-fluorescence and negligible effect from ssDNA. Based on its superior capability in DNA conformation-discrimination, high sensitivity with minimizing background interference was demonstrated for direct detection of nucleic acid, and monitoring nucleic acid-based circuitry with good reversibity, resulting in low detection limit and high capability for discriminating base-mismatching. Thus, we expect that this highly specific DNA conformation-discriminating indicator will hold good potential for application in biochemical sensing and molecular logic switching.

Electronic Raman Scattering as an Ultra-Sensitive Probe of Strain Effects in Semiconductors

NASA Astrophysics Data System (ADS)

Mascarenhas, Angelo; Fluegel, Brian; Beaton, Dan

Semiconductor strain engineering has become a critical feature of high-performance electronics due to the significant device performance enhancements it enables. These improvements that emerge from strain induced modifications to the electronic band structure necessitate new ultra-sensitive tools for probing strain in semiconductors. Using electronic Raman scattering, we recently showed that it is possible to measure minute amounts of strain in thin semiconductor epilayers. We applied this strain measurement technique to two different semiconductor alloy systems, using coherently strained epitaxial thin films specifically designed to produce lattice-mismatch strains as small as 10-4. Comparing our strain sensitivity and signal strength in AlxGa1-xAs with those obtained using the industry-standard technique of phonon Raman scattering we found a sensitivity improvement of ×200, and a signal enhancement of 4 ×103 thus obviating key constraints in semiconductor strain metrology. The sensitivity of this approach rivals that of contemporary techniques and opens up a new realm for optically probing strain effects on electronic band structure. We acknowledge the financial support of the DOE Office of Science, BES under DE-AC36-80GO28308.

Production of Toxocara cati TES-120 Recombinant Antigen and Comparison with its T. canis Homolog for Serodiagnosis of Toxocariasis

PubMed Central

Zahabiun, Farzaneh; Sadjjadi, Seyed Mahmoud; Yunus, Muhammad Hafiznur; Rahumatullah, Anizah; Moghaddam, Mohammad Hosein Falaki; Saidin, Syazwan; Noordin, Rahmah

2015-01-01

Toxocariasis is a cosmopolitan zoonotic disease caused by the infective larvae of Toxocara canis and T. cati. Diagnosis in humans is usually based on clinical symptoms and serology. Immunoglobulin G (IgG)-enzyme-linked immunosorbent assay kits using T. canis excretory–secretory (TES) larval antigens are commonly used for serodiagnosis. Differences in the antigens of the two Toxocara species may influence the diagnostic sensitivity of the test. In this study, T. cati recombinant TES-120 (rTES-120) was cloned, expressed, and compared with its T. canis homolog in an IgG4-western blot. The diagnostic sensitivity and specificity of T. cati rTES-120 were 70% (33/47) and 100% (39/39), respectively. T. canis rTES-120 showed 57.4% sensitivity and 94.4% specificity. When the results of assays using rTES-120 of both species were considered, the diagnostic sensitivity was 76%. This study shows that using antigens from both Toxocara species may improve the serodiagnosis of toxocariasis. PMID:26033026

Production of Toxocara cati TES-120 Recombinant Antigen and Comparison with its T. canis Homolog for Serodiagnosis of Toxocariasis.

PubMed

Zahabiun, Farzaneh; Sadjjadi, Seyed Mahmoud; Yunus, Muhammad Hafiznur; Rahumatullah, Anizah; Moghaddam, Mohammad Hosein Falaki; Saidin, Syazwan; Noordin, Rahmah

2015-08-01

Toxocariasis is a cosmopolitan zoonotic disease caused by the infective larvae of Toxocara canis and T. cati. Diagnosis in humans is usually based on clinical symptoms and serology. Immunoglobulin G (IgG)-enzyme-linked immunosorbent assay kits using T. canis excretory-secretory (TES) larval antigens are commonly used for serodiagnosis. Differences in the antigens of the two Toxocara species may influence the diagnostic sensitivity of the test. In this study, T. cati recombinant TES-120 (rTES-120) was cloned, expressed, and compared with its T. canis homolog in an IgG4-western blot. The diagnostic sensitivity and specificity of T. cati rTES-120 were 70% (33/47) and 100% (39/39), respectively. T. canis rTES-120 showed 57.4% sensitivity and 94.4% specificity. When the results of assays using rTES-120 of both species were considered, the diagnostic sensitivity was 76%. This study shows that using antigens from both Toxocara species may improve the serodiagnosis of toxocariasis. © The American Society of Tropical Medicine and Hygiene.

Chemical derivatization for enhancing sensitivity during LC/ESI-MS/MS quantification of steroids in biological samples: a review.

PubMed

Higashi, Tatsuya; Ogawa, Shoujiro

2016-09-01

Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are necessary for the diagnosis, pathological analysis and treatment of many diseases. Recently, liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) has been widely used for these purposes due to its specificity and versatility. However, the ESI efficiency and fragmentation behavior of some steroids are poor, which lead to a low sensitivity. Chemical derivatization is one of the most effective methods to improve the detection characteristics of steroids in ESI-MS/MS. Based on this background, this article reviews the recent advances in chemical derivatization for the trace quantification of steroids in biological samples by LC/ESI-MS/MS. The derivatization in ESI-MS/MS is based on tagging a proton-affinitive or permanently charged moiety on the target steroid. Introduction/formation of a fragmentable moiety suitable for the selected reaction monitoring by the derivatization also enhances the sensitivity. The stable isotope-coded derivatization procedures for the steroid analysis are also described. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methodological quality of diagnostic accuracy studies on non-invasive coronary CT angiography: influence of QUADAS (Quality Assessment of Diagnostic Accuracy Studies included in systematic reviews) items on sensitivity and specificity.

PubMed

Schueler, Sabine; Walther, Stefan; Schuetz, Georg M; Schlattmann, Peter; Dewey, Marc

2013-06-01

To evaluate the methodological quality of diagnostic accuracy studies on coronary computed tomography (CT) angiography using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies included in systematic reviews) tool. Each QUADAS item was individually defined to adapt it to the special requirements of studies on coronary CT angiography. Two independent investigators analysed 118 studies using 12 QUADAS items. Meta-regression and pooled analyses were performed to identify possible effects of methodological quality items on estimates of diagnostic accuracy. The overall methodological quality of coronary CT studies was merely moderate. They fulfilled a median of 7.5 out of 12 items. Only 9 of the 118 studies fulfilled more than 75 % of possible QUADAS items. One QUADAS item ("Uninterpretable Results") showed a significant influence (P = 0.02) on estimates of diagnostic accuracy with "no fulfilment" increasing specificity from 86 to 90 %. Furthermore, pooled analysis revealed that each QUADAS item that is not fulfilled has the potential to change estimates of diagnostic accuracy. The methodological quality of studies investigating the diagnostic accuracy of non-invasive coronary CT is only moderate and was found to affect the sensitivity and specificity. An improvement is highly desirable because good methodology is crucial for adequately assessing imaging technologies. • Good methodological quality is a basic requirement in diagnostic accuracy studies. • Most coronary CT angiography studies have only been of moderate design quality. • Weak methodological quality will affect the sensitivity and specificity. • No improvement in methodological quality was observed over time. • Authors should consider the QUADAS checklist when undertaking accuracy studies.

Comparison of Digital Tomosynthesis and Chest Radiography for the Detection of Noncalcified Pulmonary and Hilar Lesions.

PubMed

Galea, Angela; Adlan, Tarig; Gay, David; Roobottom, Carl; Dubbins, Paul; Riordan, Richard

2015-09-01

The aim of this study was to compare the sensitivity and specificity of chest digital tomosynthesis (DTS) with chest radiography (CXR) for the detection of noncalcified pulmonary nodules and hilar lesions using computed tomography (CT) as the reference standard. A total of 78 patients with suspected noncalcified pulmonary lesions on CXR were included in the study. Two radiologists, blinded to the history and CT, analyzed the CXR and the DTS images (separately), whereas a third radiologist analyzed the CXR and DTS images together. Noncalcified intrapulmonary nodules and hilar lesions were recorded for analysis. The interobserver agreement for CXR and DTS was assessed, and the time taken to report the images was recorded. A total of 202 lesions were recorded in 78 patients. There were 111 true lesions confirmed on CT in 53 patients; in 25 patients subsequent CT excluded a lesion. The overall sensitivity was 32% for CXR and 49% for DTS. This improved to 54% when the posteroanterior CXR and DTS were reviewed together (CXR-DTS). The overall specificities for CXR, DTS, and CXR-DTS were 49%, 96%, and 98%, respectively. There were 56 suspected hilar lesions with subgroup sensitivities of 76% for CXR, 65% for DTS, and 76% for CXR-DTS. The specificity for hilar lesions was 59%, 92%, and 97% for CXR, DTS, and CXR-DTS, respectively. DTS significantly improves the detectability of noncalcified nodules when compared with and when used in combination with CXR. The specificity and interobserver agreement of DTS in the diagnosis of suspected noncalcified pulmonary nodules and hilar lesions are significantly better than those of CXR and approaches those of CT.

Immunocytochemical detection of Mycobacterium Tuberculosis complex specific antigen, MPT64, improves diagnosis of tuberculous lymphadenitis and tuberculous pleuritis.

PubMed

Tadele, Agerie; Beyene, Demissew; Hussein, Jemal; Gemechu, Tuffa; Birhanu, Asaye; Mustafa, Tehmina; Tsegaye, Aster; Aseffa, Abraham; Sviland, Lisbet

2014-11-25

A rapid, sensitive and accurate laboratory diagnosis is of prime importance in suspected extrapulmonary tuberculosis (EPTB) cases. However, traditional techniques for the detection of acid-fast bacilli have limitations. The aim of the study was to evaluate the diagnostic value of immunocytochemical staining for detection of Mycobacterium tuberculosis complex specific antigen, MPT64, in aspirates from pleural effusions and lymph nodes, the most common presentations of EPTB. A cross-sectional study was conducted by including patients at Tikur Anbessa Specialized Hospital and the United Vision Medical Services from December 2011 to June 2012. Lymph node aspirates and pleural fluid samples were collected and analyzed from a total of 51 cases (26 tuberculous (TB) pleuritis and 25 TB lymphadenitis) and 67 non-TB controls. Each specimen was subjected to Ziehl-Neelsen (ZN) staining, culture on Lowenstein- Jensen (LJ) medium, cytological examination, Polymerase Chain Reaction (PCR) using IS1081gene sequence as a primer and immunocytochemistry (ICC) with polyclonal anti-MPT64 antibody. All patients were screened for HIV. ICC was positive in 38 of 51 cases and in the 7 of 67 controls giving an overall sensitivity and specificity of 74.5% and 89.5%, respectively. Using IS1081-PCR as a reference method, the sensitivity and specificity, positive and negative predictive value of ICC was 88.1%, 89.5%, 82.2% and 93.2%, respectively. The case detection rate increased from 13.7% by ZN stain to 19.6% by LJ culture, to 66.7% by cytology and 74.5% by ICC. Immunocytochemistry with anti-MPT64 antigen improved detection of TB in pleural effusion and lymph node aspirates. Further studies using monoclonal antibodies on samples from other sites of EPTB is recommended to validate this relatively simple diagnostic method for EPTB.

A multiplexable, microfluidic platform for the rapid quantitation of a biomarker panel for early ovarian cancer detection at the point-of-care

PubMed Central

Shadfan, Basil H.; Simmons, Archana R.; Simmons, Glennon W.; Ho, Andy; Wong, Jorge; Lu, Karen H.; Bast, Robert C.; McDevitt, John T.

2015-01-01

Point-of-care (POC) diagnostic platforms have the potential to enable low-cost, large-scale screening. As no single biomarker is shed by all ovarian cancers, multiplexed biomarker panels promise improved sensitivity and specificity to address the unmet need for early detection of ovarian cancer. We have configured the programmable bio-nano-chip (p-BNC) - a multiplexable, microfluidic, modular platform - to quantify a novel multimarker panel comprising CA125, HE4, MMP-7 and CA72-4. The p-BNC is a bead-based immunoanalyzer system with a credit-card-sized footprint that integrates automated sample metering, bubble and debris removal, reagent storage and waste disposal, permitting POC analysis. Multiplexed p-BNC immunoassays demonstrated high specificity, low cross-reactivity, low limits of detection suitable for early detection, and a short analysis time of 43 minutes. Day-to-day variability, a critical factor for longitudinally monitoring biomarkers, ranged between 5.4–10.5%, well below the biological variation for all four markers. Biomarker concentrations for 31 late-stage sera correlated well (R2 = 0.71 to 0.93 for various biomarkers) with values obtained on the Luminex® platform. In a 31 patient cohort encompassing early- and late-stage ovarian cancers along with benign and healthy controls, the multiplexed p-BNC panel was able to distinguish cases from controls with 68.7% sensitivity at 80% specificity. Utility for longitudinal biomarker monitoring was demonstrated with pre-diagnostic sera from 2 cases and 4 controls. Taken together, the p-BNC shows strong promise as a diagnostic tool for large-scale screening that takes advantage of faster results and lower costs while leveraging possible improvement in sensitivity and specificity from biomarker panels. PMID:25388014

New insights into seafood allergy.

