Prospective evaluation of radionuclide scanning in detection of intestinal necrosis in neonatal necrotizing enterocolitis

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

Haase, G.M.; Sfakianakis, G.N.; Lobe, T.E.

1981-06-01

The ability of external imaging to demonstrate intestinal infarction in neonatal necrotizing enterocolitis (NEC) was prospectively evaluated. The radiopharmaceutical technetium--99m diphosphonate was injected intravenously and the patients subsequently underwent abdominal scanning. Clinical patient care and interpretation of the images were entirely independent throughout the study. Of 33 studies, 7 were positive, 4 were suspicious, and 22 were negative. One false positive study detected ischemia without transmural infarction. The second false positive scan occurred postoperatively and was due to misinterpretation of the hyperactivity along the surgical incision. None of the suspicious cases had damaged bowel. The two false negative studies clearlymore » failed to demonstrate frank intestinal necrosis. The presence of very small areas of infarction, errors in technical settings, subjective interpretation of scans and delayed clearance of the radionuclide in a critically ill neonate may all limit the accuracy of external abdominal scanning. However, in spite of an error rate of 12%, it is likely that this technique will enhance the present clinical, laboratory, and radiologic parameters of patient management in NEC.« less

Between-litter variation in developmental studies of hormones and behavior: Inflated false positives and diminished power.

PubMed

Williams, Donald R; Carlsson, Rickard; Bürkner, Paul-Christian

2017-10-01

Developmental studies of hormones and behavior often include littermates-rodent siblings that share early-life experiences and genes. Due to between-litter variation (i.e., litter effects), the statistical assumption of independent observations is untenable. In two literatures-natural variation in maternal care and prenatal stress-entire litters are categorized based on maternal behavior or experimental condition. Here, we (1) review both literatures; (2) simulate false positive rates for commonly used statistical methods in each literature; and (3) characterize small sample performance of multilevel models (MLM) and generalized estimating equations (GEE). We found that the assumption of independence was routinely violated (>85%), false positives (α=0.05) exceeded nominal levels (up to 0.70), and power (1-β) rarely surpassed 0.80 (even for optimistic sample and effect sizes). Additionally, we show that MLMs and GEEs have adequate performance for common research designs. We discuss implications for the extant literature, the field of behavioral neuroendocrinology, and provide recommendations. Copyright © 2017 Elsevier Inc. 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.

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

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;

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.

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 .

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.

COMPARATIVE IN VITRO PULMONARY TOXICITY OF ENGINEERED, MANUFACTURED, AND ENVIRONMENTAL NANOPARTICLES

EPA Science Inventory

Engineered nanomaterials display many unique physicochemical properties for a variety of applications and due to their novel propertiesapplications may have unique routes of exposure and toxicity. This study examines the: 1) ability of the MTT assay to generate false positives or...

Differentiation of Body Fluid Stains on Fabrics Using External Reflection Fourier Transform Infrared Spectroscopy (FT-IR) and Chemometrics.

PubMed

Zapata, Félix; de la Ossa, Ma Ángeles Fernández; García-Ruiz, Carmen

2016-04-01

Body fluids are evidence of great forensic interest due to the DNA extracted from them, which allows genetic identification of people. This study focuses on the discrimination among semen, vaginal fluid, and urine stains (main fluids in sexual crimes) placed on different colored cotton fabrics by external reflection Fourier transform infrared spectroscopy (FT-IR) combined with chemometrics. Semen-vaginal fluid mixtures and potential false positive substances commonly found in daily life such as soaps, milk, juices, and lotions were also studied. Results demonstrated that the IR spectral signature obtained for each body fluid allowed its identification and the correct classification of unknown stains by means of principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA). Interestingly, results proved that these IR spectra did not show any bands due to the color of the fabric and no substance of those present in daily life which were analyzed, provided a false positive. © The Author(s) 2016.

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.

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

5 CFR 732.301 - Due process.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Due process. 732.301 Section 732.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.301 Due process. When an agency makes an...

5 CFR 732.301 - Due process.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Due process. 732.301 Section 732.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.301 Due process. When an agency makes an...

5 CFR 732.301 - Due process.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Due process. 732.301 Section 732.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.301 Due process. When an agency makes an...

5 CFR 732.301 - Due process.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Due process. 732.301 Section 732.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.301 Due process. When an agency makes an...

5 CFR 732.301 - Due process.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Due process. 732.301 Section 732.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.301 Due process. When an agency makes an...

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

[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 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.

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.

Unmodeled observation error induces bias when inferring patterns and dynamics of species occurrence via aural detections

USGS Publications Warehouse

McClintock, Brett T.; Bailey, Larissa L.; Pollock, Kenneth H.; Simons, Theodore R.

2010-01-01

The recent surge in the development and application of species occurrence models has been associated with an acknowledgment among ecologists that species are detected imperfectly due to observation error. Standard models now allow unbiased estimation of occupancy probability when false negative detections occur, but this is conditional on no false positive detections and sufficient incorporation of explanatory variables for the false negative detection process. These assumptions are likely reasonable in many circumstances, but there is mounting evidence that false positive errors and detection probability heterogeneity may be much more prevalent in studies relying on auditory cues for species detection (e.g., songbird or calling amphibian surveys). We used field survey data from a simulated calling anuran system of known occupancy state to investigate the biases induced by these errors in dynamic models of species occurrence. Despite the participation of expert observers in simplified field conditions, both false positive errors and site detection probability heterogeneity were extensive for most species in the survey. We found that even low levels of false positive errors, constituting as little as 1% of all detections, can cause severe overestimation of site occupancy, colonization, and local extinction probabilities. Further, unmodeled detection probability heterogeneity induced substantial underestimation of occupancy and overestimation of colonization and local extinction probabilities. Completely spurious relationships between species occurrence and explanatory variables were also found. Such misleading inferences would likely have deleterious implications for conservation and management programs. We contend that all forms of observation error, including false positive errors and heterogeneous detection probabilities, must be incorporated into the estimation framework to facilitate reliable inferences about occupancy and its associated vital rate parameters.

