Accounting for false-positive acoustic detections of bats using occupancy models

USGS Publications Warehouse

Clement, Matthew J.; Rodhouse, Thomas J.; Ormsbee, Patricia C.; Szewczak, Joseph M.; Nichols, James D.

2014-01-01

4. Synthesis and applications. Our results suggest that false positives sufficient to affect inferences may be common in acoustic surveys for bats. We demonstrate an approach that can estimate occupancy, regardless of the false-positive rate, when acoustic surveys are paired with capture surveys. Applications of this approach include monitoring the spread of White-Nose Syndrome, estimating the impact of climate change and informing conservation listing decisions. We calculate a site-specific probability of occupancy, conditional on survey results, which could inform local permitting decisions, such as for wind energy projects. More generally, the magnitude of false positives suggests that false-positive occupancy models can improve accuracy in research and monitoring of bats and provide wildlife managers with more reliable information.

Evaluation of the Architect HIV Ag/Ab Combo Assay in a low-prevalence setting: The role of samples with a low S/CO ratio.

PubMed

Alonso, Roberto; Pérez-García, Felipe; Gijón, Paloma; Collazos, Ana; Bouza, Emilio

2018-06-01

The Architect HIV Ag/Ab Combo Assay, a fourth-generation ELISA, has proven to be highly reliable for the diagnosis of HIV infection. However, its high sensitivity may lead to false-positive results. To evaluate the diagnostic performance of Architect in a low-prevalence population and to assess the role of the sample-to-cutoff ratio (S/CO) in reducing the frequency of false-positive results. We conducted a retrospective study of samples analyzed by Architect between January 2015 and June 2017. Positive samples were confirmed by immunoblot (RIBA) or nucleic acid amplification tests (NAATs). Different S/CO thresholds (1, 2.5, 10, 25, and 100) were analyzed to determine sensitivity, specificity, and negative and positive predictive values (NPV, PPV). ROC analysis was used to determine the optimal S/CO. A total of 69,471 samples were analyzed. 709 (1.02%) were positive by Architect. Of these, 63 (8.89%) were false-positive results. Most of them (93.65%) were in samples with S/CO < 100. However, most confirmations by NAATs (12 out of 19 cases) were also recorded for these samples. The optimal S/CO was 2.5, which provided the highest area under the ROC curve (0.9998) and no false-negative results. With this S/CO, sensitivity and specificity were 100.0%, and PPV and NPV were 95.8% and 100.0%, respectively. In addition, the frequency of false-positive results decreased significantly to 4.15%. Although Architect generates a relatively high number of false-positive results, raising the S/CO limit too much to increase specificity can lead to false-negative results, especially in newly infected individuals. Copyright © 2018 Elsevier B.V. All rights reserved.

False-Positive Xpert MTB/RIF Results in Retested Patients with Previous Tuberculosis: Frequency, Profile, and Prospective Clinical Outcomes.

PubMed

Theron, Grant; Venter, Rouxjeane; Smith, Liezel; Esmail, Aliasgar; Randall, Philippa; Sood, Vishesh; Oelfese, Suzette; Calligaro, Greg; Warren, Robin; Dheda, Keertan

2018-03-01

Globally, Xpert MTB/RIF (Xpert) is the most widely used PCR test for the diagnosis of tuberculosis (TB). Positive results in previously treated patients, which are due to old DNA or active disease, are a diagnostic dilemma. We prospectively retested sputum from 238 patients, irrespective of current symptoms, who were previously diagnosed to be Xpert positive and treated successfully. Patients who retested as Xpert positive and culture negative were exhaustively investigated (repeat culture, chest radiography, bronchoscopy with bronchoalveolar lavage, long-term clinical follow-up). We evaluated whether the duration since previous treatment completion, mycobacterial burden (the Xpert cycle threshold [ C T ] value), and reclassification of Xpert-positive results with a very low semiquantitation level to Xpert-negative results reduced the rate of false positivity. A total of 229/238 (96%) of patients were culture negative. Sixteen of 229 (7%) were Xpert positive a median of 11 months (interquartile range, 5 to 19 months) after treatment completion. The specificity was 93% (95% confidence interval [CI], 89 to 96%). Nine of 15 (40%) Xpert-positive, culture-negative patients reverted to Xpert negative after 2 to 3 months (1 patient declined further participation). Patients with false-positive Xpert results had a lower mycobacterial burden than patients with true-positive Xpert results ( C T , 28.7 [95% CI, 27.2 to 30.4] versus 17.6 [95% CI, 16.9 to 18.2]; P < 0.001), an increased likelihood of a chest radiograph not compatible with active TB (5/15 patients versus 0/5 patients; P = 0.026), and less-viscous sputum (15/16 patients versus 2/5 patients whose sputum was graded as mucoid or less; P = 0.038). All patients who initially retested as Xpert positive and culture negative ("Xpert false positive") were clinically well without treatment after follow-up. The duration since the previous treatment poorly predicted false-positive results (a duration of ≤2 years identified only 66% of patients with false-positive results). Reclassifying Xpert-positive results with a very low semiquantitation level to Xpert negative improved the specificity (+3% [95% CI, +2 to +5%]) but reduced the sensitivity (-10% [95% CI, -4 to -15%]). Patients with previous TB retested with Xpert can have false-positive results and thus not require treatment. These data inform clinical practice by highlighting the challenges in interpreting Xpert-positive results, underscore the need for culture, and have implications for next-generation ultrasensitive tests. Copyright © 2018 American Society for Microbiology.

Relevance of cutoff on a 4th generation ELISA performance in the false positive rate during HIV diagnostic in a low HIV prevalence setting.

PubMed

Chacón, Lucía; Mateos, María Luisa; Holguín, África

2017-07-01

Despite the high specificity of fourth-generation enzyme immunoassays (4th-gen-EIA) for screening during HIV diagnosis, their positive predictive value is low in populations with low HIV prevalence. Thus, screening should be optimized to reduce false positive results. The influence of sample cutoff (S/CO) values by a 4th-gen-EIA with the false positive rate during the routine HIV diagnosis in a low HIV prevalence population was evaluated. A total of 30,201 sera were tested for HIV diagnosis using Abbott Architect ® HIV-Ag/Ab-Combo 4th-gen-EIA at a hospital in Spain during 17 months. Architect S/CO values were recorded, comparing the HIV-1 positive results following Architect interpretation (S/CO≥1) with the final HIV-1 diagnosis by confirmatory tests (line immunoassay, LIA and/or nucleic acid test, NAT). ROC curve was also performed. Among the 30,201 HIV performed tests, 256 (0.85%) were positive according to Architect interpretation (S/CO≥1) but only 229 (0.76%) were definitively HIV-1 positive after LIA and/or NAT. Thus, 27 (10.5%) of 256 samples with S/CO≥1 by Architect were false positive diagnose. The false positive rate decreased when the S/CO ratio increased. All 19 samples with S/CO ≤10 were false positives and all 220 with S/CO>50 true HIV-positives. The optimal S/CO cutoff value provided by ROC curves was 32.7. No false negative results were found. We show that very low S/CO values during HIV-1 screening using Architect can result HIV negative after confirmation by LIA and NAT. The false positive rate is reduced when S/CO increases. Copyright © 2017 Elsevier B.V. All rights reserved.

False-Positive Tuberculin Skin Test Results Among Low-Risk Healthcare Workers Following Implementation of Fifty-Dose Vials of Purified Protein Derivative.

PubMed

Collins, Jeffrey M; Hunter, Mary; Gordon, Wanda; Kempker, Russell R; Blumberg, Henry M; Ray, Susan M

2018-06-01

Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.Infect Control Hosp Epidemiol 2018;39:750-752.

Bladder cancer diagnosis with CT urography: test characteristics and reasons for false-positive and false-negative results.

PubMed

Trinh, Tony W; Glazer, Daniel I; Sadow, Cheryl A; Sahni, V Anik; Geller, Nina L; Silverman, Stuart G

2018-03-01

To determine test characteristics of CT urography for detecting bladder cancer in patients with hematuria and those undergoing surveillance, and to analyze reasons for false-positive and false-negative results. A HIPAA-compliant, IRB-approved retrospective review of reports from 1623 CT urograms between 10/2010 and 12/31/2013 was performed. 710 examinations for hematuria or bladder cancer history were compared to cystoscopy performed within 6 months. Reference standard was surgical pathology or 1-year minimum clinical follow-up. False-positive and false-negative examinations were reviewed to determine reasons for errors. Ninety-five bladder cancers were detected. CT urography accuracy: was 91.5% (650/710), sensitivity 86.3% (82/95), specificity 92.4% (568/615), positive predictive value 63.6% (82/129), and negative predictive value was 97.8% (568/581). Of 43 false positives, the majority of interpretation errors were due to benign prostatic hyperplasia (n = 12), trabeculated bladder (n = 9), and treatment changes (n = 8). Other causes include blood clots, mistaken normal anatomy, infectious/inflammatory changes, or had no cystoscopic correlate. Of 13 false negatives, 11 were due to technique, one to a large urinary residual, one to artifact. There were no errors in perception. CT urography is an accurate test for diagnosing bladder cancer; however, in protocols relying predominantly on excretory phase images, overall sensitivity remains insufficient to obviate cystoscopy. Awareness of bladder cancer mimics may reduce false-positive results. Improvements in CTU technique may reduce false-negative results.

Interpreting the results of the Semmes-Weinstein monofilament test: accounting for false-positive answers in the international consensus on the diabetic foot protocol by a new model.

PubMed

Slater, Robert A; Koren, Shlomit; Ramot, Yoram; Buchs, Andreas; Rapoport, Micha J

2014-01-01

The Semmes-Weinstein monofilament is the most widely used test to diagnose the loss of protective sensation. The commonly used protocol of the International Consensus on the Diabetic Foot includes a 'sham' application that allows for false-positive answers. We sought to study the heretofore unexamined significance of false-positive answers. Forty-five patients with diabetes and a history of pedal ulceration (Group I) and 81 patients with diabetes but no history of ulceration (Group II) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, 1st metatarsal and 5th metatarsal areas were used. At each location, the test was performed three times: 2 actual and 1 "sham" applications. Scores were graded from 0 to 3 based upon correct responses. Determination of loss of protective sensation was performed with and without calculating a false-positive answer as a minus 1 score. False-positive responses were found in a significant percentage of patients with and without history of ulceration. Introducing false-positive results as minus 1 into the test outcome significantly increased the number of patients diagnosed with loss of protective sensation in both groups. False-positive answers can significantly affect Semmes-Weinstein monofilament test results and the diagnosis of LOPS. A model that accounts for false-positive answers is offered. Copyright © 2013 John Wiley & Sons, Ltd.

Accurate decisions in an uncertain world: collective cognition increases true positives while decreasing false positives.

PubMed

Wolf, Max; Kurvers, Ralf H J M; Ward, Ashley J W; Krause, Stefan; Krause, Jens

2013-04-07

In a wide range of contexts, including predator avoidance, medical decision-making and security screening, decision accuracy is fundamentally constrained by the trade-off between true and false positives. Increased true positives are possible only at the cost of increased false positives; conversely, decreased false positives are associated with decreased true positives. We use an integrated theoretical and experimental approach to show that a group of decision-makers can overcome this basic limitation. Using a mathematical model, we show that a simple quorum decision rule enables individuals in groups to simultaneously increase true positives and decrease false positives. The results from a predator-detection experiment that we performed with humans are in line with these predictions: (i) after observing the choices of the other group members, individuals both increase true positives and decrease false positives, (ii) this effect gets stronger as group size increases, (iii) individuals use a quorum threshold set between the average true- and false-positive rates of the other group members, and (iv) individuals adjust their quorum adaptively to the performance of the group. Our results have broad implications for our understanding of the ecology and evolution of group-living animals and lend themselves for applications in the human domain such as the design of improved screening methods in medical, forensic, security and business applications.

Accurate decisions in an uncertain world: collective cognition increases true positives while decreasing false positives

PubMed Central

Wolf, Max; Kurvers, Ralf H. J. M.; Ward, Ashley J. W.; Krause, Stefan; Krause, Jens

2013-01-01

In a wide range of contexts, including predator avoidance, medical decision-making and security screening, decision accuracy is fundamentally constrained by the trade-off between true and false positives. Increased true positives are possible only at the cost of increased false positives; conversely, decreased false positives are associated with decreased true positives. We use an integrated theoretical and experimental approach to show that a group of decision-makers can overcome this basic limitation. Using a mathematical model, we show that a simple quorum decision rule enables individuals in groups to simultaneously increase true positives and decrease false positives. The results from a predator-detection experiment that we performed with humans are in line with these predictions: (i) after observing the choices of the other group members, individuals both increase true positives and decrease false positives, (ii) this effect gets stronger as group size increases, (iii) individuals use a quorum threshold set between the average true- and false-positive rates of the other group members, and (iv) individuals adjust their quorum adaptively to the performance of the group. Our results have broad implications for our understanding of the ecology and evolution of group-living animals and lend themselves for applications in the human domain such as the design of improved screening methods in medical, forensic, security and business applications. PMID:23407830

Shear-wave elastography in the diagnosis of solid breast masses: what leads to false-negative or false-positive results?

PubMed

Yoon, Jung Hyun; Jung, Hae Kyoung; Lee, Jong Tae; Ko, Kyung Hee

2013-09-01

To investigate the factors that have an effect on false-positive or false-negative shear-wave elastography (SWE) results in solid breast masses. From June to December 2012, 222 breast lesions of 199 consecutive women (mean age: 45.3 ± 10.1 years; range, 21 to 88 years) who had been scheduled for biopsy or surgical excision were included. Greyscale ultrasound and SWE were performed in all women before biopsy. Final ultrasound assessments and SWE parameters (pattern classification and maximum elasticity) were recorded and compared with histopathology results. Patient and lesion factors in the 'true' and 'false' groups were compared. Of the 222 masses, 175 (78.8 %) were benign, and 47 (21.2 %) were malignant. False-positive rates of benign masses were significantly higher than false-negative rates of malignancy in SWE patterns, 36.6 % to 6.4 % (P < 0.001). Among both benign and malignant masses, factors showing significance among false SWE features were lesion size, breast thickness and lesion depth (all P < 0.05). All 47 malignant breast masses had SWE images of good quality. False SWE features were more significantly seen in benign masses. Lesion size, breast thickness and lesion depth have significance in producing false results, and this needs consideration in SWE image acquisition. • Shear-wave elastography (SWE) is widely used during breast imaging • At SWE, false-positive rates were significantly higher than false-negative rates • Larger size, breast thickness, depth and fair quality influences false-positive SWE features • Smaller size, larger breast thickness and depth influences false-negative SWE features.

Implications of false-positive results for future cancer screenings.

PubMed

Taksler, Glen B; Keating, Nancy L; Rothberg, Michael B

2018-06-01

False-positive cancer screening results may affect a patient's willingness to obtain future screening. The authors conducted logistic regression analysis of 450,484 person-years of electronic medical records (2006-2015) in 92,405 individuals aged 50 to 75 years. Exposures were false-positive breast, prostate, or colorectal cancer screening test results (repeat breast imaging or negative breast biopsy ≤3 months after screening mammography, repeat prostate-specific antigen [PSA] test ≤3 months after PSA test result ≥4.0 ng/mL or negative prostate biopsy ≤3 months after any PSA result, or negative colonoscopy [without biopsy/polypectomy] ≤6 months after a positive fecal occult blood test). Outcomes were up-to-date status with breast or colorectal cancer screening. Covariates included prior screening history, clinical information (eg, family history, obesity, and smoking status), comorbidity, and demographics. Women were more likely to be up to date with breast cancer screening if they previously had false-positive mammography findings (adjusted odds ratio [AOR], 1.43 [95% confidence interval, 1.34-1.51] without breast biopsy and AOR, 2.02 [95% confidence interval, 1.56-2.62] with breast biopsy; both P<.001). The same women were more likely to be up to date with colorectal cancer screening (AOR range, 1.25-1.47 depending on breast biopsy; both P<.001). Men who previously had false-positive PSA testing were more likely to be up to date with colorectal cancer screening (AOR, 1.22 [P = .039] without prostate imaging/biopsy and AOR, 1.60 [P = .028] with imaging/biopsy). Results were stronger for individuals with more false-positive results (all P≤.005). However, women with previous false-positive colorectal cancer fecal occult blood test screening results were found to be less likely to be up to date with breast cancer screening (AOR, 0.73; P<.001). Patients who previously had a false-positive breast or prostate cancer screening test were more likely to engage in future screening. Cancer 2018;124:2390-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

False positive circumsporozoite protein ELISA: a challenge for the estimation of the entomological inoculation rate of malaria and for vector incrimination

PubMed Central

2011-01-01

Background The entomological inoculation rate (EIR) is an important indicator in estimating malaria transmission and the impact of vector control. To assess the EIR, the enzyme-linked immunosorbent assay (ELISA) to detect the circumsporozoite protein (CSP) is increasingly used. However, several studies have reported false positive results in this ELISA. The false positive results could lead to an overestimation of the EIR. The aim of present study was to estimate the level of false positivity among different anopheline species in Cambodia and Vietnam and to check for the presence of other parasites that might interact with the anti-CSP monoclonal antibodies. Methods Mosquitoes collected in Cambodia and Vietnam were identified and tested for the presence of sporozoites in head and thorax by using CSP-ELISA. ELISA positive samples were confirmed by a Plasmodium specific PCR. False positive mosquitoes were checked by PCR for the presence of parasites belonging to the Haemosporidia, Trypanosomatidae, Piroplasmida, and Haemogregarines. The heat-stability and the presence of the cross-reacting antigen in the abdomen of the mosquitoes were also checked. Results Specimens (N = 16,160) of seven anopheline species were tested by CSP-ELISA for Plasmodium falciparum and Plasmodium vivax (Pv210 and Pv247). Two new vector species were identified for the region: Anopheles pampanai (P. vivax) and Anopheles barbirostris (Plasmodium malariae). In 88% (155/176) of the mosquitoes found positive with the P. falciparum CSP-ELISA, the presence of Plasmodium sporozoites could not be confirmed by PCR. This percentage was much lower (28% or 5/18) for P. vivax CSP-ELISAs. False positive CSP-ELISA results were associated with zoophilic mosquito species. None of the targeted parasites could be detected in these CSP-ELISA false positive mosquitoes. The ELISA reacting antigen of P. falciparum was heat-stable in CSP-ELISA true positive specimens, but not in the false positives. The heat-unstable cross-reacting antigen is mainly present in head and thorax and almost absent in the abdomens (4 out of 147) of the false positive specimens. Conclusion The CSP-ELISA can considerably overestimate the EIR, particularly for P. falciparum and for zoophilic species. The heat-unstable cross-reacting antigen in false positives remains unknown. Therefore it is highly recommended to confirm all positive CSP-ELISA results, either by re-analysing the heated ELISA lysate (100°C, 10 min), or by performing Plasmodium specific PCR followed if possible by sequencing of the amplicons for Plasmodium species determination. PMID:21767376

Analysis of false results in a series of 835 fine needle aspirates of breast lesions.

PubMed

Willis, S L; Ramzy, I

1995-01-01

To analyze cases of false diagnoses from a large series to help increase the accuracy of fine needle aspiration of palpable breast lesions. The results of FNA of 835 palpable breast lesions were analyzed to determine the reasons for false positive, false negative and false suspicious diagnoses. Of the 835 aspirates, 174 were reported as positive, 549 as negative and 66 as suspicious or atypical but not diagnostic of malignancy. Forty-six cases were considered unsatisfactory. Tissue was available for comparison in 286 cases. The cytologic diagnoses in these cases were reported as follows: positive, 125 (43.7%); suspicious, 33 (11.5%); atypical, 18 (6.2%); negative, 92 (32%); and unsatisfactory, 18 (6.2%). There was one false positive diagnosis, yielding a false positive rate of 0.8%. This lesion was a case of fibrocystic change with hyperplasia, focal fat necrosis and reparative atypia. There were 14 false negative cases, resulting in a false negative rate of 13.2%. Nearly all these cases were sampling errors and included infiltrating ductal carcinomas (9), ductal carcinomas in situ (2), infiltrating lobular carcinomas (2) and tubular carcinoma (1). Most of the suspicious and atypical lesions proved to be carcinomas (35/50). The remainder were fibroadenomas (6), fibrocystic change (4), gynecomastia (2), adenosis (2) and granulomatous mastitis (1). A positive diagnosis of malignancy by FNA is reliable in establishing the diagnosis and planning the treatment of breast cancer. The false-positive rate is very low, with only a single case reported in 835 aspirates. Most false negatives are due to sampling and not to interpretive difficulties. The category "suspicious but not diagnostic of malignancy" serves a useful purpose in management of patients with breast lumps.

Breast cancer detection risk in screening mammography after a false-positive result.

PubMed

Castells, X; Román, M; Romero, A; Blanch, J; Zubizarreta, R; Ascunce, N; Salas, D; Burón, A; Sala, M

2013-02-01

False-positives are a major concern in breast cancer screening. However, false-positives have been little evaluated as a prognostic factor for cancer detection. Our aim was to evaluate the association of false-positive results with the cancer detection risk in subsequent screening participations over a 17-year period. This is a retrospective cohort study of 762,506 women aged 45-69 years, with at least two screening participations, who underwent 2,594,146 screening mammograms from 1990 to 2006. Multilevel discrete-time hazard models were used to estimate the adjusted odds ratios (OR) of breast cancer detection in subsequent screening participations in women with false-positive results. False-positives involving a fine-needle aspiration cytology or a biopsy had a higher cancer detection risk than those involving additional imaging procedures alone (OR = 2.69; 95%CI: 2.28-3.16 and OR = 1.81; 95%CI: 1.70-1.94, respectively). The risk of cancer detection increased substantially if women with cytology or biopsy had a familial history of breast cancer (OR = 4.64; 95%CI: 3.23-6.66). Other factors associated with an increased cancer detection risk were age 65-69 years (OR = 1.84; 95%CI: 1.67-2.03), non-attendance at the previous screening invitation (OR = 1.26; 95%CI: 1.11-1.43), and having undergone a previous benign biopsy outside the screening program (OR = 1.24; 95%CI: 1.13-1.35). Women with a false-positive test have an increased risk of cancer detection in subsequent screening participations, especially those with a false-positive result involving cytology or biopsy. Understanding the factors behind this association could provide valuable information to increase the effectiveness of breast cancer screening. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Predictive factors of contamination in a blood culture with bacterial growth in an Emergency Department].

PubMed

Hernández-Bou, S; Trenchs Sainz de la Maza, V; Esquivel Ojeda, J N; Gené Giralt, A; Luaces Cubells, C

2015-06-01

The aim of this study is to identify predictive factors of bacterial contamination in positive blood cultures (BC) collected in an emergency department. A prospective, observational and analytical study was conducted on febrile children aged on to 36 months, who had no risk factors of bacterial infection, and had a BC collected in the Emergency Department between November 2011 and October 2013 in which bacterial growth was detected. The potential BC contamination predicting factors analysed were: maximum temperature, time to positivity, initial Gram stain result, white blood cell count, absolute neutrophil count, band count, and C-reactive protein (CRP). Bacteria grew in 169 BC. Thirty (17.8%) were finally considered true positives and 139 (82.2%) false positives. All potential BC contamination predicting factors analysed, except maximum temperature, showed significant differences between true positives and false positives. CRP value, time to positivity, and initial Gram stain result are the best predictors of false positives in BC. The positive predictive values of a CRP value≤30mg/L, BC time to positivity≥16h, and initial Gram stain suggestive of a contaminant in predicting a FP, are 95.1, 96.9 and 97.5%, respectively. When all 3 conditions are applied, their positive predictive value is 100%. Four (8.3%) patients with a false positive BC and discharged to home were revaluated in the Emergency Department. The majority of BC obtained in the Emergency Department that showed positive were finally considered false positives. Initial Gram stain, time to positivity, and CRP results are valuable diagnostic tests in distinguishing between true positives and false positives in BC. The early detection of false positives will allow minimising their negative consequences. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

PubMed

Tenore, Peter L

2012-01-01

In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

Diurnal rhythm and concordance between objective and subjective hot flashes: The Hilo Women’s Health Study

PubMed Central

Sievert, Lynnette L.; Reza, Angela; Mills, Phoebe; Morrison, Lynn; Rahberg, Nichole; Goodloe, Amber; Sutherland, Michael; Brown, Daniel E.

2010-01-01

Objective To test for a diurnal pattern in hot flashes in a multi-ethnic population living in a hot, humid environment. To examine rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Methods Study participants aged 45–55 were recruited from the general population of Hilo, Hawaii. Women wore a Biolog hot flash monitor, kept a diary for 24-hours, and also participated in 3-hour laboratory measures (n=199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true positive readings. Subjective hot flashes were considered the standard for computing false positive and false negative readings. True positive, false positive, and false negative readings were compared across ethnic groups by chi-square analyses. Results Frequencies of sternal, nuchal and subjective hot flashes peaked at 15:00 ± 1 hour with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true positive measures, but non-sternal electrodes picked up more false positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true positive or false positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false negative measures). Conclusions The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo was similar to results from more temperate environments. Lack of variation in sternal vs. non-sternal measures, and in true positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns. PMID:20220538

Size and Ultrasound Features Affecting Results of Ultrasound-Guided Fine-Needle Aspiration of Thyroid Nodules.

PubMed

Dong, YiJie; Mao, MinJing; Zhan, WeiWei; Zhou, JianQiao; Zhou, Wei; Yao, JieJie; Hu, YunYun; Wang, Yan; Ye, TingJun

2018-06-01

Our goal was to assess the diagnostic efficacy of ultrasound (US)-guided fine-needle aspiration (FNA) of thyroid nodules according to size and US features. A retrospective correlation was made with 1745 whole thyroidectomy and hemithyroidectomy specimens with preoperative US-guided FNA results. All cases were divided into 5 groups according to nodule size (≤5, 5.1-10, 10.1-15, 15.1-20, and >20 mm). For target nodules, static images and cine clips of conventional US and color Doppler were obtained. Ultrasound images were reviewed and evaluated by two radiologists with at least 5 years US working experience without knowing the results of pathology, and then agreement was achieved. The Bethesda category I rate was higher in nodules larger than 15 mm (P < .05). The diagnostic accuracy was best in nodules of 5 to 10 mm in diameter. The sensitivity, accuracy, PPV, and LR for negative US-guided FNA results were better in nodules with a size range of 5 to 15 mm. The specificity, negative predictive value (NPV), and LR for positive results and the Youden index rose with increasing nodule size. Seventeen false-positive and 60 false-negative results were found in this study. The false-negative rate rose with increasing nodule size. However, the false-positive rate was highest in the group containing the smallest nodules. Nodules with circumscribed margins and those that were nonsolid and nonhypoechoic and had no microcalcifications correlated with Bethesda I FNA results. Nodules with circumscribed margins and those that were nonsolid, heterogeneous, and nonhypoechoic and had increased vascularity correlated with false-negative FNA results. Borders correlated with Bethesda I false-negative and false-positive FNA results. Tiny nodules (≤5 mm) with obscure borders tended to yield false-positive FNA results. Large nodules (>20 mm) with several US features tended to yield false-negative FNA results. © 2017 by the American Institute of Ultrasound in Medicine.

Statistical approaches to account for false-positive errors in environmental DNA samples.

PubMed

Lahoz-Monfort, José J; Guillera-Arroita, Gurutzeta; Tingley, Reid

2016-05-01

Environmental DNA (eDNA) sampling is prone to both false-positive and false-negative errors. We review statistical methods to account for such errors in the analysis of eDNA data and use simulations to compare the performance of different modelling approaches. Our simulations illustrate that even low false-positive rates can produce biased estimates of occupancy and detectability. We further show that removing or classifying single PCR detections in an ad hoc manner under the suspicion that such records represent false positives, as sometimes advocated in the eDNA literature, also results in biased estimation of occupancy, detectability and false-positive rates. We advocate alternative approaches to account for false-positive errors that rely on prior information, or the collection of ancillary detection data at a subset of sites using a sampling method that is not prone to false-positive errors. We illustrate the advantages of these approaches over ad hoc classifications of detections and provide practical advice and code for fitting these models in maximum likelihood and Bayesian frameworks. Given the severe bias induced by false-negative and false-positive errors, the methods presented here should be more routinely adopted in eDNA studies. © 2015 John Wiley & Sons Ltd.

[Analysis of false-positive reaction for bacterial detection of blood samples with the automated microbial detection system BacT/ALERT 3D].

PubMed

Zhu, Li-Wei; Yang, Xue-Mei; Xu, Xiao-Qin; Xu, Jian; Lu, Huang-Jun; Yan, Li-Xing

2008-10-01

This study was aimed to analyze the results of false positive reaction in bacterial detection of blood samples with BacT/ALERT 3D system, to evaluate the specificity of this system, and to decrease the false positive reaction. Each reaction flasks in past five years were processed for bacteria isolation and identification. When the initial cultures were positive, the remaining samples and the corresponding units were recultured if still available. 11395 blood samples were detected. It is worthy of note that the incubator temperature should be stabilized, avoiding fluctuation; when the cultures were alarmed, the reaction flasks showed be kept some hours for further incubation so as to trace a sharply increasing signal to support the judgement of true bacterial growth. The results indicated that 122 samples (1.07%) wee positive at initial culture, out of them 107 samples (88.7%) were found bacterial, and 15 samples (12.3%) were found nothing. The detection curves of positive samples resulted from bacterial growth showed ascent. In conclusion, maintenance of temperature stability and avoidance of temperature fluctuation in incubator could decrease the occurrence of false-positive reaction in detection process. The reaction flasks with positive results at initial culture should be recultured, and whether existence of a sharply ascending logarilhimic growth phase in bacterial growth curve should be further detected, which are helpful to distinguish false-positive reactions from true positive, and thus increase the specificity of the BacT/ALERT system.

Skin irritation, false positives and the local lymph node assay: a guideline issue?

PubMed

Basketter, David A; Kimber, Ian

2011-10-01

Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. Copyright © 2011 Elsevier Inc. All rights reserved.

False-positive rate determination of protein target discovery using a covalent modification- and mass spectrometry-based proteomics platform.

PubMed

Strickland, Erin C; Geer, M Ariel; Hong, Jiyong; Fitzgerald, Michael C

2014-01-01

Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in complex biological mixtures. Knowing the false-positive rate of protein target discovery in proteome-wide SPROX experiments is important for the correct interpretation of results. Reported here are the results of a control SPROX experiment in which chemical denaturation data is obtained on the proteins in two samples that originated from the same yeast lysate, as would be done in a typical SPROX experiment except that one sample would be spiked with the test ligand. False-positive rates of 1.2-2.2% and <0.8% are calculated for SPROX experiments using Q-TOF and Orbitrap mass spectrometer systems, respectively. Our results indicate that the false-positive rate is largely determined by random errors associated with the mass spectral analysis of the isobaric mass tag (e.g., iTRAQ®) reporter ions used for peptide quantitation. Our results also suggest that technical replicates can be used to effectively eliminate such false positives that result from this random error, as is demonstrated in a SPROX experiment to identify yeast protein targets of the drug, manassantin A. The impact of ion purity in the tandem mass spectral analyses and of background oxidation on the false-positive rate of protein target discovery using SPROX is also discussed.

Verification of false-positive blood culture results generated by the BACTEC 9000 series by eubacterial 16S rDNA and panfungal 18S rDNA directed polymerase chain reaction (PCR).

PubMed

Daxboeck, Florian; Dornbusch, Hans Jürgen; Krause, Robert; Assadian, Ojan; Wenisch, Christoph

2004-01-01

A small but significant proportion of blood cultures processed by the BACTEC 9000 series systems is signaled positive, while subsequent Gram's stain and culture on solid media yield no pathogens. In this study, 15 "false-positive" vials (7 aerobes, 8 anaerobes) from 15 patients were investigated for the presence of bacteria and fungi by eubacterial 16S rDNA and panfungal 18S rDNA amplification, respectively. All samples turned out negative by both methods. Most patients (7) had neutropenia, which does not support the theory that high leukocyte counts enhance the generation of false-positive results. In conclusion, the results of this study indicate that false-negative results generated by the BACTEC 9000 series are inherent to the automated detection and not due to the growth of fastidious organisms.

Quality control in the diagnosis of Trichuris trichiura and Ascaris lumbricoides using the Kato-Katz technique: experience from three randomised controlled trials.

PubMed

Speich, Benjamin; Ali, Said M; Ame, Shaali M; Albonico, Marco; Utzinger, Jürg; Keiser, Jennifer

2015-02-05

An accurate diagnosis of soil-transmitted helminthiasis is important for individual patient management, for drug efficacy evaluation and for monitoring control programmes. The Kato-Katz technique is the most widely used method detecting soil-transmitted helminth eggs in faecal samples. However, detailed analyses of quality control, including false-positive and faecal egg count (FEC) estimates, have received little attention. Over a 3-year period, within the frame of a series of randomised controlled trials conducted in Pemba, United Republic of Tanzania, 10% of randomly selected Kato-Katz thick smears were re-read for Trichuris trichiura and Ascaris lumbricoides eggs. In case of discordant result (i.e. positive versus negative) the slides were re-examined a third time. A result was assumed to be false-positive or false-negative if the result from the initial reading did not agree with the quality control as well as the third reading. We also evaluated the general agreement in FECs between the first and second reading, according to internal and World Health Organization (WHO) guidelines. From the 1,445 Kato-Katz thick smears subjected to quality control, 1,181 (81.7%) were positive for T. trichiura and 290 (20.1%) were positive for A. lumbricoides. During quality control, very low rates of false-positive results were observed; 0.35% (n = 5) for T. trichiura and 0.28% (n = 4) for A. lumbricoides. False-negative readings of Kato-Katz thick smears were obtained in 28 (1.94%) and 6 (0.42%) instances for T. trichiura and A. lumbricoides, respectively. A high frequency of discordant results in FECs was observed (i.e. 10.0-23.9% for T. trichiura, and 9.0-11.4% for A. lumbricoides). Our analyses show that the rate of false-positive diagnoses of soil-transmitted helminths is low. As the probability of false-positive results increases after examination of multiple stool samples from a single individual, the potential influence of false-positive results on epidemiological studies and anthelminthic drug efficacy studies should be determined. Existing WHO guidelines for quality control might be overambitious and might have to be revised, specifically with regard to handling disagreements in FECs.

Factors associated with a second deferral among donors eligible for re-entry after a false-positive screening test for syphilis, HCV, HBV and HIV.

PubMed

Grégoire, Y; Germain, M; Delage, G

2018-05-01

Since 25 May 2010, all donors at our blood centre who tested false-positive for HIV, HBV, HCV or syphilis are eligible for re-entry after further testing. Donors who have a second false-positive screening test, either during qualification for or after re-entry, are deferred for life. This study reports on factors associated with the occurrence of such deferrals. Rates of second false-positive results were compared by year of deferral, transmissible disease marker, gender, age, donor status (new or repeat) and testing platform (same or different) both at qualification for re-entry and afterwards. Chi-square tests were used to compare proportions. Cox regression was used for multivariate analyses. Participation rates in the re-entry programme were 42·1%: 25·6% failed to qualify for re-entry [different platform: 2·7%; same platform: 42·9% (P < 0·0001)]. After re-entry, rates of deferral for second false-positive results were 8·4% after 3 years [different platform: 1·8%; same platform: 21·4% (P < 0·0001)]. Deferral rates were higher for HIV and HCV than for HBV at qualification when tested on the same platform. The risk, when analysed by multivariate analyses, of a second deferral for a false-positive result, both at qualification and 3 years after re-entry, was lower for donors deferred on a different platform; this risk was higher for HIV, HCV and syphilis than for HBV and for new donors if tested on the same platform. Re-entry is more often successful when donors are tested on a testing platform different from the one on which they obtained their first false-positive result. © 2018 International Society of Blood Transfusion.

Risk of Breast Cancer in Women with False-Positive Results according to Mammographic Features.

PubMed

Castells, Xavier; Torá-Rocamora, Isabel; Posso, Margarita; Román, Marta; Vernet-Tomas, Maria; Rodríguez-Arana, Ana; Domingo, Laia; Vidal, Carmen; Baré, Marisa; Ferrer, Joana; Quintana, María Jesús; Sánchez, Mar; Natal, Carmen; Espinàs, Josep A; Saladié, Francina; Sala, María

2016-08-01

Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article.

A False Positive Dengue Fever Rapid Diagnostic Test Result in a Case of Acute Parvovirus B19 Infection.

PubMed

Izumida, Toshihide; Sakata, Hidenao; Nakamura, Masahiko; Hayashibara, Yumiko; Inasaki, Noriko; Inahata, Ryo; Hasegawa, Sumiyo; Takizawa, Takenori; Kaya, Hiroyasu

2016-01-01

An outbreak of dengue fever occurred in Japan in August 2014. We herein report the case of a 63-year-old man who presented with a persistent fever in September 2014. Acute parvovirus B19 infection led to a false positive finding of dengue fever on a rapid diagnostic test (Panbio Dengue Duo Cassette(TM)). To the best of our knowledge, there are no previous reports of a false positive result for dengue IgM with the dengue rapid diagnostic test. We believe that epidemiological information on the prevalence of parvovirus B19 is useful for guiding the interpretation of a positive result with the dengue rapid diagnostic test.

Effects of depressive disorder on false memory for emotional information.

PubMed

Yeh, Zai-Ting; Hua, Mau-Sun

2009-01-01

This study explored with a false memory paradigm whether (1) depressed patients revealed more false memories and (2) whether more negative false than positive false recognition existed in subjects with depressive disorders. Thirty-two patients suffering from a major depressive episode (DSM-IV criteria), and 30 age- and education-matched normal control subjects participated in this study. After the presentation of a list of positive, negative, and neutral association items in the learning phase, subjects were asked to give a yes/no response in the recognition phase. They were also asked to rate 81 recognition items with emotional valence scores. The results revealed more negative false memories in the clinical depression group than in the normal control group; however, we did not find more negative false memories than positive ones in patients. When compared with the normal group, a more conservative response criterion for positive items was evident in patient groups. It was also found that when compared with the normal group, the subjects in the depression group perceived the positive items as less positive. On the basis of present results, it is suggested that depressed subjects judged the emotional information with criteria different from normal individuals, and patients' emotional memory intensity is attenuated by their mood.

Assessment of potential false positives via orbitrap-based untargeted lipidomics from rat tissues.

PubMed

Xu, Lina; Wang, Xueying; Jiao, Yupei; Liu, Xiaohui

2018-02-01

Untargeted lipidomics is increasingly popular due to the broad coverage of lipid species. Data dependent MS/MS acquisition is commonly used in order to acquire sufficient information for confident lipid assignment. However, although lipids are identified based on MS/MS confirmation, a number of false positives are still observed. Here, we discuss several causes of introducing lipid false identifications in untargeted analysis. Phosphotidylcholines and cholesteryl esters generate in-source fragmentation to produce dimethylated phosphotidylethanolamine and free cholesterol. Dimerization of fatty acid results in false identification of fatty acid ester of hydroxyl fatty acid. Realizing these false positives is able to improve confidence of results acquired from untargeted analysis. Besides, thresholds are established for lipids identified using LipidSearch v4.1.16 software to reduce unreliable results. Copyright © 2017 Elsevier B.V. All rights reserved.

Prehospital Acute ST-Elevation Myocardial Infarction Identification in San Diego: A Retrospective Analysis of the Effect of a New Software Algorithm.

PubMed

Coffey, Christanne; Serra, John; Goebel, Mat; Espinoza, Sarah; Castillo, Edward; Dunford, James

2018-05-03

A significant increase in false positive ST-elevation myocardial infarction (STEMI) electrocardiogram interpretations was noted after replacement of all of the City of San Diego's 110 monitor-defibrillator units with a new brand. These concerns were brought to the manufacturer and a revised interpretive algorithm was implemented. This study evaluated the effects of a revised interpretation algorithm to identify STEMI when used by San Diego paramedics. Data were reviewed 6 months before and 6 months after the introduction of a revised interpretation algorithm. True-positive and false-positive interpretations were identified. Factors contributing to an incorrect interpretation were assessed and patient demographics were collected. A total of 372 (234 preimplementation, 138 postimplementation) cases met inclusion criteria. There was a significant reduction in false positive STEMI (150 preimplementation, 40 postimplementation; p < 0.001) after implementation. The most common factors resulting in false positive before implementation were right bundle branch block, left bundle branch block, and atrial fibrillation. The new algorithm corrected for these misinterpretations with most postimplementation false positives attributed to benign early repolarization and poor data quality. Subsequent follow-up at 10 months showed maintenance of the observed reduction in false positives. This study shows that introducing a revised 12-lead interpretive algorithm resulted in a significant reduction in the number of false positive STEMI electrocardiogram interpretations in a large urban emergency medical services system. Rigorous testing and standardization of new interpretative software is recommended before introduction into a clinical setting to prevent issues resulting from inappropriate cardiac catheterization laboratory activations. Copyright © 2018 Elsevier Inc. All rights reserved.

The Diagnostic Validity of the 13C-Urea Breath Test in the Gastrectomized Patients: Single Tertiary Center Retrospective Cohort Study

PubMed Central

Kwon, Yong Hwan; Kim, Nayoung; Lee, Ju Yup; Choi, Yoon Jin; Yoon, Kichul; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho

2014-01-01

Background: This study was conducted to evaluate the diagnostic validity of the 13C-urea breath test (13C-UBT) in the remnant stomach after partial gastrectomy for gastric cancer. Methods: The 13C-UBT results after Helicobacter pylori eradication therapy was compared with the results of endoscopic biopsy-based methods in the patients who have received partial gastrectomy for the gastric cancer. Results: Among the gastrectomized patients who showed the positive 13C-UBT results (≥ 2.5‰, n = 47) and negative 13C-UBT results (< 2.5‰, n = 114) after H. pylori eradication, 26 patients (16.1%) and 4 patients (2.5%) were found to show false positive and false negative results based on biopsy-based methods, respectively. The sensitivity, specificity, false positive rate, and false negative rate for the cut-off value of 2.5‰ were 84.0%, 80.9%, 19.1%, and 16.0%, respectively. The positive and negative predictive values were 44.7% and 96.5%, respectively. In the multivariate analysis, two or more H. pylori eradication therapies (odds ratio = 3.248, 95% confidence interval= 1.088–9.695, P = 0.035) was associated with a false positive result of the 13C-UBT. Conclusions: After partial gastrectomy, a discordant result was shown in the positive 13C-UBT results compared to the endoscopic biopsy methods for confirming the H. pylori status after eradication. Additional endoscopic biopsy-based H. pylori tests would be helpful to avoid unnecessary treatment for H. pylori eradication in these cases. PMID:25574466

The Illusion of the Positive: The impact of natural and induced mood on older adults’ false recall

PubMed Central

Emery, Lisa; Hess, Thomas M.; Elliot, Tonya

2012-01-01

Recent research suggests that affective and motivational processes can influence age differences in memory. In the current study, we examine the impact of both natural and induced mood state on age differences in false recall. Older and younger adults performed a version of the Deese-Roediger-McDermott (DRM; Roediger & McDermott, 1995) false memory paradigm in either their natural mood state or after a positive or negative mood induction. Results indicated that, after accounting for age differences in basic cognitive function, age-related differences in positive mood during the testing session were related to increased false recall in older adults. Inducing older adults into a positive mood also exacerbated age differences in false memory. In contrast, veridical recall did not appear to be systematically influenced by mood. Together, these results suggest that positive mood states can impact older adults’ information processing and potentially increase underlying cognitive age differences. PMID:22292431

The illusion of the positive: the impact of natural and induced mood on older adults' false recall.

PubMed

Emery, Lisa; Hess, Thomas M; Elliot, Tonya

2012-11-01

Recent research suggests that affective and motivational processes can influence age differences in memory. In the current study, we examine the impact of both natural and induced mood state on age differences in false recall. Older and younger adults performed a version of the Deese-Roediger-McDermott (DRM; Roediger & McDermott, 1995 , Journal of Experimental Psychology: Learning, Memory, and Cognition, 21, 803) false memory paradigm in either their natural mood state or after a positive or negative mood induction. Results indicated that, after accounting for age differences in basic cognitive function, age-related differences in positive mood during the testing session were related to increased false recall in older adults. Inducing older adults into a positive mood also exacerbated age differences in false memory. In contrast, veridical recall did not appear to be systematically influenced by mood. Together, these results suggest that positive mood states can impact older adults' information processing and potentially increase underlying cognitive age differences.

Diurnal rhythm and concordance between objective and subjective hot flashes: the Hilo Women's Health Study.

PubMed

Sievert, Lynnette L; Reza, Angela; Mills, Phoebe; Morrison, Lynn; Rahberg, Nichole; Goodloe, Amber; Sutherland, Michael; Brown, Daniel E

2010-01-01

The aims of this study were to test for a diurnal pattern in hot flashes in a multiethnic population living in a hot, humid environment and to examine the rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Study participants aged 45 to 55 years were recruited from the general population of Hilo, HI. Women wore a Biolog hot flash monitor (UFI, Morro Bay, CA), kept a diary for 24 hours, and also participated in 3-hour laboratory measures (n = 199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true-positive readings. Subjective hot flashes were considered the standard for computing false-positive and false-negative readings. True-positive, false-positive, and false-negative readings were compared across ethnic groups by chi analyses. Frequencies of sternal, nuchal, and subjective hot flashes peaked at 1500 +/- 1 hours with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true-positive measures, but nonsternal electrodes picked up more false-positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true-positive or false-positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false-negative measures). The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo were similar to results from more temperate environments. Lack of variation in sternal versus nonsternal measures and in true-positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns.

Generalized site occupancy models allowing for false positive and false negative errors

USGS Publications Warehouse

Royle, J. Andrew; Link, W.A.

2006-01-01

Site occupancy models have been developed that allow for imperfect species detection or ?false negative? observations. Such models have become widely adopted in surveys of many taxa. The most fundamental assumption underlying these models is that ?false positive? errors are not possible. That is, one cannot detect a species where it does not occur. However, such errors are possible in many sampling situations for a number of reasons, and even low false positive error rates can induce extreme bias in estimates of site occupancy when they are not accounted for. In this paper, we develop a model for site occupancy that allows for both false negative and false positive error rates. This model can be represented as a two-component finite mixture model and can be easily fitted using freely available software. We provide an analysis of avian survey data using the proposed model and present results of a brief simulation study evaluating the performance of the maximum-likelihood estimator and the naive estimator in the presence of false positive errors.

False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review.

PubMed

Imberger, Georgina; Thorlund, Kristian; Gluud, Christian; Wetterslev, Jørn

2016-08-12

Many published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered meta-analyses. We screened The Cochrane Database of Systematic Reviews and selected 100 meta-analyses with a binary outcome, a negative result and sufficient power. We defined a negative result as one where the 95% CI for the effect included 1.00, a positive result as one where the 95% CI did not include 1.00, and sufficient power as the required information size for 80% power, 5% type 1 error, relative risk reduction of 10% or number needed to treat of 100, and control event proportion and heterogeneity taken from the included studies. We re-conducted the meta-analyses, using conventional cumulative techniques, to measure how many false positives would have occurred if these meta-analyses had been updated after each new trial. For each false positive, we performed TSA, using three different approaches. We screened 4736 systematic reviews to find 100 meta-analyses that fulfilled our inclusion criteria. Using conventional cumulative meta-analysis, false positives were present in seven of the meta-analyses (7%, 95% CI 3% to 14%), occurring more than once in three. The total number of false positives was 14 and TSA prevented 13 of these (93%, 95% CI 68% to 98%). In a post hoc analysis, we found that Cochrane meta-analyses that are negative are 1.67 times more likely to be updated (95% CI 0.92 to 2.68) than those that are positive. We found false positives in 7% (95% CI 3% to 14%) of the included meta-analyses. Owing to limitations of external validity and to the decreased likelihood of updating positive meta-analyses, the true proportion of false positives in meta-analysis is probably higher. TSA prevented 93% of the false positives (95% CI 68% to 98%). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Kepler Certified False Positive Table

NASA Technical Reports Server (NTRS)

Bryson, Stephen T.; Batalha, Natalie Marie; Colon, Knicole Dawn; Coughlin, Jeffrey Langer; Haas, Michael R.; Henze, Chris; Huber, Daniel; Morton, Tim; Rowe, Jason Frank; Mullally, Susan Elizabeth;

Uncertainty in biological monitoring: a framework for data collection and analysis to account for multiple sources of sampling bias

USGS Publications Warehouse

Ruiz-Gutierrez, Viviana; Hooten, Melvin B.; Campbell Grant, Evan H.

2016-01-01

Biological monitoring programmes are increasingly relying upon large volumes of citizen-science data to improve the scope and spatial coverage of information, challenging the scientific community to develop design and model-based approaches to improve inference.Recent statistical models in ecology have been developed to accommodate false-negative errors, although current work points to false-positive errors as equally important sources of bias. This is of particular concern for the success of any monitoring programme given that rates as small as 3% could lead to the overestimation of the occurrence of rare events by as much as 50%, and even small false-positive rates can severely bias estimates of occurrence dynamics.We present an integrated, computationally efficient Bayesian hierarchical model to correct for false-positive and false-negative errors in detection/non-detection data. Our model combines independent, auxiliary data sources with field observations to improve the estimation of false-positive rates, when a subset of field observations cannot be validated a posteriori or assumed as perfect. We evaluated the performance of the model across a range of occurrence rates, false-positive and false-negative errors, and quantity of auxiliary data.The model performed well under all simulated scenarios, and we were able to identify critical auxiliary data characteristics which resulted in improved inference. We applied our false-positive model to a large-scale, citizen-science monitoring programme for anurans in the north-eastern United States, using auxiliary data from an experiment designed to estimate false-positive error rates. Not correcting for false-positive rates resulted in biased estimates of occupancy in 4 of the 10 anuran species we analysed, leading to an overestimation of the average number of occupied survey routes by as much as 70%.The framework we present for data collection and analysis is able to efficiently provide reliable inference for occurrence patterns using data from a citizen-science monitoring programme. However, our approach is applicable to data generated by any type of research and monitoring programme, independent of skill level or scale, when effort is placed on obtaining auxiliary information on false-positive rates.

False-positive cryptococcal antigen latex agglutination caused by disinfectants and soaps.

PubMed Central

Blevins, L B; Fenn, J; Segal, H; Newcomb-Gayman, P; Carroll, K C

1995-01-01

Five disinfectants or soaps were tested to determine if any could be responsible for false-positive results obtained with the Latex-Crypto Antigen Detection System kit (Immuno-Mycologics, Inc., Norman, Okla.). Three disinfectants or soaps (Derma soap, 7X, and Bacdown) produced false-positive agglutination after repeated washing of ring slides during testing of a known negative cerebrospinal fluid specimen. PMID:7650214

Methods for threshold determination in multiplexed assays

DOEpatents

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

2014-06-24

Methods for determination of threshold values of signatures comprised in an assay are described. Each signature enables detection of a target. The methods determine a probability density function of negative samples and a corresponding false positive rate curve. A false positive criterion is established and a threshold for that signature is determined as a point at which the false positive rate curve intersects the false positive criterion. A method for quantitative analysis and interpretation of assay results together with a method for determination of a desired limit of detection of a signature in an assay are also described.

False-positive results in pharmacoepidemiology and pharmacovigilance.

PubMed

Bezin, Julien; Bosco-Levy, Pauline; Pariente, Antoine

2017-09-01

False-positive constitute an important issue in scientific research. In the domain of drug evaluation, it affects all phases of drug development and assessment, from the very early preclinical studies to the late post-marketing evaluations. The core concern associated with this false-positive is the lack of replicability of the results. Aside from fraud or misconducts, false-positive is often envisioned from the statistical angle, which considers them as a price to pay for type I error in statistical testing, and its inflation in the context of multiple testing. If envisioning this problematic in the context of pharmacoepidemiology and pharmacovigilance however, that both evaluate drugs in an observational settings, information brought by statistical testing and the significance of such should only be considered as additional to the estimates provided and their confidence interval, in a context where differences have to be a clinically meaningful upon everything, and the results appear robust to the biases likely to have affected the studies. In the following article, we consequently illustrate these biases and their consequences in generating false-positive results, through studies and associations between drug use and health outcomes that have been widely disputed. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Silastic injection for vocal fold medialization resulting in a false-positive finding on F18 FDG-PET/CT.

PubMed

Mahfouz, Ayman; Naji, Meeran; Mok, Wing Yan; Taghi, Ali S; Win, Zarni

2015-09-01

A false-positive uptake of F18-fluorodeoxyglucose (FDG) on positron-emission tomography/computed tomography (PET/CT) can result in confusion and misinterpretation of scans. Such uptakes have been previously described after injection of polytetrafluoroethylene (Teflon) into the vocal folds. Similarly, vocal fold injection of silicone elastomer (Silastic) can result not only in a false-positive FDG uptake on PET/CT, but also in chronic inflammation. We report a case of increased FDG uptake in a vocal fold after Silastic injection that was misinterpreted as a malignancy in a 70-year-old woman who had metastatic carcinoma of the stomach.

The Diagnostic Validity of Citric Acid-Free, High Dose (13)C-Urea Breath Test After Helicobacter pylori Eradication in Korea.

PubMed

Kwon, Yong Hwan; Kim, Nayoung; Lee, Ju Yup; Choi, Yoon Jin; Yoon, Kichul; Hwang, Jae Jin; Lee, Hyun Joo; Lee, AeRa; Jeong, Yeon Sang; Oh, Sooyeon; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho

2015-06-01

The (13)C-urea breath test ((13)C-UBT) is a noninvasive method for diagnosing Helicobacter pylori (H. pylori) infection. The aims of this study were to evaluate the diagnostic validity of the (13)C-UBT cutoff value and to identify influencing clinical factors responsible for aberrant results. (13)C-UBT (UBiTkit; Otsuka Pharmaceutical, cutoff value: 2.5‰) results in the range 2.0‰ to 10.0‰ after H. pylori eradication therapy were compared with the results of endoscopic biopsy results of the antrum and body. Factors considered to affect test results adversely were analyzed. Among patients with a positive (13)C-UBT result (2.5‰ to 10.0‰, n = 223) or a negative (13)C-UBT result (2.0‰ to < 2.5‰, n = 66) after H. pylori eradication, 73 patients (34.0%) were false positive, and one (1.5%) was false negative as determined by endoscopic biopsy. The sensitivity, specificity, false-positive rate, and false-negative rate for a cutoff value of 2.5‰ were 99.3%, 47.1%, 52.9%, and 0.7%, respectively, and positive and negative predictive values of the (13)C-UBT were 67.3% and 98.5%, respectively. Multivariate analysis showed that a history of two or more previous H. pylori eradication therapies (OR = 2.455, 95%CI = 1.299-4.641) and moderate to severe gastric intestinal metaplasia (OR = 3.359, 95%CI = 1.572-7.178) were associated with a false-positive (13)C-UBT result. The (13)C-UBT cutoff value currently used has poor specificity for confirming H. pylori status after eradication, and this lack of specificity is exacerbated in patients that have undergone multiple prior eradication therapies and in patients with moderate to severe gastric intestinal metaplasia. In addition, the citric-free (13)C-UBT would increase a false-positive (13)C-UBT result. © 2015 John Wiley & Sons Ltd.

Psychological distress in U.S. women who have experienced false-positive mammograms.

PubMed

Jatoi, Ismail; Zhu, Kangmin; Shah, Mona; Lawrence, William

2006-11-01

In the United States, approximately 10.7% of all screening mammograms lead to a false-positive result, but the overall impact of false-positives on psychological well-being is poorly understood. Data were analyzed from the 2000 U.S. National Health Interview Survey (NHIS), the most recent national survey that included a cancer control module. Study subjects were 9,755 women who ever had a mammogram, of which 1,450 had experienced a false-positive result. Psychological distress was assessed using the validated K6 questionnaire and logistic regression was used to discern any association with previous false-positive mammograms. In a multivariate analysis, women who had indicated a previous false-positive mammogram were more likely to report feeling sad (OR = 1.18, 95% CI, 1.03-1.35), restless (OR = 1.23, 95% CI, 1.08-1.40), worthless (OR = 1.27, 95% CI, 1.04-1.54), and finding that everything was an effort (OR = 1.27, 95% CI, 1.10-1.47). These women were also more likely to have seen a mental health professional in the 12 months preceding the survey (OR = 1.28, 95% CI, 1.03-1.58) and had a higher composite score on all items of the K6 scale (P < 0.0001), a reflection of increased psychological distress. Analyses by age and race revealed that, among women who had experienced false-positives, younger women were more likely to feel that everything was an effort, and blacks were more likely to feel restless. In a random sampling of the U.S. population, women who had previously experienced false-positive mammograms were more likely to report symptoms of anxiety and depression.

Affective valence influences participant's susceptibility to false memories and illusory recollection.

PubMed

Dehon, Hedwige; Larøi, Frank; Van der Linden, Martial

2010-10-01

This study examined the influence of emotional valence on the production of DRM false memories (Roediger & McDermott, 1995). Participants were presented with neutral, positive, or negative DRM lists for a later recognition (Experiment 1) or recall (Experiment 2) test. In both experiments, confidence and recollective experience (i.e., "Remember-Know" judgments; Tulving, 1985) were also assessed. Results consistently showed that, compared with neutral lists, affective lists induced more false recognition and recall of nonpresented critical lures. Moreover, although confidence ratings did not differ between the false remembering from the different kinds of lists, "Remember" responses were more often associated with negative than positive and neutral false remembering of the critical lures. In contrast, positive false remembering of the critical lures was more often associated with "Know" responses. These results are discussed in light of the Paradoxical Negative Emotion (PNE) hypothesis (Porter, Taylor, & ten Bricke, 2008). (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Cumulative Incidence of False-Positive Results in Repeated, Multimodal Cancer Screening

PubMed Central

Croswell, Jennifer Miller; Kramer, Barnett S.; Kreimer, Aimee R.; Prorok, Phil C.; Xu, Jian-Lun; Baker, Stuart G.; Fagerstrom, Richard; Riley, Thomas L.; Clapp, Jonathan D.; Berg, Christine D.; Gohagan, John K.; Andriole, Gerald L.; Chia, David; Church, Timothy R.; Crawford, E. David; Fouad, Mona N.; Gelmann, Edward P.; Lamerato, Lois; Reding, Douglas J.; Schoen, Robert E.

2009-01-01

PURPOSE Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program. METHODS Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period. RESULTS After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%–61.0%) for men, and 48.8% (95% CI, 48.1%–49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%–29.3%) for men and 22.1% (95% CI, 21.4%–22.7%) for women. CONCLUSIONS For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening. PMID:19433838

Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy?

PubMed

Mennuti, Michael T; Cherry, Athena M; Morrissette, Jennifer J D; Dugoff, Lorraine

2013-11-01

Testing cell-free DNA (cfDNA) in maternal blood samples has been shown to have very high sensitivity for the detection of fetal aneuploidy with very low false-positive results in high-risk patients who undergo invasive prenatal diagnosis. Recent observation in clinical practice of several cases of positive cfDNA tests for trisomy 18 and trisomy 13, which were not confirmed by cytogenetic testing of the pregnancy, may reflect a limitation of the positive predictive value of this quantitative testing, particularly when it is used to detect rare aneuploidies. Analysis of a larger number of false-positive cases is needed to evaluate whether these observations reflect the positive predictive value that should be expected. Infrequently, mechanisms (such as low percentage mosaicism or confined placental mosaicism) might also lead to positive cfDNA testing that is not concordant with standard prenatal cytogenetic diagnosis. The need to explore these and other possible causes of false-positive cfDNA testing is exemplified by 2 of these cases. Additional evaluation of cfDNA testing in clinical practice and a mechanism for the systematic reporting of false-positive and false-negative cases will be important before this test is offered widely to the general population of low-risk obstetric patients. In the meantime, incorporating information about the positive predictive value in pretest counseling and in clinical laboratory reports is recommended. These experiences reinforce the importance of offering invasive testing to confirm cfDNA results before parental decision-making. Copyright © 2013 Mosby, Inc. All rights reserved.

Categorizing mistaken false positives in regulation of human and environmental health.

PubMed

Hansen, Steffen Foss; Krayer von Krauss, Martin P; Tickner, Joel A

2007-02-01

One of the concerns often voiced by critics of the precautionary principle is that a widespread regulatory application of the principle will lead to a large number of false positives (i.e., over-regulation of minor risks and regulation of nonexisting risks). The present article proposes a general definition of a regulatory false positive, and seeks to identify case studies that can be considered authentic regulatory false positives. Through a comprehensive review of the science policy literature for proclaimed false positives and interviews with authorities on regulation and the precautionary principle we identified 88 cases. Following a detailed analysis of these cases, we found that few of the cases mentioned in the literature can be considered to be authentic false positives. As a result, we have developed a number of different categories for these cases of "mistaken false positives," including: real risks, "The jury is still out," nonregulated proclaimed risks, "Too narrow a definition of risk," and risk-risk tradeoffs. These categories are defined and examples are presented in order to illustrate their key characteristics. On the basis of our analysis, we were able to identify only four cases that could be defined as regulatory false positives in the light of today's knowledge and recognized uncertainty: the Southern Corn Leaf Blight, the Swine Flu, Saccharin, and Food Irradiation in relation to consumer health. We conclude that concerns about false positives do not represent a reasonable argument against future application of the precautionary principle.

Evaluation of MTANNs for eliminating false-positive with different computer aided pulmonary nodules detection software.

PubMed

Shi, Zhenghao; Ma, Jiejue; Feng, Yaning; He, Lifeng; Suzuki, Kenji

2015-11-01

MTANN (Massive Training Artificial Neural Network) is a promising tool, which applied to eliminate false-positive for thoracic CT in recent years. In order to evaluate whether this method is feasible to eliminate false-positive of different CAD schemes, especially, when it is applied to commercial CAD software, this paper evaluate the performance of the method for eliminating false-positives produced by three different versions of commercial CAD software for lung nodules detection in chest radiographs. Experimental results demonstrate that the approach is useful in reducing FPs for different computer aided lung nodules detection software in chest radiographs.

Oxybuprocaine induces a false-positive response in immunochromatographic SAS Adeno Test.

PubMed

Hoshino, Takeshi; Takanashi, Taiji; Okada, Morio; Uchida, Sunao

2002-04-01

To investigate whether a solution of oxybuprocaine hydrochloride, 0.4%, results in a false-positive response in an immunochromatographic SAS Adeno Test. Experimental study. Physiologic saline and 2% lidocaine. Each chemical (100 microl) was diluted in a transport medium. Five drops (200 microl) of the resultant solution were dispensed into the round sample well of a test device. Fifteen samples were tested in each group. Ten minutes after the start of the test, a colored line in the "specimen" portion of the test membrane was visually read as positive or negative by a masked technician. No positive reaction was observed in the control groups (physiologic saline and lidocaine). A false-positive reaction was observed in six samples (33.3%) in the oxybuprocaine group. The positive rate was significantly higher in the oxybuprocaine group compared with those in control groups (P = 0.0062, Fisher's extract probability test). Oxybuprocaine may induce a false-positive reaction in an immunochromatographic SAS Adeno Test. We recommend the use of lidocaine, instead of oxybuprocaine, for local anesthesia in taking eye swabs from patients with suspected adenovirus infection.

Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results.

PubMed

van Turenhout, Sietze T; Oort, Frank A; Terhaar sive Droste, Jochim S; Coupé, Veerle M H; van der Hulst, Rene W; Loffeld, Ruud J; Scholten, Pieter; Depla, Annekatrien C T M; Bouman, Anneke A; Meijer, Gerrit A; Mulder, Chris J J; van Rossum, Leo G M

2012-07-01

Colorectal cancer screening by fecal immunochemical tests (FITs) is hampered by frequent false-positive (FP) results and thereby the risk of complications and strain on colonoscopy capacity. Hemorrhoids might be a plausible cause of FP results. To determine the contribution of hemorrhoids to the frequency of FP FIT results. Retrospective analysis from prospective cohort study. Five large teaching hospitals, including 1 academic hospital. All subjects scheduled for elective colonoscopy. FIT before bowel preparation. Frequency of FP FIT results in subjects with hemorrhoids as the only relevant abnormality compared with FP FIT results in subjects with no relevant abnormalities. Logistic regression analysis to determine colonic abnormalities influencing FP results. In 2855 patients, 434 had positive FIT results: 213 had advanced neoplasia and 221 had FP results. In 9 individuals (4.1%; 95% CI, 1.4-6.8) with an FP FIT result, hemorrhoids were the only abnormality. In univariate unadjusted analysis, subjects with hemorrhoids as the only abnormality did not have more positive results (9/134; 6.7%) compared with subjects without any abnormalities (43/886; 4.9%; P = .396). Logistic regression identified hemorrhoids, nonadvanced polyps, and a group of miscellaneous abnormalities, all significantly influencing false positivity. Of 1000 subjects with hemorrhoids, 67 would have FP results, of whom 18 would have FP results because of hemorrhoids only. Potential underreporting of hemorrhoids; high-risk individuals. Hemorrhoids in individuals participating in colorectal cancer screening will probably not lead to a substantial number of false-positive test results. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Study of false positives in 5-ALA induced photodynamic diagnosis of bladder carcinoma

NASA Astrophysics Data System (ADS)

Draga, Ronald O. P.; Grimbergen, Matthijs C. M.; Kok, Esther T.; Jonges, Trudy G. N.; Bosch, J. L. H. R.

2009-02-01

Photodynamic diagnosis (PDD) is a technique that enhances the detection of tumors during cystoscopy using a photosensitizer which accumulates primarily in cancerous cells and will fluoresce when illuminated by violetblue light. A disadvantage of PDD is the relatively low specificity. In this retrospective study we aimed to identify predictors for false positive findings in PDD. Factors such as gender, age, recent transurethral resection of bladder tumors (TURBT), previous intravesical therapy (IVT) and urinary tract infections (UTIs) were examined for association with the false positive rates in a multivariate analysis. Data of 366 procedures and 200 patients were collected. Patients were instilled with 5-aminolevulinic acid (5-ALA) intravesically and 1253 biopsies were taken from tumors and suspicious lesions. Female gender and TURBT are independent predictors of false positives in PDD. However, previous intravesical therapy with Bacille Calmette-Guérin is also an important predictor of false positives. The false positive rate decreases during the first 9-12 weeks after the latest TURBT and the latest intravesical chemotherapy. Although shortly after IVT and TURBT false positives increase, PDD improves the diagnostic sensitivity and results in more adequate treatment strategies in a significant number of patients.

Evaluation of HIV testing algorithms in Ethiopia: the role of the tie-breaker algorithm and weakly reacting test lines in contributing to a high rate of false positive HIV diagnoses.

PubMed

Shanks, Leslie; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Pirou, Erwan; Ritmeijer, Koert; Masiga, Johnson; Abebe, Almaz

2015-02-03

In Ethiopia a tiebreaker algorithm using 3 rapid diagnostic tests (RDTs) in series is used to diagnose HIV. Discordant results between the first 2 RDTs are resolved by a third 'tiebreaker' RDT. Médecins Sans Frontières uses an alternate serial algorithm of 2 RDTs followed by a confirmation test for all double positive RDT results. The primary objective was to compare the performance of the tiebreaker algorithm with a serial algorithm, and to evaluate the addition of a confirmation test to both algorithms. A secondary objective looked at the positive predictive value (PPV) of weakly reactive test lines. The study was conducted in two HIV testing sites in Ethiopia. Study participants were recruited sequentially until 200 positive samples were reached. Each sample was re-tested in the laboratory on the 3 RDTs and on a simple to use confirmation test, the Orgenics Immunocomb Combfirm® (OIC). The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. 2620 subjects were included with a HIV prevalence of 7.7%. Each of the 3 RDTs had an individual specificity of at least 99%. The serial algorithm with 2 RDTs had a single false positive result (1 out of 204) to give a PPV of 99.5% (95% CI 97.3%-100%). The tiebreaker algorithm resulted in 16 false positive results (PPV 92.7%, 95% CI: 88.4%-95.8%). Adding the OIC confirmation test to either algorithm eliminated the false positives. All the false positives had at least one weakly reactive test line in the algorithm. The PPV of weakly reacting RDTs was significantly lower than those with strongly positive test lines. The risk of false positive HIV diagnosis in a tiebreaker algorithm is significant. We recommend abandoning the tie-breaker algorithm in favour of WHO recommended serial or parallel algorithms, interpreting weakly reactive test lines as indeterminate results requiring further testing except in the setting of blood transfusion, and most importantly, adding a confirmation test to the RDT algorithm. It is now time to focus research efforts on how best to translate this knowledge into practice at the field level. Clinical Trial registration #: NCT01716299.

An analysis of false positive reactions occurring with the Captia Syph G EIA.

PubMed Central

Ross, J; Moyes, A; Young, H; McMillan, A

1991-01-01

AIM--The Captia Syph G enzyme immuno assay (EAI) offers the potential for the rapid automated detection of syphilis antibodies. This study was designed to assess the role of other sexually transmitted diseases (STDs) in producing false positive reactions in the Captia Syph G EIA. The role of rheumatoid factor (RF) as a potential source of false positives was also analysed. METHODS--Patients who attended a genitourinary medicine (GUM) department and gave a false positive reaction with the EIA between 1988 and 1990 were compared with women undergoing antenatal testing and with the control clinic population (EIA negative) over the same time period. The incidence of sexually transmitted disease (STD) in the clinic population and the false positive reactors was measured in relation to gonorrhoea, chlamydia, genital warts, candidiasis, "other conditions not requiring treatment" and "other conditions requiring treatment." Male: female sex ratios were also compared. Ninety two RF positive sera were analysed with the EIA. RESULTS--The rate of false positive reactions did not differ with respect to the diagnosis within the GUM clinic population. The antenatal group of women, however, had a lower incidence of false positive reactions than the GUM clinic group. No RF positive sera were positive on Captia Syph G EIA testing. CONCLUSIONS--There is no cross reaction between Captia Syph G EIA and any specific STD or with RF positive sera. The lower incidence of false positive reactions in antenatal women is unexplained but may be related to physiological changes associated with pregnancy. PMID:1743715

Neuroblastoma Screening

MedlinePlus

... including physical and emotional problems. False-negative test results can occur. Screening test results may appear to ... even if there are symptoms. False-positive test results can occur. Screening test results may appear to ...

Cross-Reactivity of Pantoprazole with Three Commercial Cannabinoids Immunoassays in Urine.

PubMed

Gomila, Isabel; Barceló, Bernardino; Rosell, Antonio; Avella, Sonia; Sahuquillo, Laura; Dastis, Macarena

2017-11-01

Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause a false-positive cannabinoid urine screen. However, a case of false-positive urine cannabinoid screen in a patient who received a pantoprazole dose has been recently published. The purpose of this study was to determine the potential cross-reactivity of pantoprazole in the cannabinoid immunoassays: Alere Triage® TOX Drug Screen, KIMS® Cannabinoids II and DRI® Cannabinoids Assay. Drug-free urine to which pantoprazole was added up to 12,000 μg/mL produced negative results in the DRI® Cannabinoids and KIMS® Cannabinoids II. Alere Triage® TOX Drug Screen assay gave positive results at pantoprazole concentrations higher than 1,000 μg/mL. Urine samples from 8 pediatric patients were collected at the beginning of their pantoprazole treatment. Alere Triage® TOX Drug Screen assay produced positive test results in all patient samples and KIMS® Cannabinoids II immunoassay produced positive test results in one patient sample. None patient sample gave a false-positive result when analyzed by the DRI® Cannabinoids Assay. Our findings demonstrate that some cannabinoids immunoassays are susceptible to cross-reaction errors resulting from the presence in urine of pantoprazole and the resulting metabolism of the parent drug. Clinicians should be aware of the possibility of false-positive results for cannabinoids after a pantoprazole treatment. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Potential for false positive HIV test results with the serial rapid HIV testing algorithm

PubMed Central

2012-01-01

Background Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Results Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. Conclusion Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals. PMID:22429706

Skin Cancer Screening

MedlinePlus

... may have serious side effects . False-negative test results can occur. Screening test results may appear to ... even if there are symptoms. False-positive test results can occur. Screening test results may appear to ...

Discordant HIV Test Results: Implications on Perinatal and Haemotransfusion Screening for HIV Infection, Cape Coast, Ghana.

PubMed

Tetteh, Ato Kwamena; Agyarko, Edward

2017-01-01

Screening results of 488 pregnant women aged 15-44 years whose blood samples had been tested on-site, using First Response® HIV 1/2, and confirmed with INNO-LIA™ HIV I/II Score were used. Of this total, 178 were reactive (HIV I, 154; HIV II, 2; and HIV I and HIV II, 22). Of the 154 HIV I-reactive samples, 104 were confirmed to be HIV I-positive and 2 were confirmed to be HIV II-positive, while 48 were confirmed to be negative [false positive rate = 17.44% (13.56-21.32)]. The two HIV II samples submitted were confirmed to be negative with the confirmatory test. For the 22 HIV I and HIV II samples, 7 were confirmed to be HIV I-positive and 1 was confirmed to be HIV I- and HIV II-positive, while 14 were confirmed to be negative. Of the 310 nonreactive samples, 6 were confirmed to be HIV I-positive and 1 was confirmed to be HIV II-positive [false negative rate = 5.79% (1.63-8.38)], while 303 were negative. False negative outcomes will remain unconfirmed, with no management options for the client. False negative rate of 5.79% requires attention, as its resultant implications on control of HIV/AIDS could be dire.