PubMed

Lopata, Andreas L; Lehrer, Samuel B

2009-06-01

Seafood plays an important role in human nutrition worldwide, sustained by international trade of a variety of new seafood products. Increased production and consumption have resulted in more frequent reports of adverse reactions, highlighting the need for more specific diagnosis and treatment of seafood allergy. This review discusses recent literature in this field. The most recent prevalence data from Asia highlight seafood as a significant sensitizer in up to 40% of children and 33% of adults. Furthermore, the demonstration of species-specific sensitization to salt-water and fresh-water prawns and processed prawn extract should improve diagnosis. Studies on humans demonstrated for the first time that biologically active fish allergens can be detected in serum samples as early as 10 min after ingestion. These studies highlight that minute amounts of ingested seafood allergens can quickly trigger allergic symptoms; also, inhaled airborne allergens seem to induce sensitization and reactions. In the past 2 years, over 10 additional seafood allergens have been characterized. Allergen-specific detection assays in food products are available for crustacean tropomyosin; however, many specific mollusk and some fish allergens are not readily identified. Although cross-reactivity between crustacean and mollusks as well as mites is demonstrated, the often poor correlation of IgE reactivity and clinical symptoms calls for more detailed investigations. The recent development of hypoallergenic parvalbumin from carp could form the basis for safer vaccination products for treatment of fish allergy. Molecular characterization of more universal marker allergens for the three major seafood groups will improve current component-resolved clinical diagnosis and have a significant impact on the management of allergic patients, on food labeling and on future immunotherapy for seafood allergy.

Optimizing spectral wave estimates with adjoint-based sensitivity maps

NASA Astrophysics Data System (ADS)

Orzech, Mark; Veeramony, Jay; Flampouris, Stylianos

2014-04-01

A discrete numerical adjoint has recently been developed for the stochastic wave model SWAN. In the present study, this adjoint code is used to construct spectral sensitivity maps for two nearshore domains. The maps display the correlations of spectral energy levels throughout the domain with the observed energy levels at a selected location or region of interest (LOI/ROI), providing a full spectrum of values at all locations in the domain. We investigate the effectiveness of sensitivity maps based on significant wave height ( H s ) in determining alternate offshore instrument deployment sites when a chosen nearshore location or region is inaccessible. Wave and bathymetry datasets are employed from one shallower, small-scale domain (Duck, NC) and one deeper, larger-scale domain (San Diego, CA). The effects of seasonal changes in wave climate, errors in bathymetry, and multiple assimilation points on sensitivity map shapes and model performance are investigated. Model accuracy is evaluated by comparing spectral statistics as well as with an RMS skill score, which estimates a mean model-data error across all spectral bins. Results indicate that data assimilation from identified high-sensitivity alternate locations consistently improves model performance at nearshore LOIs, while assimilation from low-sensitivity locations results in lesser or no improvement. Use of sub-sampled or alongshore-averaged bathymetry has a domain-specific effect on model performance when assimilating from a high-sensitivity alternate location. When multiple alternate assimilation locations are used from areas of lower sensitivity, model performance may be worse than with a single, high-sensitivity assimilation point.

Accounting for regional variation in both natural environment and human disturbance to improve performance of multimetric indices of lotic benthic diatoms.

PubMed

Tang, Tao; Stevenson, R Jan; Infante, Dana M

2016-10-15

Regional variation in both natural environment and human disturbance can influence performance of ecological assessments. In this study we calculated 5 types of benthic diatom multimetric indices (MMIs) with 3 different approaches to account for variation in ecological assessments. We used: site groups defined by ecoregions or diatom typologies; the same or different sets of metrics among site groups; and unmodeled or modeled MMIs, where models accounted for natural variation in metrics within site groups by calculating an expected reference condition for each metric and each site. We used data from the USEPA's National Rivers and Streams Assessment to calculate the MMIs and evaluate changes in MMI performance. MMI performance was evaluated with indices of precision, bias, responsiveness, sensitivity and relevancy which were respectively measured as MMI variation among reference sites, effects of natural variables on MMIs, difference between MMIs at reference and highly disturbed sites, percent of highly disturbed sites properly classified, and relation of MMIs to human disturbance and stressors. All 5 types of MMIs showed considerable discrimination ability. Using different metrics among ecoregions sometimes reduced precision, but it consistently increased responsiveness, sensitivity, and relevancy. Site specific metric modeling reduced bias and increased responsiveness. Combined use of different metrics among site groups and site specific modeling significantly improved MMI performance irrespective of site grouping approach. Compared to ecoregion site classification, grouping sites based on diatom typologies improved precision, but did not improve overall performance of MMIs if we accounted for natural variation in metrics with site specific models. We conclude that using different metrics among ecoregions and site specific metric modeling improve MMI performance, particularly when used together. Applications of these MMI approaches in ecological assessments introduced a tradeoff with assessment consistency when metrics differed across site groups, but they justified the convenient and consistent use of ecoregions. Copyright © 2016 Elsevier B.V. All rights reserved.

Is There an Enabling Environment for Nutrition-Sensitive Agriculture in South Asia? Stakeholder Perspectives from India, Bangladesh, and Pakistan.

PubMed

van den Bold, Mara; Kohli, Neha; Gillespie, Stuart; Zuberi, Samar; Rajeesh, Sangeetha; Chakraborty, Barnali

2015-06-01

Almost half of all children in South Asia are stunted. Although agriculture has the potential to be a strong driver of undernutrition reduction and serves as the main source of livelihood for over half of South Asia's population, its potential to reduce undernutrition is currently not being realized. The Leveraging Agriculture for Nutrition in South Asia (LANSA) research consortium seeks to understand how agriculture and agrifood systems can be better designed to improve nutrition in South Asia. In 2013 and 2014, LANSA carried out interviews with stakeholders influential in, and/or knowledgeable of, agriculture-nutrition policy in India, Pakistan, and Bangladesh, to gain a better understanding of the institutional and political factors surrounding the nutrition sensitivity of agriculture in the region. Semistructured interviews were carried out in India, Bangladesh, and Pakistan with a total of 56 stakeholders representing international organizations, research, government, civil society, donors, and the private sector. The findings point to mixed perspectives on countries' policy sensitivity toward nutrition. There was consensus among stakeholders on the importance of political commitment to nutrition, improving nutrition literacy, strengthening capacities, and improving the use of financial resources. Although there are different ways in which South Asian agriculture can improve its impact on nutrition, sensitizing key influencers to the importance of nutrition for the health of a country's population appears as a critical issue. This should in turn serve as the premise for political commitment, intersectoral coordination to implement nutrition-relevant policies, adequately resourced nutrition-specific and nutrition-sensitive programs, and sufficient capacities at all levels. © The Author(s) 2015.

Modification of a deoxynivalenol-antigen-mimicking nanobody to improve immunoassay sensitivity by site-saturation mutagenesis.

PubMed

Qiu, Yu-Lou; He, Qing-Hua; Xu, Yang; Wang, Wei; Liu, Yuan-Yuan

2016-01-01

A nanobody (N-28) which can act as a deoxynivalenol (DON) antigen has been generated, and its residues Thr102-Ser106 were identified to bind with anti-DON monoclonal antibody by alanine-scanning mutagenesis. Site-saturation mutagenesis was used to analyze the plasticity of five residues and to improve the sensitivity of the N-28-based immunoassay. After mutagenesis, three mutants were selected by phage immunoassay and were sequenced. The half-maximal inhibitory concentrations of the immunoassay based on mutants N-28-T102Y, N-28-V103L, and N-28-Y105F were 24.49 ± 1.0, 51.83 ± 2.5, and 35.65 ± 1.6 ng/mL, respectively, showing the assay was, respectively, 3.2, 1.5, and 2.2 times more sensitive than the wild-type-based assay. The best mutant, N-28-T102Y, was used to develop a competitive phage ELISA to detect DON in cereals with high specificity and accuracy. In addition, the structural properties of N-28-T102Y and N-28 were investigated, revealing that the affinity of N-28-T102Y decreased because of increased steric hindrance with the large side chain. The lower-binding-affinity antigen mimetic may contribute to the improvement of the sensitivity of competitive immunoassays. These results demonstrate that nanobodies would be a favorable tool for engineering. Moreover, our results have laid a solid foundation for site-saturation mutagenesis of antigen-mimicking nanobodies to improve immunoassay sensitivity for small molecules.

Choosing a design to fit the situation: how to improve specificity and positive predictive values using Bayesian lot quality assurance sampling

PubMed Central

Olives, Casey; Pagano, Marcello

2013-01-01

Background Lot Quality Assurance Sampling (LQAS) is a provably useful tool for monitoring health programmes. Although LQAS ensures acceptable Producer and Consumer risks, the literature alleges that the method suffers from poor specificity and positive predictive values (PPVs). We suggest that poor LQAS performance is due, in part, to variation in the true underlying distribution. However, until now the role of the underlying distribution in expected performance has not been adequately examined. Methods We present Bayesian-LQAS (B-LQAS), an approach to incorporating prior information into the choice of the LQAS sample size and decision rule, and explore its properties through a numerical study. Additionally, we analyse vaccination coverage data from UNICEF’s State of the World’s Children in 1968–1989 and 2008 to exemplify the performance of LQAS and B-LQAS. Results Results of our numerical study show that the choice of LQAS sample size and decision rule is sensitive to the distribution of prior information, as well as to individual beliefs about the importance of correct classification. Application of the B-LQAS approach to the UNICEF data improves specificity and PPV in both time periods (1968–1989 and 2008) with minimal reductions in sensitivity and negative predictive value. Conclusions LQAS is shown to be a robust tool that is not necessarily prone to poor specificity and PPV as previously alleged. In situations where prior or historical data are available, B-LQAS can lead to improvements in expected performance. PMID:23378151

Integration of Attributes from Non-Linear Characterization of Cardiovascular Time-Series for Prediction of Defibrillation Outcomes

PubMed Central

Shandilya, Sharad; Kurz, Michael C.; Ward, Kevin R.; Najarian, Kayvan

2016-01-01

Objective The timing of defibrillation is mostly at arbitrary intervals during cardio-pulmonary resuscitation (CPR), rather than during intervals when the out-of-hospital cardiac arrest (OOH-CA) patient is physiologically primed for successful countershock. Interruptions to CPR may negatively impact defibrillation success. Multiple defibrillations can be associated with decreased post-resuscitation myocardial function. We hypothesize that a more complete picture of the cardiovascular system can be gained through non-linear dynamics and integration of multiple physiologic measures from biomedical signals. Materials and Methods Retrospective analysis of 153 anonymized OOH-CA patients who received at least one defibrillation for ventricular fibrillation (VF) was undertaken. A machine learning model, termed Multiple Domain Integrative (MDI) model, was developed to predict defibrillation success. We explore the rationale for non-linear dynamics and statistically validate heuristics involved in feature extraction for model development. Performance of MDI is then compared to the amplitude spectrum area (AMSA) technique. Results 358 defibrillations were evaluated (218 unsuccessful and 140 successful). Non-linear properties (Lyapunov exponent > 0) of the ECG signals indicate a chaotic nature and validate the use of novel non-linear dynamic methods for feature extraction. Classification using MDI yielded ROC-AUC of 83.2% and accuracy of 78.8%, for the model built with ECG data only. Utilizing 10-fold cross-validation, at 80% specificity level, MDI (74% sensitivity) outperformed AMSA (53.6% sensitivity). At 90% specificity level, MDI had 68.4% sensitivity while AMSA had 43.3% sensitivity. Integrating available end-tidal carbon dioxide features into MDI, for the available 48 defibrillations, boosted ROC-AUC to 93.8% and accuracy to 83.3% at 80% sensitivity. Conclusion At clinically relevant sensitivity thresholds, the MDI provides improved performance as compared to AMSA, yielding fewer unsuccessful defibrillations. Addition of partial end-tidal carbon dioxide (PetCO2) signal improves accuracy and sensitivity of the MDI prediction model. PMID:26741805

Counting Molecules by Desorption Ionization and Mass Spectrometry/Mass Spectrometry.

ERIC Educational Resources Information Center

Cooks, R. G.; Busch, K. L.

1982-01-01

Discusses two newer methods in mass spectrometry and shows how they can increase signal and signal-to-noise ratios, respectively. The first method, desorption ionization (DI), increases sensitivity while the second method, mass spectrometry/mass spectrometry (MS/MS), increases specificity. Together, the two methods offer improved analytical…

Response of three soil water sensors to variable solution electrical conductivity in different soils

USDA-ARS?s Scientific Manuscript database

Commercial dielectric soil water sensors may improve management of irrigated agriculture by providing continuous field soil water information. Use of these sensors is partly limited by sensor sensitivity to variations in soil salinity and texture, which force expensive, time consuming, soil specific...

An improved colorimetric method for the determination of proline in the presence of other ninhydrin-positive compounds

PubMed Central

Wren, J. J.; Wiggall, P. H.

1965-01-01

1. The conditions required for sensitive and specific colorimetric determination of proline with acidified ninhydrin were investigated. 2. A method applicable to protein samples was developed. 3. The only compound found to interfere appreciably was a hydroxyproline. PMID:14342233

Assessment of OmpATb as a Novel Antigen for the Diagnosis of Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

In search for better tools to control bovine tuberculosis, the development of diagnostic tests with improved specificity and sensitivity has a high priority. We chose to search for novel immunodiagnostic reagents. In this study, Rv0899 (Outer membrane protein A of Mycobacterium tuberculosis, OmpATb)...

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.

Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by real time PCR.