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.

Experimental investigation of false positive errors in auditory species occurrence surveys

USGS Publications Warehouse

Miller, David A.W.; Weir, Linda A.; McClintock, Brett T.; Grant, Evan H. Campbell; Bailey, Larissa L.; Simons, Theodore R.

2012-01-01

False positive errors are a significant component of many ecological data sets, which in combination with false negative errors, can lead to severe biases in conclusions about ecological systems. We present results of a field experiment where observers recorded observations for known combinations of electronically broadcast calling anurans under conditions mimicking field surveys to determine species occurrence. Our objectives were to characterize false positive error probabilities for auditory methods based on a large number of observers, to determine if targeted instruction could be used to reduce false positive error rates, and to establish useful predictors of among-observer and among-species differences in error rates. We recruited 31 observers, ranging in abilities from novice to expert, that recorded detections for 12 species during 180 calling trials (66,960 total observations). All observers made multiple false positive errors and on average 8.1% of recorded detections in the experiment were false positive errors. Additional instruction had only minor effects on error rates. After instruction, false positive error probabilities decreased by 16% for treatment individuals compared to controls with broad confidence interval overlap of 0 (95% CI: -46 to 30%). This coincided with an increase in false negative errors due to the treatment (26%; -3 to 61%). Differences among observers in false positive and in false negative error rates were best predicted by scores from an online test and a self-assessment of observer ability completed prior to the field experiment. In contrast, years of experience conducting call surveys was a weak predictor of error rates. False positive errors were also more common for species that were played more frequently, but were not related to the dominant spectral frequency of the call. Our results corroborate other work that demonstrates false positives are a significant component of species occurrence data collected by auditory methods. Instructing observers to only report detections they are completely certain are correct is not sufficient to eliminate errors. As a result, analytical methods that account for false positive errors will be needed, and independent testing of observer ability is a useful predictor for among-observer variation in observation error rates.

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.

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.

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

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.

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.

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.

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.

Where Have All the Interactions Gone? Estimating the Coverage of Two-Hybrid Protein Interaction Maps

PubMed Central

Huang, Hailiang; Jedynak, Bruno M; Bader, Joel S

2007-01-01

Yeast two-hybrid screens are an important method for mapping pairwise physical interactions between proteins. The fraction of interactions detected in independent screens can be very small, and an outstanding challenge is to determine the reason for the low overlap. Low overlap can arise from either a high false-discovery rate (interaction sets have low overlap because each set is contaminated by a large number of stochastic false-positive interactions) or a high false-negative rate (interaction sets have low overlap because each misses many true interactions). We extend capture–recapture theory to provide the first unified model for false-positive and false-negative rates for two-hybrid screens. Analysis of yeast, worm, and fly data indicates that 25% to 45% of the reported interactions are likely false positives. Membrane proteins have higher false-discovery rates on average, and signal transduction proteins have lower rates. The overall false-negative rate ranges from 75% for worm to 90% for fly, which arises from a roughly 50% false-negative rate due to statistical undersampling and a 55% to 85% false-negative rate due to proteins that appear to be systematically lost from the assays. Finally, statistical model selection conclusively rejects the Erdös-Rényi network model in favor of the power law model for yeast and the truncated power law for worm and fly degree distributions. Much as genome sequencing coverage estimates were essential for planning the human genome sequencing project, the coverage estimates developed here will be valuable for guiding future proteomic screens. All software and datasets are available in Datasets S1 and S2, Figures S1–S5, and Tables S1−S6, and are also available from our Web site, http://www.baderzone.org. PMID:18039026

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.

Enhancement in sample collection for the detection of MDMA using a novel planar SPME (PSPME) device coupled to ion mobility spectrometry (IMS).

PubMed

Gura, Sigalit; Guerra-Diaz, Patricia; Lai, Hanh; Almirall, José R

2009-07-01

Trace detection of illicit drugs challenges the scientific community to develop improved sensitivity and selectivity in sampling and detection techniques. Ion mobility spectrometry (IMS) is one of the prominent trace detectors for illicit drugs and explosives, mostly due to its portability, high sensitivity and fast analysis. Current sampling methods for IMS rely on wiping suspected surfaces or withdrawing air through filters to collect particulates. These methods depend greatly on the particulates being bound onto surfaces or having sufficient vapour pressure to be airborne. Many of these compounds are not readily available in the headspace due to their low vapour pressure. This research presents a novel SPME device for enhanced air sampling and shows the use of optimized IMS by genetic algorithms to target volatile markers and/or odour signatures of illicit substances. The sampling method was based on unique static samplers, planar substrates coated with sol-gel polydimethyl siloxane (PDMS) nanoparticles, also known as planar solid-phase microextraction (PSPME). Due to its surface chemistry, high surface area and capacity, PSPME provides significant increases in sensitivity over conventional fibre SPME. The results show a 50-400 times increase in the detection capacity for piperonal, the odour signature of 3,4-methylenedioxymethamphetamine (MDMA). The PSPME-IMS technique was able to detect 600 ng of piperonal in a 30 s extraction from a quart-sized can containing 5 MDMA tablets, while detection using fibre SPME-IMS was not attainable. In a blind study of six cases suspected to contain varying amounts of MDMA in the tablets, PSPME-IMS successfully detected five positive cases and also produced no false positives or false negatives. One positive case had minimal amounts of MDMA resulting in a false negative response for fibre SPME-IMS.