When good news is bad news: psychological impact of false positive diagnosis of HIV.

PubMed

Bhattacharya, Rahul; Barton, Simon; Catalan, Jose

2008-05-01

HIV testing is known to be stressful, however the impact of false positive HIV results on individuals is not well documented. This is a series of four case who developed psychological difficulties and psychiatric morbidities after being informed they had been misdiagnosed with HIV-positive status. We look into documented cases of misdiagnosis and potential risks of misdiagnosis. The case series highlights the implications a false diagnosis HIV-positive status can have, even when the diagnosis is rectified. Impact of misdiagnosis of HIV can lead to psychosocial difficulties and psychiatric morbidity, have public health and epidemiological implications and can lead to medico-legal conflict. This further reiterates the importance of HIV testing carried out ethically and sensitively, and in line with guidelines, respecting confidentiality and consent, and offering counselling pre-test and post-test, being mindful of the reality of erroneous and false positive HIV test results. The implications of misdiagnosis are for the individual, their partners and social contacts, as well as for the community.

The local lymph node assay being too sensitive?

PubMed

Hans-Werner, Vohr; Jürgen, Ahr Hans

2005-12-01

The local lymph node assay (LLNA) and modifications thereof were recently recognized by the OECD as stand-alone methods for the detection of skin-sensitizing potential. However, although the validity of the LLNA was acknowledged by the ICCVAM, attention was drawn to one major problem, i.e., the possibility of false positive results caused by non-specific cell activation as a result of inflammatory processes in the skin (irritation). This is based on the fact that inflammatory processes in the skin may lead to non-specific activation of dendritic cells, cell migration and non-specific proliferation of lymph node cells. Measuring cell proliferation by radioactive or non-radioactive methods, without taking the irritating properties of test items into account, leads thus to false positive reactions. In this paper, we have compared both endpoints: (1) cell proliferation alone and (2) cell proliferation in combination with inflammatory (irritating) processes. It turned out that a considerable number of tests were "false positive" to the definition mentioned above. By excluding such false positive results the LLNA seems not to be more sensitive than relevant guinea pig assays. These various methods and results are described here.

False positive malaria rapid diagnostic test in returning traveler with typhoid fever.

PubMed

Meatherall, Bonnie; Preston, Keith; Pillai, Dylan R

2014-07-09

Rapid diagnostic tests play a pivotal role in the early diagnosis of malaria where microscopy or polymerase chain reaction are not immediately available. We report the case of a 39 year old traveler to Canada who presented with fever, headache, and abdominal pain after visiting friends and relatives in India. While in India, the individual was not ill and had no signs or symptoms of malaria. Laboratory testing upon his return to Canada identified a false positive malaria rapid diagnostic (BinaxNOW® malaria) result for P. falciparum with coincident Salmonella Typhi bacteraemia without rheumatoid or autoimmune factors. Rapid diagnostic test false positivity for malaria coincided with the presence or absence of Salmonella Typhi in the blood. Clinicians should be aware that Salmonella Typhi infection may result in a false positive malaria rapid diagnostic test. The mechanism of this cross-reactivity is not clear.

Zero risk tolerance costs lives: loss of transplantable organs due to human immunodeficiency virus nucleic acid testing of potential donors.

PubMed

Shafer, Teresa J; Schkade, David; Schkade, Lawrence; Geier, Steven S; Orlowski, Jeffrey P; Klintmalm, Goran

2011-09-01

Patients' deaths due to the organ donor shortage make it imperative that every suitable organ be transplanted. False-positive results of tests for infection with the human immunodeficiency virus (HIV) result in lost organs. A survey of US organ procurement organizations collected the numbers of donors and ruled-out potential donors who had a positive result on an HIV test from January 1,2006, to October 31, 2008. Sixty-two percent of US organ procurement organizations participated. Of the 12397 donor/nondonor cases, 56 (0.45%) had an initial positive result on an HIV antibody or HIV nucleic acid test, and only 8 (14.3%) of those were confirmed positive. Of the false-positive results, 50% were from HIV antibody tests and 50% were from HIV nucleic acid tests. Organs are a scarce, finite, and perishable resource. Use of HIV antibody testing has produced a remarkably safe track record of avoiding HIV transmission, with 22 years of nonoccurrence between transmissions. Because false positives occur with any test, including the HIV Ab test, adding nucleic acid testing to the standard donor testing panel doubles the number of false-positive HIV test results and thus the number of medically suitable donors lost. The required HIV antibody test is 99.99% effective in preventing transmission of the HIV virus. Adding the HIV nucleic acid test to routine organ donor screening could result in as many as 761 to 1551 unnecessary deaths of patients between HIV transmission events because medically suitable organs are wasted.

Does disseminated nontuberculous mycobacterial disease cause false-positive Determine B-LAM lateral flow assay results? A retrospective review.

PubMed

Nel, Jeremy S; Lippincott, Christopher K; Berhanu, Rebecca; Spencer, David C; Sanne, Ian M; Ive, Prudence

2017-06-02

We retrospectively reviewed the Determine TB-LAM lateral flow assay (LF-LAM) results among HIV-infected patients with disseminated nontuberculous mycobacterial (NTM) disease. LF-LAM was positive in 19/21 patients without evidence of tuberculosis coinfection. Although tuberculosis-NTM coinfection may have been underdiagnosed, our results suggest that disseminated NTM disease may cause false-positive LF-LAM results. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

False Positive Probabilities for all Kepler Objects of Interest: 1284 Newly Validated Planets and 428 Likely False Positives

NASA Astrophysics Data System (ADS)

Morton, Timothy D.; Bryson, Stephen T.; Coughlin, Jeffrey L.; Rowe, Jason F.; Ravichandran, Ganesh; Petigura, Erik A.; Haas, Michael R.; Batalha, Natalie M.

2016-05-01

We present astrophysical false positive probability calculations for every Kepler Object of Interest (KOI)—the first large-scale demonstration of a fully automated transiting planet validation procedure. Out of 7056 KOIs, we determine that 1935 have probabilities <1% of being astrophysical false positives, and thus may be considered validated planets. Of these, 1284 have not yet been validated or confirmed by other methods. In addition, we identify 428 KOIs that are likely to be false positives, but have not yet been identified as such, though some of these may be a result of unidentified transit timing variations. A side product of these calculations is full stellar property posterior samplings for every host star, modeled as single, binary, and triple systems. These calculations use vespa, a publicly available Python package that is able to be easily applied to any transiting exoplanet candidate.

Risks of Skin Cancer Screening

MedlinePlus

... may have serious side effects . False-negative test results can occur. Screening test results may appear to ... even if there are symptoms. False-positive test results can occur. Screening test results may appear to ...

Rapid automated method for screening of enteric pathogens from stool specimens.

PubMed Central

Villasante, P A; Agulla, A; Merino, F J; Pérez, T; Ladrón de Guevara, C; Velasco, A C

1987-01-01

A total of 800 colonies suggestive of Salmonella, Shigella, or Yersinia species isolated on stool differential agar media were inoculated onto both conventional biochemical test media (triple sugar iron agar, urea agar, and phenylalanine agar) and Entero Pathogen Screen cards of the AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.). Based on the conventional tests, the AutoMicrobic system method yielded the following results: 587 true-negatives, 185 true-positives, 2 false-negatives, and 26 false-positives (sensitivity, 99%; specificity, 96%). Both true-positive and true-negative results were achieved considerably earlier than false results (P less than 0.001). The Entero Pathogen Screen card method is a fast, easy, and sensitive method for screening for Salmonella, Shigella, or Yersinia species. The impossibility of screening for oxidase-positive pathogens is a minor disadvantage of this method. PMID:3553230

How to limit false positives in environmental DNA and metabarcoding?

PubMed

Ficetola, Gentile Francesco; Taberlet, Pierre; Coissac, Eric

2016-05-01

Environmental DNA (eDNA) and metabarcoding are boosting our ability to acquire data on species distribution in a variety of ecosystems. Nevertheless, as most of sampling approaches, eDNA is not perfect. It can fail to detect species that are actually present, and even false positives are possible: a species may be apparently detected in areas where it is actually absent. Controlling false positives remains a main challenge for eDNA analyses: in this issue of Molecular Ecology Resources, Lahoz-Monfort et al. () test the performance of multiple statistical modelling approaches to estimate the rate of detection and false positives from eDNA data. Here, we discuss the importance of controlling for false detection from early steps of eDNA analyses (laboratory, bioinformatics), to improve the quality of results and allow an efficient use of the site occupancy-detection modelling (SODM) framework for limiting false presences in eDNA analysis. © 2016 John Wiley & Sons Ltd.

A retrospective evaluation method for in vitro mammalian genotoxicity tests using cytotoxicity index transformation formulae.

PubMed

Fujita, Yurika; Kasamatsu, Toshio; Ikeda, Naohiro; Nishiyama, Naohiro; Honda, Hiroshi

2016-01-15

Although in vitro chromosomal aberration tests and micronucleus tests have been widely used for genotoxicity evaluation, false-positive results have been reported under strong cytotoxic conditions. To reduce false-positive results, the new Organization for Economic Co-operation and Development (OECD) test guideline (TG) recommends the use of a new cytotoxicity index, relative increase in cell count or relative population doubling (RICC/RPD), instead of the traditionally used index, relative cell count (RCC). Although the use of the RICC/RPD may result in different outcomes and require re-evaluation of tested substances, it is impractical to re-evaluate all existing data. Therefore, we established a method to estimate test results from existing RCC data. First, we developed formulae to estimate RICC/RPD from RCC without cell counts by considering cell doubling time and experiment time. Next, the accuracy of the cytotoxicity index transformation formulae was verified by comparing estimated RICC/RPD and measured RICC/RPD for 3 major chemicals associated with false-positive genotoxicity test results: ethyl acrylate, eugenol and p-nitrophenol. Moreover, 25 compounds with false-positive in vitro chromosomal aberration (CA) test results were re-evaluated to establish a retrospective evaluation method based on derived estimated RICC/RPD values. The estimated RICC/RPD values were in good agreement with the measured RICC/RPD values for every concentration and chemical, and the estimated RICC suggested the possibility that 12 chemicals (48%) with previously judged false-positive results in fact had negative results. Our method enables transformation of RCC data into RICC/RPD values with a high degree of accuracy and will facilitate comprehensive retrospective evaluation of test results. Copyright © 2015 Elsevier B.V. All rights reserved.

False-positive alarms for bacterial screening of platelet concentrates with BacT/ALERT new-generation plastic bottles: a multicenter pilot study.

PubMed

Hundhausen, T; Müller, T H

2005-08-01

The microbial detection system BacT/ALERT (bioMérieux) is widely used to monitor bacterial contamination of platelet concentrates (PCs). Recently, the manufacturer introduced polycarbonate culture bottles and a modified pH-sensitive liquid emulsion sensor as microbial growth indicator. This reconfigured assay was investigated in a routine setting. In each of eight transfusion centers, samples from 500 consecutive PCs were monitored for 1 week. For all PCs with a positive BacT/ALERT signal, retained samples and, if available, original PC containers and concomitant red blood cell concentrates were analyzed independently. Initially BacT/ALERT-positive PCs without bacterial identification in any sample were defined as false-positive. BacT/ALERT-positive PCs with bacteria in the first sample only were called potentially positive. PCs with bacteria in the first sample and the same strain in at least one additional sample were accepted as positive. Five PCs (0.13%) were positive, 9 PCs (0.23%) were potentially positive, and 35 PCs (0.9%) were false-positive. The rate of false-positive BacT/ALERT results varied substantially between centers (<0.2%-3.2%). Tracings from false-positive cultures lacked an exponential increase of the signal during incubation. Most of these false-positives were due to malfunctioning cells in various BacT/ALERT incubation units. Careful assessment of individual tracings of samples with positive signals helps to identify malfunctioning incubation units. Their early shutdown or replacement minimizes the high rate of unrectifiable product rejects attributed to false-positive alarms and avoids unnecessary concern of doctors and patients after conversion to a reconfigured BacT/ALERT assay.

Reducing false-positive incidental findings with ensemble genotyping and logistic regression based variant filtering methods.

PubMed

Hwang, Kyu-Baek; Lee, In-Hee; Park, Jin-Ho; Hambuch, Tina; Choe, Yongjoon; Kim, MinHyeok; Lee, Kyungjoon; Song, Taemin; Neu, Matthew B; Gupta, Neha; Kohane, Isaac S; Green, Robert C; Kong, Sek Won

2014-08-01

As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false-positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here, we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false-negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous single nucleotide variants (SNVs); 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery in NA12878, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and an ensemble genotyping would be essential to minimize false-positive DNM candidates. © 2014 WILEY PERIODICALS, INC.

Reducing false positive incidental findings with ensemble genotyping and logistic regression-based variant filtering methods

PubMed Central

Hwang, Kyu-Baek; Lee, In-Hee; Park, Jin-Ho; Hambuch, Tina; Choi, Yongjoon; Kim, MinHyeok; Lee, Kyungjoon; Song, Taemin; Neu, Matthew B.; Gupta, Neha; Kohane, Isaac S.; Green, Robert C.; Kong, Sek Won

2014-01-01

As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous SNVs; 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and ensemble genotyping would be essential to minimize false positive DNM candidates. PMID:24829188

[False positive result in mammography and its association with the presence of obesity: a case-control study].

PubMed

Castro-Ibarra, Marisela; Menchaca-Díaz, Rufino; Cabrales-Ruvalcaba, J Jesús; Luna-V Gómez, Rosa Alicia

2016-01-01

To analyze the association between a false positive result in mammography and obesity, inside the breast cancer early detection program in women affiliated to the Institute of Security and Social Services for Government and Municipality workers of the State of Baja California (ISSSTECALI). A case-control, retrospective study was done in women affiliated to ISSSTECALI to whom a mammography was performed between 2009 and 2012. Women with a false positive result in mammography were included as cases. Controls were women with a true negative result in mammography. Three controls were randomly selected for each case. Obesity was established with the body mass index (BMI) consigned in the woman's clinical file. Age and estrogen replacement therapy were included as co-variables. Seventy nine cases were identified and 237 controls were included. Obesity was observed in 54.4% of cases and in 41.3% of controls (odds ratio: 1.69; 95% confidence interval for odds ratio: 1.01-2.82; p value: 0.043). A logistic regression model including covariables maintained the observed association (p = 0.044). No association was found with analyzed co-variables. A false positive result in mammography was associated with the presence of obesity.

Gas insufflation of minimal preparation CT of the colon reduces false-positives

PubMed Central

Slater, A; North, M; Hart, M; Ferrett, C

2012-01-01

Objectives Minimal preparation CT of the colon (MPCT colon) is used for investigation of suspected colorectal cancer in frail and/or elderly patients who would be expected to tolerate laxative bowel preparation poorly. Although it has good sensitivity for colorectal cancer it has a poor specificity. We wished to investigate whether distension of the colon with carbon dioxide alone would reduce the number of false-positives, but without making the test arduous or excessively uncomfortable. Methods 134 patients were recruited and underwent MPCT colon with gas insufflation and antispasmodics. Results were compared with a cohort of 134 patients undergoing standard protocol MPCT colon. The numbers of false-positives were compared, as was reader confidence. All trial patients were given a questionnaire documenting their experience. Results The number of false-positives was 15% in the control group and 5% in the trial group; this difference was statistically significant, (p=0.01). Reader confidence was increased in the trial group. Patient tolerance was good, with 95% saying they would have the test again. Conclusion Use of gas insufflation and antispasmodics reduces the false-positives from 15% to 5% without adversely affecting patient tolerance. PMID:21224295

Hair Follicle Bulb as a Biodosimeter for Low-Level VX Vapor Exposure: Initial Studies Validating the Presence of Potential Protein Biomarkers of Exposure in the Sprague-Dawley Rat Whisker Follicle

DTIC Science & Technology

2006-10-01

lead to false positive segmental hair analysis results.13 Due to the increased risk of false positives associated with segmental hair analysis ...to 200 mg of hair (to allow confirmation testing). 7 The segments are typically washed to remove external contaminants and the chemicals in the hair ...further confirmation. The method overcomes the false positives associated with traditional segmental hair analysis such. By measuring the

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

PubMed Central

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

2017-01-01

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

Potential for false positive HIV test results with the serial rapid HIV testing algorithm.

PubMed

Baveewo, Steven; Kamya, Moses R; Mayanja-Kizza, Harriet; Fatch, Robin; Bangsberg, David R; Coates, Thomas; Hahn, Judith A; Wanyenze, Rhoda K

2012-03-19

Rapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation. Of the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative. Although this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

Misdiagnosis of HIV infection during a South African community-based survey: implications for rapid HIV testing

PubMed Central

Kufa, Tendesayi; Kharsany, Ayesha BM; Cawood, Cherie; Khanyile, David; Lewis, Lara; Grobler, Anneke; Chipeta, Zawadi; Bere, Alfred; Glenshaw, Mary; Puren, Adrian

2017-01-01

Abstract Introduction: We describe the overall accuracy and performance of a serial rapid HIV testing algorithm used in community-based HIV testing in the context of a population-based household survey conducted in two sub-districts of uMgungundlovu district, KwaZulu-Natal, South Africa, against reference fourth-generation HIV-1/2 antibody and p24 antigen combination immunoassays. We discuss implications of the findings on rapid HIV testing programmes. Methods: Cross-sectional design: Following enrolment into the survey, questionnaires were administered to eligible and consenting participants in order to obtain demographic and HIV-related data. Peripheral blood samples were collected for HIV-related testing. Participants were offered community-based HIV testing in the home by trained field workers using a serial algorithm with two rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using two fourth-generation immunoassays with all positives in the confirmatory test considered true positives. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value and false-positive and false-negative rates were determined. Results: Of 10,236 individuals enrolled in the survey, 3740 were tested in the home (median age 24 years (interquartile range 19–31 years), 42.1% males and HIV positivity on RDT algorithm 8.0%). From those tested, 3729 (99.7%) had a definitive RDT result as well as a laboratory immunoassay result. The overall accuracy of the RDT when compared to the fourth-generation immunoassays was 98.8% (95% confidence interval (CI) 98.5–99.2). The sensitivity, specificity, positive predictive value and negative predictive value were 91.1% (95% CI 87.5–93.7), 99.9% (95% CI 99.8–100), 99.3% (95% CI 97.4–99.8) and 99.1% (95% CI 98.8–99.4) respectively. The false-positive and false-negative rates were 0.06% (95% CI 0.01–0.24) and 8.9% (95% CI 6.3–12.53). Compared to true positives, false negatives were more likely to be recently infected on limited antigen avidity assay and to report antiretroviral therapy (ART) use. Conclusions: The overall accuracy of the RDT algorithm was high. However, there were few false positives, and the sensitivity was lower than expected with high false negatives, despite implementation of quality assurance measures. False negatives were associated with recent (early) infection and ART exposure. The RDT algorithm was able to correctly identify the majority of HIV infections in community-based HIV testing. Messaging on the potential for false positives and false negatives should be included in these programmes. PMID:28872274

Marine Bacteria Cause False-Positive Results in the Colilert-18 Rapid Identification Test for Escherichia coli in Florida Waters

PubMed Central

Pisciotta, John M.; Rath, Damon F.; Stanek, Paul A.; Flanery, D. Michael; Harwood, Valerie J.

2002-01-01

The Colilert-18 system for enumeration of total coliforms and Escherichia coli is approved by the U.S. Environmental Protection Agency for use in drinking water analysis and is also used by various agencies and research studies for enumeration of indicator organisms in fresh and saline waters. During monitoring of Pinellas County, Fla., marine waters, estimates of E. coli numbers (by Colilert-18) frequently exceeded fecal coliform counts (by membrane filtration) by 1 to 3 orders of magnitude. Samples from freshwater sites did not display similar discrepancies. Fecal coliforms, including E. coli, could be cultured from 100% of yellow fluorescent wells (denoting E. coli-positive results) inoculated with freshwater samples but could be cultured from only 17.1% of the “positive” wells inoculated with marine samples. Ortho-nitrophenyl-β-d-galactopyranoside (ONPG)-positive or 4-methylumbelliferyl-β-d-glucuronide (MUG)-positive noncoliform bacteria were readily cultured from Colilert-18 test wells inoculated with marine samples. Filtered cell-free seawater did not cause false positives. Coculture preparations of as few as 5 CFU of Vibrio cholerae (ONPG positive) and Providencia sp. (MUG positive) ml−1 inoculated into Colilert-18 caused false-positive E. coli results. Salinity conditions influenced coculture results, as the concentration of coculture inoculum required to cause false positives in most wells increased from about 5 CFU ml−1 in seawater diluted 1:10 with freshwater to ≈5,000 CFU ml−1 in seawater diluted 1:20 with freshwater. Estimated E. coli numbers in various marine water samples processed at the 1:10 dilution ranged from 10 to 7,270 CFU·100 ml−1, while E. coli numbers in the same samples processed at the 1:20 dilution did not exceed 40 CFU·100 ml−1. The lower estimates of E. coli numbers corresponded well with fecal coliform counts by membrane filtration. This study indicates that assessment of E. coli in subtropical marine waters by Colilert-18 is not accurate when the recommended 1:10 sample dilution is used. The results suggest that greater dilution may diminish the false-positive problem, but further study of this possibility is recommended. PMID:11823188

Shear wave elastography in the diagnosis of breast non-mass lesions: factors associated with false negative and false positive results.

PubMed

Park, So Yoon; Choi, Ji Soo; Han, Boo-Kyung; Ko, Eun Young; Ko, Eun Sook

2017-09-01

To investigate factors related to false shear wave elastography (SWE) results for breast non-mass lesions (NMLs) detected by B-mode US. This retrospective study enrolled 152 NMLs detected by B-mode US and later pathologically confirmed (79 malignant, 73 benign). All lesions underwent B-mode US and SWE. Quantitative (mean elasticity [E mean ]) and qualitative (maximum stiffness colour) SWE parameters were assessed, and 'E mean  > 85.1 kPa' or 'stiff colour (green to red)' determined malignancy. Final SWE results were matched to pathology results. Multivariate logistic regression analysis identified factors associated with false SWE results for diagnosis of breast NMLs. Associated calcifications (E mean : odds ratio [OR] = 7.60, P < 0.01; maximum stiffness colour: OR = 6.30, P = 0.02), in situ cancer compared to invasive cancer (maximum stiffness colour: OR = 5.29, P = 0.02), and lesion size (E mean : OR = 0.90, P < 0.01; maximum stiffness colour: OR = 0.91, P = 0.01) were significantly associated with false negative SWE results for malignant NMLs. Distance from the nipple (E mean : OR = 0.84, P = 0.03; maximum stiffness colour: OR = 0.93, P = 0.04) was significantly associated with false positive SWE results for benign NMLs. Presence of associated calcifications, absence of the invasive component, and smaller lesion size for malignant NMLs and shorter distance from the nipple for benign NMLs are factors significantly associated with false SWE results. • Calcification and size are associated with false negative SWE in malignant NMLs. • In situ cancer is associated with false negative SWE in malignant NMLs. • Distance from the nipple is associated with false positive SWE in benign NMLs. • These factors need consideration when performing SWE on breast NMLs.

The local lymph node assay: current position in the regulatory classification of skin sensitizing chemicals.

PubMed

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is being used increasingly in the identification of skin sensitizing chemicals for regulatory purposes. In the context of new chemicals legislation (REACH) in Europe, it is the preferred assay. The rationale for this is that the LLNA quantitative and objective approach to skin sensitization testing allied with the important animal welfare benefits that the method offers. However, as with certain guinea pig sensitization tests before it, this increasing use also brings experience with an increasingly wide range of industrial and other chemicals where the outcome of the assay does not always necessarily meet with the expectations of those conducting it. Sometimes, the result appears to be a false negative, but rather more commonly, the complaint is that the chemical represents a false positive. Against this background we have here reviewed a number of instances where false positive and false negative results have been described and have sought to reconcile science with expectation. Based on these analyses, it is our conclusion that false positives and false negatives do occur in the LLNA, as they do with any other skin sensitization assay (and indeed with all tests used for hazard identification), and that this occurs for a number of reasons. We further conclude, however, that false positive results in the LLNA, as with the guinea pig maximization test, arise most commonly via failure to distinguish what is scientifically correct from that which is unpalatable. The consequences of this confusion are discussed in the article, particularly in relation to the need to integrate both potency measurement and risk assessments into classification and labelling schemes that aim to manage potential risks to human health.

False-positive cerebrospinal fluid cryptococcus antigen in Libman-Sacks endocarditis.

PubMed

Isseh, Iyad N; Bourgi, Kassem; Nakhle, Asaad; Ali, Mahmoud; Zervos, Marcus J

2016-12-01

Cryptococcus meningoencephalitis is a serious opportunistic infection associated with high morbidity and mortality in immunocompromised hosts, particularly patients with advanced AIDS disease. The diagnosis is established through cerebrospinal fluid (CSF) cryptococcus antigen detection and cultures. Cryptococcus antigen testing is usually the initial test of choice due its high sensitivity and specificity along with the quick availability of the results. We hereby report a case of a false-positive CSF cryptococcus antigen assay in a patient with systemic lupus erythematosus presenting with acute confusion. While initial CSF evaluation revealed a positive cryptococcus antigen assay, the patient's symptoms were inconsistent with cryptococcus meningoencephalitis. A repeat CSF evaluation, done 3 days later, revealed a negative CSF cryptococcus antigen assay. Given the patient's active lupus disease and the elevated antinuclear antibody titers, we believe that the initial positive result was a false positive caused by interference from autoantibodies.

A Demonstration of Regression False Positive Selection in Data Mining

ERIC Educational Resources Information Center

Pinder, Jonathan P.

2014-01-01

Business analytics courses, such as marketing research, data mining, forecasting, and advanced financial modeling, have substantial predictive modeling components. The predictive modeling in these courses requires students to estimate and test many linear regressions. As a result, false positive variable selection ("type I errors") is…

Do positive schizotypal symptoms predict false perceptual experiences in nonclinical populations?

PubMed

Tsakanikos, Elias; Reed, Phil

2005-12-01

We examined whether positive schizotypy (i.e., reports of hallucinatory and delusional-like experiences) in nonclinical participants could predict false perceptual experiences during detection of fast-moving words beyond a possible response bias. The participants (N = 160) were assigned to one of two conditions: they were asked either to make presence/absence judgments (loose criterion) or to read aloud every detected word (strict criterion). Regression analysis showed that high levels of positive schizotypy predicted false alarms in the loose condition and false perceptions of words in the strict condition. The obtained effects were independent of detection accuracy, task order, impulsivity, and social desirability. We discuss the results in the context of information processing biases linked to the positive symptomatology of schizophrenia. Clinical and theoretical implications are also considered.

Influence of clinical and laboratory variables on faecal antigen ELISA results in dogs with canine parvovirus infection.

PubMed

Proksch, A L; Unterer, S; Speck, S; Truyen, U; Hartmann, K

2015-06-01

False negative faecal canine parvovirus (CPV) antigen ELISA results in dogs with CPV infection are common, but the factors that lead to these false negative results are still unknown. The aim of this study was to investigate whether dogs with a false negative faecal CPV antigen ELISA result have milder clinical signs and laboratory changes, a lower faecal virus load, higher faecal and serum CPV antibody titres and a faster recovery than dogs with a positive result. Eighty dogs with CPV infection, confirmed by the presence of clinical signs and a positive faecal CPV polymerase chain reaction (PCR), were assigned to two groups according to their faecal antigen ELISA result. Time until presentation, severity of symptoms, laboratory parameters, faecal virus load, faecal and serum antibody titres, and CPV sequencing data were compared between both groups. In 38/80 dogs that were hospitalised until recovery, the time to recovery, mortality, and the course of the disease were compared between dogs with positive and negative faecal antigen ELISA results. Of the 80 dogs included, 41 (51.3%) had a false negative faecal antigen ELISA result. ELISA-negative dogs had a significantly shorter time until presentation, lower frequency of defaecation, lower faecal virus load, and higher serum antibody concentrations than ELISA-positive dogs. Laboratory changes, CPV shedding, and outcomes were not associated with faecal antigen ELISA results. In conclusion, low faecal CPV load and antibodies binding to CPV antigen in faeces are likely to be important reasons for false negative faecal antigen ELISA results. Dogs with clinical signs of CPV infection should be retested by faecal PCR. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-05-14

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

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

PubMed

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

2017-07-03

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

Diagnosing periprosthetic infection: false-positive intraoperative Gram stains.

PubMed

Oethinger, Margret; Warner, Debra K; Schindler, Susan A; Kobayashi, Hideo; Bauer, Thomas W

2011-04-01

Intraoperative Gram stains have a reported low sensitivity but high specificity when used to help diagnose periprosthetic infections. In early 2008, we recognized an unexpectedly high frequency of apparent false-positive Gram stains from revision arthroplasties. The purpose of this report is to describe the cause of these false-positive test results. We calculated the sensitivity and specificity of all intraoperative Gram stains submitted from revision arthroplasty cases during a 3-month interval using microbiologic cultures of the same samples as the gold standard. Methods of specimen harvesting, handling, transport, distribution, specimen processing including tissue grinding/macerating, Gram staining, and interpretation were studied. After a test modification, results of specimens were prospectively collected for a second 3-month interval, and the sensitivity and specificity of intraoperative Gram stains were calculated. The retrospective review of 269 Gram stains submitted from revision arthroplasties indicated historic sensitivity and specificity values of 23% and 92%, respectively. Systematic analysis of all steps of the procedure identified Gram-stained but nonviable bacteria in commercial broth reagents used as diluents for maceration of periprosthetic membranes before Gram staining and culture. Polymerase chain reaction and sequencing showed mixed bacterial DNA. Evaluation of 390 specimens after initiating standardized Millipore filtering of diluent fluid revealed a reduced number of positive Gram stains, yielding 9% sensitivity and 99% specificity. Clusters of false-positive Gram stains have been reported in other clinical conditions. They are apparently rare related to diagnosing periprosthetic infections but have severe consequences if used to guide treatment. Even occasional false-positive Gram stains should prompt review of laboratory methods. Our observations implicate dead bacteria in microbiologic reagents as potential sources of false-positive Gram stains.

VarBin, a novel method for classifying true and false positive variants in NGS data

PubMed Central

2013-01-01

Background Variant discovery for rare genetic diseases using Illumina genome or exome sequencing involves screening of up to millions of variants to find only the one or few causative variant(s). Sequencing or alignment errors create "false positive" variants, which are often retained in the variant screening process. Methods to remove false positive variants often retain many false positive variants. This report presents VarBin, a method to prioritize variants based on a false positive variant likelihood prediction. Methods VarBin uses the Genome Analysis Toolkit variant calling software to calculate the variant-to-wild type genotype likelihood ratio at each variant change and position divided by read depth. The resulting Phred-scaled, likelihood-ratio by depth (PLRD) was used to segregate variants into 4 Bins with Bin 1 variants most likely true and Bin 4 most likely false positive. PLRD values were calculated for a proband of interest and 41 additional Illumina HiSeq, exome and whole genome samples (proband's family or unrelated samples). At variant sites without apparent sequencing or alignment error, wild type/non-variant calls cluster near -3 PLRD and variant calls typically cluster above 10 PLRD. Sites with systematic variant calling problems (evident by variant quality scores and biases as well as displayed on the iGV viewer) tend to have higher and more variable wild type/non-variant PLRD values. Depending on the separation of a proband's variant PLRD value from the cluster of wild type/non-variant PLRD values for background samples at the same variant change and position, the VarBin method's classification is assigned to each proband variant (Bin 1 to Bin 4). Results To assess VarBin performance, Sanger sequencing was performed on 98 variants in the proband and background samples. True variants were confirmed in 97% of Bin 1 variants, 30% of Bin 2, and 0% of Bin 3/Bin 4. Conclusions These data indicate that VarBin correctly classifies the majority of true variants as Bin 1 and Bin 3/4 contained only false positive variants. The "uncertain" Bin 2 contained both true and false positive variants. Future work will further differentiate the variants in Bin 2. PMID:24266885

[Interpretation of false positive results of biochemical prenatal tests].

PubMed

Sieroszewski, Piotr; Słowakiewicz, Katarzyna; Perenc, Małgorzata

2010-03-01

Modern, non-invasive prenatal diagnostics based on biochemical and ultrasonographic markers of fetal defects allows us to calculate the risk of fetal chromosomal aneuploidies with high sensitivity and specificity An introduction of biochemical, non-invasive prenatal tests turned out to result in frequent false positive results of these tests in cases when invasive diagnostics does not confirm fetal defects. However prospective analysis of these cases showed numerous complications in the third trimester of the pregnancies.

Two-step glutamate dehydrogenase antigen real-time polymerase chain reaction assay for detection of toxigenic Clostridium difficile.

PubMed

Goldenberg, S D; Cliff, P R; Smith, S; Milner, M; French, G L

2010-01-01

Current diagnosis of Clostridium difficile infection (CDI) relies upon detection of toxins A/B in stool by enzyme immunoassay [EIA(A/B)]. This strategy is unsatisfactory because it has a low sensitivity resulting in significant false negatives. We investigated the performance of a two-step algorithm for diagnosis of CDI using detection of glutamate dehydrogenase (GDH). GDH-positive samples were tested for C. difficile toxin B gene (tcdB) by polymerase chain reaction (PCR). The performance of the two-step protocol was compared with toxin detection by the Meridian Premier EIA kit in 500 consecutive stool samples from patients with suspected CDI. The reference standard among samples that were positive by either EIA(A/B) or GDH testing was culture cytotoxin neutralisation (culture/CTN). Thirty-six (7%) of 500 samples were identified as true positives by culture/CTN. EIA(A/B) identified 14 of the positive specimens with 22 false negatives and two false positives. The two-step protocol identified 34 of the positive samples with two false positives and two false negatives. EIA(A/B) had a sensitivity of 39%, specificity of 99%, positive predictive value of 88% and negative predictive value of 95%. The two-step algorithm performed better, with corresponding values of 94%, 99%, 94% and 99% respectively. Screening for GDH before confirmation of positives by PCR is cheaper than screening all specimens by PCR and is an effective method for routine use. Current EIA(A/B) tests for CDI are of inadequate sensitivity and should be replaced; however, this may result in apparent changes in CDI rates that would need to be explained in national surveillance statistics. Copyright 2009 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.

Variation in false-positive rates of mammography reading among 1067 radiologists: a population-based assessment.

PubMed

Tan, Alai; Freeman, Daniel H; Goodwin, James S; Freeman, Jean L

2006-12-01

The accuracy of mammography reading varies among radiologists. We conducted a population-based assessment on radiologist variation in false- positive rates of screening mammography and its associated radiologist characteristics. About 27,394 screening mammograms interpreted by 1067 radiologists were identified from a 5% non-cancer sample of Medicare claims during 1998-1999. The data were linked to the American Medical Association Masterfile to obtain radiologist characteristics. Multilevel logistic regression models were used to examine the radiologist variation in false-positive rates of screening mammography and the associated radiologist characteristics. Radiologists varied substantially in the false-positive rates of screening mammography (ranging from 1.5 to 24.1%, adjusting for patient characteristics). A longer time period since graduation is associated with lower false-positive rates (odds ratio [OR] for every 10 years increase: 0.87, 95% Confidence Interval [CI], 0.81-0.94) and female radiologists had higher false-positive rates than male radiologists (OR = 1.25, 95% CI, 1.05-1.49), adjusting for patient and other radiologist characteristics. The unmeasured factors contributed to about 90% of the between-radiologist variance. Radiologists varied greatly in accuracy of mammography reading. Female and more recently trained radiologists had higher false-positive rates. The variation among radiologists was largely due to unmeasured factors, especially unmeasured radiologist factors. If our results are confirmed in further studies, they suggest that system-level interventions would be required to reduce variation in mammography interpretation.

Case report of a false positive result of the Xpert® MTB/RIF assay for rifampicin resistance in Mycobacterium tuberculosis complex.

PubMed

Claessens, Jolien; Mathys, Vanessa; Derdelinckx, Inge; Saegeman, Veroniek

2017-06-01

In the present case, we report a false positive result for the detection of rifampicin (RIF) resistance by the Xpert ® MTB/RIF assay, version G4.Miliary Mycobacterium tuberculosis infection (miliary TB) was suspected in a 50-year old Angolan woman. Imaging of the thorax and abdomen displayed diffuse lesions. The Xpert ® MTB/RIF assay conducted on the broncho-alveolar lavage (BAL) fluid was positive for TB and positive for RIF resistance. Confirmatory molecular tests and the phenotypic drug susceptibility determination supported the diagnosis of TB but not RIF resistance. The patient was treated successfully with a conventional therapeutic scheme. Because, the Xpert ® MTB/RIF assay allows the simultaneous detection of TB and RIF resistance, the World Health Organisation (WHO) recommends its use as initial diagnostic test, over microscopy, culture and phenotypic drug susceptibility testing. Even though specificity of the Xpert ® MTB/RIF assay version G4 is high, false positive test results remain possible and have to be considered for the interpretation of the RIF resistance detection by Xpert ® MTB/RIF assay.

Ranitidine interference with standard amphetamine immunoassay.

PubMed

Liu, Li; Wheeler, Sarah E; Rymer, Jacqueline A; Lower, Darla; Zona, Jayne; Peck Palmer, Octavia M; Tamama, Kenichi

2015-01-01

We recently encountered several cases of possible false positive results of amphetamine on the Beckman Coulter AMPH assay, but not on the Siemens EMIT II Plus assay. Our clinical chart review suggested that ranitidine interference may be responsible for the false positive results of the AMPH assays. Blank urine specimens spiked with ranitidine concentrations ranging from 5μg/ml to 5mg/ml were analyzed on both the AMPH and EMIT II Plus assays. To examine if the false positive results were due to assay specific reagent/sample ratios, we prepared 3 different sample to reagent ratios and analyzed them for amphetamine reaction rates on both assays. Ranitidine at 160μg/ml caused a positive interference on the AMPH assay. No interference was observed by ranitidine on the EMIT II Plus assay. Specifically, the sample to reagent ratios tested neither eliminated the positive inference on the AMP assay nor introduced an interference on the EMIT II Plus assay. Unlike the EMIT II Plus assay, the AMPH assay has cross-activity with ranitidine, which is independent of sample to reagent ratio. Copyright © 2014 Elsevier B.V. All rights reserved.

Double versus single reading of mammograms in a breast cancer screening programme: a cost-consequence analysis.

PubMed

Posso, Margarita C; Puig, Teresa; Quintana, Ma Jesus; Solà-Roca, Judit; Bonfill, Xavier

2016-09-01

To assess the costs and health-related outcomes of double versus single reading of digital mammograms in a breast cancer screening programme. Based on data from 57,157 digital screening mammograms from women aged 50-69 years, we compared costs, false-positive results, positive predictive value and cancer detection rate using four reading strategies: double reading with and without consensus and arbitration, and single reading with first reader only and second reader only. Four highly trained radiologists read the mammograms. Double reading with consensus and arbitration was 15 % (Euro 334,341) more expensive than single reading with first reader only. False-positive results were more frequent at double reading with consensus and arbitration than at single reading with first reader only (4.5 % and 4.2 %, respectively; p < 0.001). The positive predictive value (9.3 % and 9.1 %; p = 0.812) and cancer detection rate were similar for both reading strategies (4.6 and 4.2 per 1000 screens; p = 0.283). Our results suggest that changing to single reading of mammograms could produce savings in breast cancer screening. Single reading could reduce the frequency of false-positive results without changing the cancer detection rate. These results are not conclusive and cannot be generalized to other contexts with less trained radiologists. • Double reading of digital mammograms is more expensive than single reading. • Compared to single reading, double reading yields a higher proportion of false-positive results. • The cancer detection rate was similar for double and single readings. • Single reading may be a cost-effective strategy in breast cancer screening programmes.

False positive or negative results of shear-wave elastography in differentiating benign from malignant breast masses: analysis of clinical and ultrasonographic characteristics.

PubMed

Kim, Mi Young; Choi, Nami; Yang, Jung-Hyun; Yoo, Young Bum; Park, Kyoung Sik

2015-10-01

Shear-wave elastography (SWE) has the potential to improve diagnostic performance of conventional ultrasound (US) in differentiating benign from malignant breast masses. To investigate false positive or negative results of SWE in differentiating benign from malignant breast masses and to analyze clinical and imaging characteristics of the masses with false SWE findings. From May to October 2013, 166 breast lesions of 164 consecutive women (mean age, 45.3 ± 10.1 years) who had been scheduled for biopsy were included. Conventional US and SWE were performed in all women before biopsy. Clinical, ultrasonographic morphologic features and SWE parameters (pattern classification and standard deviation [SD]) were recorded and compared with the histopathology results. Patient and lesion factors in the "true" and "false" groups were compared. Of the 166 masses, 118 (71.1%) were benign and 48 (28.9%) were malignant. False SWE features were more frequently observed in benign masses. False positive rates of benign masses and false negative rates of malignancy were 53% and 8.2%, respectively, using SWE pattern analysis and were 22.4% and 10.3%, respectively, using SD values. A lesion boundary of the masses on US (P = 0.039) and younger patient age (P = 0.047) were significantly associated with false SWE findings. These clinical and ultrasonographic features need to be carefully evaluated in performance and interpretation of SWE examinations. © The Foundation Acta Radiologica 2014.

Comparison of culture, PCR, and different serologic tests for detection of Mycoplasma gallisepticum and Mycoplasma synoviae infections.

PubMed

Feberwee, A; Mekkes, D R; de Wit, J J; Hartman, E G; Pijpers, A

2005-06-01

In this study, the technical performance of culture, two commercially available polymerase chain reaction (PCR) tests, rapid plate agglutination (RPA) test, hemagglutination inhibition (HI) test, and eight commercially available enzyme-linked immunosorbent assays (ELISAs) were compared for the detection of avian mycoplasma infections from 3 days postinfection (d.p.i.) through 35 d.p.i. The tests were carried out on samples from specified pathogen-free layers that were infected at 66 wk of age with recent Mycoplasma synoviae (MS) and Mycoplasma gallisepticum (MG) field strains, MS and MG ATCC strains, and Mycoplasma imitans (MIM), respectively. Results showed a high percentage of positive samples in the homologous infected groups and a high percentage of negative samples (100%) in the uninfected and heterologous infected groups during 35 d.p.i. of both culture and PCR tests. For the group infected with the MG 15302 ATCC strain, serology was more sensitive than bacteriology. All MG and MS tests, with the exception of MG ELISA kit D showed a lower percentage of positive samples during 35 d.p.i. for the detection of the MG and MS ATCC strain infection compared with that of the field strains. Also, the number of cross-reactions (false positives) in the serologic tests was lower after infection with an ATCC strain than after an infection with the MG or MS field strain. Contradictory to other studies, the ELISAs and the RPA test using undiluted serum showed a relatively high number of false-positive results. The MG ELISAs (except ELISA kit D) showed more false-positive results (up to 37%) in the MIM-infected group than in the MS-infected groups. This was not unexpected, as MIM and MG have a close antigenic relationship. The results of the serologic tests in this study showed that a certain level of false-positive results can be expected in about any serologic test. Although the level of false-positive results varied between several serologic tests, this study showed that it is not advisable to rely completely on one test (system) only.

Cross-reactivity between Lyme and syphilis screening assays: Lyme disease does not cause false-positive syphilis screens.

PubMed

Patriquin, Glenn; LeBlanc, Jason; Heinstein, Charles; Roberts, Catherine; Lindsay, Robbin; Hatchette, Todd F

2016-03-01

Increased rates of Lyme disease and syphilis in the same geographic area prompted an assessment of screening test cross-reactivity. This study supports the previously described cross-reactivity of Lyme screening among syphilis-positive sera and reports evidence against the possibility of false-positive syphilis screening tests resulting from previous Borrelia burgdorferi infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Performance assessment of the Capilia TB assay and the BD ProbeTec ET system for rapid culture confirmation of Mycobacterium tuberculosis.

PubMed

Wang, Jann-Yuan; Lee, Li-Na; Lai, Hsin-Chih; Hsu, Hsiao-Leng; Jan, I-Shiow; Yu, Chong-Jen; Hsueh, Po-Ren; Yang, Pan-Chyr

2007-12-01

Because of the increasing numbers of nontuberculous mycobacterial isolates from clinical specimens, rapid and accurate methods for culture confirmation of Mycobacterium tuberculosis are urgently needed. The study evaluated the performance of the Capilia TB immunochromatographic assay (TAUNS, Numazu, Japan) for culture confirmation of M. tuberculosis using 242 culture-positive liquid media in 2 mycobacterial laboratories from November 2005 to February 2006. Among the 242 samples, 183 were also tested with the BD ProbeTec ET (CTB) assay (Becton Dickinson, Sparks, MD). The results of both assays were compared to the culture results and to each other. The overall sensitivity and specificity of the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 97.3% and 97.1%, respectively. The positive and negative predictive values for the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 98.2% and 95.8%, respectively. Among the 183 samples tested with both assays, 8 had discrepant results, including Capilia-TB-false-positive in 2, CTB-false-positive in another 2, CTB-false-negative in 2, Capilia TB-false-negative in 1, and both assays with false-negative results in the remaining one. This study demonstrated that the Capilia TB assay has a similar diagnostic value with the CTB assay. In addition, with the immunochromatographic method, it is less time-consuming and does not require other laboratory equipment.

Nonbleeding adenomas: Evidence of systematic false-negative fecal immunochemical test results and their implications for screening effectiveness-A modeling study.

PubMed

van der Meulen, Miriam P; Lansdorp-Vogelaar, Iris; van Heijningen, Else-Mariëtte B; Kuipers, Ernst J; van Ballegooijen, Marjolein

2016-06-01

If some adenomas do not bleed over several years, they will cause systematic false-negative fecal immunochemical test (FIT) results. The long-term effectiveness of FIT screening has been estimated without accounting for such systematic false-negativity. There are now data with which to evaluate this issue. The authors developed one microsimulation model (MISCAN [MIcrosimulation SCreening ANalysis]-Colon) without systematic false-negative FIT results and one model that allowed a percentage of adenomas to be systematically missed in successive FIT screening rounds. Both variants were adjusted to reproduce the first-round findings of the Dutch CORERO FIT screening trial. The authors then compared simulated detection rates in the second screening round with those observed, and adjusted the simulated percentage of systematically missed adenomas to those data. Finally, the authors calculated the impact of systematic false-negative FIT results on the effectiveness of repeated FIT screening. The model without systematic false-negativity simulated higher detection rates in the second screening round than observed. These observed rates could be reproduced when assuming that FIT systematically missed 26% of advanced and 73% of nonadvanced adenomas. To reduce the false-positive rate in the second round to the observed level, the authors also had to assume that 30% of false-positive findings were systematically false-positive. Systematic false-negative FIT testing limits the long-term reduction of biennial FIT screening in the incidence of colorectal cancer (35.6% vs 40.9%) and its mortality (55.2% vs 59.0%) in participants. The results of the current study provide convincing evidence based on the combination of real-life and modeling data that a percentage of adenomas are systematically missed by repeat FIT screening. This impairs the efficacy of FIT screening. Cancer 2016;122:1680-8. © 2016 American Cancer Society. © 2016 American Cancer Society.

False-negative BRAF V600E mutation results on fine-needle aspiration cytology of papillary thyroid carcinoma.

PubMed

Paek, Se Hyun; Kim, Byung Seup; Kang, Kyung Ho; Kim, Hee Sung

2017-11-13

The BRAF V600E mutation is highly specific for papillary thyroid carcinoma (PTC). A test for this mutation can increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), but a considerably high false-negative rate for the BRAF V600E mutation on FNAC has been reported. In this study, we investigated the risk factors associated with false-negative BRAF V600E mutation results on FNAC. BRAF V600E mutation results of 221 PTC nodules between December 2011 and June 2013 were retrospectively reviewed. BRAF V600E mutation results on both preoperative FNAC and postoperative formalin-fixed, paraffin-embedded (FFPE) samples were compared. We investigated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BRAF V600E mutation results on FNAC. And, we identified the risk factors associated with false-negative results. Of 221 PTC nodules, 150 (67.9%) on FNAC and 185 (83.7%) on FFPE samples were BRAF V600E mutation positive. The sensitivity, specificity, PPV, and NPV for BRAF V600E mutation testing with FNAC were 80.5, 97.2, 99.3, and 49.3%, respectively. Thirty-six (16.3%) BRAF V600E mutation-negative nodules on FNAC were mutation positive on FFPE sample analysis. Risk factors for these false-negative results were age, indeterminate FNAC results (nondiagnostic, atypia of undetermined significance (AUS), and findings suspicious for PTC), and PTC subtype. False-negative rate of BRAF mutation testing with FNAC for thyroid nodules is increased in cases of old age, indeterminate FNAC pathology results, and certain PTC subtypes. Therapeutic surgery can be considered for these cases. A well-designed prospective study with informed consent of patients will be essential for more informative results.

False Positives in Exoplanet Detection

NASA Astrophysics Data System (ADS)

Leuquire, Jacob; Kasper, David; Jang-Condell, Hannah; Kar, Aman; Sorber, Rebecca; Suhaimi, Afiq; KELT (Kilodegree Extremely Little Telescope)

2018-06-01

Our team at the University of Wyoming uses a 0.6 m telescope at RBO (Red Buttes Observatory) to help confirm results on potential exoplanet candidates from low resolution, wide field surveys shared by the KELT (Kilodegree Extremely Little Telescope) team. False positives are common in this work. We carry out transit photometry, and this method comes with special types of false positives. The most common false positive seen at the confirmation level is an EB (eclipsing binary). Low resolution images are great in detecting multiple sources for photometric dips in light curves, but they lack the precision to decipher single targets at an accurate level. For example, target star KC18C030621 needed RBO’s photometric precision to determine there was a nearby EB causing exoplanet type light curves. Identifying false positives with our telescope is important work because it helps eliminate the waste of time taken by more expensive telescopes trying to rule out negative candidate stars. It also furthers the identification of other types of photometric events, like eclipsing binaries, so they can be studied on their own.

Neural events that underlie remembering something that never happened.

PubMed

Gonsalves, B; Paller, K A

2000-12-01

We induced people to experience a false-memory illusion by first asking them to visualize common objects when cued with the corresponding word; on some trials, a photograph of the object was presented 1800 ms after the cue word. We then tested their memory for the photographs. Posterior brain potentials in response to words at encoding were more positive if the corresponding object was later falsely remembered as a photograph. Similar brain potentials during the memory test were more positive for true than for false memories. These results implicate visual imagery in the generation of false memories and provide neural correlates of processing differences between true and false memories.

Experience with a tuberculosis antigen test in Rhodesia.

PubMed

Cookson, J B; Cruickshank, J G; Ellis, B P

1977-10-01

Experience with a new serological method for the diagnosis of tuberculosis is reported in a predominantly black population. We have found that in only 69% of 167 patients was there agreement between serology and the presence or absence of tuberculosis. Both false positive and false negative results were common. Of 47 healthy controls, 80% were positive. These results are less satisfactory than previous studies but differences in the reading of the results seems an unlikely explanation. Differences in the populations studied may be an important factor.

Standoff detection of chemical and biological threats using laser-induced breakdown spectroscopy.

PubMed

Gottfried, Jennifer L; De Lucia, Frank C; Munson, Chase A; Miziolek, Andrzej W

2008-04-01

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for real-time chemical and biological warfare agent detection in the field. We have demonstrated the detection and discrimination of the biological warfare agent surrogates Bacillus subtilis (BG) (2% false negatives, 0% false positives) and ovalbumin (0% false negatives, 1% false positives) at 20 meters using standoff laser-induced breakdown spectroscopy (ST-LIBS) and linear correlation. Unknown interferent samples (not included in the model), samples on different substrates, and mixtures of BG and Arizona road dust have been classified with reasonable success using partial least squares discriminant analysis (PLS-DA). A few of the samples tested such as the soot (not included in the model) and the 25% BG:75% dust mixture resulted in a significant number of false positives or false negatives, respectively. Our preliminary results indicate that while LIBS is able to discriminate biomaterials with similar elemental compositions at standoff distances based on differences in key intensity ratios, further work is needed to reduce the number of false positives/negatives by refining the PLS-DA model to include a sufficient range of material classes and carefully selecting a detection threshold. In addition, we have demonstrated that LIBS can distinguish five different organophosphate nerve agent simulants at 20 meters, despite their similar stoichiometric formulas. Finally, a combined PLS-DA model for chemical, biological, and explosives detection using a single ST-LIBS sensor has been developed in order to demonstrate the potential of standoff LIBS for universal hazardous materials detection.

The clinical impact of a false-positive urine cocaine screening result on a patient's pain management.

PubMed

Kim, James A; Ptolemy, Adam S; Melanson, Stacy E F; Janfaza, David R; Ross, Edgar L

2015-06-01

The urine of a patient admitted for chest and epigastric pain tested positive for cocaine using an immunoassay-based drug screening method (positive/negative cutoff concentration 150 ng/mL). Despite the patient's denial of recent cocaine use, this positive cocaine screening result in conjunction with a remote history of drug misuse impacted the patient's recommended pain therapy. Specifically, these factors prompted the clinical team to question the appropriateness of opioids and other potentially addictive therapeutics during the treatment of cancer pain from previously undetected advanced pancreatic carcinoma. After pain management and clinical pathology consultation, it was decided that the positive cocaine screening result should be confirmed by gas chromatography-mass spectrometry (GC-MS) testing. This more sensitive and specific analytical technique revealed that both cocaine and its primary metabolite benzoylecgonine were undetectable (i.e., less than the assay detection limit of 50 ng/mL), thus indicating that the positive urine screening result was falsely positive. With this confirmation, the pain management service team was reassured in offering intrathecal pump (ITP) therapy for pain control. ITP implantation was well tolerated, and the patient eventually achieved excellent pain relief. However, ITP therapy most likely would not have been utilized without the GC-MS confirmation testing unless alternative options failed and extensive vigilant monitoring was initiated. As exemplified in this case, confirmatory drug testing should be performed on specimens with unexpected immunoassay-based drug screening results. To our knowledge, this is the first report of a false-positive urine cocaine screening result and its impact on patient management. Wiley Periodicals, Inc.

False Memories for Affective Information in Schizophrenia.

PubMed

Fairfield, Beth; Altamura, Mario; Padalino, Flavia A; Balzotti, Angela; Di Domenico, Alberto; Mammarella, Nicola

2016-01-01

Studies have shown a direct link between memory for emotionally salient experiences and false memories. In particular, emotionally arousing material of negative and positive valence enhanced reality monitoring compared to neutral material since emotional stimuli can be encoded with more contextual details and thereby facilitate the distinction between presented and imagined stimuli. Individuals with schizophrenia appear to be impaired in both reality monitoring and memory for emotional experiences. However, the relationship between the emotionality of the to-be-remembered material and false memory occurrence has not yet been studied. In this study, 24 patients and 24 healthy adults completed a false memory task with everyday episodes composed of 12 photographs that depicted positive, negative, or neutral outcomes. Results showed how patients with schizophrenia made a higher number of false memories than normal controls ( p  < 0.05) when remembering episodes with positive or negative outcomes. The effect of valence was apparent in the patient group. For example, it did not affect the production causal false memories ( p  > 0.05) resulting from erroneous inferences but did interact with plausible, script consistent errors in patients (i.e., neutral episodes yielded a higher degree of errors than positive and negative episodes). Affective information reduces the probability of generating causal errors in healthy adults but not in patients suggesting that emotional memory impairments may contribute to deficits in reality monitoring in schizophrenia when affective information is involved.

False Memories for Affective Information in Schizophrenia

PubMed Central

Fairfield, Beth; Altamura, Mario; Padalino, Flavia A.; Balzotti, Angela; Di Domenico, Alberto; Mammarella, Nicola

2016-01-01

Studies have shown a direct link between memory for emotionally salient experiences and false memories. In particular, emotionally arousing material of negative and positive valence enhanced reality monitoring compared to neutral material since emotional stimuli can be encoded with more contextual details and thereby facilitate the distinction between presented and imagined stimuli. Individuals with schizophrenia appear to be impaired in both reality monitoring and memory for emotional experiences. However, the relationship between the emotionality of the to-be-remembered material and false memory occurrence has not yet been studied. In this study, 24 patients and 24 healthy adults completed a false memory task with everyday episodes composed of 12 photographs that depicted positive, negative, or neutral outcomes. Results showed how patients with schizophrenia made a higher number of false memories than normal controls (p < 0.05) when remembering episodes with positive or negative outcomes. The effect of valence was apparent in the patient group. For example, it did not affect the production causal false memories (p > 0.05) resulting from erroneous inferences but did interact with plausible, script consistent errors in patients (i.e., neutral episodes yielded a higher degree of errors than positive and negative episodes). Affective information reduces the probability of generating causal errors in healthy adults but not in patients suggesting that emotional memory impairments may contribute to deficits in reality monitoring in schizophrenia when affective information is involved. PMID:27965600

False positive computed tomographic angiography for Stanford type A aortic dissection.

PubMed

Bandali, Murad F; Hatem, Muhammed A; Appoo, Jehangir J; Hutchison, Stuart J; Wong, Jason K

2015-12-01

Computed tomographic angiography (CTA) has emerged as the defacto imaging test to rule out acute aortic dissection; however, it is not without flaws. We report a case of a false-positive CTA with respect to Stanford Type A aortic dissection. A 52 year-old male presented with sudden onset shortness of breath. He denied chest pain. Due to severe hypertension and an Emergency Department bedside ultrasound suggesting an intimal flap in the aorta, CTA was requested to better assess the ascending aorta and was interpreted as consistent with Stanford Type A aortic dissection with thrombosis of the false lumen in the ascending aorta. However, intra-operative imaging (TEE and epi-aortic scanning) did not identify an intimal flap or dissection, and neither did definitive surgical inspection of the aorta. The suspected aortic dissection and thrombosed false lumen were not visualized on repeat CTA two days later. False positive diagnosis of Stanford Type A aortic dissection on CTA can be the result of technical factors, streak artifacts, motion artifacts, and periaortic structures. In this case, non-uniform arterial contrast enhancement secondary to unrecognized biventricular dysfunction resulted in the false positive CTA appearance of an intimal flap and mural thrombus. Intra-operative TEE and epi-aortic scanning were proven correct in excluding aortic dissection by the standard of definitive surgical inspection of the aorta.

49 CFR 219.605 - Positive drug test results; procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2012-10-01 2012-10-01 false Positive drug test results; procedures. 219.605...

49 CFR 219.605 - Positive drug test results; procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2010-10-01 2010-10-01 false Positive drug test results; procedures. 219.605...

49 CFR 219.605 - Positive drug test results; procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2011-10-01 2011-10-01 false Positive drug test results; procedures. 219.605...

49 CFR 219.605 - Positive drug test results; procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2013-10-01 2013-10-01 false Positive drug test results; procedures. 219.605...

49 CFR 219.605 - Positive drug test results; procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.605 Positive drug test results; procedures. (a) [Reserved] (b) Procedures for administrative... 49 Transportation 4 2014-10-01 2014-10-01 false Positive drug test results; procedures. 219.605...

Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

PubMed Central

2015-01-01

Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets. PMID:25189630

False Memory in Adults With ADHD: A Comparison Between Subtypes and Normal Controls.

PubMed

Soliman, Abdrabo Moghazy; Elfar, Rania Mohamed

2017-10-01

To examine the performance on the Deese-Roediger-McDermott task of adults divided into ADHD subtypes and compares their performance to that of healthy controls to examine whether adults with ADHD are more susceptible to the production of false memories under experimental conditions. A total of 128 adults with ADHD (50% females), classified into three Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV-TR) subtypes, were compared with 48 controls. The results indicated that the ADHD participants recalled and recognized fewer studied words than the controls, the ADHD groups produced more false memories than the control group, no differences in either the false positives or the false negatives. The ADHD-combined (ADHD-CT) group recognized significantly more critical words than the control, ADHD-predominantly inattentive (ADHD-IA), and ADHD-predominantly hyperactive-impulsive (ADHD-HI) groups. The ADHD groups recalled and recognized more false positives, were more confident in their false responses, and displayed more knowledge corruption than the controls. The ADHD-CT group recalled and recognized more false positives than the other ADHD groups. The adults with ADHD have more false memories than the controls and that false memory formation varied with the ADHD subtypes.

Preschool children's vision screening in New Zealand: a retrospective evaluation of referral accuracy

PubMed Central

Langeslag-Smith, Miriam A; Vandal, Alain C; Briane, Vincent; Thompson, Benjamin; Anstice, Nicola S

2015-01-01

Objectives To assess the accuracy of preschool vision screening in a large, ethnically diverse, urban population in South Auckland, New Zealand. Design Retrospective longitudinal study. Methods B4 School Check vision screening records (n=5572) were compared with hospital eye department data for children referred from screening due to impaired acuity in one or both eyes who attended a referral appointment (n=556). False positive screens were identified by comparing screening data from the eyes that failed screening with hospital data. Estimation of false negative screening rates relied on data from eyes that passed screening. Data were analysed using logistic regression modelling accounting for the high correlation between results for the two eyes of each child. Primary outcome measure Positive predictive value of the preschool vision screening programme. Results Screening produced high numbers of false positive referrals, resulting in poor positive predictive value (PPV=31%, 95% CI 26% to 38%). High estimated negative predictive value (NPV=92%, 95% CI 88% to 95%) suggested most children with a vision disorder were identified at screening. Relaxing the referral criteria for acuity from worse than 6/9 to worse than 6/12 improved PPV without adversely affecting NPV. Conclusions The B4 School Check generated numerous false positive referrals and consequently had a low PPV. There is scope for reducing costs by altering the visual acuity criterion for referral. PMID:26614622

Prolactin as a Marker of Successful Catheterization during IPSS in Patients with ACTH-Dependent Cushing's Syndrome

PubMed Central

Sharma, S. T.; Raff, H.

2011-01-01

Context: Anomalous venous drainage can lead to false-negative inferior petrosal sinus sampling (IPSS) results. Baseline inferior petrosal sinus to peripheral (IPS/P) prolactin ratio higher than 1.8 ipsilateral to the highest ACTH ratio has been proposed to verify successful catheterization. Prolactin-normalized ACTH IPS/P ratios may differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Objective: Our objective was to examine the utility of prolactin measurement during IPSS. Design, Setting, and Participants: We conducted a retrospective analysis of prolactin levels in basal and CRH-stimulated IPSS samples in ACTH-dependent Cushing's syndrome (2007–2010). Results: Twenty-five of 29 patients had a pathologically proven diagnosis (17 CD and eight EAS). IPSS results were partitioned into true positive for CD (n = 16), true negative (n = 7), false negative (n = 1), and false positive (n = 1). Prolactin IPS/P ratio suggested successful IPSS in eight of 11 with abnormal venograms. Baseline prolactin IPS/P ratio was helpful in two patients with abnormal venograms and false-negative (catheterization unsuccessful) or true-negative (catheterization successful) IPSS results; the normalized ratio correctly diagnosed their disease. Normalized ACTH IPS/P ratio was at least 1.3 in all with CD, but prolactin IPS/P ratios were misleadingly low in two. One patient with cyclic EAS had a false-positive IPSS when eucortisolemic (baseline prolactin IPS/P = 1.7; normalized ratio = 5.6). All other EAS patients had normalized ratios no higher than 0.7. Conclusion: Prolactin measurement and evaluation of the venogram can improve diagnostic accuracy when IPSS results suggest EAS but is not necessary with positive IPSS results. Confirmation of hypercortisolemia remains a prerequisite for IPSS. A normalized ratio of 0.7–1.3 was not diagnostic. PMID:22031511

False Position, Double False Position and Cramer's Rule

ERIC Educational Resources Information Center

Boman, Eugene

2009-01-01

We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

Results of newborn screening for hearing loss: effects on the family in the first 2 years of life.

PubMed

Vohr, Betty R; Jodoin-Krauzyk, Julie; Tucker, Richard; Johnson, Mary Jane; Topol, Deborah; Ahlgren, Marianne

2008-03-01

To determine whether there was increased stress and impact on the family for mothers of infants whose screening results and subsequent diagnostic findings indicated hearing loss (HL) and mothers of infants with a positive screening result who subsequently pass the rescreening (false-positive group), compared with mothers of infants who pass the initial screening (control group), when their children were aged 6 to 10, 12 to 16, and 18 to 24 months. Matched cohort analytic study. Home visits. Patients/ Mothers of 33 infants with confirmed HL, 42 infants with a false-positive screening result, and 70 infants in the control group. Screening for HL. Scores on the Parenting Stress Index and the Impact on Family-Adapted Version G. Mothers of infants in the false-positive group did not report increased stress or impact. Mothers of infants with HL reported greater financial impact, total impact, and caretaker burden compared with mothers of infants in the control group. In multivariate analysis of the total cohort, the presence of HL was associated with increased total impact on the family; a neonatal intensive care unit stay was associated with increased stress and total impact on the family; and older maternal age and greater family resources were associated with decreased stress and total impact on the family. Although a false-positive result or a pass of the screening for HL was not associated with increased stress or impact, identification of HL was independently associated with greater total impact on the family when the child was 18 to 24 months of age.

A novel gamma-fitting statistical method for anti-drug antibody assays to establish assay cut points for data with non-normal distribution.

PubMed

Schlain, Brian; Amaravadi, Lakshmi; Donley, Jean; Wickramasekera, Ananda; Bennett, Donald; Subramanyam, Meena

2010-01-31

In recent years there has been growing recognition of the impact of anti-drug or anti-therapeutic antibodies (ADAs, ATAs) on the pharmacokinetic and pharmacodynamic behavior of the drug, which ultimately affects drug exposure and activity. These anti-drug antibodies can also impact safety of the therapeutic by inducing a range of reactions from hypersensitivity to neutralization of the activity of an endogenous protein. Assessments of immunogenicity, therefore, are critically dependent on the bioanalytical method used to test samples, in which a positive versus negative reactivity is determined by a statistically derived cut point based on the distribution of drug naïve samples. For non-normally distributed data, a novel gamma-fitting method for obtaining assay cut points is presented. Non-normal immunogenicity data distributions, which tend to be unimodal and positively skewed, can often be modeled by 3-parameter gamma fits. Under a gamma regime, gamma based cut points were found to be more accurate (closer to their targeted false positive rates) compared to normal or log-normal methods and more precise (smaller standard errors of cut point estimators) compared with the nonparametric percentile method. Under a gamma regime, normal theory based methods for estimating cut points targeting a 5% false positive rate were found in computer simulation experiments to have, on average, false positive rates ranging from 6.2 to 8.3% (or positive biases between +1.2 and +3.3%) with bias decreasing with the magnitude of the gamma shape parameter. The log-normal fits tended, on average, to underestimate false positive rates with negative biases as large a -2.3% with absolute bias decreasing with the shape parameter. These results were consistent with the well known fact that gamma distributions become less skewed and closer to a normal distribution as their shape parameters increase. Inflated false positive rates, especially in a screening assay, shifts the emphasis to confirm test results in a subsequent test (confirmatory assay). On the other hand, deflated false positive rates in the case of screening immunogenicity assays will not meet the minimum 5% false positive target as proposed in the immunogenicity assay guidance white papers. Copyright 2009 Elsevier B.V. All rights reserved.

Direct versus indirect molecular diagnosis of fragile X mental retardation in 40 German families at risk.

PubMed

Knobloch, O; Pelz, F; Wick, U; Nelson, D L; Zoll, B

1993-03-01

In order to test whether the direct molecular diagnostic approach for fragile X mental retardation (Martin-Bell syndrome, MBS) really makes diagnosis of this disease more precise, we evaluated the results of direct diagnosis in 40 German families at risk together with the results of an earlier study with closely linked flanking markers in the same families. Of 84 men analysed, 43 showed clinical signs. In 39 of these affected men the disease could be confirmed by direct diagnosis. Compared to cytogenetic data, one man was false negative and two were false positive. Two men, whose status could not be determined by means of RFLP data, proved to be normal transmitting males (NTMs). However, the possibility of being an NTM had to be rejected in one case on RFLP data. Fragile X syndrome could be confirmed in 10 of the 13 women with clinical signs. Compared to cytogenetic data there were three cases of false negative results and one of false positive. All 36 obligate carrier women were detected by the direct approach. In addition, 22 women were newly identified as normal transmitting females (NTFs), among them one woman who could not be identified by cytogenetic means or by analysis with closely linked markers. These findings are discussed in view of the relative reliability of the three diagnostic approaches to MBS. Special attention is drawn to the significance of false negative and false positive results in direct diagnosis.

The risk factor of false-negative and false-positive for T-SPOT.TB in active tuberculosis.

PubMed

Di, Li; Li, Yan

2018-02-01

T-SPOT.TB is a promising diagnosis tool to identify both pulmonary tuberculosis and extrapulmonary tuberculosis, as well as latent tuberculosis; however, the factors that affect the results of T-SPOT.TB remains unclear. In this study, we aim to figure out the risk factor of T-SPOT.TB for active TB. A total of 349 patients were recruited between January 1st, 2016 and January 22st, 2017 at Renmin Hospital of Wuhan University, including 98 subjects with TB and 251 subjects with non-TB disease, and received T-SPOT.TB (Oxford Immunotec Ltd). Statistics were analyzed by SPSS 19.0 using logistic regression. The overall specificity and sensitivity of the T-SPOT.TB was 92.83% (233/251; 95%CI 0.8872-0.9557) and 83.67% (82/98; 95%CI 0.7454-0.9010), respectively. Patients with tuberculous meningitis were more likely to have false-negative results (OR 17.4, 95%CI 3.068-98.671; P<.001) while patients with cured TB tended to induce false-positive results (OR 30.297; 95%CI 7.069-129.849; P<.001). The results were not affected by sex, age, onset time, smoke, alcohol, treatment, allergic history, co-morbidity, TB (exclude tuberculous meningitis) (P>.05). Tuberculous meningitis was a risk factor of false-negative for T-SPOT.TB, while cured TB was a risk factor of false-positive. © 2017 Wiley Periodicals, Inc.

Proteins interacting with cloning scars: a source of false positive protein-protein interactions.

PubMed

Banks, Charles A S; Boanca, Gina; Lee, Zachary T; Florens, Laurence; Washburn, Michael P

2015-02-23

A common approach for exploring the interactome, the network of protein-protein interactions in cells, uses a commercially available ORF library to express affinity tagged bait proteins; these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. Control experiments can be used to limit false-positive results, but in many cases, there are still a surprising number of prey proteins that appear to copurify specifically with the bait. Here, we have identified one source of false-positive interactions in such studies. We have found that a combination of: 1) the variable sequence of the C-terminus of the bait with 2) a C-terminal valine "cloning scar" present in a commercially available ORF library, can in some cases create a peptide motif that results in the aberrant co-purification of endogenous cellular proteins. Control experiments may not identify false positives resulting from such artificial motifs, as aberrant binding depends on sequences that vary from one bait to another. It is possible that such cryptic protein binding might occur in other systems using affinity tagged proteins; this study highlights the importance of conducting careful follow-up studies where novel protein-protein interactions are suspected.

Proteins interacting with cloning scars: a source of false positive protein-protein interactions

PubMed Central

Banks, Charles A. S.; Boanca, Gina; Lee, Zachary T.; Florens, Laurence; Washburn, Michael P.

2015-01-01

A common approach for exploring the interactome, the network of protein-protein interactions in cells, uses a commercially available ORF library to express affinity tagged bait proteins; these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. Control experiments can be used to limit false-positive results, but in many cases, there are still a surprising number of prey proteins that appear to copurify specifically with the bait. Here, we have identified one source of false-positive interactions in such studies. We have found that a combination of: 1) the variable sequence of the C-terminus of the bait with 2) a C-terminal valine “cloning scar” present in a commercially available ORF library, can in some cases create a peptide motif that results in the aberrant co-purification of endogenous cellular proteins. Control experiments may not identify false positives resulting from such artificial motifs, as aberrant binding depends on sequences that vary from one bait to another. It is possible that such cryptic protein binding might occur in other systems using affinity tagged proteins; this study highlights the importance of conducting careful follow-up studies where novel protein-protein interactions are suspected. PMID:25704442

True detection limits in an experimental linearly heteroscedastic system. Part 1

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-11-01

Using a lab-constructed laser-excited filter fluorimeter deliberately designed to exhibit linearly heteroscedastic, additive Gaussian noise, it has been shown that accurate estimates may be made of the true theoretical Currie decision levels ( YC and XC) and true Currie detection limits ( YD and XD) for the detection of rhodamine 6 G tetrafluoroborate in ethanol. The obtained experimental values, for 5% probability of false positives and 5% probability of false negatives, were YC = 56.1 mV, YD = 125. mV, XC = 0.132 μg /mL and XD = 0.294 μg /mL. For 5% probability of false positives and 1% probability of false negatives, the obtained detection limits were YD = 158. mV and XD = 0.372 μg /mL. These decision levels and corresponding detection limits were shown to pass the ultimate test: they resulted in observed probabilities of false positives and false negatives that were statistically equivalent to the a priori specified values.