PubMed

McNees, Adrienne L; White, Zoe S; Zanwar, Preeti; Vilchez, Regis A; Butel, Janet S

2005-09-01

The polyomaviruses that infect humans, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40), typically establish subclinical persistent infections. However, reactivation of these viruses in immunocompromised hosts is associated with renal nephropathy and hemorrhagic cystitis (HC) caused by BKV and with progressive multifocal leukoencephalopathy (PML) caused by JCV. Additionally, SV40 is associated with several types of human cancers including primary brain and bone cancers, mesotheliomas, and non-Hodgkin's lymphoma. Advancements in detection of these viruses may contribute to improved diagnosis and treatment of affected patients. To develop sensitive and specific real time quantitative polymerase chain reaction (RQ-PCR) assays for the detection of T-antigen DNA sequences of the human polyomaviruses BKV, JCV, and SV40 using the ABI Prism 7000 Sequence Detection System. Assays for absolute quantification of the viral T-ag sequences were designed and the sensitivity and specificity were evaluated. A quantitative assay to measure the single copy human RNAse P gene was also developed and evaluated in order to normalize viral gene copy numbers to cell numbers. Quantification of the target genes is sensitive and specific over a 7 log dynamic range. Ten copies each of the viral and cellular genes are reproducibly and accurately detected. The sensitivity of detection of the RQ-PCR assays is increased 10- to 100-fold compared to conventional PCR and agarose gel protocols. The primers and probes used to detect the viral genes are specific for each virus and there is no cross reactivity within the dynamic range of the standard dilutions. The sensitivity of detection for these assays is not reduced in human cellular extracts; however, different DNA extraction protocols may affect quantification. These assays provide a technique for rapid and specific quantification of polyomavirus genomes per cell in human samples.

Serum oestradiol and beta-HCG measurements after day 3 or 5 embryo transfers in interpreting pregnancy outcome.

PubMed

Kumbak, Banu; Oral, Engin; Karlikaya, Guvenc; Lacin, Selman; Kahraman, Semra

2006-10-01

The aim of this study was to assess the clinical value of serum oestradiol concentration 8 days after embryo transfer (D8E2) and beta-human chorionic gonadotrophin (HCG-beta) concentration 12 days after embryo transfer (D12HCG-beta) in the prediction of pregnancy and the outcome of pregnancy following assisted reproduction, taking into account the day of transfer, which was either day 3 (D3) or day 5 (D5). The objective was to improve patient counselling by giving quantitative and reliable predictive information instead of non-specific uncertainties. A total of 2035 embryo transfer cycles performed between January 2003 and June 2005 were analysed retrospectively. Biochemical pregnancy, ectopic pregnancy and first-trimester abortions were classified as non-viable pregnancies; pregnancies beyond 12 weeks gestation were classified as ongoing pregnancies (OP). Significantly higher D8E2 and D12HCG-beta were obtained in D5 transfers compared with D3 transfers with regard to pregnancy and OP (P

CSF soluble amyloid precursor proteins in the diagnosis of incipient Alzheimer disease.

PubMed

Perneczky, R; Tsolakidou, A; Arnold, A; Diehl-Schmid, J; Grimmer, T; Förstl, H; Kurz, A; Alexopoulos, P

2011-07-05

To explore if soluble amyloid precursor proteins (sAPP) in CSF improve the identification of patients with incipient Alzheimer disease (AD) in a group of patients with mild cognitive impairment (MCI). A cohort study with follow-up assessments of 58 patients with MCI with baseline CSF sampling was conducted: 21 patients had progressed to probable AD (MCI-AD), 27 still had MCI, 8 had reverted to normal (MCI-NAD), and 2 patients with frontotemporal dementia (FTD) were excluded. Sixteen additional patients with FTD were included to explore the specificity of the CSF markers. CSF concentrations of sAPPα, sAPPβ, tau, and Aβ(1-42) were measured with sensitive and specific ELISAs. Associations between diagnostic status, CSF protein concentrations, and other patient characteristics were explored using multiple logistic regression analyses with stepwise variable selection. The optimal sensitivity and specificity of the best models were derived from receiver operating characteristic curves. The MCI-AD group had significantly higher sAPPβ concentrations than the MCI-NAD and the FTD groups. A combination of sAPPβ, tau, and age differentiated the MCI-AD and the MCI-NAD groups with a sensitivity of 80.00% and a specificity of 81.00%. The best model for the differentiation of the MCI-AD and the FTD groups included sAPPβ and tau, and showed a sensitivity of 95.20% and a specificity of 81.20%. Aβ(1-42) and sAPPα did not significantly contribute to the models. These findings suggest that sAPPβ may be clinically useful, and superior to Aβ(1-42), in the early and differential diagnosis of incipient AD.

Quantitative site-specific reactivity profiling of S-nitrosylation in mouse skeletal muscle using cysteinyl peptide enrichment coupled with mass spectrometry

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

Su, Dian; Shukla, Anil K.; Chen, Baowei

2013-04-01

S-nitrosylation (SNO) is an important reversible thiol oxidation event that has been increasingly recognized for its role in cell signaling. While many proteins susceptible to S-nitrosylation have been reported, site-specific identification of physiologically relevant SNO modifications remains an analytical challenge due to the low-abundance and labile nature of the modification. Herein we present further improvement and optimization of the recently reported, resin-assisted cysteinyl peptide enrichment protocol for SNO identification and the extension of this application to mouse skeletal muscle to identify specific sites sensitive to S-nitrosylation by quantitative reactivity profiling. The results of our data indicate that the protein- andmore » peptide-level enrichment protocols provide comparable specificity and coverage of SNO-peptide identifications. S-nitrosylation reactivity profiling was performed by quantitatively comparing the site-specific SNO modification levels in samples treated with S-nitrosoglutathione (GSNO), an NO donor, at two different physiologically relevant concentrations (i.e., 10 μM and 100 μM). The reactivity profiling experiments overall identified 489 SNO-modified cysteine sites from 197 proteins with the specificity of 95.2% at the unique-peptide-level based on the percentage of Cys-peptides. Among these sites, 260 sites from 135 proteins were observed with relatively high reactivity to S-nitrosylation; such SNO-sensitive sites are more likely to be physiologically relevant. Many of the SNO-sensitive proteins are preferentially localized in mitochondria, contractile fiber and actin cytoskeleton, suggesting the susceptibility of these subcellular compartments to redox regulation. Moreover, the SNO-sensitive proteins seem to be primarily involved in metabolic pathways, including TCA cycle, glycolysis/gluconeogenesis, glutathione metabolism, and fatty acid metabolism, suggesting the importance of redox regulation in muscle metabolism and insulin action.« less

Combining skin prick, immediate skin application and specific-IgE testing in the diagnosis of peanut allergy in children.

PubMed

Wainstein, Brynn Kevin; Yee, Anthony; Jelley, Donna; Ziegler, Mary; Ziegler, John B

2007-05-01

Previous studies have suggested various diagnostic cut-offs of allergy tests for the diagnosis of clinical peanut allergy in children. There are few data relating to the use of combinations of these tests in children. We aimed to determine the validity of previously reported diagnostic cut-off levels of peanut allergen skin tests and peanut specific-immunoglobulin (Ig) E, as well as the usefulness of combinations of these, for predicting clinical peanut allergy in our Allergy Clinic. Children attending the Allergy Clinic with a positive peanut skin prick test (SPT; n = 84) were included in the study. Immediate skin application food tests (I-SAFT) using 1 g of peanut butter (positive if any wheals were detected at 15 min), peanut specific-IgE levels and open-label peanut food challenges were performed. Fifty-two of 85 peanut challenges were positive. Skin prick test specificity was 67% at >or=8 mm and 100% at >or=15 mm. The I-SAFT was 82% specific. A peanut specific-IgE level of 0.37 kU/l was 98% sensitive but 33% specific. A level of 10 kU/l was 100% specific. Combinations of a SPT of >or=8 mm with a positive I-SAFT and a peanut specific-IgE >or=0.37 kU/l were 88% specific with a sensitivity of 38%. Using challenge outcomes as the standard, available in vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and specificity and combining them does not significantly improve their clinical usefulness. Previously described diagnostic cut-off levels do not have general applicability. Allergy practitioners may need to interpret results of allergy tests in the context of their own practices.

Multispectral photoacoustic tomography for detection of small tumors inside biological tissues

NASA Astrophysics Data System (ADS)

Hirasawa, Takeshi; Okawa, Shinpei; Tsujita, Kazuhiro; Kushibiki, Toshihiro; Fujita, Masanori; Urano, Yasuteru; Ishihara, Miya

2018-02-01

Visualization of small tumors inside biological tissue is important in cancer treatment because that promotes accurate surgical resection and enables therapeutic effect monitoring. For sensitive detection of tumor, we have been developing photoacoustic (PA) imaging technique to visualize tumor-specific contrast agents, and have already succeeded to image a subcutaneous tumor of a mouse using the contrast agents. To image tumors inside biological tissues, extension of imaging depth and improvement of sensitivity were required. In this study, to extend imaging depth, we developed a PA tomography (PAT) system that can image entire cross section of mice. To improve sensitivity, we discussed the use of the P(VDF-TrFE) linear array acoustic sensor that can detect PA signals with wide ranges of frequencies. Because PA signals produced from low absorbance optical absorbers shifts to low frequency, we hypothesized that the detection of low frequency PA signals improves sensitivity to low absorbance optical absorbers. We developed a PAT system with both a PZT linear array acoustic sensor and the P(VDF-TrFE) sensor, and performed experiment using tissue-mimicking phantoms to evaluate lower detection limits of absorbance. As a result, PAT images calculated from low frequency components of PA signals detected by the P(VDF-TrFE) sensor could visualize optical absorbers with lower absorbance.

The accuracy of parent-reported height and weight for 6-12 year old U.S. children.

PubMed

Wright, Davene R; Glanz, Karen; Colburn, Trina; Robson, Shannon M; Saelens, Brian E

2018-02-12

Previous studies have examined correlations between BMI calculated using parent-reported and directly-measured child height and weight. The objective of this study was to validate correction factors for parent-reported child measurements. Concordance between parent-reported and investigator measured child height, weight, and BMI (kg/m 2 ) among participants in the Neighborhood Impact on Kids Study (n = 616) was examined using the Lin coefficient, where a value of ±1.0 indicates perfect concordance and a value of zero denotes non-concordance. A correction model for parent-reported height, weight, and BMI based on commonly collected demographic information was developed using 75% of the sample. This model was used to estimate corrected measures for the remaining 25% of the sample and measured concordance between correct parent-reported and investigator-measured values. Accuracy of corrected values in classifying children as overweight/obese was assessed by sensitivity and specificity. Concordance between parent-reported and measured height, weight and BMI was low (0.007, - 0.039, and - 0.005 respectively). Concordance in the corrected test samples improved to 0.752 for height, 0.616 for weight, and 0.227 for BMI. Sensitivity of corrected parent-reported measures for predicting overweight and obesity among children in the test sample decreased from 42.8 to 25.6% while specificity improved from 79.5 to 88.6%. Correction factors improved concordance for height and weight but did not improve the sensitivity of parent-reported measures for measuring child overweight and obesity. Future research should be conducted using larger and more nationally-representative samples that allow researchers to fully explore demographic variance in correction coefficients.

Insight into D-A-π-A Structured Sensitizers: A Promising Route to Highly Efficient and Stable Dye-Sensitized Solar Cells.

PubMed

Wu, Yongzhen; Zhu, Wei-Hong; Zakeeruddin, Shaik M; Grätzel, Michael

2015-05-13

The dye-sensitized solar cell (DSSC) is one of the most promising photovoltaic technologies with potential of low cost, light weight, and good flexibility. The practical application of DSSCs requires further improvement in power conversion efficiency and long-term stability. Recently, significant progress has been witnessed in DSSC research owing to the novel concept of the D-A-π-A motif for the molecular engineering of organic photosensitizers. New organic and porphyrin dyes based on the D-A-π-A motif can not only enhance photovoltaic performance, but also improve durability in DSSC applications. This Spotlight on Applications highlights recent advances in the D-A-π-A-based photosensitizers, specifically focusing on the mechanism of efficiency and stability enhancements. Also, we find insight into the additional acceptor as well as the trade-off of long wavelength response. The basic principles are involved in molecular engineering of efficient D-A-π-A sensitizers, providing a clear road map showing how to modulate the energy bands, rationally extending the response wavelength, and optimizing photovoltaic efficiency step by step.

Celiac Disease and Nonceliac Gluten Sensitivity: A Review.

PubMed

Leonard, Maureen M; Sapone, Anna; Catassi, Carlo; Fasano, Alessio

2017-08-15

The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (HLA-DQ2 and HLA-DQ8 genes) and autoantibodies (antitissue transglutaminase and antiendomysial). Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, extraintestinal signs or symptoms, or both, suggesting that celiac disease is a systemic disease. Nonceliac gluten sensitivity is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. The clinical variability and the lack of validated biomarkers for nonceliac gluten sensitivity make establishing the prevalence, reaching a diagnosis, and further study of this condition difficult. Nevertheless, it is possible to differentiate specific gluten-related disorders from other conditions, based on currently available investigations and algorithms. Clinicians cannot distinguish between celiac disease and nonceliac gluten sensitivity by symptoms, as they are similar in both. Therefore, screening for celiac disease must occur before a gluten-free diet is implemented, since once a patient initiates a gluten-free diet, testing for celiac disease is no longer accurate. Celiac disease and nonceliac gluten sensitivity are common. Although both conditions are treated with a gluten-free diet, distinguishing between celiac disease and nonceliac gluten sensitivity is important for long-term therapy. Patients with celiac disease should be followed up closely for dietary adherence, nutritional deficiencies, and the development of possible comorbidities.