[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.

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

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/

Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

PubMed

Joyce, K M; McInerney, N M; Piggott, R P; Martin, F; Jones, D M; Hussey, A J; Kerin, M J; Kelly, J L; Regan, P J

2017-11-01

Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

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.

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

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.

Detecting false positive sequence homology: a machine learning approach.

PubMed

Fujimoto, M Stanley; Suvorov, Anton; Jensen, Nicholas O; Clement, Mark J; Bybee, Seth M

2016-02-24

Accurate detection of homologous relationships of biological sequences (DNA or amino acid) amongst organisms is an important and often difficult task that is essential to various evolutionary studies, ranging from building phylogenies to predicting functional gene annotations. There are many existing heuristic tools, most commonly based on bidirectional BLAST searches that are used to identify homologous genes and combine them into two fundamentally distinct classes: orthologs and paralogs. Due to only using heuristic filtering based on significance score cutoffs and having no cluster post-processing tools available, these methods can often produce multiple clusters constituting unrelated (non-homologous) sequences. Therefore sequencing data extracted from incomplete genome/transcriptome assemblies originated from low coverage sequencing or produced by de novo processes without a reference genome are susceptible to high false positive rates of homology detection. In this paper we develop biologically informative features that can be extracted from multiple sequence alignments of putative homologous genes (orthologs and paralogs) and further utilized in context of guided experimentation to verify false positive outcomes. We demonstrate that our machine learning method trained on both known homology clusters obtained from OrthoDB and randomly generated sequence alignments (non-homologs), successfully determines apparent false positives inferred by heuristic algorithms especially among proteomes recovered from low-coverage RNA-seq data. Almost ~42 % and ~25 % of predicted putative homologies by InParanoid and HaMStR respectively were classified as false positives on experimental data set. Our process increases the quality of output from other clustering algorithms by providing a novel post-processing method that is both fast and efficient at removing low quality clusters of putative homologous genes recovered by heuristic-based approaches.

A false positive newborn screening result due to a complex allele carrying two frequent CF-causing variants.

PubMed

Bergougnoux, Anne; Boureau-Wirth, Amandine; Rouzier, Cécile; Altieri, Jean-Pierre; Verneau, Fanny; Larrieu, Lise; Koenig, Michel; Claustres, Mireille; Raynal, Caroline

2016-05-01

The detection of two frequent CFTR disease-causing variations in the context of a newborn screening program (NBS) usually leads to the diagnosis of cystic fibrosis (CF) and a relevant genetic counseling in the family. In the present study, CF-causing variants p.Phe508del (F508del) and c.3140-26A>G (3272-26A>G) were identified on a neonate with positive ImmunoReactive Trypsinogen test by the Elucigene™ CF30 kit. The CF diagnosis initially suggested, despite three inconclusive Sweat Chloride Tests (SCT), was finally ruled out after the familial segregation study combined with a negative SCT. Haplotype studies, based on the comparison of 80 p.Phe508del haplotypes, suggested a probable de novo occurrence of c.3140-26A>G on the p.Phe508del ancestral allele in this family. This false positive case emphasizes the importance of SCT in the NBS strategy. Moreover, it raises the need for familial segregation studies in CF and in overall molecular diagnosis strategy of autosomal recessive diseases. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Modeling Kepler Transit Light Curves as False Positives: Rejection of Blend Scenarios for Kepler-9, and Validation of Kepler-9 d, a Super-Earth-Size Planet in a Multiple System

NASA Technical Reports Server (NTRS)

Torres, Guillermo; Fressin, Francois; Batalha, Natalie M.; Borucki, William J.; Brown, Timothy M.; Bryson, Stephen T.; Buchhave, Lars A.; Charbonneau, David; Ciardi, David R.; Dunham, Edward W.;

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.

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

Optimized molecular resolution of cross-contamination alerts in clinical mycobacteriology laboratories.

PubMed

Martín, Ana; Herranz, Marta; Lirola, Miguel Martínez; Fernández, Rosa Fernández; Bouza, Emilio; García de Viedma, Darío

2008-02-14

The phenomenon of misdiagnosing tuberculosis (TB) by laboratory cross-contamination when culturing Mycobacterium tuberculosis (MTB) has been widely reported and it has an obvious clinical, therapeutic and social impact. The final confirmation of a cross-contamination event requires the molecular identification of the same MTB strain cultured from both the potential source of the contamination and from the false-positive candidate. The molecular tool usually applied in this context is IS6110-RFLP which takes a long time to provide an answer, usually longer than is acceptable for microbiologists and clinicians to make decisions. Our purpose in this study is to evaluate a novel PCR-based method, MIRU-VNTR as an alternative to assure a rapid and optimized analysis of cross-contamination alerts. MIRU-VNTR was prospectively compared with IS6110-RFLP for clarifying 19 alerts of false positivity from other laboratories. MIRU-VNTR highly correlated with IS6110-RFLP, reduced the response time by 27 days and clarified six alerts unresolved by RFLP. Additionally, MIRU-VNTR revealed complex situations such as contamination events involving polyclonal isolates and a false-positive case due to the simultaneous cross-contamination from two independent sources. Unlike standard RFLP-based genotyping, MIRU-VNTR i) could help reduce the impact of a false positive diagnosis of TB, ii) increased the number of events that could be solved and iii) revealed the complexity of some cross-contamination events that could not be dissected by IS6110-RFLP.