How pH, Temperature, and Time of Incubation Affect False-Positive Responses and Uncertainty of the LAL Gel-Clot Test.

PubMed

Lourenço, Felipe Rebello; Botelho, Túlia De Souza; Pinto, Terezinha De Jesus Andreoli

2012-01-01

The limulus amebocyte lysate (LAL) test is the simplest and most widely used procedure for detection of endotoxin in parenteral drugs. The LAL test demands optimal pH, ionic strength, temperature, and time of incubation. Slight changes in these parameters may increase the frequency of false-positive responses and the estimated uncertainty of the LAL test. The aim of this paper is to evaluate how changes in the pH, temperature, and time of incubation affect the occurrence of false-positive responses in the LAL test. LAL tests were performed in nominal conditions (37 °C, 60 min, and pH 7) and in different conditions of temperature (36 °C and 38 °C), time of incubation (58 and 62 min), and pH (6 and 8). Slight differences in pH increase the frequency of false-positive responses 5-fold (relative risk 5.0), resulting in an estimated of uncertainty 7.6%. Temperature and time of incubation affect the LAL test less, showing relative risks of 1.5 and 1.0, respectively. Estimated uncertainties in 36 °C or 38 °C temperatures and 58 or 62 min of incubation were found to be 2.0% and 1.0%, respectively. Simultaneous differences in these parameters significantly increase the frequency of false-positive responses. The limulus amebocyte lysate (LAL) gel-clot test is a simple test for detection of endotoxin from Gram-negative bacteria. The test is based on a gel formation when a certain amount of endotoxin is present; it is a pass/fail test. The LAL test requires optimal pH, ionic strength, temperature, and time of incubation. Slight difference in these parameters may increase the frequency of false-positive responses. The aim of this paper is to evaluate how changes in the pH, temperature, and time of incubation affect the occurrence of false-positive responses in the LAL test. We find that slight differences in pH increase the frequency of false-positive responses 5-fold. Temperature and time of incubation affect the LAL test less. Simultaneous differences in these parameters significantly increase the frequency of false-positive responses.

Comparison of scanty AFB smears against culture in an area with high HIV prevalence.

PubMed

Lawson, L; Yassin, M A; Ramsay, A; Emenyonu, N E; Squire, S B; Cuevas, L E

2005-08-01

To verify among tuberculosis (TB) suspects attending hospitals in Abuja, Nigeria, if sputum smears graded as scanty are false-positive, sputum smears from 1068 patients were graded with the International Union Against Tuberculosis and Lung Disease classification. One specimen was cultured. Eight hundred and twenty-four (26%) smears were positive, 137 (4%) scanty and 2243 negative. Of 1068 cultures, 680 (64%) were positive. One hundred and thirty (95%) scanty and 809 (98%) positive smears were culture-positive. Twelve of 18 patients with a single scanty smear and 51 of 52 with > or = 2 scanty smears were culture-positive. Fewer than < 5% scanty results, < 1% of the patients treated for TB, are false-positive.

Comparing diagnostic tests on benefit-risk.

PubMed

Pennello, Gene; Pantoja-Galicia, Norberto; Evans, Scott

2016-01-01

Comparing diagnostic tests on accuracy alone can be inconclusive. For example, a test may have better sensitivity than another test yet worse specificity. Comparing tests on benefit risk may be more conclusive because clinical consequences of diagnostic error are considered. For benefit-risk evaluation, we propose diagnostic yield, the expected distribution of subjects with true positive, false positive, true negative, and false negative test results in a hypothetical population. We construct a table of diagnostic yield that includes the number of false positive subjects experiencing adverse consequences from unnecessary work-up. We then develop a decision theory for evaluating tests. The theory provides additional interpretation to quantities in the diagnostic yield table. It also indicates that the expected utility of a test relative to a perfect test is a weighted accuracy measure, the average of sensitivity and specificity weighted for prevalence and relative importance of false positive and false negative testing errors, also interpretable as the cost-benefit ratio of treating non-diseased and diseased subjects. We propose plots of diagnostic yield, weighted accuracy, and relative net benefit of tests as functions of prevalence or cost-benefit ratio. Concepts are illustrated with hypothetical screening tests for colorectal cancer with test positive subjects being referred to colonoscopy.

Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children.

PubMed

Kaplan, Justin; Shah, Pooja; Faley, Brian; Siegel, Mark E

2015-12-01

Urine drug screens (UDSs) are used to identify the presence of certain medications. One limitation of UDSs is the potential for false-positive results caused by cross-reactivity with other substances. Amphetamines have an extensive list of cross-reacting medications. The literature contains reports of false-positive amphetamine UDSs with multiple antidepressants and antipsychotics. We present 2 cases of presumed false-positive UDSs for amphetamines after ingestion of aripiprazole. Case 1 was a 16-month-old girl who accidently ingested 15 to 45 mg of aripiprazole. She was lethargic and ataxic at home with 1 episode of vomiting containing no identifiable tablets. She remained sluggish with periods of irritability and was admitted for observation. UDS on 2 consecutive days came back positive for amphetamines. Case 2 was of a 20-month-old girl who was brought into the hospital after accidental ingestion of an unknown quantity of her father's medications which included aripiprazole. UDS on the first day of admission came back positive only for amphetamines. Confirmatory testing with gas chromatography-mass spectrometry (GC-MS) on the blood and urine samples were also performed for both patients on presentation to detect amphetamines and were subsequently negative. Both patients returned to baseline and were discharged from the hospital. To our knowledge, these cases represent the first reports of false-positive amphetamine urine drug tests with aripiprazole. In both cases, aripiprazole was the drug with the highest likelihood of causing the positive amphetamine screen. The implications of these false-positives include the possibility of unnecessary treatment and monitoring of patients. Copyright © 2015 by the American Academy of Pediatrics.

Risk assessment of false-positive quantitative real-time PCR results in food, due to detection of DNA originating from dead cells.

PubMed

Wolffs, Petra; Norling, Börje; Rådström, Peter

2005-03-01

Real-time PCR technology is increasingly used for detection and quantification of pathogens in food samples. A main disadvantage of nucleic acid detection is the inability to distinguish between signals originating from viable cells and DNA released from dead cells. In order to gain knowledge concerning risks of false-positive results due to detection of DNA originating from dead cells, quantitative PCR (qPCR) was used to investigate the degradation kinetics of free DNA in four types of meat samples. Results showed that the fastest degradation rate was observed (1 log unit per 0.5 h) in chicken homogenate, whereas the slowest rate was observed in pork rinse (1 log unit per 120.5 h). Overall results indicated that degradation occurred faster in chicken samples than in pork samples and faster at higher temperatures. Based on these results, it was concluded that, especially in pork samples, there is a risk of false-positive PCR results. This was confirmed in a quantitative study on cell death and signal persistence over a period of 28 days, employing three different methods, i.e. viable counts, direct qPCR, and finally floatation, a recently developed discontinuous density centrifugation method, followed by qPCR. Results showed that direct qPCR resulted in an overestimation of up to 10 times of the amount of cells in the samples compared to viable counts, due to detection of DNA from dead cells. However, after using floatation prior to qPCR, results resembled the viable count data. This indicates that by using of floatation as a sample treatment step prior to qPCR, the risk of false-positive PCR results due to detection of dead cells, can be minimized.

Effect of protocol-related variables and women's characteristics on the cumulative false-positive risk in breast cancer screening

PubMed Central

Román, R.; Sala, M.; Salas, D.; Ascunce, N.; Zubizarreta, R.; Castells, X.

2012-01-01

Background: Reducing the false-positive risk in breast cancer screening is important. We examined how the screening-protocol and women's characteristics affect the cumulative false-positive risk. Methods: This is a retrospective cohort study of 1 565 364 women aged 45–69 years who underwent 4 739 498 screening mammograms from 1990 to 2006. Multilevel discrete hazard models were used to estimate the cumulative false-positive risk over 10 sequential mammograms under different risk scenarios. Results: The factors affecting the false-positive risk for any procedure and for invasive procedures were double mammogram reading [odds ratio (OR) = 2.06 and 4.44, respectively], two mammographic views (OR = 0.77 and 1.56, respectively), digital mammography (OR = 0.83 for invasive procedures), premenopausal status (OR = 1.31 and 1.22, respectively), use of hormone replacement therapy (OR = 1.03 and 0.84, respectively), previous invasive procedures (OR = 1.52 and 2.00, respectively), and a familial history of breast cancer (OR = 1.18 and 1.21, respectively). The cumulative false-positive risk for women who started screening at age 50–51 was 20.39% [95% confidence interval (CI) 20.02–20.76], ranging from 51.43% to 7.47% in the highest and lowest risk profiles, respectively. The cumulative risk for invasive procedures was 1.76% (95% CI 1.66–1.87), ranging from 12.02% to 1.58%. Conclusions: The cumulative false-positive risk varied widely depending on the factors studied. These findings are relevant to provide women with accurate information and to improve the effectiveness of screening programs. PMID:21430183

The probability of false positives in zero-dimensional analyses of one-dimensional kinematic, force and EMG trajectories.

PubMed

Pataky, Todd C; Vanrenterghem, Jos; Robinson, Mark A

2016-06-14

A false positive is the mistake of inferring an effect when none exists, and although α controls the false positive (Type I error) rate in classical hypothesis testing, a given α value is accurate only if the underlying model of randomness appropriately reflects experimentally observed variance. Hypotheses pertaining to one-dimensional (1D) (e.g. time-varying) biomechanical trajectories are most often tested using a traditional zero-dimensional (0D) Gaussian model of randomness, but variance in these datasets is clearly 1D. The purpose of this study was to determine the likelihood that analyzing smooth 1D data with a 0D model of variance will produce false positives. We first used random field theory (RFT) to predict the probability of false positives in 0D analyses. We then validated RFT predictions via numerical simulations of smooth Gaussian 1D trajectories. Results showed that, across a range of public kinematic, force/moment and EMG datasets, the median false positive rate was 0.382 and not the assumed α=0.05, even for a simple two-sample t test involving N=10 trajectories per group. The median false positive rate for experiments involving three-component vector trajectories was p=0.764. This rate increased to p=0.945 for two three-component vector trajectories, and to p=0.999 for six three-component vectors. This implies that experiments involving vector trajectories have a high probability of yielding 0D statistical significance when there is, in fact, no 1D effect. Either (a) explicit a priori identification of 0D variables or (b) adoption of 1D methods can more tightly control α. Copyright © 2016 Elsevier Ltd. All rights reserved.

Accuracy of BRT and Delvotest microbial inhibition tests as affected by composition of ewe's milk.

PubMed

Althaus, Rafael; Torres, Antonio; Peris, Cristofol; Beltran, M Carmen; Fernandez, Nemesio; Molina, M Pilar

2003-03-01

The presence of drug residues in ewe's milk samples can be determined by microbial assays. The main limitation of these tests is the large number of false-positive results associated with them. False-positive results can be explained by the interaction of certain substances naturally existing in ewe's milk with the growth of the microorganism used in the test. In this study, milk chemical composition (fat, protein, lactose, total solids), somatic cell counts (SCCs), free fatty acid concentrations, and lactoperoxidase system components were determined in order to investigate their influence on the rate of false-positive results for the BRT and Delvotest microbiological inhibitor tests. Milk samples were obtained after morning milking of Manchega ewes at 15, 30, 45, 60, 75, 90, 105, 120, and 135 days after parturition. The animals did not receive any kind of treatment or medicated feed throughout the experiment. The false-positive rates for BRT and Delvotest were 3.75 and 2.4%, respectively. When the logistic regression model was applied, the percentages of total solids for positive samples were significantly different from those for negative samples (16.90 versus 18.42% for BRT, 16.05 versus 18.45% for Delvotest), while the SCC logarithmic transformation was significantly higher for the positive samples than for the negative samples (5.38 versus 5.11 log units for BRT, 5.32 versus 5.11 log units for Delvotest). Moreover, Delvotest-positive samples exhibited thiocyanate concentrations higher than those of Delvotest-negative samples (8.18 mg/liter versus 6.85 mg/liter). Further analyses are needed to confirm the possible presence of antimicrobial residues in this particular type of milk sample.

Rapid Identification of Laboratory Contamination with Mycobacterium tuberculosis Using Variable Number Tandem Repeat Analysis

PubMed Central

Gascoyne-Binzi, Deborah M.; Barlow, Rachael E. L.; Frothingham, Richard; Robinson, Grant; Collyns, Timothy A.; Gelletlie, Ruth; Hawkey, Peter M.

2001-01-01

Compared with solid media, broth-based mycobacterial culture systems have increased sensitivity but also have higher false-positive rates due to cross-contamination. Systematic strain typing is rarely undertaken because the techniques are technically demanding and the data are difficult to organize. Variable number tandem repeat (VNTR) analysis by PCR is rapid and reproducible. The digital profile is easily manipulated in a database. We undertook a retrospective study of Mycobacterium tuberculosis isolates collected over an 18-month period following the introduction of the BACTEC MGIT 960 system. VNTR allele profiles were determined with early positive broth cultures and entered into a database with the specimen processing date and other specimen data. We found 36 distinct VNTR profiles in cultures from 144 patients. Three common VNTR profiles accounted for 45% of true-positive cases. By combining VNTR results with specimen data, we identified nine cross-contamination incidents, six of which were previously unsuspected. These nine incidents resulted in 34 false-positive cultures for 29 patients. False-positive cultures were identified for three patients who had previously been culture positive for tuberculosis and were receiving treatment. Identification of cross-contamination incidents requires careful documentation of specimen data and good communication between clinical and laboratory staff. Automated broth culture systems should be supplemented with molecular analysis to identify cross-contamination events. VNTR analysis is reproducible and provides timely results when applied to early positive broth cultures. This method should ensure that patients are not placed on unnecessary tuberculosis therapy or that cases are not falsely identified as treatment failures. In addition, areas where existing procedures may be improved can be identified. PMID:11136751

Cross-reactions in specific Brachyspira spp. PCR assays caused by "Brachyspira hampsonii" isolates: implications for detection.

PubMed

Aller-Morán, Luis M; Martínez-Lobo, F Javier; Rubio, Pedro; Carvajal, Ana

2016-11-01

An emerging novel spirochete in swine, provisionally designated "Brachyspira hampsonii," has been detected worldwide. It has been associated with swine dysentery and cannot be differentiated from B. hyodysenteriae, the classical etiologic agent of this disease, using standard phenotypic methods. We evaluated cross-reactions of "B. hampsonii" isolates recovered from avian species in some of the currently available species-specific polymerase chain reaction (PCR) assays for the identification of swine Brachyspira species. Ten avian "B. hampsonii" isolates recovered from wild waterfowl were used. No false-positive results were recorded with a B. pilosicoli-specific PCR based on the amplification of a fragment of the 16S rRNA gene. However, the percentage of false-positive results varied, with a range of 10-80%, in the evaluated B. hyodysenteriae-specific assays based on the amplification of the 23S rRNA, nox, and tlyA genes. Similarly, results of the B. intermedia-specific PCR assays yielded poor specificity, with up to 80% of the "B. hampsonii" isolates tested giving false-positive results. Finally, 2 "B. hampsonii" avian isolates yielded a positive result in a B. innocens- and B. murdochii-specific PCR. This result should be interpreted very cautiously as these 2 isolates could represent a recombinant genotype. © 2016 The Author(s).

Case report: false negative serum cryptococcal latex agglutination test in a patient with disseminated cryptococcal disease.

PubMed

Navabi, Nazlee; Montebatsi, Milton; Scott, Michelle; Gluckman, Stephen J; Reid, Michael J A

2015-01-01

A case of false-negative serum latex agglutination cryptococcal antigen (CRAG) test in a 45-year-old HIV-positive male with Cryptococcus-positive culture is described. The patient was presented to a hospital in Botswana, with breathlessness and a diffuse papular rash. His CD4 count was 25 cells/μL. Despite the suspicion for disseminated cryptococcal disease, an initial serum CRAG latex test was negative. Results of subsequent Indian ink staining, culture of cerebrospinal fluid and skin scrapings, and serum lateral flow immunoassay (LFA) were all positive for Cryptococcus neoformans. There are several possible explanations for the false-negative CRAG latex test. Given the positive LFA result, we speculate that disease may have been caused by Cryptococcus gattii, which is estimated to be responsible for between 15% and 30% of all cryptococcal diseases in Botswana. Reduced sensitivity of CRAG latex assays for detecting C gattii may lead to underdiagnosis of cryptococcal infection. © The Author(s) 2014.

Test Performance and Test-Retest Reliability of the Vestibular/Ocular Motor Screening and King-Devick Test in Adolescent Athletes During a Competitive Sport Season.

PubMed

Worts, Phillip R; Schatz, Philip; Burkhart, Scott O

2018-05-01

The Vestibular/Ocular Motor Screening (VOMS) and King-Devick (K-D) test are tools designed to assess ocular or vestibular function after a sport-related concussion. To determine the test-retest reliability and rate of false-positive results of the VOMS and K-D test in a healthy athlete sample. Cohort study (diagnosis); Level of evidence, 2. Forty-five healthy high school student-athletes (mean age, 16.11 ± 1.43 years) completed self-reported demographics and medical history and were administered the VOMS and K-D test during rest on day 1 (baseline). The VOMS and K-D test were administered again once during rest (prepractice) and once within 5 minutes of removal from sport practice on day 2 (removal). The Borg rating of perceived exertion scale was administered at removal. Intraclass correlation coefficients were used to determine test-retest reliability on the K-D test and the average near point of convergence (NPC) distance on the VOMS. Level of agreement was used to examine VOMS symptom provocation over the 3 administration times. Multivariate base rates were used to determine the rate of false-positive results when simultaneously considering multiple clinical cutoffs. Test-retest reliability of total time on the K-D test (0.91 [95% CI, 0.86-0.95]) and NPC distance (0.91 [95% CI, 0.85-0.95]) was high across the 3 administration times. Level of agreement ranged from 48.9% to 88.9% across all 3 times for the VOMS items. Using established clinical cutoffs, false-positive results occurred in 2% of the sample using the VOMS at removal and 36% using the K-D test. The VOMS displayed a false-positive rate of 2% in this high school student-athlete cohort. The K-D test's false-positive rate was 36% while maintaining a high level of test-retest reliability (0.91). Results from this study support future investigation of VOMS administration in an acutely injured high school athletic sample. Going forward, the VOMS may be more stable than other neurological and symptom report screening measures and less vulnerable to false-positive results than the K-D test.

Influence of ECG measurement accuracy on ECG diagnostic statements.

PubMed

Zywietz, C; Celikag, D; Joseph, G

1996-01-01

Computer analysis of electrocardiograms (ECGs) provides a large amount of ECG measurement data, which may be used for diagnostic classification and storage in ECG databases. Until now, neither error limits for ECG measurements have been specified nor has their influence on diagnostic statements been systematically investigated. An analytical method is presented to estimate the influence of measurement errors on the accuracy of diagnostic ECG statements. Systematic (offset) errors will usually result in an increase of false positive or false negative statements since they cause a shift of the working point on the receiver operating characteristics curve. Measurement error dispersion broadens the distribution function of discriminative measurement parameters and, therefore, usually increases the overlap between discriminative parameters. This results in a flattening of the receiver operating characteristics curve and an increase of false positive and false negative classifications. The method developed has been applied to ECG conduction defect diagnoses by using the proposed International Electrotechnical Commission's interval measurement tolerance limits. These limits appear too large because more than 30% of false positive atrial conduction defect statements and 10-18% of false intraventricular conduction defect statements could be expected due to tolerated measurement errors. To assure long-term usability of ECG measurement databases, it is recommended that systems provide its error tolerance limits obtained on a defined test set.

Occupancy models for data with false positive and false negative errors and heterogeneity across sites and surveys

Treesearch

Paige F.B. Ferguson; Michael J. Conroy; Jeffrey Hepinstall-Cymerman; Nigel Yoccoz

2015-01-01

False positive detections, such as species misidentifications, occur in ecological data, although many models do not account for them. Consequently, these models are expected to generate biased inference.The main challenge in an analysis of data with false positives is to distinguish false positive and false negative...

False-negative rapid diagnostic tests for malaria and deletion of the histidine-rich repeat region of the hrp2 gene.

PubMed

Koita, Ousmane A; Doumbo, Ogobara K; Ouattara, Amed; Tall, Lalla K; Konaré, Aoua; Diakité, Mahamadou; Diallo, Mouctar; Sagara, Issaka; Masinde, Godfred L; Doumbo, Safiatou N; Dolo, Amagana; Tounkara, Anatole; Traoré, Issa; Krogstad, Donald J

2012-02-01

We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered.

Clinical significance of FDG-PET/CT at the postoperative surveillance in the breast cancer patients.

PubMed

Jung, Na Young; Yoo, Ie Ryung; Kang, Bong Joo; Kim, Sung Hun; Chae, Byung Joo; Seo, Ye Young

2016-01-01

We evaluated the clinical role of [(18)F]-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) compared with conventional imaging (CI) to detect locoregional recurrence or distant metastasis during postoperative surveillance of patients with breast cancer. We included 1,819 examinations of 1,161 patients, who underwent FDG-PET/CT and CI, including mammography, breast ultrasound, whole-body bone scintigraphy, and chest radiography for postoperative surveillance. All patients had a history of surgery with or without adjuvant treatment due to more than stage II breast cancer between November 2003 and November 2009. We evaluated the diagnostic performance of CI, FDG-PET/CT, and combined CI and FDG-PET/CT for detecting locoregional recurrence, distant metastasis, and incidental cancer. We also analyzed false-positive and false-negative results in both FDG-PET/CT and CI. Sensitivity, specificity, positive predictive value, and negative predictive value of CI were 75.4, 98.7, 93.4, and 94.3 %. Those of FDG-PET/CT were 97.5, 98.8, 95.4, and 99.4 %. Those of the combined results were 98.6, 98.2, 96.7, and 99.7 %. Sensitivity of FDG-PET/CT was significantly higher than that of CI (P < 0.05). Sensitivity of combined CI and FDG-PET/CT results improved, but they were not significantly different from those of FDG-PET/CT alone (P = 0.43). Seventeen false-positive and nine false-negative cases were detected with FDG-PET/CT, and 19 false-positive and 88 false-negative cases were detected with CI. FDG-PET/CT is considered as an acceptable diagnostic imaging modality for postoperative surveillance of patients with breast cancer.

The accuracy of HIV rapid testing in integrated bio-behavioral surveys of men who have sex with men across 5 Provinces in South Africa

PubMed Central

Kufa, Tendesayi; Lane, Tim; Manyuchi, Albert; Singh, Beverley; Isdahl, Zachary; Osmand, Thomas; Grasso, Mike; Struthers, Helen; McIntyre, James; Chipeta, Zawadi; Puren, Adrian

2017-01-01

Abstract We describe the accuracy of serial rapid HIV testing among men who have sex with men (MSM) in South Africa and discuss the implications for HIV testing and prevention. This was a cross-sectional survey conducted at five stand-alone facilities from five provinces. Demographic, behavioral, and clinical data were collected. Dried blood spots were obtained for HIV-related testing. Participants were offered rapid HIV testing using 2 rapid diagnostic tests (RDTs) in series. In the laboratory, reference HIV testing was conducted using a third-generation enzyme immunoassay (EIA) and a fourth-generation EIA as confirmatory. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, false-positive, and false-negative rates were determined. Between August 2015 and July 2016, 2503 participants were enrolled. Of these, 2343 were tested by RDT on site with a further 2137 (91.2%) having definitive results on both RDT and EIA. Sensitivity, specificity, positive predictive value, negative predictive value, false-positive rates, and false-negative rates were 92.6% [95% confidence interval (95% CI) 89.6–94.8], 99.4% (95% CI 98.9–99.7), 97.4% (95% CI 95.2–98.6), 98.3% (95% CI 97.6–98.8), 0.6% (95% CI 0.3–1.1), and 7.4% (95% CI 5.2–10.4), respectively. False negatives were similar to true positives with respect to virological profiles. Overall accuracy of the RDT algorithm was high, but sensitivity was lower than expected. Post-HIV test counseling should include discussions of possible false-negative results and the need for retesting among HIV negatives. PMID:28700474

Whole-body scintigraphy with radioiodine-131. A comprehensive list of false-positives with some examples.

PubMed

McDougall, I R

1995-10-01

Whole-body scintigraphy with radioiodine-131 is an important diagnostic test in the management of patients with differentiated thyroid cancer who have undergone surgical treatment. The scan can demonstrate the presence of residual thyroid or functioning metastases in lymph nodes or distant sites. However, there are a number of potential pitfalls in the interpretation of this scan that could lead to a false-positive diagnosis of cancer. The scintiscans are presented for five patients in whom uptake outside of the thyroid was not due to functioning metastases. Some of these abnormalities are physiologic, such as uptake of iodine in the gastrointestinal tract. A comprehensive list of false-positive results are tabulated.

A case of placental trisomy 18 mosaicism causing a false negative NIPT result.

PubMed

Yang, Jiexia; Qi, Yiming; Guo, Fangfang; Hou, Yaping; Peng, Haishan; Wang, Dongmei; Oy, Haoxin; Yin, Aihua

2017-01-01

The non-invasive prenatal testing that evaluates circulating cell free DNA, and has been established as an additional pregnancy test for detecting the common fetal trisomies 21, 18 and 13 is rapidly revolutionizing prenatal screening as a result of its increased sensitivity and specificity. However, false positive and false negative results still exist. We presented a case in which the non-invasive prenatal testing results were normal at 15 gestational age (GA), but an ultrasound examination at 30GA showed that the fetus had heart abnormalities, and the third trimester ultrasound at 33GA noted multiple anomalies including a 3.0 mm ventricular septal defect. Along with cordocentesis at 33GA, the cord blood sample cytogenetics analysis showed a mos 47,XN,+18[61]/46,XN[39] T18 karyotype. Six placental biopsies confirmed that the chromosome 18 placenta chimerism ratio had changed from 33% to 72%. Ultimately, the pregnancy was interrupted at 34GA. We presented this case to highlight the need to clearly explain false positive or false negative results to patients. We believe that this information will also influence the development of future diagnostic test methodologies.

Minimizing false positive error with multiple performance validity tests: response to Bilder, Sugar, and Hellemann (2014 this issue).

PubMed

Larrabee, Glenn J

2014-01-01

Bilder, Sugar, and Hellemann (2014 this issue) contend that empirical support is lacking for use of multiple performance validity tests (PVTs) in evaluation of the individual case, differing from the conclusions of Davis and Millis (2014), and Larrabee (2014), who found no substantial increase in false positive rates using a criterion of failure of ≥ 2 PVTs and/or Symptom Validity Tests (SVTs) out of multiple tests administered. Reconsideration of data presented in Larrabee (2014) supports a criterion of ≥ 2 out of up to 7 PVTs/SVTs, as keeping false positive rates close to and in most cases below 10% in cases with bona fide neurologic, psychiatric, and developmental disorders. Strategies to minimize risk of false positive error are discussed, including (1) adjusting individual PVT cutoffs or criterion for number of PVTs failed, for examinees who have clinical histories placing them at risk for false positive identification (e.g., severe TBI, schizophrenia), (2) using the history of the individual case to rule out conditions known to result in false positive errors, (3) using normal performance in domains mimicked by PVTs to show that sufficient native ability exists for valid performance on the PVT(s) that have been failed, and (4) recognizing that as the number of PVTs/SVTs failed increases, the likelihood of valid clinical presentation decreases, with a corresponding increase in the likelihood of invalid test performance and symptom report.

Interval Breast Cancer Rates and Histopathologic Tumor Characteristics after False-Positive Findings at Mammography in a Population-based Screening Program.

PubMed

Hofvind, Solveig; Sagstad, Silje; Sebuødegård, Sofie; Chen, Ying; Roman, Marta; Lee, Christoph I

2018-04-01

Purpose To compare rates and tumor characteristics of interval breast cancers (IBCs) detected after a negative versus false-positive screening among women participating in the Norwegian Breast Cancer Screening Program. Materials and Methods The Cancer Registry Regulation approved this retrospective study. Information about 423 445 women aged 49-71 years who underwent 789 481 full-field digital mammographic screening examinations during 2004-2012 was extracted from the Cancer Registry of Norway. Rates and odds ratios of IBC among women with a negative (the reference group) versus a false-positive screening were estimated by using logistic regression models adjusted for age at diagnosis and county of residence. Results A total of 1302 IBCs were diagnosed after 789 481 screening examinations, of which 7.0% (91 of 1302) were detected among women with a false-positive screening as the most recent breast imaging examination before detection. By using negative screening as the reference, adjusted odds ratios of IBCs were 3.3 (95% confidence interval [CI]: 2.6, 4.2) and 2.8 (95% CI: 1.8, 4.4) for women with a false-positive screening without and with needle biopsy, respectively. Women with a previous negative screening had a significantly lower proportion of tumors that were 10 mm or less (14.3% [150 of 1049] vs 50.0% [seven of 14], respectively; P < .01) and grade I tumors (13.2% [147 of 1114] vs 42.9% [six of 14]; P < .01), but a higher proportion of cases with lymph nodes positive for cancer (40.9% [442 of 1080] vs 13.3% [two of 15], respectively; P = .03) compared with women with a previous false-positive screening with benign biopsy. A retrospective review of the screening mammographic examinations identified 42.9% (39 of 91) of the false-positive cases to be the same lesion as the IBC. Conclusion By using a negative screening as the reference, a false-positive screening examination increased the risk of an IBC three-fold. The tumor characteristics of IBC after a negative screening were less favorable compared with those detected after a previous false-positive screening. © RSNA, 2017 Online supplemental material is available for this article.

Comparative analyses across cattle genders and breeds reveal the pitfalls caused by false positive and lineage-differential copy number variations.

PubMed

Zhou, Yang; Utsunomiya, Yuri T; Xu, Lingyang; Hay, El Hamidi Abdel; Bickhart, Derek M; Sonstegard, Tad S; Van Tassell, Curtis P; Garcia, Jose Fernando; Liu, George E

2016-07-06

We compared CNV region (CNVR) results derived from 1,682 Nellore cattle with equivalent results derived from our previous analysis of Bovine HapMap samples. By comparing CNV segment frequencies between different genders and groups, we identified 9 frequent, false positive CNVRs with a total length of 0.8 Mbp that were likely caused by assembly errors. Although there was a paucity of lineage specific events, we did find one 54 kb deletion on chr5 significantly enriched in Nellore cattle. A few highly frequent CNVRs present in both datasets were detected within genomic regions containing olfactory receptor, ATP-binding cassette, and major histocompatibility complex genes. We further evaluated their impacts on downstream bioinformatics and CNV association analyses. Our results revealed pitfalls caused by false positive and lineage-differential copy number variations and will increase the accuracy of future CNV studies in both taurine and indicine cattle.

Statistics provide guidance for indigenous organic carbon detection on Mars missions.

PubMed

Sephton, Mark A; Carter, Jonathan N

2014-08-01

Data from the Viking and Mars Science Laboratory missions indicate the presence of organic compounds that are not definitively martian in origin. Both contamination and confounding mineralogies have been suggested as alternatives to indigenous organic carbon. Intuitive thought suggests that we are repeatedly obtaining data that confirms the same level of uncertainty. Bayesian statistics may suggest otherwise. If an organic detection method has a true positive to false positive ratio greater than one, then repeated organic matter detection progressively increases the probability of indigeneity. Bayesian statistics also reveal that methods with higher ratios of true positives to false positives give higher overall probabilities and that detection of organic matter in a sample with a higher prior probability of indigenous organic carbon produces greater confidence. Bayesian statistics, therefore, provide guidance for the planning and operation of organic carbon detection activities on Mars. Suggestions for future organic carbon detection missions and instruments are as follows: (i) On Earth, instruments should be tested with analog samples of known organic content to determine their true positive to false positive ratios. (ii) On the mission, for an instrument with a true positive to false positive ratio above one, it should be recognized that each positive detection of organic carbon will result in a progressive increase in the probability of indigenous organic carbon being present; repeated measurements, therefore, can overcome some of the deficiencies of a less-than-definitive test. (iii) For a fixed number of analyses, the highest true positive to false positive ratio method or instrument will provide the greatest probability that indigenous organic carbon is present. (iv) On Mars, analyses should concentrate on samples with highest prior probability of indigenous organic carbon; intuitive desires to contrast samples of high prior probability and low prior probability of indigenous organic carbon should be resisted.

Evaluation of microtiter-plate enzyme-linked immunosorbent assay for the analysis of triazine and chloroacetanilide herbicides in rainfall

USGS Publications Warehouse

Pomes, M.L.; Thurman, E.M.; Aga, D.S.; Goolsby, D.A.

1998-01-01

Triazine and chloroacetanilide concentrations in rainfall samples collected from a 23-state region of the United States were analyzed with microtiter-plate enzyme-linked immunosorbent assay (ELISA). Thirty-six percent of rainfall samples (2072 out of 5691) were confirmed using gas chromatography/mass spectrometry (GC/MS) to evaluate the operating performance of ELISA as a screening test. Comparison of ELISA to GC/MS results showed that the two ELISA methods accurately reported GC/MS results (m = 1), but with more variability evident with the triazine than with the chloroacetanilide ELISA. Bayes's rule, a standardized method to report the results of screening tests, indicated that the two ELISA methods yielded comparable predictive values (80%), but the triazine ELISA yielded a false- positive rate of 11.8% and the chloroacetanilide ELISA yielded a false- negative rate of 23.1%. The false-positive rate for the triazine ELISA may arise from cross reactivity with an unknown triazine or metabolite. The false-negative rate of the chloroacetanilide ELISA probably resulted from a combination of low sensitivity at the reporting limit of 0.15 ??g/L and a distribution characterized by 75% of the samples at or below the reporting limit of 0.15 ??g/L.Triazine and chloroacetanilide concentrations in rainfall samples collected from a 23-state region of the United States were analyzed with microtiter-plate enzyme-linked immunosorbent assay (ELISA). Thirty-six percent of rainfall samples (2072 out of 5691) were confirmed using gas chromatography/mass spectrometry (GC/MS) to evaluate the operating performance of ELISA as a screening test. Comparison of ELISA to GC/MS results showed that the two ELISA methods accurately reported GC/MS results (m = 1), but with more variability evident with the triazine than with the chloroacetanilide ELISA. Bayes's rule, a standardized method to report the results of screening tests, indicated that the two ELISA methods yielded comparable predictive values (80%), but the triazine ELISA yielded a false-positive rate of 11.8% and the chloroacetanilide ELISA yielded a false-negative rate of 23.1%. The false-positive rate for the triazine ELISA may arise from cross reactivity with an unknown triazine or metabolite. The false-negative rate of the chloroacetanilide ELISA probably resulted from a combination of low sensitivity at the reporting limit of 0.15 ??g/L and a distribution characterized by 75% of the samples at or below the reporting limit of 0.15 ??g/L.

Six years' experience of using the BacT/ALERT system to screen all platelet concentrates, and additional testing of outdated platelet concentrates to estimate the frequency of false-negative results.

PubMed

Larsen, C P; Ezligini, F; Hermansen, N O; Kjeldsen-Kragh, J

2005-02-01

Approximately 1 in every 2000 units of platelets is contaminated with bacteria. The BacT/ALERT automated blood culture system can be used to screen platelet concentrates (PCs) for bacterial contamination. Data were collected from May 1998 until May 2004. The number of PCs tested during this period was 36 896, most of which were produced from pools of four buffy-coats. On the day following blood collection or platelet apheresis, a 5-10 ml sample of the PC was aseptically transferred to a BacT/ALERT culture bottle for detection of aerobic bacteria. The sample was monitored for bacterial growth during the entire storage period of the PC (6.5 days). When a positive signal was generated, the culture bottle, the PC and the erythrocyte concentrates were tested for bacterial growth. In order to determine the frequency of false-negative BacT/ALERT signals, 1061 outdated PCs were tested during the period from May 2002 to May 2004. Eighty-eight positive signals were detected by the BacT/ALERT system, of which 12 were interpreted as truly positive. Fourteen signals were interpreted as truly false positive. Thirty-three signals were interpreted to be probably false positive. Two of 1061 outdated units tested positive, and Bacillus spp. and Staphylococcus epidermidis, respectively, were isolated from these PCs. Between 0.03% and 0.12% of the PCs were contaminated with bacteria. BacT/ALERT is an efficient tool for monitoring PCs for bacterial contamination; however, it is important to realize that false-negative results may occur.

Impact of false-negative sentinel lymph node biopsy on survival in patients with cutaneous melanoma.

PubMed

Caracò, C; Marone, U; Celentano, E; Botti, G; Mozzillo, N

2007-09-01

Sentinel lymph node biopsy is widely accepted as standard care in melanoma despite lack of pertinent randomized trials results. A possible pitfall of this procedure is the inaccurate identification of the sentinel lymph node leading to biopsy and analysis of a nonsentinel node. Such a technical failure may yield a different prognosis. The purpose of this study is to analyze the incidence of false negativity and its impact on clinical outcome and to try to understand its causes. The Melanoma Data Base at National Cancer Institute of Naples was analyzed comparing results between false-negative and tumor-positive sentinel node patients focusing on overall survival and prognostic factors influencing the clinical outcome. One hundred fifty-one cases were diagnosed to be tumor-positive after sentinel lymph node biopsy and were subjected to complete lymph node dissection. Thirty-four (18.4%)patients with tumor-negative sentinel node subsequently developed lymph node metastases in the basin site of the sentinel procedure. With a median follow-up of 42.8 months the 5-year overall survival was 48.4% and 66.3% for false-negative and tumor-positive group respectively with significant statistical differences (P < .03). The sensitivity of sentinel lymph node biopsy was 81.6%, and a regional nodal basin recurrence after negative-sentinel node biopsy means a worse prognosis, compared with patients submitted to complete lymph node dissection after a positive sentinel biopsy. The evidence of higher number of tumor-positive nodes after delayed lymphadenectomy in false-negative group compared with tumor-positive sentinel node cases, confirmed the importance of an early staging of lymph nodal involvement. Further data will better clarify the role of prognostic factors to identify cases with a more aggressive biological behavior of the disease.

76 FR 59410 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... tumors. The experimental results (average of 91.4% true positive volume fraction and 4.0% of false... test for the tumor marker CA-125. The CA-125 test only returns a true positive result for about 50% of...

New Constraints on the False Positive Rate for Short-Period Kepler Planet Candidates

NASA Astrophysics Data System (ADS)

Colón, Knicole D.; Morehead, Robert C.; Ford, Eric B.

2015-01-01

The Kepler space mission has discovered thousands of potential planets orbiting other stars, thereby setting the stage for in-depth studies of different populations of planets. We present new multi-wavelength transit photometry of small (Rp < 6 Earth radii), short-period (P < 6 days) Kepler planet candidates acquired with the Gran Telescopio Canarias. Multi-wavelength transit photometry allows us to search for wavelength-dependent transit depths and subsequently identify eclipsing binary false positives (which are especially prevalent at the shortest orbital periods). We combine these new observations of three candidates with previous results for five other candidates (Colón & Ford 2011 and Colón, Ford, & Morehead 2012) to provide new constraints on the false positive rate for small, close-in candidates. In our full sample, we identify four candidates as viable planets and four as eclipsing binary false positives. We therefore find a higher false positive rate for small, close-in candidates compared to the lower false positive rate of ~10% determined by other studies for the full sample of Kepler planet candidates (e.g. Fressin et al. 2013). We also discuss the dearth of known planets with periods less than ~2.5 days and radii between ~3 and 11 Earth radii (the so-called 'sub-Jovian desert'), since the majority of the candidates in our study are located in or around this 'desert.' The lack of planets with these orbital and physical properties is not expected to be due to observational bias, as short-period planets are generally easier to detect (especially if they are larger or more massive than Earth). We consider the implications of our results for the other ~20 Kepler planet candidates located in this desert. Characterizing these candidates will allow us to better understand the formation processes of this apparently rare class of planets.

Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications

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

Mordang, Jan-Jurre, E-mail: Jan-Jurre.Mordang@radboudumc.nl; Gubern-Mérida, Albert; Karssemeijer, Nico

Purpose: In the past decades, computer-aided detection (CADe) systems have been developed to aid screening radiologists in the detection of malignant microcalcifications. These systems are useful to avoid perceptual oversights and can increase the radiologists’ detection rate. However, due to the high number of false positives marked by these CADe systems, they are not yet suitable as an independent reader. Breast arterial calcifications (BACs) are one of the most frequent false positives marked by CADe systems. In this study, a method is proposed for the elimination of BACs as positive findings. Removal of these false positives will increase the performancemore » of the CADe system in finding malignant microcalcifications. Methods: A multistage method is proposed for the removal of BAC findings. The first stage consists of a microcalcification candidate selection, segmentation and grouping of the microcalcifications, and classification to remove obvious false positives. In the second stage, a case-based selection is applied where cases are selected which contain BACs. In the final stage, BACs are removed from the selected cases. The BACs removal stage consists of a GentleBoost classifier trained on microcalcification features describing their shape, topology, and texture. Additionally, novel features are introduced to discriminate BACs from other positive findings. Results: The CADe system was evaluated with and without BACs removal. Here, both systems were applied on a validation set containing 1088 cases of which 95 cases contained malignant microcalcifications. After bootstrapping, free-response receiver operating characteristics and receiver operating characteristics analyses were carried out. Performance between the two systems was compared at 0.98 and 0.95 specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52% and the sensitivity increased from 62% up to 76% at a specificity of 0.95. Partial areas under the curve in the specificity range of 0.8–1.0 were significantly different between the system without BACs removal and the system with BACs removal, 0.129 ± 0.009 versus 0.144 ± 0.008 (p<0.05), respectively. Additionally, the sensitivity at one false positive per 50 cases and one false positive per 25 cases increased as well, 37% versus 51% (p<0.05) and 58% versus 67% (p<0.05) sensitivity, respectively. Additionally, the CADe system with BACs removal reduces the number of false positives per case by 29% on average. The same sensitivity at one false positive per 50 cases in the CADe system without BACs removal can be achieved at one false positive per 80 cases in the CADe system with BACs removal. Conclusions: By using dedicated algorithms to detect and remove breast arterial calcifications, the performance of CADe systems can be improved, in particular, at false positive rates representative for operating points used in screening.« less

DNA typing by microbead arrays and PCR-SSP: apparent false-negative or -positive hybridization or amplification signals disclose new HLA-B and -DRB1 alleles.

PubMed

Rahal, M; Kervaire, B; Villard, J; Tiercy, J-M

2008-03-01

Human leukocyte antigen (HLA) typing by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) hybridization on solid phase (microbead assay) or polymerase chain reaction-sequence-specific primers (PCR-SSP) requires interpretation softwares to detect all possible allele combinations. These programs propose allele calls by taking into account false-positive or false-negative signal(s). The laboratory has the option to validate typing results in the presence of strongly cross-reacting or apparent false-negative signals. Alternatively, these seemingly aberrant signals may disclose novel variants. We report here four new HLA-B (B*5620 and B*5716) and HLA-DRB1 alleles (DRB1*110107 and DRB1*1474) that were detected by apparent false-negative or -positive hybridization or amplification patterns, and ultimately resolved by sequencing. To avoid allele misassignments, a comprehensive evaluation of acquired data as documented in a quality assurance system is therefore required to confirm unambiguous typing interpretation.

Urine drug screens: Considerations for the psychiatric pharmacist

PubMed Central

Hale, Genevieve M.; Ross, Clint

2016-01-01

Introduction: Proper psychiatric evaluation of patients necessitates that the clinician be vigilant in ruling out secondary causes of symptoms, such as substance-induced symptoms. Immunoassay-type urine drug screens (UDSs) offer clinicians rapid drug screen results, ease of use, and inexpensive cost. Unfortunately, these screens are not without their limitations. This review aims to outline the nuances and limitations of immunoassay UDSs and to provide the clinician with information that facilitates more accurate interpretation of UDS results. Specifically, false positive results associated with psychiatric medications and the availability and methods for acquisition of commercialized UDS masking agents will be reviewed. Methods: A literature review was conducted to identify false positive UDSs associated with psychiatric medications. References for each article identified were also reviewed. Additionally, a Google® search was conducted to identify commercially available preparations used to mask UDS results and the methods of acquisition of these products. Results: A total of 14 articles were identified using PubMed. No articles for mood stabilizing agents were identified. Entering the phrase how to pass a drug test into Google® search yielded about 12.6 million results, and select references were reviewed based on relevance and user reviews. Discussion: Several psychiatric medications are documented as potential sources of false positive UDSs. Additionally, several agents are available for consumer purchase that may result in false negative UDSs. The clinician must be vigilant in interpreting immunoassay UDS results and should utilize more advanced forms of testing as clinically appropriate.

Differential specificity of selective culture media for enumeration of pathogenic vibrios: advantages and limitations of multi-plating methods.

PubMed

Nigro, Olivia D; Steward, Grieg F

2015-04-01

Plating environmental samples on vibrio-selective chromogenic media is a commonly used technique that allows one to quickly estimate concentrations of putative vibrio pathogens or to isolate them for further study. Although this approach is convenient, its usefulness depends directly on how well the procedure selects against false positives. We tested whether a chromogenic medium, CHROMagar Vibrio (CaV), used alone (single-plating) or in combination (double-plating) with a traditional medium thiosulfate-citrate-bile-salts (TCBS), could improve the discrimination among three pathogenic vibrio species (Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus) and thereby decrease the number of false-positive colonies that must be screened by molecular methods. Assays were conducted on water samples from two estuarine environments (one subtropical, one tropical) in a variety of seasonal conditions. The results of the double-plating method were confirmed by PCR and 16S rRNA sequencing. Our data indicate that there is no significant difference in the false-positive rate between CaV and TCBS when using a single-plating technique, but determining color changes on the two media sequentially (double-plating) reduced the rate of false positive identification in most cases. The improvement achieved was about two-fold on average, but varied greatly (from 0- to 5-fold) and depended on the sampling time and location. The double-plating method was most effective for V. vulnificus in warm months, when overall V. vulnificus abundance is high (false positive rates as low as 2%, n=178). Similar results were obtained for V. cholerae (minimum false positive rate of 16%, n=146). In contrast, the false positive rate for V. parahaemolyticus was always high (minimum of 59%, n=109). Sequence analysis of false-positive isolates indicated that the majority of confounding isolates are from the Vibrionaceae family, however, members of distantly related bacterial groups were also able to grow on vibrio-selective media, even when using the double-plating method. In conclusion, the double-plating assay is a simple means to increase the efficiency of identifying pathogenic vibrios in aquatic environments and to reduce the number of molecular assays required for identity confirmation. However, the high spatial and temporal variability in the performance of the media mean that molecular approaches are still essential to obtain the most accurate vibrio abundance estimates from environmental samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of Reverse Transcriptase -PCR (RT-PCR) for rapid detection of viable Escherichia coli in drinking water samples.

PubMed

Molaee, Neda; Abtahi, Hamid; Ghannadzadeh, Mohammad Javad; Karimi, Masoude; Ghaznavi-Rad, Ehsanollah

2015-01-01

Polymerase chain reaction (PCR) is preferred to other methods for detecting Escherichia coli (E. coli) in water in terms of speed, accuracy and efficiency. False positive result is considered as the major disadvantages of PCR. For this reason, reverse transcriptase-polymerase chain reaction (RT-PCR) can be used to solve this problem. The aim of present study was to determine the efficiency of RT-PCR for rapid detection of viable Escherichia coli in drinking water samples and enhance its sensitivity through application of different filter membranes. Specific primers were designed for 16S rRNA and elongation Factor II genes. Different concentrations of bacteria were passed through FHLP and HAWP filters. Then, RT-PCR was performed using 16srRNA and EF -Tu primers. Contamination of 10 wells was determined by RT-PCR in Arak city. To evaluate RT-PCR efficiency, the results were compared with most probable number (MPN) method. RT-PCR is able to detect bacteria in different concentrations. Application of EF II primers reduced false positive results compared to 16S rRNA primers. The FHLP hydrophobic filters have higher ability to absorb bacteria compared with HAWB hydrophilic filters. So the use of hydrophobic filters will increase the sensitivity of RT-PCR. RT-PCR shows a higher sensitivity compared to conventional water contamination detection method. Unlike PCR, RT-PCR does not lead to false positive results. The use of EF-Tu primers can reduce the incidence of false positive results. Furthermore, hydrophobic filters have a higher ability to absorb bacteria compared to hydrophilic filters.

Likelihood of early detection of breast cancer in relation to false-positive risk in life-time mammographic screening: population-based cohort study.

PubMed

Otten, J D M; Fracheboud, J; den Heeten, G J; Otto, S J; Holland, R; de Koning, H J; Broeders, M J M; Verbeek, A L M

2013-10-01

Women require balanced, high-quality information when making an informed decision on screening benefits and harms before attending biennial mammographic screening. The cumulative risk of a false-positive recall and/or (small) screen-detected or interval cancer over 13 consecutive screening examinations for women aged 50 from the start of screening were estimated using data from the Nijmegen programme, the Netherlands. Women who underwent 13 successive screens in the period 1975-1976 had a 5.3% cumulative chance of a screen-detected cancer, with a 4.2% risk of at least one false-positive recall. The risk of being diagnosed with interval cancer was 3.7%. Two decades later, these estimates were 6.9%, 7.3% and 2.9%, respectively. The chance of detection of a small, favourable invasive breast cancer, anticipating a normal life-expectancy, rose from 2.3% to 3.7%. Extrapolation to digital screening mammography indicates that the proportion of false-positive results will rise to 16%. Dutch women about to participate in the screening programme can be reassured that the chance of false-positive recall in the Netherlands is relatively low. A new screening policy and improved mammography have increased the detection of an early screening carcinoma and lowering the risk of interval carcinoma.

Improving computer-aided detection assistance in breast cancer screening by removal of obviously false-positive findings.

PubMed

Mordang, Jan-Jurre; Gubern-Mérida, Albert; Bria, Alessandro; Tortorella, Francesco; den Heeten, Gerard; Karssemeijer, Nico

2017-04-01

Computer-aided detection (CADe) systems for mammography screening still mark many false positives. This can cause radiologists to lose confidence in CADe, especially when many false positives are obviously not suspicious to them. In this study, we focus on obvious false positives generated by microcalcification detection algorithms. We aim at reducing the number of obvious false-positive findings by adding an additional step in the detection method. In this step, a multiclass machine learning method is implemented in which dedicated classifiers learn to recognize the patterns of obvious false-positive subtypes that occur most frequently. The method is compared to a conventional two-class approach, where all false-positive subtypes are grouped together in one class, and to the baseline CADe system without the new false-positive removal step. The methods are evaluated on an independent dataset containing 1,542 screening examinations of which 80 examinations contain malignant microcalcifications. Analysis showed that the multiclass approach yielded a significantly higher sensitivity compared to the other two methods (P < 0.0002). At one obvious false positive per 100 images, the baseline CADe system detected 61% of the malignant examinations, while the systems with the two-class and multiclass false-positive reduction step detected 73% and 83%, respectively. Our study showed that by adding the proposed method to a CADe system, the number of obvious false positives can decrease significantly (P < 0.0002). © 2017 American Association of Physicists in Medicine.

False Positive and False Negative Effects on Network Attacks

NASA Astrophysics Data System (ADS)

Shang, Yilun

2018-01-01

Robustness against attacks serves as evidence for complex network structures and failure mechanisms that lie behind them. Most often, due to detection capability limitation or good disguises, attacks on networks are subject to false positives and false negatives, meaning that functional nodes may be falsely regarded as compromised by the attacker and vice versa. In this work, we initiate a study of false positive/negative effects on network robustness against three fundamental types of attack strategies, namely, random attacks (RA), localized attacks (LA), and targeted attack (TA). By developing a general mathematical framework based upon the percolation model, we investigate analytically and by numerical simulations of attack robustness with false positive/negative rate (FPR/FNR) on three benchmark models including Erdős-Rényi (ER) networks, random regular (RR) networks, and scale-free (SF) networks. We show that ER networks are equivalently robust against RA and LA only when FPR equals zero or the initial network is intact. We find several interesting crossovers in RR and SF networks when FPR is taken into consideration. By defining the cost of attack, we observe diminishing marginal attack efficiency for RA, LA, and TA. Our finding highlights the potential risk of underestimating or ignoring FPR in understanding attack robustness. The results may provide insights into ways of enhancing robustness of network architecture and improve the level of protection of critical infrastructures.

Cumulative False-Positive QuantiFERON-TB Interferon-γ Release Assay Results.

PubMed

Gamsky, Thomas E; Lum, Thomas; Hung-Fan, Melody; Green, Jon A

2016-05-01

Despite reports of unreliability, the QuantiFERON-TB interferon-γ release assay is increasingly used for the annual screening of individuals at risk for latent tuberculosis. Continued use of the QuantiFERON-TB assay suggests the need for more definitive evidence of its reproducibility and accuracy. To examine reproducibility and the accumulation of false-positive test results when the QuantiFERON-TB is repeated annually and to examine the validity of confirming positive test results with the performance of a second QuantiFERON-TB. We performed a retrospective, longitudinal evaluation of results from serial screening of a cohort of emergency responders from 2001 to 2013. Results of tuberculin tests and QuantiFERON-TB tests performed annually as part of a mandated first responder examination were retroactively reviewed. In this population, positive results occurred in new individuals each year. QuantiFERON-TB results were positive in 80 of 557 tuberculin test-negative individuals examined annually for a maximum of 7 years. Only 10 individuals with initially positive results remained positive when the test was repeated the next year, and 9 of these 10 were QuantiFERON-TB-negative within 3 years. The number of individuals with a positive result increased annually, and, after 7 years, 32 (27.4%) of 117 people had a positive result. When viewed in the context of the extensive literature documenting unreliable QuantiFERON-TB test performance, our findings of frequent, cumulative, sporadic, and irreproducible positive results support discontinuing the use of the QuantiFERON-TB assay for the diagnosis of latent tuberculosis in low-risk populations.

Quality control in molecular immunohistochemistry

PubMed Central

2008-01-01

Immunoperoxidase histochemistry is a widespread method of assessing expression of biomolecules in tissue samples. Accurate assessment of the expression levels of genes is critical for the management of disease, particularly as therapy targeted to specific molecules becomes more widespread. Determining the quality of preservation of macromolecules in tissue is important to avoid false negative and false positive results. In this review we discuss (1) issues of sensitivity (false negativity) and specificity (false positivity) of immunohistochemical stains, (2) approaches to better understanding differences in immunostains done by different laboratories (including the recently proposed MISFISHIE specification for tissue localization studies), and (3) approaches to assessing the quality of preservation of macromolecules in tissue, particularly in small biopsy samples. PMID:18648842

Evaluation of the black light test for screening aflatoxin-contaminated maize in the Brazilian food industry.

PubMed

Gloria, E M; Fonseca, H; Calori-Domingues, M A; Souza, I M

1998-01-01

The results of the black light test for aflatoxin-contaminated maize carried out in a large food factory in the State of São Paulo was evaluated against bi-directional thin layer chromatography (TLC) analysis for 286 samples of maize. All 286 samples were accepted by the black light test (< 7 fluorescent points), however, the results from TLC analysis showed that 96 samples were contaminated and 14 showed aflatoxin B1 contamination levels higher than 20 micrograms/kg. There were 14 false negative results and no false positives and out of the 14 samples, six did not show visible fluorescent points. If the rejection criterion of one or more fluorescent points were applied, the six samples would be accepted by the black light test. But, in this case, 95 samples would be rejected and 87 results would be false positives because they did not have contamination levels over 20 micrograms/kg which is the acceptance limit of the black light test. The results indicate that the black light test, as utilized by this factory, was not able to indicate lots with possible contamination and the black light test, as recommended in the literature, would produce a high number of false positives. It is necessary to make more studies on the use of black light as a screening test for possible aflatoxin B1-contaminated maize.

Performance of CT scan of abdomen and pelvis in detecting asymptomatic synchronous metastasis in breast cancer.

PubMed

James, Justin; Teo, Melanie; Ramachandran, Vivekananda; Law, Michael; Stoney, David; Cheng, Michael

2017-10-01

In many centres in Australia, CT scan of abdomen and pelvis (CTAP) is a commonly used staging investigation to detect asymptomatic synchronous metastasis (ASM) in newly diagnosed breast cancer. However, its routine use is not supported by strong evidence either on its cost effectiveness or on specificity. Despite contrary recommendations by international guidelines this staging investigation is widely used among new early breast cancers(EBC). This retrospective study aims to assess the cost effectiveness and usefulness of CTAP in new breast cancers. All patients with primary invasive breast cancers who underwent breast cancer treatment through Eastern health breast unit during 50-month period from January 2012 were included in the study. All staging CTAP results were reviewed to evaluate its yield, false positive rate and cost of investigation per single positive result. Odds ratio for positive test results were calculated for five possible risk factors (Age less than 40 years, stage III disease, presence of LVI, HER2 positive disease and presence of metastasis in lymph node). 49% (n = 285) of all breast cancer patient underwent staging CTAP which lead to the detection of 4 ASM. (Over all yield of 1%) Overall false positive rate was 15% because of 42 indeterminate results needing further tests. Based merely on approved billing rates this amounted to $ 40733 per single ASM identified. Presence of lymph node metastasis did not increase the chance of positive test result (OR = 1.3; CI:0.13-12.69). Staging CTAP is associated with high incidence of false positive rates and low yield, especially among EBCs. It is desirable to choose this investigation more selectively than currently practiced. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Restricted Boltzmann machines based oversampling and semi-supervised learning for false positive reduction in breast CAD.

PubMed

Cao, Peng; Liu, Xiaoli; Bao, Hang; Yang, Jinzhu; Zhao, Dazhe

2015-01-01

The false-positive reduction (FPR) is a crucial step in the computer aided detection system for the breast. The issues of imbalanced data distribution and the limitation of labeled samples complicate the classification procedure. To overcome these challenges, we propose oversampling and semi-supervised learning methods based on the restricted Boltzmann machines (RBMs) to solve the classification of imbalanced data with a few labeled samples. To evaluate the proposed method, we conducted a comprehensive performance study and compared its results with the commonly used techniques. Experiments on benchmark dataset of DDSM demonstrate the effectiveness of the RBMs based oversampling and semi-supervised learning method in terms of geometric mean (G-mean) for false positive reduction in Breast CAD.

Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors.

PubMed

Combet, Emilie; Lean, Michael E J; Boyle, James G; Crozier, Alan; Davidson, D Fraser

2011-01-14

Urinary homovanillic acid (HVA) measurement is used routinely as a marker of the first test for the screening of catecholamine-secreting tumors and dopamine metabolism, but generates a large number of false-positive results. With no guidelines for dietary restrictions prior to the test, we hypothesize that consumption of flavonol-rich foods (such as onions, tomatoes, tea) prior to urinary catecholamine screening could be responsible for false-positive urinary HVA in healthy subjects. A randomized, crossover dietary intervention was carried out in healthy subjects (n=17). Volunteers followed either a low or high-flavonol diet, for a duration of 3 days, prior to providing a 24-h urine sample for HVA measurement using a routine, validated liquid chromatography method as well as a gas chromatography-mass spectrometry method. Dietary flavonol intake significantly increased urinary HVA excretion (p < 0.001), with 3 out of 17 volunteers (20%) exceeding the 40 μmol/24 h upper limit of normal for HVA excretion (false-positive result). Dietary flavonols commonly found in foodstuff such as tomatoes, onions, and tea, interfered with the routine urinary HVA screening test and should be avoided in the three-day run-up to the test. Copyright © 2010 Elsevier B.V. All rights reserved.

One Hundred False-Positive Amphetamine Specimens Characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry.

PubMed

Marin, Stephanie J; Doyle, Kelly; Chang, Annie; Concheiro-Guisan, Marta; Huestis, Marilyn A; Johnson-Davis, Kamisha L

2016-01-01

Some amphetamine (AMP) and ecstacy (MDMA) urine immunoassay (IA) kits are prone to false-positive results due to poor specificity of the antibody. We employed two techniques, high-resolution mass spectrometry (HRMS) and an in silico structure search, to identify compounds likely to cause false-positive results. Hundred false-positive IA specimens for AMP and/or MDMA were analyzed by an Agilent 6230 time-of-flight (TOF) mass spectrometer. Separately, SciFinder (Chemical Abstracts) was used as an in silico structure search to generate a library of compounds that are known to cross-react with AMP/MDMA IAs. Chemical formulas and exact masses of 145 structures were then compared against masses identified by TOF. Compounds known to have cross-reactivity with the IAs were identified in the structure-based search. The chemical formulas and exact masses of 145 structures (of 20 chemical formulas) were compared against masses identified by TOF. Urine analysis by HRMS correlates accurate mass with chemical formulae, but provides little information regarding compound structure. Structural data of targeted antigens can be utilized to correlate HRMS-derived chemical formulas with structural analogs. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

False positives complicate ancient pathogen identifications using high-throughput shotgun sequencing

PubMed Central

2014-01-01

Background Identification of historic pathogens is challenging since false positives and negatives are a serious risk. Environmental non-pathogenic contaminants are ubiquitous. Furthermore, public genetic databases contain limited information regarding these species. High-throughput sequencing may help reliably detect and identify historic pathogens. Results We shotgun-sequenced 8 16th-century Mixtec individuals from the site of Teposcolula Yucundaa (Oaxaca, Mexico) who are reported to have died from the huey cocoliztli (‘Great Pestilence’ in Nahautl), an unknown disease that decimated native Mexican populations during the Spanish colonial period, in order to identify the pathogen. Comparison of these sequences with those deriving from the surrounding soil and from 4 precontact individuals from the site found a wide variety of contaminant organisms that confounded analyses. Without the comparative sequence data from the precontact individuals and soil, false positives for Yersinia pestis and rickettsiosis could have been reported. Conclusions False positives and negatives remain problematic in ancient DNA analyses despite the application of high-throughput sequencing. Our results suggest that several studies claiming the discovery of ancient pathogens may need further verification. Additionally, true single molecule sequencing’s short read lengths, inability to sequence through DNA lesions, and limited ancient-DNA-specific technical development hinder its application to palaeopathology. PMID:24568097

Chronic bacterial osteomyelitis: prospective comparison of (18)F-FDG imaging with a dual-head coincidence camera and (111)In-labelled autologous leucocyte scintigraphy.

PubMed

Meller, J; Köster, G; Liersch, T; Siefker, U; Lehmann, K; Meyer, I; Schreiber, K; Altenvoerde, G; Becker, W

2002-01-01

Indium-111-labelled white blood cells ((111)In-WBCs) are currently considered the tracer of choice in the diagnostic work-up of suspected active chronic osteomyelitis (COM). Previous studies in a limited number of patients, performed with dedicated PET systems, have shown that [(18)F]2'-deoxy-2-fluoro- D-glucose (FDG) imaging may offer at least similar diagnostic accuracy. The aim of this prospective study was to compare FDG imaging with a dual-head coincidence camera (DHCC) and (111)In-WBC imaging in patients with suspected COM. Thirty consecutive non-diabetic patients with possible COM underwent combined skeletal scintigraphy (30/30 patients), (111)In-WBC imaging (28/30 patients) and FDG-PET with a DHCC (30/30 patients). During diagnostic work-up, COM was proven in 11/36 regions of suspected skeletal infection and subsequently excluded in 25/36 regions. In addition, soft tissue infection was present in five patients and septic arthritis in three. (111)In-WBC imaging in 28 patients was true positive in 2/11 regions with proven COM and true negative in 21/23 regions without further evidence of COM. False-positive results occurred in two regions and false-negative results in nine regions suspected for COM. Most of the false-negative results (7/9) occurred in the central skeleton. If the analysis was restricted to the 18 regions with available histology ( n=17) or culture ( n=1), (111)In-WBC imaging was true positive in 2/18 regions, true negative in 8/18 regions, false negative in 7/18 regions and false positive in 1/18 regions. FDG-DHCC imaging was true positive in 11/11 regions with proven COM and true negative in 23/25 regions without further evidence of COM. False-positive results occurred in two regions. If the analysis was restricted to the 19 regions with available histology ( n=18) or culture ( n=1), FDG-DHCC imaging was true positive in 9/9 regions with proven COM and true negative in 10/10 regions without further evidence of COM. It is concluded that FDG-DHCC imaging is superior to (111)In-WBC scintigraphy in the diagnosis of COM in the central skeleton and therefore should be considered the method of choice for this indication. This seems to hold true for peripheral lesions as well, but in our series the number of cases with proven infection was too small to permit a final conclusion.

Six consecutive false positive cases from cell-free fetal DNA testing in a single referring centre

PubMed Central

Dugo, Nella; Padula, Francesco; Mobili, Luisa; Brizzi, Cristiana; D’Emidio, Laura; Cignini, Pietro; Mesoraca, Alvaro; Bizzoco, Domenico; Cima, Antonella; Giorlandino, Claudio

2014-01-01

Introduction recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive Prenatal Testing) in routine clinical practice emphasizing its high sensibility and specificity. In any case, false positive and false negative findings may result from placental mosaicism, because cell-free fetal DNA originates mainly from placenta. Case we report six cases of women who underwent chorionic villus sampling (CVS) or amniocentesis to confirm the results from NIPT: two Turner syndromes, two Triple X, one Patau syndrome, one Edward syndrome. Results using classic cytogenetic analysis and, also, Array - Comparative Genomic Hybridization (Array CGH) the karyotype of all 5 fetuses was found to be normal. Conclusion results from NIPT must always be confirmed by invasive prenatal diagnosis. It is mandatory to inform the patient that the CVS and amniocentesis still represent the only form of prenatal diagnostic test available. PMID:25332757

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an artificial neural network classifier. The multi-stage system allows tuning the detection sensitivity and the identification specificity individually in each stage. It is easier to achieve optimized ATR operation based on its specific goal. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar and video image datasets.

A Closer Look at Self-Reported Suicide Attempts: False Positives and False Negatives

ERIC Educational Resources Information Center

Ploderl, Martin; Kralovec, Karl; Yazdi, Kurosch; Fartacek, Reinhold

2011-01-01

The validity of self-reported suicide attempt information is undermined by false positives (e.g., incidences without intent to die), or by unreported suicide attempts, referred to as false negatives. In a sample of 1,385 Austrian adults, we explored the occurrence of false positives and false negatives with detailed, probing questions. Removing…

[Evaluation of performance of five bioinformatics software for the prediction of missense mutations].

PubMed

Chen, Qianting; Dai, Congling; Zhang, Qianjun; Du, Juan; Li, Wen

2016-10-01

To study the prediction performance evaluation with five kinds of bioinformatics software (SIFT, PolyPhen2, MutationTaster, Provean, MutationAssessor). From own database for genetic mutations collected over the past five years, Chinese literature database, Human Gene Mutation Database, and dbSNP, 121 missense mutations confirmed by functional studies, and 121 missense mutations suspected to be pathogenic by pedigree analysis were used as positive gold standard, while 242 missense mutations with minor allele frequency (MAF)>5% in dominant hereditary diseases were used as negative gold standard. The selected mutations were predicted with the five software. Based on the results, the performance of the five software was evaluated for their sensitivity, specificity, positive predict value, false positive rate, negative predict value, false negative rate, false discovery rate, accuracy, and receiver operating characteristic curve (ROC). In terms of sensitivity, negative predictive value and false negative rate, the rank was MutationTaster, PolyPhen2, Provean, SIFT, and MutationAssessor. For specificity and false positive rate, the rank was MutationTaster, Provean, MutationAssessor, SIFT, and PolyPhen2. For positive predict value and false discovery rate, the rank was MutationTaster, Provean, MutationAssessor, PolyPhen2, and SIFT. For area under the ROC curve (AUC) and accuracy, the rank was MutationTaster, Provean, PolyPhen2, MutationAssessor, and SIFT. The prediction performance of software may be different when using different parameters. Among the five software, MutationTaster has the best prediction performance.

Evaluation of Second-Level Inference in fMRI Analysis

PubMed Central

Roels, Sanne P.; Loeys, Tom; Moerkerke, Beatrijs

2016-01-01

We investigate the impact of decisions in the second-level (i.e., over subjects) inferential process in functional magnetic resonance imaging on (1) the balance between false positives and false negatives and on (2) the data-analytical stability, both proxies for the reproducibility of results. Second-level analysis based on a mass univariate approach typically consists of 3 phases. First, one proceeds via a general linear model for a test image that consists of pooled information from different subjects. We evaluate models that take into account first-level (within-subjects) variability and models that do not take into account this variability. Second, one proceeds via inference based on parametrical assumptions or via permutation-based inference. Third, we evaluate 3 commonly used procedures to address the multiple testing problem: familywise error rate correction, False Discovery Rate (FDR) correction, and a two-step procedure with minimal cluster size. Based on a simulation study and real data we find that the two-step procedure with minimal cluster size results in most stable results, followed by the familywise error rate correction. The FDR results in most variable results, for both permutation-based inference and parametrical inference. Modeling the subject-specific variability yields a better balance between false positives and false negatives when using parametric inference. PMID:26819578

The reproducibility of research and the misinterpretation of p-values

PubMed Central

2017-01-01

We wish to answer this question: If you observe a ‘significant’ p-value after doing a single unbiased experiment, what is the probability that your result is a false positive? The weak evidence provided by p-values between 0.01 and 0.05 is explored by exact calculations of false positive risks. When you observe p = 0.05, the odds in favour of there being a real effect (given by the likelihood ratio) are about 3 : 1. This is far weaker evidence than the odds of 19 to 1 that might, wrongly, be inferred from the p-value. And if you want to limit the false positive risk to 5%, you would have to assume that you were 87% sure that there was a real effect before the experiment was done. If you observe p = 0.001 in a well-powered experiment, it gives a likelihood ratio of almost 100 : 1 odds on there being a real effect. That would usually be regarded as conclusive. But the false positive risk would still be 8% if the prior probability of a real effect were only 0.1. And, in this case, if you wanted to achieve a false positive risk of 5% you would need to observe p = 0.00045. It is recommended that the terms ‘significant’ and ‘non-significant’ should never be used. Rather, p-values should be supplemented by specifying the prior probability that would be needed to produce a specified (e.g. 5%) false positive risk. It may also be helpful to specify the minimum false positive risk associated with the observed p-value. Despite decades of warnings, many areas of science still insist on labelling a result of p < 0.05 as ‘statistically significant’. This practice must contribute to the lack of reproducibility in some areas of science. This is before you get to the many other well-known problems, like multiple comparisons, lack of randomization and p-hacking. Precise inductive inference is impossible and replication is the only way to be sure. Science is endangered by statistical misunderstanding, and by senior people who impose perverse incentives on scientists. PMID:29308247

Utility of percutaneous joint aspiration and synovial biopsy in identifying culture-positive infected hip arthroplasty.

PubMed

Cross, M Connor; Kransdorf, Mark J; Chivers, F Spencer; Lorans, Roxanne; Roberts, Catherine C; Schwartz, Adam J; Beauchamp, Christopher P

2014-02-01

Percutaneous synovial biopsy has recently been reported to have a high diagnostic value in the preoperative identification of periprosthetic infection of the hip. We report our experience with this technique in the evaluation of patients undergoing revision hip arthroplasty, comparing results of preoperative synovial biopsy with joint aspiration in identifying an infected hip arthroplasty by bacteriological analysis. We retrospectively reviewed the results of the 110 most recent revision hip arthroplasties in which preoperative synovial biopsy and joint aspiration were both performed. Revision surgery for these patients occurred during the period from September 2005 to March 2012. Using this study group, results from preoperative cultures were compared with preoperative laboratory studies and the results of intraoperative cultures. Synovial aspiration was done using an 18- or 20-gauge spinal needle. Synovial biopsy was done coaxially following aspiration using a 22-gauge Chiba needle or 21-gauge Sure-Cut needle. Standard microbiological analysis was performed on preoperative synovial fluid aspirate and synovial biopsy. Intraoperative tissue biopsy bacteriological analysis results at surgical revision were accepted as the "gold standard" for the presence or absence of infection. Seventeen of 110 (15 %) of patients had intraoperative culture-positive periprosthetic infection. Of these 17 cases, there were ten cases where either the synovial fluid aspiration and/or the synovial biopsy were true positive (sensitivity of 59 %, specificity of 100 %, positive predictive value of 100 % and accuracy of 94 %). There were seven cases where aspiration and biopsy results were both falsely negative, but no false-positive results. Similar results were found for synovial fluid aspiration alone. The results of synovial biopsy alone resulted in the identification of seven infected joints with no false-positive result (sensitivity of 41 %, specificity of 100 %, positive predictive value of 100 %, and accuracy of 91 %). Standard microbiological analyses performed on percutaneous synovial biopsy specimen during the preoperative evaluation of patients undergoing revision hip arthroplasty did not improve detection of culture-positive periprosthetic infection as compared to synovial fluid aspiration alone.