Computerized Detection of Lung Nodules by Means of “Virtual Dual-Energy” Radiography

PubMed Central

Chen, Sheng; Suzuki, Kenji

2014-01-01

Major challenges in current computer-aided detection (CADe) schemes for nodule detection in chest radiographs (CXRs) are to detect nodules that overlap with ribs and/or clavicles and to reduce the frequent false positives (FPs) caused by ribs. Detection of such nodules by a CADe scheme is very important, because radiologists are likely to miss such subtle nodules. Our purpose in this study was to develop a CADe scheme with improved sensitivity and specificity by use of “virtual dual-energy” (VDE) CXRs where ribs and clavicles are suppressed with massive-training artificial neural networks (MTANNs). To reduce rib-induced FPs and detect nodules overlapping with ribs, we incorporated the VDE technology in our CADe scheme. The VDE technology suppressed rib and clavicle opacities in CXRs while maintaining soft-tissue opacity by use of the MTANN technique that had been trained with real dual-energy imaging. Our scheme detected nodule candidates on VDE images by use of a morphologic filtering technique. Sixty morphologic and gray-level-based features were extracted from each candidate from both original and VDE CXRs. A nonlinear support vector classifier was employed for classification of the nodule candidates. A publicly available database containing 140 nodules in 140 CXRs and 93 normal CXRs was used for testing our CADe scheme. All nodules were confirmed by computed tomography examinations, and the average size of the nodules was 17.8 mm. Thirty percent (42/140) of the nodules were rated “extremely subtle” or “very subtle” by a radiologist. The original scheme without VDE technology achieved a sensitivity of 78.6% (110/140) with 5 (1165/233) FPs per image. By use of the VDE technology, more nodules overlapping with ribs or clavicles were detected and the sensitivity was improved substantially to 85.0% (119/140) at the same FP rate in a leave-one-out cross-validation test, whereas the FP rate was reduced to 2.5 (583/233) per image at the same sensitivity level as the original CADe scheme obtained (Difference between the specificities of the original and the VDE-based CADe schemes was statistically significant). In particular, the sensitivity of our VDE-based CADe scheme for subtle nodules (66.7% = 28/42) was statistically significantly higher than that of the original CADe scheme (57.1% = 24/42). Therefore, by use of VDE technology, the sensitivity and specificity of our CADe scheme for detection of nodules, especially subtle nodules, in CXRs were improved substantially. PMID:23193306

Computerized detection of lung nodules by means of "virtual dual-energy" radiography.

PubMed

Chen, Sheng; Suzuki, Kenji

2013-02-01

Major challenges in current computer-aided detection (CADe) schemes for nodule detection in chest radiographs (CXRs) are to detect nodules that overlap with ribs and/or clavicles and to reduce the frequent false positives (FPs) caused by ribs. Detection of such nodules by a CADe scheme is very important, because radiologists are likely to miss such subtle nodules. Our purpose in this study was to develop a CADe scheme with improved sensitivity and specificity by use of "virtual dual-energy" (VDE) CXRs where ribs and clavicles are suppressed with massive-training artificial neural networks (MTANNs). To reduce rib-induced FPs and detect nodules overlapping with ribs, we incorporated the VDE technology in our CADe scheme. The VDE technology suppressed rib and clavicle opacities in CXRs while maintaining soft-tissue opacity by use of the MTANN technique that had been trained with real dual-energy imaging. Our scheme detected nodule candidates on VDE images by use of a morphologic filtering technique. Sixty morphologic and gray-level-based features were extracted from each candidate from both original and VDE CXRs. A nonlinear support vector classifier was employed for classification of the nodule candidates. A publicly available database containing 140 nodules in 140 CXRs and 93 normal CXRs was used for testing our CADe scheme. All nodules were confirmed by computed tomography examinations, and the average size of the nodules was 17.8 mm. Thirty percent (42/140) of the nodules were rated "extremely subtle" or "very subtle" by a radiologist. The original scheme without VDE technology achieved a sensitivity of 78.6% (110/140) with 5 (1165/233) FPs per image. By use of the VDE technology, more nodules overlapping with ribs or clavicles were detected and the sensitivity was improved substantially to 85.0% (119/140) at the same FP rate in a leave-one-out cross-validation test, whereas the FP rate was reduced to 2.5 (583/233) per image at the same sensitivity level as the original CADe scheme obtained (Difference between the specificities of the original and the VDE-based CADe schemes was statistically significant). In particular, the sensitivity of our VDE-based CADe scheme for subtle nodules (66.7% = 28/42) was statistically significantly higher than that of the original CADe scheme (57.1% = 24/42). Therefore, by use of VDE technology, the sensitivity and specificity of our CADe scheme for detection of nodules, especially subtle nodules, in CXRs were improved substantially.

Developing a Screening Algorithm for Type II Diabetes Mellitus in the Resource-Limited Setting of Rural Tanzania.

PubMed

West, Caroline; Ploth, David; Fonner, Virginia; Mbwambo, Jessie; Fredrick, Francis; Sweat, Michael

2016-04-01

Noncommunicable diseases are on pace to outnumber infectious disease as the leading cause of death in sub-Saharan Africa, yet many questions remain unanswered with concern toward effective methods of screening for type II diabetes mellitus (DM) in this resource-limited setting. We aim to design a screening algorithm for type II DM that optimizes sensitivity and specificity of identifying individuals with undiagnosed DM, as well as affordability to health systems and individuals. Baseline demographic and clinical data, including hemoglobin A1c (HbA1c), were collected from 713 participants using probability sampling of the general population. We used these data, along with model parameters obtained from the literature, to mathematically model 8 purposed DM screening algorithms, while optimizing the sensitivity and specificity using Monte Carlo and Latin Hypercube simulation. An algorithm that combines risk assessment and measurement of fasting blood glucose was found to be superior for the most resource-limited settings (sensitivity 68%, sensitivity 99% and cost per patient having DM identified as $2.94). Incorporating HbA1c testing improves the sensitivity to 75.62%, but raises the cost per DM case identified to $6.04. The preferred algorithms are heavily biased to diagnose those with more severe cases of DM. Using basic risk assessment tools and fasting blood sugar testing in lieu of HbA1c testing in resource-limited settings could allow for significantly more feasible DM screening programs with reasonable sensitivity and specificity. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

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

Simonsson, Carl, E-mail: carl.simonsson@chem.gu.se; Stenfeldt, Anna-Lena; Karlberg, Ann-Therese

2012-10-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we havemore » explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.« less

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.

MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data.

PubMed

Fan, Yu; Xi, Liu; Hughes, Daniel S T; Zhang, Jianjun; Zhang, Jianhua; Futreal, P Andrew; Wheeler, David A; Wang, Wenyi

2016-08-24

Subclonal mutations reveal important features of the genetic architecture of tumors. However, accurate detection of mutations in genetically heterogeneous tumor cell populations using next-generation sequencing remains challenging. We develop MuSE ( http://bioinformatics.mdanderson.org/main/MuSE ), Mutation calling using a Markov Substitution model for Evolution, a novel approach for modeling the evolution of the allelic composition of the tumor and normal tissue at each reference base. MuSE adopts a sample-specific error model that reflects the underlying tumor heterogeneity to greatly improve the overall accuracy. We demonstrate the accuracy of MuSE in calling subclonal mutations in the context of large-scale tumor sequencing projects using whole exome and whole genome sequencing.

A novel SPECT camera for molecular imaging of the prostate

NASA Astrophysics Data System (ADS)

Cebula, Alan; Gilland, David; Su, Li-Ming; Wagenaar, Douglas; Bahadori, Amir

2011-10-01

The objective of this work is to develop an improved SPECT camera for dedicated prostate imaging. Complementing the recent advancements in agents for molecular prostate imaging, this device has the potential to assist in distinguishing benign from aggressive cancers, to improve site-specific localization of cancer, to improve accuracy of needle-guided prostate biopsy of cancer sites, and to aid in focal therapy procedures such as cryotherapy and radiation. Theoretical calculations show that the spatial resolution/detection sensitivity of the proposed SPECT camera can rival or exceed 3D PET and further signal-to-noise advantage is attained with the better energy resolution of the CZT modules. Based on photon transport simulation studies, the system has a reconstructed spatial resolution of 4.8 mm with a sensitivity of 0.0001. Reconstruction of a simulated prostate distribution demonstrates the focal imaging capability of the system.

The pressing need for real-time risk assessment of hospital-acquired acute kidney injury.

PubMed

Warnock, David G

2017-05-01

Acute Kidney Injury (AKI) is associated with short- and long-term outcomes that reflect the severity of the injury. Recent studies have suggested that 'early' initiation of renal replacement therapy may alter the course of AKI and improve short-term outcomes like inpatient mortality. The current Kidney Disease Improving Global Outcomes (KDIGO) consensus definition of AKI has been criticized for misclassification bias, lack of sensitivity and the static manner in which AKI stages are defined. This editorial reviews various approaches to improving the specificity and sensitivity of the KDIGO AKI criteria, and also concludes that a staging system based on creatinine trajectories would be better suited for developing a prognostic index for real-time, dynamic risk assessment that the current KDIGO staging criteria. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

PubMed Central

Zhang, Chenzi; Yu, Wenjun; Wang, Lin; Zhao, Mingna; Guo, Qiaomei; Lv, Shaogang; Hu, Xiaomeng; Lou, Jiatao

2017-01-01

Introduction: Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. Patients and Methods: BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Results: Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. Conclusion: The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer diagnosis, especially in an early stage. It could be used as a promising noninvasive biomarker for auxiliary diagnosis of lung cancer. PMID:29151944

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.

Assessment of the diagnostic sensitivity and specificity of an indirect ELISA kit for the diagnosis of Brucella ovis infection in rams.

PubMed

Praud, Anne; Champion, Jean-Luc; Corde, Yannick; Drapeau, Antoine; Meyer, Laurence; Garin-Bastuji, Bruno

2012-07-09

Brucella ovis causes an infectious disease responsible for infertility and subsequent economic losses in sheep production. The standard serological test to detect B. ovis infection in rams is the complement fixation test (CFT), which has imperfect sensitivity and specificity in addition to technical drawbacks. Other available tests include the indirect enzyme-linked immunosorbent assays (I-ELISA) but no I-ELISA kit has been fully evaluated.The study aimed to compare an I-ELISA kit and the standard CFT. Our study was carried out on serum samples from 4599 rams from the South of France where the disease is enzootic. A Bayesian approach was used to estimate tests characteristics (diagnostic sensitivity, Se and diagnostic specificity, Sp). The tests were then studied together in order to optimise testing strategies to detect B. ovis. After optimising the cut-off values in order to avoid doubtful results without deteriorating the concordance between the results of the two tests, the I-ELISA appeared to be slightly more sensitive than CFT (Se I-ELISA=0.917 [0.822; 0.992], 95% Credibility Interval (CrI) compared to Se CFT=0.860 [0.740; 0.967], 95% CrI). However, CFT was slightly more specific than I-ELISA (Sp CFT=0.988 [0.947; 1.0], 95% CrI) compared to Sp I-ELISA =0.952 [0.901; 1.0], 95% CrI).The tests were then associated with two different interpretation schemes. The series association increased the specificity of screening and could be used for pre-movement testing in rams from uninfected flocks. The parallel association increased sequence sensitivity, thus appearing more suitable for eradicating the disease in infected flocks. The high sensitivity and acceptable specificity of this I-ELISA kit support its potential interest to avoid the limitations of CFT. The two tests could also be used together or combined with other diagnostic methods such as semen culture to improve the testing strategy. The choice of test sequence and interpretation criteria depends on the epidemiological context, screening objectives and the financial and practical constraints.

Disease spectrum of abnormal serum free light chain ratio and its diagnostic significance

PubMed Central

Xu, Bin; Tang, Yi; Zhou, Jianfeng; Zhang, Peiling; Li, Huijun

2017-01-01

Objective To analyze the spectrum of abnormal serum free light chain ratio (sFLC κ/λ ratio), and to redefine the range of sFLC κ/λ ratio, so as to achieve hierarchical diagnosis of diseases with abnormal sFLC κ/λ ratio, resulting in the increased sensitivity and specificity in the diagnosis of monoclonal plasma diseases. Methods Enrolled 1,340 patients with abnormal sFLC κ/λ ratio (<0.26 or >1.65) were grouped: (1) group A: malignant plasma diseases; (2) group B: monoclonal gammopathies of undetermined significance (MGUS); (3) group C: reactive plasma diseases. These patients were further divided by renal function eGFR <60 or >60 ml/min/1.73m2 to eliminate renal diseases influencing the results. Statistical analyses was performed by using SPSS 22 software. Results When sFLC κ/λ ratio >3.49 and eGFR >60ml/min/1.73m2, the sensitivity and specificity of the diagnosis of malignant plasma diseases were 86.1% and 94.0%, respectively. When sFLC κ/λ ratio >2.89 and eGFR <60ml/min/1.73m2, the sensitivity and specificity of the diagnosis of malignant plasma diseases were 92.0% and 97.0%, respectively. Conclusion The sensitivity and specificity of the diagnosis of monoclonal plasma diseases can be significantly improved by redefining the cut-off value of sFLC κ/λ ratio and the renal function index of eGFR. PMID:29137262

Digital breast tomosynthesis for breast cancer screening and diagnosis in women with dense breasts - a systematic review and meta-analysis.

PubMed

Phi, Xuan-Anh; Tagliafico, Alberto; Houssami, Nehmat; Greuter, Marcel J W; de Bock, Geertruida H

2018-04-03

This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%-90%) versus DM alone (69%-86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02-1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20-1.47 for retrospective studies; RR: 1.52, 95% CI 1.08-2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64-0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76-1.63). In women with mammographically dense breasts, DBT+/-DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/-DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

Imaging modalities in the diagnosis of pancreatic adenocarcinoma: A systematic review and meta-analysis of sensitivity, specificity and diagnostic accuracy.