Cumulative risk of false positive test in relation to breast symptoms in mammography screening: a historical prospective cohort study.

PubMed

Singh, Deependra; Pitkäniemi, Janne; Malila, Nea; Anttila, Ahti

2016-09-01

Mammography has been found effective as the primary screening test for breast cancer. We estimated the cumulative probability of false positive screening test results with respect to symptom history reported at screen. A historical prospective cohort study was done using individual screening data from 413,611 women aged 50-69 years with 2,627,256 invitations for mammography screening between 1992 and 2012 in Finland. Symptoms (lump, retraction, and secretion) were reported at 56,805 visits, and 48,873 visits resulted in a false positive mammography result. Generalized linear models were used to estimate the probability of at least one false positive test and true positive at screening visits. The estimates were compared among women with and without symptoms history. The estimated cumulative probabilities were 18 and 6 % for false positive and true positive results, respectively. In women with a history of a lump, the cumulative probabilities of false positive test and true positive were 45 and 16 %, respectively, compared to 17 and 5 % with no reported lump. In women with a history of any given symptom, the cumulative probabilities of false positive test and true positive were 38 and 13 %, respectively. Likewise, women with a history of a 'lump and retraction' had the cumulative false positive probability of 56 %. The study showed higher cumulative risk of false positive tests and more cancers detected in women who reported symptoms compared to women who did not report symptoms at screen. The risk varies substantially, depending on symptom types and characteristics. Information on breast symptoms influences the balance of absolute benefits and harms of screening.

The problem of false positives and false negatives in violent video game experiments.

PubMed

Ferguson, Christopher J

The problem of false positives and negatives has received considerable attention in behavioral research in recent years. The current paper uses video game violence research as an example of how such issues may develop in a field. Despite decades of research, evidence on whether violent video games (VVGs) contribute to aggression in players has remained mixed. Concerns have been raised in recent years that experiments regarding VVGs may suffer from both "false positives" and "false negatives." The current paper examines this issue in three sets of video game experiments, two sets of video game experiments on aggression and prosocial behaviors identified in meta-analysis, and a third group of recent null studies. Results indicated that studies of VVGs and aggression appear to be particularly prone to false positive results. Studies of VVGs and prosocial behavior, by contrast are heterogeneous and did not demonstrate any indication of false positive results. However, their heterogeneous nature made it difficult to base solid conclusions on them. By contrast, evidence for false negatives in null studies was limited, and little evidence emerged that null studies lacked power in comparison those highlighted in past meta-analyses as evidence for effects. These results are considered in light of issues related to false positives and negatives in behavioral science more broadly. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Discovery of a Candidate Companion to a Transiting System KOI-94: A Direct Imaging Study for a Possibility of a False Positive

NASA Technical Reports Server (NTRS)

Takahashi, Yasuhiro; Narita, Norio; Hirano, Teruyuki; Kuzuhara, Masayuki; Tamura, Motohide; Kudo, Tomoyuki; Kusakabe, Nobuhiko; Hashimoto, Jun; Sato, Bun'ei; Abe, Lyu;

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.

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.

Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening.

PubMed

Arias, Angela; Corbella, Marc; Fons, Carmen; Sempere, Angela; García-Villoria, Judit; Ormazabal, Aida; Poo, Pilar; Pineda, Mercé; Vilaseca, María Antonia; Campistol, Jaume; Briones, Paz; Pàmpols, Teresa; Salomons, Gajja S; Ribes, Antonia; Artuch, Rafael

2007-11-01

To report the prevalence of creatine transporter deficiency in males with mental retardation and to study whether a protein-rich food intake might be a potential diagnostic pitfall. We determined creatine/creatinine ratio in urine samples from 1600 unrelated male patients with mental retardation and/or autism. Urine creatine was analyzed by HPLC-MS/MS. Thirty-three of 1600 cases showed increased urine creatine/creatinine ratio. Four out of these thirty-three cases were definitively diagnosed with creatine transporter deficiency, while the other 29 were false positive results. Significantly higher values were observed for urine Cr/Crn ratio in healthy volunteers after a meal based on beef or oily fish as compared to eggs, pasta or salad (Wilcoxon test: p<0.005). False positive results may be observed in biochemical screening for creatine transporter deficiency, and they may be due to intake of meals rich in creatine prior to urine samples analysis.

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.

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

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

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.

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.

Detection of insect damage in almonds

NASA Astrophysics Data System (ADS)

Kim, Soowon; Schatzki, Thomas F.