Correcting false positive medium-chain acyl-CoA dehydrogenase deficiency results from newborn screening; synthesis, purification, and standardization of branched-chain C8 acylcarnitines for use in their selective and accurate absolute quantitation by UHPLC-MS/MS.

PubMed

Minkler, Paul E; Stoll, Maria S K; Ingalls, Stephen T; Hoppel, Charles L

2017-04-01

While selectively quantifying acylcarnitines in thousands of patient samples using UHPLC-MS/MS, we have occasionally observed unidentified branched-chain C8 acylcarnitines. Such observations are not possible using tandem MS methods, which generate pseudo-quantitative acylcarnitine "profiles". Since these "profiles" select for mass alone, they cannot distinguish authentic signal from isobaric and isomeric interferences. For example, some of the samples containing branched-chain C8 acylcarnitines were, in fact, expanded newborn screening false positive "profiles" for medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Using our fast, highly selective, and quantitatively accurate UHPLC-MS/MS acylcarnitine determination method, we corrected the false positive tandem MS results and reported the sample results as normal for octanoylcarnitine (the marker for MCADD). From instances such as these, we decided to further investigate the presence of branched-chain C8 acylcarnitines in patient samples. To accomplish this, we synthesized and chromatographically characterized several branched-chain C8 acylcarnitines (in addition to valproylcarnitine): 2-methylheptanoylcarnitine, 6-methylheptanoylcarnitine, 2,2-dimethylhexanoylcarnitine, 3,3-dimethylhexanoylcarnitine, 3,5-dimethylhexanoylcarnitine, 2-ethylhexanoylcarnitine, and 2,4,4-trimethylpentanoylcarnitine. We then compared their behavior with branched-chain C8 acylcarnitines observed in patient samples and demonstrated our ability to chromographically resolve, and thus distinguish, octanoylcarnitine from branched-chain C8 acylcarnitines, correcting false positive MCADD results from expanded newborn screening. Copyright © 2017 Elsevier Inc. All rights reserved.

Performance of a semi-quantitative whole blood test for human heart-type fatty acid-binding protein (H-FABP).

PubMed

Hiura, Masahito; Nakajima, Osamu; Mori, Toshizumi; Kitano, Katsuya

2005-10-01

We evaluated the accuracy of visually reading the whole blood Rapicheck H-FABP panel test using the quantitative plasma H-FABP concentration as the reference. Consecutive patients with chest pain (n = 237) who were suspected of having acute myocardial infarction were recruited. The appearance of an evident test line within 5 min was given a grade of +3 (strongly positive), appearance within 15 min +2 (moderately positive) and the appearance of a weak test line within 15 min +1 (weakly positive). The concordance rates were 91.8% for positive, 70.1% for negative and 80.2% for overall. Plasma H-FABP concentrations were above the cut-off value for 9.2% of negative (0) results. Fifty percent of weakly positive (+1) and 25.0% of moderately positive (+2) results had H-FABP concentrations lower than the cut-off value. All of the strongly positive (+3) were above the cut-off value. These results suggested that the false-positive and false-negative results of Rapicheck H-FABP were caused by over or underestimation in visual reading when the plasma H-FABP concentration was near the cut-off concentration. Low accuracy of visual reading of Rapicheck H-FABP was due to poor estimation by manual reading around the cut-off value.

The incidence and clinical implication of sputum with positive acid-fast bacilli smear but negative in mycobacterial culture in a tertiary referral hospital in South Korea.

PubMed

Lee, Jae Seok; Kim, Eui-Chong; Joo, Sei Ick; Lee, Sang-Min; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Shim, Young-Soo; Yim, Jae-Joon

2008-10-01

Although it is not rare to find sputum that is positive acid-fast bacilli (AFB) smear but subsequent culture fails to isolate mycobacteria in clinical practice, the incidence and clinical implication of those sputa from new patients has not been clearly elucidated. The aim of this study was to determine the incidence and clinical implication of sputum with positive AFB smear but negative in mycobacterial culture. All sputa that were positive AFB smear requested during diagnostic work up for new patients visiting Seoul National University Hospital from 1 January 2005 through 31 December 2006 were included. Sputa producing a positive AFB smear but negative mycobacterial culture were classified into one of four categories: laboratory failure to isolate mycobacteria, false positive AFB smear, pathogen may show a positive AFB smear other than mycobacteria, and indeterminate results. Out of 447 sputa with a positive AFB smear, 29 (6.5%) failed to culture any organism. Among these 29 sputa, 18 were caused by laboratory failure to isolate mycobacteria, six were false positive smears, and five indeterminate. Although most sputum with a positive AFB smear but negative culture could be classified as a laboratory failure, clinicians should consider the possibility of false positive AFB smear.

The Alpha-Defensin Test for Diagnosing Periprosthetic Joint Infection in the Setting of an Adverse Local Tissue Reaction Secondary to a Failed Metal-on-Metal Bearing or Corrosion at the Head-Neck Junction.

PubMed

Okroj, Kamil T; Calkins, Tyler E; Kayupov, Erdan; Kheir, Michael M; Bingham, Joshua S; Beauchamp, Christopher P; Parvizi, Javad; Della Valle, Craig J

2018-06-01

In patients with adverse local tissue reaction (ALTR) secondary to a failed metal-on-metal (MoM) bearing or corrosion at the head-neck junction in a metal-on-polyethylene bearing, ruling in or out periprosthetic joint infection (PJI) can be challenging. Alpha-defensin has emerged as an accurate test for PJI. The purpose of this multicenter, retrospective study was to evaluate the accuracy of the alpha-defensin synovial fluid test in detecting PJI in patients with ALTR. We reviewed medical records of 26 patients from 3 centers with ALTR that had an alpha-defensin test performed. Patients were assessed for PJI using the Musculoskeletal Infection Society criteria. Thirteen of these subjects had MoM total hip arthroplasty, 9 had ALTR secondary to head-neck corrosion, and 4 had MoM hip resurfacing. Only 1 of the 26 patients met Musculoskeletal Infection Society criteria for infection. However, 9 hips were alpha-defensin positive, including 1 true positive and 8 that were falsely positive (31%). All 8 of the false positives were also Synovasure positive, although 5 of 8 had an accompanying warning stating the results may be falsely positive due to a low synovial C-reactive protein value. Similar to synovial fluid white blood cell count, alpha-defensin testing is prone to false-positive results in the setting of ALTR. Therefore, we recommend an aggressive approach to ruling out PJI including routine aspiration of all hips with ALTR before revision surgery to integrate the synovial fluid blood cell count, differential, cultures and adjunctive tests like alpha-defensin to allow for accurate diagnosis preoperatively. Copyright © 2018 Elsevier Inc. All rights reserved.

"False Positive" Claims of Near-Death Experiences and "False Negative" Denials of Near-Death Experiences

ERIC Educational Resources Information Center

Greyson, Bruce

2005-01-01

Some persons who claim to have had near-death experiences (NDEs) fail research criteria for having had NDEs ("false positives"); others who deny having had NDEs do meet research criteria for having had NDEs ("false negatives"). The author evaluated false positive claims and false negative denials in an organization that promotes near-death…

Preschool children's vision screening in New Zealand: a retrospective evaluation of referral accuracy.

PubMed

Langeslag-Smith, Miriam A; Vandal, Alain C; Briane, Vincent; Thompson, Benjamin; Anstice, Nicola S

2015-11-27

To assess the accuracy of preschool vision screening in a large, ethnically diverse, urban population in South Auckland, New Zealand. Retrospective longitudinal study. B4 School Check vision screening records (n=5572) were compared with hospital eye department data for children referred from screening due to impaired acuity in one or both eyes who attended a referral appointment (n=556). False positive screens were identified by comparing screening data from the eyes that failed screening with hospital data. Estimation of false negative screening rates relied on data from eyes that passed screening. Data were analysed using logistic regression modelling accounting for the high correlation between results for the two eyes of each child. Positive predictive value of the preschool vision screening programme. Screening produced high numbers of false positive referrals, resulting in poor positive predictive value (PPV=31%, 95% CI 26% to 38%). High estimated negative predictive value (NPV=92%, 95% CI 88% to 95%) suggested most children with a vision disorder were identified at screening. Relaxing the referral criteria for acuity from worse than 6/9 to worse than 6/12 improved PPV without adversely affecting NPV. The B4 School Check generated numerous false positive referrals and consequently had a low PPV. There is scope for reducing costs by altering the visual acuity criterion for referral. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract.

PubMed

Wang, Zhiqiang; Kwon, Shin Hwa; Hwang, Seung Hwan; Kang, Young-Hee; Lee, Jae-Yong; Lim, Soon Sung

2017-03-24

The purpose of this study was to assess the possibility of using competitive binding experiments with ultrafiltration-HPLC analysis to identify potent xanthine oxidase (XO) inhibitors from the Perilla frutescens extract as an attempt to reduce the number of false positive results. To isolate the enzyme-ligand complex from unbound compounds, the P. frutescens extract was either incubated in the absence of XO, in the presence of XO, or with the active site blocked XO before the ultrafiltration was performed. Allopurinaol was used as the XO active site blocker. The unbound compounds were subjected to HPLC analysis. The degree of total binding (TBD) and degree of specific binding (SBD) of each compound were calculated using the peak areas. TBD represents the binding affinities of compounds from the P. frutescens extract for the XO binding site. SBD represents the XO competitive binding between allopurinol and ligands from the extract samples. Two criteria were applied to select putative targets that could help avoid false positives. These include TBD>30% and SBD>10%. Using that approach, kaempferol-3-O-rutinoside, rosmarinic acid, methyl-rosmarinic acid, apigenin, and 4',5,7-trimethoxyflavone were identified, from total 11 compounds, as potent XO inhibitors. Finally, apigenin, 4',5,7-trimethoxyflavone, and luteolin were XO inhibitors verified through an XO inhibition assay and structural simulation of the complex. These results showed that the newly developed strategy has the advantage that the number of targets identified via ultrafiltration-HPLC can be narrowed from many false positives. However, not all false positives can be eliminated with this approach. Some potent inhibitors might also be excluded with the use of this method. The limitations of this method are also discussed herein. Copyright © 2017 Elsevier B.V. All rights reserved.

[A pseudo-outbreak of pharyngeal gonorrhoea related to a false-positive PCR-result].

PubMed

Verzijl, A; Berretty, P J M; Erceg, A; Krekels, G A M; Van den Brule, A J C; Boel, C H E

2007-03-24

Nucleic acid amplification tests, including the polymerase chain reaction (PCR), are sensitive and specific tests that are often used for diagnosing sexually transmitted diseases (STDs). A pseudo-outbreak of pharyngeal gonorrhoea in a group of prostitutes turned out to have been caused by false-positive test results due to commensal oropharyngeal Neisseria species. Specific molecular tests may yield erroneous results. When the results of an STD study have major consequences at a legal or social level, it is advisable, in consultation with a medical microbiologist, to take a sample for culture or to carry out a second molecular test aimed at a different part of the bacterial genome.

The value of a transformation zone component in anal cytology to detect HSIL.

PubMed

Roberts, Jennifer M; Jin, Fengyi; Thurloe, Julia K; Ekman, Deborah; Adams, Marjorie K; McDonald, Ross L; Biro, Clare; Poynten, I Mary; Grulich, Andrew E; Farnsworth, Annabelle

2016-08-01

In a cytology-based screening program intended to prevent anal cancer, the anal transformation zone (TZ) should be adequately sampled because it is the site most susceptible to the development of the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). An adequate TZ component is defined as comprising at least 10 rectal columnar or squamous metaplastic cells. In the current study, the authors examined whether the presence of a TZ component in anal cytology correlated with the detection of histological HSIL. In a natural history study of anal human papillomavirus infection in homosexual men, all participants underwent liquid-based cytology and high-resolution anoscopy (HRA) with or without biopsy at each visit. True-negative cytology (negative cytology with non-HSIL biopsy or negative HRA), false-negative cytology (negative cytology with HSIL biopsy), and true-positive cytology (abnormal cytology with HSIL biopsy) were compared with regard to the presence or absence of a TZ component. Of 617 participants, baseline results included 155 true-positive results, 191 true-negative results, and 31 false-negative results. The absence of an adequate TZ component was found to be significantly higher for false-negative (32.3%) than for either true-positive (11.0%; P = .0034) or true-negative (13.1%; P = .0089) results. Significantly more false-negative cases lacked a TZ component compared with either true-positive or true-negative cases. TZ cells may be an important indicator of sample quality for anal cytology because, unlike cervical sampling, the anal canal is not visualized during cytology sampling. Cancer Cytopathol 2016;124:596-601. © 2016 American Cancer Society. © 2016 American Cancer Society.

Evaluation of Epstein-Barr Virus infection in hypopharyngeal carcinomas from 37 Japanese patients.

PubMed

Zhou, L; Miyagi, Y; Hiroshi, E; Tanaka, Y; Aoki, I; Tsukuda, M

1998-06-01

Thirty-seven biopsy specimens from primary sites, 18 surgically removed metastatic neck nodes, and 18 surgically removed primary sites from 37 patients with hypopharyngeal carcinoma (HPC) were evaluated for the presence of Epstein-Barr Virus (EBV) infection by in situ hybridization (ISH) and polymerase chain reaction (PCR). Although some of normal lymphocytes in 6 of 18 metastatic nodes were positive by ISH, there were no positive results from HPC tumor cells themselves. Our results indicate that EBV-infected non-neoplastic cells such as lymphocytes can be a cause of false positivity, if a study were conducted with PCR alone. Because ISH for EBV-encoded early RNAs was highly sensitive, even more sensitive than PCR from paraffin-embedded samples in our study, this method should be the first choice for identification of EBV infection to avoid false positives.

Are false-positive rates leading to an overestimation of noise-induced hearing loss?

PubMed

Schlauch, Robert S; Carney, Edward

2011-04-01

To estimate false-positive rates for rules proposed to identify early noise-induced hearing loss (NIHL) using the presence of notches in audiograms. Audiograms collected from school-age children in a national survey of health and nutrition (the Third National Health and Nutrition Examination Survey [NHANES III]; National Center for Health Statistics, 1994) were examined using published rules for identifying noise notches at various pass-fail criteria. These results were compared with computer-simulated "flat" audiograms. The proportion of these identified as having a noise notch is an estimate of the false-positive rate for a particular rule. Audiograms from the NHANES III for children 6-11 years of age yielded notched audiograms at rates consistent with simulations, suggesting that this group does not have significant NIHL. Further, pass-fail criteria for rules suggested by expert clinicians, applied to NHANES III audiometric data, yielded unacceptably high false-positive rates. Computer simulations provide an effective method for estimating false-positive rates for protocols used to identify notched audiograms. Audiometric precision could possibly be improved by (a) eliminating systematic calibration errors, including a possible problem with reference levels for TDH-style earphones; (b) repeating and averaging threshold measurements; and (c) using earphones that yield lower variability for 6.0 and 8.0 kHz--2 frequencies critical for identifying noise notches.

FTA-ABS test

MedlinePlus

... rule out a possible false-negative result. Normal Results A negative or nonreactive result means that you ... meaning of your specific test results. What Abnormal Results Mean A positive FTA-ABS is often a ...

Are overreferrals on developmental screening tests really a problem?

PubMed

Glascoe, F P

2001-01-01

Developmental screening tests, even those meeting standards for screening test accuracy, produce numerous false-positive results for 15% to 30% of children. This is thought to produce unnecessary referrals for diagnostic testing or special services and increase the cost of screening programs. To explore whether children who pass screening tests differ in important ways from those who do not and to determine whether children overreferred for testing benefit from the scrutiny of diagnostic testing and treatment planning. Subjects were a national sample of 512 parents and their children (age range of the children, 7 months to 8 years) who participated in validation studies of various screening tests. Psychological examiners adhering to standardized directions obtained informed consent and administered at least 2 developmental screening measures (the Brigance Screens, the Battelle Developmental Inventory Screening Test, the Denver-II, and the Parents' Evaluations of Developmental Status) and a concurrent battery of diagnostic measures, including tests of intelligence, language, and academic achievement (for children aged 2(1/2) years and older). The performance on diagnostic measures of children who failed screening but were not found to have a disability (false positives) was compared with that of children who passed screening and did not have a disability on diagnostic testing (true negatives). Children with false-positive scores performed significantly (P<.001) lower on diagnostic measures than did children with true-negative scores. The false-positive group had scores in adaptive behavior, language, intelligence, and academic achievement that were 9 to 14 points lower than the scores of those in the true-negative group. When viewing the likelihood of scoring below the 25th percentile on diagnostic measures, children with false-positive scores had a relative risk of 2.6 in adaptive behavior (95% confidence interval [CI], 1.67-4.21), 3.1 in language skills (95% CI, 1.90-5.20), 6.7 on intelligence tests (95% CI, 3.28-13.50), and 4.9 on academic measures (95% CI, 2.61-9.28). Overall, 151 (70%) of the children with false-positive results scored below the 25th percentile on 1 or more diagnostic measures (the point at which most children have difficulty benefiting from typical classroom instruction) in contrast with 64 (29%) of the children with true-negative scores (odds ratio, 5.6; 95% CI, 3.73-8.49). Children with false-positive scores were also more likely to be nonwhite and to have parents who had not graduated from high school. Performance differences between children with true-negative scores and children with false-positive scores continued to be significant (P<.001) even after adjusting for sociodemographic differences between groups. Children overreferred for diagnostic testing by developmental screens perform substantially lower than children with true-negative scores on measures of intelligence, language, and academic achievement-the 3 best predictors of school success. These children also carry more psychosocial risk factors, such as limited parental education and minority status. Thus, children with false-positive screening results are an at-risk group for whom diagnostic testing may not be an unnecessary expense but rather a beneficial and needed service that can help focus intervention efforts. Although such testing will not indicate a need for special education placement, it can be useful in identifying children's needs for other programs known to improve language, cognitive, and academic skills, such as Head Start, Title I services, tutoring, private speech-language therapy, and quality day care.

Predicting the carcinogenicity of chemicals with alternative approaches: recent advances.

PubMed

Benigni, Romualdo

2014-09-01

Alternative approaches to the rodent bioassay are necessary for early identification of problematic drugs and biocides during the development process, and are the only practicable tool for assessing environmental chemicals with no or adequate safety documentation. This review informs on: i) the traditional prescreening through genotoxicity testing; ii) an integrative approach that assesses DNA-reactivity and ability to disorganize tissues; iii) new applications of omics technologies (ToxCast/Tox21 project); iv) a pragmatic approach aimed at filling data gaps by intrapolating/extrapolating from similar chemicals (read-across, category formation). The review also approaches the issue of the concerns about false-positive and false-negative results that prevents a wider acceptance and use of alternatives. The review addresses strengths and limitations of various proposals, and concludes on the need of differential approaches to the issue of false negatives and false positives. False negatives can be eliminated or reduced below the variability of the animal assay with conservative quantitative structure-activity relationships or in vitro tests; false positives can be cleared with ad hoc mechanistically based follow-ups. This framework can permit a reduction of animal testing and a better protection of human health.

Cross-Reactivity of Chloroquine and Hydroxychloroquine With DRI Amphetamine Immunoassay.

PubMed

Gomila, Isabel; Quesada, Loreto; López-Corominas, Victoria; Fernández, Julia; Servera, Miguel Á; Sahuquillo, Laura; Dastis, Macarena; Torrents, Albert; Barceló, Bernardino

2017-04-01

Chloroquine and hydroxychloroquine are medical drugs used to treat the chemoprophylaxis of malaria and a second-line anti-inflammatory drug. We performed a study of cross-reactivity of chloroquine and hydroxychloroquine in the DRI Amphetamine Assay inspired by a case report of a self-ingestion of chloroquine after a family dispute, that involved the following: (1) an in vitro study with control samples of healthy subjects, (2) an in vivo study with samples of patients with rheumatoid arthritis, and (3) an evaluation of the cross-reactivity of chloroquine and hydroxychloroquine in 3 additional immunoassays. In the case report, the Amphetamine DRI assay resulted positive both at 1000 ng/mL cutoff (1507 and 1137 ng/mL) and at 500 ng/mL cutoff (1178 and 642 ng/mL). Chloroquine urine levels were 103,900 and 100,900 ng/mL at 5 and 9 hours after ingestion. The results with control samples showed a positive cross-reactivity of chloroquine in the DRI Amphetamine Assay (approximately 0.74% and 0.89% at cutoff of 1000 and 500 ng/mL, respectively). Hydroxychloroquine did not cross-react with the DRI Amphetamine Assay up to 1,000,000 ng/mL. In patients treated with chloroquine or hydroxychloroquine, DRI Amphetamine did not produce false-positive results. The comparative assay study showed a positive cross-reactivity of chloroquine in the Emit II Plus Amphetamines Assay with control samples. Chloroquine can cause false-positive results in the DRI Amphetamine Assay when it is present at high concentrations. Hydroxychloroquine did not produce false-positive results neither in the DRI Amphetamine Assay nor in the others immunoassays evaluated.

False memories to emotional stimuli are not equally affected in right- and left-brain-damaged stroke patients.

PubMed

Buratto, Luciano Grüdtner; Zimmermann, Nicolle; Ferré, Perrine; Joanette, Yves; Fonseca, Rochele Paz; Stein, Lilian Milnitsky

2014-10-01

Previous research has attributed to the right hemisphere (RH) a key role in eliciting false memories to visual emotional stimuli. These results have been explained in terms of two right-hemisphere properties: (i) that emotional stimuli are preferentially processed in the RH and (ii) that visual stimuli are represented more coarsely in the RH. According to this account, false emotional memories are preferentially produced in the RH because emotional stimuli are both more strongly and more diffusely activated during encoding, leaving a memory trace that can be erroneously reactivated by similar but unstudied emotional items at test. If this right-hemisphere hypothesis is correct, then RH damage should result in a reduction in false memories to emotional stimuli relative to left-hemisphere lesions. To investigate this possibility, groups of right-brain-damaged (RBD, N=15), left-brain-damaged (LBD, N=15) and healthy (HC, N=30) participants took part in a recognition memory experiment with emotional (negative and positive) and non-emotional pictures. False memories were operationalized as incorrect responses to unstudied pictures that were similar to studied ones. Both RBD and LBD participants showed similar reductions in false memories for negative pictures relative to controls. For positive pictures, however, false memories were reduced only in RBD patients. The results provide only partial support for the right-hemisphere hypothesis and suggest that inter-hemispheric cooperation models may be necessary to fully account for false emotional memories. Copyright © 2014 Elsevier Inc. All rights reserved.

Mixed group validation: a method to address the limitations of criterion group validation in research on malingering detection.

PubMed

Frederick, R I

2000-01-01

Mixed group validation (MGV) is offered as an alternative to criterion group validation (CGV) to estimate the true positive and false positive rates of tests and other diagnostic signs. CGV requires perfect confidence about each research participant's status with respect to the presence or absence of pathology. MGV determines diagnostic efficiencies based on group data; knowing an individual's status with respect to pathology is not required. MGV can use relatively weak indicators to validate better diagnostic signs, whereas CGV requires perfect diagnostic signs to avoid error in computing true positive and false positive rates. The process of MGV is explained, and a computer simulation demonstrates the soundness of the procedure. MGV of the Rey 15-Item Memory Test (Rey, 1958) for 723 pre-trial criminal defendants resulted in higher estimates of true positive rates and lower estimates of false positive rates as compared with prior research conducted with CGV. The author demonstrates how MGV addresses all the criticisms Rogers (1997b) outlined for differential prevalence designs in malingering detection research. Copyright 2000 John Wiley & Sons, Ltd.

Diagnostic value and cost utility analysis for urine Gram stain and urine microscopic examination as screening tests for urinary tract infection.

PubMed

Wiwanitkit, Viroj; Udomsantisuk, Nibhond; Boonchalermvichian, Chaiyaporn

2005-06-01

The aim of this study was to evaluate the diagnostic properties of urine Gram stain and urine microscopic examination for screening for urinary tract infection (UTI), and to perform an additional cost utility analysis. This descriptive study was performed on 95 urine samples sent for urine culture to the Department of Microbiology, Faculty of Medicine, Chulalongkorn University. The first part of the study was to determine the diagnostic properties of two screening tests (urine Gram stain and urine microscopic examination). Urine culture was set as the gold standard and the results from both methods were compared to this. The second part of this study was to perform a cost utility analysis. The sensitivity of urine Gram stain was 96.2%, the specificity 93.0%, the positive predictive value 94.3% and the negative predictive value 95.2%. False positives occurred with a frequency of 7.0% and false negatives 3.8%. For the microscopic examination, the sensitivity was 65.4%, specificity 74.4%, positive predictive value 75.6% and negative predictive value 64.0%. False positives occurred with a frequency of 25.6% and false negatives 34.6%. Combining urine Gram stain and urine microscopic examination, the sensitivity was 98.1%, specificity 74.4%, positive predictive value 82.3% and negative predictive value 97.0%. False positives occurred with a frequency of 25.6% and false negatives 1.9%. However, the cost per utility of the combined method was higher than either urine microscopic examination or urine Gram stain alone. Urine Gram stain provided the lowest cost per utility. Economically, urine Gram stain is the proper screening tool for presumptive diagnosis of UTI.

Reduction of false-positives in a CAD scheme for automated detection of architectural distortion in digital mammography

NASA Astrophysics Data System (ADS)

de Oliveira, Helder C. R.; Mencattini, Arianna; Casti, Paola; Martinelli, Eugenio; di Natale, Corrado; Catani, Juliana H.; de Barros, Nestor; Melo, Carlos F. E.; Gonzaga, Adilson; Vieira, Marcelo A. C.

2018-02-01

This paper proposes a method to reduce the number of false-positives (FP) in a computer-aided detection (CAD) scheme for automated detection of architectural distortion (AD) in digital mammography. AD is a subtle contraction of breast parenchyma that may represent an early sign of breast cancer. Due to its subtlety and variability, AD is more difficult to detect compared to microcalcifications and masses, and is commonly found in retrospective evaluations of false-negative mammograms. Several computer-based systems have been proposed for automated detection of AD in breast images. The usual approach is automatically detect possible sites of AD in a mammographic image (segmentation step) and then use a classifier to eliminate the false-positives and identify the suspicious regions (classification step). This paper focus on the optimization of the segmentation step to reduce the number of FPs that is used as input to the classifier. The proposal is to use statistical measurements to score the segmented regions and then apply a threshold to select a small quantity of regions that should be submitted to the classification step, improving the detection performance of a CAD scheme. We evaluated 12 image features to score and select suspicious regions of 74 clinical Full-Field Digital Mammography (FFDM). All images in this dataset contained at least one region with AD previously marked by an expert radiologist. The results showed that the proposed method can reduce the false positives of the segmentation step of the CAD scheme from 43.4 false positives (FP) per image to 34.5 FP per image, without increasing the number of false negatives.

False HDAC Inhibition by Aurone Compound.

PubMed

Itoh, Yukihiro; Suzuki, Miki; Matsui, Taiji; Ota, Yosuke; Hui, Zi; Tsubaki, Kazunori; Suzuki, Takayoshi

2016-01-01

Fluorescence assays are useful tools for estimating enzymatic activity. Their simplicity and manageability make them suitable for screening enzyme inhibitors in drug discovery studies. However, researchers need to pay attention to compounds that show auto-fluorescence and quench fluorescence, because such compounds lower the accuracy of the fluorescence assay systems by producing false-positive or negative results. In this study, we found that aurone compound 7, which has been reported as a histone deacetylase (HDAC) inhibitor, gave false-positive results. Although compound 7 was identified by an in vitro HDAC fluorescence assay, it did not show HDAC inhibitory activity in a cell-based assay, leading us to suspect its in vitro HDAC inhibitory activity. As a result of verification experiments, we found that compound 7 interferes with the HDAC fluorescence assay by quenching the HDAC fluorescence signal. Our findings underscore the faults of fluorescence assays and call attention to careless interpretation.

Signal detection of adverse events with imperfect confirmation rates in vaccine safety studies using self-controlled case series design.

PubMed

Xu, Stanley; Newcomer, Sophia; Nelson, Jennifer; Qian, Lei; McClure, David; Pan, Yi; Zeng, Chan; Glanz, Jason

2014-05-01

The Vaccine Safety Datalink project captures electronic health record data including vaccinations and medically attended adverse events on 8.8 million enrollees annually from participating managed care organizations in the United States. While the automated vaccination data are generally of high quality, a presumptive adverse event based on diagnosis codes in automated health care data may not be true (misclassification). Consequently, analyses using automated health care data can generate false positive results, where an association between the vaccine and outcome is incorrectly identified, as well as false negative findings, where a true association or signal is missed. We developed novel conditional Poisson regression models and fixed effects models that accommodate misclassification of adverse event outcome for self-controlled case series design. We conducted simulation studies to evaluate their performance in signal detection in vaccine safety hypotheses generating (screening) studies. We also reanalyzed four previously identified signals in a recent vaccine safety study using the newly proposed models. Our simulation studies demonstrated that (i) outcome misclassification resulted in both false positive and false negative signals in screening studies; (ii) the newly proposed models reduced both the rates of false positive and false negative signals. In reanalyses of four previously identified signals using the novel statistical models, the incidence rate ratio estimates and statistical significances were similar to those using conventional models and including only medical record review confirmed cases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterisation of false-positive observations in botanical surveys

PubMed Central

2017-01-01

Errors in botanical surveying are a common problem. The presence of a species is easily overlooked, leading to false-absences; while misidentifications and other mistakes lead to false-positive observations. While it is common knowledge that these errors occur, there are few data that can be used to quantify and describe these errors. Here we characterise false-positive errors for a controlled set of surveys conducted as part of a field identification test of botanical skill. Surveys were conducted at sites with a verified list of vascular plant species. The candidates were asked to list all the species they could identify in a defined botanically rich area. They were told beforehand that their final score would be the sum of the correct species they listed, but false-positive errors counted against their overall grade. The number of errors varied considerably between people, some people create a high proportion of false-positive errors, but these are scattered across all skill levels. Therefore, a person’s ability to correctly identify a large number of species is not a safeguard against the generation of false-positive errors. There was no phylogenetic pattern to falsely observed species; however, rare species are more likely to be false-positive as are species from species rich genera. Raising the threshold for the acceptance of an observation reduced false-positive observations dramatically, but at the expense of more false negative errors. False-positive errors are higher in field surveying of plants than many people may appreciate. Greater stringency is required before accepting species as present at a site, particularly for rare species. Combining multiple surveys resolves the problem, but requires a considerable increase in effort to achieve the same sensitivity as a single survey. Therefore, other methods should be used to raise the threshold for the acceptance of a species. For example, digital data input systems that can verify, feedback and inform the user are likely to reduce false-positive errors significantly. PMID:28533972

Prediction-Oriented Marker Selection (PROMISE): With Application to High-Dimensional Regression.

PubMed

Kim, Soyeon; Baladandayuthapani, Veerabhadran; Lee, J Jack

2017-06-01

In personalized medicine, biomarkers are used to select therapies with the highest likelihood of success based on an individual patient's biomarker/genomic profile. Two goals are to choose important biomarkers that accurately predict treatment outcomes and to cull unimportant biomarkers to reduce the cost of biological and clinical verifications. These goals are challenging due to the high dimensionality of genomic data. Variable selection methods based on penalized regression (e.g., the lasso and elastic net) have yielded promising results. However, selecting the right amount of penalization is critical to simultaneously achieving these two goals. Standard approaches based on cross-validation (CV) typically provide high prediction accuracy with high true positive rates but at the cost of too many false positives. Alternatively, stability selection (SS) controls the number of false positives, but at the cost of yielding too few true positives. To circumvent these issues, we propose prediction-oriented marker selection (PROMISE), which combines SS with CV to conflate the advantages of both methods. Our application of PROMISE with the lasso and elastic net in data analysis shows that, compared to CV, PROMISE produces sparse solutions, few false positives, and small type I + type II error, and maintains good prediction accuracy, with a marginal decrease in the true positive rates. Compared to SS, PROMISE offers better prediction accuracy and true positive rates. In summary, PROMISE can be applied in many fields to select regularization parameters when the goals are to minimize false positives and maximize prediction accuracy.

Clinical outcome of subchromosomal events detected by whole‐genome noninvasive prenatal testing

PubMed Central

Helgeson, J.; Wardrop, J.; Boomer, T.; Almasri, E.; Paxton, W. B.; Saldivar, J. S.; Dharajiya, N.; Monroe, T. J.; Farkas, D. H.; Grosu, D. S.

2015-01-01

Abstract Objective A novel algorithm to identify fetal microdeletion events in maternal plasma has been developed and used in clinical laboratory‐based noninvasive prenatal testing. We used this approach to identify the subchromosomal events 5pdel, 22q11del, 15qdel, 1p36del, 4pdel, 11qdel, and 8qdel in routine testing. We describe the clinical outcomes of those samples identified with these subchromosomal events. Methods Blood samples from high‐risk pregnant women submitted for noninvasive prenatal testing were analyzed using low coverage whole genome massively parallel sequencing. Sequencing data were analyzed using a novel algorithm to detect trisomies and microdeletions. Results In testing 175 393 samples, 55 subchromosomal deletions were reported. The overall positive predictive value for each subchromosomal aberration ranged from 60% to 100% for cases with diagnostic and clinical follow‐up information. The total false positive rate was 0.0017% for confirmed false positives results; false negative rate and sensitivity were not conclusively determined. Conclusion Noninvasive testing can be expanded into the detection of subchromosomal copy number variations, while maintaining overall high test specificity. In the current setting, our results demonstrate high positive predictive values for testing of rare subchromosomal deletions. © 2015 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:26088833

Avoiding False Positive Antigen Detection by Flow Cytometry on Blood Cell Derived Microparticles: The Importance of an Appropriate Negative Control

PubMed Central

Crompot, Emerence; Van Damme, Michael; Duvillier, Hugues; Pieters, Karlien; Vermeesch, Marjorie; Perez-Morga, David; Meuleman, Nathalie; Mineur, Philippe; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

2015-01-01

Background Microparticles (MPs), also called microvesicles (MVs) are plasma membrane-derived fragments with sizes ranging from 0.1 to 1μm. Characterization of these MPs is often performed by flow cytometry but there is no consensus on the appropriate negative control to use that can lead to false positive results. Materials and Methods We analyzed MPs from platelets, B-cells, T-cells, NK-cells, monocytes, and chronic lymphocytic leukemia (CLL) B-cells. Cells were purified by positive magnetic-separation and cultured for 48h. Cells and MPs were characterized using the following monoclonal antibodies (CD19,20 for B-cells, CD3,8,5,27 for T-cells, CD16,56 for NK-cells, CD14,11c for monocytes, CD41,61 for platelets). Isolated MPs were stained with annexin-V-FITC and gated between 300nm and 900nm. The latex bead technique was then performed for easy detection of MPs. Samples were analyzed by Transmission (TEM) and Scanning Electron microscopy (SEM). Results Annexin-V positive events within a gate of 300-900nm were detected and defined as MPs. Our results confirmed that the characteristic antigens CD41/CD61 were found on platelet-derived-MPs validating our technique. However, for MPs derived from other cell types, we were unable to detect any antigen, although they were clearly expressed on the MP-producing cells in the contrary of several data published in the literature. Using the latex bead technique, we confirmed detection of CD41,61. However, the apparent expression of other antigens (already deemed positive in several studies) was determined to be false positive, indicated by negative controls (same labeling was used on MPs from different origins). Conclusion We observed that mother cell antigens were not always detected on corresponding MPs by direct flow cytometry or latex bead cytometry. Our data highlighted that false positive results could be generated due to antibody aspecificity and that phenotypic characterization of MPs is a difficult field requiring the use of several negative controls. PMID:25978814

Response time as a discriminator between true- and false-positive responses in suprathreshold perimetry.

PubMed

Artes, Paul H; McLeod, David; Henson, David B

2002-01-01

To report on differences between the latency distributions of responses to stimuli and to false-positive catch trials in suprathreshold perimetry. To describe an algorithm for defining response time windows and to report on its performance in discriminating between true- and false-positive responses on the basis of response time (RT). A sample of 435 largely inexperienced patients underwent suprathreshold visual field examination on a perimeter that was modified to record RTs. Data were analyzed from 60,500 responses to suprathreshold stimuli and from 523 false-positive responses to catch trials. False-positive responses had much more variable latencies than responses to suprathreshold stimuli. An algorithm defining RT windows on the basis of z-transformed individual latency samples correctly identified more than 70% of false-positive responses to catch trials, whereas fewer than 3% of responses to suprathreshold stimuli were classified as false-positive responses. Latency analysis can be used to detect a substantial proportion of false-positive responses in suprathreshold perimetry. Rejection of such responses may increase the reliability of visual field screening by reducing variability and bias in a small but clinically important proportion of patients.

Prenatal Genetic Screening Tests

MedlinePlus

... information about the rates of false-positive and false-negative results for each test. What should I consider when deciding whether to have prenatal genetic testing? It is your choice whether to have prenatal testing. Your personal beliefs and values are important factors in the decision ...

When the Single Matters more than the Group (II): Addressing the Problem of High False Positive Rates in Single Case Voxel Based Morphometry Using Non-parametric Statistics.

PubMed

Scarpazza, Cristina; Nichols, Thomas E; Seramondi, Donato; Maumet, Camille; Sartori, Giuseppe; Mechelli, Andrea

2016-01-01

In recent years, an increasing number of studies have used Voxel Based Morphometry (VBM) to compare a single patient with a psychiatric or neurological condition of interest against a group of healthy controls. However, the validity of this approach critically relies on the assumption that the single patient is drawn from a hypothetical population with a normal distribution and variance equal to that of the control group. In a previous investigation, we demonstrated that family-wise false positive error rate (i.e., the proportion of statistical comparisons yielding at least one false positive) in single case VBM are much higher than expected (Scarpazza et al., 2013). Here, we examine whether the use of non-parametric statistics, which does not rely on the assumptions of normal distribution and equal variance, would enable the investigation of single subjects with good control of false positive risk. We empirically estimated false positive rates (FPRs) in single case non-parametric VBM, by performing 400 statistical comparisons between a single disease-free individual and a group of 100 disease-free controls. The impact of smoothing (4, 8, and 12 mm) and type of pre-processing (Modulated, Unmodulated) was also examined, as these factors have been found to influence FPRs in previous investigations using parametric statistics. The 400 statistical comparisons were repeated using two independent, freely available data sets in order to maximize the generalizability of the results. We found that the family-wise error rate was 5% for increases and 3.6% for decreases in one data set; and 5.6% for increases and 6.3% for decreases in the other data set (5% nominal). Further, these results were not dependent on the level of smoothing and modulation. Therefore, the present study provides empirical evidence that single case VBM studies with non-parametric statistics are not susceptible to high false positive rates. The critical implication of this finding is that VBM can be used to characterize neuroanatomical alterations in individual subjects as long as non-parametric statistics are employed.

Fine-Needle Aspiration, Touch Imprint, and Crush Preparation Cytology for Diagnosing Thyroid Malignancies in Thyroid Nodules.

PubMed

Ahmadinejad, Mojtaba; Aliepour, Asghar; Anbari, Khatereh; Kaviani, Mojhgan; Ganjizadeh, Hasan; Nadri, Sedigheh; Foroutani, Niloufar; Meysami, Masoumeh; Almasi, Vahid

2015-12-01

Several methods are used to evaluate the thyroid nodules. The aim of this study was to determine the sensitivity, specificity, false positive and negative rates, positive predictive value (PPV), and negative predictive value (NPV) of touch imprint, crush preparation, and fine-needle aspiration (FNA) methods. This cross-sectional study was done in Shohada-ye Ashayer University Hospital in Khorramabad. All the patients who underwent thyroid surgery due to thyroid nodules in this hospital between March and September 2011 were evaluated. The thyroid nodules of all the patients were evaluated by touch imprint, crush preparation, FNA, and permanent pathology methods. Finally, the results of the first three methods were compared with the result of permanent pathology method. The mean age of 104 patients who underwent thyroid surgery was 42.6 ± 11.9 years old. Based on permanent pathology, touch imprint, crush preparation, and FNA methods, 15.3, 6.25, 6.25, and 4.4 % of thyroid nodules were malignant, respectively. Sensitivity, specificity, false positive rate, false negative rate, PPV, and NPV of FNA biopsy were 62.5, 100, 0, 37.5, 100, and 95.3 %, respectively. Also, sensitivity, specificity, false positive rate, false negative rate, PPV, and NPV of touch imprint and crush preparation were equal and were 80, 100, 0, 20, 100, and 96.7 %, respectively. Using touch imprint and crush preparation in evaluation of thyroid nodules for rapid evaluation of these nodules in operating rooms seems to be logical, and it can prevent further surgeries.

Effect of obesity on preterm delivery prediction by transabdominal recording of uterine electromyography.

PubMed

Lucovnik, Miha; Chambliss, Linda R; Blumrick, Richard; Balducci, James; Gersak, Ksenija; Garfield, Robert E

2016-10-01

It has been shown that noninvasive uterine electromyography (EMG) can identify true preterm labor more accurately than methods available to clinicians today. The objective of this study was to evaluate the effect of body mass index (BMI) on the accuracy of uterine EMG in predicting preterm delivery. Predictive values of uterine EMG for preterm delivery were compared in obese versus overweight/normal BMI patients. Hanley-McNeil test was used to compare receiver operator characteristics curves in these groups. Previously reported EMG cutoffs were used to determine groups with false positive/false negative and true positive/true negative EMG results. BMI in these groups was compared with Student t test (p < 0.05 significant). A total of 88 patients were included: 20 obese, 64 overweight, and four with normal BMI. EMG predicted preterm delivery within 7 days with area under the curve = 0.95 in the normal/overweight group, and with area under the curve = 1.00 in the obese group (p = 0.08). Six patients in true preterm labor (delivering within 7 days from EMG measurement) had low EMG values (false negative group). There were no false positive results. No significant differences in patient's BMI were noted between false negative group patients and preterm labor patients with high EMG values (true positive group) and nonlabor patients with low EMG values (true negative group; p = 0.32). Accuracy of noninvasive uterine EMG monitoring and its predictive value for preterm delivery are not affected by obesity. Copyright © 2016. Published by Elsevier B.V.

Factors that influence standard automated perimetry test results in glaucoma: test reliability, technician experience, time of day, and season.

PubMed

Junoy Montolio, Francisco G; Wesselink, Christiaan; Gordijn, Marijke; Jansonius, Nomdo M

2012-10-09

To determine the influence of several factors on standard automated perimetry test results in glaucoma. Longitudinal Humphrey field analyzer 30-2 Swedish interactive threshold algorithm data from 160 eyes of 160 glaucoma patients were used. The influence of technician experience, time of day, and season on the mean deviation (MD) was determined by performing linear regression analysis of MD against time on a series of visual fields and subsequently performing a multiple linear regression analysis with the MD residuals as dependent variable and the factors mentioned above as independent variables. Analyses were performed with and without adjustment for the test reliability (fixation losses and false-positive and false-negative answers) and with and without stratification according to disease stage (baseline MD). Mean follow-up was 9.4 years, with on average 10.8 tests per patient. Technician experience, time of day, and season were associated with the MD. Approximately 0.2 dB lower MD values were found for inexperienced technicians (P < 0.001), tests performed after lunch (P < 0.001), and tests performed in the summer or autumn (P < 0.001). The effects of time of day and season appeared to depend on disease stage. Independent of these effects, the percentage of false-positive answers strongly influenced the MD with a 1 dB increase in MD per 10% increase in false-positive answers. Technician experience, time of day, season, and the percentage of false-positive answers have a significant influence on the MD of standard automated perimetry.

Effects of positive results for Mycobacterium avium subsp paratuberculosis as determined by microbial culture of feces or antibody ELISA on results of caudal fold tuberculin test and interferon-gamma assay for tuberculosis in cattle.

PubMed

Dunn, John R; Kaneene, John B; Grooms, Daniel L; Bolin, Steven R; Bolin, Carole A; Bruning-Fann, Colleen S

2005-02-01

To determine whether cattle testing positive for Mycobacterium avium subsp paratuberculosis as determined by microbial culture of feces or antibody ELISA were more likely to have false-positive responses on the caudal fold tuberculin (CFT) test or interferon-gamma (IFN-gamma) assay for Mycobacterium bovis than cattle testing negative for M paratuberculosis. 1043 cattle from 10 herds in Michigan. Feces and blood samples for plasma were collected from cattle > or =24 months old on the day the CFT test was read. Fecal samples were submitted for microbial culture for M paratuberculosis. Plasma samples were tested for antibody against M paratuberculosis, and IFN-gamma after stimulation with purified protein derivative tuberculin from M bovis or M avium. Of 1043 cattle, 180 (17.3%) had positive CFT test results (suspects) and 8 (0.8%) had positive IFN-gamma assay results after stimulation with purified protein derivative tuberculin from M bovis. Forty-five (4.3%) and 115 (11.0%) cattle tested positive for M paratuberculosis as determined by microbial culture of feces and antibody ELISA, respectively. Cattle with positive responses for M paratuberculosis appeared to have an increased likelihood of false-positive results on the CFT test, although this association was not significant. No significant association was detected among cattle testing positive for M paratuberculosis as determined by microbial culture of feces and antibody ELISA and positive CFT test and IFN-gamma assay results for M bovis.

Kinetics of a Tuberculosis-Specific Gamma Interferon Release Assay in Military Personnel with a Positive Tuberculin Skin Test▿ †

PubMed Central

van Brummelen, Sigrid E.; Bauwens, Anja M.; Schlösser, Noël J.; Arend, Sandra M.

2010-01-01

Treatment of latent Mycobacterium tuberculosis infection on the basis of the tuberculin skin test (TST) result is inaccurate due to the false-positive TST results that occur after Mycobacterium bovis BCG vaccination or exposure to nontuberculous mycobacteria (NTM). Gamma interferon release assays (IGRAs) are based on M. tuberculosis-specific antigens. In a previous study among BCG-naïve military employees, a positive TST result after deployment was mostly associated with a negative IGRA result, suggesting exposure to NTM. Data regarding the kinetics of IGRAs are limited and controversial. The present study aimed to reassess the rate of false-positive TST results and to evaluate the kinetics of the Quantiferon TB Gold In-Tube assay (QFT-Git) in military personnel with a positive TST result. QFT-Git was performed at the time of inclusion in the study and was repeated after 2, 6, 12, and 18 or 24 months. Of 192 participants, 17 were recruits and 175 were screened after deployment (n = 169) or because of travel or health care work. Baseline positive QFT-Git results were observed in 7/17 (41.2%) and 12/174 (6.9%) participants, respectively. During follow-up, a negative QFT-Git result remained negative in 163/165 (98.8%) participants. Of 18 subjects with an initial positive QFT-Git result, reversion to a negative result occurred in 1/6 (16%) recruits, whereas it occurred in 8/12 (66%) subjects after deployment or with other risk factors (P = 0.046). The quantitative result was significantly lower in subjects with reversion than in those with consistent positive results (P = 0.017). This study confirmed a low rate of positive QFT-Git results among military personnel with a positive TST result after deployment, supporting the hypothesis of exposure to NTM. Reversion of the majority of initially low-positive QFT-Git results indicates that QFT-Git may be useful for the diagnosis of later reinfections. PMID:20375241

[Examination about utility of a Streptococcus pneumoniae capsular antigen swiftness search kit urine in a pneumonia patient].

PubMed

Hashikita, Giichi; Yamaguti, Toshiyuki; Tachi, Yoshimi; Kishi, Etsuko; Kawamura, Toru; Takahashi, Shun; Arai, Yukie; Koyama, Sachie; Huruhata, Toshihumi; Itabashi, Akira; Oka, Yoko; Yamazaki, Tsutomu; Maesaki, Sigefumi

2005-01-01

We investigated the usefullness of Binax NOW urine antigen test, an immunochromatographic assay that binds any soluble Streptococcus pneumoniae antigen (C polysaccharide) for the diagnosis of penumoniae form September 2003 to March 2005. We used 372 samples form the patinets with pneumoniae diagnosed for blood or sputum cultuter or gram-stained sputum smear. Out of 24 culture positive specimens, Binax NOW urine antigen test, showed positive in 18 (75%) specimens. The sensitivity of sputum and blood culture was 71.7% and 83.3%, respectively. Binax NOW urine antigen test was seemed false positives in 55 samples, false negatives in 6 samples. The specificity of Binax NOW urine antigen test was evaluated 84.1%. Overall agreement among tests was 83.6%. When compared to culture, false negative urine antigen may be the result of colonizing S. pneumoniae in sputum or pneumonia caused by an agent other than S. pneumoniae. CRP values for cases were both urine antigen and culture were positive ranged from 40 mg/dl to 10 mg/dl while urine antigen and culture negative cases were predominantly less than 10 mg/dl. Positive blood and pleural fluid culture cases were consistently associated with strongly positive urine antigen tests. Non-agreement between urine antigen, culture, and microscopy may be the result of specimen quality, labile nature of S. pneumoniae and antimicrobial therapy.

Neural Network Target Identification System for False Alarm Reduction

NASA Technical Reports Server (NTRS)

Ye, David; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

2009-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feed forward back propagation neural network (NN) is then trained to classify each feature vector and remove false positives. This paper discusses the test of the system performance and parameter optimizations process which adapts the system to various targets and datasets. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar image dataset.

A note on the false discovery rate of novel peptides in proteogenomics.

PubMed

Zhang, Kun; Fu, Yan; Zeng, Wen-Feng; He, Kun; Chi, Hao; Liu, Chao; Li, Yan-Chang; Gao, Yuan; Xu, Ping; He, Si-Min

2015-10-15

Proteogenomics has been well accepted as a tool to discover novel genes. In most conventional proteogenomic studies, a global false discovery rate is used to filter out false positives for identifying credible novel peptides. However, it has been found that the actual level of false positives in novel peptides is often out of control and behaves differently for different genomes. To quantitatively model this problem, we theoretically analyze the subgroup false discovery rates of annotated and novel peptides. Our analysis shows that the annotation completeness ratio of a genome is the dominant factor influencing the subgroup FDR of novel peptides. Experimental results on two real datasets of Escherichia coli and Mycobacterium tuberculosis support our conjecture. yfu@amss.ac.cn or xupingghy@gmail.com or smhe@ict.ac.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Comparison of normalization methods for the analysis of metagenomic gene abundance data.

PubMed

Pereira, Mariana Buongermino; Wallroth, Mikael; Jonsson, Viktor; Kristiansson, Erik

2018-04-20

In shotgun metagenomics, microbial communities are studied through direct sequencing of DNA without any prior cultivation. By comparing gene abundances estimated from the generated sequencing reads, functional differences between the communities can be identified. However, gene abundance data is affected by high levels of systematic variability, which can greatly reduce the statistical power and introduce false positives. Normalization, which is the process where systematic variability is identified and removed, is therefore a vital part of the data analysis. A wide range of normalization methods for high-dimensional count data has been proposed but their performance on the analysis of shotgun metagenomic data has not been evaluated. Here, we present a systematic evaluation of nine normalization methods for gene abundance data. The methods were evaluated through resampling of three comprehensive datasets, creating a realistic setting that preserved the unique characteristics of metagenomic data. Performance was measured in terms of the methods ability to identify differentially abundant genes (DAGs), correctly calculate unbiased p-values and control the false discovery rate (FDR). Our results showed that the choice of normalization method has a large impact on the end results. When the DAGs were asymmetrically present between the experimental conditions, many normalization methods had a reduced true positive rate (TPR) and a high false positive rate (FPR). The methods trimmed mean of M-values (TMM) and relative log expression (RLE) had the overall highest performance and are therefore recommended for the analysis of gene abundance data. For larger sample sizes, CSS also showed satisfactory performance. This study emphasizes the importance of selecting a suitable normalization methods in the analysis of data from shotgun metagenomics. Our results also demonstrate that improper methods may result in unacceptably high levels of false positives, which in turn may lead to incorrect or obfuscated biological interpretation.

Abnormal urinalysis results are common, regardless of specimen collection technique, in women without urinary tract infections.

PubMed

Frazee, Bradley W; Enriquez, Kayla; Ng, Valerie; Alter, Harrison

2015-06-01

Voided urinalysis to test for urinary tract infection (UTI) is prone to false-positive results for a number of reasons. Specimens are often collected at triage from women with any abdominal complaint, creating a low UTI prevalence population. Improper collection technique by the patient may affect the result. At least four indices, if positive, can indicate UTI. We examine the impact of voided specimen collection technique on urinalysis indicators of UTI and on urine culture contamination in disease-free women. In this crossover design, 40 menstrual-age female emergency department staff without UTI symptoms collected urine two ways: directly in a cup ("non-clean") and midstream clean catch ("ideal"). Samples underwent standard automated urinalysis and culture. Urinalysis indices and culture contamination were compared. The proportion of abnormal results from samples collected by "non-clean" vs. "ideal" technique, respectively, were: leukocyte esterase (>trace) 50%, 35% (95% confidence interval for difference -6% to 36%); nitrites (any) 2.5%, 2.5% (difference -2.5 to 2.5%); white blood cells (>5/high-powered field [HPF]) 50%, 27.5% (difference 4 to 41%); bacteria (any/HPF) 77.5%, 62.5%, (difference -7 to 37%); epithelial cells (>few) 65%, 30% (difference 13 to 56%); culture contamination (>1000 colony-forming units of commensal or >2 species) 77%, 63% (difference -5 to 35%). No urinalysis index was positively correlated with culture contamination. Contemporary automated urinalysis indices were often abnormal in a disease-free population of women, even using ideal collection technique. In clinical practice, such false-positive results could lead to false-positive UTI diagnosis. Only urine nitrite showed a high specificity. Culture contamination was common regardless of collection technique and was not predicted by urinalysis results. Copyright © 2015 Elsevier Inc. All rights reserved.

Performance of an HRP-2 Rapid Diagnostic Test in Nigerian Children Less Than 5 Years of Age

PubMed Central

Ajumobi, Olufemi; Sabitu, Kabir; Nguku, Patrick; Kwaga, Jacob; Ntadom, Godwin; Gitta, Sheba; Elizeus, Rutebemberwa; Oyibo, Wellington; Nsubuga, Peter; Maire, Mark; Poggensee, Gabriele

2015-01-01

The diagnostic performance of histidine-rich protein 2 (HRP-2)–based malaria rapid diagnostic test (RDT) was evaluated in a mesoendemic area for malaria, Kaduna, Nigeria. We compared RDT results with expert microscopy results of blood samples from 295 febrile children under 5 years. Overall, 11.9% (35/295) tested positive with RDT compared with 10.5% (31/295) by microscopy: sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 98.5%, 88.6%, and 100%, respectively. The RDT sensitivity was not affected by transmission season, parasite density, and age. Specificity and positive PV decreased slightly during the high-transmission season (97.5% and 83.3%). The RDT test positivity rates in the low- and high-transmission seasons were 9.4% and 13.5%, respectively. Overall, the test performance of this RDT was satisfactory. The findings of a low proportion of RDT false positives, no invalid and no false-negative results should validate the performance of RDTs in this context. PMID:25711608

Applying a CAD-generated imaging marker to assess short-term breast cancer risk

NASA Astrophysics Data System (ADS)

Mirniaharikandehei, Seyedehnafiseh; Zarafshani, Ali; Heidari, Morteza; Wang, Yunzhi; Aghaei, Faranak; Zheng, Bin

2018-02-01

Although whether using computer-aided detection (CAD) helps improve radiologists' performance in reading and interpreting mammograms is controversy due to higher false-positive detection rates, objective of this study is to investigate and test a new hypothesis that CAD-generated false-positives, in particular, the bilateral summation of false-positives, is a potential imaging marker associated with short-term breast cancer risk. An image dataset involving negative screening mammograms acquired from 1,044 women was retrospectively assembled. Each case involves 4 images of craniocaudal (CC) and mediolateral oblique (MLO) view of the left and right breasts. In the next subsequent mammography screening, 402 cases were positive for cancer detected and 642 remained negative. A CAD scheme was applied to process all "prior" negative mammograms. Some features from CAD scheme were extracted, which include detection seeds, the total number of false-positive regions, an average of detection scores and the sum of detection scores in CC and MLO view images. Then the features computed from two bilateral images of left and right breasts from either CC or MLO view were combined. In order to predict the likelihood of each testing case being positive in the next subsequent screening, two logistic regression models were trained and tested using a leave-one-case-out based cross-validation method. Data analysis demonstrated the maximum prediction accuracy with an area under a ROC curve of AUC=0.65+/-0.017 and the maximum adjusted odds ratio of 4.49 with a 95% confidence interval of [2.95, 6.83]. The results also illustrated an increasing trend in the adjusted odds ratio and risk prediction scores (p<0.01). Thus, the study showed that CAD-generated false-positives might provide a new quantitative imaging marker to help assess short-term breast cancer risk.

False negative PCR despite high levels of JC virus DNA in spinal fluid: Implications for diagnostic testing

PubMed Central

Landry, Marie L.; Eid, Tore; Bannykh, Serguei; Major, Eugene

2009-01-01

Genome amplification methods such as polymerase chain reaction (PCR) have revolutionized our ability to detect viruses in spinal fluids of patients with neurologic diseases. It is not as well appreciated among clinicians that PCR protocols, quality assurance, and technical expertise vary significantly among laboratories. In a multi-laboratory blinded study of herpes simplex virus PCR, the most widely used and best validated CSF PCR assay, low-level positives were often missed and false positives were not uncommon [Schloss L, van Loon AM, Cinque P, Cleator G, Echevarria JM, Falk KI, et al. An international external quality assessment of nucleic acid amplification of herpes simplex virus. J Clin Virol 2003;28(2):175–85]. In addition, genome variability and mutations, which are increasingly recognized for a number of different viruses, can lead to falsely low or negative results. Both clinicians and laboratories must recognize the limitations of PCR, since misleading results may have serious consequences. We present here a case of a rapidly progressive, fatal neurologic illness in a young mother, whose CSF JCV DNA PCR at a reference laboratory was falsely negative. Ultimately, brain biopsy established the diagnosis of progressive multifocal leukoencephalopathy (PML). Repeat PCR testing of the same CSF targeting a different region of the genome yielded a high positive result. PMID:18701345

An assessment of false positive rates for malaria rapid diagnostic tests caused by non-Plasmodium infectious agents and immunological factors.

PubMed

Gatton, Michelle L; Ciketic, Sadmir; Barnwell, John W; Cheng, Qin; Chiodini, Peter L; Incardona, Sandra; Bell, David; Cunningham, Jane; González, Iveth J

2018-01-01

Malaria rapid diagnostic tests (RDTs) can produce false positive (FP) results in patients with human African trypanosomiasis and rheumatoid factor (RF), but specificity against other infectious agents and immunological factors is largely unknown. Low diagnostic specificity caused by cross-reactivity may lead to over-estimates of the number of malaria cases and over-use of antimalarial drugs, at the cost of not diagnosing and treating the true underlying condition. Data from the WHO Malaria RDT Product Testing Programme was analysed to assess FP rates of 221 RDTs against four infectious agents (Chagas, dengue, Leishmaniasis and Schistosomiasis) and four immunological factors (anti-nuclear antibody, human anti-mouse antibody (HAMA), RF and rapid plasma regain). Only RDTs with a FP rate against clean negative samples less than 10% were included. Paired t-tests were used to compare product-specific FP rates on clean negative samples and samples containing non-Plasmodium infectious agents and immunological factors. Forty (18%) RDTs showed no FP results against any tested infectious agent or immunological factor. In the remaining RDTs significant and clinically relevant increases in FP rates were observed for samples containing HAMA and RF (P<0.001). There were significant correlations between product-matched FP rates for RF and HAMA on all RDT test bands (P<0.001), and FP rates for each infectious agent and immunological factor were also correlated between test bands of combination RDTs (P≤0.002). False positive results against non-Plasmodium infectious agents and immunological factors does not appear to be a universal property of malaria RDTs. However, since many malaria RDTs have elevated FP rates against HAMA and RF positive samples practitioners may need to consider the possibility of false positive results for malaria in patients with conditions that stimulate HAMA or RF.

Automated microaneurysm detection method based on double ring filter in retinal fundus images

NASA Astrophysics Data System (ADS)

Mizutani, Atsushi; Muramatsu, Chisako; Hatanaka, Yuji; Suemori, Shinsuke; Hara, Takeshi; Fujita, Hiroshi

2009-02-01

The presence of microaneurysms in the eye is one of the early signs of diabetic retinopathy, which is one of the leading causes of vision loss. We have been investigating a computerized method for the detection of microaneurysms on retinal fundus images, which were obtained from the Retinopathy Online Challenge (ROC) database. The ROC provides 50 training cases, in which "gold standard" locations of microaneurysms are provided, and 50 test cases without the gold standard locations. In this study, the computerized scheme was developed by using the training cases. Although the results for the test cases are also included, this paper mainly discusses the results for the training cases because the "gold standard" for the test cases is not known. After image preprocessing, candidate regions for microaneurysms were detected using a double-ring filter. Any potential false positives located in the regions corresponding to blood vessels were removed by automatic extraction of blood vessels from the images. Twelve image features were determined, and the candidate lesions were classified into microaneurysms or false positives using the rule-based method and an artificial neural network. The true positive fraction of the proposed method was 0.45 at 27 false positives per image. Forty-two percent of microaneurysms in the 50 training cases were considered invisible by the consensus of two co-investigators. When the method was evaluated for visible microaneurysms, the sensitivity for detecting microaneurysms was 65% at 27 false positives per image. Our computerized detection scheme could be improved for helping ophthalmologists in the early diagnosis of diabetic retinopathy.

The diagnostic significance of lactate dehydrogenase isoenzymes in urinary cytology.

PubMed Central

Nishikawa, A.; Tanaka, T.; Takeuchi, T.; Fujihiro, S.; Mori, H.

1991-01-01

Lactate dehydrogenase (LDH) isoenzyme distribution was examined in 106 urine samples being tested cytologically for evidence of bladder cancer; the samples were selected to have less than 20 leucocytes and erythrocytes per high power field and the LDH pattern determined by electrophoresis. The Papanicolaou stained-smears showed 68 negative, 17 suspicious and 21 positive. The LDH M-fraction of the urinary supernatant in cytologically positive cases was significantly greater than in negative cases, although the latter included a few false negative samples. Some of the false negatives gave positive results for the LDH M-fraction; these results suggest that the determination of LDH isoenzymes in the urine is useful in diagnosing urinary tract cancers, including early stage, and for follow-up of patients with bladder cancers after surgical resection. PMID:2039708

Emotions and false memories: valence or arousal?

PubMed

Corson, Yves; Verrier, Nadège

2007-03-01

The effects of mood on false memories have not been studied systematically until recently. Some results seem to indicate that negative mood may reduce false recall and thus suggest an influence of emotional valence on false memory. The present research tested the effects of both valence and arousal on recall and recognition and indicates that the effect is actually due to arousal. In fact, whether participants' mood is positive, negative, or neutral, false memories are significantly more frequent under conditions of high arousal than under conditions of low arousal.

The epidemiology of pertussis in the Australian Capital Territory, 1999 to 2005--epidemics of testing, disease or false positives?

PubMed

Wylks, Clare E; Ewald, Ben; Guest, Charles

2007-12-01

The increase in pertussis notifications since the 1990s in many countries, including Australia, has been attributed to improved diagnosis. This study aimed to describe the epidemiology of pertussis in the Australian Capital Territory from 1999 to 2005, determine whether the apparent changes could be accounted for by greater recognition and testing, and explore the impact of false positive serology results associated with faulty test kits. The Australian Capital Territory resident notification, laboratory and separation data from 1999 to 2005 were examined and the proportions of positive tests across time periods and age groups compared. Notification rates increased in the years 2000, 2003 and 2005. There was a shift in the age distribution of cases, from children and teenagers in 2000, to teenagers in 2003 and adults in 2005. Testing activity and notification activity were closely related. Comparing the epidemic periods to the preceding inter-epidemic periods, the proportion of positive tests was maintained or increased for all age groups combined and for adults and children (e.g. statistically significant increase from 7.8% to 14.0% in the 2005 epidemic in adults). During each epidemic the proportion of positive tests was statistically significantly higher in the age group with the highest notification activity. Despite similar testing rates in adults in 2003 and 2005, greater disease activity was reported in 2005. Although the numbers were small, polymerase chain reaction and culture positive test results increased in 2003 but not in 2005. The proportion of positive polymerase chain reaction results increased in 2003, providing strong evidence that the apparent epidemic of 2003 was due to a true increase in underlying disease activity. Because of the uncertainty surrounding the timing of the false positive serology results, the study provides weaker support for a true epidemic of pertussis in 2005.

Robust Detection of Rare Species Using Environmental DNA: The Importance of Primer Specificity

PubMed Central

Wilcox, Taylor M.; McKelvey, Kevin S.; Young, Michael K.; Jane, Stephen F.; Lowe, Winsor H.; Whiteley, Andrew R.; Schwartz, Michael K.

2013-01-01

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method’s sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design. PMID:23555689

Robust detection of rare species using environmental DNA: the importance of primer specificity.

PubMed

Wilcox, Taylor M; McKelvey, Kevin S; Young, Michael K; Jane, Stephen F; Lowe, Winsor H; Whiteley, Andrew R; Schwartz, Michael K

2013-01-01

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method's sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/µl. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design.

Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model.

PubMed

Moses, Mark W; Zwerling, Alice; Cattamanchi, Adithya; Denkinger, Claudia M; Banaei, Niaz; Kik, Sandra V; Metcalfe, John; Pai, Madhukar; Dowdy, David

2016-07-29

Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8-25.5) of the entire population testing false-positive over ten years. Raising the cutoff to >1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95%UR: 2.0-2.6%) or 4.1% (95%UR: 3.7-4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95%UR: 66.3-84.6%) to 54.8% (95%UR: 44.6-64.5%) or 61.5% (95%UR: 51.6-70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections.

10 CFR 26.103 - Determining a confirmed positive test result for alcohol.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Determining a confirmed positive test result for alcohol. 26.103 Section 26.103 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting... fitness indicates that the donor is fit to safely and competently perform his or her duties. ...

10 CFR 26.103 - Determining a confirmed positive test result for alcohol.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Determining a confirmed positive test result for alcohol. 26.103 Section 26.103 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting... fitness indicates that the donor is fit to safely and competently perform his or her duties. ...

10 CFR 26.103 - Determining a confirmed positive test result for alcohol.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Determining a confirmed positive test result for alcohol. 26.103 Section 26.103 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting... fitness indicates that the donor is fit to safely and competently perform his or her duties. ...

10 CFR 26.103 - Determining a confirmed positive test result for alcohol.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Determining a confirmed positive test result for alcohol. 26.103 Section 26.103 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting... fitness indicates that the donor is fit to safely and competently perform his or her duties. ...

10 CFR 26.103 - Determining a confirmed positive test result for alcohol.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Determining a confirmed positive test result for alcohol. 26.103 Section 26.103 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Collecting... fitness indicates that the donor is fit to safely and competently perform his or her duties. ...

Comparison of bronchoalveolar lavage cytology and transbronchial biopsy in the diagnosis of carcinoma of lung.

PubMed

Ahmed, Ayesha; Ahmed, Sajjad

2004-01-01

The objectives of this study were to compare bronchoalveolar lavage (BAL) cytology and transbronchial biopsy in the diagnosis of carcinoma lung and to determine accuracy of BAL cytology using histopathlologic examination of transbronchial biopsy as gold standard at our center. This study was carried out at Department of Histopathology, Ayub Medical College, Abbottabad, from 1.09.2000 to 28.02.2003. BAL fluid and bronchial biopsy were received and processed simultaneously. Four cytology and a set of histopathology slides were prepared. These were screened and diagnosis recorded. Sensitivity, Specificity, False Positive, False Negative, Positive predictive value and Negative predictive value of BAL cytology were determined using histopathology of transbronchial biopsy as gold standard. We found the sensitivity of BAL cytology to be 93.44% as compared with transbronchial biopsy. The specificity was 100%. There was no false positive while false negative results were 6.55 %. The positive predictive value was 100 %, while the negative predictive value was 75 %. The overall diagnostic efficacy of BAL cytology was 94.52 %. BAL cytology is a highly sensitive and specific test for diagnosis of carcinoma lung. It can be used as a quick and reliable diagnostic method for diagnosis of lung malignancy.

Evaluation of EMIT and RIA high volume test procedures for THC metabolites in urine utilizing GC/MS confirmation.

PubMed

Abercrombie, M L; Jewell, J S

1986-01-01

Results of EMIT, Abuscreen RIA, and GC/MS tests for THC metabolites in a high volume random urinalysis program are compared. Samples were field tested by non-laboratory personnel with an EMIT system using a 100 ng/mL cutoff. Samples were then sent to the Army Forensic Toxicology Drug Testing Laboratory (WRAMC) at Fort Meade, Maryland, where they were tested by RIA (Abuscreen) using a statistical 100 ng/mL cutoff. Confirmations of all RIA positives were accomplished using a GC/MS procedure. EMIT and RIA results agreed for 91% of samples. Data indicated a 4% false positive rate and a 10% false negative rate for EMIT field testing. In a related study, results for samples which tested positive by RIA for THC metabolites using a statistical 100 ng/mL cutoff were compared with results by GC/MS utilizing a 20 ng/mL cutoff for the THCA metabolite. Presence of THCA metabolite was detected in 99.7% of RIA positive samples. No relationship between quantitations determined by the two tests was found.

Hormone replacement therapy and false positive recall in the Million Women Study: patterns of use, hormonal constituents and consistency of effect

PubMed Central

Banks, Emily; Reeves, Gillian; Beral, Valerie; Bull, Diana; Crossley, Barbara; Simmonds, Moya; Hilton, Elizabeth; Bailey, Stephen; Barrett, Nigel; Briers, Peter; English, Ruth; Jackson, Alan; Kutt, Elizabeth; Lavelle, Janet; Rockall, Linda; Wallis, Matthew G; Wilson, Mary; Patnick, Julietta

2006-01-01

Introduction Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall. Methods A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome. Results Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43–1.83), 1.80 (1.62–2.01) and 0.76 (0.52–1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43–1.91), 1.49 (1.22–1.81) and 2.11 (1.45–3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67–2.04) and 1.75 (1.49–2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics. Conclusion Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening. PMID:16417651

Experimental investigation of observation error in anuran call surveys

USGS Publications Warehouse

McClintock, B.T.; Bailey, L.L.; Pollock, K.H.; Simons, T.R.

2010-01-01

Occupancy models that account for imperfect detection are often used to monitor anuran and songbird species occurrence. However, presenceabsence data arising from auditory detections may be more prone to observation error (e.g., false-positive detections) than are sampling approaches utilizing physical captures or sightings of individuals. We conducted realistic, replicated field experiments using a remote broadcasting system to simulate simple anuran call surveys and to investigate potential factors affecting observation error in these studies. Distance, time, ambient noise, and observer abilities were the most important factors explaining false-negative detections. Distance and observer ability were the best overall predictors of false-positive errors, but ambient noise and competing species also affected error rates for some species. False-positive errors made up 5 of all positive detections, with individual observers exhibiting false-positive rates between 0.5 and 14. Previous research suggests false-positive errors of these magnitudes would induce substantial positive biases in standard estimators of species occurrence, and we recommend practices to mitigate for false positives when developing occupancy monitoring protocols that rely on auditory detections. These recommendations include additional observer training, limiting the number of target species, and establishing distance and ambient noise thresholds during surveys. ?? 2010 The Wildlife Society.

To err is human, to correct is public health: a systematic review examining poor quality testing and misdiagnosis of HIV status.

PubMed

Johnson, Cheryl C; Fonner, Virginia; Sands, Anita; Ford, Nathan; Obermeyer, Carla Mahklouf; Tsui, Sharon; Wong, Vincent; Baggaley, Rachel

2017-08-29

In accordance with global testing and treatment targets, many countries are seeking ways to reach the "90-90-90" goals, starting with diagnosing 90% of all people with HIV. Quality HIV testing services are needed to enable people with HIV to be diagnosed and linked to treatment as early as possible. It is essential that opportunities to reach people with undiagnosed HIV are not missed, diagnoses are correct and HIV-negative individuals are not inadvertently initiated on life-long treatment. We conducted this systematic review to assess the magnitude of misdiagnosis and to describe poor HIV testing practices using rapid diagnostic tests. We systematically searched peer-reviewed articles, abstracts and grey literature published from 1 January 1990 to 19 April 2017. Studies were included if they used at least two rapid diagnostic tests and reported on HIV misdiagnosis, factors related to potential misdiagnosis or described quality issues and errors related to HIV testing. Sixty-four studies were included in this review. A small proportion of false positive (median 3.1%, interquartile range (IQR): 0.4-5.2%) and false negative (median: 0.4%, IQR: 0-3.9%) diagnoses were identified. Suboptimal testing strategies were the most common factor in studies reporting misdiagnoses, particularly false positive diagnoses due to using a "tiebreaker" test to resolve discrepant test results. A substantial proportion of false negative diagnoses were related to retesting among people on antiretroviral therapy. Conclusions HIV testing errors and poor practices, particularly those resulting in false positive or false negative diagnoses, do occur but are preventable. Efforts to accelerate HIV diagnosis and linkage to treatment should be complemented by efforts to improve the quality of HIV testing services and strengthen the quality management systems, particularly the use of validated testing algorithms and strategies, retesting people diagnosed with HIV before initiating treatment and providing clear messages to people with HIV on treatment on the risk of a "false negative" test result.