PubMed

Toft, James; Hadden, William J; Laurence, Jerome M; Lam, Vincent; Yuen, Lawrence; Janssen, Anna; Pleass, Henry

2017-07-01

Pancreatic cancer, primarily pancreatic ductal adenocarcinoma (PDAC), accounts for 2.4% of cancer diagnoses and 5.8% of cancer death annually. Early diagnoses can improve 5-year survival in PDAC. The aim of this systematic review was to determine the sensitivity, specificity and diagnostic accuracy values for MRI, CT, PET&PET/CT, EUS and transabdominal ultrasound (TAUS) in the diagnosis of PDAC. A systematic review was undertaken to identify studies reporting sensitivity, specificity and/or diagnostic accuracy for the diagnosis of PDAC with MRI, CT, PET, EUS or TAUS. Proportional meta-analysis was performed for each modality. A total of 5399 patients, 3567 with PDAC, from 52 studies were included. The sensitivity, specificity and diagnostic accuracy were 93% (95% CI=88-96), 89% (95% CI=82-94) and 90% (95% CI=86-94) for MRI; 90% (95% CI=87-93), 87% (95% CI=79-93) and 89% (95% CI=85-93) for CT; 89% (95% CI=85-93), 70% (95% CI=54-84) and 84% (95% CI=79-89) for PET; 91% (95% CI=87-94), 86% (95% CI=81-91) and 89% (95% CI=87-92) for EUS; and 88% (95% CI=86-90), 94% (95% CI=87-98) and 91% (95% C=87-93) for TAUS. This review concludes all modalities, except for PET, are equivalent within 95% confidence intervals for the diagnosis of PDAC. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnostic Cutoff Value for Ultrasonography of the Common Fibular Neuropathy at the Fibular Head

PubMed Central

2016-01-01

Objective To establish the diagnostic cutoff value of ultrasonographic measurement for common fibular neuropathy (CFN) at the fibular head (FH). Methods Twenty patients with electrodiagnostically diagnosed CFN at the FH and 30 healthy controls were included in the study. The cross-sectional area (CSA) of sciatic nerve at mid-thigh level, common fibular nerve at popliteal fossa (PF), and common fibular (CF) nerve at FH were measured. Additionally, the difference of CF nerve CSA at the FH between symptomatic side and asymptomatic side (ΔSx–Asx), the ratio of CF nerve CSA at FH to at PF (FH/PF), and the ratio of CF nerve CSA at the FH symptomatic side to asymptomatic side (Ratio Sx–Asx) were calculated. Results CSA at the FH, FH/PF, ΔSx–Asx, and Ratio Sx–Asx showed significant differences between the patient and control groups. The cutoff value for diagnosing CFN at the FH was 11.7 mm2 for the CSA at the FH (sensitivity 85.0%, specificity 90.0%), 1.70 mm2 for the ΔSx–Asx (sensitivity 83.3%, specificity 97.0%), 1.11 for the FH/PF (sensitivity 47.1%, specificity 93.3%), and 1.24 for the Ratio Sx–Asx (sensitivity 72.2%, specificity 96.7%). Conclusion The ultrasonographic measurement and cutoff value could be a valuable reference in diagnosing CFN at the FH and improving diagnostic reliability and efficacy. PMID:28119836

Can the efficiency of modified Alvarado scoring system in the diagnosis acute appendicitis be increased with tenesmus?

PubMed

Bulus, Hakan; Tas, Adnan; Morkavuk, Baris; Koklu, Seyfettin; Soy, Derya; Coskun, Ali

2013-01-01

Acute appendicitis is one of the main pathological conditions requiring emergency surgical intervention. The most widely accepted scoring system is modified Alvarado scoring system (MASS). In this study we aimed to improve the efficiency of MASS by adding a new parameter and to evaluate its efficiency in the diagnosis of acute appendicitis. This study included 158 patients who underwent acute appendectomy in Keçiören Training and Research Hospital General Surgery Department. In addition to criteria of MASS, all patients were questioned about the presence of tenesmus. The validity of MASS and MASS with additional parameter was evaluated with respect to sensitivity, specificity and positive and negative predictive values. Accuracy rates of MASS, clinical findings, ultrasonography and MASS with additional parameter in the diagnosis of acute appendicitis were 64, 76, 85 and 80 %. False positivity rates for clinical findings, MASS and MASS with additional parameter in the diagnosis of acute appendicitis were 17, 26 and 10 %, respectively. Sensitivity and specificity of clinical findings in the diagnosis of acute appendicitis were 83 and 66 %, respectively. Sensitivity and specificity of MASS in the diagnosis of acute appendicitis were 74 and 39 %, respectively, and those of MASS with additional parameter were appendicitis increased to 83 and 66 %, respectively. MASS is a simple, cheap and objective scoring system and does not require expertise. When tenesmus is added to standard MASS, rates of accuracy, sensitivity and specificity become better than those in MASS in the diagnosis of acute appendicitis.

Type-specific identification of anogenital herpes simplex virus infections by use of a commercially available nucleic acid amplification test.

PubMed

Van Der Pol, Barbara; Warren, Terri; Taylor, Stephanie N; Martens, Mark; Jerome, Keith R; Mena, Leandro; Lebed, Joel; Ginde, Savita; Fine, Paul; Hook, Edward W

2012-11-01

Herpes infections are among the most common sexually transmitted infections (STI), but diagnostic methods for genital herpes have not kept pace with the movement toward molecular testing. Here, we describe an FDA-approved molecular assay that identifies and types herpes simplex virus (HSV) infections for use in routine clinical settings. Paired samples from anogenital lesions were tested using the BD ProbeTec HSV Q(x) (HSVQ(x)) system, HSV culture and, a laboratory-developed PCR assay. Family planning, obstetrics/gynecology (OB/GYN), or sexually transmitted disease (STD) clinics in the United States served as recruitment sites. Sensitivity and specificity estimates, head-to-head comparisons, measures of agreement, and latent-class analyses were performed to provide robust estimates of performance. A total of 508 participants (174 men and 334 women) with anogenital lesions were included; 260 HSV-2 and 73 HSV-1 infections were identified. No differences in test performance based on gender, clinic type, location of the lesion, or type of lesion were observed. The sensitivity of HSV-2 detection ranged from 98.4 to 100% depending on the analytical approach, while the specificity ranged from 80.6%, compared to the less sensitive culture method, to 97.0%, compared to PCR. For HSV-1, the sensitivity and specificity ranges were 96.7 to 100% and 95.1 to 99.4%, respectively. This assay may improve our ability to accurately diagnose anogenital lesions due to herpes infection.

The power of data mining in diagnosis of childhood pneumonia.

PubMed

Naydenova, Elina; Tsanas, Athanasios; Howie, Stephen; Casals-Pascual, Climent; De Vos, Maarten

2016-07-01

Childhood pneumonia is the leading cause of death of children under the age of 5 years globally. Diagnostic information on the presence of infection, severity and aetiology (bacterial versus viral) is crucial for appropriate treatment. However, the derivation of such information requires advanced equipment (such as X-rays) and clinical expertise to correctly assess observational clinical signs (such as chest indrawing); both of these are often unavailable in resource-constrained settings. In this study, these challenges were addressed through the development of a suite of data mining tools, facilitating automated diagnosis through quantifiable features. Findings were validated on a large dataset comprising 780 children diagnosed with pneumonia and 801 age-matched healthy controls. Pneumonia was identified via four quantifiable vital signs (98.2% sensitivity and 97.6% specificity). Moreover, it was shown that severity can be determined through a combination of three vital signs and two lung sounds (72.4% sensitivity and 82.2% specificity); addition of a conventional biomarker (C-reactive protein) further improved severity predictions (89.1% sensitivity and 81.3% specificity). Finally, we demonstrated that aetiology can be determined using three vital signs and a newly proposed biomarker (lipocalin-2) (81.8% sensitivity and 90.6% specificity). These results suggest that a suite of carefully designed machine learning tools can be used to support multi-faceted diagnosis of childhood pneumonia in resource-constrained settings, compensating for the shortage of expensive equipment and highly trained clinicians. © 2016 The Authors.

Dialysate bacterial endotoxin as a prognostic indicator of peritoneal dialysis related peritonitis.

PubMed

Szeto, Cheuk-Chun; Lai, Ka-Bik; Chow, Kai-Ming; Kwan, Bonnie Ching-Ha; Law, Man-Ching; Pang, Wing-Fai; Ma, Terry King-Wing; Leung, Chi-Bon; Li, Philip Kam-Tao

2016-12-01

Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our present study is to explore the prognostic value of endotoxin level in PD effluent for the prediction of treatment failure in PD-related peritonitis. We studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected every 5 days for endotoxin level and leukocyte count. Patients were followed for relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and 22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial growth, and none of the culture negative episodes or those by Gram positive organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%, respectively, for predicting primary treatment failure. In contrast, PDE leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of 88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not improve the sensitivity or specificity. We conclude that detectable endotoxin in PDE 5 days after antibiotic therapy might predict primary treatment failure in peritonitis episodes caused by Gram negative organisms. However, the sensitivity and specificity of PDE endotoxin assay was inferior to PDE leukocyte count. © 2016 Asian Pacific Society of Nephrology.

Role of shear wave sonoelastography in differentiation between focal breast lesions.

PubMed

Dobruch-Sobczak, Katarzyna; Nowicki, Andrzej

2015-02-01

Our goal in this study was to evaluate the relevance of shear wave sonoelastography (SWE) in the differential diagnosis of masses in the breast with respect to ultrasound (US). US and SWE were performed (Aixplorer System, SuperSonic Imagine, Aix en Provence, France) in 76 women (aged 24 to 85) with 84 lesions (43 malignant, 41 benign). The study included BI-RADS-US (Breast Imaging Reporting and Data System for Ultrsound) category 3-5 lesions. In elastograms, the following values were calculated: mean elasticity in lesions (E(av.l)) and in fat tissue (E(av.f.)) and maximal (E(max.adj.)) and mean (E(av.adj.)) elasticity in lesions and adjacent tissues. The sensitivity and specificity of the BI-RADS category 4a/4b cutoff value were 97.7% and 90.2%. For an E(av.adj.) of 68.5 kPa, the cutoff sensitivity was 86.1% and the specificity was 87.8%, and for an E(max.adj.) of 124.1 kPa, 74.4% and 92.7%, respectively. For BI-RADS-US category 3 lesions, E(av.l), E(max.adj.) and E(av.adj.) were below cutoff levels. On the basis of our findings, E(av.adj.) had lower sensitivity and specificity compared with US. Emax.adj. improved the specificity of breast US with loss of sensitivity. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Predicting coronary artery disease using different artificial neural network models.

PubMed

Colak, M Cengiz; Colak, Cemil; Kocatürk, Hasan; Sağiroğlu, Seref; Barutçu, Irfan

2008-08-01

Eight different learning algorithms used for creating artificial neural network (ANN) models and the different ANN models in the prediction of coronary artery disease (CAD) are introduced. This work was carried out as a retrospective case-control study. Overall, 124 consecutive patients who had been diagnosed with CAD by coronary angiography (at least 1 coronary stenosis > 50% in major epicardial arteries) were enrolled in the work. Angiographically, the 113 people (group 2) with normal coronary arteries were taken as control subjects. Multi-layered perceptrons ANN architecture were applied. The ANN models trained with different learning algorithms were performed in 237 records, divided into training (n=171) and testing (n=66) data sets. The performance of prediction was evaluated by sensitivity, specificity and accuracy values based on standard definitions. The results have demonstrated that ANN models trained with eight different learning algorithms are promising because of high (greater than 71%) sensitivity, specificity and accuracy values in the prediction of CAD. Accuracy, sensitivity and specificity values varied between 83.63%-100%, 86.46%-100% and 74.67%-100% for training, respectively. For testing, the values were more than 71% for sensitivity, 76% for specificity and 81% for accuracy. It may be proposed that the use of different learning algorithms other than backpropagation and larger sample sizes can improve the performance of prediction. The proposed ANN models trained with these learning algorithms could be used a promising approach for predicting CAD without the need for invasive diagnostic methods and could help in the prognostic clinical decision.

Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity

PubMed Central

Ta, Von; Weldon, Brittany; Yu, Grace; Humblet, Olivier; Neale-May, Susan; Nadeau, Kari

2012-01-01

Aims To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. Study design Prospective study. Place and Duration of Study Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. Methodology We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock’s criteria. Results Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. Conclusion These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2). PMID:22993721

Specific and sensitive detection of the conifer pathogen Gremmeniella abietina by nested PCR

PubMed Central

Zeng, Qing-Yin; Hansson, Per; Wang, Xiao-Ru

2005-01-01

Background Gremmeniella abietina (Lagerb.) Morelet is an ascomycete fungus that causes stem canker and shoot dieback in many conifer species. The fungus is widespread and causes severe damage to forest plantations in Europe, North America and Asia. To facilitate early diagnosis and improve measures to control the spread of the disease, rapid, specific and sensitive detection methods for G. abietina in conifer hosts are needed. Results We designed two pairs of specific primers for G. abietina based on the 18S rDNA sequence variation pattern. These primers were validated against a wide range of fungi and 14 potential conifer hosts. Based on these specific primers, two nested PCR systems were developed. The first system employed universal fungal primers to enrich the fungal DNA targets in the first round, followed by a second round selective amplification of the pathogen. The other system employed G. abietina-specific primers in both PCR steps. Both approaches can detect the presence of G. abietina in composite samples with high sensitivity, as little as 7.5 fg G. abietina DNA in the host genomic background. Conclusion The methods described here are rapid and can be applied directly to a wide range of conifer species, without the need for fungal isolation and cultivation. Therefore, it represents a promising alternative to disease inspection in forest nurseries, plantations and quarantine control facilities. PMID:16280082

Molecular diagnosis and immunotherapy.

PubMed

Sastre, Joaquín; Sastre-Ibañez, Marina

2016-12-01

To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.

Enhanced sensitivity in detection of antiviral antibody responses using biotinylation of foot-and-mouth disease virus (FMDV) capsids.