1999-01-01

Pinhole insect damage in natural almonds is very difficult to detect on-line. Further, evidence exists relating insect damage to aflatoxin contamination. Hence, for quality and health reasons, methods to detect and remove such damaged nuts are of great importance in this study, we explored the possibility of using x-ray imaging to detect pinhole damage in almonds by insects. X-ray film images of about 2000 almonds and x-ray linescan images of only 522 pinhole damaged almonds were obtained. The pinhole damaged region appeared slightly darker than non-damaged region in x-ray negative images. A machine recognition algorithm was developed to detect these darker regions. The algorithm used the first order and the second order information to identify the damaged region. To reduce the possibility of false positive results due to germ region in high resolution images, germ detection and removal routines were also included. With film images, the algorithm showed approximately an 81 percent correct recognition ratio with only 1 percent false positives whereas line scan images correctly recognized 65 percent of pinholes with about 9 percent false positives. The algorithms was very fast and efficient requiring only minimal computation time. If implemented on line, theoretical throughput of this recognition system would be 66 nuts/second.

Performance of Momguard, a new non-invasive prenatal testing protocol developed in Korea.

PubMed

Lee, Mi-Young; Cho, Dae-Yeon; Won, Hye-Sung; Hwang, Ah Reum; Jeong, Bada; Kim, Jihun; Oh, Mijin

2015-09-01

To evaluate the performance of Momguard, non-invasive prenatal test (NIPT) for detecting trisomy (T) 21, T18, T13, and sex-chromosome abnormalities recently developed in Korea. This preliminary study formed part of a large prospective cohort study conducted at Asan Medical Center, Seoul, Korea. Only pregnant women who underwent both NIPT and confirmatory karyotyping were included in this study. NIPT results were compared with those of karyotype analyses. Among 93 eligible cases, NIPT results could not be obtained in one case due to a low fetal cell-free DNA fraction. Based on NIPT, eight cases of fetal aneuploidies, including T21 (n=5), T18 (n=2), and T13 (n=1), were identified. For T21 and T18, the sensitivity and specificity of NIPT were both 100%, with a false-positive and false-negative rate of 0% and a positive-predictive value of 100%. One patient classified as having intermediate risk for T13 by NIPT was confirmed to have T13 by karyotyping, and there were no false-negative cases. No cases of sex-chromosome anomalies were detected by NIPT or karyotyping during the study period. Momguard is a reliable screening tool for detecting T21 and T18. For T13 and sex-chromosome anomalies, further prospective studies are necessary to confirm its utility.

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.

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.

Optimization and validation of CEDIA drugs of abuse immunoassay tests in serum on Hitachi 912.

PubMed

Kirschbaum, Katrin M; Musshoff, Frank; Schmithausen, Ricarda; Stockhausen, Sarah; Madea, Burkhard

2011-10-10

Due to sensitive limits of detection of chromatographic methods and low limit values regarding the screening of drugs under the terms of impairment in safe driving (§ 24a StVG, Street Traffic Law in Germany), preliminary immunoassay (IA) tests should be able to detect also low concentrations of legal and illegal drugs in serum in forensic cases. False-negatives should be avoided, the rate of false-positive samples should be low due to cost and time. An optimization of IA cutoff values and a validation of the assay is required for each laboratory. In a retrospective study results for serum samples containing amphetamine, methylenedioxy derivatives, cannabinoids, benzodiazepines, cocaine (metabolites), methadone and opiates obtained with CEDIA drugs of abuse reagents on a Hitachi 912 autoanalyzer were compared with quantitative results of chromatographic methods (gas or liquid chromatography coupled with mass spectrometry (GC/MS or LC/MS)). Firstly sensitivity, specificity, positive and negative predictive values and overall misclassification rates were evaluated by contingency tables and compared to ROC-analyses and Youden-Indices. Secondly ideal cutoffs were statistically calculated on the basis of sensitivity and specificity as decisive statistical criteria with focus on a high sensitivity (low rates of false-negatives), i.e. using the Youden-Index. Immunoassay (IA) and confirmatory results were available for 3014 blood samples. Sensitivity was 90% or more for nearly all analytes: amphetamines (IA cutoff 9.5 ng/ml), methylenedioxy derivatives (IA cutoff 5.5 ng/ml), cannabinoids (IA cutoff 14.5 ng/ml), benzodiazepines (IA cutoff >0 ng/ml). Test of opiates showed a sensitivity of 86% for a IA cutoff value of >0 ng/ml. Values for specificity ranged between 33% (methadone, IA cutoff 10 ng/ml) and 90% (cocaine, IA cutoff 20 ng/ml). Lower cutoff values as recommended by ROC analyses were chosen for most tests to decrease the rate of false-negatives. Analyses enabled the definition of cutoff values with good values for sensitivity. Small rates of false-positives can be accepted in forensic cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.

Psychosocial Distress and Knowledge Deficiencies in Parents of Children in Ireland Who Carry an Altered Cystic Fibrosis Gene.

PubMed

Quigley, S J; Linnane, B; Connellan, S; Ward, A; Ryan, P

2018-06-01

Significant gaps have been identified in parental understanding of CF newborn screening and the consequences of carrying an altered CF gene. Seven potential causes of psychosocial adversity arising from false positive newborn screening for CF have been identified. The current study aimed to increase parents understanding of CF, reduce their levels of stress, and investigate psychosocial adversity arising from false-positive screening. This national study was run over one year in the Republic of Ireland. Parents were recruited for the study following a diagnostic sweat test confirming their child carried a single altered CF gene. Parents were randomly assigned into a control and intervention group, with those in the intervention group receiving a carefully designed information pack. All parents took part in semi-structured interviews. Parents (n = 16) who received an information pack had significantly higher CF knowledge scores than parents (n = 16) in the control group. 66% of parents in the control group misunderstood the health implications of carrying an altered CF gene, no parents in the intervention group had the same misunderstanding. There was no significant difference in stress scores between the groups. Parents of infants who had more than one sweat test due to insufficient sweat quantity had higher overall stress percentiles (50%), than parents of infants who had one sweat test (30%), indicating greater parental stress. The combination of written and audio-visual information contained in the information pack successfully increased parents comprehension of CF. The study also evaluates the potential for psychosocial adversity following false positive newborn screening for CF.