Thyroid Fine-Needle Aspiration Cytology:Causes of false-positive results.

PubMed

Malheiros, Daniela C; Canberk, Sule; Poller, David N; Schmitt, Fernando

2018-05-16

In this paper, we aim to focus on false positive results in the evaluation of thyroid aspirations, covering cystic, inflammatory, follicular and oncocytic lesions, papillary carcinoma, and medullary carcinoma of thyroid. The recently described entity, "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP), is also discussed detailing the impact of its introduction on the sensitivity and specificity of thyroid FNA, as well as the use of molecular tests for diagnostics. Medicolegal issues in relation to current practice in English law are also described. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

49 CFR 40.149 - May the MRO change a verified drug test result?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false May the MRO change a verified drug test result? 40... § 40.149 May the MRO change a verified drug test result? (a) As the MRO, you may change a verified test... positive. You would change X's test result from positive to negative and contact Y to conduct a...

The reliability of fine-needle aspiration biopsy in terms of malignancy in patients with Hashimoto thyroiditis.

PubMed

Kapan, Murat; Onder, Akin; Girgin, Sadullah; Ulger, Burak Veli; Firat, Ugur; Uslukaya, Omer; Oguz, Abdullah

2015-02-01

The aim of this study was to analyze the presence of malignancy in patients with Hashimoto's thyroiditis and to investigate the reliability of preoperative fine-needle aspiration biopsy (FNAB). The retrospective study included 44 patients who were operated on for nodular goiter between December 2010 and October 2011. The patients underwent thyroidectomy following a cytologic analysis plus FNAB. Hashimoto's thyroiditis was confirmed on histopathology in all patients. FNAB results were defined as benign in 14 (31.8%), suspicion for malignancy in 17 (38.6%), malignant in 9 (20.5%), and inadequate in 4 (9.1%). Following the thyroidectomy, presence of papillary thyroid carcinoma and follicular variant of papillary thyroid carcinoma were detected in 10 patients (22.7%) and 1 (2.3%) patient, respectively. The FNAB results were interpreted in terms of malignancy, which revealed the sensitivity as 80%; specificity, 40%; false positives, 69.2%; false negatives, 14.3%; positive predictive value, 31.8%; negative predictive value, 85.7%; and diagnostic accuracy, 50%. The coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma is quite common. The FNAB results for such cases are hard to evaluate, and they are likely to increase the number of false positives.

Evaluation of health benefits and harms of the breast cancer screening programme in the Basque Country using discrete event simulation.

PubMed

Arrospide, Arantzazu; Rue, Montserrat; van Ravesteyn, Nicolien T; Comas, Merce; Larrañaga, Nerea; Sarriugarte, Garbiñe; Mar, Javier

2015-10-12

Since the breast cancer screening programme in the Basque Country (BCSPBC) was started in 1996, more than 400,000 women aged 50 to 69 years have been invited to participate. Based on epidemiological observations and simulation techniques it is possible to extend observed short term data into anticipated long term results. The aim of this study was to assess the effectiveness of the programme through 2011 by quantifying the outcomes in breast cancer mortality, life-years gained, false positive results, and overdiagnosis. A discrete event simulation model was constructed to reproduce the natural history of breast cancer (disease-free, pre-clinical, symptomatic, and disease-specific death) and the actual observed characteristics of the screening programme during the evaluated period in the Basque women population. Goodness-of-fit statistics were applied for model validation. The screening effects were measured as differences in benefits and harms between the screened and unscreened populations. Breast cancer mortality reduction and life-years gained were considered as screening benefits, whereas, overdiagnosis and false positive results were assessed as harms. Results for a single cohort were also obtained. The screening programme yielded a 16 % reduction in breast cancer mortality and a 10 % increase in the incidence of breast cancer through 2011. Almost 2 % of all the women in the programme had a false positive result during the evaluation period. When a single cohort was analysed, the number of deaths decreased by 13 %, and 4 % of screen-detected cancers were overdiagnosed. Each woman with BC detected by the screening programme gained 2.5 life years due to early detection corrected by lead time. Fifteen years after the screening programme started, this study supports an important decrease in breast cancer mortality due to the screening programme, with reasonable risk of overdiagnosis and false positive results, and sustains the continuation of the breast cancer screening programme in the Basque population.

Memory for media: investigation of false memories for negatively and positively charged public events.

PubMed

Porter, Stephen; Taylor, Kristian; Ten Brinke, Leanne

2008-01-01

Despite a large body of false memory research, little has addressed the potential influence of an event's emotional content on susceptibility to false recollections. The Paradoxical Negative Emotion (PNE) hypothesis predicts that negative emotion generally facilitates memory but also heightens susceptibility to false memories. Participants were asked whether they could recall 20 "widely publicised" public events (half fictitious) ranging in emotional valence, with or without visual cues. Participants recalled a greater number of true negative events (M=3.31/5) than true positive (M=2.61/5) events. Nearly everyone (95%) came to recall at least one false event (M=2.15 false events recalled). Further, more than twice as many participants recalled any false negative (90%) compared to false positive (41.7%) events. Negative events, in general, were associated with more detailed memories and false negative event memories were more detailed than false positive event memories. Higher dissociation scores were associated with false recollections of negative events, specifically.

A prospective study: Is handheld micropower impulse radar technology (Pneumoscan) a promising method to detect pneumothorax?

PubMed

Hocagil, Hilal; Hocagil, Abdullah Cüneyt; Karacabey, Sinan; Akkaya, Tuğba; Şimşek, Gözde; Sanrı, Erkman

2015-09-01

This study aimed to discuss the effectiveness of Pneumoscan working with micropower impulse radar (MIR) technology in diagnosing pneumothorax (PTX) in the emergency department. Patients with suspicion of PTX and indication for thorax tomography (CT) were included into the study. Findings of the Thorax CT were compared with the results of Pneumoscan. Chi-square and Fisher's exact tests were used in categorical variables. One hundred and fifteen patients were included into the study group; twelve patients presented with PTX diagnosed by CT, 10 of which were detected by Pneumoscan. Thirty-six true negative results, sixty-seven false positive results, and two false negative results were obtained, which resulted in an overall sensitivity of 83.3%, specificity of 35.0% for Pneumoscan. There was no statistically significant difference between the effectiveness of Pneumoscan and CT on the detection of PTX (p=0.33). There was no difference between the size of PTX diagnosed by CT and PTX diagnosed by Pneumoscan (p=0.47). There was no statistically significant difference between Pneumoscan and CT on detecting the localisation of the PTX (p=1.00). For the 10 cases diagnosed by Pneumoscan, mean chest wall thickness was determined as 50.3 mm while mean chest wall thickness for two false negatives diagnosed by Pneumoscan was 56.5 mm. However, no statistically significant difference was found between the chest wall thickness and the effectiveness of Pneumoscan on the detection of the PTX (p=0.77). Among sixty-seven false positives diagnosed by Pneumoscan, 46.3% had additional medical signs such as bronchiectasis, pulmonary consolidation, pulmonary edema or pulmonary tumor when they had a reading with CT. The relationship between having additional medical signs at the reading with CT and the effectiveness of Pneumoscan on the detection of the PTX was investigated and no significant difference was found (p=0.472). Using Pneumoscan to detect PTX is controversial since the device has a high false positive ratio. Wherein, false positive diagnosis can cause unjustifiable chest tube insertion. In addition, the device failed to show the size of the PTX, and therefore, it did not aid in determining the treatment and prognosis on contrary to traditional diagnostic methods. The findings could not demonstrate that the device was efficient in emergency care. Further studies and increasing experience may change this outcome in upcoming years.

Underpowered samples, false negatives, and unconscious learning.

PubMed

Vadillo, Miguel A; Konstantinidis, Emmanouil; Shanks, David R

2016-02-01

The scientific community has witnessed growing concern about the high rate of false positives and unreliable results within the psychological literature, but the harmful impact of false negatives has been largely ignored. False negatives are particularly concerning in research areas where demonstrating the absence of an effect is crucial, such as studies of unconscious or implicit processing. Research on implicit processes seeks evidence of above-chance performance on some implicit behavioral measure at the same time as chance-level performance (that is, a null result) on an explicit measure of awareness. A systematic review of 73 studies of contextual cuing, a popular implicit learning paradigm, involving 181 statistical analyses of awareness tests, reveals how underpowered studies can lead to failure to reject a false null hypothesis. Among the studies that reported sufficient information, the meta-analytic effect size across awareness tests was d z = 0.31 (95 % CI 0.24-0.37), showing that participants' learning in these experiments was conscious. The unusually large number of positive results in this literature cannot be explained by selective publication. Instead, our analyses demonstrate that these tests are typically insensitive and underpowered to detect medium to small, but true, effects in awareness tests. These findings challenge a widespread and theoretically important claim about the extent of unconscious human cognition.

Custom Array Comparative Genomic Hybridization: the Importance of DNA Quality, an Expert Eye, and Variant Validation

PubMed Central

Lantieri, Francesca; Malacarne, Michela; Gimelli, Stefania; Santamaria, Giuseppe; Coviello, Domenico; Ceccherini, Isabella

2017-01-01

The presence of false positive and false negative results in the Array Comparative Genomic Hybridization (aCGH) design is poorly addressed in literature reports. We took advantage of a custom aCGH recently carried out to analyze its design performance, the use of several Agilent aberrations detection algorithms, and the presence of false results. Our study provides a confirmation that the high density design does not generate more noise than standard designs and, might reach a good resolution. We noticed a not negligible presence of false negative and false positive results in the imbalances call performed by the Agilent software. The Aberration Detection Method 2 (ADM-2) algorithm with a threshold of 6 performed quite well, and the array design proved to be reliable, provided that some additional filters are applied, such as considering only intervals with average absolute log2ratio above 0.3. We also propose an additional filter that takes into account the proportion of probes with log2ratio exceeding suggestive values for gain or loss. In addition, the quality of samples was confirmed to be a crucial parameter. Finally, this work raises the importance of evaluating the samples profiles by eye and the necessity of validating the imbalances detected. PMID:28287439

Buffer substitution in malaria rapid diagnostic tests causes false-positive results

PubMed Central

2010-01-01

Background Malaria rapid diagnostic tests (RDTs) are kits that generally include 20 to 25 test strips or cassettes, but only a single buffer vial. In field settings, laboratory staff occasionally uses saline, distilled water (liquids for parenteral drugs dilution) or tap water as substitutes for the RDT kit's buffer to compensate for the loss of a diluent bottle. The present study assessed the effect of buffer substitution on the RDT results. Methods Twenty-seven RDT brands were run with EDTA-blood samples of five malaria-free subjects, who were negative for rheumatoid factor and antinuclear antibodies. Saline, distilled water and tap water were used as substitute liquids. RDTs were also run with distilled water, without adding blood. Results were compared to those obtained with the RDT kit's buffer and Plasmodium positive samples. Results Only eight cassettes (in four RDT brands) showed no control line and were considered invalid. Visible test lines occurred for at least one malaria-free sample and one of the substitutes in 20/27 (74%) RDT brands (saline: n = 16; distilled water: n = 17; and tap water: n = 20), and in 15 RDTs which were run with distilled water only. They occurred for all Plasmodium antigens and RDT formats (two-, three- and four-band RDTs). Clearance of the background of the strip was excellent except for saline. The aspects (colour, intensity and crispness) of the control and the false-positive test lines were similar to those obtained with the RDT kits' buffer and Plasmodium positive samples. Conclusion Replacement of the RDT kit's dedicated buffer by saline, distilled water and tap water can cause false-positive test results. PMID:20650003

[Evaluation of performance and false positivity of Mediace RPR test that uses a chemistry autoanalyzer].

PubMed

Noh, Jaekwang; Ko, Hak Hyun; Yun, Yeomin; Choi, Young Sook; Lee, Sang Gon; Shin, Sue; Han, Kyou Sup; Song, Eun Young

2008-08-01

We evaluated the performance and false positive rate of Mediace RPR test (Sekisui, Japan), a newly introduced nontreponemal test using a chemistry autoanalyzer. The sensitivity of Mediace RPR test was analyzed using sera from 50 patients with syphilis in different stages (8 primary, 7 secondary, and 35 latent), 14 sera positive with fluorescent treponemal antibody absorption (FTA-ABS) IgM, and 74 sera positive with conventional rapid plasma regain (RPR) card test (Asan, Korea) and also positive with Treponema pallidum hemagglutination (TPHA) test or FTA-ABS IgG test. The specificity was analyzed on 108 healthy blood donors. We also performed RPR card test on 302 sera that had been tested positive with Mediace RPR test and also performed TPHA or FTA-ABS IgG test to analyze the false positive rate of Mediace RPR test. A cutoff value of 0.5 R.U. (RPR unit) was used for Mediace RPR test. Mediace RPR test on syphilitic sera of different stages (primary, secondary, and latent stages) and FTA-ABS IgM positive sera showed a sensitivity of 100%, 100%, 82.9% and 100%, respectively. Among the 74 sera positive with conventional RPR card test and TPHA or FTA-ABS IgG test, 55 were positive with Mediace test. The specificity of Mediace RPR test on blood donors was 97.2%. Among the 302 sera positive with Mediace RPR test, 137 sera (45.4%) were negative by RPR card and TPHA/FTA-ABS IgG tests. Although the sensitivities of Mediace RPR were good for primary and secondary syphilis, due to its high negative rate of Mediace RPR over the conventional RPR positive samples, further studies are necessary whether it can replace conventional nontreponemal test for screening purpose. Moreover, in view of the high false positive rate, positive results by Mediace RPR test should be confirmed with treponemal tests.

The semantics of emotion in false memory.

PubMed

Brainerd, C J; Bookbinder, S H

2018-03-26

The emotional valence of target information has been a centerpiece of recent false memory research, but in most experiments, it has been confounded with emotional arousal. We sought to clarify the results of such research by identifying a shared mathematical relation between valence and arousal ratings in commonly administered normed materials. That relation was then used to (a) decide whether arousal as well as valence influences false memory when they are confounded and to (b) determine whether semantic properties that are known to affect false memory covary with valence and arousal ratings. In Study 1, we identified a quadratic relation between valence and arousal ratings of words and pictures that has 2 key properties: Arousal increases more rapidly as function of negative valence than positive valence, and hence, a given level of negative valence is more arousing than the same level of positive valence. This quadratic function predicts that if arousal as well as valence affects false memory when they are confounded, false memory data must have certain fine-grained properties. In Study 2, those properties were absent from norming data for the Cornell-Cortland Emotional Word Lists, indicating that valence but not arousal affects false memory in those norms. In Study 3, we tested fuzzy-trace theory's explanation of that pattern: that valence ratings are positively related to semantic properties that are known to increase false memory, but arousal ratings are not. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Arousal-But Not Valence-Reduces False Memories at Retrieval.

PubMed

Mirandola, Chiara; Toffalini, Enrico

2016-01-01

Mood affects both memory accuracy and memory distortions. However, some aspects of this relation are still poorly understood: (1) whether valence and arousal equally affect false memory production, and (2) whether retrieval-related processes matter; the extant literature typically shows that mood influences memory performance when it is induced before encoding, leaving unsolved whether mood induced before retrieval also impacts memory. We examined how negative, positive, and neutral mood induced before retrieval affected inferential false memories and related subjective memory experiences. A recognition-memory paradigm for photographs depicting script-like events was employed. Results showed that individuals in both negative and positive moods-similar in arousal levels-correctly recognized more target events and endorsed fewer false memories (and these errors were linked to remember responses less frequently), compared to individuals in neutral mood. This suggests that arousal (but not valence) predicted memory performance; furthermore, we found that arousal ratings provided by participants were more adequate predictors of memory performance than their actual belonging to either positive, negative or neutral mood groups. These findings suggest that arousal has a primary role in affecting memory, and that mood exerts its power on true and false memory even when induced at retrieval.

Arousal—But Not Valence—Reduces False Memories at Retrieval

PubMed Central

Mirandola, Chiara; Toffalini, Enrico

2016-01-01

Mood affects both memory accuracy and memory distortions. However, some aspects of this relation are still poorly understood: (1) whether valence and arousal equally affect false memory production, and (2) whether retrieval-related processes matter; the extant literature typically shows that mood influences memory performance when it is induced before encoding, leaving unsolved whether mood induced before retrieval also impacts memory. We examined how negative, positive, and neutral mood induced before retrieval affected inferential false memories and related subjective memory experiences. A recognition-memory paradigm for photographs depicting script-like events was employed. Results showed that individuals in both negative and positive moods–similar in arousal levels–correctly recognized more target events and endorsed fewer false memories (and these errors were linked to remember responses less frequently), compared to individuals in neutral mood. This suggests that arousal (but not valence) predicted memory performance; furthermore, we found that arousal ratings provided by participants were more adequate predictors of memory performance than their actual belonging to either positive, negative or neutral mood groups. These findings suggest that arousal has a primary role in affecting memory, and that mood exerts its power on true and false memory even when induced at retrieval. PMID:26938737

Prevention. How much harm? How much benefit? 3. Physical, psychological and social harm.

PubMed Central

Marshall, K G

1996-01-01

Harm caused by preventive programs may be physical, psychological, social or, if informed consent has not been obtained, ethical. Adverse effects of preventive screening programs may occur at any of the three levels of the "screening cascade", the screening procedure itself, the investigation of abnormal results of screening tests or the treatment of detected abnormalities or diseases. The greatest harm occurs at the second and third levels. Examples of procedures that may cause physical harm are venipuncture, mammography, colonoscopy, breast biopsy, transrectal ultrasonography, prostate biopsy, weight-reducing and cholesterol-lowering diets and radical prostatectomy. The psychological and social harm of preventive programs involves anticipated discomfort or perception of adverse effects of preventive interventions; unpleasant interactions with health care workers, time required for preventive programs, excessive overall awareness of health, anxiety over the results of a screening test implications of a positive screening test, consequences of being labelled as "sick" or "at risk," psychopathologic effects induced directly by preventive programs and, in the case of a false-negative test result, false assurance of disease-free status. Since the positive predictive value of screening tests in the general population is always low, most abnormal test results are "false-positive," these engender a great deal of psychological discuss among patients. PMID:8800074

On the feasibility of linking census samples to the National Death Index for epidemiologic studies: a progress report.

PubMed Central

Rogot, E; Feinleib, M; Ockay, K A; Schwartz, S H; Bilgrad, R; Patterson, J E

1983-01-01

To test the feasibility of using large national probability samples provided by the US Census Bureau, a pilot project was initiated to link 230,000 Census-type records to the National Death Index (NDI). Using strict precautions to maintain the complete confidentiality of individual records, the Current Population Survey files of one month in 1973 and one month in 1978 were matched by computer to the 1979 NDI file. The basic question to be addressed was whether deaths so obtained are seriously underestimated when there is no Social Security Number (SSN) in the Census record. The search of the NDI file resulted in 5,542 matches of which about 1,800 appear to be "true positives" representing deaths, the remainder are "false positives." Of the deaths, 80 per cent would still have been detected without SSN in the Census record. The main reasons for missing deaths (false negatives) were discrepancies in the year of birth and in the given name. Assuming certain changes in the NDI matching algorithm, the 80 per cent figure could increase to 85 per cent or higher; however, this could also cause significant increases in the number of false positives. The National Heart, Lung and Blood Institute (NHLBI) and Census Bureau staff are currently developing a probabilistic method to eliminate false positives from the NDI output tape. The results of the pilot study indicate that a larger research project is clearly feasible. PMID:6625029

The psychological impact of a false-positive screening mammogram in Barcelona.

PubMed

Espasa, Rebecca; Murta-Nascimento, Cristiane; Bayés, Ramón; Sala, Maria; Casamitjana, Montserrat; Macià, Francesc; Castells, Xavier

2012-12-01

The purpose of this study was to ascertain the psychological impact of mammographic screening for women who receive negative results and for those who need additional non-invasive and invasive complementary investigations to exclude breast cancer (false positives). One hundred fifty women who attended a breast cancer screening programme in Barcelona, aged 50-69 years, were included in this study: 50 with negative results and 100 with false positive mammograms (50 underwent non-invasive and 50 underwent invasive complementary investigations). Participants worried little until they underwent mammography, but worries increased when a telephone call notified the women of the need for further testing. A substantial proportion of women requiring further assessment reported that they were at least somewhat worried about having breast cancer throughout the screening process (P < 0.0001). Nevertheless, levels of anxiety and depression, measured by the Hospital Anxiety and Depression Scale, showed no statistically significant differences among the three groups. In conclusion, although the women showed no psychological morbidity, there is a substantial psychological response in those with an abnormal screening mammogram.

CNNdel: Calling Structural Variations on Low Coverage Data Based on Convolutional Neural Networks

PubMed Central

2017-01-01

Many structural variations (SVs) detection methods have been proposed due to the popularization of next-generation sequencing (NGS). These SV calling methods use different SV-property-dependent features; however, they all suffer from poor accuracy when running on low coverage sequences. The union of results from these tools achieves fairly high sensitivity but still produces low accuracy on low coverage sequence data. That is, these methods contain many false positives. In this paper, we present CNNdel, an approach for calling deletions from paired-end reads. CNNdel gathers SV candidates reported by multiple tools and then extracts features from aligned BAM files at the positions of candidates. With labeled feature-expressed candidates as a training set, CNNdel trains convolutional neural networks (CNNs) to distinguish true unlabeled candidates from false ones. Results show that CNNdel works well with NGS reads from 26 low coverage genomes of the 1000 Genomes Project. The paper demonstrates that convolutional neural networks can automatically assign the priority of SV features and reduce the false positives efficaciously. PMID:28630866

Critical Congenital Heart Disease Screening by Pulse Oximetry in a Neonatal Intensive Care Unit

PubMed Central

Manja, Veena; Mathew, Bobby; Carrion, Vivien; Lakshminrusimha, Satyan

2014-01-01

Critical congenital heart disease (CCHD) screening is effective in asymptomatic late preterm and term newborn infants with a low false positive rate (0.035%). Objective (1) To compare 2817 NICU discharges before and after implementation of CCHD screening; and (2) to evaluate CCHD screening at < 35 weeks gestation. Methods collection of results of CCHD screening including preductal and postductal SpO2 values. Results During the pre-CCHD screen period, 1247 infants were discharged from the NICU and one case of CCHD was missed. After 3/1/12, 1508 CCHD screens were performed among 1570 discharges and no CCHDs were missed. The preductal and postductal SpO2 values were 98.8±1.4% and 99±1.3% respectively in preterm and 98.9±1.3% and 98.9±1.4% in term infants. Ten infants had false positive screens (10/1508=0.66%). Conclusions Performing universal screening in the NICU is feasible but is associated with a higher false positive rate compared to asymptomatic newborn infants. PMID:25058746

Efficacy of 67 gallium ECT imaging in lymphoma, infection, and lung carcinoma: A comparison with planar imaging

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

Harwood, S.J.; Anderson, M.W.; Klein, R.C.

1984-01-01

Emission computed tomography (ECT) studies were performed on a GE 400 A/T camera and ADAC computers (system 3 and system 3300). Thirty-three sets of ECT and planar images were obtained in 20 patients over a six month period. Imaging was performed 48 hours after the intravenous administration of 5 mc of Gallium 67 citrate. No bowel preparation was employed. Comparison is made of the initial nuclear medicine report derived from planar and ECT imaging aided by clinical knowledge versus the consensus opinion of two nuclear medicine physicians reading the planar images along with minimal clinical information. The lymphoma series consistsmore » of 18 scans in 10 patients. There were 5 scans in which a false negative planar interpretation was changed to a true positive ECT interpretation. Sensitivity of planar imaging for lymphoma was 58% which rose to 100% with addition of ECT information. There were no false positives by either technique. There were 5 sets of scans in 5 lung carcinoma patients. Sensitivity of the planar images was 60% because of 2 false negative results. Sensitivity of the ECT technique was 100%. There were no false positives. The infection series consists of 10 scans in 5 patients. Sensitivity of ECT was 100%, sensitivity of planar was 66%. There was 1 false positive planar. For the total series the accuracy of planar imaging was 69% and the predictive value of a negative planar interpretation was 44%. Corresponding values for ECT imaging were 100%. The authors' experience demonstrates significant increase in sensitivity without loss of specificity resulting from the use of Emission Computed Tomography in both chest and abdomen in patients with lymphoma, infection, and lung cancer.« less

Publication bias and the canonization of false facts.

PubMed

Nissen, Silas Boye; Magidson, Tali; Gross, Kevin; Bergstrom, Carl T

2016-12-20

Science is facing a "replication crisis" in which many experimental findings cannot be replicated and are likely to be false. Does this imply that many scientific facts are false as well? To find out, we explore the process by which a claim becomes fact. We model the community's confidence in a claim as a Markov process with successive published results shifting the degree of belief. Publication bias in favor of positive findings influences the distribution of published results. We find that unless a sufficient fraction of negative results are published, false claims frequently can become canonized as fact. Data-dredging, p-hacking, and similar behaviors exacerbate the problem. Should negative results become easier to publish as a claim approaches acceptance as a fact, however, true and false claims would be more readily distinguished. To the degree that the model reflects the real world, there may be serious concerns about the validity of purported facts in some disciplines.

Avoiding false positive antigen detection by flow cytometry on blood cell derived microparticles: the importance of an appropriate negative control.

PubMed

Crompot, Emerence; Van Damme, Michael; Duvillier, Hugues; Pieters, Karlien; Vermeesch, Marjorie; Perez-Morga, David; Meuleman, Nathalie; Mineur, Philippe; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

2015-01-01

Microparticles (MPs), also called microvesicles (MVs) are plasma membrane-derived fragments with sizes ranging from 0.1 to 1μm. Characterization of these MPs is often performed by flow cytometry but there is no consensus on the appropriate negative control to use that can lead to false positive results. We analyzed MPs from platelets, B-cells, T-cells, NK-cells, monocytes, and chronic lymphocytic leukemia (CLL) B-cells. Cells were purified by positive magnetic-separation and cultured for 48h. Cells and MPs were characterized using the following monoclonal antibodies (CD19,20 for B-cells, CD3,8,5,27 for T-cells, CD16,56 for NK-cells, CD14,11c for monocytes, CD41,61 for platelets). Isolated MPs were stained with annexin-V-FITC and gated between 300nm and 900nm. The latex bead technique was then performed for easy detection of MPs. Samples were analyzed by Transmission (TEM) and Scanning Electron microscopy (SEM). Annexin-V positive events within a gate of 300-900nm were detected and defined as MPs. Our results confirmed that the characteristic antigens CD41/CD61 were found on platelet-derived-MPs validating our technique. However, for MPs derived from other cell types, we were unable to detect any antigen, although they were clearly expressed on the MP-producing cells in the contrary of several data published in the literature. Using the latex bead technique, we confirmed detection of CD41,61. However, the apparent expression of other antigens (already deemed positive in several studies) was determined to be false positive, indicated by negative controls (same labeling was used on MPs from different origins). We observed that mother cell antigens were not always detected on corresponding MPs by direct flow cytometry or latex bead cytometry. Our data highlighted that false positive results could be generated due to antibody aspecificity and that phenotypic characterization of MPs is a difficult field requiring the use of several negative controls.

Predictive Value of Parkinsonian Primates in Pharmacologic Studies: A Comparison between the Macaque, Marmoset, and Squirrel Monkey.

PubMed

Veyres, Nicolas; Hamadjida, Adjia; Huot, Philippe

2018-05-01

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

First European interlaboratory comparison of tetracycline and age determination with red fox teeth following oral rabies vaccination programs.

PubMed

Robardet, Emmanuelle; Demerson, Jean-Michel; Andrieu, Sabrina; Cliquet, Florence

2012-10-01

The first European interlaboratory comparison of tetracycline and age determination with red fox (Vulpes vulpes) tooth samples was organized by the European Union Reference Laboratory for rabies. Performance and procedures implemented by member states were compared. These techniques are widely used to monitor bait uptake in European oral rabies vaccination campaigns. A panel of five red fox half-mandibles comprising one weak positive juvenile sample, two positive adult samples, one negative juvenile sample, and one negative adult sample were sent, along with a technical questionnaire, to 12 laboratories participating on a voluntary basis. The results of only three laboratories (25%) were 100% correct. False-negative results were more frequently seen in weak positive juvenile samples (58%) but were infrequent in positive adult samples (4%), probably due to differences in the ease of reading the two groups of teeth. Four laboratories (44%) had correct results for age determination on all samples. Ages were incorrectly identified in both adult and juvenile samples, with 11 and 17% of discordant results, respectively. Analysis of the technical questionnaires in parallel with test results suggested that all laboratories cutting mandible sections between the canine and first premolar obtained false results. All the laboratories using longitudinal rather than transverse sections and those not using a mounting medium also produced false results. Section thickness appeared to affect the results; no mistakes were found in laboratories using sections <150 μm thick. Factors having a potential impact on the success of laboratories were discussed, and recommendations proposed. Such interlaboratory trials underline the importance of using standardized procedures for biomarker detection in oral rabies vaccination campaigns. Several changes can be made to improve analysis quality and increase the comparability of bait uptake frequencies among member states.

Automated detection scheme of architectural distortion in mammograms using adaptive Gabor filter

NASA Astrophysics Data System (ADS)

Yoshikawa, Ruriha; Teramoto, Atsushi; Matsubara, Tomoko; Fujita, Hiroshi

2013-03-01

Breast cancer is a serious health concern for all women. Computer-aided detection for mammography has been used for detecting mass and micro-calcification. However, there are challenges regarding the automated detection of the architectural distortion about the sensitivity. In this study, we propose a novel automated method for detecting architectural distortion. Our method consists of the analysis of the mammary gland structure, detection of the distorted region, and reduction of false positive results. We developed the adaptive Gabor filter for analyzing the mammary gland structure that decides filter parameters depending on the thickness of the gland structure. As for post-processing, healthy mammary glands that run from the nipple to the chest wall are eliminated by angle analysis. Moreover, background mammary glands are removed based on the intensity output image obtained from adaptive Gabor filter. The distorted region of the mammary gland is then detected as an initial candidate using a concentration index followed by binarization and labeling. False positives in the initial candidate are eliminated using 23 types of characteristic features and a support vector machine. In the experiments, we compared the automated detection results with interpretations by a radiologist using 50 cases (200 images) from the Digital Database of Screening Mammography (DDSM). As a result, true positive rate was 82.72%, and the number of false positive per image was 1.39. There results indicate that the proposed method may be useful for detecting architectural distortion in mammograms.

Hiatal hernia uptake of iodine-131 mimicking mediastinal metastasis of papillary thyroid carcinoma.

PubMed

Haghighatafshar, Mahdi; Khajehrahimi, Farnaz

2015-01-01

There are a few case reports of hiatal hernia demonstrating thoracic uptake on I-131 scintigraphy. In this case, high thyroglobulin levels in combination with misinterpretation of I-131 uptake in the mediastinum, leaded to mismanagement of the patient. Here we present a case of focal I-131 uptake within a hiatal hernia initially mimicking an isolated mediastinal metastasis. There are many potential causes of false-positive I-131 scan result. In this case, adjunctive chest computed tomography and gastroesophageal barium study helped to elucidate the true nature of this I-131 uptake. False-positive findings may be caused by a wide variety of nonthyroidal carcinomas, which can concentrate radioiodine or from skin contamination. Several organs, such as the gastric, salivary glands, renal cyst, pericardial effusion, and ovarian can accumulate I-131. It should be borne in mind as a potential source of false-positive whole-body I-131 imaging.

Biased lineup instructions and face identification from video images.

PubMed

Thompson, W Burt; Johnson, Jaime

2008-01-01

Previous eyewitness memory research has shown that biased lineup instructions reduce identification accuracy, primarily by increasing false-positive identifications in target-absent lineups. Because some attempts at identification do not rely on a witness's memory of the perpetrator but instead involve matching photos to images on surveillance video, the authors investigated the effects of biased instructions on identification accuracy in a matching task. In Experiment 1, biased instructions did not affect the overall accuracy of participants who used video images as an identification aid, but nearly all correct decisions occurred with target-present photo spreads. Both biased and unbiased instructions resulted in high false-positive rates. In Experiment 2, which focused on video-photo matching accuracy with target-absent photo spreads, unbiased instructions led to more correct responses (i.e., fewer false positives). These findings suggest that investigators should not relax precautions against biased instructions when people attempt to match photos to an unfamiliar person recorded on video.

Recursive regularization for inferring gene networks from time-course gene expression profiles

PubMed Central

Shimamura, Teppei; Imoto, Seiya; Yamaguchi, Rui; Fujita, André; Nagasaki, Masao; Miyano, Satoru

2009-01-01

Background Inferring gene networks from time-course microarray experiments with vector autoregressive (VAR) model is the process of identifying functional associations between genes through multivariate time series. This problem can be cast as a variable selection problem in Statistics. One of the promising methods for variable selection is the elastic net proposed by Zou and Hastie (2005). However, VAR modeling with the elastic net succeeds in increasing the number of true positives while it also results in increasing the number of false positives. Results By incorporating relative importance of the VAR coefficients into the elastic net, we propose a new class of regularization, called recursive elastic net, to increase the capability of the elastic net and estimate gene networks based on the VAR model. The recursive elastic net can reduce the number of false positives gradually by updating the importance. Numerical simulations and comparisons demonstrate that the proposed method succeeds in reducing the number of false positives drastically while keeping the high number of true positives in the network inference and achieves two or more times higher true discovery rate (the proportion of true positives among the selected edges) than the competing methods even when the number of time points is small. We also compared our method with various reverse-engineering algorithms on experimental data of MCF-7 breast cancer cells stimulated with two ErbB ligands, EGF and HRG. Conclusion The recursive elastic net is a powerful tool for inferring gene networks from time-course gene expression profiles. PMID:19386091

Evaluating gold standard corpora against gene/protein tagging solutions and lexical resources

PubMed Central

2013-01-01

Motivation The identification of protein and gene names (PGNs) from the scientific literature requires semantic resources: Terminological and lexical resources deliver the term candidates into PGN tagging solutions and the gold standard corpora (GSC) train them to identify term parameters and contextual features. Ideally all three resources, i.e. corpora, lexica and taggers, cover the same domain knowledge, and thus support identification of the same types of PGNs and cover all of them. Unfortunately, none of the three serves as a predominant standard and for this reason it is worth exploring, how these three resources comply with each other. We systematically compare different PGN taggers against publicly available corpora and analyze the impact of the included lexical resource in their performance. In particular, we determine the performance gains through false positive filtering, which contributes to the disambiguation of identified PGNs. Results In general, machine learning approaches (ML-Tag) for PGN tagging show higher F1-measure performance against the BioCreative-II and Jnlpba GSCs (exact matching), whereas the lexicon based approaches (LexTag) in combination with disambiguation methods show better results on FsuPrge and PennBio. The ML-Tag solutions balance precision and recall, whereas the LexTag solutions have different precision and recall profiles at the same F1-measure across all corpora. Higher recall is achieved with larger lexical resources, which also introduce more noise (false positive results). The ML-Tag solutions certainly perform best, if the test corpus is from the same GSC as the training corpus. As expected, the false negative errors characterize the test corpora and – on the other hand – the profiles of the false positive mistakes characterize the tagging solutions. Lex-Tag solutions that are based on a large terminological resource in combination with false positive filtering produce better results, which, in addition, provide concept identifiers from a knowledge source in contrast to ML-Tag solutions. Conclusion The standard ML-Tag solutions achieve high performance, but not across all corpora, and thus should be trained using several different corpora to reduce possible biases. The LexTag solutions have different profiles for their precision and recall performance, but with similar F1-measure. This result is surprising and suggests that they cover a portion of the most common naming standards, but cope differently with the term variability across the corpora. The false positive filtering applied to LexTag solutions does improve the results by increasing their precision without compromising significantly their recall. The harmonisation of the annotation schemes in combination with standardized lexical resources in the tagging solutions will enable their comparability and will pave the way for a shared standard. PMID:24112383

The diagnosis of aortoiliac disease. A noninvasive femoral cuff technique.

PubMed Central

Barringer, M; Poole, G V; Shircliffe, A C; Meredith, J W; Hightower, F; Plonk, G W

1983-01-01

An inexpensive femoral "cuff" developed in this noninvasive vascular laboratory allows pulse volume recordings and systolic pressure measurements of the femoral arteries. Using the parameters 1) femoral/brachial systolic pressure ratio, 2) wave amplitude, and 3) status of the dicrotic notch for assessment of results, it was found that the cuff correctly identified 59 of 62 limbs with at least 50% aortoiliac stenosis, with only two false-positive results, for an accuracy of 97%. The high, wide thigh cuff identified 57 of the 62 limbs, but had 45 false-positive results (77% accuracy). Use of the femoral "cuff" has refined the ability to identify the anatomic location of significant arterial stenoses in the lower extremities. Images Fig. 1. Fig. 2. PMID:6824373

To err is human, to correct is public health: a systematic review examining poor quality testing and misdiagnosis of HIV status

PubMed Central

Johnson, Cheryl C.; Fonner, Virginia; Sands, Anita; Ford, Nathan; Obermeyer, Carla Mahklouf; Tsui, Sharon; Wong, Vincent; Baggaley, Rachel

2017-01-01

Abstract Introduction: In accordance with global testing and treatment targets, many countries are seeking ways to reach the “90-90-90” goals, starting with diagnosing 90% of all people with HIV. Quality HIV testing services are needed to enable people with HIV to be diagnosed and linked to treatment as early as possible. It is essential that opportunities to reach people with undiagnosed HIV are not missed, diagnoses are correct and HIV-negative individuals are not inadvertently initiated on life-long treatment. We conducted this systematic review to assess the magnitude of misdiagnosis and to describe poor HIV testing practices using rapid diagnostic tests. Methods: We systematically searched peer-reviewed articles, abstracts and grey literature published from 1 January 1990 to 19 April 2017. Studies were included if they used at least two rapid diagnostic tests and reported on HIV misdiagnosis, factors related to potential misdiagnosis or described quality issues and errors related to HIV testing. Results: Sixty-four studies were included in this review. A small proportion of false positive (median 3.1%, interquartile range (IQR): 0.4-5.2%) and false negative (median: 0.4%, IQR: 0-3.9%) diagnoses were identified. Suboptimal testing strategies were the most common factor in studies reporting misdiagnoses, particularly false positive diagnoses due to using a “tiebreaker” test to resolve discrepant test results. A substantial proportion of false negative diagnoses were related to retesting among people on antiretroviral therapy. Conclusions: HIV testing errors and poor practices, particularly those resulting in false positive or false negative diagnoses, do occur but are preventable. Efforts to accelerate HIV diagnosis and linkage to treatment should be complemented by efforts to improve the quality of HIV testing services and strengthen the quality management systems, particularly the use of validated testing algorithms and strategies, retesting people diagnosed with HIV before initiating treatment and providing clear messages to people with HIV on treatment on the risk of a “false negative” test result. PMID:28872271

False-Positive Gen-Probe Direct Mycobacterium tuberculosis Amplification Test Results for Patients with Pulmonary M. kansasii and M. avium Infections

PubMed Central

Jorgensen, James H.; Salinas, Jesse R.; Paxson, Rosemary; Magnon, Karen; Patterson, Jan E.; Patterson, Thomas F.

1999-01-01

The Gen-Probe Amplified Mycobacterium Tuberculosis Direct (MTD) test has been approved for use in the United States for the rapid diagnosis of pulmonary tuberculosis in patients with acid-fast smear-positive sputum samples since 1996. Four patients infected with human immunodeficiency virus and one chronic pulmonary-disease patient seen in our institutions with abnormal chest radiographs and fluorochrome stain-positive sputa were evaluated for tuberculosis, including performance of the MTD test on expectorated sputum samples. Three of these five patients’ sputa were highly smear-positive (i.e., more than 100 bacilli per high-power field), while two patient’s sputa contained 1 to 10 bacilli per field. MTD results on sputum specimens from these patients ranged from 43,498 to 193,858 relative light units (RLU). Gen-Probe has defined values of at least 30,000 RLU as indicative of a positive test, i.e., the presence of Mycobacterium tuberculosis RNA. Four of the patients’ sputum cultures yielded growth of M. kansasii within 6 to 12 days, and the fifth produced growth of M. avium only. One patient’s culture contained both M. kansasii and M. avium, but none of the initial or follow-up cultures from these five patients revealed M. tuberculosis. However, subsequent cultures from three of the patients again revealed M. kansasii. During the period of this study, in which MTD tests were performed on smear-positive sputum specimens from 82 patients, four of seven patients with culture-proven M. kansasii pulmonary infections yielded one or more false-positive MTD tests. The MTD sensitivity observed in this study was 93.8%, and the specificity was 85.3%. Five cultures of M. kansasii (including three of these patients’ isolates and M. kansasii ATCC 12478), and cultures of several other species were examined at densities of 105 to 107 viable CFU/ml by the MTD test. All five isolates of M. kansasii and three of three isolates of M. simiae yielded false-positive test results, with readings of 75,191 to 335,591 RLU. These findings indicate that low-level false-positive MTD results can occur due to the presence of M. kansasii, M. avium, and possibly other Mycobacterium species other than M. tuberculosis in sputum. Low-level positive MTD results of 30,000 to 500,000 RLU should be interpreted in light of these findings. It remains to be determined if the enhanced MTD test (MTD 2) recently released by Gen-Probe will provide greater specificity than that observed in this report with its first-generation test. PMID:9854086

Computer-aided diagnosis of contrast-enhanced spectral mammography: A feasibility study.

PubMed

Patel, Bhavika K; Ranjbar, Sara; Wu, Teresa; Pockaj, Barbara A; Li, Jing; Zhang, Nan; Lobbes, Mark; Zhang, Bin; Mitchell, J Ross

2018-01-01

To evaluate whether the use of a computer-aided diagnosis-contrast-enhanced spectral mammography (CAD-CESM) tool can further increase the diagnostic performance of CESM compared with that of experienced radiologists. This IRB-approved retrospective study analyzed 50 lesions described on CESM from August 2014 to December 2015. Histopathologic analyses, used as the criterion standard, revealed 24 benign and 26 malignant lesions. An expert breast radiologist manually outlined lesion boundaries on the different views. A set of morphologic and textural features were then extracted from the low-energy and recombined images. Machine-learning algorithms with feature selection were used along with statistical analysis to reduce, select, and combine features. Selected features were then used to construct a predictive model using a support vector machine (SVM) classification method in a leave-one-out-cross-validation approach. The classification performance was compared against the diagnostic predictions of 2 breast radiologists with access to the same CESM cases. Based on the SVM classification, CAD-CESM correctly identified 45 of 50 lesions in the cohort, resulting in an overall accuracy of 90%. The detection rate for the malignant group was 88% (3 false-negative cases) and 92% for the benign group (2 false-positive cases). Compared with the model, radiologist 1 had an overall accuracy of 78% and a detection rate of 92% (2 false-negative cases) for the malignant group and 62% (10 false-positive cases) for the benign group. Radiologist 2 had an overall accuracy of 86% and a detection rate of 100% for the malignant group and 71% (8 false-positive cases) for the benign group. The results of our feasibility study suggest that a CAD-CESM tool can provide complementary information to radiologists, mainly by reducing the number of false-positive findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Is there a positive bias in false recognition? Evidence from confabulating amnesia patients.

PubMed

Alkathiri, Nura H; Morris, Robin G; Kopelman, Michael D

2015-10-01

Although there is some evidence for a positive emotional bias in the content of confabulations in brain damaged patients, findings have been inconsistent. The present study used the semantic-associates procedure to induce false recall and false recognition in order to examine whether a positive bias would be found in confabulating amnesic patients, relative to non-confabulating amnesic patients and healthy controls. Lists of positive, negative and neutral words were presented in order to induce false recall or false recognition of non-presented (but semantically associated) words. The latter were termed 'critical intrusions'. Thirteen confabulating amnesic patients, 13 non-confabulating amnesic patients and 13 healthy controls were investigated. Confabulating patients falsely recognised a higher proportion of positive (but unrelated) words, compared with non-confabulating patients and healthy controls. No differences were found for recall memory. Signal detection analysis, however, indicated that the positive bias for false recognition memory might reflect weaker memory in the confabulating amnesic group. This suggested that amnesia patients with weaker memory are more likely to confabulate and the content of these confabulations are more likely to be positive. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of Breast Cancer Screening and Its Association with Later Use of Preventive Services among Medicare Beneficiaries.

PubMed

Kang, Stella K; Jiang, Miao; Duszak, Richard; Heller, Samantha L; Hughes, Danny R; Moy, Linda

2018-06-05

Purpose To retrospectively assess whether there is an association between screening mammography and the use of a variety of preventive services in women who are enrolled in Medicare. Materials and Methods U.S. Medicare claims from 2010 to 2014 Research Identifiable Files were reviewed to retrospectively identify a group of women who underwent screening mammography and a control group without screening mammography in 2012. The screened group was divided into positive versus negative results at screening, and the positive subgroup was divided into false-positive and true-positive findings. Multivariate logistic regression models and inverse probability of treatment weighting were used to examine the relationship between screening status and the probabilities of undergoing Papanicolaou test, bone mass measurement, or influenza vaccination in the following 2 years. Results The cohort consisted of 555 705 patients, of whom 185 625 (33.4%) underwent mammography. After adjusting for patient demographics, comorbidities, geographic covariates, and baseline preventive care, women who underwent index screening mammography (with either positive or negative results) were more likely than unscreened women to later undergo Papanicolaou test (odds ratio [OR], 1.49; 95% confidence interval: 1.40, 1.58), bone mass measurement (OR, 1.70; 95% confidence interval: 1.63, 1.78), and influenza vaccine (OR, 1.45; 95% confidence interval: 1.37, 1.53). In women who had not undergone these preventive measures in the 2 years before screening mammography, use of these three services after false-positive findings at screening was no different than after true-negative findings at screening. Conclusion In beneficiaries of U.S. Medicare, use of screening mammography was associated with higher likelihood of adherence to other preventive guidelines, without a negative association between false-positive results and cervical cancer screening. © RSNA, 2018 Online supplemental material is available for this article.

Detection of lymph node metastases with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in oesophageal cancer: a feasibility study

PubMed Central

van der Jagt, E.J.; van Westreenen, H.L.; van Dullemen, H.M.; Kappert, P.; Groen, H.; Sietsma, J.; Oudkerk, M.; Plukker, J.Th.M.; van Dam, G.M.

2009-01-01

Abstract Aim: In this feasibility study we investigated whether magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) can be used to identify regional and distant lymph nodes, including mediastinal and celiac lymph node metastases in patients with oesophageal cancer. Patients and methods: Ten patients with a potentially curative resectable cancer of the oesophagus were eligible for this study. All patients included in the study had positive lymph nodes on conventional staging (including endoscopic ultrasound, computed tomography and fluorodeoxyglucose-positron emission tomography). Nine patients underwent MRI + USPIO before surgery. Results were restricted to those patients who had both MRI + USPIO and histological examination. Results were compared with conventional staging and histopathologic findings. Results: One patient was excluded due to expired study time. Five out of 9 patients underwent an exploration; in 1 patient prior to surgery MRI + USPIO diagnosed liver metastases and in 3 patients an oesophageal resection was performed. USPIO uptake in mediastinal lymph nodes was seen in 6 out of 9 patients; in 3 patients non-malignant nodes were not visible. In total, 9 lymph node stations (of 6 patients) were separately analysed; 7 lymph node stations were assessed as positive (N1) on MRI+USPIO compared with 9 by conventional staging. According to histology findings, there was one false-positive and one false-negative result in MRI + USPIO. Also, conventional staging modalities had one false-positive and one false-negative result. MRI + USPIO had surplus value in one patient. Not all lymph node stations could be compared due to unforeseen explorations. No adverse effects occurred after USPIO infusion. Conclusion: MRI+USPIO identified the majority of mediastinal and celiac (suspect) lymph nodes in 9 patients with oesophageal cancer. MRI+USPIO could have an additional value in loco-regional staging; however, more supplementary research is needed. PMID:19414293

Sensitive and selective culture medium for detection of environmental Clostridium difficile isolates without requirement for anaerobic culture conditions.

PubMed

Cadnum, Jennifer L; Hurless, Kelly N; Deshpande, Abhishek; Nerandzic, Michelle M; Kundrapu, Sirisha; Donskey, Curtis J

2014-09-01

Effective and easy-to-use methods for detecting Clostridium difficile spore contamination would be useful for identifying environmental reservoirs and monitoring the effectiveness of room disinfection. Culture-based detection methods are sensitive for detecting C. difficile, but their utility is limited due to the requirement of anaerobic culture conditions and microbiological expertise. We developed a low-cost selective broth medium containing thioglycolic acid and l-cystine, termed C. difficile brucella broth with thioglycolic acid and l-cystine (CDBB-TC), for the detection of C. difficile from environmental specimens under aerobic culture conditions. The sensitivity and specificity of CDBB-TC (under aerobic culture conditions) were compared to those of CDBB (under anaerobic culture conditions) for the recovery of C. difficile from swabs collected from hospital room surfaces. CDBB-TC was significantly more sensitive than CDBB for recovering environmental C. difficile (36/41 [88%] versus 21/41 [51%], respectively; P = 0.006). C. difficile latex agglutination, an enzyme immunoassay for toxins A and B or glutamate dehydrogenase, and a PCR for toxin B genes were all effective as confirmatory tests. For 477 total environmental cultures, the specificity of CDBB-TC versus that of CDBB based upon false-positive yellow-color development of the medium without recovery of C. difficile was 100% (0 false-positive results) versus 96% (18 false-positive results), respectively. False-positive cultures for CDBB were attributable to the growth of anaerobic non-C. difficile organisms that did not grow in CDBB-TC. Our results suggest that CDBB-TC provides a sensitive and selective medium for the recovery of C. difficile organisms from environmental samples, without the need for anaerobic culture conditions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Multi-scale textural feature extraction and particle swarm optimization based model selection for false positive reduction in mammography.

PubMed

Zyout, Imad; Czajkowska, Joanna; Grzegorzek, Marcin

2015-12-01

The high number of false positives and the resulting number of avoidable breast biopsies are the major problems faced by current mammography Computer Aided Detection (CAD) systems. False positive reduction is not only a requirement for mass but also for calcification CAD systems which are currently deployed for clinical use. This paper tackles two problems related to reducing the number of false positives in the detection of all lesions and masses, respectively. Firstly, textural patterns of breast tissue have been analyzed using several multi-scale textural descriptors based on wavelet and gray level co-occurrence matrix. The second problem addressed in this paper is the parameter selection and performance optimization. For this, we adopt a model selection procedure based on Particle Swarm Optimization (PSO) for selecting the most discriminative textural features and for strengthening the generalization capacity of the supervised learning stage based on a Support Vector Machine (SVM) classifier. For evaluating the proposed methods, two sets of suspicious mammogram regions have been used. The first one, obtained from Digital Database for Screening Mammography (DDSM), contains 1494 regions (1000 normal and 494 abnormal samples). The second set of suspicious regions was obtained from database of Mammographic Image Analysis Society (mini-MIAS) and contains 315 (207 normal and 108 abnormal) samples. Results from both datasets demonstrate the efficiency of using PSO based model selection for optimizing both classifier hyper-parameters and parameters, respectively. Furthermore, the obtained results indicate the promising performance of the proposed textural features and more specifically, those based on co-occurrence matrix of wavelet image representation technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

One or two serological assay testing strategy for diagnosis of HBV and HCV infection? The use of predictive modelling.

PubMed

Parry, John V; Easterbrook, Philippa; Sands, Anita R

2017-11-01

Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing. Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the two assays. Modeling demonstrated that applying a single assay (HBsAg or anti-HCV), even with high specificity (99%), may result in considerable numbers of false positive diagnoses and low positive predictive values (PPV), particularly in lower prevalence settings. Even at very low prevalences shifting to a two-assay testing strategy would result in a PPV approaching 1.0. When test sensitivity is high (>99%) false negative reactions are rare at all but the highest prevalences; but a two-test strategy might yield more false negative diagnoses. The order in which the tests are used has no impact on the overall accuracy of a two-assay strategy though it may impact the total number of tests needed to complete the diagnostic strategy, incurring added cost and complexity. HBsAg assays may have a low sensitivity (<90%), and result in large numbers of false negative diagnoses, particularly in high prevalence settings, which would be exacerbated in the two-assay testing strategy. In contrast, most anti-HCV assays have high sensitivity and lead to fewer false negative results, both in the one-assay and two-assay testing strategies. At prevalences ≤2% the number of tests needed using a second assay was nearly always small, at <300 per 10,000 individuals tested, making sustainability of a second assay uncertain in such a setting. A key public health objective of an effective testing strategy is to identify all individuals who would benefit from treatment. Therefore, a strategy that prioritizes a high NPV (minimal false negatives) may be acceptable even if the PPV is suboptimal (some false positives) as the implementation of such a public health programme must also take account of other factors such as costs, feasibility, impact on testing uptake and linkage to care, and consequences of a false-positive test. This rationale informed the development of the WHO Viral Hepatitis Testing Guidelines, with a conditional recommendation for a one-assay serological testing strategy in most testing settings and populations (≥0.4% prevalence in population tested). A one-test strategy results in few failures to diagnose infection and, although it is associated under most assumptions with a sub-optimal PPV, benefits include greater simplicity, easier implementation, lower costs and better feasibility, uptake and linkage to care. Furthermore, prior to antiviral therapy all those diagnosed either HBsAg or anti-HCV positive will require confirmation of viræmia, preventing unnecessary treatment of those who may be false positive on serology. For HBsAg, in low-prevalence settings (≤0.4%), a second recommendation was made to consider a two-assay testing strategy, using a confirmatory neutralization step or a second different HBsAg assay.

The Effect of Reactive atypia/Inflammation on the Laser-Induced Fluorescence Diagnosis of Non-dysplastic Barrett’s Esophagus

PubMed Central

Panjehpour, Masoud; Overholt, Bergein F.; Vo-Dinh, Tuan; Coppola, Domenico

2012-01-01

Background and Objectives Differential Normalized Fluorescence (DNF) technique has been used to distinguish high-grade dysplasia from non-dysplastic Barrett’s esophagus. This technology may assist gastroenterologists in targeting biopsies, reducing the number of biopsies using the standard protocol. In the presence of reactive atypia/inflammation, it becomes difficult for the pathologist to differentiate non-dysplastic Barrett’s esophagus from Barrett’s esophagus with low grade dysplasia. Before DNF technique may be used to guide target biopsies, it is critical to know whether reactive atypia/inflammation in non-dysplastic Barrett’s may result in false positives. This study was conducted to determine whether DNF technique is adversely affected by the presence of reactive atypia/inflammation in non-dysplastic Barrett’s esophagus resulting in false positives. Study Design/Materials and Methods 410-nm laser light was used to induce autofluorescence of Barrett's mucosa in 49 patients. The clinical study included 37 males and 12 females. This was a blinded retrospective data analysis study. A total of 303 spectra were collected and matched to non-dysplastic Barrett’s biopsy results. 175 spectra were collected from areas with a pathology of non-dysplastic Barrett’s esophagus with reactive atypia/inflammation. 128 spectra were collected from areas with non-dysplastic Barrett’s esophagus without reactive changes/ inflammation. The spectra were analyzed using the DNF Index at 480 nm and classified as positive or negative using the threshold of −0.75 × 10−03 . Results Using DNF technique, 92.6% of non-dysplastic samples with reactive atypia/inflammation were classified correctly (162/175). 92.2 % of non-dysplastic samples without reactive atypia/inflammation were classified correctly (118/128). Comparing the ratios of false positives among the two sample groups, there was not a statistically significant difference between the two groups. Conclusion Using Differential Normalized Fluorescence technique for classification of non-dysplastic Barrett’s mucosa doesn’t result in false positive readings due to reactive atypia/inflammation. Target biopsies guided by DNF technique may drastically reduce the number of pinch biopsies using the standard biopsy protocol. PMID:22535652

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

Effect of postmortem sampling technique on the clinical significance of autopsy blood cultures.

PubMed

Hove, M; Pencil, S D

1998-02-01

Our objective was to investigate the value of postmortem autopsy blood cultures performed with an iodine-subclavian technique relative to the classical method of atrial heat searing and antemortem blood cultures. The study consisted of a prospective autopsy series with each case serving as its own control relative to subsequent testing, and a retrospective survey of patients coming to autopsy who had both autopsy blood cultures and premortem blood cultures. A busy academic autopsy service (600 cases per year) at University of Texas Medical Branch Hospitals, Galveston, Texas, served as the setting for this work. The incidence of non-clinically relevant (false-positive) culture results were compared using different methods for collecting blood samples in a prospective series of 38 adult autopsy specimens. One hundred eleven adult autopsy specimens in which both postmortem and antemortem blood cultures were obtained were studied retrospectively. For both studies, positive culture results were scored as either clinically relevant or false positives based on analysis of the autopsy findings and the clinical summary. The rate of false-positive culture results obtained by an iodine-subclavian technique from blood drawn soon after death were statistically significantly lower (13%) than using the classical method of obtaining blood through the atrium after heat searing at the time of the autopsy (34%) in the same set of autopsy subjects. When autopsy results were compared with subjects' antemortem blood culture results, there was no significant difference in the rate of non-clinically relevant culture results in a paired retrospective series of antemortem blood cultures and postmortem blood cultures using the iodine-subclavian postmortem method (11.7% v 13.5%). The results indicate that autopsy blood cultures obtained using the iodine-subclavian technique have reliability equivalent to that of antemortem blood cultures.

Serologic screening for Trypanosoma cruzi among blood donors in central Brazil.

PubMed

de Andrade, A L; Martelli, C M; Luquetti, A O; de Oliveira, O S; Almeida e Silva, S; Zicker, F

1992-01-01

The study reported here compares results obtained by blood banks screening sera for chagasic (Trypanosoma cruzi) infection with results obtained by the Chagas' Disease Reference Laboratory of the Federal University of Goiás in Goiânia, Brazil. It also evaluates results obtained using the ELISA technique to screen the study sera. The survey used data from six of eight blood banks serving the city of Goiânia, an urban region of Central Brazil where Chagas' disease is highly endemic. The survey population consisted of 1,513 voluntary first-time blood donors whose donations occurred between October 1988 and April 1989. This group included 50% of all the first-time blood donors in that period. The six participating blood banks, which accounted for about 90% of all blood donations in Goiânia during the study period, routinely used indirect hemagglutination (IHA) and complement fixation (CF) tests to screen sera for antibodies to T. cruzi. Comparison of the results provided by the blood banks with the reference laboratory's results indicated a relative sensitivity of 77%, which ranged from 50% to 100% depending on the blood bank studied. The comparison, which found 12 false negative results, indicated that transfusions of infected blood might have occurred despite the serologic screening performed by the blood banks. Relative to the standard of positivity established for the study, the enzyme-linked immunosorbent assay (ELISA) technique was found to have a sensitivity of 96.3%. Considering as positive only those sera yielding positive IHA and indirect immunofluorescence (IIF) test results, the ELISA technique yielded 2 false negative and 41 false positive responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Do mammographic technologists affect radiologists’ diagnostic mammography interpretative performance?

PubMed Central

Henderson, Louise M.; Benefield, Thad; Bowling, J. Michael; Durham, Danielle; Marsh, Mary W.; Schroeder, Bruce F.; Yankaskas, Bonnie C.

2015-01-01

Objective The purpose of this study was to determine whether the technologist has an effect on the radiologists’ interpretative performance of diagnostic mammography. Materials and Methods Using data from a community based mammography registry from 1994 to 2009, we identified 162,755 diagnostic mammograms interpreted by 286 radiologists and performed by 303 mammographic technologists. We calculated sensitivity, false positive rate, and positive predictive value of biopsy (PPV2) for examinations performed (images taken) by each mammographic technologist, separately for film and digital modalities. We assessed the variability of these performance measures among mammographic technologists, using mixed effects logistic regression and taking into account the clustering of examinations within women, radiologists, and radiology practice. Results Among the 291 technologists performing film examinations, mean sensitivity of the examinations they performed was 83.0% (95% Confidence Interval (CI)=80.8–85.2%), mean false positive rate was 8.5 per 1000 examinations (95%CI: 8.0–9.0%), and mean PPV2 was 27.1% (95%CI: 24.8–29.4). For the 45 technologists performing digital examinations, mean sensitivity of the examinations they performed was 79.6% (95%CI: 73.1–86.2%), mean false positive rate was 8.8 (95%CI: 7.5–10.0%), and mean PPV2 was 23.6% (95%CI: 18.8–28.4%). We found significant variation by technologist in the sensitivity, false positive rate, and PPV2 for film but not digital mammography (p<0.0001 for all 3 film performance measures). Conclusions Our results suggest that the technologist has an influence on radiologists’ performance of diagnostic film mammography but not digital. Future work should examine why this difference by modality exists and determine if similar patterns are observed for screening mammography. PMID:25794085

Laxative-free CT colonography

PubMed Central

Slater, A; Betts, M; D'Costa, H

2012-01-01

Objectives The aim of this study was to determine if the introduction of faecal tagging to CT colonography (CTC) made the examination easier to tolerate or reduced the number of false-positives. Methods Our department changed bowel preparation for CT colonography from Picolax (Ferring Pharmaceuticals Ltd, London, UK) to Gastrografin® (Bracco Diagnostics Inc, Princeton, NJ) only with a modified diet. Questionnaires were given to a subgroup of patients within these cohorts. The numbers of false-positives were compared between two cohorts before and after this change. false-positives were defined as lesions reported on CT that were not confirmed by subsequent endoscopic examination. Polyps were matched if they were in the same or adjacent segments, and were within 5 mm of the reported size. Results 412 patients were identified from the Picolax cohort, and 116 from the Gastrografin cohort. 62 patients in each group completed questionnaires. Gastrografin produced less diarrhoea; 34% had five or more bowel motions in the previous day and night, compared with 77% for Picolax (p<0.001), although more patients found drinking it unpleasant compared with Picolax (85% reported drinking Picolax as “easy” vs 61% for Gastrografin; p=0.002). Picolax produced more non-diagnostic examinations, although this difference was not statistically significant. There was not a significant reduction in the numbers of false-positives (2 out of 112 for Gastrografin group, 14 out of 389 for the Picolax group; p=0.54). Conclusion Switching from Picolax to Gastrografin as a CTC preparation technique produced less diarrhoea, but did not reduce the number of false-positives. PMID:22167512

False-positive ethyl glucuronide immunoassay screening caused by a propyl alcohol-based hand sanitizer.

PubMed

Arndt, Torsten; Grüner, Joachim; Schröfel, Stefanie; Stemmerich, Karsten

2012-11-30

Urine ethyl glucuronide (EtG) is considered as a specific marker of recent ethanol consumption. We describe false-positive DRI(®) EIA EtG enzyme immunoassay results caused by propyl glucuronides in urine after using a propanol-based hand sanitizer. EtG screening was done with the DRI(®) EIA EtG assay (Microgenics), using a cut-off of 0.5 mg/L as recommended by the manufacturer and of 0.1 mg/L as demanded by the German Regulations for Reissuing Drivers Licenses. Confirmatory EtG analysis was done with the ClinMass(®) EtG LC-MS/MS testkit (Recipe), extended by the mass transitions 235.1→75.1, 235.1→85.1, and 235.1→113.1 for the detection of the 1- and 2-propyl glucuronides. Self-experiments were done by staff members of our lab (n=7), using 3 mL Sterillium(®) Classic Pure (30 g/100 g 1-propanol and 45 g/100 g 2-propanol) for hand sanitation every quarter of an hour for 8 h according to DIN EN 1500:2011-05 with and without an exhauster and by passive inhalation of the sanitizer vapor. Spot urine samples were taken immediately before and up to 24 h after the first sanitizer use. False-positive immunoassay results of up to 4 mg/L or 2.3 mg/g creatinine were obtained after normal use of the sanitizer and also after passive inhalation of the sanitizer vapor (up to 0.89 mg/L or 0.61 mg/g). Immunoassay results were positive even after 4-fold use of the sanitizer (up to 0.14 mg/L or 0.38 mg/g) and up to 6 h after the last sanitizer contact (maximum 0.63 mg/L and 0.33 mg/g for sanitizer users and 0.25 mg/g after passive inhalation). Spiking of EtG-free urine with 1-propyl glucuronide (Athena Environmental Sciences) between 0.05 and 10 mg/L clearly demonstrated a cross reaction of the immunoassay of approx. 10% as compared to EtG. LC-MS/MS of urines with a positive immunoassay EtG result did not show EtG signals, but distinct signals of 1-propyl glucuronide (n-propyl glucuronide) and 2-propyl glucuronide (iso-propyl glucuronide). An exhauster effectively prevented the inhalation of the sanitizer vapor, the formation of propyl glucuronides and thus false-positive DRI(®) EIA EtG screening results, proving that propyl alcohols are almost exclusively taken up by respiration. The widespread use of propanol-containing products such as hand sanitizers may lead to sufficient uptake of propyl alcohols and excretion of significant amounts of propyl glucuronides to yield false-positive DRI(®) EIA EtG screening results. Thus, positive EtG immunoassay results have to be controlled by mass-spectrometry, in clinical cases at least if ethanol intake is denied by the patient. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Evaluation of an enzyme immunoassay system for measuring herpes simplex virus (HSV) type 1-specific and HSV type 2-specific IgG antibodies.

PubMed

Prince, H E; Ernst, C E; Hogrefe, W R

2000-01-01

MRL Diagnostics has developed a dual enzyme immunoassay (EIA) system that employs the recombinant Herpes Simplex Virus (HSV) type-specific glycoproteins G1 (HSV1) and G2 (HSV2) to detect HSV type-specific IgG antibodies. This system was evaluated using 155 consecutive sera previously tested in a conventional dual EIA system (Zeus) that employs multiple HSV1 and HSV2 proteins to detect type-common as well as type-specific antibodies. Sera were also analyzed by Western blot to determine the true HSV type-specific IgG reactivity pattern. Of 110 sera giving concordant reactivity patterns in the MRL and Zeus EIA systems, 108 (98%) also displayed concordant Western blot patterns; two sera gave false positive HSV2 reactivity in both EIA systems. Of 45 sera giving discordant MRL and Zeus EIA reactivity patterns, 41 (91%) displayed a Western blot reactivity pattern that matched the MRL reactivity pattern. Both the HSV1 IgG component and the HSV2 IgG component of the MRL EIA system were 100% sensitive and > 95% specific. In contrast, the Zeus HSV1 IgG EIA was 98% sensitive and 79% specific, and the Zeus HSV2 IgG EIA was 85% sensitive and 79% specific. An analysis of the distribution of index values in the MRL EIA system showed that low-positive values (1.0-3.0) were rare, but, when detected, often represented false positive results; only 11 MRL low-positive results were observed, but all 6 MRL false positive results were found within this low-positive subgroup. These findings show that the MRL dual EIA system effectively detects HSV type-specific IgG antibodies. Copyright 2000 Wiley-Liss, Inc.

Intrathoracic stomach mimicking bone metastasis from thyroid cancer in whole-body iodine-131 scan diagnosed by SPECT/CT.

PubMed

García-Gómez, Francisco Javier; la Riva-Pérez, Pablo Antonio de; Calvo-Morón, Cinta; Buján-Lloret, Cristina; Cambil-Molina, Teresa; Castro-Montaño, Juan

2017-01-01

The whole-body iodine-131 scintigraphy is an imaging technique in monitoring patients with a history of thyroid cancer. Although the rate of false positives is negligible, it is not nonexistent. We report the case of an intervened and treated patient for thyroid cancer with good clinical and biochemical response. Scintigraphic findings were consistent with unsuspected bone metastasis. Fused SPECT/CT data allowed accurate diagnosis of giant diaphragmatic hernia associated with intrathoracic stomach, a very rare pathology that can lead to false positive results.

[Comparison between rapid detection method of enzyme substrate technique and multiple-tube fermentation technique in water coliform bacteria detection].

PubMed

Sun, Zong-ke; Wu, Rong; Ding, Pei; Xue, Jin-Rong

2006-07-01

To compare between rapid detection method of enzyme substrate technique and multiple-tube fermentation technique in water coliform bacteria detection. Using inoculated and real water samples to compare the equivalence and false positive rate between two methods. Results demonstrate that enzyme substrate technique shows equivalence with multiple-tube fermentation technique (P = 0.059), false positive rate between the two methods has no statistical difference. It is suggested that enzyme substrate technique can be used as a standard method for water microbiological safety evaluation.

Efficacy of a Deep Learning System for Detecting Glaucomatous Optic Neuropathy Based on Color Fundus Photographs.

PubMed

Li, Zhixi; He, Yifan; Keel, Stuart; Meng, Wei; Chang, Robert T; He, Mingguang

2018-03-02

To assess the performance of a deep learning algorithm for detecting referable glaucomatous optic neuropathy (GON) based on color fundus photographs. A deep learning system for the classification of GON was developed for automated classification of GON on color fundus photographs. We retrospectively included 48 116 fundus photographs for the development and validation of a deep learning algorithm. This study recruited 21 trained ophthalmologists to classify the photographs. Referable GON was defined as vertical cup-to-disc ratio of 0.7 or more and other typical changes of GON. The reference standard was made until 3 graders achieved agreement. A separate validation dataset of 8000 fully gradable fundus photographs was used to assess the performance of this algorithm. The area under receiver operator characteristic curve (AUC) with sensitivity and specificity was applied to evaluate the efficacy of the deep learning algorithm detecting referable GON. In the validation dataset, this deep learning system achieved an AUC of 0.986 with sensitivity of 95.6% and specificity of 92.0%. The most common reasons for false-negative grading (n = 87) were GON with coexisting eye conditions (n = 44 [50.6%]), including pathologic or high myopia (n = 37 [42.6%]), diabetic retinopathy (n = 4 [4.6%]), and age-related macular degeneration (n = 3 [3.4%]). The leading reason for false-positive results (n = 480) was having other eye conditions (n = 458 [95.4%]), mainly including physiologic cupping (n = 267 [55.6%]). Misclassification as false-positive results amidst a normal-appearing fundus occurred in only 22 eyes (4.6%). A deep learning system can detect referable GON with high sensitivity and specificity. Coexistence of high or pathologic myopia is the most common cause resulting in false-negative results. Physiologic cupping and pathologic myopia were the most common reasons for false-positive results. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Anti-Neospora caninum and anti-Sarcocystis spp. specific antibodies cross-react with Besnoitia besnoiti and influence the serological diagnosis of bovine besnoitiosis.

PubMed

García-Lunar, P; Moré, G; Campero, L; Ortega-Mora, L M; Álvarez-García, G

2015-11-30

Bovine besnoitiosis control remains a challenge because the disease continues to spread and control relies solely on accurate diagnosis coupled to management measures. However, recent studies have reported that routinely used ELISAs may raise a high number of false-positive results. Herein, cross-reactions between Besnoitia besnoiti antigens and anti-Neospora caninum and/or anti-Sarcocystis spp.-specific antibodies were studied in an in house ELISA since N. caninum and Sarcocystis spp. are closely related parasites, and both infections are highly prevalent in cattle worldwide. The serum panel was composed of the following categories: sera from B. besnoiti-seronegative (n=75) and -seropositive cattle (n=66), B. besnoiti-based-ELISA false-positive reactors (n=96) together with N. caninum (n=36) and Sarcocystis spp. (n=42) -seropositive reference cattle sera. B. besnoiti tachyzoite based western blot (WB) results classified animals as seropositive or seronegative. Sera were analyzed for the detection of anti-N. caninum by WB and ELISA and anti-Sarcocystis spp.-specific antibodies by WB and IFAT. Those samples recognizing a Sarcocystis spp. 18-20 kDa antigenic region and N. caninum 17-18 kDa immunodominant antigen were considered to be Sarcocystis spp. and N. caninum seropositive, respectively. The category of B. besnoiti based-ELISA false-positive reactors showed the highest number of sera with specific anti-Sarcocystis spp. and anti-N. caninum antibodies (74%; 71/96), followed by the N. caninum-seropositive cattle category (52.8%; 19/36). In contrast, few B. besnoiti-seronegative and -seropositive cattle showed antibodies against Sarcocystis spp. and N. caninum (10.7%; 8/75 and 1.5%; 1/66), respectively). This study revealed that B. besnoiti false-positive ELISA results were associated not only with the presence of anti-N. caninum and anti-Sarcocystis spp. antibodies (χ(2): 78.36; p<0.0001; OR: 34.6; CI: 14-88) but also with high antibody levels against them using ELISA and IFAT tests, respectively (p<0.05; t-test). These results may explain why only some animals seropositive to Sarcocystis spp. and/or N. caninum are Besnoitia false-positive reactors. Therefore, sera meeting these requirements should be included in future validations of serological tests for bovine besnoitiosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Pre-operative prediction of cervical nodal metastasis in papillary thyroid cancer by 99mTc-MIBI SPECT/CT; a pilot study.