PubMed

Kenney, Mary; Waters, Ryan A; Rieder, Elizabeth; Pega, Juan; Perez-Filguera, Mariano; Golde, William T

2017-11-01

Analysis of the immune response to infection of livestock by foot-and-mouth disease virus (FMDV) is most often reported as the serum antibody response to the virus. While measurement of neutralizing antibody has been sensitive and specific, measurements of the quality of the antibody response are less robust. Determining the immunoglobulin (Ig) isotype of the serum antibody response provides a deeper understanding of the biology of the response and more sensitive methods for these assays will facilitate analyses of B cell mediated immunity. We tested the hypothesis that using the virus as the molecular probe could be achieved by adding tags to the surface of the FMDV capsid, and that would enhance sensitivity in assays for anti-FMDV antibody responses. The use of a FLAG-tagged virus in these assays failed to yield improvement whereas chemically biotinylating the virus capsid resulted in significant enhancement of the signal. Here we describe methods using biotinylated virus for measuring anti-viral antibody in serum and antibody secreting cells (ASCs) in blood that are sensitive and specific. Finally, we describe using the biotinylated virus in flow cytometry where such assays should greatly enhance the analysis of anti-virus antibody producing B cells, allowing the investigator to focus on only the FMDV specific B cells when analyzing the development of the B cell response to either infection or vaccination. Published by Elsevier B.V.

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

PubMed

Aljakna, Aleksandra; Fracasso, Tony; Sabatasso, Sara

2018-03-01

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

Improved Diagnosis of Prosthetic Joint Infection by Culturing Periprosthetic Tissue Specimens in Blood Culture Bottles

PubMed Central

Peel, Trisha N.; Dylla, Brenda L.; Hughes, John G.; Lynch, David T.; Greenwood-Quaintance, Kerryl E.; Cheng, Allen C.; Mandrekar, Jayawant N.

2016-01-01

ABSTRACT Despite known low sensitivity, culture of periprosthetic tissue specimens on agars and in broths is routine. Culture of periprosthetic tissue samples in blood culture bottles (BCBs) is potentially more convenient, but it has been evaluated in a limited way and has not been widely adopted. The aim of this study was to compare the sensitivity and specificity of inoculation of periprosthetic tissue specimens into blood culture bottles with standard agar and thioglycolate broth culture, applying Bayesian latent class modeling (LCM) in addition to applying the Infectious Diseases Society of America (IDSA) criteria for prosthetic joint infection. This prospective cohort study was conducted over a 9-month period (August 2013 to April 2014) at the Mayo Clinic, Rochester, MN, and included all consecutive patients undergoing revision arthroplasty. Overall, 369 subjects were studied; 117 (32%) met IDSA criteria for prosthetic joint infection, and 82% had late chronic infection. Applying LCM, inoculation of tissues into BCBs was associated with a 47% improvement in sensitivity compared to the sensitivity of conventional agar and broth cultures (92.1 versus 62.6%, respectively); this magnitude of change was similar when IDSA criteria were applied (60.7 versus 44.4%, respectively; P = 0.003). The time to microorganism detection was shorter with BCBs than with standard media (P < 0.0001), with aerobic and anaerobic BCBs yielding positive results within a median of 21 and 23 h, respectively. Results of our study demonstrate that the semiautomated method of periprosthetic tissue culture in blood culture bottles is more sensitive than and as specific as agar and thioglycolate broth cultures and yields results faster. PMID:26733067

Monitoring and improving the sensitivity of dengue nested RT-PCR used in longitudinal surveillance in Thailand.

PubMed

Klungthong, Chonticha; Manasatienkij, Wudtichai; Phonpakobsin, Thipwipha; Chinnawirotpisan, Piyawan; Rodpradit, Prinyada; Hussem, Kittinun; Thaisomboonsuk, Butsaya; Ong-ajchaowlerd, Prapapun; Nisalak, Ananda; Kalayanarooj, Siripen; Buddhari, Darunee; Gibbons, Robert V; Jarman, Richard G; Yoon, In-Kyu; Fernandez, Stefan

2015-02-01

AFRIMS longitudinal dengue surveillance in Thailand depends on the nested RT-PCR and the dengue IgM/IgG ELISA. To examine and improve the sensitivity of the nested RT-PCR using a panel of archived samples collected during dengue surveillance. A retrospective analysis of 16,454 dengue IgM/IgG ELISA positive cases collected between 2000 and 2013 was done to investigate the sensitivity of the nested RT-PCR. From these cases, 318 acute serum specimens or extracted RNA, previously found to be negative by the nested RT-PCR, were tested using TaqMan real-time RT-PCR (TaqMan rRT-PCR). To improve the sensitivity of nested RT-PCR, we designed a new primer based on nucleotide sequences from contemporary strains found to be positive by the TaqMan rRT-PCR. Sensitivity of the new nested PCR was calculated using a panel of 87 samples collected during 2011-2013. The percentage of dengue IgM/IgG ELISA positive cases that were negative by the nested RT-PCR varied from 17% to 42% for all serotypes depending on the year. Using TaqMan rRT-PCR, dengue RNA was detected in 194 (61%) of the 318 acute sera or extracted RNA previously found to be negative by the nested RT-PCR. The newly designed DENV-1 specific primer increased the sensitivity of DENV-1 detection by the nested RT-PCR from 48% to 88%, and of all 4 serotypes from 73% to 87%. These findings demonstrate the impact of genetic diversity and signal erosion on the sensitivity of PCR-based methods. Published by Elsevier B.V.

Molecular Diagnostic Testing for Aspergillus

PubMed Central

Powers-Fletcher, Margaret V.

2016-01-01

The direct detection of Aspergillus nucleic acid in clinical specimens has the potential to improve the diagnosis of aspergillosis by offering more rapid and sensitive identification of invasive infections than is possible with traditional techniques, such as culture or histopathology. Molecular tests for Aspergillus have been limited historically by lack of standardization and variable sensitivities and specificities. Recent efforts have been directed at addressing these limitations and optimizing assay performance using a variety of specimen types. This review provides a summary of standardization efforts and outlines the complexities of molecular testing for Aspergillus in clinical mycology. PMID:27487954

Evaluation of Four Diagnostic Tests for Insulin Dysregulation in Adult Light-Breed Horses.

PubMed

Dunbar, L K; Mielnicki, K A; Dembek, K A; Toribio, R E; Burns, T A

2016-05-01

Several tests have been evaluated in horses for quantifying insulin dysregulation to support a diagnosis of equine metabolic syndrome. Comparing the performance of these tests in the same horses will provide clarification of their accuracy in the diagnosis of equine insulin dysregulation. The aim of this study was to evaluate the agreement between basal serum insulin concentrations (BIC), the oral sugar test (OST), the combined glucose-insulin test (CGIT), and the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGTT). Twelve healthy, light-breed horses. Randomized, prospective study. Each of the above tests was performed on 12 horses. Minimal model analysis of the FSIGTT was considered the reference standard and classified 7 horses as insulin resistant (IR) and 5 as insulin sensitive (IS). In contrast, BIC and OST assessment using conventional cut-off values classified all horses as IS. Kappa coefficients, measuring agreement among BIC, OST, CGIT, and FSIGTT were poor to fair. Sensitivity of the CGIT (positive phase duration of the glucose curve >45 minutes) was 85.7% and specificity was 40%, whereas CGIT ([insulin]45 >100 μIU/mL) sensitivity and specificity were 28.5% and 100%, respectively. Area under the glucose curve (AUCg0-120 ) was significantly correlated among the OST, CGIT, and FSIGTT, but Bland-Altman method and Lin's concordance coefficient showed a lack of agreement. Current criteria for diagnosis of insulin resistance using BIC and the OST are highly specific but lack sensitivity. The CGIT displayed better sensitivity and specificity, but modifications may be necessary to improve agreement with minimal model analysis. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity

PubMed Central

Kråkenes, Jostein; Brauckhoff, Katrin; Haugland, Hans Kristian; Heinecke, Achim; Akslen, Lars A; Varhaug, Jan Erik; Brauckhoff, Michael

2015-01-01

Background Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131). Purpose To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT. Material and Methods Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard. Results Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%). Conclusion In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed. PMID:25770086

Fusion positron emission/computed tomography underestimates the presence of hilar nodal metastases in patients with resected non-small cell lung cancer.

PubMed

Carrillo, Sergio A; Daniel, Vincent C; Hall, Nathan; Hitchcock, Charles L; Ross, Patrick; Kassis, Edmund S

2012-05-01

The 5-year survival for patients with resected stage II (N1) non-small cell lung cancer ranges from 40% to 55%. No data exist addressing the benefit of neoadjuvant therapy for patients with stage II disease. This is largely in part due to the lack of a reliable, minimally invasive method to assess hilar nodes. This study is aimed at determining the ability of fusion positron emission/computed tomography (PET/CT) to identify hilar metastases in patients with resected non-small cell lung cancer. A retrospective review of surgically resected patients with fusion PET/CT within 30 days of resection was performed. The sensitivity, specificity, positive predictive value, and negative predictive value for PET/CT in detecting hilar nodal metastases was calculated for a range of maximum standardized uptake values (SUVmax). Hilar nodes from patients with falsely positive PET/CT scans were analyzed for the presence of histoplasmosis. Additionally, the impact of hilar node size greater than 1 centimeter on the calculated values was assessed. There were 119 patients evaluated. The number of lymph nodes resected ranged from 1 to 12 (X=2.98). There was decreased sensitivity and increased specificity with higher SUVmax cutoff values. At the standard SUVmax value of 2.5, the sensitivity and specificity were only 48.5% and 80.2%. The addition of size of hilar node by CT led to a modest improvement in sensitivity at all SUVmax cutoff values. Fusion PET/CT lacks sensitivity and specificity in identifying hilar nodal metastasis in patients with resected non-small cell lung cancer. Further prospective studies assessing the utility of PET/CT versus alternative sampling techniques are warranted. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Determinants of Cervical Cancer Screening Accuracy for Visual Inspection with Acetic Acid (VIA) and Lugol’s Iodine (VILI) Performed by Nurse and Physician

PubMed Central

Raifu, Amidu O.; El-Zein, Mariam; Sangwa-Lugoma, Ghislain; Ramanakumar, Agnihotram; Walter, Stephen D.

2017-01-01

Background Visual inspection with acetic acid (VIA) and Lugol’s iodine (VILI) are used to screen women for cervical cancer in low-resource settings. Little is known about correlates of their diagnostic accuracy by healthcare provider. We examined determinants of VIA and VILI screening accuracy by examiner in a cross-sectional screening study of 1528 women aged 30 years or older in a suburb of Kinshasa, Democratic Republic of Congo. Methods We used a logistic regression model for sensitivity and specificity to estimate the diagnostic accuracy of VIA and VILI, independently performed by nurse and physician, as a function of sociodemographic and reproductive health characteristics. Results Nurses rated tests as positive more often than physicians (36.3% vs 30.2% for VIA, 26.2% vs 25.2% for VILI). Women’s age was the most important determinant of performance. It was inversely associated with sensitivity (nurse’s VIA: p<0.001, nurse’s VILI: p = 0.018, physician’s VIA: p = 0.005, physician’s VILI: p = 0.006) but positively associated with specificity (all four combinations: p<0.001). Increasing parity adversely affected sensitivity and specificity, but the effects on sensitivity were significant for nurses only. The screening performance of physician’s assessment was significantly better than the nurse’s (difference in sensitivity: VIA = 13%, VILI = 16%; difference in specificity: VIA = 6%, VILI = 1%). Conclusions Age and parity influence the performance of visual tests for cervical cancer screening. Proper training of local healthcare providers in the conduct of these tests should take into account these factors for improved performance of VIA and VILI in detecting cervical precancerous lesions among women in limited-resource settings. PMID:28107486

Efficient strategies to find diagnostic test accuracy studies in kidney journals.

PubMed

Rogerson, Thomas E; Ladhani, Maleeka; Mitchell, Ruth; Craig, Jonathan C; Webster, Angela C

2015-08-01

Nephrologists looking for quick answers to diagnostic clinical questions in MEDLINE can use a range of published search strategies or Clinical Query limits to improve the precision of their searches. We aimed to evaluate existing search strategies for finding diagnostic test accuracy studies in nephrology journals. We assessed the accuracy of 14 search strategies for retrieving diagnostic test accuracy studies from three nephrology journals indexed in MEDLINE. Two investigators hand searched the same journals to create a reference set of diagnostic test accuracy studies to compare search strategy results against. We identified 103 diagnostic test accuracy studies, accounting for 2.1% of all studies published. The most specific search strategy was the Narrow Clinical Queries limit (sensitivity: 0.20, 95% CI 0.13-0.29; specificity: 0.99, 95% CI 0.99-0.99). Using the Narrow Clinical Queries limit, a searcher would need to screen three (95% CI 2-6) articles to find one diagnostic study. The most sensitive search strategy was van der Weijden 1999 Extended (sensitivity: 0.95; 95% CI 0.89-0.98; specificity 0.55, 95% CI 0.53-0.56) but required a searcher to screen 24 (95% CI 23-26) articles to find one diagnostic study. Bachmann 2002 was the best balanced search strategy, which was sensitive (0.88, 95% CI 0.81-0.94), but also specific (0.74, 95% CI 0.73-0.75), with a number needed to screen of 15 (95% CI 14-17). Diagnostic studies are infrequently published in nephrology journals. The addition of a strategy for diagnostic studies to a subject search strategy in MEDLINE may reduce the records needed to screen while preserving adequate search sensitivity for routine clinical use. © 2015 Asian Pacific Society of Nephrology.

Sensitive, microliter PCR with consensus degenerate primers for Epstein Barr virus amplification

PubMed Central

Oh, Kyudam; Pak, Nikita; Saunders, D. Curtis; Conrardy, Christina; Landers, James P.; Tong, Suxiang; Forest, Craig R.