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.

Heidelberg Retina Tomography Analysis in Optic Disks with Anatomic Particularities

PubMed Central

Alexandrescu, C; Pascu, R; Ilinca, R; Popescu, V; Ciuluvica, R; Voinea, L; Celea, C

2010-01-01

Due to its objectivity, reproducibility and predictive value confirmed by many large scale statistical clinical studies, Heidelberg Retina Tomography has become one of the most used computerized image analysis of the optic disc in glaucoma. It has been signaled, though, that the diagnostic value of Moorfieds Regression Analyses and Glaucoma Probability Score decreases when analyzing optic discs with extreme sizes. The number of false positive results increases in cases of megalopapilllae and the number of false negative results increases in cases of small size optic discs. The present paper is a review of the aspects one should take into account when analyzing a HRT result of an optic disc with anatomic particularities. PMID:21254731

Emotionally Negative Pictures Enhance Gist Memory

PubMed Central

Bookbinder, S. H.; Brainerd, C. J.

2016-01-01

In prior work on how true and false memory are influenced by emotion, valence and arousal have often been conflated. Thus, it is difficult to say which specific effects are due to valence and which are due to arousal. In the present research, we used a picture-memory paradigm that allowed emotional valence to be manipulated with arousal held constant. Negatively-valenced pictures elevated both true and false memory, relative to positive and neutral pictures. Conjoint recognition modeling revealed that negative valence (a) reduced erroneous suppression of true memories and (b) increased the familiarity of the semantic content of both true and false memories. Overall, negative valence impaired the verbatim side of episodic memory but enhanced the gist side, and these effects persisted even after a week-long delay. PMID:27454002

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.

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

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.

Comparison of 4th-Generation HIV Antigen/Antibody Combination Assay With 3rd-Generation HIV Antibody Assays for the Occurrence of False-Positive and False-Negative Results.

PubMed

Muthukumar, Alagarraju; Alatoom, Adnan; Burns, Susan; Ashmore, Jerry; Kim, Anne; Emerson, Brian; Bannister, Edward; Ansari, M Qasim

2015-01-01

To assess the false-positive and false-negative rates of a 4th-generation human immunodeficiency virus (HIV) assay, the Abbott ARCHITECT, vs 2 HIV 3rd-generation assays, the Siemens Centaur and the Ortho-Clinical Diagnostics Vitros. We examined 123 patient specimens. In the first phase of the study, we compared 99 specimens that had a positive screening result via the 3rd-generation Vitros assay (10 positive, 82 negative, and 7 indeterminate via confirmatory immunofluorescent assay [IFA]/Western blot [WB] testing). In the second phase, we assessed 24 HIV-1 RNA-positive (positive result via the nuclear acid amplification test [NAAT] and negative/indeterminate results via the WB test) specimens harboring acute HIV infection. The 4th-generation ARCHITECT assay yielded fewer false-positive results (n = 2) than the 3rd-generation Centaur (n = 9; P = .02) and Vitros (n = 82; P <.001) assays. One confirmed positive case had a false-negative result via the Centaur assay. When specimens from the 24 patients with acute HIV-1 infection were tested, the ARCHITECT assay yielded fewer false-negative results (n = 5) than the Centaur (n = 10) (P = .13) and the other 3rd-generation tests (n = 16) (P = .002). This study indicates that the 4th-generation ARCHITECT HIV assay yields fewer false-positive and false-negative results than the 3rd-generation HIV assays we tested. Copyright© by the American Society for Clinical Pathology (ASCP).

Finding False Positives Planet Candidates Due To Background Eclipsing Binaries in K2

NASA Astrophysics Data System (ADS)

Mullally, Fergal; Thompson, Susan E.; Coughlin, Jeffrey; DAVE Team

2016-06-01

We adapt the difference image centroid approach, used for finding background eclipsing binaries, to vet K2 planet candidates. Difference image centroids were used with great success to vet planet candidates in the original Kepler mission, where the source of a transit could be identified by subtracting images of out-of-transit cadences from in-transit cadences. To account for K2's roll pattern, we reconstruct out-of-transit images from cadences that are nearby in both time and spacecraft roll angle. We describe the method and discuss some K2 planet candidates which this method suggests are false positives.

[Serum PTH levels as a predictive factor of hypocalcaemia after total thyroidectomy].