PubMed

Tangjaturonrasme, Napadon; Vasavid, Pataramon; Sombuntham, Premsuda; Keelawat, Somboon

2013-06-01

Papillary thyroid cancer has a high prevalence of cervical nodal metastasis. There is no "gold standard" imaging for pre-operative diagnosis. The aim of the present study was to assess the accuracy of pre-operative 99mTc-MBI SPECT/CT in diagnosis of cervical nodal metastasis in patients with papillary thyroid cancer Fifteen patients were performed 99Tc-MlBI SPECT/CT pre-operatively. Either positive pathological report of neck dissection or positive post-treatment I-131 whole body scan with SPECT/CT of neck was concluded for definite neck metastasis. The PPV, NPV, and accuracy of 99mTc-MIBI SPECT/CT were analyzed. The PPV NPV and accuracy were 80%, 88.89%, and 85.71%, respectively. 99mTc-MIBI SPECT/CT could localize the abnormal lymph nodes groups correctly in most cases when compared with pathological results. However the authors found one false positive case with caseating granulomatous lymphadenitis and one false negative case with positive post-treatment 1-131 whole body scan with SPECT/CT of neck on cervical nodes zone II and IV CONCLUSION: 99mTc-MIBI SPECT/CTseem promising for pre-operative staging of cervical nodal involvement in patients with papillary thyroid cancer without the need of using iodinated contrast that may complicate subsequence 1-131 treatment. However, false positive result in granulomatous inflammatory nodes should be aware of especially in endemic areas. 99mTc-MIBI SPECT/CT scan shows a good result when compared with previous study of CT or MRI imaging. The comparative study between different imaging modality and the extension of neck dissection according to MIBI result seems interesting.

Establishing a sample-to cut-off ratio for lab-diagnosis of hepatitis C virus in Indian context.

PubMed

Tiwari, Aseem K; Pandey, Prashant K; Negi, Avinash; Bagga, Ruchika; Shanker, Ajay; Baveja, Usha; Vimarsh, Raina; Bhargava, Richa; Dara, Ravi C; Rawat, Ganesh

2015-01-01

Lab-diagnosis of hepatitis C virus (HCV) is based on detecting specific antibodies by enzyme immuno-assay (EIA) or chemiluminescence immuno-assay (CIA). Center for Disease Control reported that signal-to-cut-off (s/co) ratios in anti-HCV antibody tests like EIA/CIA can be used to predict the probable result of supplemental test; above a certain s/co value it is most likely to be true-HCV positive result and below that certain s/co it is most likely to be false-positive result. A prospective study was undertaken in patients in tertiary care setting for establishing this "certain" s/co value. The study was carried out in consecutive patients requiring HCV testing for screening/diagnosis and medical management. These samples were tested for anti-HCV on CIA (VITROS(®) Anti-HCV assay, Ortho-Clinical Diagnostics, New Jersey) for calculating s/co value. The supplemental nucleic acid test used was polymerase chain reaction (PCR) (Abbott). PCR test results were used to define true negatives, false negatives, true positives, and false positives. Performance of different putative s/co ratios versus PCR was measured using sensitivity, specificity, positive predictive value and negative predictive value and most appropriate s/co was considered on basis of highest specificity at sensitivity of at least 95%. An s/co ratio of ≥6 worked out to be over 95% sensitive and almost 92% specific in 438 consecutive patient samples tested. The s/co ratio of six can be used for lab-diagnosis of HCV infection; those with s/co higher than six can be diagnosed to have HCV infection without any need for supplemental assays.

Pre-Participation Musculoskeletal and Cardiac Screening of Male Athletes in the United Arab Emirates

PubMed Central

Alattar, A; Ghani, S; Mahdy, N; Hussain, H; Maffulli, N

2014-01-01

This study presents the results of pre-participation musculoskeletal and cardiac screening using the Lausanne recommendations, which include a personal and family history, physical examination and electrocardiography. Cross sectional study using the Lausanne screenings and the European Society of Cardiology (ESC) recommendations carried out at Al-Ahli club in Dubai, United Arab Emirates. 230 male athletes participating in organised sports were included. Exclusion criteria were those under 14 or over 35 years old, females and athletes with established cardiovascular disease. Primary outcome are the results of Lausanne screening with outline of the negative, positive and false positive results and number needed to screen. Secondary outcomes include the results of musculoskeletal and neurological screening. A total of 174 (76%) athletes had a negative screening result. Fifty-four athletes (23%) underwent additional testing. Forty-seven athletes (20.4%) had false positive screening results. Seven athletes (3%) had a positive screening result and four athletes (2%) were restricted from sport. The number of athletes needed to screen to detect one lethal cardiovascular condition was 33 athletes. The Lausanne recommendations are well suited for the United Arab Emirates. The number needed to screen to detect one athlete with serious cardiovascular disease is acceptable at 33. PMID:24809035

Disfluent presentations lead to the creation of more false memories.

PubMed

Sanchez, Christopher A; Naylor, Jamie S

2018-01-01

The creation of false memories within the Deese-Roediger-McDermott (DRM) paradigm has been shown to be sensitive to many factors such as task instructions, participant mood, or even presentation modality. However, do other simple perceptual differences also impact performance on the DRM and the creation of false memories? This study explores the potential impact of changes in perceptual disfluency on DRM performance. To test for a potential influence of disfluency on false memory creation, participants viewed lists under either perceptually disfluent conditions or not. Results indicated that disfluency did significantly impact performance in the DRM paradigm; more disfluent presentations significantly increased the recall and recognition of unpresented information, although they did not impact recall or recognition of presented information. Thus, although disfluency did impact performance, disfluency did not produce a positive benefit related to overall task performance. This finding instead suggests that more disfluent presentations can increase the likelihood that false memories are created, and provide little positive performance benefit.

Disfluent presentations lead to the creation of more false memories

PubMed Central

Naylor, Jamie S.

2018-01-01

The creation of false memories within the Deese-Roediger-McDermott (DRM) paradigm has been shown to be sensitive to many factors such as task instructions, participant mood, or even presentation modality. However, do other simple perceptual differences also impact performance on the DRM and the creation of false memories? This study explores the potential impact of changes in perceptual disfluency on DRM performance. To test for a potential influence of disfluency on false memory creation, participants viewed lists under either perceptually disfluent conditions or not. Results indicated that disfluency did significantly impact performance in the DRM paradigm; more disfluent presentations significantly increased the recall and recognition of unpresented information, although they did not impact recall or recognition of presented information. Thus, although disfluency did impact performance, disfluency did not produce a positive benefit related to overall task performance. This finding instead suggests that more disfluent presentations can increase the likelihood that false memories are created, and provide little positive performance benefit. PMID:29370255

Advance in diagnosis of female genital tract tumor with laser fluorescence

NASA Astrophysics Data System (ADS)

Ding, Ai-Hua; Tseng, Quen; Lian, Shao-Hui

1998-11-01

In order to improve the diagnostic accuracy of malignant tumors with laser fluorescence, in 1996, our group successfully created the computerized laser fluorescence spectrograph type II with more reliable images shown overshadowing the naked eye method before 74 cases of female genital tract diseases had been examined by the LFS II resulting in 10 positive cases which were also proven pathologically as malignant tumors, without nay false negative, 3 cases presented suspicious positive but all were proven pathologically as non-tumors lesions, the false positive rate was 4 percent. Our work showed that the method of LFS II can provide a more rapid and accurate diagnosis for the clinical malignant tumors.

When a Step Is Not a Step! Specificity Analysis of Five Physical Activity Monitors.

PubMed

O'Connell, Sandra; ÓLaighin, Gearóid; Quinlan, Leo R

2017-01-01

Physical activity is an essential aspect of a healthy lifestyle for both physical and mental health states. As step count is one of the most utilized measures for quantifying physical activity it is important that activity-monitoring devices be both sensitive and specific in recording actual steps taken and disregard non-stepping body movements. The objective of this study was to assess the specificity of five activity monitors during a variety of prescribed non-stepping activities. Participants wore five activity monitors simultaneously for a variety of prescribed activities including deskwork, taking an elevator, taking a bus journey, automobile driving, washing and drying dishes; functional reaching task; indoor cycling; outdoor cycling; and indoor rowing. Each task was carried out for either a specific duration of time or over a specific distance. Activity monitors tested were the ActivPAL micro™, NL-2000™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2)™, Fitbit One™ and Jawbone UP™. Participants were video-recorded while carrying out the prescribed activities and the false positive step count registered on each activity monitor was obtained and compared to the video. All activity monitors registered a significant number of false positive steps per minute during one or more of the prescribed activities. The Withings™ activity performed best, registering a significant number of false positive steps per minute during the outdoor cycling activity only (P = 0.025). The Jawbone™ registered a significant number of false positive steps during the functional reaching task and while washing and drying dishes, which involved arm and hand movement (P < 0.01 for both). The ActivPAL™ registered a significant number of false positive steps during the cycling exercises (P < 0.001 for both). As a number of false positive steps were registered on the activity monitors during the non-stepping activities, the authors conclude that non-stepping physical activities can result in the false detection of steps. This can negatively affect the quantification of physical activity with regard to step count as an output. The Withings™ activity monitor performed best with regard to specificity during the activities of daily living tested.

Diagnostic performance of influenza viruses and RSV rapid antigen detection tests in children in tertiary care.

PubMed

Moesker, F M; van Kampen, J J A; Aron, G; Schutten, M; van de Vijver, D A M C; Koopmans, M P G; Osterhaus, A D M E; Fraaij, P L A

2016-06-01

Rapid antigen detection tests (RADTs) are increasingly used to detect influenza viruses and respiratory syncytial virus (RSV). However, their sensitivity and specificity are a matter of debate, challenging their clinical usefulness. Comparing diagnostic performances of BinaxNow Influenza AB(®) (BNI) and BinaxNow RSV(®) (BNR), to those of real-time reverse transcriptase PCR (RT-PCR), virus isolation and direct immunofluorescence (D-IF) in paediatric patients. Between November 2005 and September 2013, 521 nasal washings from symptomatic children (age <5 years) attending our tertiary care centre were tested, with a combination of the respective assays using RT-PCR as gold standard. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BNI were 69% (confidence interval [CI] [51-83]), 96% [94-97], 55% [39-70] and 98% [96-99] respectively. Of eleven false-negative samples, RT-PCR Ct-values were higher than all RT-PCR positive test results (27 vs 22, p=0.012). Of twenty false-positive samples, none were culture positive and two tested positive in D-IF. Sensitivity, specificity, PPV and NPV for BNR were 79% [73-85], 98% [96-99], 97% [93-99] and 88% [84-91]. Of the 42 false-negative samples the median Ct-value was higher than that of all RT-PCR positive samples (31 vs 23, p<0.0001). Five false-positive samples were detected. Three of these tested positive for RSV in virus isolation and D-IF. RADTs have a high specificity with BNR being superior to BNI. However, their relative low sensitivity limits their usefulness for clinical decision making in a tertiary care paediatric hospital. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Performance of the Epstein-Barr Virus and Herpes Simplex Virus Immunoglobulin M Assays on the Liaison Platform with Sera from Patients Displaying Acute Parvovirus B19 Infection▿

PubMed Central

Costa, Elisa; Tormo, Nuria; Clari, María Ángeles; Bravo, Dayana; Muñoz-Cobo, Beatriz; Navarro, David

2009-01-01

Acute parvovirus B19 infection has been reported to cause false-positive results frequently in the Epstein-Barr (EBV) and herpes simplex virus (HSV) immunoglobulin M (IgM) assays from DiaSorin performed on the Liaison platform. We tested 65 sera from patients with a presumptive or conclusive diagnosis of acute parvovirus B19 infection in both assays and obtained no false-positive results in the EBV IgM test and 10.4% nonspecific reactivities in the HSV IgM assay. Our data support the specificity of both assays in this clinical setting. PMID:19571110

Serial testing for latent tuberculosis using QuantiFERON-TB Gold In-Tube: A Markov model

PubMed Central

Moses, Mark W.; Zwerling, Alice; Cattamanchi, Adithya; Denkinger, Claudia M.; Banaei, Niaz; Kik, Sandra V.; Metcalfe, John; Pai, Madhukar; Dowdy, David

2016-01-01

Healthcare workers (HCWs) in low-incidence settings are often serially tested for latent TB infection (LTBI) with the QuantiFERON-TB Gold In-Tube (QFT) assay, which exhibits frequent conversions and reversions. The clinical impact of such variability on serial testing remains unknown. We used a microsimulation Markov model that accounts for major sources of variability to project diagnostic outcomes in a simulated North American HCW cohort. Serial testing using a single QFT with the recommended conversion cutoff (IFN-g > 0.35 IU/mL) resulted in 24.6% (95% uncertainty range, UR: 23.8–25.5) of the entire population testing false-positive over ten years. Raising the cutoff to >1.0 IU/mL or confirming initial positive results with a (presumed independent) second test reduced this false-positive percentage to 2.3% (95%UR: 2.0–2.6%) or 4.1% (95%UR: 3.7–4.5%), but also reduced the proportion of true incident infections detected within the first year of infection from 76.5% (95%UR: 66.3–84.6%) to 54.8% (95%UR: 44.6–64.5%) or 61.5% (95%UR: 51.6–70.9%), respectively. Serial QFT testing of HCWs in North America may result in tremendous over-diagnosis and over-treatment of LTBI, with nearly thirty false-positives for every true infection diagnosed. Using higher cutoffs for conversion or confirmatory tests (for initial positives) can mitigate these effects, but will also diagnose fewer true infections. PMID:27469388

Ventilation/perfusion single-photon emission computed tomography: a service evaluation.

PubMed

Parekh, Amit; Graham, Richard; Redman, Stewart

2017-08-01

To identify the positive rate and negative predictive value (NPV) of our ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) service as respective markers of overcalling (false positives) and undercalling (false negatives). We also identified the indeterminate rate as an indicator of the technical quality of the scans and reporter confidence. V/Q SPECT studies carried out over 5 years were classified into positive, negative and indeterminate results. Patients who had died or had pulmonary emboli on imaging within 3 months of a negative V/Q SPECT were identified as false negatives, from which the NPV was calculated. The total number of positive and indeterminate studies as a proportion of all studies was calculated as the positive and indeterminate rates. The positive rate, NPV and indeterminate rates in nonpregnant patients were 24, 98.7-100 and 3.6%, respectively. The positive rate, NPV and indeterminate rates in pregnant patients were 6.8, 100 and 2.3%, respectively. The positive rate and NPV for nonpregnant patients were similar to the published literature. This suggests that we provide a safe service. The indeterminate rate was slightly higher than the stated guidelines. The study shows that the positive rate and NPV are achievable indicators of potential overcalling and undercalling in a V/Q SPECT service.This is also one of the first studies to report a positive rate in pregnant patients undergoing V/Q SPECT that other institutions can use as a standard when evaluating their services.

[CLINICAL UTILITY OF T-SPOT.TB ASSAY WITH T-Cell Xtend REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS IN THE FIELD TEST AT OUR HOSPITAL].

PubMed

Nemoto, Kenji; Oh-ishi, Shuji; Taguchi, Masato; Hyodo, Kentaro; Kanazawa, Jun; Miura, Yukiko; Takaku, Takio; Usui, Shingo; Hayashihara, Kenji; Saito, Takefumi

2016-04-01

T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.

Limited Agreement of Independent RNAi Screens for Virus-Required Host Genes Owes More to False-Negative than False-Positive Factors

PubMed Central

Wang, Zhishi; Craven, Mark; Newton, Michael A.; Ahlquist, Paul

2013-01-01

Systematic, genome-wide RNA interference (RNAi) analysis is a powerful approach to identify gene functions that support or modulate selected biological processes. An emerging challenge shared with some other genome-wide approaches is that independent RNAi studies often show limited agreement in their lists of implicated genes. To better understand this, we analyzed four genome-wide RNAi studies that identified host genes involved in influenza virus replication. These studies collectively identified and validated the roles of 614 cell genes, but pair-wise overlap among the four gene lists was only 3% to 15% (average 6.7%). However, a number of functional categories were overrepresented in multiple studies. The pair-wise overlap of these enriched-category lists was high, ∼19%, implying more agreement among studies than apparent at the gene level. Probing this further, we found that the gene lists implicated by independent studies were highly connected in interacting networks by independent functional measures such as protein-protein interactions, at rates significantly higher than predicted by chance. We also developed a general, model-based approach to gauge the effects of false-positive and false-negative factors and to estimate, from a limited number of studies, the total number of genes involved in a process. For influenza virus replication, this novel statistical approach estimates the total number of cell genes involved to be ∼2,800. This and multiple other aspects of our experimental and computational results imply that, when following good quality control practices, the low overlap between studies is primarily due to false negatives rather than false-positive gene identifications. These results and methods have implications for and applications to multiple forms of genome-wide analysis. PMID:24068911

Masking as an effective quality control method for next-generation sequencing data analysis.

PubMed

Yun, Sajung; Yun, Sijung

2014-12-13

Next generation sequencing produces base calls with low quality scores that can affect the accuracy of identifying simple nucleotide variation calls, including single nucleotide polymorphisms and small insertions and deletions. Here we compare the effectiveness of two data preprocessing methods, masking and trimming, and the accuracy of simple nucleotide variation calls on whole-genome sequence data from Caenorhabditis elegans. Masking substitutes low quality base calls with 'N's (undetermined bases), whereas trimming removes low quality bases that results in a shorter read lengths. We demonstrate that masking is more effective than trimming in reducing the false-positive rate in single nucleotide polymorphism (SNP) calling. However, both of the preprocessing methods did not affect the false-negative rate in SNP calling with statistical significance compared to the data analysis without preprocessing. False-positive rate and false-negative rate for small insertions and deletions did not show differences between masking and trimming. We recommend masking over trimming as a more effective preprocessing method for next generation sequencing data analysis since masking reduces the false-positive rate in SNP calling without sacrificing the false-negative rate although trimming is more commonly used currently in the field. The perl script for masking is available at http://code.google.com/p/subn/. The sequencing data used in the study were deposited in the Sequence Read Archive (SRX450968 and SRX451773).

Computerized scheme for vertebra detection in CT scout image

NASA Astrophysics Data System (ADS)

Guo, Wei; Chen, Qiang; Zhou, Hanxun; Zhang, Guodong; Cong, Lin; Li, Qiang

2016-03-01

Our purposes are to develop a vertebra detection scheme for automated scan planning, which would assist radiological technologists in their routine work for the imaging of vertebrae. Because the orientations of vertebrae were various, and the Haar-like features were only employed to represent the subject on the vertical, horizontal, or diagonal directions, we rotated the CT scout image seven times to make the vertebrae roughly horizontal in least one of the rotated images. Then, we employed Adaboost learning algorithm to construct a strong classifier for the vertebra detection by use of Haar-like features, and combined the detection results with the overlapping region according to the number of times they were detected. Finally, most of the false positives were removed by use of the contextual relationship between them. The detection scheme was evaluated on a database with 76 CT scout image. Our detection scheme reported 1.65 false positives per image at a sensitivity of 94.3% for initial detection of vertebral candidates, and then the performance of detection was improved to 0.95 false positives per image at a sensitivity of 98.6% for the further steps of false positive reduction. The proposed scheme achieved a high performance for the detection of vertebrae with different orientations.

Chemical applicability domain of the Local Lymph Node Assay (LLNA) for skin sensitisation potency. Part 3. Apparent discrepancies between LLNA and GPMT sensitisation potential: False positives or differences in sensitivity?

PubMed

Roberts, David W; Schultz, Terry W; Api, Anne Marie

2016-10-01

The Local Lymph Node Assay (LLNA) is the gold standard regulatory toxicology test for skin sensitisation along with the guinea pig maximisation test (GPMT). Compared with the GPMT, LLNA uses fewer animals, it is quantitative, and it gives a numerical prediction of potency. However several concerns have been raised with this assay, mainly related to false positives and false negatives. Over the years, many authors, including the developers of the assay, have presented cases where there have been discrepancies between the GMPT and LLNA results. Several theories have been put forward for these discrepancies, the main one being the "over-sensitivity" of the GPMT. This paper analyses the data from a systematic study, published in three papers from 2008 to 2011, covering several classes of chemicals, in particular unsaturated fatty acids, sugar surfactants and ethoxylated alcohols, with many cases of chemicals testing positive in the LLNA being negative in the GPMT. Based on consideration of reaction chemistry and structural alerts, it is concluded that these discrepancies are not LLNA false positives, but can be rationalised in terms of the different protocols of the assays. Copyright © 2016 Elsevier Inc. All rights reserved.

To Control False Positives in Gene-Gene Interaction Analysis: Two Novel Conditional Entropy-Based Approaches

PubMed Central

Lin, Meihua; Li, Haoli; Zhao, Xiaolei; Qin, Jiheng

2013-01-01

Genome-wide analysis of gene-gene interactions has been recognized as a powerful avenue to identify the missing genetic components that can not be detected by using current single-point association analysis. Recently, several model-free methods (e.g. the commonly used information based metrics and several logistic regression-based metrics) were developed for detecting non-linear dependence between genetic loci, but they are potentially at the risk of inflated false positive error, in particular when the main effects at one or both loci are salient. In this study, we proposed two conditional entropy-based metrics to challenge this limitation. Extensive simulations demonstrated that the two proposed metrics, provided the disease is rare, could maintain consistently correct false positive rate. In the scenarios for a common disease, our proposed metrics achieved better or comparable control of false positive error, compared to four previously proposed model-free metrics. In terms of power, our methods outperformed several competing metrics in a range of common disease models. Furthermore, in real data analyses, both metrics succeeded in detecting interactions and were competitive with the originally reported results or the logistic regression approaches. In conclusion, the proposed conditional entropy-based metrics are promising as alternatives to current model-based approaches for detecting genuine epistatic effects. PMID:24339984

Occupational exposure assessment of magnetic fields generated by induction heating equipment-the role of spatial averaging.

PubMed

Kos, Bor; Valič, Blaž; Kotnik, Tadej; Gajšek, Peter

2012-10-07

Induction heating equipment is a source of strong and nonhomogeneous magnetic fields, which can exceed occupational reference levels. We investigated a case of an induction tempering tunnel furnace. Measurements of the emitted magnetic flux density (B) were performed during its operation and used to validate a numerical model of the furnace. This model was used to compute the values of B and the induced in situ electric field (E) for 15 different body positions relative to the source. For each body position, the computed B values were used to determine their maximum and average values, using six spatial averaging schemes (9-285 averaging points) and two averaging algorithms (arithmetic mean and quadratic mean). Maximum and average B values were compared to the ICNIRP reference level, and E values to the ICNIRP basic restriction. Our results show that in nonhomogeneous fields, the maximum B is an overly conservative predictor of overexposure, as it yields many false positives. The average B yielded fewer false positives, but as the number of averaging points increased, false negatives emerged. The most reliable averaging schemes were obtained for averaging over the torso with quadratic averaging, with no false negatives even for the maximum number of averaging points investigated.

The Development of Theory of Mind and Positive and Negative Reciprocity in Preschool Children

PubMed Central

Schug, Joanna; Takagishi, Haruto; Benech, Catalina; Okada, Hiroyuki

2016-01-01

This study examined the relation between the acquisition of false-beliefs theory of mind (ToM) and reciprocity in preschoolers. Preschool-aged children completed a task assessing the understanding of false beliefs, and played an Ultimatum Game (UG) with another child in a face-to-face setting. Negative reciprocity was assessed by examining the rejection of unfair offers made by another child in the UG, while positive reciprocity was assessed by examining allocations made by participants in a Dictator Game (DG) following the UG. The results indicated that children who had passed a task assessing first-order false beliefs were more likely to make generous offers in a DG following a fair offer made by their partner in a proceeding UG, but that false beliefs ToM was unrelated to the rejection of unfair offers in the UG. PMID:27445881

The Development of Theory of Mind and Positive and Negative Reciprocity in Preschool Children.

PubMed

Schug, Joanna; Takagishi, Haruto; Benech, Catalina; Okada, Hiroyuki

2016-01-01

This study examined the relation between the acquisition of false-beliefs theory of mind (ToM) and reciprocity in preschoolers. Preschool-aged children completed a task assessing the understanding of false beliefs, and played an Ultimatum Game (UG) with another child in a face-to-face setting. Negative reciprocity was assessed by examining the rejection of unfair offers made by another child in the UG, while positive reciprocity was assessed by examining allocations made by participants in a Dictator Game (DG) following the UG. The results indicated that children who had passed a task assessing first-order false beliefs were more likely to make generous offers in a DG following a fair offer made by their partner in a proceeding UG, but that false beliefs ToM was unrelated to the rejection of unfair offers in the UG.

False alarms and incorrect rejections in an information security center: correlation with the frequency of incidents.

PubMed

Bruno, Thiers; Abrahão, Julia

2012-01-01

This study examines the actions taken by operators aimed at preventing and combating information security incidents at a banking organization. The work utilizes the theoretical framework of ergonomics and cognitive psychology. The method is workplace ergonomic analysis. Its focus is directed towards examining the cognitive dimension of the work environment with special attention to the occurrence of correlations between variability in incident frequency and the results of sign detection actions. It categorizes 45,142 operator decisions according to the theory of signal detection (Sternberg, 2000). It analyzes the correlation between incident proportions (indirectly associated with the cognitive efforts demanded from the operator) and operator decisions. The study demonstrated the existence of a positive correlation between incident proportions and false positive decisions (false alarms). However, this correlation could not be observed in relation to decisions of the false-negative type (incorrect rejection).

[Transthoracic needle-biopsy in coin-lesions of the lung-comparison of the results of different procedures (author's transl)].

PubMed

Dürschmied, H; Polak, J

1980-01-01

This report deals with the results and the complications of transthoracic needle-biopsy performed with different methods at two cooperating hospitals (Prague and Bad Berka). Each hospital investigated 200 persons. As for tumours thin-needle biopsy yielded more positive results for tumours also more false positive results. As for other localized lung diseases the biopsy by means of a Hauser-needle was more successful.

Clinical experience of laboratory follow-up with noninvasive prenatal testing using cell-free DNA and positive microdeletion results in 349 cases.

PubMed

Schwartz, S; Kohan, M; Pasion, R; Papenhausen, P R; Platt, L D

2018-02-01

Screening via noninvasive prenatal testing (NIPT) involving the analysis of cell-free DNA (cfDNA) from plasma has become readily available to screen for chromosomal and DNA aberrations through maternal blood. This report reviews a laboratory's experience with follow-up of positive NIPT screens for microdeletions. Patients that were screened positive by NIPT for a microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies by either chorionic villus sampling or amniocentesis were evaluated. The overall positive predictive value for 349 patients was 9.2%. When a microdeletion was confirmed, 39.3% of the cases had additional abnormal microarray findings. Unrelated abnormal microarray findings were detected in 11.8% of the patients in whom the screen positive microdeletion was not confirmed. Stretches of homozygosity in the microdeletion were frequently associated with a false positive cfDNA microdeletion result. Overall, this report reveals that while cfDNA analysis will screen for microdeletions, the positive predictive value is low; in our series it is 9.2%. Therefore, the patient should be counseled accordingly. Confirmatory diagnostic microarray studies are imperative because of the high percentage of false positives and the frequent additional abnormalities not delineated by cfDNA analysis. © 2018 John Wiley & Sons, Ltd.

Consensus-based identification of factors related to false-positives in ultrasound scanning of synovitis and tenosynovitis.

PubMed

Ikeda, Kei; Narita, Akihiro; Ogasawara, Michihiro; Ohno, Shigeru; Kawahito, Yutaka; Kawakami, Atsushi; Ito, Hiromu; Matsushita, Isao; Suzuki, Takeshi; Misaki, Kenta; Ogura, Takehisa; Kamishima, Tamotsu; Seto, Yohei; Nakahara, Ryuichi; Kaneko, Atsushi; Nakamura, Takayuki; Henmi, Mihoko; Fukae, Jun; Nishida, Keiichiro; Sumida, Takayuki; Koike, Takao

2016-01-01

We aimed to identify causes of false-positives in ultrasound scanning of synovial/tenosynovial/bursal inflammation and provide corresponding imaging examples. We first performed systematic literature review to identify previously reported causes of false-positives. We next determined causes of false-positives and corresponding example images for educational material through Delphi exercises and discussion by 15 experts who were an instructor and/or a lecturer in the 2013 advanced course for musculoskeletal ultrasound organized by Japan College of Rheumatology Committee for the Standardization of Musculoskeletal Ultrasonography. Systematic literature review identified 11 articles relevant to sonographic false-positives of synovial/tenosynovial inflammation. Based on these studies, 21 candidate causes of false-positives were identified in the consensus meeting. Of these items, 11 achieved a predefined consensus (≥ 80%) in Delphi exercise and were classified as follows: (I) Gray-scale assessment [(A) non-specific synovial findings and (B) normal anatomical structures which can mimic synovial lesions due to either their low echogenicity or anisotropy]; (II) Doppler assessment [(A) Intra-articular normal vessels and (B) reverberation)]. Twenty-four corresponding examples with 49 still and 23 video images also achieved consensus. Our study provides a set of representative images that can help sonographers to understand false-positives in ultrasound scanning of synovitis and tenosynovitis.

Automated Detection, Localization, and Classification of Traumatic Vertebral Body Fractures in the Thoracic and Lumbar Spine at CT

PubMed Central

Burns, Joseph E.; Yao, Jianhua; Muñoz, Hector

2016-01-01

Purpose To design and validate a fully automated computer system for the detection and anatomic localization of traumatic thoracic and lumbar vertebral body fractures at computed tomography (CT). Materials and Methods This retrospective study was HIPAA compliant. Institutional review board approval was obtained, and informed consent was waived. CT examinations in 104 patients (mean age, 34.4 years; range, 14–88 years; 32 women, 72 men), consisting of 94 examinations with positive findings for fractures (59 with vertebral body fractures) and 10 control examinations (without vertebral fractures), were performed. There were 141 thoracic and lumbar vertebral body fractures in the case set. The locations of fractures were marked and classified by a radiologist according to Denis column involvement. The CT data set was divided into training and testing subsets (37 and 67 subsets, respectively) for analysis by means of prototype software for fully automated spinal segmentation and fracture detection. Free-response receiver operating characteristic analysis was performed. Results Training set sensitivity for detection and localization of fractures within each vertebra was 0.82 (28 of 34 findings; 95% confidence interval [CI]: 0.68, 0.90), with a false-positive rate of 2.5 findings per patient. The sensitivity for fracture localization to the correct vertebra was 0.88 (23 of 26 findings; 95% CI: 0.72, 0.96), with a false-positive rate of 1.3. Testing set sensitivity for the detection and localization of fractures within each vertebra was 0.81 (87 of 107 findings; 95% CI: 0.75, 0.87), with a false-positive rate of 2.7. The sensitivity for fracture localization to the correct vertebra was 0.92 (55 of 60 findings; 95% CI: 0.79, 0.94), with a false-positive rate of 1.6. The most common cause of false-positive findings was nutrient foramina (106 of 272 findings [39%]). Conclusion The fully automated computer system detects and anatomically localizes vertebral body fractures in the thoracic and lumbar spine on CT images with a high sensitivity and a low false-positive rate. © RSNA, 2015 Online supplemental material is available for this article. PMID:26172532

Extraction of advanced geospatial intelligence (AGI) from commercial synthetic aperture radar imagery

NASA Astrophysics Data System (ADS)

Kanberoglu, Berkay; Frakes, David

2017-04-01

The extraction of objects from advanced geospatial intelligence (AGI) products based on synthetic aperture radar (SAR) imagery is complicated by a number of factors. For example, accurate detection of temporal changes represented in two-color multiview (2CMV) AGI products can be challenging because of speckle noise susceptibility and false positives that result from small orientation differences between objects imaged at different times. These cases of apparent motion can result in 2CMV detection, but they obviously differ greatly in terms of significance. In investigating the state-of-the-art in SAR image processing, we have found that differentiating between these two general cases is a problem that has not been well addressed. We propose a framework of methods to address these problems. For the detection of the temporal changes while reducing the number of false positives, we propose using adaptive object intensity and area thresholding in conjunction with relaxed brightness optical flow algorithms that track the motion of objects across time in small regions of interest. The proposed framework for distinguishing between actual motion and misregistration can lead to more accurate and meaningful change detection and improve object extraction from a SAR AGI product. Results demonstrate the ability of our techniques to reduce false positives up to 60%.

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

False Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease-Disinhibition or Amnesia?

PubMed

Flanagan, Emma C; Wong, Stephanie; Dutt, Aparna; Tu, Sicong; Bertoux, Maxime; Irish, Muireann; Piguet, Olivier; Rao, Sulakshana; Hodges, John R; Ghosh, Amitabha; Hornberger, Michael

2016-01-01

Episodic memory recall processes in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits-false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

[False positive results or what's the probability that a significant P-value indicates a true effect?

PubMed

Cucherat, Michel; Laporte, Silvy

2017-09-01

The use of statistical test is central in the clinical trial. At the statistical level, obtaining a P<0.05 allows to claim the effectiveness of the new studied treatment. However, given its underlying mathematical logic the concept of "P value" is often misinterpreted. It is often assimilated, mistakenly, to the likelihood that treatment is ineffective. Actually the "P value" gives an indirect information about the plausibility of the existence of treatment effect. With "P<0.05", the probability that the treatment is effective may vary depending on other statistical parameters which are the alpha level of risk, the power of the study and especially the a priori probability of the existence of treatment effect. A "P<0.05" does not always produce the same degree of certainty. Thus there exist situations where the risk of a result "P<0.05" is in reality a false positive is very high. This is the case if the power is low, if there is an inflation of the alpha risk or if the result is exploratory or chance discoveries. This possibility is important to take into consideration when interpreting the results of clinical trials in order to avoid pushing ahead significant results in appearance, but which are likely to be actually false positive results. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Discrepancy between culture and DNA probe analysis for the detection of periodontal bacteria.

PubMed

van Steenbergen, T J; Timmerman, M F; Mikx, F H; de Quincey, G; van der Weijden, G A; van der Velden, U; de Graaff, J

1996-10-01

The purpose of this study was to compare a commercially available DNA probe technique with conventional cultural techniques for the detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque samples. Samples from 20 patients with moderate to severe periodontitis were evaluated at baseline and during a 15 months period of periodontal treatment. Paperpoints from 4 periodontal pockets per patient were forwarded to Omnigene for DNA probe analysis, and simultaneously inserted paperpoints from the same pockets were analyzed by standard culture techniques. In addition, mixed bacterial samples were constructed harbouring known proportions of 25 strains of A. actinomycetemcomitans, P. gingivalis and P. intermedia each. A relatively low concordance was found between both methods. At baseline a higher detection frequency was found for A. actinomycetemcomitans and P. gingivalis for the DNA probe technique; for P. intermedia the detection frequency by culture was higher. For A. actinomycetemcomitans, 21% of the culture positive samples was positive with the DNA probe. Testing the constructed bacterial samples with the DNA probe method resulted in about 16% false positive results for the 3 species tested. Furthermore, 40% of P. gingivalis strains were not detected by the DNA probe. The present data suggest that at least part of the discrepancies found between the DNA probe technique used and cultural methods are caused by false positive and false negative DNA probe results. Therefore, the value of this DNA probe method for the detection of periodontal pathogens is questionable.

Accuracy of a Plasmodium falciparum specific histidine-rich protein 2 rapid diagnostic test in the context of the presence of non-malaria fevers, prior anti-malarial use and seasonal malaria transmission.

PubMed

Kiemde, Francois; Bonko, Massa Dit Achille; Tahita, Marc Christian; Lompo, Palpouguini; Rouamba, Toussaint; Tinto, Halidou; van Hensbroek, Michael Boele; Mens, Petra F; Schallig, Henk D F H

2017-07-20

It remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. This study was designed to determine the influence of other causes of fever, prior anti-malarial treatment, and a possible seasonality of the performance of a PfHRP2 RDT for the diagnosis of malaria in children under-5 years of age living in a malaria endemic area. A prospective etiology study was conducted in 2015 among febrile children under 5 years of age in Burkina Faso. In order to assess the influence of other febrile illnesses, prior treatment and seasonality on the performance of a PfHRP2 RDT in diagnosing malaria, the RDT results were compared with the gold standard (expert microscopic diagnosis of Plasmodium falciparum) and test results were analysed by assuming that prior anti-malarial use and bacterial/viral infection status would have been known prior to testing. To assess bacterial and viral infection status blood, urine and stool samples were analysed. In total 683 blood samples were analysed with microscopy and RDT-PfHRP2. Plasmodium falciparum malaria was diagnosed in 49.8% (340/683) by microscopy compared to 69.5% (475/683) by RDT-PfHRP2. The RDT-PfHRP2 reported 29.7% (141/475) false positive results and 1.8% (6/340) false negative cases. The RDT-PfHRP2 had a high sensitivity (98.2%) and negative predictive value (97.1%), but a low specificity (58.9%) and positive predictive value (70.3%). Almost 50% of the alternative cause of fever were diagnosed by laboratory testing in the RDT false positive malaria group. The use of a malaria RDT-PfHRP2 in a malaria endemic area may cause misdiagnosis of the actual cause of fever due to false positive test results. The development of a practical diagnostic tool to screen for other causes of fever in malaria endemic areas is required to save lives.

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

Biological false-positive venereal disease research laboratory test in cerebrospinal fluid in the diagnosis of neurosyphilis - a case-control study.

PubMed

Zheng, S; Lin, R J; Chan, Y H; Ngan, C C L

2018-03-01

There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) test from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis but is widely known to be insensitive. In this study, we compared the clinical and laboratory characteristics of true-positive VDRL-CSF cases with biological false-positive VDRL-CSF cases. We retrospectively identified cases of true and false-positive VDRL-CSF across a 3-year period received by the Immunology and Serology Laboratory, Singapore General Hospital. A biological false-positive VDRL-CSF is defined as a reactive VDRL-CSF with a non-reactive Treponema pallidum particle agglutination (TPPA)-CSF and/or negative Line Immuno Assay (LIA)-CSF IgG. A true-positive VDRL-CSF is a reactive VDRL-CSF with a concordant reactive TPPA-CSF and/or positive LIA-CSF IgG. During the study period, a total of 1254 specimens underwent VDRL-CSF examination. Amongst these, 60 specimens from 53 patients tested positive for VDRL-CSF. Of the 53 patients, 42 (79.2%) were true-positive cases and 11 (20.8%) were false-positive cases. In our setting, a positive non-treponemal serology has 97.6% sensitivity, 100% specificity, 100% positive predictive value and 91.7% negative predictive value for a true-positive VDRL-CSF based on our laboratory definition. HIV seropositivity was an independent predictor of a true-positive VDRL-CSF. Biological false-positive VDRL-CSF is common in a setting where patients are tested without first establishing a serological diagnosis of syphilis. Serological testing should be performed prior to CSF evaluation for neurosyphilis. © 2017 European Academy of Dermatology and Venereology.

Discordance between MTB/RIF and Real-Time Tuberculosis-Specific Polymerase Chain Reaction Assay in Bronchial Washing Specimen and Its Clinical Implications.

PubMed

Jo, Yong Suk; Park, Ju-Hee; Lee, Jung Kyu; Heo, Eun Young; Chung, Hee Soon; Kim, Deog Kyeom

2016-01-01

The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied. The clinical risk factors for discordance and false positivity of assays were also studied. Among 130 patients who were clinically diagnosed with PTB, 64 patients showed positive acid-fast bacilli culture results, 56 patients showed positive results in molecular methods and clinician diagnosed PTB without results of microbiology in 10 patients. The sensitivity, specificity, PPV, and NPV were 80.0%, 98.95%, 98.1%, and 87.9%, respectively, for Xpert MTB/RIF and 81.5%, 92.6%, 88.3%, and 88.0%, respectively, for TB/NTM PCR. The discordant proportion was 16.9% and was higher in culture-negative PTB compared to culture-confirmed PTB (24.3% vs. 9.4%, p = 0.024). However, there were no significant differences in the clinical characteristics, regardless of the discordance. The diagnostic yield increased with an additional assay (7.7% for Xpert MTB/RIF and 9.2% for TB/NTM PCR). False positivity was less common in patients tested with Xpert MTB/RIF (1.05% vs. 7.37%, p = 0.0035). No host-related risk factor for false positivity was identified. The Xpert MTB/RIF and TB/NTM PCR assay in bronchial washing specimens can improve the diagnostic yields for PTB, although there were considerable discordant results without any patient-related risk factors.

[Evaluation of mycobacterial microscopy and culture results of Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital: A 3-year analysis].

PubMed

Akduman Alaşehir, Elçin; Balıkçı, Ahmet; Partal, Mualla; Çatmabacak, Gülay; Yaman, Görkem

2016-09-01

Effective diagnosis of tuberculosis is of great importance for transmission control and treatment success. The purpose of this study is to evaluate microscopic examination results of Ehrlich-Ziehl Neelsen (EZN) and Auramine-Rhodamine staining methods and automated BACTEC MGIT 960™ system and Löwenstein-Jensen (L-J) culture results of various clinical samples in the light of recent data from the world and Turkey. Specimens that were sent from various clinics to Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital Microbiology Laboratory from January 2012 to December 2015 were evaluated retrospectively. From a total of 62456 samples; 60923 (97.5%) were pulmonary and 1533 (2.5%) were non-pulmonary samples, especially pleura. 2853 (4.6%) Acid-resistant bacilli (ARB) positivity was detected and mycobacterial culture positivity was in total 12.2%. 7076 (93%) and 535 (7%) mycobacteria other than tuberculosis (MOTT) strains were isolated. In 356 specimens the cultures were negative in despite the positive ARB results. Considering mycobacterial culture as the gold standard; the sensitivity, specificity, positive and negative predictive values of ARB microscopy were 32.8%, 99.4%, 87.5% and 91.4%, respectively. The contamination rates in total were within acceptable limits being 2.7% for L-J and 3.8% for MGIT. Analysis of our data indicated that the sensitivity of microscopy is low and it should be evaluated together with the mycobacterial culture to rule out tuberculosis infection. With the use of fluorescent staining and also L-J and MGIT broth together for routine culture since 2013; ARB false negativity rate was observed to fall to 51.7% from 74.1% compared to the years. The follow-up of data such as the sensitivity of microscopy, culture positivity, false-positivity and false-negativity rates and contamination values is of great importance in terms of assessing compliance with laboratory quality standards and contributing to the surveillance studies.

The Lifetime Economic Burden of Inaccurate HER2 Testing: Estimating the Costs of False-Positive and False-Negative HER2 Test Results in US Patients with Early-Stage Breast Cancer.

PubMed

Garrison, Louis P; Babigumira, Joseph B; Masaquel, Anthony; Wang, Bruce C M; Lalla, Deepa; Brammer, Melissa

2015-06-01

Patients with breast cancer whose tumors test positive for human epidermal growth factor receptor 2 (HER2) are treated with HER2-targeted therapies such as trastuzumab, but limitations with HER2 testing may lead to false-positive (FP) or false-negative (FN) results. To develop a US-level model to estimate the effect of tumor misclassification on health care costs and patient quality-adjusted life-years (QALYs). Decision analysis was used to estimate the number of patients with early-stage breast cancer (EBC) whose HER2 status was misclassified in 2012. FP results were assumed to generate unnecessary trastuzumab costs and unnecessary cases of trastuzumab-related cardiotoxicity. FN results were assumed to save money on trastuzumab, but with a loss of QALYs and greater risk of disease recurrence and its associated costs. QALYs were valued at $100,000 under a net monetary benefit approach. Among 226,870 women diagnosed with EBC in 2012, 3.12% (n = 7,070) and 2.18% (n = 4,955) were estimated to have had FP and FN test results, respectively. Approximately 8400 QALYs (discounted, lifetime) were lost among women not receiving trastuzumab because of FN results. The estimated incremental per-patient lifetime burden of FP or FN results was $58,900 and $116,000, respectively. The implied incremental losses to society were $417 million and $575 million, respectively. HER2 tests result in misclassification and nonoptimal treatment of approximately 12,025 US patients with EBC annually. The total economic societal loss of nearly $1 billion suggests that improvements in HER2 testing accuracy are needed and that further clinical and economic studies are warranted. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

77 FR 48045 - Supplemental Nutrition Assistance Program: Disqualified Recipient Reporting and Computer Matching...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

... false positive match rate of 10 percent. Making the match mandatory for the States who did not perform... number of prisoners from 1995 to 2013 and assumed a 10 percent false positive match rate. Finally, we... matches are false positives. We estimate that mandatory matches at certification will identify an...

Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

PubMed Central

Jadhav, Swati S; Lila, Anurag R; Kasaliwal, Rajeev; Khare, Shruti; Yerawar, Chaitanya G; Hira, Priya; Phadke, Uday; Shah, Hina; Lele, Vikram R; Malhotra, Gaurav; Bandgar, Tushar; Shah, Nalini S

2016-01-01

Background Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. Materials and methods Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared. Results Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). Conclusion CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID:27006371

Application of Template Matching for Improving Classification of Urban Railroad Point Clouds

PubMed Central

Arastounia, Mostafa; Oude Elberink, Sander

2016-01-01

This study develops an integrated data-driven and model-driven approach (template matching) that clusters the urban railroad point clouds into three classes of rail track, contact cable, and catenary cable. The employed dataset covers 630 m of the Dutch urban railroad corridors in which there are four rail tracks, two contact cables, and two catenary cables. The dataset includes only geometrical information (three dimensional (3D) coordinates of the points) with no intensity data and no RGB data. The obtained results indicate that all objects of interest are successfully classified at the object level with no false positives and no false negatives. The results also show that an average 97.3% precision and an average 97.7% accuracy at the point cloud level are achieved. The high precision and high accuracy of the rail track classification (both greater than 96%) at the point cloud level stems from the great impact of the employed template matching method on excluding the false positives. The cables also achieve quite high average precision (96.8%) and accuracy (98.4%) due to their high sampling and isolated position in the railroad corridor. PMID:27973452

The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis.

PubMed

Dunning, Lorna; Francke, Jordan A; Mallampati, Divya; MacLean, Rachel L; Penazzato, Martina; Hou, Taige; Myer, Landon; Abrams, Elaine J; Walensky, Rochelle P; Leroy, Valériane; Freedberg, Kenneth A; Ciaranello, Andrea

2017-11-01

The specificity of nucleic acid amplification tests (NAATs) used for early infant diagnosis (EID) of HIV infection is <100%, leading some HIV-uninfected infants to be incorrectly identified as HIV-infected. The World Health Organization recommends that infants undergo a second NAAT to confirm any positive test result, but implementation is limited. Our objective was to determine the impact and cost-effectiveness of confirmatory HIV testing for EID programmes in South Africa. Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model, we simulated EID testing at age 6 weeks for HIV-exposed infants without and with confirmatory testing. We assumed a NAAT cost of US$25, NAAT specificity of 99.6%, NAAT sensitivity of 100% for infants infected in pregnancy or at least 4 weeks prior to testing, and a mother-to-child transmission (MTCT) rate at 12 months of 4.9%; we simulated guideline-concordant rates of testing uptake, result return, and antiretroviral therapy (ART) initiation (100%). After diagnosis, infants were linked to and retained in care for 10 years (false-positive) or lifelong (true-positive). All parameters were varied widely in sensitivity analyses. Outcomes included number of infants with false-positive diagnoses linked to ART per 1,000 ART initiations, life expectancy (LE, in years) and per-person lifetime HIV-related healthcare costs. Both without and with confirmatory testing, LE was 26.2 years for HIV-infected infants and 61.4 years for all HIV-exposed infants; clinical outcomes for truly infected infants did not differ by strategy. Without confirmatory testing, 128/1,000 ART initiations were false-positive diagnoses; with confirmatory testing, 1/1,000 ART initiations were false-positive diagnoses. Because confirmatory testing averted costly HIV care and ART in truly HIV-uninfected infants, it was cost-saving: total cost US$1,790/infant tested, compared to US$1,830/infant tested without confirmatory testing. Confirmatory testing remained cost-saving unless NAAT cost exceeded US$400 or the HIV-uninfected status of infants incorrectly identified as infected was ascertained and ART stopped within 3 months of starting. Limitations include uncertainty in the data used in the model, which we examined with sensitivity and uncertainty analyses. We also excluded clinical harms to HIV-uninfected infants incorrectly treated with ART after false-positive diagnosis (e.g., medication toxicities); including these outcomes would further increase the value of confirmatory testing. Without confirmatory testing, in settings with MTCT rates similar to that of South Africa, more than 10% of infants who initiate ART may reflect false-positive diagnoses. Confirmatory testing prevents inappropriate HIV diagnosis, is cost-saving, and should be adopted in all EID programmes.

Mood-congruent true and false memory: effects of depression.

PubMed

Howe, Mark L; Malone, Catherine

2011-02-01

The Deese/Roediger-McDermott paradigm was used to investigate the effect of depression on true and false recognition. In this experiment true and false recognition was examined across positive, neutral, negative, and depression-relevant lists for individuals with and without a diagnosis of major depressive disorder. Results showed that participants with major depressive disorder falsely recognised significantly more depression-relevant words than non-depressed controls. These findings also parallel recent research using recall instead of recognition and show that there are clear mood congruence effects for depression on false memory performance. © 2011 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

[Analysis for Discordance of Positive and Negative Blood Typing by Gel Card].

PubMed

Li, Cui-Ying; Xu, Hong; Lei, Hui-Fen; Liu, Juan; Li, Xiao-Wei

2017-08-01

To explore the method of Gel card identifying ABO blood group, determine the inconsistent cause and the distribution of disease affecting factors, and put forward a method of its solutions. To collect 240 positive and negative typing-discordant blood speciments from patients examined by Gel card and send these speciments to blood type reference laboratory for examining with the classic tube method and serological test, such as salivary blood-group substance, in order to performe genotyping method when serologic test can not be determined. Among 240 positive and negative typing-discordant blood speciments from patients examined by Gel card, 107 blood speciments were positive and negative consistent examined by false agglutination test (44.58%), 133 blood specinents were discordent examined by false agglutination (55.42%), out of them, 35 cases (14.58%) with inconsistent cold agglutination test, 22 cases (9.17%) with weakened AB antigenicity, 16 cases (6.67%) with ABO subtyping, 12 cases (5.00%) with positive direct antiglobulin test, 11 cases (4.58%) with reduced or without antibodies, 11 cases (4.58%) with false aggregation caused by drugs or protein, 11 cases (4.58%) with salivary blood-type substances, 8 cases (3.33%) with non-ABO alloantibody, and 7 cases (2.92%) with allogeneic bone marrow transplantation. The distribution of disease were following: blood disease (16.83%), tumor (11.88%), and cardiopulmonary diseases (11.39%); chi-square test results indicated that the distribution significantly different. The analysis of ABO blood grouping shows a variety factors influencing positive and negative blood typing, and the Gel Card identification can produc more false positive blood types. Therefore, more attention should be paid on the high incidence diseases, such as blood disease, tumor, and cardiopulmonary disease.

Evaluation of inadequate, indeterminate, false-negative and false-positive cases in cytological examination for breast cancer according to histological type

PubMed Central

2012-01-01

Background We previously investigated the current status of breast cytology cancer screening at seven institutes in our area of southern Fukuoka Prefecture, and found some differences in diagnostic accuracy among the institutions. In the present study, we evaluated the cases involved and noted possible reasons for their original cytological classification as inadequate, indeterminate, false-negative and false-positive according to histological type. Methods We evaluated the histological findings in 5693 individuals who underwent cytological examination for breast cancer (including inadequate, indeterminate, false-negative and false-positive cases), to determine the most common histological types and/or features in these settings and the usefulness/limitations of cytological examination for the diagnosis of breast cancer. Results Among 1152 cytologically inadequate cases, histology revealed that 75/173 (43.6%) cases were benign, including mastopathy (fibrocystic disease) in 38.6%, fibroadenoma in 24.0% and papilloma in 5.3%. Ninety-five of 173 (54.9%) cases were histologically malignant, with scirrhous growing type, invasive ductal carcinoma (SIDC) being significantly more frequent (49.5%) than papillotubular growing type (Papi-tub) (P < 0.0001), solid-tubular growing type (P = 0.0001) and ductal carcinoma in situ (DCIS) (P = 0.0001). Among 458 indeterminate cases, 54/139 (38.8%) were histologically benign (mastopathy, 30.0%; fibroadenoma, 27.8%; papilloma, 26.0%) and 73/139 (52.5%) were malignant, with SIDC being the most frequent malignant tumor (37.0%). Among 52 false-negative cases, SIDC was significantly more frequent (42.3%) than DCIS (P = 0.0049) and Papi-tub (P = 0.001). There were three false-positive cases, with one each of fibroadenoma, epidermal cyst and papilloma. Conclusions The inadequate, indeterminate, false-negative and false-positive cases showed similar histological types, notably SIDC for malignant tumors, and mastopathy, fibroadenoma and papilloma for benign cases. We need to pay particular attention to the collection and assessment of aspirates for these histological types of breast disease. In particular, several inadequate, indeterminate and false-negative cases with samples collected by aspiration were diagnosed as SIDC. These findings should encourage the use of needle biopsy rather than aspiration when this histological type is identified on imaging. Namely, good communication between clinicians and pathological staff, and triple assessment (i.e., clinical, pathological and radiological assessment), are important for accurate diagnosis of aspiration samples. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7349809170055423 PMID:22607447

False Belief vs. False Photographs: A Test of Theory of Mind or Working Memory?

PubMed

Callejas, Alicia; Shulman, Gordon L; Corbetta, Maurizio

2011-01-01

Theory of mind (ToM), the ability to reason about other people's thoughts and beliefs, has been traditionally studied in behavioral and neuroimaging experiments by comparing performance in "false belief" and "false photograph" (control) stories. However, some evidence suggests that these stories are not matched in difficulty, complicating the interpretation of results. Here, we more fully evaluated the relative difficulty of comprehending these stories and drawing inferences from them. Subjects read false belief and false photograph stories followed by comprehension questions that probed true ("reality" questions) or false beliefs ("representation" questions) appropriate to the stories. Stories and comprehension questions were read and answered, respectively, more slowly in the false photograph than false belief conditions, indicating their greater difficulty. Interestingly, accuracy on representation questions for false photograph stories was significantly lower than for all other conditions and correlated positively with participants' working memory span scores. These results suggest that drawing representational inferences from false photo stories is particularly difficult and places heavy demands on working memory. Extensive naturalistic practice with ToM reasoning may enable a more flexible and efficient mental representation of false belief stories, resulting in lower memory load requirements. An important implication of these results is that the differential modulation of right temporal-parietal junction (RTPJ) during ToM and "false photo" control conditions may reflect the documented negative correlation of RTPJ activity with working memory load rather than a specialized involvement in ToM processes.

[False positive of DUPAN-2 caused by IgM-human anti mouse antibody].

PubMed

Abe, Masaki; Hyoki, Miyuki; Abe, Ikurou; Kaito, Ken; Takagi, Ichirou

2012-11-01

We investigated a case in our experience presenting false-positive for DUPAN-2 by IgM-human anti mouse antibody (HAMA). A female aged 40s has been treated in our hospital from 2003. Her serum level of DUPAN-2 in 2005 and 2006 were 110 U/mL and 140 U/mL respectively. While this level was increased to 770 U/ml in 2007, and kept in the higher level so far. Around years of 2007, no meaning changes was detected by radiological and laboratory tests, and there was no significant change in her clinical signs and symptoms and medications. The elevation of DUPAN-2 was thought as a false-positive phenomenon and the mechanism was investigated. As results, no dilution lineality was found, and absorption test showed a 95% reduction of DUPAN-2 levels not by IgG and IgA, but IgM-specific antiserum. Dithiothreitoldeacylation test with neuraminidase, and absorption test with HBR-1, IIR, and mouse IgM serum, it was suggested that the IgM with HAMA activity of the patient reacted with mouse monoclonal antibodies in reagents. Moreover, the HPLC-eluted fraction of DUPAN-2 of this patients was detected in the fraction of IgM, which as different from that of a control pancreatic cancer patient. Above these data, elevation of DUPAN-2 in this patient was a false positive phenomenon by IgM-HAMA reacting with mouse monoclonal antibodies in reagents. Although there are few reported cases of false positive phenomenon in DUPAN-2 measurement, we have to pay attention to such phenomenon when detecting an unlikely higher levels that could not be explained by clinical information.

False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis

PubMed Central

Gillet, Philippe; Mumba Ngoyi, Dieudonné; Lukuka, Albert; Kande, Viktor; Atua, Benjamin; van Griensven, Johan; Muyembe, Jean-Jacques; Jacobs, Jan; Lejon, Veerle

2013-01-01

Background In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests. PMID:23638201

Publication bias and the canonization of false facts

PubMed Central

Nissen, Silas Boye; Magidson, Tali; Gross, Kevin; Bergstrom, Carl T

2016-01-01

Science is facing a “replication crisis” in which many experimental findings cannot be replicated and are likely to be false. Does this imply that many scientific facts are false as well? To find out, we explore the process by which a claim becomes fact. We model the community’s confidence in a claim as a Markov process with successive published results shifting the degree of belief. Publication bias in favor of positive findings influences the distribution of published results. We find that unless a sufficient fraction of negative results are published, false claims frequently can become canonized as fact. Data-dredging, p-hacking, and similar behaviors exacerbate the problem. Should negative results become easier to publish as a claim approaches acceptance as a fact, however, true and false claims would be more readily distinguished. To the degree that the model reflects the real world, there may be serious concerns about the validity of purported facts in some disciplines. DOI: http://dx.doi.org/10.7554/eLife.21451.001 PMID:27995896

Sample Selection for Training Cascade Detectors.

PubMed

Vállez, Noelia; Deniz, Oscar; Bueno, Gloria

2015-01-01

Automatic detection systems usually require large and representative training datasets in order to obtain good detection and false positive rates. Training datasets are such that the positive set has few samples and/or the negative set should represent anything except the object of interest. In this respect, the negative set typically contains orders of magnitude more images than the positive set. However, imbalanced training databases lead to biased classifiers. In this paper, we focus our attention on a negative sample selection method to properly balance the training data for cascade detectors. The method is based on the selection of the most informative false positive samples generated in one stage to feed the next stage. The results show that the proposed cascade detector with sample selection obtains on average better partial AUC and smaller standard deviation than the other compared cascade detectors.

Screening for gonorrhoea using samples collected through the English National Chlamydia Screening Programme and risk of false positives: a national survey of Local Authorities

PubMed Central

Field, Nigel; Kennedy, Iain; Folkard, Kate; Duffell, Stephen; Town, Katy; Ison, Catherine A; Hughes, Gwenda

2014-01-01

Objectives To investigate use of dual tests for Chlamydia trachomatis and Neisseria gonorrhoeae on samples collected through the National Chlamydia Screening Programme (NCSP) in England. Design and setting During May–July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15–24 years. Main outcome measures (1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%. Results 64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450–4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17–67%. Conclusions Over half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed. PMID:25324326

Effects of ecstasy/polydrug use on memory for associative information.

PubMed

Gallagher, Denis T; Fisk, John E; Montgomery, Catharine; Judge, Jeannie; Robinson, Sarita J; Taylor, Paul J

2012-08-01

Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value.

Comparative evaluation of paired blood culture (aerobic/aerobic) and single blood culture, along with clinical importance in catheter versus peripheral line at a tertiary care hospital.

PubMed

Tarai, B; Das, P; Kumar, D; Budhiraja, S

2012-01-01

Paired blood culture (PBC) is uncommon practice in hospitals in India, leading to delayed and inadequate diagnosis. Also contamination remains a critical determinant in hampering the definitive diagnosis. To establish the need of PBC over single blood culture (SBC) along with the degree of contamination, this comparative retrospective study was initiated. We processed 2553 PBC and 4350 SBC in BacT/ALERT 3D (bioMerieux) between October 2010 and June 2011. The positive cultures were identified in VITEK 2 Compact (bioMerieux). True positivity and contaminants were also analyzed in 486 samples received from catheter and peripheral line. Out of 2553 PBC samples, positivity was seen in 350 (13.70%). In 4350 SBC samples, positivity was seen in 200 samples (4.59%). In PBC true pathogens were 267 (10.45%) and contaminants were 83 (3.25%), whereas in SBC 153 (3.51%) were true positives and contaminants were 47 (1.08%). Most of the blood cultures (99.27 %) grew within 72 h and 95.8% were isolated within 48 h. In 486 PBCs received from catheter/periphery (one each), catheter positivity was found in 85 (true positives were 48, false positives 37). In peripheral samples true positives were 50 and false positives were 8. Significantly higher positive rates were seen in PBCs compared with SBCs. Automated blood culture and identification methods significantly reduced the time required for processing of samples and also facilitated yield of diverse/rare organisms. Blood culture from catheter line had higher false positives than peripheral blood culture. Thus every positive result from a catheter must be correlated with clinical findings and requires further confirmation.

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

PubMed

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

2012-11-01

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

False-positive results after environmental pinworm PCR testing due to Rhabditid nematodes in Corncob bedding.

PubMed

Leblanc, Mathias; Berry, Kristina; Graciano, Sandy; Becker, Brandon; Reuter, Jon D

2014-11-01

Modern rodent colonies are housed in individually ventilated cages to protect the animals from contamination with adventitious pathogens. Standard health monitoring through soiled-bedding sentinels does not always detect infections, especially in the context of low pathogen prevalence. Recently proposed alternatives include analyzing environmental samples from the cages or rack exhaust by PCR to improve the detection of rodent pathogens but optimal sampling strategies have not yet been established for different microorganisms. Although generally very sensitive and specific, these molecular assays are not foolproof and subject to false-positive and -negative results and should always be interpreted cautiously with an overall understanding of the intrinsic controls and all the variables that may affect the results. Here, we report a limited Aspiculuris tetraptera outbreak in a mouse barrier facility that was detected by fecal PCR in sentinels and confirmed by fecal flotation and direct cecal examination of both sentinels and colony animals. The outbreak led to a widespread survey of all facilities for pinworms by using environmental PCR from ventilated rack exhaust plenums. Environmental PCR suggested an unexpected widespread contamination of all ventilated racks holding nonautoclaved cages, but results could not be confirmed in sentinel or colony animals by fecal flotation, cecal and colonic examination, or cage PCR testing. After additional investigation, the unexpected environmental PCR results were confirmed as false-positive findings due to the nonspecificity of the assay, leading to the amplification of rhabditid nematodes, which are not infectious in rodents but which contaminated the corncob bedding.

Performing Testicular Self-Examination, Driving Automobiles, and Anxiety: What Is the Logical Link?

PubMed

Rovito, Michael J

2018-05-01

The debate of whether testicular self-examination (TSE) should be promoted among males generally centers on a harm-benefit corollary. The benefits of TSE include improving health outcomes, inclusive of an increase in both quality of life and knowledge/awareness of potential health concerns, as well as promoting proactivity in achieving wellness. The harms include claims that false-positive results can increase anxiety and produce costs via unnecessary treatments and therapies. Further claims point to the lack of evidence suggesting TSE decreases testicular cancer mortality. This commentary primarily discusses the anxiety portion of this debate from a logic-based perspective. The argument that TSE should not be promoted among males due to the risk of inciting false-positive anxiety appears to be flawed. A 5-point perspective is presented on the illogical discouragement of TSE due to theorized levels of false-positive anxiety while existing evidence suggests late-stage testicular cancer is associated with anxiety and depression.

Automatic abdominal lymph node detection method based on local intensity structure analysis from 3D x-ray CT images

NASA Astrophysics Data System (ADS)

Nakamura, Yoshihiko; Nimura, Yukitaka; Kitasaka, Takayuki; Mizuno, Shinji; Furukawa, Kazuhiro; Goto, Hidemi; Fujiwara, Michitaka; Misawa, Kazunari; Ito, Masaaki; Nawano, Shigeru; Mori, Kensaku

2013-03-01

This paper presents an automated method of abdominal lymph node detection to aid the preoperative diagnosis of abdominal cancer surgery. In abdominal cancer surgery, surgeons must resect not only tumors and metastases but also lymph nodes that might have a metastasis. This procedure is called lymphadenectomy or lymph node dissection. Insufficient lymphadenectomy carries a high risk for relapse. However, excessive resection decreases a patient's quality of life. Therefore, it is important to identify the location and the structure of lymph nodes to make a suitable surgical plan. The proposed method consists of candidate lymph node detection and false positive reduction. Candidate lymph nodes are detected using a multi-scale blob-like enhancement filter based on local intensity structure analysis. To reduce false positives, the proposed method uses a classifier based on support vector machine with the texture and shape information. The experimental results reveal that it detects 70.5% of the lymph nodes with 13.0 false positives per case.

One-day fluorescent-antibody procedure for detecting salmonellae in frozen and dried foods.

PubMed

Goepfert, J M; Mann, M E; Hicks, R

1970-12-01

The indirect fluorescent-antibody technique was used to examine 422 food samples for the presence of salmonellae. A cultural phase involving a 16-hr preenrichment in buffered nutrient broth-milk medium followed by a 4- to 5-hr subculture into fresh medium of the same composition was evaluated. This procedure yielded a sufficient population of salmonellae so that no false-negative results were obtained. Of the 31 false-positives obtained, 12 samples yielded positive cultural results upon extensive subculture of the original enrichment broths. Yeast cells and both vegetative and spore forms of bacilli were observed to fluoresce when stained with anti-Salmonella serum. Efforts to ascertain the cause of these cross-reactions and several alternate explanations are discussed.

Reducing false positives of microcalcification detection systems by removal of breast arterial calcifications.

PubMed

Mordang, Jan-Jurre; Gubern-Mérida, Albert; den Heeten, Gerard; Karssemeijer, Nico

2016-04-01

In the past decades, computer-aided detection (CADe) systems have been developed to aid screening radiologists in the detection of malignant microcalcifications. These systems are useful to avoid perceptual oversights and can increase the radiologists' detection rate. However, due to the high number of false positives marked by these CADe systems, they are not yet suitable as an independent reader. Breast arterial calcifications (BACs) are one of the most frequent false positives marked by CADe systems. In this study, a method is proposed for the elimination of BACs as positive findings. Removal of these false positives will increase the performance of the CADe system in finding malignant microcalcifications. A multistage method is proposed for the removal of BAC findings. The first stage consists of a microcalcification candidate selection, segmentation and grouping of the microcalcifications, and classification to remove obvious false positives. In the second stage, a case-based selection is applied where cases are selected which contain BACs. In the final stage, BACs are removed from the selected cases. The BACs removal stage consists of a GentleBoost classifier trained on microcalcification features describing their shape, topology, and texture. Additionally, novel features are introduced to discriminate BACs from other positive findings. The CADe system was evaluated with and without BACs removal. Here, both systems were applied on a validation set containing 1088 cases of which 95 cases contained malignant microcalcifications. After bootstrapping, free-response receiver operating characteristics and receiver operating characteristics analyses were carried out. Performance between the two systems was compared at 0.98 and 0.95 specificity. At a specificity of 0.98, the sensitivity increased from 37% to 52% and the sensitivity increased from 62% up to 76% at a specificity of 0.95. Partial areas under the curve in the specificity range of 0.8-1.0 were significantly different between the system without BACs removal and the system with BACs removal, 0.129 ± 0.009 versus 0.144 ± 0.008 (p<0.05), respectively. Additionally, the sensitivity at one false positive per 50 cases and one false positive per 25 cases increased as well, 37% versus 51% (p<0.05) and 58% versus 67% (p<0.05) sensitivity, respectively. Additionally, the CADe system with BACs removal reduces the number of false positives per case by 29% on average. The same sensitivity at one false positive per 50 cases in the CADe system without BACs removal can be achieved at one false positive per 80 cases in the CADe system with BACs removal. By using dedicated algorithms to detect and remove breast arterial calcifications, the performance of CADe systems can be improved, in particular, at false positive rates representative for operating points used in screening.

Substances that interfere with guaiac card tests: implications for gastric aspirate testing.

PubMed

Gogel, H K; Tandberg, D; Strickland, R G

1989-09-01

Previous studies have shown that acidic pH and several ingestible substances can cause misleading guaiac tests of gastric aspirates. In this in vitro study, over 100 foods, beverages, and drugs were diluted to concentrations potentially present in the stomachs of outpatients being evaluated for gastrointestinal bleeding. These were mixed with known concentrations of blood and tested with different brands of guaiac cards. Decreased guaiac test sensitivity was associated with activated charcoal, dimethylaminoethanol, red chile, N-acetylcysteine, rifampin, red Jell-O (General Foods Corp, White Plains, NY), orange juice, Pepto-Bismol (Norwich Eaton Pharmaceuticals, Norwich, NY), simethicone, spaghetti sauce, and several red wines. Chlorophyll and methylene blue-containing tablets produced false-positive results, but other blue and blue-green colored tablets did not, except at high concentrations. Previously described false-negative results with vitamin C, bile, and certain antacids were confirmed, as were false-positive results with iodide, bromide, cupric sulfate, iron salts, and hypochlorite. Physicians should exercise caution when interpreting guaiac card tests of gastric aspirates, especially in the outpatient setting.

Performance of two strategies for urgent ANCA and anti-GBM analysis in vasculitis.

PubMed

de Joode, Anoek A E; Roozendaal, Caroline; van der Leij, Marcel J; Bungener, Laura B; Sanders, Jan Stephan F; Stegeman, Coen A

2014-02-01

In anti-neutrophil cytoplasmic antibodies (ANCA) associated small vessel vasculitis (AAV), rapid testing for ANCA and anti-glomerular basement membrane (GBM) antibodies may be beneficial for therapeutic purpose. We analysed the diagnostic performance of two rapid ANCA and anti-GBM test methods in 260 patients with suspected AAV. Between January 2004 and November 2010, we analysed 260 samples by qualitative Dotblot (Biomedical Diagnostics); retrospective analysis followed with directly coated highly sensitive automated Phadia ELiA and ELiA anti-GBM. Results were related to the final clinical diagnosis and compared with routine capture ELISA. Seventy-four patients had a final diagnosis of AAV (n=62) or anti-GBM disease (n=12). Both Dotblot and ELiA detected all 12 cases of anti-GBM disease; 2 false positive results were found. Dotblot detected ANCA in 56 of 62 AAV patients (sensitivity 90%, NPV 97%), and showed 5 false positives (specificity 97%, PPV 90%). The Phadia ELiA anti-PR3(s) or anti-MPO(s) was positive in 57 of 62 AAV patients (sensitivity 92%, NPV 97%), and had 5 false positives (specificity 97%, PPV 88%). Routine capture ELISA was equally accurate (sensitivity 94%, specificity 97%, PPV 88%, NPV 98%). The Dotblot and Phadia ELiA on anti-GBM, anti-PR3(s) and anti-MPO(s) performed excellently; results were almost identical to routine ELISA. When suspicion of AAV or anti-GBM disease is high and diagnosis is urgently needed, both tests are very powerful for rapid serological diagnosis. Further studies have to confirm the test performances in samples routinely presented for ANCA testing and in follow-up of positive patients. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

MicroRNA array normalization: an evaluation using a randomized dataset as the benchmark.

PubMed

Qin, Li-Xuan; Zhou, Qin

2014-01-01

MicroRNA arrays possess a number of unique data features that challenge the assumption key to many normalization methods. We assessed the performance of existing normalization methods using two microRNA array datasets derived from the same set of tumor samples: one dataset was generated using a blocked randomization design when assigning arrays to samples and hence was free of confounding array effects; the second dataset was generated without blocking or randomization and exhibited array effects. The randomized dataset was assessed for differential expression between two tumor groups and treated as the benchmark. The non-randomized dataset was assessed for differential expression after normalization and compared against the benchmark. Normalization improved the true positive rate significantly in the non-randomized data but still possessed a false discovery rate as high as 50%. Adding a batch adjustment step before normalization further reduced the number of false positive markers while maintaining a similar number of true positive markers, which resulted in a false discovery rate of 32% to 48%, depending on the specific normalization method. We concluded the paper with some insights on possible causes of false discoveries to shed light on how to improve normalization for microRNA arrays.