2016-01-01

Sensitive identification of the etiology of viral diseases is key to implementing appropriate prevention and treatment. The gold standard for virus identification is the polymerase chain reaction (PCR), a technique that allows for highly specific and sensitive detection of pathogens by exponentially amplifying a specific region of DNA from as little as a single copy through thermocycling a biochemical cocktail. Today, molecular biology laboratories use commercial instruments that operate in 0.5–2 h/analysis using reaction volumes of 5–50 μL contained within polymer tubes or chambers. Towards reducing this volume and maintaining performance, we present a semi-quantitative, systematic experimental study of how PCR yield is affected by tube/chamber substrate, surface-area-to-volume ratio (SA:V), and passivation methods. We perform PCR experiments using traditional PCR tubes as well as using disposable polymer microchips with 1 μL reaction volumes thermocycled using water baths. We report the first oil encapsulation microfluidic PCR method without fluid flow and its application to the first microfluidic amplification of Epstein Barr virus using consensus degenerate primers, a powerful and broad PCR method to screen for both known and novel members of a viral family. The limit of detection is measured as 140 starting copies of DNA from a starting concentration of 3×105 copies/mL, regarded as an accepted sensitivity threshold for diagnostic purposes, and reaction specificity was improved as compared to conventional methods. Also notable, these experiments were conducted with conventional reagent concentrations, rather than commonly spiked enzyme and/or template mixtures. This experimental study of the effects of substrate, SA:V, and passivation, together with sensitive and specific microfluidic PCR with consensus degenerate primers represent advances towards lower cost and higher throughput pathogen screening. PMID:23080522

Evaluation of magnetic resonance imaging for the differentiation of inflammatory, neoplastic, and vascular intradural spinal cord diseases in the dog.

PubMed

Masciarelli, Amanda E; Griffin, John F; Fosgate, Geoffrey T; Hecht, Silke; Mankin, Joseph M; Holmes, Shannon P; Platt, Simon R; Kent, Marc; Pancotto, Theresa E; Chen, Annie V; Levine, Jonathan M

2017-07-01

Magnetic resonance imaging (MRI) is a common test for dogs with suspected intradural spinal cord lesions, however studies on diagnostic performance for this test are lacking. Objectives of this multi-institutional, retrospective, case-control study were to estimate sensitivity and specificity of MRI for (1) distinguishing between histopathologically confirmed intradural spinal cord disease versus degenerative myelopathy in dogs, (2) categorizing intradural spinal cord diseases as neoplastic, inflammatory, or vascular; and (3) determining tumor type within the etiologic category of neoplasia. Additional aims were to (1) determine whether knowledge of clinical data affects sensitivity and specificity of MRI diagnoses; and (2) report interrater agreement for MRI classification of intradural spinal lesions. Cases were recruited from participating hospital databases over a 7-year period. Three reviewers independently evaluated each MRI study prior to and after provision of clinical information. A total of 87 cases were sampled (17 degenerative myelopathy, 53 neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions but specificity varied before and after provision of clinical data (68.6% vs. 82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower for classifying inflammatory lesions but improved with provision of clinical data (48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for diagnosing vascular lesions (25.0%). Interrater agreement was very good for correctly diagnosing dogs with intradural lesions (ĸ = 0.882-0.833), and good (ĸ = 0.726-0.671) for diagnosing dogs with neoplasia. © 2017 American College of Veterinary Radiology.

Meaningful improvement in gait speed in hip fracture recovery.

PubMed

Alley, Dawn E; Hicks, Gregory E; Shardell, Michelle; Hawkes, William; Miller, Ram; Craik, Rebecca L; Mangione, Kathleen K; Orwig, Denise; Hochberg, Marc; Resnick, Barbara; Magaziner, Jay

2011-09-01

To estimate meaningful improvements in gait speed observed during recovery from hip fracture and to evaluate the sensitivity and specificity of gait speed changes in detecting change in self-reported mobility. Secondary longitudinal data analysis from two randomized controlled trials Twelve hospitals in the Baltimore, Maryland, area. Two hundred seventeen women admitted with hip fracture. Usual gait speed and self-reported mobility (ability to walk 1 block and climb 1 flight of stairs) measured 2 and 12 months after fracture. Effect size-based estimates of meaningful differences were 0.03 for small differences and 0.09 for substantial differences. Depending on the anchor (stairs vs walking) and method (mean difference vs regression), anchor-based estimates ranged from 0.10 to 0.17 m/s for small meaningful improvements and 0.17 to 0.26 m/s for substantial meaningful improvement. Optimal gait speed cutpoints yielded low sensitivity (0.39-0.62) and specificity (0.57-0.76) for improvements in self-reported mobility. Results from this sample of women recovering from hip fracture provide only limited support for the 0.10-m/s cut point for substantial meaningful change previously identified in community-dwelling older adults experiencing declines in walking abilities. Anchor-based estimates and cut points derived from receiver operating characteristic curve analysis suggest that greater improvements in gait speed may be required for substantial perceived mobility improvement in female hip fracture patients. Furthermore, gait speed change performed poorly in discriminating change in self-reported mobility. Estimates of meaningful change in gait speed may differ based on the direction of change (improvement vs decline) or between patient populations. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Meaningful Improvement in Gait Speed in Hip Fracture Recovery

PubMed Central

Alley, Dawn E.; Hicks, Gregory E.; Shardell, Michelle; Hawkes, William; Miller, Ram; Craik, Rebecca L.; Mangione, Kathleen K.; Orwig, Denise; Hochberg, Marc; Resnick, Barbara; Magaziner, Jay

2011-01-01

OBJECTIVES To estimate meaningful improvements in gait speed observed during recovery from hip fracture and to evaluate the sensitivity and specificity of gait speed changes in detecting change in self-reported mobility. DESIGN Secondary longitudinal data analysis from two randomized controlled trials SETTING Twelve hospitals in the Baltimore, Maryland, area. PARTICIPANTS Two hundred seventeen women admitted with hip fracture. MEASUREMENTS Usual gait speed and self-reported mobility (ability to walk 1 block and climb 1 flight of stairs) measured 2 and 12 months after fracture. RESULTS Effect size–based estimates of meaningful differences were 0.03 for small differences and 0.09 for substantial differences. Depending on the anchor (stairs vs walking) and method (mean difference vs regression), anchor-based estimates ranged from 0.10 to 0.17 m/s for small meaningful improvements and 0.17 to 0.26 m/s for substantial meaningful improvement. Optimal gait speed cut-points yielded low sensitivity (0.39–0.62) and specificity (0.57–0.76) for improvements in self-reported mobility. CONCLUSION Results from this sample of women recovering from hip fracture provide only limited support for the 0.10-m/s cut point for substantial meaningful change previously identified in community-dwelling older adults experiencing declines in walking abilities. Anchor-based estimates and cut points derived from receiver operating characteristic curve analysis suggest that greater improvements in gait speed may be required for substantial perceived mobility improvement in female hip fracture patients. Furthermore, gait speed change performed poorly in discriminating change in self-reported mobility. Estimates of meaningful change in gait speed may differ based on the direction of change (improvement vs decline) or between patient populations. PMID:21883109

Process improvement methods increase the efficiency, accuracy, and utility of a neurocritical care research repository.

PubMed

O'Connor, Sydney; Ayres, Alison; Cortellini, Lynelle; Rosand, Jonathan; Rosenthal, Eric; Kimberly, W Taylor

2012-08-01

Reliable and efficient data repositories are essential for the advancement of research in Neurocritical care. Various factors, such as the large volume of patients treated within the neuro ICU, their differing length and complexity of hospital stay, and the substantial amount of desired information can complicate the process of data collection. We adapted the tools of process improvement to the data collection and database design of a research repository for a Neuroscience intensive care unit. By the Shewhart-Deming method, we implemented an iterative approach to improve the process of data collection for each element. After an initial design phase, we re-evaluated all data fields that were challenging or time-consuming to collect. We then applied root-cause analysis to optimize the accuracy and ease of collection, and to determine the most efficient manner of collecting the maximal amount of data. During a 6-month period, we iteratively analyzed the process of data collection for various data elements. For example, the pre-admission medications were found to contain numerous inaccuracies after comparison with a gold standard (sensitivity 71% and specificity 94%). Also, our first method of tracking patient admissions and discharges contained higher than expected errors (sensitivity 94% and specificity 93%). In addition to increasing accuracy, we focused on improving efficiency. Through repeated incremental improvements, we reduced the number of subject records that required daily monitoring from 40 to 6 per day, and decreased daily effort from 4.5 to 1.5 h/day. By applying process improvement methods to the design of a Neuroscience ICU data repository, we achieved a threefold improvement in efficiency and increased accuracy. Although individual barriers to data collection will vary from institution to institution, a focus on process improvement is critical to overcoming these barriers.

Anomaly metrics to differentiate threat sources from benign sources in primary vehicle screening.

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

Cohen, Israel Dov; Mengesha, Wondwosen

2011-09-01

Discrimination of benign sources from threat sources at Port of Entries (POE) is of a great importance in efficient screening of cargo and vehicles using Radiation Portal Monitors (RPM). Currently RPM's ability to distinguish these radiological sources is seriously hampered by the energy resolution of the deployed RPMs. As naturally occurring radioactive materials (NORM) are ubiquitous in commerce, false alarms are problematic as they require additional resources in secondary inspection in addition to impacts on commerce. To increase the sensitivity of such detection systems without increasing false alarm rates, alarm metrics need to incorporate the ability to distinguish benign andmore » threat sources. Principal component analysis (PCA) and clustering technique were implemented in the present study. Such techniques were investigated for their potential to lower false alarm rates and/or increase sensitivity to weaker threat sources without loss of specificity. Results of the investigation demonstrated improved sensitivity and specificity in discriminating benign sources from threat sources.« less

Integrating functional genomics to accelerate mechanistic personalized medicine.

PubMed

Tyner, Jeffrey W

2017-03-01

The advent of deep sequencing technologies has resulted in the deciphering of tremendous amounts of genetic information. These data have led to major discoveries, and many anecdotes now exist of individual patients whose clinical outcomes have benefited from novel, genetically guided therapeutic strategies. However, the majority of genetic events in cancer are currently undrugged, leading to a biological gap between understanding of tumor genetic etiology and translation to improved clinical approaches. Functional screening has made tremendous strides in recent years with the development of new experimental approaches to studying ex vivo and in vivo drug sensitivity. Numerous discoveries and anecdotes also exist for translation of functional screening into novel clinical strategies; however, the current clinical application of functional screening remains largely confined to small clinical trials at specific academic centers. The intersection between genomic and functional approaches represents an ideal modality to accelerate our understanding of drug sensitivities as they relate to specific genetic events and further understand the full mechanisms underlying drug sensitivity patterns.

Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid.

PubMed

Jankásková, J; Horváth, O N; Varga, R; Arenberger, P; Schmidt, E; Ruzicka, T; Sárdy, M

2018-04-01

Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG subclasses. To determine the operating characteristics of an IgG subclass in IIF. We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG 1 , IgG 3 and IgG 4 autoantibodies. The sensitivities of IIF in detecting IgG 1 , IgG 3 , IgG 4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%. Detection of IgG subclass (especially IgG 1 and IgG 4 ) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP. © 2018 British Association of Dermatologists.

An evaluation of computer-aided disproportionality analysis for post-marketing signal detection.

PubMed

Lehman, H P; Chen, J; Gould, A L; Kassekert, R; Beninger, P R; Carney, R; Goldberg, M; Goss, M A; Kidos, K; Sharrar, R G; Shields, K; Sweet, A; Wiholm, B E; Honig, P K

2007-08-01

To understand the value of computer-aided disproportionality analysis (DA) in relation to current pharmacovigilance signal detection methods, four products were retrospectively evaluated by applying an empirical Bayes method to Merck's post-marketing safety database. Findings were compared with the prior detection of labeled post-marketing adverse events. Disproportionality ratios (empirical Bayes geometric mean lower 95% bounds for the posterior distribution (EBGM05)) were generated for product-event pairs. Overall (1993-2004 data, EBGM05> or =2, individual terms) results of signal detection using DA compared to standard methods were sensitivity, 31.1%; specificity, 95.3%; and positive predictive value, 19.9%. Using groupings of synonymous labeled terms, sensitivity improved (40.9%). More of the adverse events detected by both methods were detected earlier using DA and grouped (versus individual) terms. With 1939-2004 data, diagnostic properties were similar to those from 1993 to 2004. DA methods using Merck's safety database demonstrate sufficient sensitivity and specificity to be considered for use as an adjunct to conventional signal detection methods.

Photoacoustic and ultrasound characterization of bone composition

NASA Astrophysics Data System (ADS)

Lashkari, Bahman; Yang, Lifeng; Liu, Lixian; Tan, Joel W. Y.; Mandelis, Andreas

2015-02-01

This study examines the sensitivity and specificity of backscattered ultrasound (US) and backscattering photoacoustic (PA) signals for bone composition variation assessment. The conventional approach in the evaluation of bone health relies on measurement of bone mineral density (BMD). Although, a crucial and probably the most important parameter, BMD is not the only factor defining the bone health. New trends in osteoporosis research, also pursue the changes in collagen content and cross-links with bone diseases and aging. Therefore, any non-invasive method that can assess any of these parameters can improve the diagnostic tools and also can help with the biomedical studies on the diseases themselves. Our previous studies show that both US and PA are responsive to changes in the BMD, PA is, in addition, sensitive to changes in the collagen content of the bone. Measurements were performed on bone samples before and after mild demineralization and decollagenization at the exact same points. Results show that combining both modalities can enhance the sensitivity and specificity of diagnostic tool.