PubMed

Díez Alonso, Manuel; Sánchez López, José Daniel; Sánchez-Seco Peña, María Isabel; Ratia Jiménez, Tomás; Arribas Gómez, Ignacio; Rodríguez Pascual, Angel; Martín-Duce, Antonio; Guadalix Hidalgo, Gregorio; Hernández Domínguez, Sara; Granell Vicent, Javier

2009-02-01

Postoperative parathyroid hormone (PTH) levels as a predictor of hypocalcaemia in patients subjected to total thyroidectomy is analyzed. Prospective study involving 67 patients who underwent total thyroidectomy due to a benign disease. Serum PTH and ionised calcium were measured 20 h after surgery. Sensitivity, specificity and predictive values of PTH and ionised calcium levels were calculated to predict clinical and analytical hypocalcaemia. A total of 42 (62.7%) patients developed hypocalcaemia (ionised calcium<0.95 mmol/l), but only 20 (29.9%) presented with symptoms. PTH concentration the day after surgery was significantly lower in the group that developed symptomatic hypocalcaemia (5.57+/-6.4 pg/ml) than in the asymptomatic (21.5+/-15.3 pg/ml) or normocalcaemic (26.8+/-24.9 pg/ml) groups (p=0.001). Taking the value of 13 pg/ml as a cut-off point of PTH levels, sensitivity, specificity, positive predictive value and negative predictive value were 54%, 72%, 76% and 48%, respectively. On the other hand, sensitivity for predicting symptomatic hypocalcaemia was 95% and specificity was 76%. The test showed a high incidence of false positives (11/30, 36%). Negative predictive value was 97% and positive predictive value was 65%. In multivariate analysis, PTH and ionised calcium were the only perioperative factors that showed an independent predictive value as risk indicators of symptomatic hypocalcaemia. Normal PTH levels 20 h after surgery practically rule out the subsequent appearance of hypocalcaemia symptoms. On the other hand, low PTH levels are not necessarily associated to symptomatic hypocalcaemia due to the high number of false positives.

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.

A simulation study to quantify the impacts of exposure measurement error on air pollution health risk estimates in copollutant time-series models.

PubMed

Dionisio, Kathie L; Chang, Howard H; Baxter, Lisa K

2016-11-25

Exposure measurement error in copollutant epidemiologic models has the potential to introduce bias in relative risk (RR) estimates. A simulation study was conducted using empirical data to quantify the impact of correlated measurement errors in time-series analyses of air pollution and health. ZIP-code level estimates of exposure for six pollutants (CO, NO x , EC, PM 2.5 , SO 4 , O 3 ) from 1999 to 2002 in the Atlanta metropolitan area were used to calculate spatial, population (i.e. ambient versus personal), and total exposure measurement error. Empirically determined covariance of pollutant concentration pairs and the associated measurement errors were used to simulate true exposure (exposure without error) from observed exposure. Daily emergency department visits for respiratory diseases were simulated using a Poisson time-series model with a main pollutant RR = 1.05 per interquartile range, and a null association for the copollutant (RR = 1). Monte Carlo experiments were used to evaluate the impacts of correlated exposure errors of different copollutant pairs. Substantial attenuation of RRs due to exposure error was evident in nearly all copollutant pairs studied, ranging from 10 to 40% attenuation for spatial error, 3-85% for population error, and 31-85% for total error. When CO, NO x or EC is the main pollutant, we demonstrated the possibility of false positives, specifically identifying significant, positive associations for copollutants based on the estimated type I error rate. The impact of exposure error must be considered when interpreting results of copollutant epidemiologic models, due to the possibility of attenuation of main pollutant RRs and the increased probability of false positives when measurement error is present.

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.

Mobile chemical detector (AP2C+SP4E) as an aid for medical decision making in the battlefield.

PubMed

Eisenkraft, Arik; Markel, Gal; Simovich, Shirley; Layish, Ido; Hoffman, Azik; Finkelstein, Arseny; Rotman, Eran; Dushnitsky, Tsvika; Krivoy, Amir

2007-09-01

The combination of the AP2C unit with the SP4E kit composes a lightweight mobile detector of chemical warfare agents (CWA), such as nerve and mustard agents, with both vapor- and liquid-sampling capabilities. This apparatus was recently introduced into our military medical units as an aid for detection of CWA on casualties. Importantly, critical information regarding the applicability in the battlefield was absent. In view of the serious consequences that might follow a proclamation of CWA recognition in battlefield, a high false-positive rate positions the utilization of this apparatus as a medical decision tool in question. We have therefore conducted a field experiment to test the false-positive rate as well as analyze possible factors leading to false-positive readings with this device. The experiment was carried out before and after a 4-day army field exercise, using a standard AP2C device, a SP4E surface sampling kit, and a specially designed medical sampling kit for casualties, intended for medical teams. Soldiers were examined at rest, after mild exercise, and after 4 days in the field. The readings with AP2C alone were compared to the combination of AP2C and SP4E and to the medical sampling kit. Various body fluids served as negative controls. Remarkably, we found a false-positive rate of 57% at rest and after mild exercise, and an even higher rate of 64% after the 4-day field exercise with the AP2C detector alone, as compared to almost no false-positive readings with the combination of AP2C and SP4E. Strikingly, the medical sampling kit has yielded numerous false-positive readings, even in normal body fluids such as blood, urine, and saliva. We therefore see no place for using the medical sampling kit due to an unaccepted high rate of false-positive readings. Finally, we have designed an algorithm that uses the entire apparatus of AP2C and SP4E as a reliable validation tool for medical triage in the setting of exposure to nerve agents in the battlefield.

Contrast Extravasation versus Hemorrhage after Thrombectomy in Patients with Acute Stroke.