MicroRNA Array Normalization: An Evaluation Using a Randomized Dataset as the Benchmark

PubMed Central

Qin, Li-Xuan; Zhou, Qin

2014-01-01

MicroRNA arrays possess a number of unique data features that challenge the assumption key to many normalization methods. We assessed the performance of existing normalization methods using two microRNA array datasets derived from the same set of tumor samples: one dataset was generated using a blocked randomization design when assigning arrays to samples and hence was free of confounding array effects; the second dataset was generated without blocking or randomization and exhibited array effects. The randomized dataset was assessed for differential expression between two tumor groups and treated as the benchmark. The non-randomized dataset was assessed for differential expression after normalization and compared against the benchmark. Normalization improved the true positive rate significantly in the non-randomized data but still possessed a false discovery rate as high as 50%. Adding a batch adjustment step before normalization further reduced the number of false positive markers while maintaining a similar number of true positive markers, which resulted in a false discovery rate of 32% to 48%, depending on the specific normalization method. We concluded the paper with some insights on possible causes of false discoveries to shed light on how to improve normalization for microRNA arrays. PMID:24905456

False-belief understanding in 2.5-year-olds: Evidence from two novel verbal spontaneous-response tasks

PubMed Central

Scott, Rose M.; He, Zijing; Baillargeon, Renée; Cummins, Denise

2011-01-01

Recent research indicates that toddlers and infants succeed at various non-verbal spontaneous-response false-belief tasks; here we asked whether toddlers would also succeed at verbal spontaneous-response false-belief tasks that imposed significant linguistic demands. 2.5-year-olds were tested using two novel tasks: a preferential-looking task in which children listened to a false-belief story while looking at a picture book (with matching and non-matching pictures), and a violation-of-expectation task in which children watched an adult “Subject” answer (correctly or incorrectly) a standard false-belief question. Positive results were obtained with both tasks, despite their linguistic demands. These results (1) support the distinction between spontaneous-and elicited-response tasks by showing that toddlers succeed at verbal false-belief tasks that do not require them to answer direct questions about agents’ false beliefs, (2) reinforce claims of robust continuity in early false-belief understanding as assessed by spontaneous-response tasks, and (3) provide researchers with new experimental tasks for exploring early false-belief understanding in neurotypical and autistic populations. PMID:22356174

False-belief understanding in 2.5-year-olds: evidence from two novel verbal spontaneous-response tasks.

PubMed

Scott, Rose M; He, Zijing; Baillargeon, Renée; Cummins, Denise

2012-03-01

Recent research indicates that toddlers and infants succeed at various non-verbal spontaneous-response false-belief tasks; here we asked whether toddlers would also succeed at verbal spontaneous-response false-belief tasks that imposed significant linguistic demands. We tested 2.5-year-olds using two novel tasks: a preferential-looking task in which children listened to a false-belief story while looking at a picture book (with matching and non-matching pictures), and a violation-of-expectation task in which children watched an adult 'Subject' answer (correctly or incorrectly) a standard false-belief question. Positive results were obtained with both tasks, despite their linguistic demands. These results (1) support the distinction between spontaneous- and elicited-response tasks by showing that toddlers succeed at verbal false-belief tasks that do not require them to answer direct questions about agents' false beliefs, (2) reinforce claims of robust continuity in early false-belief understanding as assessed by spontaneous-response tasks, and (3) provide researchers with new experimental tasks for exploring early false-belief understanding in neurotypical and autistic populations. © 2011 Blackwell Publishing Ltd.

Positive Streptobacillus moniliformis PCR in guinea pigs likely due to Leptotrichia spp.

PubMed

Boot, Ron; Van de Berg, Lia; Reubsaet, Frans A G; Vlemminx, Maurice J

2008-04-30

Streptobacillus moniliformis is a zoonotic bacterium. We obtained positive S. moniliformis PCR results in oral swab samples from guinea pigs from an experimental colony and the breeding colony of origin. Comparison of the DNA sequence of an amplicon with deposited 16S rDNA sequences revealed that Leptotrichia sp. can be the source of a false positive S. moniliformis PCR outcome.

Comparison of false-negative/positive results of intraoperative evoked potential monitoring between no and partial neuromuscular blockade in patients receiving propofol/remifentanil-based anesthesia during cerebral aneurysm clipping surgery: A retrospective analysis of 685 patients.

PubMed

Kim, Sung-Hoon; Jin, Seok-Joon; Karm, Myong-Hwan; Moon, Young-Jin; Jeong, Hye-Won; Kim, Jae-Won; Ha, Seung-Il; Kim, Joung-Uk

2016-08-01

Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False-negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

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

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age.

PubMed

Johnson, Susan L; Tabaei, Bahman P; Herman, William H

2005-02-01

To simulate the outcomes of alternative strategies for screening the U.S. population 45-74 years of age for type 2 diabetes. We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs. At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion. Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.

A Cross-Reactivity of Fenofibric Acid With MDMA DRI Assay.

PubMed

Bugier, Sarah; Garcia-Hejl, Carine; Vest, Philippe; Plantamura, Julie; Chianea, Denis; Renard, Christophe

2016-09-01

Within the framework of routine fitness examinations, French Air Force military crew underwent urine testing for 3,4 methylenedioxymetamphetamine (MDMA [ecstasy]). The cross-reactivity of a dyslipidemic drug, fenofibrate, with an MDMA immunoassay was studied and confirmed on a large population sample. A 3-year retrospective study was performed on the MDMA DRI Ecstasy Assay on the Unicel DXC 600. In the event of positive test result, a confirmatory testing was carried out by gas chromatography/mass spectrometry (GC/MS) to establish the presence of MDMA. When analysis by GC/MS did not confirm the presence of MDMA, a false-positive result was suspected and the samples were analyzed by high-performance liquid chromatography-mass spectrometry to identify a potential interfering substance. A total of 15,169 urine samples, from 7,803 patients, were tested for 3 years. Of the tested samples, 22 (0.15%) were positive by DRI Ecstasy Assay. None of them were positive by GC/MS. A cross-reactivity of fenofibrate's metabolite with MDMA using this assay was systematically found. Fenofibrate's interference with MDMA immunoassay was confirmed. Fenofibrate being widely prescribed, physicians had to be alerted that this treatment could lead to false-positive results. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Texture-based CAD improves diagnosis for low-dose CT colonography

NASA Astrophysics Data System (ADS)

Liang, Zhengrong; Cohen, Harris; Posniak, Erica; Fiore, Eddie; Wang, Zigang; Li, Bin; Andersen, Joseph; Harrington, Donald

2008-03-01

Computed tomography (CT)-based virtual colonoscopy or CT colonography (CTC) currently utilizes oral contrast solutions to tag the colonic fluid and possibly residual stool for differentiation from the colon wall and polyps. The enhanced image density of the tagged colonic materials causes a significant partial volume (PV) effect into the colon wall as well as the lumen space (filled with air or CO II). The PV effect on the colon wall can "bury" polyps of size as large as 5mm by increasing their image densities to a noticeable level, resulting in false negatives. It can also create false positives when PV effect goes into the lumen space. We have been modeling the PV effect for mixture-based image segmentation and developing text-based computer-aided detection of polyp (CADpolyp) by utilizing the PV mixture-based image segmentation. This work presents some preliminary results of developing and applying texture-based CADpolyp technique to low-dose CTC studies. A total of 114 studies of asymptomatic patients older than 50, who underwent CTC and then optical colonoscopy (OC) on the same day, were selected from a database, which was accumulated in the past decade and contains various bowel preparations and CT scanning protocols. The participating radiologists found ten polyps of greater than 5 mm from a total of 16 OC proved polyps, i.e., a detection sensitivity of 63%. They scored 23 false positives from the database, i.e., a 20% false positive rate. Approximately 70% of the datasets were marked as imperfect bowel cleansing and/or presence of image artifacts. The impact of imperfect bowel cleansing and image artifacts on VC performance is significant. The texture-based CADpolyp detected all the polyps with an average of 2.68 false positives per patient. This indicates that texture-based CADpolyp can improve the CTC performance in the cases of imperfect cleansed bowels and presence of image artifacts.

A Retrospective Analysis of Urine Drugs of Abuse Immunoassay True Positive Rates at a National Reference Laboratory.

PubMed

Johnson-Davis, Kamisha L; Sadler, Aaron J; Genzen, Jonathan R

2016-03-01

Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ∼14%, ∼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An assessment of public health surveillance of Zika virus infection and potentially associated outcomes in Latin America.

PubMed

Bautista, Leonelo E; Herrera, Víctor M

2018-05-24

We evaluated whether outbreaks of Zika virus (ZIKV) infection, newborn microcephaly, and Guillain-Barré syndrome (GBS) in Latin America may be detected through current surveillance systems, and how cases detected through surveillance may increase health care burden. We estimated the sensitivity and specificity of surveillance case definitions using published data. We assumed a 10% ZIKV infection risk during a non-outbreak period and hypothetical increases in risk during an outbreak period. We used sensitivity and specificity estimates to correct for non-differential misclassification, and calculated a misclassification-corrected relative risk comparing both periods. To identify the smallest hypothetical increase in risk resulting in a detectable outbreak we compared the misclassification-corrected relative risk to the relative risk corresponding to the upper limit of the endemic channel (mean + 2 SD). We also estimated the proportion of false positive cases detected during the outbreak. We followed the same approach for microcephaly and GBS, but assumed the risk of ZIKV infection doubled during the outbreak, and ZIKV infection increased the risk of both diseases. ZIKV infection outbreaks were not detectable through non-serological surveillance. Outbreaks were detectable through serologic surveillance if infection risk increased by at least 10%, but more than 50% of all cases were false positive. Outbreaks of severe microcephaly were detected if ZIKV infection increased prevalence of this condition by at least 24.0 times. When ZIKV infection did not increase the prevalence of severe microcephaly, 34.7 to 82.5% of all cases were false positive, depending on diagnostic accuracy. GBS outbreaks were detected if ZIKV infection increased the GBS risk by at least seven times. For optimal GBS diagnosis accuracy, the proportion of false positive cases ranged from 29 to 54% and from 45 to 56% depending on the incidence of GBS mimics. Current surveillance systems have a low probability of detecting outbreaks of ZIKV infection, severe microcephaly, and GBS, and could result in significant increases in health care burden, due to the detection of large numbers of false positive cases. In view of these limitations, Latin American countries should consider alternative options for surveillance.

Language of administration and neuropsychological test performance in neurologically intact Hispanic American bilingual adults.

PubMed

Gasquoine, Philip Gerard; Croyle, Kristin L; Cavazos-Gonzalez, Cynthia; Sandoval, Omar

2007-11-01

This study compared the performance of Hispanic American bilingual adults on Spanish and English language versions of a neuropsychological test battery. Language achievement test scores were used to divide 36 bilingual, neurologically intact, Hispanic Americans from south Texas into Spanish-dominant, balanced, and English-dominant bilingual groups. They were administered the eight subtests of the Bateria Neuropsicologica and the Matrix Reasoning subtest of the WAIS-III in Spanish and English. Half the participants were tested in Spanish first. Balanced bilinguals showed no significant differences in test scores between Spanish and English language administrations. Spanish and/or English dominant bilinguals showed significant effects of language of administration on tests with higher language compared to visual perceptual weighting (Woodcock-Munoz Language Survey-Revised, Letter Fluency, Story Memory, and Stroop Color and Word Test). Scores on tests with higher visual-perceptual weighting (Matrix Reasoning, Figure Memory, Wisconsin Card Sorting Test, and Spatial Span), were not significantly affected by language of administration, nor were scores on the Spanish/California Verbal Learning Test, and Digit Span. A problem was encountered in comparing false positive rates in each language, as Spanish norms fell below English norms, resulting in a much higher false positive rate in English across all bilingual groupings. Use of a comparison standard (picture vocabulary score) reduced false positive rates in both languages, but the higher false positive rate in English persisted.

Imaging in gynaecology: How good are we in identifying endometriomas?

PubMed Central

Van Holsbeke, C.; Van Calster, B.; Guerriero, S.; Savelli, L.; Leone, F.; Fischerova, D; Czekierdowski, A.; Fruscio, R.; Veldman, J.; Van de Putte, G.; Testa, A.C.; Bourne, T.; Valentin, L.; Timmerman, D.

2009-01-01

Aim: To evaluate the performance of subjective evaluation of ultrasound findings (pattern recognition) to discriminate endometriomas from other types of adnexal masses and to compare the demographic and ultrasound characteristics of the true positive cases with those cases that were presumed to be an endometrioma but proved to have a different histology (false positive cases) and the endometriomas missed by pattern recognition (false negative cases). Methods: All patients in the International Ovarian Tumor Analysis (IOTA ) studies were included for analysis. In the IOTA studies, patients with an adnexal mass that were preoperatively examined by expert sonologists following the same standardized ultrasound protocol were prospectively included in 21 international centres. Sensitivity and specificity to discriminate endometriomas from other types of adnexal masses using pattern recognition were calculated. Ultrasound and some demographic variables of the masses presumed to be an endometrioma were analysed (true positives and false positives) and compared with the variables of the endometriomas missed by pattern recognition (false negatives) as well as the true negatives. Results: IOTA phase 1, 1b and 2 included 3511 patients of which 2560 were benign (73%) and 951 malignant (27%). The dataset included 713 endometriomas. Sensitivity and specificity for pattern recognition were 81% (577/713) and 97% (2723/2798). The true positives were more often unilocular with ground glass echogenicity than the masses in any other category. Among the 75 false positive cases, 66 were benign but 9 were malignant (5 borderline tumours, 1 rare primary invasive tumour and 3 endometrioid adenocarcinomas). The presumed diagnosis suggested by the sonologist in case of a missed endometrioma was mostly functional cyst or cystadenoma. Conclusion: Expert sonologists can quite accurately discriminate endometriomas from other types of adnexal masses, but in this dataset 1% of the masses that were classified as endometrioma by pattern recognition proved to be malignancies. PMID:25478066

Colonoscopic Findings in Patients With Incidental Colonic Focal FDG Uptake.

PubMed

Keyzer, Caroline; Dhaene, Benjamin; Blocklet, Didier; De Maertelaer, Viviane; Goldman, Serge; Gevenois, Pierre Alain

2015-05-01

The purpose of this study was to investigate the nature of FDG-avid and non-FDG-avid lesions detected at colonoscopy in patients presenting with incidental focal colonic FDG uptake at PET/CT. Among 9073 patients who underwent PET/CT over a 4-year period, 82 patients without a history of colonic disease had focal colonic FDG uptake and underwent colonoscopy. In consensus, a radiologist and a nuclear physician read images from these PET/CT examinations. They recorded the location of focal FDG uptake in the colon and associated CT abnormalities and measured maximum standardized uptake value (SUVmax) and metabolic volume (MV). Readings were performed twice--first without and second with knowledge of lesion location at colonoscopy. The final diagnosis was based on colonoscopic findings and histopathologic results categorized into benign, premalignant, or malignant. One hundred seven foci of colonic FDG uptake at PET/CT and 150 lesions at colonoscopy were detected. Among 107 foci of FDG uptake, 65 (61%) corresponded to a lesion at colonoscopy (true-positive findings), and 42 (39%) did not (false-positive findings). Among 150 lesions found at colonoscopy, 85 (57%) were not FDG avid (false-negative findings). The MV of true-positive findings was lower than that of false-positive findings (4.0 ± 0.4 cm(3) vs 6.2 ± 0.7 cm(3); p = 0.006), but SUVmax did not differ (7.4 ± 0.5 vs 7.7 ± 0.5; p = 0.649). Considering the histopathologic categories of the lesions and the false-positive findings, there was no difference in SUVmax (p = 0.103), but MV was lower in premalignant lesions than in false-positive findings (p = 0.005). Focal colonic FDG uptake may indicate the presence of a benign, pre-malignant, or malignant lesion. Subsequent colonoscopy should not be restricted to the colonic site of FDG uptake.

Can False Memories Prime Problem Solutions for Healthy Older Adults and those with Alzheimer 's Disease?

PubMed

Akhtar, Shazia; Howe, Mark L; Hoepstine, Kedron

2018-06-05

Recent research has shown that false memories can have a positive consequence on human cognition in both children and young adults. The present experiment investigated whether false memories could have similar positive effects by priming solutions to insight-based problems in healthy older adults and people with Alzheimer's disease. Participants were asked to solve compound remote associate task (CRAT) problems, half of which had been preceded by the presentation of Deese/Roediger-McDermott (DRM) lists whose critical lures were also the solutions to those problems. The results showed that regardless of cognitive ability, when the critical lure was falsely recognized, CRAT problems were solved more often and reliably faster than problems that were not primed by a DRM list. When the critical lure was not falsely recognized, CRAT problem solution rates and times were no different from when there was no DRM priming. These findings are consistent with predictions from theories of associative activation and demonstrate the importance of automatic spreading activation processes in memory across the lifespan.

Ability To Serologically Confirm Recent Zika Virus Infection in Areas with Varying Past Incidence of Dengue Virus Infection in the United States and U.S. Territories in 2016.

PubMed

Lindsey, Nicole P; Staples, J Erin; Powell, Krista; Rabe, Ingrid B; Fischer, Marc; Powers, Ann M; Kosoy, Olga I; Mossel, Eric C; Munoz-Jordan, Jorge L; Beltran, Manuela; Hancock, W Thane; Toews, Karrie-Ann E; Ellis, Esther M; Ellis, Brett R; Panella, Amanda J; Basile, Alison J; Calvert, Amanda E; Laven, Janeen; Goodman, Christin H; Gould, Carolyn V; Martin, Stacey W; Thomas, Jennifer D; Villanueva, Julie; Mataia, Mary L; Sciulli, Rebecca; Gose, Remedios; Whelen, A Christian; Hills, Susan L

2018-01-01

Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Splenomegaly Segmentation using Global Convolutional Kernels and Conditional Generative Adversarial Networks

PubMed Central

Huo, Yuankai; Xu, Zhoubing; Bao, Shunxing; Bermudez, Camilo; Plassard, Andrew J.; Liu, Jiaqi; Yao, Yuang; Assad, Albert; Abramson, Richard G.; Landman, Bennett A.

2018-01-01

Spleen volume estimation using automated image segmentation technique may be used to detect splenomegaly (abnormally enlarged spleen) on Magnetic Resonance Imaging (MRI) scans. In recent years, Deep Convolutional Neural Networks (DCNN) segmentation methods have demonstrated advantages for abdominal organ segmentation. However, variations in both size and shape of the spleen on MRI images may result in large false positive and false negative labeling when deploying DCNN based methods. In this paper, we propose the Splenomegaly Segmentation Network (SSNet) to address spatial variations when segmenting extraordinarily large spleens. SSNet was designed based on the framework of image-to-image conditional generative adversarial networks (cGAN). Specifically, the Global Convolutional Network (GCN) was used as the generator to reduce false negatives, while the Markovian discriminator (PatchGAN) was used to alleviate false positives. A cohort of clinically acquired 3D MRI scans (both T1 weighted and T2 weighted) from patients with splenomegaly were used to train and test the networks. The experimental results demonstrated that a mean Dice coefficient of 0.9260 and a median Dice coefficient of 0.9262 using SSNet on independently tested MRI volumes of patients with splenomegaly.

Overnight dexamethasone suppression test: a reliable screen for Cushing's syndrome in the obese.

PubMed

Ness-Abramof, Rosane; Nabriski, Dan; Apovian, Caroline M; Niven, Mark; Weiss, Eliahu; Shapiro, Menachem S; Shenkman, Louis

2002-12-01

Reevaluation of the validity of the 1-mg overnight dexamethasone suppression test (ODST) as a screening test for Cushing's syndrome in obese patients. Eighty-six obese patients (body mass index, 30 to 53 kg/m(2)) that were referred to a general endocrine outpatient clinic for evaluation of simple obesity, diabetes mellitus, hypertension, polycystic ovary disease, or pituitary tumor. One milligram dexamethasone was administered orally at 11:00 PM, and serum cortisol levels were measured the following morning between 8:00 AM and 9:00 AM. Suppression of serum cortisol to <80 nM (3 micro g/dL) was chosen as the cut-off point for normal suppression. Patients with serum cortisol levels > or =80 nM were evaluated for Cushing's syndrome. Suppression of morning cortisol levels to <80 nM occurred in 79 of the 86 obese patients. Seven patients had serum cortisol levels higher than 80 nM; five were eventually diagnosed with Cushing's syndrome and two were considered false positive results in view of normal 24-hour free urinary cortisol and normal suppression on a low dose dexamethasone suppression test (0.5 mg of dexamethasone every 6 hours for 2 days). We found a false positive rate of 2.3% for the ODST using a cut-off serum cortisol of 80 nM. The ODST is a valid screening test for Cushing's syndrome in the obese population. The false positive rate was 2.3%, even when using a strict cut-off serum cortisol of 80 nM. Abnormal cortisol suppression in obese patients should be investigated and not be considered false positive results.

Computerized mass detection in whole breast ultrasound images: reduction of false positives using bilateral subtraction technique

NASA Astrophysics Data System (ADS)

Ikedo, Yuji; Fukuoka, Daisuke; Hara, Takeshi; Fujita, Hiroshi; Takada, Etsuo; Endo, Tokiko; Morita, Takako

2007-03-01

The comparison of left and right mammograms is a common technique used by radiologists for the detection and diagnosis of masses. In mammography, computer-aided detection (CAD) schemes using bilateral subtraction technique have been reported. However, in breast ultrasonography, there are no reports on CAD schemes using comparison of left and right breasts. In this study, we propose a scheme of false positive reduction based on bilateral subtraction technique in whole breast ultrasound images. Mass candidate regions are detected by using the information of edge directions. Bilateral breast images are registered with reference to the nipple positions and skin lines. A false positive region is detected based on a comparison of the average gray values of a mass candidate region and a region with the same position and same size as the candidate region in the contralateral breast. In evaluating the effectiveness of the false positive reduction method, three normal and three abnormal bilateral pairs of whole breast images were employed. These abnormal breasts included six masses larger than 5 mm in diameter. The sensitivity was 83% (5/6) with 13.8 (165/12) false positives per breast before applying the proposed reduction method. By applying the method, false positives were reduced to 4.5 (54/12) per breast without removing a true positive region. This preliminary study indicates that the bilateral subtraction technique is effective for improving the performance of a CAD scheme in whole breast ultrasound images.

BlackOPs: increasing confidence in variant detection through mappability filtering.

PubMed

Cabanski, Christopher R; Wilkerson, Matthew D; Soloway, Matthew; Parker, Joel S; Liu, Jinze; Prins, Jan F; Marron, J S; Perou, Charles M; Hayes, D Neil

2013-10-01

Identifying variants using high-throughput sequencing data is currently a challenge because true biological variants can be indistinguishable from technical artifacts. One source of technical artifact results from incorrectly aligning experimentally observed sequences to their true genomic origin ('mismapping') and inferring differences in mismapped sequences to be true variants. We developed BlackOPs, an open-source tool that simulates experimental RNA-seq and DNA whole exome sequences derived from the reference genome, aligns these sequences by custom parameters, detects variants and outputs a blacklist of positions and alleles caused by mismapping. Blacklists contain thousands of artifact variants that are indistinguishable from true variants and, for a given sample, are expected to be almost completely false positives. We show that these blacklist positions are specific to the alignment algorithm and read length used, and BlackOPs allows users to generate a blacklist specific to their experimental setup. We queried the dbSNP and COSMIC variant databases and found numerous variants indistinguishable from mapping errors. We demonstrate how filtering against blacklist positions reduces the number of potential false variants using an RNA-seq glioblastoma cell line data set. In summary, accounting for mapping-caused variants tuned to experimental setups reduces false positives and, therefore, improves genome characterization by high-throughput sequencing.

Plausibility assessment of a 2-state self-paced mental task-based BCI using the no-control performance analysis.

PubMed

Faradji, Farhad; Ward, Rabab K; Birch, Gary E

2009-06-15

The feasibility of having a self-paced brain-computer interface (BCI) based on mental tasks is investigated. The EEG signals of four subjects performing five mental tasks each are used in the design of a 2-state self-paced BCI. The output of the BCI should only be activated when the subject performs a specific mental task and should remain inactive otherwise. For each subject and each task, the feature coefficient and the classifier that yield the best performance are selected, using the autoregressive coefficients as the features. The classifier with a zero false positive rate and the highest true positive rate is selected as the best classifier. The classifiers tested include: linear discriminant analysis, quadratic discriminant analysis, Mahalanobis discriminant analysis, support vector machine, and radial basis function neural network. The results show that: (1) some classifiers obtained the desired zero false positive rate; (2) the linear discriminant analysis classifier does not yield acceptable performance; (3) the quadratic discriminant analysis classifier outperforms the Mahalanobis discriminant analysis classifier and performs almost as well as the radial basis function neural network; and (4) the support vector machine classifier has the highest true positive rates but unfortunately has nonzero false positive rates in most cases.

Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation.

PubMed

Nelson, Heidi D; Pappas, Miranda; Cantor, Amy; Griffin, Jessica; Daeges, Monica; Humphrey, Linda

2016-02-16

In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure. MEDLINE and Cochrane databases through December 2014. English-language systematic reviews, randomized trials, and observational studies of screening. Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus. Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer-specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100,000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone. Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models. False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely. Agency for Healthcare Research and Quality.

Comparison of results for morphine urinalyses by radioimmunoassay and thin-layer chromatography in a narcotic clinic setting.

PubMed

Kokoski, R J; Jain, M

1975-03-01

Radioimmunoassay (RIA) and thin-layer chromatography (TLC) were compared for morphine detection in an actual narcotic clinic setting. A choice of urines from all those screened by TLC allowed a critical comparison as to actual use or non-use of narcotic drugs, rather than a sampling at random in which the question of possible false positives or negatives cannot be conclusively answered. Although RIA is more sensitive than TLC, its advantage is apparent only in those cases where urine specimens are difficult to obtain frequently regularly or where the use of morphine is suspected by the positive identification of quinine in urine that was morphine-negative by TLC. In a selected group of negative and positive specimens chosen without conscious bias, the two methods gave consistently similar results, indicating that the modified TLC method provided a few or no false positives or negatives if the negatives were from those cases that were not positive anytime up to 3-4 days before urine collection. We conclude that RIA can be of significant value as a supplement to a TLC screening program, without sacrificing the many advantages that TLC has to offer.

Evaluation of fluorescent-antibody tests as a means of confirming infant botulism.

PubMed Central

Glasby, C; Hatheway, C L

1984-01-01

Fluorescent-antibody techniques were evaluated for confirming infant botulism. Seventy-seven stool specimens from suspected cases were examined. All 34 specimens containing viable Clostridium botulinum at time of study gave positive results (29 on direct smears and 34 on enrichments). Two false-positive reactions were observed. Images PMID:6394626

Accuracy of self-reports of fecal occult blood tests and test results among individuals in the carpentry trade.

PubMed

Lipkus, Isaac M; Samsa, Gregory P; Dement, John; Skinner, Celette Sugg; Green, La Sonya G; Pompeii, Lisa; Ransohoff, David F

2003-11-01

Inaccuracy in self-reports of colorectal cancer (CRC) screening procedures (e.g., over- or underreporting) may interfere with individuals adhering to appropriate screening intervals, and can blur the true effects of physician recommendations to screen and the effects of interventions designed to promote screening. We assessed accuracy of self-report of having a fecal occult blood test (FOBT) within a 1-year window based on receipt of FOBT kits among individuals aged 50 and older in the carpentry trade (N = 658) who were off-schedule for having had a FOBT. Indices of evaluating accuracy of self-reports (concordance, specificity, false-positive and false-negative rates) were calculated relative to receipt of a mailed FOBT. Among those who mailed a completed FOBT, we assessed accuracy of reporting the test result. Participants underestimated having performed a FOBT (false-negative rate of 44%). Accuracy was unrelated to perceptions of getting or worrying about CRC or family history. Self-reports of having a negative FOBT result more consistently matched the laboratory result (specificity 98%) than having a positive test result (sensitivity 63%). Contrary to other findings, participants under- rather than over reported FOBT screening. Results suggest greater efforts are needed to enhance accurate recall of FOBT screening.

Sherlock Holmes and child psychopathology assessment approaches: the case of the false-positive.

PubMed

Jensen, P S; Watanabe, H

1999-02-01

To explore the relative value of various methods of assessing childhood psychopathology, the authors compared 4 groups of children: those who met criteria for one or more DSM diagnoses and scored high on parent symptom checklists, those who met psychopathology criteria on either one of these two assessment approaches alone, and those who met no psychopathology assessment criterion. Parents of 201 children completed the Child Behavior Checklist (CBCL), after which children and parents were administered the Diagnostic Interview Schedule for Children (version 2.1). Children and parents also completed other survey measures and symptom report inventories. The 4 groups of children were compared against "external validators" to examine the merits of "false-positive" and "false-negative" cases. True-positive cases (those that met DSM criteria and scored high on the CBCL) differed significantly from the true-negative cases on most external validators. "False-positive" and "false-negative" cases had intermediate levels of most risk factors and external validators. "False-positive" cases were not normal per se because they scored significantly above the true-negative group on a number of risk factors and external validators. A similar but less marked pattern was noted for "false-negatives." Findings call into question whether cases with high symptom checklist scores despite no formal diagnoses should be considered "false-positive." Pending the availability of robust markers for mental illness, researchers and clinicians must resist the tendency to reify diagnostic categories or to engage in arcane debates about the superiority of one assessment approach over another.

Retrospective imaging study on the diagnosis of pathological false positive iodine-131 scans in patients with thyroid cancer.

PubMed

Jia, Qiang; Meng, Zhaowei; Tan, Jian; Zhang, Guizhi; He, Yajing; Sun, Haoran; Yu, Chunshui; Li, Dong; Zheng, Wei; Wang, Renfei; Wang, Shen; Li, Xue; Zhang, Jianping; Hu, Tianpeng; Liu, N A; Upadhyaya, Arun

2015-11-01

Iodine-131 (I-131) therapy and post-therapy I-131 scanning are essential in the management of differentiated thyroid cancer (DTC). However, pathological false positive I-131 scans can lead to misdiagnosis and inappropriate I-131 treatment. This retrospective study aimed to investigate the best imaging modality for the diagnosis of pathological false positive I-131 scans in a DTC patient cohort, and to determine its incidence. DTC patient data archived from January 2008 to January 2010 was retrieved. Post-therapeutic I-131 scans were conducted and interpreted. The imaging modalities of magnetic resonance imaging (MRI), computed tomography and ultrasonography were applied and compared to check all suspected lesions. Biopsy or needle aspiration was conducted for patients who consented to the acquisition of histopathological confirmation. Data for 156 DTC patients were retrieved. Only 6 cases of pathological false-positives were found among these (incidence, 3.85%), which included 3 cases of thymic hyperplasia in the mediastinum, 1 case of pleomorphic adenoma in the parapharyngeal space and 1 case of thyroglossal duct cyst in the neck. MRI was demonstrated as the best imaging modality for diagnosis due to its superior soft tissue resolution. However, no imaging modality was able to identify the abdominal false positive-lesions observed in 2 cases, one of whom also had thymic hyperplasia. In conclusion, pathological false positive I-131 scans occurred with an incidence of 3.85%. MRI was the best imaging modality for diagnosing these pathological false-positives.

Accurate indel prediction using paired-end short reads

PubMed Central

2013-01-01

Background One of the major open challenges in next generation sequencing (NGS) is the accurate identification of structural variants such as insertions and deletions (indels). Current methods for indel calling assign scores to different types of evidence or counter-evidence for the presence of an indel, such as the number of split read alignments spanning the boundaries of a deletion candidate or reads that map within a putative deletion. Candidates with a score above a manually defined threshold are then predicted to be true indels. As a consequence, structural variants detected in this manner contain many false positives. Results Here, we present a machine learning based method which is able to discover and distinguish true from false indel candidates in order to reduce the false positive rate. Our method identifies indel candidates using a discriminative classifier based on features of split read alignment profiles and trained on true and false indel candidates that were validated by Sanger sequencing. We demonstrate the usefulness of our method with paired-end Illumina reads from 80 genomes of the first phase of the 1001 Genomes Project ( http://www.1001genomes.org) in Arabidopsis thaliana. Conclusion In this work we show that indel classification is a necessary step to reduce the number of false positive candidates. We demonstrate that missing classification may lead to spurious biological interpretations. The software is available at: http://agkb.is.tuebingen.mpg.de/Forschung/SV-M/. PMID:23442375

Azithromycin treatment failure for Chlamydia trachomatis among heterosexual men with nongonococcal urethritis

PubMed Central

Kissinger, Patricia; White, Scott; Manhart, Lisa E.; Schwebke, Jane; Taylor, Stephanie N; Mena, Leandro; Khosropour, Christine M; Wilcox, Larissa; Schmidt, Norine; Martin, David H

2016-01-01

Background Three recent prospective studies have suggested that the 1 g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%–22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to re-examine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. Methods Men who had sex with women, who received 1 g azithromycin under directly observed therapy (DOT) for presumptive treatment of nongonococcal urethritis (NGU) with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine and TOC screening was performed on urine using nucleic acid amplification tests (NAAT). Post-treatment vaginal sexual exposure was elicited at TOC. Data from the three studies was obtained and re-analyzed. Rates of Ct re-test positive were examined for all cases and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. Results The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). Conclusion In these samples of men who have sex with women with Ct-related NGU, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization’s target chlamydia treatment failure rate of < 5%. PMID:27631353

Guess LOD approach: sufficient conditions for robustness.

PubMed

Williamson, J A; Amos, C I

1995-01-01

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012–2013

PubMed Central

Zucker, Jane R.; Giancotti, Francesca R.; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L.; Rosen, Jennifer B.

2017-01-01

ABSTRACT The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. PMID:28701468

[Evaluation of quality of HIV diagnostic procedures in Poland].

PubMed

Parczewski, Miłosz; Madaliński, Kazimierz; Leszczyszyn-Pynka, Magdalena; Boroń-Kaczmarska, Anna

2010-01-01

The aim of this work was quality assessment of HIV diagnostic procedures in Poland, including human and technical resources as well as laboratory practice. Sixty questionnaires were distributed among diagnostic centers to obtain qualitative data. Basing on the survey data serological control using coded panels of HIV-1/2 samples was performed. Thirty-one filled questionnaires were received (50.8%). Surveyed laboratories perform from 350 to 5500 serological screening tests per year. In most of laboratories fourth generation assays are available, while Blood Donation Centers screen the blood both with serological assays and by HIV-RNA detection. Sanitary and Epidemiological Stations and academic laboratories hold the ISO/IEC 17025 or IS0 9001:2001 accreditation, five of the surveyed centers participate in Labquality assurance and two in Quality Control in Molecular Diagnostics programs. Data of control serological testing were received from 21 centers. In the quality control assessment 194 analyses were performed with 91 true negative, 2 false negative, 96 true positive and 5 false positive results. False negative rate of % and false positive rate of 5.2% was noted for this study. Currently, virtually no guidelines related to the HIV-diagnostics quality assurance and control in Poland are in delineated. Development of the national unified quality control system, basing on the central institution is highly desirable. National certification within the frames of the quality control and assurance program should be mandatory for all the diagnostic labs, and aim at improvement of reliability of the result distributed among clinicians and patients.

The efficacy of protoporphyrin as a predictive biomarker for lead exposure in canvasback ducks: effect of sample storage time

USGS Publications Warehouse

Franson, J.C.; Hohman, W.L.; Moore, J.L.; Smith, M.R.

1996-01-01

We used 363 blood samples collected from wild canvasback dueks (Aythya valisineria) at Catahoula Lake, Louisiana, U.S.A. to evaluate the effect of sample storage time on the efficacy of erythrocytic protoporphyrin as an indicator of lead exposure. The protoporphyrin concentration of each sample was determined by hematofluorometry within 5 min of blood collection and after refrigeration at 4 °C for 24 and 48 h. All samples were analyzed for lead by atomic absorption spectrophotometry. Based on a blood lead concentration of ≥0.2 ppm wet weight as positive evidence for lead exposure, the protoporphyrin technique resulted in overall error rates of 29%, 20%, and 19% and false negative error rates of 47%, 29% and 25% when hematofluorometric determinations were made on blood at 5 min, 24 h, and 48 h, respectively. False positive error rates were less than 10% for all three measurement times. The accuracy of the 24-h erythrocytic protoporphyrin classification of blood samples as positive or negative for lead exposure was significantly greater than the 5-min classification, but no improvement in accuracy was gained when samples were tested at 48 h. The false negative errors were probably due, at least in part, to the lag time between lead exposure and the increase of blood protoporphyrin concentrations. False negatives resulted in an underestimation of the true number of canvasbacks exposed to lead, indicating that hematofluorometry provides a conservative estimate of lead exposure.

How Reliable Is the Alpha-defensin Immunoassay Test for Diagnosing Periprosthetic Joint Infection? A Prospective Study.

PubMed

Bonanzinga, Tommaso; Zahar, Akos; Dütsch, Michael; Lausmann, Christian; Kendoff, Daniel; Gehrke, Thorsten

2017-02-01

A key issue in the treatment of periprosthetic joint infection (PJI) is the correct diagnosis. The main problem is lack of diagnostic tools able to diagnose a PJI with high accuracy. Alpha-defensin has been proposed as a possible solution, but in the current literature, there is a lack of independent validation. We performed a prospective study to determine (1) what is the sensitivity, specificity, and positive and the negative predictive values of the alpha-defensin immunoassay test in diagnosing PJI; and (2) which clinical features may be responsible for false-positive and false-negative results? Preoperative aspiration was performed in all patients presenting with a painful hip/knee arthroplasty, including both primary and revision implants. Metallosis, other inflammatory comorbidities, and previous/concomitant antibiotic therapy were not considered as exclusion criteria. An inadequate amount of synovial fluid for culture was an exclusion criterion. A total of 156 patients (65 knees, 91 hips) were included in this prospective study. At the time of revision, synovial fluid samples were taken to perform the alpha-defensin assay. During surgical débridement of tissue, samples for cultures and histologic evaluation were taken, and samples were cultured until positive or until negative at 14 days. A diagnosis of PJI was confirmed in 29 patients according to the International Consensus Group on PJI. The sensitivity of the alpha-defensin immunoassay was 97% (95% confidence interval [CI], 92%-99%), the specificity was 97% (95% CI, 92%-99%), the positive predictive value was 88% (95% CI, 81%-92%), and the negative predictive value was 99% (95% CI, 96%-99%). Among four false-positive patients, two had metallosis and one had polyethylene wear. The false-negative case presented with a draining sinus, and intraoperative cultures were also negative. Alpha-defensin assay appears to be a reliable test, but followup evaluation is needed to estimate longer term performance of the test. The authors believe that alpha-defensin has demonstrated itself to be sufficiently robust that PJI diagnostic criteria now should include this test. Future studies are needed to compare the differences among the diagnostic capability of the available tests, in particular when metallosis is present, because metallosis may predispose the test to a false-positive result. Level I, diagnostic study.

Histoplasma Urinary Antigen Testing Obviates the Need for Coincident Serum Antigen Testing.

PubMed

Libert, Diane; Procop, Gary W; Ansari, Mohammad Q

2018-03-07

Serum and urine antigen (SAg, UAg) detection are common tests for Histoplasma capsulatum. UAg detection is more widely used and reportedly has a higher sensitivity. We investigated whether SAg detection contributes meaningfully to the initial evaluation of patients with suspected histoplasmosis. We reviewed 20,285 UAg and 1,426 SAg tests ordered from 1997 to 2016 and analyzed paired UAg and SAg tests completed on the same patient within 1 week. We determined the positivity rate for each test. Of 601 paired specimens, 542 were concurrent negatives and 48 were concurrent positives (98% agreement). Medical records were available for eight of 11 pairs with discrepant results. UAg was falsely positive in six instances, truly positive once, and falsely negative once. These findings support using a single antigen detection test, rather than both UAg and SAg, as an initial screen for suspected histoplasmosis. This aligns with the current practice of most physicians.

Quantification of human epidermal growth factor receptor 2 immunohistochemistry using the Ventana Image Analysis System: correlation with gene amplification by fluorescence in situ hybridization: the importance of instrument validation for achieving high (>95%) concordance rate.

PubMed

Dennis, Jake; Parsa, Rezvaneh; Chau, Donnie; Koduru, Prasad; Peng, Yan; Fang, Yisheng; Sarode, Venetia Rumnong

2015-05-01

The use of computer-based image analysis for scoring human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) has gained a lot of interest recently. We investigated the performance of the Ventana Image Analysis System (VIAS) in HER2 quantification by IHC and its correlation with fluorescence in situ hybridization (FISH). We specifically compared the 3+ IHC results using the manufacturer's machine score cutoffs versus laboratory-defined cutoffs with the FISH assay. Using the manufacturer's 3+ cutoff (VIAS score; 2.51 to 3.5), 181/536 (33.7%) were scored 3+, and FISH was positive in 147/181 (81.2%), 2 (1.1%) were equivocal, and 32 (17.6%) were FISH (-). Using the laboratory-defined 3+ cutoff (VIAS score 3.5), 52 (28.7%) cases were downgraded to 2+, of which 29 (55.7%) were FISH (-), and 23 (44.2%) were FISH (+). With the revised cutoff, there were improvements in the concordance rate from 89.1% to 97.0% and in the positive predictive value from 82.1% to 97.6%. The false-positive rate for 3+ decreased from 9.0% to 0.8%. Six of 175 (3.4%) IHC (-) cases were FISH (+). Three cases with a VIAS score 3.5 showed polysomy of chromosome 17. In conclusion, the VIAS may be a valuable tool for assisting pathologists in HER2 scoring; however, the positive cutoff defined by the manufacturer is associated with a high false-positive rate. This study highlights the importance of instrument validation/calibration to reduce false-positive results.

Solid pulmonary nodule risk assessment and decision analysis: comparison of four prediction models in 285 cases.

PubMed

Perandini, Simone; Soardi, Gian Alberto; Motton, Massimiliano; Rossi, Arianna; Signorini, Manuel; Montemezzi, Stefania

2016-09-01

The aim of this study was to compare classification results from four major risk prediction models in a wide population of incidentally detected solitary pulmonary nodules (SPNs) which were selected to crossmatch inclusion criteria for the selected models. A total of 285 solitary pulmonary nodules with a definitive diagnosis were evaluated by means of four major risk assessment models developed from non-screening populations, namely the Mayo, Gurney, PKUPH and BIMC models. Accuracy was evaluated by receiver operating characteristic (ROC) area under the curve (AUC) analysis. Each model's fitness to provide reliable help in decision analysis was primarily assessed by adopting a surgical threshold of 65 % and an observation threshold of 5 % as suggested by ACCP guidelines. ROC AUC values, false positives, false negatives and indeterminate nodules were respectively 0.775, 3, 8, 227 (Mayo); 0.794, 41, 6, 125 (Gurney); 0.889, 42, 0, 144 (PKUPH); 0.898, 16, 0, 118 (BIMC). Resultant data suggests that the BIMC model may be of greater help than Mayo, Gurney and PKUPH models in preoperative SPN characterization when using ACCP risk thresholds because of overall better accuracy and smaller numbers of indeterminate nodules and false positive results. • The BIMC and PKUPH models offer better characterization than older prediction models • Both the PKUPH and BIMC models completely avoided false negative results • The Mayo model suffers from a large number of indeterminate results.

Characteristics of enzyme-linked immunosorbent assay for detection of IgG antibodies specific to Сhlamydia trachomatis heat shock protein (HSP-60)

PubMed

Galkin, O Yu; Besarab, A B; Lutsenko, T N

2017-01-01

The goal of this work was to study sensitivity and specificity of the developed ELISA set for the identification of IgG antibodies against Chlamydia trachomatis HSP-60 (using biotinylated tyramine-based signal amplification system). The study was conducted using a panel of characterized sera, as well as two reference ELISA sets of similar purpose. According to the results of ELISA informative value parameters, the ELISA we have developed showed the highest specificity and sensitivity parameters (no false negative or false positive results were registered). In 4 out of 15 intralaboratory panel serum samples initially identified as negative, anti-HSP-60 IgG-antibodies test result in reference ELISA sets upon dilution changed from negative to positive. The nature of titration curves of false negative sera and commercial monoclonal antibodies А57-В9 against C. trachomatis HSP-60 after incubation for 24 h was indicative of the presence of anti-idiotypic antibodies in these samples. Upon sera dilution, idiotypic-anti-idiotypic complexes dissociated, which caused the change of test result. High informative value of the developed ELISA set for identification of IgG antibodies against C. trachomatis HSP-60 has been proven. Anti-idiotypic antibodies possessing C. trachomatis anti-HSP-60 activity and being one of the causes of false negative results of the relevant ELISA-based tests have been identified in blood sera of individuals infected with chlamydial genitourinary infection agents.

Working memory affects false memory production for emotional events.

PubMed

Mirandola, Chiara; Toffalini, Enrico; Ciriello, Alfonso; Cornoldi, Cesare

2017-01-01

Whereas a link between working memory (WM) and memory distortions has been demonstrated, its influence on emotional false memories is unclear. In two experiments, a verbal WM task and a false memory paradigm for negative, positive or neutral events were employed. In Experiment 1, we investigated individual differences in verbal WM and found that the interaction between valence and WM predicted false recognition, with negative and positive material protecting high WM individuals against false remembering; the beneficial effect of negative material disappeared in low WM participants. In Experiment 2, we lowered the WM capacity of half of the participants with a double task request, which led to an overall increase in false memories; furthermore, consistent with Experiment 1, the increase in negative false memories was larger than that of neutral or positive ones. It is concluded that WM plays a critical role in determining false memory production, specifically influencing the processing of negative material.

Characterization of Exoplanet Atmospheres and Kepler Planet Candidates with Multi-Color Photometry from the Gran Telescopio Canarias

NASA Astrophysics Data System (ADS)

Colon, Knicole; Ford, E. B.

2012-01-01

With over 180 confirmed transiting exoplanets and NASA's Kepler mission's recent discovery of over 1200 transiting exoplanet candidates, we can conduct detailed investigations into the (i) properties of exoplanet atmospheres and (ii) false positive rates for planet search surveys. To aid these investigations, we developed a novel technique of using the Optical System for Imaging and low Resolution Integrated Spectroscopy (OSIRIS) installed on the 10.4-meter Gran Telescopio Canarias (GTC) to acquire near-simultaneous multi-color photometry of (i) HD 80606b in bandpasses around the potassium (K I) absorption feature, (ii) GJ 1214b in bandpasses around a possible methane absorption feature and (iii) several Kepler planet candidates. For HD 80606b, we measure a significant color change during transit between wavelengths that probe the K I line core and the K I wing, equivalent to a 4.2% change in the apparent planetary radius. We hypothesize that the excess absorption may be due to K I in a high-speed wind being driven from the exoplanet's exosphere. This is one of the first detections of K I in an exoplanet atmosphere. For GJ 1214b, we compare the transit depths measured "on” and "off” a possible methane absorption feature and use our results to help resolve conflicting results from other studies regarding the composition of this super-Earth-size planet's atmosphere. For Kepler candidates, we use the color change during transit to reject candidates that are false positives (e.g., a blend with an eclipsing binary either in the background/foreground or bound to the target star). We target small planets (<6 Earth radii) with short orbital periods (<6 days), since eclipsing binaries can mimic planets in this regime. Our results include identification of two false positives and test recent predictions of the false positive rates for the Kepler sample. This research demonstrates the value of the GTC for exoplanet follow-up.

Limitations of Rapid Diagnostic Testing in Patients with Suspected Malaria: A Diagnostic Accuracy Evaluation from Swaziland, a Low-Endemicity Country Aiming for Malaria Elimination

PubMed Central

Ranadive, Nikhil; Kunene, Simon; Darteh, Sarah; Ntshalintshali, Nyasatu; Nhlabathi, Nomcebo; Dlamini, Nomcebo; Chitundu, Stanley; Saini, Manik; Murphy, Maxwell; Soble, Adam; Schwartz, Alanna; Greenhouse, Bryan

2017-01-01

Abstract Background. The performance of Plasmodium falciparum–specific histidine-rich protein 2–based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Methods. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2–based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. Results. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. Conclusions. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts. PMID:28369268

The Relations Between False Positive and Negative Screens and Smoking Cessation and Relapse in the National Lung Screening Trial: Implications for Public Health.

PubMed

Clark, Melissa A; Gorelick, Jeremy J; Sicks, JoRean D; Park, Elyse R; Graham, Amanda L; Abrams, David B; Gareen, Ilana F

2016-01-01

Lung screening is an opportunity for smoking cessation and relapse prevention, but smoking behaviors may differ across screening results. Changes in smoking were evaluated among 18 840 current and former smokers aged 55-74 scheduled to receive three annual lung screenings. Participants were randomized to low-dose computed tomography or single-view chest radiography in the American College of Radiology/National Lung Screening Trial. Outcome measures included point and sustained (6-month) abstinence and motivation to quit among smokers; and relapse among smokers who quit during follow-up, recent quitters (quit < 6 months), and long-term former smokers (quit ≥ 6 months). During five years of follow-up, annual point prevalence quit rates ranged from 11.6%-13.4%; 48% of current smokers reported a quit attempt and 7% of long-term former smokers relapsed. Any false positive screening result was associated with subsequent increased point (multivariable hazard ratio HR = 1.23, 95% CI = 1.13, 1.35) and sustained (HR = 1.28, 95% CI = 1.15, 1.43) abstinence among smokers. Recent quitters with ≥1 false positive screen were less likely to relapse (HR = 0.72, 95% CI = 0.54, 0.96). Screening result was not associated with relapse among long-term former smokers or among baseline smokers who quit during follow-up. A false positive screen was associated with increased smoking cessation and less relapse among recent quitters. Consistently negative screens were not associated with greater relapse among long-term former smokers. Given the Affordable Care Act requires most health plans to cover smoking cessation and lung screening, the impact and cost-effectiveness of lung screening could be further enhanced with the addition of smoking cessation interventions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Towards Risk-Based Test Protocols: Estimating the Contribution of Intensive Testing to the UK Bovine Tuberculosis Problem

PubMed Central

van Dijk, Jan

2013-01-01

Eradicating disease from livestock populations involves the balancing act of removing sufficient numbers of diseased animals without removing too many healthy individuals in the process. As ever more tests for bovine tuberculosis (BTB) are carried out on the UK cattle herd, and each positive herd test triggers more testing, the question arises whether ‘false positive’ results contribute significantly to the measured BTB prevalence. Here, this question is explored using simple probabilistic models of test behaviour. When the screening test is applied to the average UK herd, the estimated proportion of test-associated false positive new outbreaks is highly sensitive to small fluctuations in screening test specificity. Estimations of this parameter should be updated as a priority. Once outbreaks have been confirmed in screening-test positive herds, the following rounds of intensive testing with more sensitive, albeit less specific, tests are highly likely to remove large numbers of false positive animals from herds. Despite this, it is unlikely that significantly more truly infected animals are removed. BTB test protocols should become based on quantified risk in order to prevent the needless slaughter of large numbers of healthy animals. PMID:23717517

Challenges associated with post-deployment screening for mild traumatic brain injury in military personnel.

PubMed

Iverson, Grant L; Langlois, Jean A; McCrea, Michael A; Kelly, James P

2009-11-01

There is ongoing debate regarding the epidemiology of mild traumatic brain injury (MTBI) in military personnel. Accurate and timely estimates of the incidence of brain injury and the prevalence of long-term problems associated with brain injuries among active duty service members and veterans are essential for (a) operational planning, and (b) to allocate sufficient resources for rehabilitation and ongoing services and supports. The purpose of this article is to discuss challenges associated with post-deployment screening for MTBI. Multiple screening methods have been used in military, Veterans Affairs, and independent studies, which complicate cross-study comparisons of the resulting epidemiological data. We believe that post-deployment screening is important and necessary--but no screening methodology will be flawless, and false positives and false negatives are inevitable. Additional research is necessary to refine the sequential screening methodology, with the goal of minimizing false negatives during initial post-deployment screening and minimizing false positives during follow-up evaluations.

Can We Forget What We Know in a False-Belief Task? An Investigation of the True-Belief Default.

PubMed

Rubio-Fernández, Paula

2017-01-01

It has been generally assumed in the Theory of Mind literature of the past 30 years that young children fail standard false-belief tasks because they attribute their own knowledge to the protagonist (what Leslie and colleagues called a "true-belief default"). Contrary to the traditional view, we have recently proposed that the children's bias is task induced. This alternative view was supported by studies showing that 3 year olds are able to pass a false-belief task that allows them to focus on the protagonist, without drawing their attention to the target object in the test phase. For a more accurate comparison of these two accounts, the present study tested the true-belief default with adults. Four experiments measuring eye movements and response inhibition revealed that (a) adults do not have an automatic tendency to respond to the false-belief question according to their own knowledge and (b) the true-belief response need not be inhibited in order to correctly predict the protagonist's actions. The positive results observed in the control conditions confirm the accuracy of the various measures used. I conclude that the results of this study undermine the true-belief default view and those models that posit mechanisms of response inhibition in false-belief reasoning. Alternatively, the present study with adults and recent studies with children suggest that participants' focus of attention in false-belief tasks may be key to their performance. Copyright © 2015 Cognitive Science Society, Inc.

Classification of radiological errors in chest radiographs, using support vector machine on the spatial frequency features of false- negative and false-positive regions

NASA Astrophysics Data System (ADS)

Pietrzyk, Mariusz W.; Donovan, Tim; Brennan, Patrick C.; Dix, Alan; Manning, David J.

2011-03-01

Aim: To optimize automated classification of radiological errors during lung nodule detection from chest radiographs (CxR) using a support vector machine (SVM) run on the spatial frequency features extracted from the local background of selected regions. Background: The majority of the unreported pulmonary nodules are visually detected but not recognized; shown by the prolonged dwell time values at false-negative regions. Similarly, overestimated nodule locations are capturing substantial amounts of foveal attention. Spatial frequency properties of selected local backgrounds are correlated with human observer responses either in terms of accuracy in indicating abnormality position or in the precision of visual sampling the medical images. Methods: Seven radiologists participated in the eye tracking experiments conducted under conditions of pulmonary nodule detection from a set of 20 postero-anterior CxR. The most dwelled locations have been identified and subjected to spatial frequency (SF) analysis. The image-based features of selected ROI were extracted with un-decimated Wavelet Packet Transform. An analysis of variance was run to select SF features and a SVM schema was implemented to classify False-Negative and False-Positive from all ROI. Results: A relative high overall accuracy was obtained for each individually developed Wavelet-SVM algorithm, with over 90% average correct ratio for errors recognition from all prolonged dwell locations. Conclusion: The preliminary results show that combined eye-tracking and image-based features can be used for automated detection of radiological error with SVM. The work is still in progress and not all analytical procedures have been completed, which might have an effect on the specificity of the algorithm.

Improving sensitivity in proteome studies by analysis of false discovery rates for multiple search engines

PubMed Central

Jones, Andrew R.; Siepen, Jennifer A.; Hubbard, Simon J.; Paton, Norman W.

2010-01-01

Tandem mass spectrometry, run in combination with liquid chromatography (LC-MS/MS), can generate large numbers of peptide and protein identifications, for which a variety of database search engines are available. Distinguishing correct identifications from false positives is far from trivial because all data sets are noisy, and tend to be too large for manual inspection, therefore probabilistic methods must be employed to balance the trade-off between sensitivity and specificity. Decoy databases are becoming widely used to place statistical confidence in results sets, allowing the false discovery rate (FDR) to be estimated. It has previously been demonstrated that different MS search engines produce different peptide identification sets, and as such, employing more than one search engine could result in an increased number of peptides being identified. However, such efforts are hindered by the lack of a single scoring framework employed by all search engines. We have developed a search engine independent scoring framework based on FDR which allows peptide identifications from different search engines to be combined, called the FDRScore. We observe that peptide identifications made by three search engines are infrequently false positives, and identifications made by only a single search engine, even with a strong score from the source search engine, are significantly more likely to be false positives. We have developed a second score based on the FDR within peptide identifications grouped according to the set of search engines that have made the identification, called the combined FDRScore. We demonstrate by searching large publicly available data sets that the combined FDRScore can differentiate between between correct and incorrect peptide identifications with high accuracy, allowing on average 35% more peptide identifications to be made at a fixed FDR than using a single search engine. PMID:19253293

False-positive LSD testing in urine samples from intensive care patients.

PubMed

Röhrich, J; Zörntlein, S; Lotz, J; Becker, J; Kern, T; Rittner, C

1998-09-01

Unexpected positive results for lysergic acid diethylamide (LSD) were found in urine samples from 12 patients in an intensive care unit in a routine screening using the CEDIA DAU assay. None of these test results could be confirmed by high-performance liquid chromatography analysis, but all samples contained the mucolytic drug ambroxol. Further studies demonstrated that ambroxol exhibits a significant cross-reactivity in the CEDIA DAU LSD assay. Therefore, positive LSD results obtained with the CEDIA DAU assay have to be critically evaluated, particularly during the cold season, when infections of the respiratory tract often result in more frequent use of mucolytic medications.

Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the Detect Fluid Early from Intrathoracic Impedance Monitoring study).

PubMed

Heist, E Kevin; Herre, John M; Binkley, Philip F; Van Bakel, Adrian B; Porterfield, James G; Porterfield, Linda M; Qu, Fujian; Turkel, Melanie; Pavri, Behzad B

2014-10-15

Detect Fluid Early from Intrathoracic Impedance Monitoring (DEFEAT-PE) is a prospective, multicenter study of multiple intrathoracic impedance vectors to detect pulmonary congestion (PC) events. Changes in intrathoracic impedance between the right ventricular (RV) coil and device can (RVcoil→Can) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs (CRT-Ds) are used clinically for the detection of PC events, but other impedance vectors and algorithms have not been studied prospectively. An initial 75-patient study was used to derive optimal impedance vectors to detect PC events, with 2 vector combinations selected for prospective analysis in DEFEAT-PE (ICD vectors: RVring→Can + RVcoil→Can, detection threshold 13 days; CRT-D vectors: left ventricular ring→Can + RVcoil→Can, detection threshold 14 days). Impedance changes were considered true positive if detected <30 days before an adjudicated PC event. One hundred sixty-two patients were enrolled (80 with ICDs and 82 with CRT-Ds), all with ≥1 previous PC event. One hundred forty-four patients provided study data, with 214 patient-years of follow-up and 139 PC events. Sensitivity for PC events of the prespecified algorithms was as follows: ICD: sensitivity 32.3%, false-positive rate 1.28 per patient-year; CRT-D: sensitivity 32.4%, false-positive rate 1.66 per patient-year. An alternative algorithm, ultimately approved by the US Food and Drug Administration (RVring→Can + RVcoil→Can, detection threshold 14 days), resulted in (for all patients) sensitivity of 21.6% and a false-positive rate of 0.9 per patient-year. The CRT-D thoracic impedance vector algorithm selected in the derivation study was not superior to the ICD algorithm RVring→Can + RVcoil→Can when studied prospectively. In conclusion, to achieve an acceptably low false-positive rate, the intrathoracic impedance algorithms studied in DEFEAT-PE resulted in low sensitivity for the prediction of heart failure events. Copyright © 2014 Elsevier Inc. All rights reserved.

Detection and Species Determination of Malaria Parasites by PCR: Comparison with Microscopy and with ParaSight-F and ICT Malaria Pf Tests in a Clinical Environment

PubMed Central

Tham, Jill M.; Lee, Szu Hee; Tan, Theresa M. C.; Ting, Robert C. Y.; Kara, Ursula A. K.

1999-01-01

A rapid procedure for the diagnosis of malaria infections directly from dried blood spots by PCR amplification was evaluated with samples from 52 patients. Plasmodium infections were identified with a genus-specific primer set, and species differentiation between Plasmodium falciparum and Plasmodium vivax was analyzed by multiplex PCR. The PCR test with any of the three primer sets was able to detect as few as four parasites per microliter by gel electrophoresis or by nonisotopic paper hybridization chromatography. The diagnoses obtained by PCR correlated closely with those obtained by Giemsa staining except for two samples observed to have mixed P. falciparum-P. vivax infections. These were initially missed by microscopic analysis. In comparison with antigen-capture assays for P. falciparum, the PCR assays were able to detect three infections that were missed by the ParaSight-F test. The PCR test was negative for nine ParaSight-F-positive samples and one ICT Malaria Pf-positive sample, and these were confirmed to be false-positive results. The PCR thus gave no false-negative or false-positive results. Patients undergoing antimalarial therapy were also monitored by the PCR assay. Four of seven patients who were PCR positive for P. vivax at the time of discharge were later readmitted to the hospital with a recurrence of P. vivax infection. We would like to propose that PCR is a sensitive and easy method that can serve as a useful addition to microscopy for the diagnosis and the clinical monitoring of treatment of malaria. PMID:10203469

The etiology of Rubella IgM positivity in patients with rubella-like illness in Iran from 2011 to 2013.

PubMed

Khorrami, Seyed Mahmood Seyed; Mokhtari-Azad, Talat; Yavarian, Jila; Nasab, Gazal Sadat Fatemi; Naseri, Maryam; Jandaghi, Nazanin Zahra Shafiei

2015-11-01

Rubella is a mild self-limiting contagious viral disease caused by the rubella virus (RV). Although symptoms are often mild, the concern is centralized around the possible effect on a fetus growth and development in case of primary infection during early months of pregnancy. Recently acquired rubella is commonly confirmed by RV-specific IgM antibody detection in the serum. However, rubella primary infection is not always the only cause of IgM positivity. Other possible causes of rubella IgM positivity may include IgM persistence following vaccination or naturally acquired infection or even re-infection. Moreover, nonspecific IgM reactivity can cause false-positive results. There are few articles to differentiate the aetiology of rash in rubella-like illnesses. However, limited studies have been conducted on clarifying the source of IgM positivity in these cases. This article reports the study of 10,896 clinical cases demonstrating rubella-like illness between 2011 and 2013 in Iran. The rate of IgM positivity among these cases was 0.52% (57 cases). As predicted based on the high coverage of vaccination in Iran fewer than 16% of cases with ELISA IgM positive result, were due to current rubella primary infections. The greater part of the positive IgM reactions occurred in cross reactivity with other viruses (31.6%) or in prolonged IgM response post vaccination (24.6%). This research confirmed that the positive result of rubella IgM assay in vaccinated individuals is mainly caused by prolonged IgM production, rubella re-infection, and false positivity due to infection with other viruses, rather than the rubella primary infection itself. © 2015 Wiley Periodicals, Inc.

Are Hemorrhoids Associated with False-Positive Fecal Immunochemical Test Results?

PubMed

Kim, Nam Hee; Park, Jung Ho; Park, Dong Il; Sohn, Chong Il; Choi, Kyuyong; Jung, Yoon Suk

2017-01-01

False-positive (FP) results of fecal immunochemical tests (FITs) conducted in colorectal cancer (CRC) screening could lead to performing unnecessary colonoscopies. Hemorrhoids are a possible cause of FP FIT results; however, studies on this topic are extremely rare. We investigated whether hemorrhoids are associated with FP FIT results. A retrospective study was conducted at a university hospital in Korea from June 2013 to May 2015. Of the 34547 individuals who underwent FITs, 3946 aged ≥50 years who underwent colonoscopies were analyzed. Logistic regression analysis was performed to determine factors associated with FP FIT results. Among 3946 participants, 704 (17.8%) showed positive FIT results and 1303 (33.0%) had hemorrhoids. Of the 704 participants with positive FIT results, 165 had advanced colorectal neoplasia (ACRN) and 539 had no ACRN (FP results). Of the 1303 participants with hemorrhoids, 291 showed FP results, of whom 81 showed FP results because of hemorrhoids only. Participants with hemorrhoids had a higher rate of FP results than those without hemorrhoids (291/1176, 24.7% vs. 248/2361, 10.5%; p<0.001). Additionally, the participants with hemorrhoids as the only abnormality had a higher rate of FP results than those experiencing no such abnormalities (81/531, 15.3% vs. 38/1173, 3.2%; p<0.001). In multivariate analysis, the presence of hemorrhoids was identified as an independent predictor of FP results (adjusted odds ratio, 2.76; 95% confidence interval, 2.24-3.40; p<0.001). Hemorrhoids are significantly associated with FP FIT results. Their presence seemed to be a non-negligible contributor of FP results in FIT-based CRC screening programs.

p-hacking by post hoc selection with multiple opportunities: Detectability by skewness test?: Comment on Simonsohn, Nelson, and Simmons (2014).

PubMed

Ulrich, Rolf; Miller, Jeff

2015-12-01

Simonsohn, Nelson, and Simmons (2014) have suggested a novel test to detect p-hacking in research, that is, when researchers report excessive rates of "significant effects" that are truly false positives. Although this test is very useful for identifying true effects in some cases, it fails to identify false positives in several situations when researchers conduct multiple statistical tests (e.g., reporting the most significant result). In these cases, p-curves are right-skewed, thereby mimicking the existence of real effects even if no effect is actually present. (c) 2015 APA, all rights reserved).

Bone marrow cells stained by azide-conjugated Alexa fluors in the absence of an alkyne label.

PubMed

Lin, Guiting; Ning, Hongxiu; Banie, Lia; Qiu, Xuefeng; Zhang, Haiyang; Lue, Tom F; Lin, Ching-Shwun

2012-09-01

Thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) has recently been introduced as an alternative to 5-bromo-2-deoxyuridine (BrdU) for cell labeling and tracking. Incorporation of EdU into replicating DNA can be detected by azide-conjugated fluors (eg, Alexa-azide) through a Cu(i)-catalyzed click reaction between EdU's alkyne moiety and azide. While this cell labeling method has proven to be valuable for tracking transplanted stem cells in various tissues, we have found that some bone marrow cells could be stained by Alexa-azide in the absence of EdU label. In intact rat femoral bone marrow, ~3% of nucleated cells were false-positively stained, and in isolated bone marrow cells, ~13%. In contrast to true-positive stains, which localize in the nucleus, the false-positive stains were cytoplasmic. Furthermore, while true-positive staining requires Cu(i), false-positive staining does not. Reducing the click reaction time or reducing the Alexa-azide concentration failed to improve the distinction between true- and false-positive staining. Hematopoietic and mesenchymal stem cell markers CD34 and Stro-1 did not co-localize with the false-positively stained cells, and these cells' identity remains unknown.

[Quality assurance of rapid on-site evaluation of CT-guided fine-needle aspiration cytology of lung nodules].

PubMed

Bak, Mihály; Hidvégi, Judit; Andi, Judit; Bahéry, Mária; Kovács, Eszter; Schneider, Ferenc; Kostic, Szilárd; Rényi-Vámos, Ferenc; Szőke, János; Nyári, Tibor; Gődény, Mária; Kásler, Miklós

2013-01-06

The methods available for the diagnosis of lung cancer include radiologic, cytologic and pathologic procedures. The aim of this study was to determine the quality assurance of CT guided fine needle aspiration cytology of lung nodules. Cytology results were rated to 4 categories (positive; suspicious; negative; not representative). All cytology reports were compared with the final histology diagnosis. A total of 128 patients underwent CT-guided percutaneous fine-needle aspiration biopsy cytology (63 males; 65 females; mean age 62.8 years). Smears were adequate in 99 cases and inadequate in 29 cases. The average diameter of the nodules was 3.28 cm. Thirty three (25.6%) of the cases were histologically verified and 2 falsely negative and 2 falsely positive cases were detected. The sensitivity and the positive predictive value were 88.8% and 88.8%, respectively. Pneumothorax developed in 7 (5.4%) cases. These results suggest that CT-guided transthoracic fine needle aspiration cytology has a high diagnostic accuracy and an acceptable complication rate. The auditing valves of the results meet the proposed threshold values.

False-Positive Results after Environmental Pinworm PCR Testing due to Rhabditid Nematodes in Corncob Bedding

PubMed Central

Leblanc, Mathias; Berry, Kristina; Graciano, Sandy; Becker, Brandon; Reuter, Jon D

2014-01-01

Modern rodent colonies are housed in individually ventilated cages to protect the animals from contamination with adventitious pathogens. Standard health monitoring through soiled-bedding sentinels does not always detect infections, especially in the context of low pathogen prevalence. Recently proposed alternatives include analyzing environmental samples from the cages or rack exhaust by PCR to improve the detection of rodent pathogens but optimal sampling strategies have not yet been established for different microorganisms. Although generally very sensitive and specific, these molecular assays are not foolproof and subject to false-positive and –negative results and should always be interpreted cautiously with an overall understanding of the intrinsic controls and all the variables that may affect the results. Here, we report a limited Aspiculuris tetraptera outbreak in a mouse barrier facility that was detected by fecal PCR in sentinels and confirmed by fecal flotation and direct cecal examination of both sentinels and colony animals. The outbreak led to a widespread survey of all facilities for pinworms by using environmental PCR from ventilated rack exhaust plenums. Environmental PCR suggested an unexpected widespread contamination of all ventilated racks holding nonautoclaved cages, but results could not be confirmed in sentinel or colony animals by fecal flotation, cecal and colonic examination, or cage PCR testing. After additional investigation, the unexpected environmental PCR results were confirmed as false-positive findings due to the nonspecificity of the assay, leading to the amplification of rhabditid nematodes, which are not infectious in rodents but which contaminated the corncob bedding. PMID:25650980

Sustained Performance of a "Physicianless" System of Automated Prehospital STEMI Diagnosis and Catheterization Laboratory Activation.

PubMed

Potter, Brian J; Matteau, Alexis; Mansour, Samer; Naim, Charbel; Riahi, Mounir; Essiambre, Richard; Montigny, Martine; Sareault, Isabelle; Gobeil, François

2017-01-01

Treatment times for primary percutaneous coronary intervention frequently exceed the recommended maximum delay. Automated "physicianless" systems of prehospital cardiac catheterization laboratory (CCL) activation show promise, but have been met with resistance over concerns regarding the potential for false positive and inappropriate activations (IAs). From 2010 to 2015, first responders performed electrocardiograms (ECGs) in the field for all patients with a complaint of chest pain or dyspnea. An automated machine diagnosis of "acute myocardial infarction" resulted in immediate CCL activation and direct transfer without transmission or human reinterpretation of the ECG prior to patient arrival. Any activation resulting from a nondiagnostic ECG (no ST-elevation) was deemed an IA, whereas activations resulting from ECG's compatible with ST-elevation myocardial infarction but without angiographic evidence of a coronary event were deemed false positive. In 2012, the referral algorithm was modified to exclude supraventricular tachycardia and left bundle branch block. There were 155 activations in the early cohort (2010-2012; prior to algorithm modification) and 313 in the late cohort (2012-2015). Algorithm modification resulted in a 42% relative decrease in the rate of IAs (12% vs 7%; P < 0.01) without a significant effect on treatment delay. A combination of prehospital automated ST-elevation myocardial infarction diagnosis and "physicianless" CCL activation is safe and effective in improving treatment delay and these results are sustainable over time. The performance of the referral algorithm in terms of IA and false positive is at least on par with systems that ensure real-time human oversight. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Lymphangiography

PubMed Central

Kadin, Michael R.; Thompson, Ronald W.

1974-01-01

Since the introduction of “staging laparotomy” (to determine the disease's stage) in assessing Hodgkin's disease, some observers have argued that lymphangiography could be safely omitted in the initial diagnostic evaluation. To test these opinions a series of 75 patients with Hodgkin's disease who had a staging laparotomy and histological correlation with lymphangiograms was reviewed. Of 16 examinations with positive results, one proved to be a false positive. Of the 14 examinations with equivocal results, one proved histologically positive. In the remaining 45 lymphangiograms, five were falsely negative. In all five of these patients abdominal lymph nodes were involved, but in areas that do not routinely opacify on lower extremity lymphangiography. The overall accuracy was 90 percent. Therapeutically, the lymphangiogram permits accurate planning for treatment by radiation therapy so that all known disease is treated and yet bone marrow is not excessively irradiated. Changes in lymph node architecture after therapy provide valuable information as to regression of the disease or signs of its early recurrence. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:4816398

True detection limits in an experimental linearly heteroscedastic system.. Part 2

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-11-01

Despite much different processing of the experimental fluorescence detection data presented in Part 1, essentially the same estimates were obtained for the true theoretical Currie decision levels ( YC and XC) and true Currie detection limits ( YD and XD). The obtained experimental values, for 5% probability of false positives and 5% probability of false negatives, were YC = 56.0 mV, YD = 125. mV, XC = 0.132 μg/mL and XD = 0.293 μg/mL. For 5% probability of false positives and 1% probability of false negatives, the obtained detection limits were YD = 158 . mV and XD = 0.371 μg/mL. Furthermore, by using bootstrapping methodology on the experimental data for the standards and the analytical blank, it was possible to validate previously published experimental domain expressions for the decision levels ( yC and xC) and detection limits ( yD and xD). This was demonstrated by testing the generated decision levels and detection limits for their performance in regard to false positives and false negatives. In every case, the obtained numbers of false negatives and false positives were as specified a priori.

Differential diagnosis of solitary pulmonary nodules based on 99mTc-EDDA/HYNIC-TOC scintigraphy: the effect of tumour size on the optimal method of image assessment.