Highly sensitive detection of target molecules using a new fluorescence-based bead assay

NASA Astrophysics Data System (ADS)

Scheffler, Silvia; Strauß, Denis; Sauer, Markus

2007-07-01

Development of immunoassays with improved sensitivity, specificity and reliability are of major interest in modern bioanalytical research. We describe the development of a new immunomagnetic fluorescence detection (IM-FD) assay based on specific antigen/antibody interactions and on accumulation of the fluorescence signal on superparamagnetic PE beads in combination with the use of extrinsic fluorescent labels. IM-FD can be easily modified by varying the order of coatings and assay conditions. Depending on the target molecule, antibodies (ABs), entire proteins, or small protein epitopes can be used as capture molecules. The presence of target molecules is detected by fluorescence microscopy using fluorescently labeled secondary or detection antibodies. Here, we demonstrate the potential of the new assay detecting the two tumor markers IGF-I and p53 antibodies in the clinically relevant concentration range. Our data show that the fluorescence-based bead assay exhibits a large dynamic range and a high sensitivity down to the subpicomolar level.

Enzyme immunoassay of two nicergoline metabolites, 10 alpha-methoxy-9, 10-dihydrolysergol (MDL) and 1-methyl-10 alpha-methoxy-9, 10-dihydrolysergol (MMDL).

PubMed

Chen, P; Tian, Z; Digenis, G A; Tai, H H

1996-06-01

Specific and sensitive enzyme immunoassays for two nicergoline metabolites, 10 alpha-methoxy-9, 10-dihydrolysergol (MDL) and 1-methyl-10 alpha-methoxy-9, 10-dihydrolysergol (MMDL) have been developed. The hydroxyl group of hydroxymethyl at position 8 of either MDL or MMDL was carboxymethylated to introduce a carboxyl group for protein conjugation. Antibodies generated from O-carboxymethyl MDL or MMDL recognized the spacer arm between the hapten and the carrier protein and the molecular domain near the conjugation site as well. A heterologous bridge strategy was used to improve the affinity of the hapten-enzyme conjugate to the antibodies. The sensitivity of both assays was greatly increased by using such an approach. Both antibodies are specific for their own haptens. Little cross reactivity was observed with nicergoline and other metabolites. Determination of MDL and MMDL from both spiked plasma and urine showed nearly quantitative recovery. Detection of MDL and MMDL can be as sensitive as 10 pg/ml.

Triton Hodge Test: Improved Protocol for Modified Hodge Test for Enhanced Detection of NDM and Other Carbapenemase Producers

PubMed Central

Pasteran, Fernando; Gonzalez, Lisandro J.; Albornoz, Ezequiel; Bahr, Guillermo; Vila, Alejandro J.

2015-01-01

Accurate detection of carbapenemase-producing Gram-negative bacilli is of utmost importance for the control of nosocomial spread and the initiation of appropriate antimicrobial therapy. The modified Hodge test (MHT), a carbapenem inactivation assay, has shown poor sensitivity in detecting the worldwide spread of New Delhi metallo-β-lactamase (NDM). Recent studies demonstrated that NDM is a lipoprotein anchored to the outer membrane in Gram-negative bacteria, unlike all other known carbapenemases. Here we report that membrane anchoring of β-lactamases precludes detection of carbapenemase activity by the MHT. We also show that this limitation can be overcome by the addition of Triton X-100 during the test, which allows detection of NDM. We propose an improved version of the assay, called the Triton Hodge test (THT), which allows detection of membrane-bound carbapenemases with the addition of this nonionic surfactant. This test was challenged with a panel of 185 clinical isolates (145 carrying known carbapenemase-encoding genes and 40 carbapenemase nonproducers). The THT displayed test sensitivity of >90% against NDM-producing clinical isolates, while improving performance against other carbapenemases. Ertapenem provided the highest sensitivity (97 to 100%, depending on the type of carbapenemase), followed by meropenem (92.5 to 100%). Test specificity was not affected by the addition of Triton (87.5% and 92.5% with ertapenem and meropenem, respectively). This simple inexpensive test confers a large improvement to the sensitivity of the MHT for the detection of NDM and other carbapenemases. PMID:26719442

Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.

PubMed

O'Flaherty, Brigid M; Li, Yan; Tao, Ying; Paden, Clinton R; Queen, Krista; Zhang, Jing; Dinwiddie, Darrell L; Gross, Stephen M; Schroth, Gary P; Tong, Suxiang

2018-06-01

Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. © 2018 O'Flaherty et al.; Published by Cold Spring Harbor Laboratory Press.

[Sensitivity and specificity of the cerebral blood flow reactions to acupuncture in the newborn infants presenting with hypoxic ischemic encephalopathy].

PubMed

Filonenko, A V; Vasilenko, A M; Khan, M A

2015-01-01

To evaluate the effects of acupuncture integrated into the standard therapy, the condition of cerebral blood flow, and other syndromes associated with cerebral ischemia in the newborn infants. MATERIAL AND METHODS. A total of 131 pairs of puerperae and newborns with hypoxic ischemic encephalopathy were divided into four treatment groups. 34 children of the first group were given standard therapy (control), in the second group comprised of 33 mothers and children the standard treatment was supplemented by acupuncture, the third group included only 32 mothers given the acupuncture treatment alone, and the fourth group contained only 32 newborn infants treated by acupuncture. Each course of acupuncture treatment consisted of five sessions. Sensitivity and specificity of cerebral blood flow reactions were determined based on the results of the ROC-analysis and the area under the curve before and after the treatment. The treatment with the use of acupuncture greatly improved the cerebrospinal hemodynamics (p < 0.05). Other symptoms, viz. sleep disorders, vegetative reactivity and excitability were significantly reduced. The ROC analysis confirmed the effectiveness of acupuncture as a tool for the treatment of the impaired cerebral blood flow in the newborn babies. The high level of sensitivity (84.4-94.8%) associated with good specificity makes it possible to distinguish between the true positive and true negative cases. Acupuncture integrated into the treatment of "mother-baby" pairs presenting with hypoxic ischemic encephalopathy can be used to improve the initially low level of cerebral blood flow in neonates presenting with this condition.

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

PubMed

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

2009-02-01

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

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

PubMed

Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

2016-01-01

There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

Microbial Diagnostic Microarrays for the Detection and Typing of Food- and Water-Borne (Bacterial) Pathogens

PubMed Central

Kostić, Tanja; Sessitsch, Angela

2011-01-01

Reliable and sensitive pathogen detection in clinical and environmental (including food and water) samples is of greatest importance for public health. Standard microbiological methods have several limitations and improved alternatives are needed. Most important requirements for reliable analysis include: (i) specificity; (ii) sensitivity; (iii) multiplexing potential; (iv) robustness; (v) speed; (vi) automation potential; and (vii) low cost. Microarray technology can, through its very nature, fulfill many of these requirements directly and the remaining challenges have been tackled. In this review, we attempt to compare performance characteristics of the microbial diagnostic microarrays developed for the detection and typing of food and water pathogens, and discuss limitations, points still to be addressed and issues specific for the analysis of food, water and environmental samples. PMID:27605332

Ability among adolescents for the metabolic syndrome to predict elevations in factors associated with type 2 diabetes and cardiovascular disease: data from the national health and nutrition examination survey 1999-2006.

PubMed

DeBoer, Mark D; Gurka, Matthew J

2010-08-01

The aim of this study was to compare currently proposed sets of pediatric metabolic syndrome criteria for the ability to predict elevations in "surrogate" factors that are associated with metabolic syndrome and with future cardiovascular disease and type 2 diabetes mellitus. These surrogate factors were fasting insulin, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (hsCRP), and uric acid. Waist circumference (WC), blood pressure, triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting glucose, fasting insulin, HbA1c, hsCRP, and uric acid measurements were obtained from 2,624 adolescent (12-18 years old) participants of the 1999-2006 National Health and Nutrition Examination Surveys. We identified children with metabolic syndrome as defined by six commonly used sets of pediatric metabolic syndrome criteria. We then defined elevations in the surrogate factors as values in the top 5% for the cohort and calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each set of metabolic syndrome criteria and for each surrogate factor. Current pediatric metabolic syndrome criteria exhibited variable sensitivity and specificity for surrogate predictions. Metabolic syndrome criteria had the highest sensitivity for predicting fasting insulin (40-70%), followed by uric acid (31-54%), hsCRP (13-31%), and HbA1c (7-21%). The criteria of de Ferranti (which includes children with WC >75(th) percentile, compared to all other sets including children with WC >90(th) percentile) exhibited the highest sensitivity for predicting each of the surrogates, with only modest decrease in specificity compared to the other sets of criteria. However, the de Ferranti criteria also exhibited the lowest PPV values. Conversely, the pediatric International Diabetes Federation criteria exhibited the lowest sensitivity and the highest specificity. Pediatric metabolic syndrome criteria exhibit moderate sensitivity for detecting elevations in surrogate factors associated with metabolic syndrome and with risk for future disease. Inclusion of children with more modestly elevated WC improved sensitivity.

Engineering of Yersinia Phytases to Improve Pepsin and Trypsin Resistance and Thermostability and Application Potential in the Food and Feed Industry.

PubMed

Niu, Canfang; Yang, Peilong; Luo, Huiying; Huang, Huoqing; Wang, Yaru; Yao, Bin

2017-08-30

Susceptibility to proteases usually limits the application of phytase. We sought to improve the pepsin and trypsin resistance of YeAPPA from Yersinia enterocolitica and YkAPPA from Y. kristensenii by optimizing amino acid polarity and charge. The predicted pepsin/trypsin cleavage sites F89/K226 in pepsin/trypsin-sensitive YeAPPA and the corresponding sites (F89/E226) in pepsin-sensitive but trypsin-resistant YkAPPA were substituted with S and H, respectively. Six variants were produced in Pichia pastoris for catalytic and biochemical characterization. F89S, E226H, and F89S/E226H elevated pepsin resistance and thermostability and K226H and F89S/K226H improved pepsin and trypsin resistance and stability at 60 °C and low pH. All the variants increased the ability of the proteins to hydrolyze phytate in corn meal by 2.6-14.9-fold in the presence of pepsin at 37 °C and low pH. This study developed a genetic manipulation strategy specific for pepsin/trypsin-sensitive phytases that can improve enzyme tolerance against proteases and heat and benefit the food and feed industry in a cost-effective way.

Diagnosis of mold allergy by RAST and skin prick testing.

PubMed

Nordvall, S L; Agrell, B; Malling, H J; Dreborg, S

1990-11-01

Sera from 33 patients with mold allergy proven by bronchial provocation were analyzed for specific IgE against six mold species comparing an improved Phadebas RAST with four other techniques. The new method was more sensitive and gave significantly higher IgE antibody concentrations for all tested molds except Cladosporium herbarum.

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

ERIC Educational Resources Information Center

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

2017-01-01

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

Sex and gender differences in therapy of type 2 diabetes.

PubMed

Kautzky-Willer, Alexandra; Harreiter, Jürgen

2017-09-01

Clinical guidelines for the management of type 2 diabetes recommend individual therapy considering age, duration of disease, presence of complication and risk of hypoglycaemia. However, at present, the patient's sex has no impact on clinical decisions. Yet, there is mounting data pointing at biological and psychosocial differences between men and women with great impact on progression of disease and complications. Moreover, choices and preferences of therapeutic strategies as well as adherence to lifestyle and pharmacological interventions differ in both sexes. In addition, drug therapy may have sex-specific side effects. Therefore, there is need of more research on biological differences and of evidence-based individualised targeted sex-sensitive therapeutic concepts. Clinical guidelines must consider relevant sex-differences. Development and implementation of sex-specific programs may help to improve adherence to therapy and to reduce progression of disease and development of complications. A more gender-sensitive clinical approach may improve quality of life and increase health and life expectancy in men and women with type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

NMP22 BladderChek Test: point-of-care technology with life- and money-saving potential.

PubMed

Tomera, Kevin M

2004-11-01

A new, relatively obscure tumor marker assay, the NMP22 BladderChek Test (Matritech, Inc.), represents a paradigm shift in the diagnosis and management of urinary bladder cancer (transitional cell carcinoma). Specifically, BladderChek should be employed every time a cystoscopy is performed, with corresponding changes in the diagnostic protocol and the guidelines of the American Urological Association for the diagnosis and management of bladder cancer. Currently, cystoscopy is the reference standard and NMP22 BladderChek Test in combination with cystoscopy improves the performance of cystoscopy. At every stage of disease, BladderChek provides a higher sensitivity for the detection of bladder cancer than cytology, which now represents the adjunctive standard of care. Moreover, BladderChek is four-times more sensitive than cytology and is available at half the cost. Early detection of bladder cancer improves prognosis, quality of life and survival. BladderChek may be analogous to the prostate-specific antigen test and eventually expand beyond the urologic setting into the primary care setting for the testing of high-risk patients characterized by smoking history, occupational exposures or age.

Improved porous silicon (P-Si) microarray based PSA (prostate specific antigen) immunoassay by optimized surface density of the capture antibody

PubMed Central

Lee, SangWook; Kim, Soyoun; Malm, Johan; Jeong, Ok Chan; Lilja, Hans; Laurell, Thomas

2014-01-01

Enriching the surface density of immobilized capture antibodies enhances the detection signal of antibody sandwich microarrays. In this study, we improved the detection sensitivity of our previously developed P-Si (porous silicon) antibody microarray by optimizing concentrations of the capturing antibody. We investigated immunoassays using a P-Si microarray at three different capture antibody (PSA - prostate specific antigen) concentrations, analyzing the influence of the antibody density on the assay detection sensitivity. The LOD (limit of detection) for PSA was 2.5ngmL−1, 80pgmL−1, and 800fgmL−1 when arraying the PSA antibody, H117 at the concentration 15µgmL−1, 35µgmL−1 and 154µgmL−1, respectively. We further investigated PSA spiked into human female serum in the range of 800fgmL−1 to 500ngmL−1. The microarray showed a LOD of 800fgmL−1 and a dynamic range of 800 fgmL−1 to 80ngmL−1 in serum spiked samples. PMID:24016590