PubMed

Płachcińska, Anna; Mikołajczak, Renata; Kozak, Józef; Rzeszutek, Katarzyna; Kuśmierek, Jacek

2006-09-01

The aim of the study was to determine an optimal method for the evaluation of scintigrams obtained with (99m)Tc-EDDA/HYNIC-TOC for the purpose of differential diagnosis of solitary pulmonary nodules (SPNs) and to assess the diagnostic value of the method. Eighty-five patients (48 males and 37 females, mean age 57 years, range 34-78 years) were enrolled in the study. Patients underwent (99m)Tc-EDDA/HYNIC-TOC scintigraphy for the purpose of differential diagnosis of SPNs (size between 1 and 4 cm). Images of all patients were evaluated visually in a prospective manner. Positive scintigraphic results were found in 37 out of 40 (93%) patients with malignant SPNs including 34 out of 35 (97%) patients with primary lung carcinoma. Two remaining false negative cases turned out to be metastatic lesions of malignant melanoma and leiomyosarcoma. Among 45 benign tumours, negative results were obtained in 31 cases (69%) and positive results in 14. The accuracy of the method was 80%. Analysis of the results of the visual assessment of scintigrams revealed a significantly higher frequency of false positive results among larger nodules (diameter at least 1.4 cm). Uptake of the tracer in those nodules was therefore assessed semi-quantitatively (using the tumour-to-background ratio), in expectation of an improvement in the low specificity of the visual method. The semi-quantitative assessment reduced the total number of false positive results in a subgroup of larger nodules from 13 to six, while preserving the high sensitivity of the method. The combination of visual analysis (for lesions smaller than 1.4 cm in diameter) and semi-quantitative assessment (for larger lesions) provided a high sensitivity of the method and significantly improved its specificity (84%) and accuracy (88%) in comparison with visual analysis (p<0.05).

Detection of simulated microcalcifications in fixed mammary tissue: An ROC study of the effect of local versus global histogram equalization.

PubMed

Sund, T; Olsen, J B

2006-09-01

To investigate whether sliding window adaptive histogram equalization (SWAHE) of digital mammograms improves the detection of simulated calcifications, as compared to images normalized by global histogram equalization (GHE). Direct digital mammograms were obtained from mammary tissue phantoms superimposed with different frames. Each frame was divided into forty squares by a wire mesh, and contained granular calcifications randomly positioned in about 50% of the squares. Three radiologists read the mammograms on a display monitor. They classified their confidence in the presence of microcalcifications in each square on a scale of 1 to 5. Images processed with GHE were first read and used as a reference. In a later session, the same images processed with SWAHE were read. The results were compared using ROC methodology. When the total areas AZ were compared, the results were completely equivocal. When comparing the high-specificity partial ROC area AZ,0.2 below false-positive fraction (FPF) 0.20, two of the three observers performed best with the images processed with SWAHE. The difference was not statistically significant. When the reader's confidence threshold in malignancy is set at a high level, increasing the contrast of mammograms with SWAHE may enhance the visibility of microcalcifications without adversely affecting the false-positive rate. When the reader's confidence threshold is set at a low level, the effect of SWAHE is an increase of false positives. Further investigation is needed to confirm the validity of the conclusions.

Designing occupancy studies when false-positive detections occur

USGS Publications Warehouse

Clement, Matthew

2016-01-01

1.Recently, estimators have been developed to estimate occupancy probabilities when false-positive detections occur during presence-absence surveys. Some of these estimators combine different types of survey data to improve estimates of occupancy. With these estimators, there is a tradeoff between the number of sample units surveyed, and the number and type of surveys at each sample unit. Guidance on efficient design of studies when false positives occur is unavailable. 2.For a range of scenarios, I identified survey designs that minimized the mean square error of the estimate of occupancy. I considered an approach that uses one survey method and two observation states and an approach that uses two survey methods. For each approach, I used numerical methods to identify optimal survey designs when model assumptions were met and parameter values were correctly anticipated, when parameter values were not correctly anticipated, and when the assumption of no unmodelled detection heterogeneity was violated. 3.Under the approach with two observation states, false positive detections increased the number of recommended surveys, relative to standard occupancy models. If parameter values could not be anticipated, pessimism about detection probabilities avoided poor designs. Detection heterogeneity could require more or fewer repeat surveys, depending on parameter values. If model assumptions were met, the approach with two survey methods was inefficient. However, with poor anticipation of parameter values, with detection heterogeneity, or with removal sampling schemes, combining two survey methods could improve estimates of occupancy. 4.Ignoring false positives can yield biased parameter estimates, yet false positives greatly complicate the design of occupancy studies. Specific guidance for major types of false-positive occupancy models, and for two assumption violations common in field data, can conserve survey resources. This guidance can be used to design efficient monitoring programs and studies of species occurrence, species distribution, or habitat selection, when false positives occur during surveys.

A statistical model of false negative and false positive detection of phase singularities.

PubMed

Jacquemet, Vincent

2017-10-01

The complexity of cardiac fibrillation dynamics can be assessed by analyzing the distribution of phase singularities (PSs) observed using mapping systems. Interelectrode distance, however, limits the accuracy of PS detection. To investigate in a theoretical framework the PS false negative and false positive rates in relation to the characteristics of the mapping system and fibrillation dynamics, we propose a statistical model of phase maps with controllable number and locations of PSs. In this model, phase maps are generated from randomly distributed PSs with physiologically-plausible directions of rotation. Noise and distortion of the phase are added. PSs are detected using topological charge contour integrals on regular grids of varying resolutions. Over 100 × 10 6 realizations of the random field process are used to estimate average false negative and false positive rates using a Monte-Carlo approach. The false detection rates are shown to depend on the average distance between neighboring PSs expressed in units of interelectrode distance, following approximately a power law with exponents in the range of 1.14 to 2 for false negatives and around 2.8 for false positives. In the presence of noise or distortion of phase, false detection rates at high resolution tend to a non-zero noise-dependent lower bound. This model provides an easy-to-implement tool for benchmarking PS detection algorithms over a broad range of configurations with multiple PSs.

Optimising in situ gamma measurements to identify the presence of radioactive particles in land areas.

PubMed

Rostron, Peter D; Heathcote, John A; Ramsey, Michael H

2014-12-01

High-coverage in situ surveys with gamma detectors are the best means of identifying small hotspots of activity, such as radioactive particles, in land areas. Scanning surveys can produce rapid results, but the probabilities of obtaining false positive or false negative errors are often unknown, and they may not satisfy other criteria such as estimation of mass activity concentrations. An alternative is to use portable gamma-detectors that are set up at a series of locations in a systematic sampling pattern, where any positive measurements are subsequently followed up in order to determine the exact location, extent and nature of the target source. The preliminary survey is typically designed using settings of detector height, measurement spacing and counting time that are based on convenience, rather than using settings that have been calculated to meet requirements. This paper introduces the basis of a repeatable method of setting these parameters at the outset of a survey, for pre-defined probabilities of false positive and false negative errors in locating spatially small radioactive particles in land areas. It is shown that an un-collimated detector is more effective than a collimated detector that might typically be used in the field. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluation of the on-site immunoassay drug-screening device Triage-TOX in routine forensic autopsy.

PubMed

Tominaga, Mariko; Michiue, Tomomi; Maeda, Hitoshi

2015-11-01

Instrumental identification of drugs with quantification is essential in forensic toxicology, while on-site immunoassay urinalysis drug-screening devices conveniently provide preliminary information when adequately used. However, suitable or sufficient urine specimens are not always available. The present study evaluated the efficacy of a new on-site immunoassay drug-screening device Triage-TOX (Alere Inc., San Diego, CA, USA), which has recently been developed to provide objective data on the one-step automated processor, using 51 urine and 19 pericardial fluid samples from 66 forensic autopsy cases, compared with Triage-Drug of Abuse (DOA) and Monitect-9. For benzodiazepines, the positive predictive value and specificity of Triage-TOX were higher than those of Triage-DOA; however, sensitivity was higher with Monitect-9, despite frequent false-positives. The results for the other drugs with the three devices also included a few false-negatives and false-positives. These observations indicate the applicability of Triage-TOX in preliminary drug screening using urine or alternative materials in routine forensic autopsy, when a possible false-negative is considered, especially for benzodiazepines, providing objective information; however, the combined use of another device such as Monitect-9 can help minimize misinterpretation prior to instrumental analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Correlation between lumbo-ventricular perfusion and MRI-CSF flow studies in idiopathic normal pressure hydrocephalus.

PubMed

Hakim, R; Black, P M

1998-01-01

After the initial description of normal pressure hydrocephalus (NPH) and its clinical triad, there has been a continuous interest from clinicians and researchers to set different diagnostic criteria that would make the selection of candidates for shunt surgery easier and more precise. A preliminary group of 12 patients was given a diagnosis of idiopathic normal pressure hydrocephalus by clinical and radiologic criteria. Each patient underwent two different tests: a magnetic resonance imaging-cerebrospinal fluid (MRI-CSF) flow study and a lumbo-ventricular perfusion test. The purpose was to compare the correlation of the results obtained with these tests and the clinical results obtained after CSF diversion. Eleven patients were given shunts and one was managed with lumbar punctures. One year after treatment, 10 of the 12 patients had improved with good results. The MRI-CSF flow studies were reliable in six patients; there were five false negatives and one false positive. The lumbo-ventricular perfusion test showed reliability in nine patients; there were two false negatives and one false positive. In only three patients were the results of both of these tests in accordance with the outcome. Even though there are few patients in this study so far, the data suggests that at the present time the most predictive guides for the diagnosis of NPH and its outcome after shunting are the clinical criteria and the radiological findings in computed tomography (CT) and/or MRI rather than lumbo-ventricular perfusion and CSF flow studies.

Tests for a disease-susceptibility locus allowing for an inbreeding coefficient (F).

PubMed

Song, Kijoung; Elston, Robert C

2003-11-01

We begin by discussing the false positive test results that arise because of cryptic relatedness and population substructure when testing a disease susceptibility locus. We extend and evaluate the Hardy-Weinberg disequilibrium (HWD) method, allowing for an inbreeding coefficient (F) in a similar way that Devlin and Roeder (1999) allowed for inbreeding in a case-control study. Then we compare the HWD measure and the common direct measure of linkage disequilibrium, both when there is no population substructure (F = 0) and when there is population substructure (F not = 0), for a single marker. The HWD test statistic gives rise to false positives caused by population stratification. These false positives can be controlled by adjusting the test statistic for the amount of variance inflation caused by the inbreeding coefficient (F). The power loss for the HWD test that arises when controlling for population structure is much less than that which arises for the common direct measure of linkage disequilibrium. However, in the multiplicative model, the HWD test has virtually no power even when allowing for non-zero F.

Robust Correlation Analyses: False Positive and Power Validation Using a New Open Source Matlab Toolbox

PubMed Central

Pernet, Cyril R.; Wilcox, Rand; Rousselet, Guillaume A.

2012-01-01

Pearson’s correlation measures the strength of the association between two variables. The technique is, however, restricted to linear associations and is overly sensitive to outliers. Indeed, a single outlier can result in a highly inaccurate summary of the data. Yet, it remains the most commonly used measure of association in psychology research. Here we describe a free Matlab(R) based toolbox (http://sourceforge.net/projects/robustcorrtool/) that computes robust measures of association between two or more random variables: the percentage-bend correlation and skipped-correlations. After illustrating how to use the toolbox, we show that robust methods, where outliers are down weighted or removed and accounted for in significance testing, provide better estimates of the true association with accurate false positive control and without loss of power. The different correlation methods were tested with normal data and normal data contaminated with marginal or bivariate outliers. We report estimates of effect size, false positive rate and power, and advise on which technique to use depending on the data at hand. PMID:23335907

Robust correlation analyses: false positive and power validation using a new open source matlab toolbox.

PubMed

Pernet, Cyril R; Wilcox, Rand; Rousselet, Guillaume A

2012-01-01

Pearson's correlation measures the strength of the association between two variables. The technique is, however, restricted to linear associations and is overly sensitive to outliers. Indeed, a single outlier can result in a highly inaccurate summary of the data. Yet, it remains the most commonly used measure of association in psychology research. Here we describe a free Matlab((R)) based toolbox (http://sourceforge.net/projects/robustcorrtool/) that computes robust measures of association between two or more random variables: the percentage-bend correlation and skipped-correlations. After illustrating how to use the toolbox, we show that robust methods, where outliers are down weighted or removed and accounted for in significance testing, provide better estimates of the true association with accurate false positive control and without loss of power. The different correlation methods were tested with normal data and normal data contaminated with marginal or bivariate outliers. We report estimates of effect size, false positive rate and power, and advise on which technique to use depending on the data at hand.

New closed tube loop mediated isothermal amplification assay for prevention of product cross-contamination

PubMed Central

Karthik, K.; Rathore, Rajesh; Thomas, Prasad; Arun, T.R.; Viswas, K.N.; Dhama, Kuldeep; Agarwal, R.K.

2014-01-01

Loop mediated isothermal amplification (LAMP) assay, a promising diagnostic test, has been developed for detection of different pathogens of human as well as animals. Various positive points support its use as a field level test but the major problem is product cross contamination leading to false positive results. Different methods were adopted by various researchers to control this false positive amplification due to cross contamination but all have their own advantages and disadvantages. A new closed tube LAMP assay based on agar dye capsule was developed in the present study and this technique has some advantages over the other closed tube technique.•Agar at the concentration of 1.5% was used to sandwich SYBR green dye I with the aid of intradermal syringe. This agar dye capsule was placed over the LAMP reaction mixture before it was amplified.•To eliminate the hazardous nature of Ultra Violet (UV) light during result visualization of LAMP products, the present study demonstrates the use of Light Emitting Diode (LED) lights for result visualization.•LAMP was carried out for Brucella species detection using this modified techniques yielding good results without any cross contamination and LED showed similar fluorescence compared to UV. PMID:26150945

New closed tube loop mediated isothermal amplification assay for prevention of product cross-contamination.

PubMed

Karthik, K; Rathore, Rajesh; Thomas, Prasad; Arun, T R; Viswas, K N; Dhama, Kuldeep; Agarwal, R K

2014-01-01

Loop mediated isothermal amplification (LAMP) assay, a promising diagnostic test, has been developed for detection of different pathogens of human as well as animals. Various positive points support its use as a field level test but the major problem is product cross contamination leading to false positive results. Different methods were adopted by various researchers to control this false positive amplification due to cross contamination but all have their own advantages and disadvantages. A new closed tube LAMP assay based on agar dye capsule was developed in the present study and this technique has some advantages over the other closed tube technique.•Agar at the concentration of 1.5% was used to sandwich SYBR green dye I with the aid of intradermal syringe. This agar dye capsule was placed over the LAMP reaction mixture before it was amplified.•To eliminate the hazardous nature of Ultra Violet (UV) light during result visualization of LAMP products, the present study demonstrates the use of Light Emitting Diode (LED) lights for result visualization.•LAMP was carried out for Brucella species detection using this modified techniques yielding good results without any cross contamination and LED showed similar fluorescence compared to UV.

A novel seizure detection algorithm informed by hidden Markov model event states

NASA Astrophysics Data System (ADS)

Baldassano, Steven; Wulsin, Drausin; Ung, Hoameng; Blevins, Tyler; Brown, Mesha-Gay; Fox, Emily; Litt, Brian

2016-06-01

Objective. Recently the FDA approved the first responsive, closed-loop intracranial device to treat epilepsy. Because these devices must respond within seconds of seizure onset and not miss events, they are tuned to have high sensitivity, leading to frequent false positive stimulations and decreased battery life. In this work, we propose a more robust seizure detection model. Approach. We use a Bayesian nonparametric Markov switching process to parse intracranial EEG (iEEG) data into distinct dynamic event states. Each event state is then modeled as a multidimensional Gaussian distribution to allow for predictive state assignment. By detecting event states highly specific for seizure onset zones, the method can identify precise regions of iEEG data associated with the transition to seizure activity, reducing false positive detections associated with interictal bursts. The seizure detection algorithm was translated to a real-time application and validated in a small pilot study using 391 days of continuous iEEG data from two dogs with naturally occurring, multifocal epilepsy. A feature-based seizure detector modeled after the NeuroPace RNS System was developed as a control. Main results. Our novel seizure detection method demonstrated an improvement in false negative rate (0/55 seizures missed versus 2/55 seizures missed) as well as a significantly reduced false positive rate (0.0012 h versus 0.058 h-1). All seizures were detected an average of 12.1 ± 6.9 s before the onset of unequivocal epileptic activity (unequivocal epileptic onset (UEO)). Significance. This algorithm represents a computationally inexpensive, individualized, real-time detection method suitable for implantable antiepileptic devices that may considerably reduce false positive rate relative to current industry standards.

False-positive IgM for CMV in pregnant women with autoimmune disease: a novel prognostic factor for poor pregnancy outcome.

PubMed

De Carolis, S; Santucci, S; Botta, A; Garofalo, S; Martino, C; Perrelli, A; Salvi, S; Degennaro, Va; de Belvis, Ag; Ferrazzani, S; Scambia, G

2010-06-01

Our aims were to assess the frequency of false-positive IgM antibodies for cytomegalovirus in pregnant women with autoimmune diseases and in healthy women (controls) and to determine their relationship with pregnancy outcome. Data from 133 pregnancies in 118 patients with autoimmune diseases and from 222 pregnancies in 198 controls were assessed. When positive IgM for cytomegalovirus was detected, IgG avidity, cytomegalovirus isolation and polymerase chain reaction for CMV-DNA in maternal urine and amniotic fluid samples were performed in order to identify primary infection or false positivity. A statistically significantly higher rate of false-positive IgM was found in pregnancies with autoimmune diseases (16.5%) in comparison with controls (0.9%). A worse pregnancy outcome was observed among patients with autoimmune disease and false cytomegalovirus IgM in comparison with those without false positivity: earlier week of delivery (p = 0.017), lower neonatal birth weight (p = 0.0004) and neonatal birth weight percentile (p = 0.002), higher rate of intrauterine growth restriction (p = 0.02) and babies weighing less than 2000 g (p = 0.025) were encountered. The presence of false cytomegalovirus IgM in patients with autoimmune diseases could be used as a novel prognostic index of poor pregnancy outcome: it may reflect a non-specific activation of the immune system that could negatively affect pregnancy outcome. Lupus (2010) 19, 844-849.

Comparison of Six Automated Treponema-Specific Antibody Assays.

PubMed

Park, Borae G; Yoon, Jihoon G; Rim, John Hoon; Lee, Anna; Kim, Hyon-Suk

2016-01-01

Six different Treponema (TP)-specific immunoassays were compared to the fluorescent treponemal antibody absorption (FTA-ABS) test. A total of 615 samples were tested. The overall percent agreement, analytical sensitivity, and analytical specificity of each assay compared to the FTA-ABS test were as follows: Architect Syphilis TP, 99.2%, 96.8%, and 100%; Cobas Syphilis, 99.8%, 99.4%, and 100%; ADVIA Centaur Syphilis, 99.8%, 99.4%, and 100%; HISCL Anti-TP assay kit, 99.7%, 98.7%, and 100%; Immunoticles Auto3 TP, 99.0%, 97.5%, and 99.6%; Mediace TPLA, 98.0%, 98.1%, and 98.0%. All results that were discrepant between the TP-specific assays were associated with samples from noninfectious cases (11 immunoassay false positives and 7 from previous syphilis cases). Our study demonstrated that TP-specific immunoassays generally showed high sensitivities, specificities, and percentages of agreement compared to FTA-ABS, with rare cases of false-positive or false-negative results. Therefore, most TP-specific immunoassays are acceptable for use in screening for syphilis. However, it is important to perform a thorough review of a patient's clinical and treatment history for interpreting the results of syphilis serology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[EXPERIENCE OF STUDY AND POSSIBLE WAYS OF ELIMINATION OF FALSE POSITIVE AND FALSE NEGATIVE RESULTS DURING EXECUTION OF POLYMERASE CHAIN REACTION ON AN EXAMPLE OF JUNIN VIRUS RNA DETECTION].

PubMed

Sizikova, T E; Lebedev, V N; Pantyukhov, V B; Borisevich, S V; Merkulov, V A

2015-01-01

Experience of study and possible ways of elimination of false positive and false negative results during execution of polymerase chain reaction on an example of Junin virus RNA detection. MATERIALSS AND METHODS: Junin virus--causative agent of Argentine hemorrhagic fever (AHF) strain XJpR37/5787 was obtained from the State collection of pathogenicity group I causative agents of the 48th Central Research Institute. Reagent kit for detection of Junin virus RNA by RT-PCR was developed in the Institute and consists of 4 sets: for isolation of RNA, execution of reverse-transcription reaction, execution of PCR and electrophoretic detection of PCR products. RT-PCR was carried out by a standard technique. Continuous cell cultures of African green monkey Vero B, GMK-AH-1(D) were obtained from the museum of cell culture department of the Centre. An experimental study of the effect of various factors of impact on the sample under investigation ("thawing-freezing", presence of formaldehyde, heparin) on the obtaining of false negative results during Junin virus RNA detection by using RT-PCR was studied. Addition of 0.01% heparin to the samples was shown to completely inhibit PCR. Addition of 0.05% formaldehyde significantly reduces sensitivity of the method. A possibility of reduction of analysis timeframe from 15 to 5 days was shown during detection of the causative agent in samples with low concentration of the latter by growing the samples and subsequent analysis of the material obtained by using RT-PCR. During detection of causative agent by using RT-PCR false negative results could appear in the presence of formaldehyde and heparin in the sample. A possibility of elimination of false negative PCR results due to concentration of the causative agent in the sample under investigation at a level below sensitivity threshold was shown on the example of Junin virus RNA detection by using growing of the pathogen in appropriate accumulation system with subsequent analysis of the material obtained using PCR.

40 CFR 799.12 - Test results.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Test results. 799.12 Section 799.12...) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.12 Test results. Except as set forth in specific chemical test rules in subpart B of this part, a positive or...

40 CFR 799.12 - Test results.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Test results. 799.12 Section 799.12...) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.12 Test results. Except as set forth in specific chemical test rules in subpart B of this part, a positive or...

An Evaluation of Unit and ½ Mass Correction Approaches as a Means of Minimizing the False Positives Produced by M+2 species in US EPA Method 200.8 using ICP-MS

EPA Science Inventory

Rare earth elements (REE) and certain alkaline earths can produce M+2 interferences in ICP-MS because they have sufficiently low second ionization energies. Four REEs (150Sm, 150Nd, 156Gd and 156Dy) produce false positives on 75As and 78Se and 132Ba can produce a false positive ...

Algorithm of reducing the false positives in IDS based on correlation Analysis

NASA Astrophysics Data System (ADS)

Liu, Jianyi; Li, Sida; Zhang, Ru

2018-03-01

This paper proposes an algorithm of reducing the false positives in IDS based on correlation Analysis. Firstly, the algorithm analyzes the distinguishing characteristics of false positives and real alarms, and preliminary screen the false positives; then use the method of attribute similarity clustering to the alarms and further reduces the amount of alarms; finally, according to the characteristics of multi-step attack, associated it by the causal relationship. The paper also proposed a reverse causation algorithm based on the attack association method proposed by the predecessors, turning alarm information into a complete attack path. Experiments show that the algorithm simplifies the number of alarms, improve the efficiency of alarm processing, and contribute to attack purposes identification and alarm accuracy improvement.

Blood culture

MedlinePlus

... into (contaminating) the blood sample and causing a false-positive result (see below). The sample is sent to a laboratory. There, it is placed in a special dish (culture). It is then watched to see if bacteria ...

40 CFR 799.12 - Test results.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Test results. 799.12 Section 799.12... results. Except as set forth in specific chemical test rules in subpart B of this part, a positive or negative test result in any of the tests required under subpart B is defined in the TSCA test guidelines...

40 CFR 799.12 - Test results.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 33 2012-07-01 2012-07-01 false Test results. 799.12 Section 799.12... results. Except as set forth in specific chemical test rules in subpart B of this part, a positive or negative test result in any of the tests required under subpart B is defined in the TSCA test guidelines...

Presence of Cross-Reactions with Other Viral Encephalitides in the Indirect Fluorescent-Antibody Test for Diagnosis of Rabies

PubMed Central

Appler, Kim A.; Wong, Susan J.

2013-01-01

The antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. A combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. Modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. However, medical intervention efforts require a rapid and accurate diagnosis as early in the course of clinical disease as possible. Indirect fluorescent-antibody (IFA) testing on cerebrospinal fluid and serum specimens provides rapid results, but the specificity of the assay has not been well studied. Because false-positive IFA results could significantly affect patient treatment and outcomes, it is critical to understand the specificity of this assay. In this study, IFA testing was performed on 135 cerebrospinal fluid and serum specimens taken from patients with viral encephalitis or a presumed viral infection involving an agent other than rabies virus. Results indicate that false-positive results can occur in interpreting the rabies IFA test. Staining patterns morphologically similar to antirabies staining were observed in 7 of the 135 cerebrospinal fluid specimens examined. In addition, a majority of the cerebrospinal fluid specimens tested from patients with encephalitis presented immunoglobulin that bound to antigens present in the cell culture substrate. Of marked concern was the frequent presence of cross-reactive antibodies in encephalitis cases associated with West Nile and Powassan flaviviruses. Because IFA testing for rabies on human specimens may result in false-positive results, it should not be used as the sole basis for initiating antirabies treatment. PMID:24088851

Presence of cross-reactions with other viral encephalitides in the indirect fluorescent-antibody test for diagnosis of rabies.

PubMed

Rudd, Robert J; Appler, Kim A; Wong, Susan J

2013-12-01

The antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. A combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. Modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. However, medical intervention efforts require a rapid and accurate diagnosis as early in the course of clinical disease as possible. Indirect fluorescent-antibody (IFA) testing on cerebrospinal fluid and serum specimens provides rapid results, but the specificity of the assay has not been well studied. Because false-positive IFA results could significantly affect patient treatment and outcomes, it is critical to understand the specificity of this assay. In this study, IFA testing was performed on 135 cerebrospinal fluid and serum specimens taken from patients with viral encephalitis or a presumed viral infection involving an agent other than rabies virus. Results indicate that false-positive results can occur in interpreting the rabies IFA test. Staining patterns morphologically similar to antirabies staining were observed in 7 of the 135 cerebrospinal fluid specimens examined. In addition, a majority of the cerebrospinal fluid specimens tested from patients with encephalitis presented immunoglobulin that bound to antigens present in the cell culture substrate. Of marked concern was the frequent presence of cross-reactive antibodies in encephalitis cases associated with West Nile and Powassan flaviviruses. Because IFA testing for rabies on human specimens may result in false-positive results, it should not be used as the sole basis for initiating antirabies treatment.

An effect size filter improves the reproducibility in spectral counting-based comparative proteomics.

PubMed

Gregori, Josep; Villarreal, Laura; Sánchez, Alex; Baselga, José; Villanueva, Josep

2013-12-16

The microarray community has shown that the low reproducibility observed in gene expression-based biomarker discovery studies is partially due to relying solely on p-values to get the lists of differentially expressed genes. Their conclusions recommended complementing the p-value cutoff with the use of effect-size criteria. The aim of this work was to evaluate the influence of such an effect-size filter on spectral counting-based comparative proteomic analysis. The results proved that the filter increased the number of true positives and decreased the number of false positives and the false discovery rate of the dataset. These results were confirmed by simulation experiments where the effect size filter was used to evaluate systematically variable fractions of differentially expressed proteins. Our results suggest that relaxing the p-value cut-off followed by a post-test filter based on effect size and signal level thresholds can increase the reproducibility of statistical results obtained in comparative proteomic analysis. Based on our work, we recommend using a filter consisting of a minimum absolute log2 fold change of 0.8 and a minimum signal of 2-4 SpC on the most abundant condition for the general practice of comparative proteomics. The implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of the results obtained among independent laboratories and MS platforms. Quality control analysis of microarray-based gene expression studies pointed out that the low reproducibility observed in the lists of differentially expressed genes could be partially attributed to the fact that these lists are generated relying solely on p-values. Our study has established that the implementation of an effect size post-test filter improves the statistical results of spectral count-based quantitative proteomics. The results proved that the filter increased the number of true positives whereas decreased the false positives and the false discovery rate of the datasets. The results presented here prove that a post-test filter applying a reasonable effect size and signal level thresholds helps to increase the reproducibility of statistical results in comparative proteomic analysis. Furthermore, the implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of results obtained among independent laboratories and MS platforms. This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

The Developmental Progression of Understanding of Mind during a Hiding Game

PubMed Central

Nelson, P. Brooke; Adamson, Lauren B.; Bakeman, Roger

2011-01-01

In this longitudinal study, 52 typically developing preschoolers engaged in a hiding game with their mothers when children were 42-, 54-, and 66-months old. Children's understanding of mind, positive affect, and engagement with the task were rated, and mothers' utterances were coded for role and content. Analyses confirmed that some facets of children's understanding of mind developed sequentially; specifically, they expressed an understanding of knowledge access before an understanding of deception and false beliefs, and expressed an understanding of deception before an understanding of false beliefs. Children's understanding of mind increased across visits and positively correlated with false belief task performance. Results suggest that mothers may tailor the content of their utterances to the child's growing expertise, but the role of mothers' utterances did not change. Observing preschoolers engaged in a playful hiding game revealed that children's understanding of mind not only increased with age but also developed sequentially. PMID:25960610

False memory and the associative network of happiness.

PubMed

Koo, Minkyung; Oishi, Shigehiro

2009-02-01

This research examines the relationship between individuals' levels of life satisfaction and their associative networks of happiness. Study 1 measured European Americans' degree of false memory of happiness using the Deese-Roediger-McDermott paradigm. Scores on the Satisfaction With Life Scale predicted the likelihood of false memory of happiness but not of other lure words such as sleep . In Study 2, European American participants completed an association-judgment task in which they judged the extent to which happiness and each of 15 positive emotion terms were associated with each other. Consistent with Study 1's findings, chronically satisfied individuals exhibited stronger associations between happiness and other positive emotion terms than did unsatisfied individuals. However, Koreans and Asian Americans did not exhibit such a pattern regarding their chronic level of life satisfaction (Study 3). In combination, results suggest that there are important individual and cultural differences in the cognitive structure and associative network of happiness.

[Molecular beacon based PNA-FISH method combined with fluorescence scanning for rapid detection of Listeria monocytogenes].

PubMed

Wu, Shan; Zhang, Xiaofeng; Shuai, Jiangbing; Li, Ke; Yu, Huizhen; Jin, Chenchen

2016-07-04

To simplify the PNA-FISH (Peptide nucleic acid-fluorescence in situ hybridization) test, molecular beacon based PNA probe combined with fluorescence scanning detection technology was applied to replace the original microscope observation to detect Listeria monocytogenes The 5′ end and 3′ end of the L. monocytogenes specific PNA probes were labeled with the fluorescent group and the quenching group respectively, to form a molecular beacon based PNA probe. When PNA probe used for fluorescence scanning and N1 treatment as the control, the false positive rate was 11.4%, and the false negative rate was 0; when N2 treatment as the control, the false positive rate decreased to 4.3%, but the false negative rate rose to 18.6%. When beacon based PNA probe used for fluorescence scanning, taken N1 treatment as blank control, the false positive rate was 8.6%, and the false negative rate was 1.4%; taken N2 treatment as blank control, the false positive rate was 5.7%, and the false negative rate was 1.4%. Compared with PNA probe, molecular beacon based PNA probe can effectively reduce false positives and false negatives. The success rates of hybridization of the two PNA probes were 83.3% and 95.2% respectively; and the rates of the two beacon based PNA probes were 91.7% and 90.5% respectively, which indicated that labeling the both ends of the PNA probe dose not decrease the hybridization rate with the target bacteria. The combination of liquid phase PNA-FISH and fluorescence scanning method, can significantly improve the detection efficiency.

Autofluorescence imaging to optimize 5-ALA-induced fluorescence endoscopy of bladder carcinoma.

PubMed

Frimberger, D; Zaak, D; Stepp, H; Knüchel, R; Baumgartner, R; Schneede, P; Schmeller, N; Hofstetter, A

2001-09-01

To design an optical system for detecting autofluorescence (AF) of bladder tumors and to determine the success of reducing the false-positive rate of 5-aminolevulinic acid-induced fluorescence endoscopy (AFE). AFE provides significantly higher sensitivity in detecting and localizing bladder carcinoma compared with white light endoscopy. The specificity of AFE is equivalent to white light endoscopy, mostly because of the false-positive fluorescence of chronic cystitis lesions. Laser-induced spectral autofluorescence detection is also an efficient method in the diagnosis of bladder carcinoma. Bladder tissue was excited to AF using the D-Light (375 to 440 nm) after regular AFE with detection of fluorescence-positive areas. The optical image was produced using a special RGB camera. Biopsies were taken from AFE-positive areas, the peritumoral edges, and normal bladder mucosa. The AF images of the suspicious areas were compared with the AFE images and the histologic results. A total of 43 biopsies were histologically examined (24 benign and 19 neoplastic). AF imaging showed contrast differences between papillary tumors, flat lesions, and normal mucosa. The combination of AFE with AF raised the specificity of AFE alone from 67% to 88%. AF imaging is possible. The value of the method in reducing the false-positive rate of the highly sensitive AFE needs to be validated with higher numbers. The combination of AF with AFE had a 20% higher specificity than AFE alone in our study.

False memories and memory confidence in borderline patients.

PubMed

Schilling, Lisa; Wingenfeld, Katja; Spitzer, Carsten; Nagel, Matthias; Moritz, Steffen

2013-12-01

Mixed results have been obtained regarding memory in patients with borderline personality disorder (BPD). Prior reports and anecdotal evidence suggests that patients with BPD are prone to false memories but this assumption has to been put to firm empirical test, yet. Memory accuracy and confidence was assessed in 20 BPD patients and 22 healthy controls using a visual variant of the false memory (Deese-Roediger-McDermott) paradigm which involved a negative and a positive-valenced picture. Groups did not differ regarding veridical item recognition. Importantly, patients did not display more false memories than controls. At trend level, borderline patients rated more items as new with high confidence compared to healthy controls. The results tentatively suggest that borderline patients show uncompromised visual memory functions and display no increased susceptibility for distorted memories. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effect of information about false negative and false positive rates on people's attitudes towards colorectal cancer screening using faecal occult blood testing (FOBt).

PubMed

Miles, Anne; Rodrigues, Vania; Sevdalis, Nick

2013-11-01

To examine the impact of numeric risk information about false negative (FN) and false positive (FP) rates in faecal occult blood testing (FOBt) on attitudes towards screening. 95 people aged 45-59, living in England, read 6 hypothetical vignettes presented online about the use of FOB testing to detect bowel cancer, in which information about FN and FP rates was systematically varied. Both verbal and numeric FN risk information reduced people's interest in screening compared with no FN information. Numeric FN risk information reduced people's perceptions of screening effectiveness and lowered perceived trust in the results of screening compared with both verbal FN information and no FN information. FP information did not affect attitudes towards FOB testing. There was limited evidence that FN information reduced interest and perceptions of screening effectiveness more in educated groups. Numeric FN risk information decreased people's perceptions of screening effectiveness and trust in the results of screening but did not affect people's interest in screening anymore than verbal FN risk information. Numeric FN information could be added to patient information without affecting interest in screening, although this needs to be replicated in a larger, more representative sample. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis.

PubMed

Kissinger, Patricia J; White, Scott; Manhart, Lisa E; Schwebke, Jane; Taylor, Stephanie N; Mena, Leandro; Khosropour, Christine M; Wilcox, Larissa; Schmidt, Norine; Martin, David H

2016-10-01

Three recent prospective studies have suggested that the 1-g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%-22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to reexamine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. Men who had sex with women, who received 1-g azithromycin under directly observed therapy for presumptive treatment of nongonococcal urethritis with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine, and TOC screening was performed on urine using nucleic acid amplification tests. Posttreatment vaginal sexual exposure was elicited at TOC. Data from the 3 studies were obtained and reanalyzed. Rates of Ct retest positive were examined for all cases, and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). In these samples of men who have sex with women with Ct-related nongonococcal urethritis, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization's target chlamydia treatment failure rate of < 5%.

Are Hemorrhoids Associated with False-Positive Fecal Immunochemical Test Results?

PubMed Central

Kim, Nam Hee; Park, Jung Ho; Park, Dong Il; Sohn, Chong Il; Choi, Kyuyong

2017-01-01

Purpose False-positive (FP) results of fecal immunochemical tests (FITs) conducted in colorectal cancer (CRC) screening could lead to performing unnecessary colonoscopies. Hemorrhoids are a possible cause of FP FIT results; however, studies on this topic are extremely rare. We investigated whether hemorrhoids are associated with FP FIT results. Materials and Methods A retrospective study was conducted at a university hospital in Korea from June 2013 to May 2015. Of the 34547 individuals who underwent FITs, 3946 aged ≥50 years who underwent colonoscopies were analyzed. Logistic regression analysis was performed to determine factors associated with FP FIT results. Results Among 3946 participants, 704 (17.8%) showed positive FIT results and 1303 (33.0%) had hemorrhoids. Of the 704 participants with positive FIT results, 165 had advanced colorectal neoplasia (ACRN) and 539 had no ACRN (FP results). Of the 1303 participants with hemorrhoids, 291 showed FP results, of whom 81 showed FP results because of hemorrhoids only. Participants with hemorrhoids had a higher rate of FP results than those without hemorrhoids (291/1176, 24.7% vs. 248/2361, 10.5%; p<0.001). Additionally, the participants with hemorrhoids as the only abnormality had a higher rate of FP results than those experiencing no such abnormalities (81/531, 15.3% vs. 38/1173, 3.2%; p<0.001). In multivariate analysis, the presence of hemorrhoids was identified as an independent predictor of FP results (adjusted odds ratio, 2.76; 95% confidence interval, 2.24–3.40; p<0.001). Conclusion Hemorrhoids are significantly associated with FP FIT results. Their presence seemed to be a non-negligible contributor of FP results in FIT-based CRC screening programs. PMID:27873508

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

PubMed Central

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ≥90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID:22301692

Evaluation of the LDBIO point of care test for the combined detection of toxoplasmic IgG and IgM.

PubMed

Chapey, Emmanuelle; Wallon, Martine; Peyron, François

2017-01-01

The toxoplasma ICT IgG-IgM rapid diagnostic test for the simultaneous detection of specific toxoplasmic immunoglobulin (Ig) G and IgM was compared with the Architect fully automated chemiluminescence test. Four hundred sera were included, among which 248 scored negative in Architect. The cassettes were easily read with the naked eye. Diagnostic sensitivity and specificity were 97% and 96%, respectively. The test scored 8 false-positive IgG and yielded negative results in 3 sera displaying unspecific IgM in Architect. The LDBIO appears to be a reliable first line test, although the false-positive results for IgG deserve further investigation. Such an easily performed test could be used advantageously for screening for toxoplasmosis in pregnant women. Copyright © 2016 Elsevier B.V. All rights reserved.

Amplification of Mitochondrial DNA for detection of Plasmodiumvivax in Balochistan.

PubMed

Shahwani, Muhammad Naeem; Nisar, Samia; Aleem, Abdul; Panezai, Marina; Afridi, Sarwat; Malik, Shaukat Iqbal

2017-05-01

To access a new step using PCR to amplify the targeted mtDNA sequence for detecting specifically Plasmodium vivax and its co-infections, false positive and false negative results with Plasmodium falciparum. In this study we have standardized a new technical approach in which the target mitochondrial DNA sequence (mtDNA) was amplified by using a PCR technique as a tool to detect Plasmodium spp. Species specific primers were designed to hybridize with cytochrome c oxidase gene of P. vivax (cox I) and P. falciparum (cox III). Two hundred blood samples were collected on the basis of clinical symptoms which were initially examined through microscopic analysis after preparing Giemsa stained thick and thin blood smears. Afterwards genomic DNA was extracted from all samples and was then subjected to PCR amplification by using species specific primers and amplified segments were sequenced for confirmation of results. One-hundred and thirty-two blood samples were detected as positive for malaria by PCR, out of which 64 were found to be positive by PCR and 53 by both microscopy and PCR for P.vivax infection. Nine samples were found to be false negative, one P.vivax mono infection was declared as co infection by PCR and 3 samples identified as having P.falciparum gametes were confirmed as P.vivax by PCR amplification. Sensitivity and specificity were found to be 85% and 92% respectively. Results obtained through PCR method were comparatively better and reliable than microscopy.

Adaptive error detection for HDR/PDR brachytherapy: Guidance for decision making during real-time in vivo point dosimetry

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

Kertzscher, Gustavo, E-mail: guke@dtu.dk; Andersen, Claus E., E-mail: clan@dtu.dk; Tanderup, Kari, E-mail: karitand@rm.dk

Purpose: This study presents an adaptive error detection algorithm (AEDA) for real-timein vivo point dosimetry during high dose rate (HDR) or pulsed dose rate (PDR) brachytherapy (BT) where the error identification, in contrast to existing approaches, does not depend on an a priori reconstruction of the dosimeter position. Instead, the treatment is judged based on dose rate comparisons between measurements and calculations of the most viable dosimeter position provided by the AEDA in a data driven approach. As a result, the AEDA compensates for false error cases related to systematic effects of the dosimeter position reconstruction. Given its nearly exclusivemore » dependence on stable dosimeter positioning, the AEDA allows for a substantially simplified and time efficient real-time in vivo BT dosimetry implementation. Methods: In the event of a measured potential treatment error, the AEDA proposes the most viable dosimeter position out of alternatives to the original reconstruction by means of a data driven matching procedure between dose rate distributions. If measured dose rates do not differ significantly from the most viable alternative, the initial error indication may be attributed to a mispositioned or misreconstructed dosimeter (false error). However, if the error declaration persists, no viable dosimeter position can be found to explain the error, hence the discrepancy is more likely to originate from a misplaced or misreconstructed source applicator or from erroneously connected source guide tubes (true error). Results: The AEDA applied on twoin vivo dosimetry implementations for pulsed dose rate BT demonstrated that the AEDA correctly described effects responsible for initial error indications. The AEDA was able to correctly identify the major part of all permutations of simulated guide tube swap errors and simulated shifts of individual needles from the original reconstruction. Unidentified errors corresponded to scenarios where the dosimeter position was sufficiently symmetric with respect to error and no-error source position constellations. The AEDA was able to correctly identify all false errors represented by mispositioned dosimeters contrary to an error detection algorithm relying on the original reconstruction. Conclusions: The study demonstrates that the AEDA error identification during HDR/PDR BT relies on a stable dosimeter position rather than on an accurate dosimeter reconstruction, and the AEDA’s capacity to distinguish between true and false error scenarios. The study further shows that the AEDA can offer guidance in decision making in the event of potential errors detected with real-timein vivo point dosimetry.« less

RAPTR-SV: a hybrid method for the detection of structural variants

USDA-ARS?s Scientific Manuscript database

Motivation: Identification of Structural Variants (SV) in sequence data results in a large number of false positive calls using existing software, which overburdens subsequent validation. Results: Simulations using RAPTR-SV and another software package that uses a similar algorithm for SV detection...

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012-2013.

PubMed

Isaac, Beth M; Zucker, Jane R; Giancotti, Francesca R; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L; Rosen, Jennifer B

2017-09-01

The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. Copyright © 2017 American Society for Microbiology.

[Sequential monitoring of renal transplant with aspiration cytology].

PubMed

Manfro, R C; Gonçalves, L F; de Moura, L A

1998-01-01

To evaluate the utility of kidney aspiration cytology in the sequential monitorization of acute rejection in renal transplant patients. Thirty patients were submitted to 376 aspirations. The clinical diagnoses were independently established. The representativity of the samples reached 82.7%. The total corrected increment index and the number of immunoactivated cells were higher during acute rejection as compared to normal allograft function, acute tubular necrosis, and cyclosporine nephrotoxicity. The parameters to the diagnosis of acute rejection were sensitivity: 71.8%, specificity: 87.3%, positive predictive value: 50.9%, negative predictive value: 94.9% and accuracy 84.9%. The false positive results were mainly related to cytomegalovirus infection or to the administration of OKT3. In 10 out of 11 false negative results incipient immunoactivation was present alerting to the possibility of acute rejection. Kidney aspiration cytology is a useful tool for the sequential monitorization of acute rejection in renal transplant patients. The best results are reached when the results of aspiration cytology are analyzed with the clinical data.

Development of Technologies for Early Detection and Stratification of Breast Cancer

DTIC Science & Technology

2012-10-01

at the time of screening, and has an 8-10% false positive rate.3 These drawbacks lead to inaccurate patient diagnosis, which can allow potentially...95% recovery efficiency. Furthermore, using whole blood from healthy donors, we determined we have a zero false positive rate; that is, we have not...detected a single false positive event out of the dozen samples we ran. The technology we developed here is not only useful for the isolation of CTCs

An Evaluation of Unit and ½ Mass Correction Approaches as a Means of Minimizing the False Positives Produced by M+2 species in US EPA Method 200.8 using ICP-MS (webinar presentation)

EPA Science Inventory

Rare earth elements (REE) and certain alkaline earths can produce M+2 interferences in ICP-MS because they have sufficiently low second ionization energies. Four REEs (150Sm, 150Nd, 156Gd and 156Dy) produce false positives on 75As and 78Se and 132Ba can produce a false positive ...

Detection of right-to-left shunts: comparison between the International Consensus and Spencer Logarithmic Scale criteria.

PubMed

Lao, Annabelle Y; Sharma, Vijay K; Tsivgoulis, Georgios; Frey, James L; Malkoff, Marc D; Navarro, Jose C; Alexandrov, Andrei V

2008-10-01

International Consensus Criteria (ICC) consider right-to-left shunt (RLS) present when Transcranial Doppler (TCD) detects even one microbubble (microB). Spencer Logarithmic Scale (SLS) offers more grades of RLS with detection of >30 microB corresponding to a large shunt. We compared the yield of ICC and SLS in detection and quantification of a large RLS. We prospectively evaluated paradoxical embolism in consecutive patients with ischemic strokes or transient ischemic attack (TIA) using injections of 9 cc saline agitated with 1 cc of air. Results were classified according to ICC [negative (no microB), grade I (1-20 microB), grade II (>20 microB or "shower" appearance of microB), and grade III ("curtain" appearance of microB)] and SLS criteria [negative (no microB), grade I (1-10 microB), grade II (11-30 microB), grade III (31100 microB), grade IV (101300 microB), grade V (>300 microB)]. The RLS size was defined as large (>4 mm) using diameter measurement of the septal defects on transesophageal echocardiography (TEE). TCD comparison to TEE showed 24 true positive, 48 true negative, 4 false positive, and 2 false negative cases (sensitivity 92.3%, specificity 92.3%, positive predictive value (PPV) 85.7%, negative predictive value (NPV) 96%, and accuracy 92.3%) for any RLS presence. Both ICC and SLS were 100% sensitive for detection of large RLS. ICC and SLS criteria yielded a false positive rate of 24.4% and 7.7%, respectively when compared to TEE. Although both grading scales provide agreement as to any shunt presence, using the Spencer Scale grade III or higher can decrease by one-half the number of false positive TCD diagnoses to predict large RLS on TEE.

False feedback and beliefs influence name recall in younger and older adults.

PubMed

Strickland-Hughes, Carla M; West, Robin Lea; Smith, Kimberly A; Ebner, Natalie C

2017-09-01

Feedback is an important self-regulatory process that affects task effort and subsequent performance. Benefits of positive feedback for list recall have been explored in research on goals and feedback, but the effect of negative feedback on memory has rarely been studied. The current research extends knowledge of memory and feedback effects by investigating face-name association memory and by examining the potential mediation of feedback effects, in younger and older adults, through self-evaluative beliefs. Beliefs were assessed before and after name recognition and name recall testing. Repeated presentation of false positive feedback was compared to false negative feedback and a no feedback condition. Results showed that memory self-efficacy declined over time for participants in the negative and no feedback conditions but was sustained for those receiving positive feedback. Furthermore, participants who received negative feedback felt older after testing than before testing. For name recall, the positive feedback group outperformed the negative feedback and no feedback groups combined, with no age interactions. The observed feedback-related effects on memory were fully mediated by changes in memory self-efficacy. These findings advance our understanding of how beliefs are related to feedback in memory and inform future studies examining the importance of self-regulation in memory.

[Prospective performance evaluation of first trimester screenings in Germany for risk calculation through http://www.firsttrimester.net].

PubMed

Kleinsorge, F; Smetanay, K; Rom, J; Hörmansdörfer, C; Hörmannsdörfer, C; Scharf, A; Schmidt, P

2010-12-01

In 2008, 2 351 first trimester screenings were calculated by a newly developed internet database ( http:// www.firsttrimester.net ) to evaluate the risk for the presence of Down's syndrome. All data were evaluated by the conventional first trimester screening according to Nicolaides (FTS), based on the previous JOY Software, and by the advanced first trimester screening (AFS). After receiving the feedback of the karyotype as well as the rates of the correct positives, correct negatives, false positives, false negatives, the sensitivity and specificity were calculated and compared. Overall 255 cases were investigated which were analysed by both methods. These included 2 cases of Down's syndrome and one case of trisomy 18. The FTS and the AFS had a sensitivity of 100%. The specificity was 88.5% for the FTS and 93.0% for the AFS. As already shown in former studies, the higher specificity of the AFS is a result of a reduction of the false positive rate (28 to 17 cases). As a consequence of the AFS with a detection rate of 100% the rate of further invasive diagnostics in pregnant women is decreased by having 39% fewer positive tested women. © Georg Thieme Verlag KG Stuttgart · New York.

Hog Charm II tetracycline test screening results compared with a liquid chromatography tandem mass spectrometry 10-μg/kg method.

PubMed

Salter, Robert; Holmes, Steven; Legg, David; Coble, Joel; George, Bruce

2012-02-01

Pork tissue samples that tested positive and negative by the Charm II tetracycline test screening method in the slaughter plant laboratory were tested with the modified AOAC International liquid chromatography tandem mass spectrometry (LC-MS-MS) method 995.09 to determine the predictive value of the screening method at detecting total tetracyclines at 10 μg/kg of tissue, in compliance with Russian import regulations. There were 218 presumptive-positive tetracycline samples of 4,195 randomly tested hogs. Of these screening test positive samples, 83% (182) were positive, >10 μg/kg by LC-MS-MS; 12.8% (28) were false violative, greater than limit of detection (LOD) but <10 μg/kg; and 4.2% (8) were not detected at the LC-MS-MS LOD. The 36 false-violative and not-detected samples represent 1% of the total samples screened. Twenty-seven of 30 randomly selected tetracycline screening negative samples tested below the LC-MS-MS LOD, and 3 samples tested <3 μg/kg chlortetracycline. Results indicate that the Charm II tetracycline test is effective at predicting hogs containing >10 μg/kg total tetracyclines in compliance with Russian import regulations.

Experimental layout, data analysis, and thresholds in ELISA testing of maize for aphid-borne viruses.

PubMed

Caciagli, P; Verderio, A

2003-06-30

Several aspects of enzyme-linked immunosorbent assay (ELISA) procedures and data analysis have been examined in an attempt to find a rapid and reliable method for discriminating between 'positive' and 'negative' results when testing a large number of samples. A layout of ELISA plates was designed to reduce uncontrolled variation and to optimize the number of negative and positive controls. A transformation using the fourth root (A(1/4)) of the optical density readings corrected for the blank (A) stabilized the variance of most ELISA data examined. Transformed A values were used to calculate the true limits, at a set protection level, for false positive (C) and false negative (D). Methods are discussed to reduce the number of undifferentiated samples, i.e. the samples with response falling between C and D. The whole procedure was set up for use with an electronic spreadsheet. With the addition of few instructions of the type 'if em leader then em leader else' in the spreadsheet, the ELISA results were obtained in the simple trichotomous form 'negative/undefined/positive'. This allowed rapid analysis of more than 1100 maize samples testing for the presence of seven aphid-borne viruses-in fact almost 8000 ELISA samples.

Impact of data fragmentation across healthcare centers on the accuracy of a high-throughput clinical phenotyping algorithm for specifying subjects with type 2 diabetes mellitus

PubMed Central

Wei, Wei-Qi; Leibson, Cynthia L; Ransom, Jeanine E; Kho, Abel N; Caraballo, Pedro J; Chai, High Seng; Yawn, Barbara P; Pacheco, Jennifer A

2012-01-01

Objective To evaluate data fragmentation across healthcare centers with regard to the accuracy of a high-throughput clinical phenotyping (HTCP) algorithm developed to differentiate (1) patients with type 2 diabetes mellitus (T2DM) and (2) patients with no diabetes. Materials and methods This population-based study identified all Olmsted County, Minnesota residents in 2007. We used provider-linked electronic medical record data from the two healthcare centers that provide >95% of all care to County residents (ie, Olmsted Medical Center and Mayo Clinic in Rochester, Minnesota, USA). Subjects were limited to residents with one or more encounter January 1, 2006 through December 31, 2007 at both healthcare centers. DM-relevant data on diagnoses, laboratory results, and medication from both centers were obtained during this period. The algorithm was first executed using data from both centers (ie, the gold standard) and then from Mayo Clinic alone. Positive predictive values and false-negative rates were calculated, and the McNemar test was used to compare categorization when data from the Mayo Clinic alone were used with the gold standard. Age and sex were compared between true-positive and false-negative subjects with T2DM. Statistical significance was accepted as p<0.05. Results With data from both medical centers, 765 subjects with T2DM (4256 non-DM subjects) were identified. When single-center data were used, 252 T2DM subjects (1573 non-DM subjects) were missed; an additional false-positive 27 T2DM subjects (215 non-DM subjects) were identified. The positive predictive values and false-negative rates were 95.0% (513/540) and 32.9% (252/765), respectively, for T2DM subjects and 92.6% (2683/2898) and 37.0% (1573/4256), respectively, for non-DM subjects. Age and sex distribution differed between true-positive (mean age 62.1; 45% female) and false-negative (mean age 65.0; 56.0% female) T2DM subjects. Conclusion The findings show that application of an HTCP algorithm using data from a single medical center contributes to misclassification. These findings should be considered carefully by researchers when developing and executing HTCP algorithms. PMID:22249968

Visual field progression in glaucoma: what is the specificity of the Guided Progression Analysis?

PubMed

Artes, Paul H; O'Leary, Neil; Nicolela, Marcelo T; Chauhan, Balwantray C; Crabb, David P

2014-10-01

To estimate the specificity of the Guided Progression Analysis (GPA) (Carl Zeiss Meditec, Dublin, CA) in individual patients with glaucoma. Observational cohort study. Thirty patients with open-angle glaucoma. In 30 patients with open-angle glaucoma, 1 eye (median mean deviation [MD], -2.5 decibels [dB]; interquartile range, -4.4 to -1.3 dB) was tested 12 times over 3 months (Humphrey Field Analyzer, Carl Zeiss Meditec; SITA Standard, 24-2). "Possible progression" and "likely progression" were determined with the GPA. These analyses were repeated after the order of the tests had been randomly rearranged (1000 unique permutations). Rate of false-positive alerts of "possible progression" and "likely progression" with the GPA. On average, the specificity of the GPA "likely progression" alert was high-for the entire sample, the mean rate of false-positive alerts after 10 follow-up tests was 2.6%. With "possible progression," the specificity was considerably lower (false-positive rate, 18.5%). Most important, the cumulative rate of false-positive alerts varied substantially among patients, from <1% to 80% with "possible progression" and from <0.1% to 20% with "likely progression." Factors associated with false-positive alerts were visual field variability (standard deviation of MD, Spearman's rho = 0.41, P<0.001) and the reliability indices (proportion of false-positive and false-negative responses, fixation losses, rho>0.31, P≤0.10). On average, progression criteria currently used in the GPA have high specificity, but some patients are more likely to show false-positive alerts than others. This is a natural consequence of population-based change criteria and may not matter in clinical trials and studies in which large groups of patients are compared. However, it must be considered when the GPA is used in clinical practice where specificity needs to be controlled for individual patients. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Screening for ALK in non-small cell lung carcinomas: 5A4 and D5F3 antibodies perform equally well, but combined use with FISH is recommended.

PubMed

Savic, Spasenija; Diebold, Joachim; Zimmermann, Anne-Katrin; Jochum, Wolfram; Baschiera, Betty; Grieshaber, Susanne; Tornillo, Luigi; Bisig, Bettina; Kerr, Keith; Bubendorf, Lukas

2015-08-01

Immunohistochemistry (IHC) has become a promising method for pre-screening ALK-rearrangements in non-small cell lung carcinomas (NSCLC). Various ALK antibodies, detection systems and automated immunostainers are available. We therefore aimed to compare the performance of the monoclonal 5A4 (Novocastra, Leica) and D5F3 (Cell Signaling, Ventana) antibodies using two different immunostainers. Additionally we analyzed the accuracy of prospective ALK IHC-testing in routine diagnostics. Seventy-two NSCLC with available ALK FISH results and enriched for FISH-positive carcinomas were retrospectively analyzed. IHC was performed on BenchMarkXT (Ventana) using 5A4 and D5F3, respectively, and additionally with 5A4 on Bond-MAX (Leica). Data from our routine diagnostics on prospective ALK-testing with parallel IHC, using 5A4, and FISH were available from 303 NSCLC. All three IHC protocols showed congruent results. Only 1/25 FISH-positive NSCLC (4%) was false negative by IHC. For all three IHC protocols the sensitivity, specificity, positive (PPV) and negative predictive values (NPV) compared to FISH were 96%, 100%, 100% and 97.8%, respectively. In the prospective cohort 3/32 FISH-positive (9.4%) and 2/271 FISH-negative (0.7%) NSCLC were false negative and false positive by IHC, respectively. In routine diagnostics the sensitivity, specificity, PPV and NPV of IHC compared to FISH were 90.6%, 99.3%, 93.5% and 98.9%, respectively. 5A4 and D5F3 are equally well suited for detecting ALK-rearranged NSCLC. BenchMark and BOND-MAX immunostainers can be used for IHC with 5A4. True discrepancies between IHC and FISH results do exist and need to be addressed when implementing IHC in an ALK-testing algorithm. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Dana Kelly; Kurt Vedros; Robert Youngblood

This paper examines false indication probabilities in the context of the Mitigating System Performance Index (MSPI), in order to investigate the pros and cons of different approaches to resolving two coupled issues: (1) sensitivity to the prior distribution used in calculating the Bayesian-corrected unreliability contribution to the MSPI, and (2) whether (in a particular plant configuration) to model the fuel oil transfer pump (FOTP) as a separate component, or integrally to its emergency diesel generator (EDG). False indication probabilities were calculated for the following situations: (1) all component reliability parameters at their baseline values, so that the true indication ismore » green, meaning that an indication of white or above would be false positive; (2) one or more components degraded to the extent that the true indication would be (mid) white, and “false” would be green (negative) or yellow (negative) or red (negative). In key respects, this was the approach taken in NUREG-1753. The prior distributions examined were the constrained noninformative (CNI) prior used currently by the MSPI, a mixture of conjugate priors, the Jeffreys noninformative prior, a nonconjugate log(istic)-normal prior, and the minimally informative prior investigated in (Kelly et al., 2010). The mid-white performance state was set at ?CDF = ?10 ? 10-6/yr. For each simulated time history, a check is made of whether the calculated ?CDF is above or below 10-6/yr. If the parameters were at their baseline values, and ?CDF > 10-6/yr, this is counted as a false positive. Conversely, if one or all of the parameters are set to values corresponding to ?CDF > 10-6/yr but that time history’s ?CDF < 10-6/yr, this is counted as a false negative indication. The false indication (positive or negative) probability is then estimated as the number of false positive or negative counts divided by the number of time histories (100,000). Results are presented for a set of base case parameter values, and three sensitivity cases in which the number of FOTP demands was reduced, along with the Birnbaum importance of the FOTP.« less

The power of emotion versus the power of suggestion: memory for emotional events in the misinformation paradigm.

PubMed

Van Damme, Ilse; Smets, Karolien

2014-04-01

Research has shown that emotional events are remembered better than neutral events, but might also elicit an increase in false memories. The present study was designed to disentangle the influences of valence and arousal on event memory in the misinformation paradigm. Participants were shown six types of photographs (positive with high/low arousal, negative with high/low arousal, ambiguous, neutral), after which half of them were exposed to misleading information. A recognition test assessed memory for both correct and false central and peripheral details. Negative and ambiguous events elicited fewer correct and more false memories for peripheral details than positive and neutral events, regardless of previous exposure to misinformation. Arousal improved memory for correct central details, and both negative valence and arousal inhibited control participants' tendency to endorse false central details. The power of emotion was overruled by the power of suggestion, however, as the latter effect disappeared with previous exposure to misinformation. Results are discussed in the light of earlier research on emotion and cognition, recent motivational theories, and implications for forensic practice.

Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology.

PubMed

Bianchi, Diana W; Parsa, Saba; Bhatt, Sucheta; Halks-Miller, Meredith; Kurtzman, Kathryn; Sehnert, Amy J; Swanson, Amy

2015-02-01

To describe the clinical experience with noninvasive prenatal testing for fetal sex chromosomes using sequencing of maternal plasma cell-free DNA in a commercial laboratory. A noninvasive prenatal testing laboratory data set was examined for samples in which fetal sex chromosomes were reported. Available clinical outcomes were reviewed. Of 18,161 samples with sex chromosome results, no sex chromosome aneuploidy was detected in 98.9% and the fetal sex was reported as XY (9,236) or XX (8,721). In 4 of 32 cases in which the fetal sex was reportedly discordant between noninvasive prenatal testing and karyotype or ultrasonogram, a potential biological reason for the discordance exists, including two cases of documented co-twin demise, one case of a maternal kidney transplant from a male donor, and one case of fetal ambiguous genitalia. In the remaining 204 samples (1.1%), one of four sex chromosome aneuploidies (monosomy X, XXX, XXY, or XYY) was detected. The frequency of false positive results for sex chromosome aneuploidies is a minimum of 0.26% and a maximum of 1.05%. All but one of the discordant sex chromosome aneuploidy results involved the X chromosome. In two putative false-positive XXX cases, maternal XXX was confirmed by karyotype. For the false-positive cases, mean maternal age was significantly higher in monosomy X (P<.001) and lower in XXX (P=.008). Noninvasive prenatal testing results for sex chromosome aneuploidy can be confounded by maternal or fetal biological phenomena. When a discordant noninvasive prenatal testing result is encountered, resolution requires additional maternal history, detailed fetal ultrasonography, and determination of fetal and possibly maternal karyotypes.

Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases.

PubMed

Pavletic, Adriana J; Marques, Adriana R

2017-07-15

False-positive serology for Lyme disease was reported in patients with acute infectious mononucleosis. Here we describe 2 patients with early disseminated Lyme disease who were misdiagnosed with infectious mononucleosis based on false-positive tests for primary Epstein-Barr virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Current methodological issues in the economic assessment of personalized medicine.

PubMed

Annemans, Lieven; Redekop, Ken; Payne, Katherine

2013-01-01

There is a need for methodological scrutiny in the economic assessment of personalized medicine. In this article, we present a list of 10 specific issues that we argue pose specific methodological challenges that require careful consideration when designing and conducting robust model-based economic evaluations in the context of personalized medicine. Key issues are related to the correct framing of the research question, interpretation of test results, data collection of medical management options after obtaining test results, and expressing the value of tests. The need to formulate the research question clearly and be explicit and specific about the technology being evaluated is essential because various test kits can have the same purpose and yet differ in predictive value, costs, and relevance to practice and patient populations. The correct reporting of sensitivity/specificity, and especially the false negatives and false positives (which are population dependent), of the investigated tests is also considered as a key element. This requires additional structural complexity to establish the relationship between the test result and the consecutive treatment changes and outcomes. This process involves translating the test characteristics into clinical utility, and therefore outlining the clinical and economic consequences of true and false positives and true and false negatives. Information on treatment patterns and on their costs and outcomes, however, is often lacking, especially for false-positive and false-negative test results. The analysis can even become very complex if different tests are combined or sequentially used. This potential complexity can be handled by explicitly showing how these tests are going to be used in practice and then working with the combined sensitivities and specificities of the tests. Each of these issues leads to a higher degree of uncertainty in economic models designed to assess the added value of personalized medicine compared with their simple pharmaceutical counterparts. To some extent, these problems can be overcome by performing early population-level simulations, which can lead to the identification and collection of data on critical input parameters. Finally, it is important to understand that a test strategy does not necessarily lead to more quality-adjusted life-years (QALYs). It is possible that the test will lead to not only fewer QALYs but also fewer costs, which can be defined as "decremental" cost per QALYs. Different decision criteria are needed to interpret such results. © 2013 Published by Elsevier Inc. on behalf of International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Relative Packing Groups in Template-Based Structure Prediction: Cooperative Effects of True Positive Constraints

PubMed Central

Day, Ryan; Qu, Xiaotao; Swanson, Rosemarie; Bohannan, Zach; Bliss, Robert

2011-01-01

Abstract Most current template-based structure prediction methods concentrate on finding the correct backbone conformation and then packing sidechains within that backbone. Our packing-based method derives distance constraints from conserved relative packing groups (RPGs). In our refinement approach, the RPGs provide a level of resolution that restrains global topology while allowing conformational sampling. In this study, we test our template-based structure prediction method using 51 prediction units from CASP7 experiments. RPG-based constraints are able to substantially improve approximately two-thirds of starting templates. Upon deeper investigation, we find that true positive spatial constraints, especially those non-local in sequence, derived from the RPGs were important to building nearer native models. Surprisingly, the fraction of incorrect or false positive constraints does not strongly influence the quality of the final candidate. This result indicates that our RPG-based true positive constraints sample the self-consistent, cooperative interactions of the native structure. The lack of such reinforcing cooperativity explains the weaker effect of false positive constraints. Generally, these findings are encouraging indications that RPGs will improve template-based structure prediction. PMID:21210729

Automatic detection of apical roots in oral radiographs

NASA Astrophysics Data System (ADS)

Wu, Yi; Xie, Fangfang; Yang, Jie; Cheng, Erkang; Megalooikonomou, Vasileios; Ling, Haibin

2012-03-01

The apical root regions play an important role in analysis and diagnosis of many oral diseases. Automatic detection of such regions is consequently the first step toward computer-aided diagnosis of these diseases. In this paper we propose an automatic method for periapical root region detection by using the state-of-theart machine learning approaches. Specifically, we have adapted the AdaBoost classifier for apical root detection. One challenge in the task is the lack of training cases especially for diseased ones. To handle this problem, we boost the training set by including more root regions that are close to the annotated ones and decompose the original images to randomly generate negative samples. Based on these training samples, the Adaboost algorithm in combination with Haar wavelets is utilized in this task to train an apical root detector. The learned detector usually generates a large amount of true and false positives. In order to reduce the number of false positives, a confidence score for each candidate detection result is calculated for further purification. We first merge the detected regions by combining tightly overlapped detected candidate regions and then we use the confidence scores from the Adaboost detector to eliminate the false positives. The proposed method is evaluated on a dataset containing 39 annotated digitized oral X-Ray images from 21 patients. The experimental results show that our approach can achieve promising detection accuracy.

10 CFR 26.139 - Reporting initial validity and drug test results.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Reporting initial validity and drug test results. 26.139... § 26.139 Reporting initial validity and drug test results. (a) The licensee testing facility shall... permitted under § 26.75(h), positive test results from initial drug tests at the licensee testing facility...

10 CFR 26.139 - Reporting initial validity and drug test results.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Reporting initial validity and drug test results. 26.139... § 26.139 Reporting initial validity and drug test results. (a) The licensee testing facility shall... permitted under § 26.75(h), positive test results from initial drug tests at the licensee testing facility...

Do 15-month-old infants understand false beliefs?

PubMed

Onishi, Kristine H; Baillargeon, Renée

2005-04-08

For more than two decades, researchers have argued that young children do not understand mental states such as beliefs. Part of the evidence for this claim comes from preschoolers' failure at verbal tasks that require the understanding that others may hold false beliefs. Here, we used a novel nonverbal task to examine 15-month-old infants' ability to predict an actor's behavior on the basis of her true or false belief about a toy's hiding place. Results were positive, supporting the view that, from a young age, children appeal to mental states--goals, perceptions, and beliefs--to explain the behavior of others.

False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences.

PubMed

Piketty, Marie-Liesse; Polak, Michel; Flechtner, Isabelle; Gonzales-Briceño, Laura; Souberbielle, Jean-Claude

2017-05-01

Immunoassays are now commonly used for hormone measurement, in high throughput analytical platforms. Immunoassays are generally robust to interference. However, endogenous analytical error may occur in some patients; this may be encountered in biotin supplementation or in the presence of anti-streptavidin antibody, in immunoassays involving streptavidin-biotin interaction. In these cases, the interference may induce both false positive and false negative results, and simulate a seemingly coherent hormonal profile. It is to be feared that this type of errors will be more frequently observed. This review underlines the importance of keeping close interactions between biologists and clinicians to be able to correlate the hormonal assay results with the clinical picture.

How Fuzzy-Trace Theory Predicts True and False Memories for Words, Sentences, and Narratives

PubMed Central

Reyna, Valerie F.; Corbin, Jonathan C.; Weldon, Rebecca B.; Brainerd, Charles J.

2016-01-01

Fuzzy-trace theory posits independent verbatim and gist memory processes, a distinction that has implications for such applied topics as eyewitness testimony. This distinction between precise, literal verbatim memory and meaning-based, intuitive gist accounts for memory paradoxes including dissociations between true and false memory, false memories outlasting true memories, and developmental increases in false memory. We provide an overview of fuzzy-trace theory, and, using mathematical modeling, also present results demonstrating verbatim and gist memory in true and false recognition of narrative sentences and inferences. Results supported fuzzy-trace theory's dual-process view of memory: verbatim memory was relied on to reject meaning-consistent, but unpresented, sentences (via recollection rejection). However, verbatim memory was often not retrieved, and gist memory supported acceptance of these sentences (via similarity judgment and phantom recollection). Thus, mathematical models of words can be extended to explain memory for complex stimuli, such as narratives, the kind of memory interrogated in law. PMID:27042402

Inflammatory disorders mimicking periprosthetic joint infections may result in false positive α-defensin.

PubMed

Plate, Andreas; Stadler, Laura; Sutter, Reto; Anagnostopoulos, Alexia; Frustaci, Dario; Zbinden, Reinhard; Fucentese, Sandro F; Zinkernagel, Annelies S; Zingg, Patrick O; Achermann, Yvonne

2018-02-26

The antimicrobial peptide α-defensin has recently been introduced as potential "single" biomarker with a high sensitivity and specificity for the preoperative diagnosis of periprosthetic joint infections (PJIs). However, most studies assessed the benefits of the test with exclusion of patients with rheumatic diseases. We aimed to evaluate the α-defensin test in a cohort study without exclusion of cases with inflammatory diseases. Between June 2016 and June 2017, we prospectively included cases with a suspected PJI and an available lateral flow test α-defensin (Synovasure®) in synovial fluid. We compared the test result to the diagnostic criteria for PJIs published by an International Consensus Group in 2013. We included 109 cases (49 hips, 60 knees) in which preoperative α-defensin tests had been performed. Thereof, 20 PJIs (16 hips, 4 knees) were diagnosed. Preoperative α-defensin tests were positive in 25 cases (22.9%) with a test sensitivity and specificity of 90% and 92.1% (95% confidence interval [CI], 68.3 - 98.8% and 84.5 - 96.8%, respectively), and a high negative predictive value of 97.6% (95% CI, 91.7 - 99.4%). We interpreted seven α-defensin tests as false positive, mainly in cases with inflammatory rheumatic diseases, including crystal deposition diseases. A negative synovial α-defensin test can reliably rule out a PJI. However, the test can be false positive in conjunction with an underlying non-infectious inflammatory disease. We therefore propose to use the α-defensin test only in addition to MSIS criteria and assessment for crystals in synovial aspirates. Copyright © 2018. Published by Elsevier Ltd.

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

PubMed

Schaarschmidt, Benedikt Michael; Grueneisen, Johannes; Stebner, Vanessa; Klode, Joachim; Stoffels, Ingo; Umutlu, Lale; Schadendorf, Dirk; Heusch, Philipp; Antoch, Gerald; Pöppel, Thorsten Dirk

2018-06-06

To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true positive findings could not be increased. In conclusion, integrated 18F-FDG PET/MR does not reliably differentiate N-positive from N-negative melanoma patients. Additional DWI does not increase the sensitivity of 18F-FDG PET/MR. Hence, sentinel lymph node biopsy cannot be replaced by 18F-FDG-PE/MR or 18F-FDG-PET/CT.

Positive events protect children from causal false memories for scripted events.

PubMed

Melinder, Annika; Toffalini, Enrico; Geccherle, Eleonora; Cornoldi, Cesare

2017-11-01

Adults produce fewer inferential false memories for scripted events when their conclusions are emotionally charged than when they are neutral, but it is not clear whether the same effect is also found in children. In the present study, we examined this issue in a sample of 132 children aged 6-12 years (mean 9 years, 3 months). Participants encoded photographs depicting six script-like events that had a positively, negatively, or a neutral valenced ending. Subsequently, true and false recognition memory of photographs related to the observed scripts was tested as a function of emotionality. Causal errors-a type of false memory thought to stem from inferential processes-were found to be affected by valence: children made fewer causal errors for positive than for neutral or negative events. Hypotheses are proposed on why adults were found protected against inferential false memories not only by positive (as for children) but also by negative endings when administered similar versions of the same paradigm.