PubMed

Yedavalli, Vivek; Sammet, Steffen

2017-11-01

Intra-arterial recanalization postprocedural imaging in stroke patients can result in diagnostic complications due to hyperdensities on noncontrast computed tomography (CT), which may represent either contrast extravasation or intracranial hemorrhage. If these lesions are hemorrhage, then they are risk factors becoming symptomatic, which, if not distinguished, can alter clinical management. We investigate the effects of iodinated contrast on postprocedural magnetic resonance imaging (MRI) and prevalence of equivocal imaging interpretations of postprocedural extravasated contrast versus hemorrhage while identifying protocol pitfalls. We identified 10 patients diagnosed with ischemic stroke who underwent intra-arterial recanalization in a 5-year period. These patients demonstrated a hyperdensity on a postprocedural CT within 24 hours, underwent an MRI within 48 hours, and an additional confirmatory noncontrast CT at least 72 hours postprocedure. Postprocedural MRI in all 10 stroke patients demonstrated T 1 - and T 2 -relaxation time changes due to residual iodine contrast agents. This lead to false positive postprocedural hemorrhage MRI interpretations in 2/10 patients, 3/10 false negative interpretations of contrast extravasation, and 5/10 equivocal interpretations suggesting extravasation or hemorrhage. Of these five cases, two were performed with gadolinium. MRI done within 48 hours postprocedure can lead to false positive hemorrhage or false negative contrast extravasation interpretations in stroke patients possibly due to effects from the administered angiographic contrast. Additionally, MRI should be done both after 72 hours for confirmation and without gadolinium contrast as the effects of the gadolinium contrast and residual angiographic contrast could lead to misdiagnosis. Copyright © 2017 by the American Society of Neuroimaging.

Evidence for false-positive results for boldenone testing of veal urine due to faecal cross-contamination during sampling.

PubMed

Sgoifo Rossi, C A; Arioli, F; Bassini, A; Chiesa, L M; Dell'Orto, V; Montana, M; Pompa, G

2004-08-01

European Directive 96/22/EC, which controls veterinary residues in animals, does not permit the presence of synthetic growth promoters in products of animal origin or in livestock. Boldenone is categorized in class A3 (growth promoters -- steroids) and is thus a banned substance. Testing of veal urine for banned substances is part of the European Union statutory programme for animals going into the food chain. In relation to this monitoring, three studies were conducted to investigate the apparent presence of the banned growth promoter boldenone in veal urine, which was suspected as being caused by interference from faecal contamination of the sample. In the first study, urine samples were collected at different times (time 0 and after 30 min) using (1) a conventional zoonotechnical apron and (2) a technique designed specifically to avoid faecal contamination ('kettle'). This resulted in samples that were, respectively, positive and negative for the presence of alpha-boldenone (alpha-BOL). In a second study, urine samples negative to alpha-BOL were collected from eight veal calves, but became positive after deliberate faecal contamination. In a third study, data obtained from the Italian RNP (Residual National Program) indicated that 18.1% of 3295 urine samples collected using the zootechnical apron were positive for alpha-BOL and 2.1% for beta-boldenone (beta-BOL), whilst of 902 samples collected using the kettle, beta-BOL was not detected in any samples and only 0.2% were positive to alpha-BOL, in concentrations lower than 2 ng ml(-1). These results further support the supposition that faecal contamination of the urine during sample collection can lead to false-positive results during boldenone analysis.

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.

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.

Are we making good use of our public resources? The false-positive rate of screening by fundus photography for diabetic macular oedema.

PubMed

Wong, R Lm; Tsang, C W; Wong, D Sh; McGhee, S; Lam, C H; Lian, J; Lee, J Wy; Lai, J Sm; Chong, V; Wong, I Yh

2017-08-01

A large proportion of patients diagnosed with diabetic maculopathy using fundus photography and hence referred to specialist clinics following the current screening guidelines adopted in Hong Kong and United Kingdom are found to be false-positive, implying that they did not have macular oedema. This study aimed to evaluate the false-positive rate of diabetic maculopathy screening using the objective optical coherence tomography scan. This was a cross-sectional observational study. Consecutive diabetic patients from the Hong Kong West Cluster Diabetic Retinopathy Screening Programme with fundus photographs graded R1M1 were recruited between October 2011 and June 2013. Spectral-domain optical coherence tomography imaging was performed. Central macular thickness of ≥300 μm and/or the presence of optical coherence tomography signs of diabetic macular oedema were used to define the presence of diabetic macular oedema. Patients with conditions other than diabetes that might affect macular thickness were excluded. The mean central macular thickness in various subgroups of R1M1 patients was calculated and the proportion of subjects with central macular thickness of ≥300 μm was used to assess the false-positive rate of this screening strategy. A total of 491 patients were recruited during the study period. Of the 352 who were eligible for analysis, 44.0%, 17.0%, and 38.9% were graded as M1 due to the presence of foveal 'haemorrhages', 'exudates', or 'haemorrhages and exudates', respectively. The mean (±standard deviation) central macular thickness was 265.1±55.4 μm. Only 13.4% (95% confidence interval, 9.8%-17.0%) of eyes had a central macular thickness of ≥300 μm, and 42.9% (95% confidence interval, 37.7%-48.1%) of eyes had at least one optical coherence tomography sign of diabetic macular oedema. For patients with retinal haemorrhages only, 9.0% (95% confidence interval, 4.5%-13.5%) had a central macular thickness of ≥300 μm; 23.2% (95% confidence interval, 16.6%-29.9%) had at least one optical coherence tomography sign of diabetic macular oedema. The false-positive rate of the current screening strategy for diabetic macular oedema was 86.6%. The high false-positive rate of the current diabetic macular oedema screening adopted by the United Kingdom and Hong Kong may lead to unnecessary psychological stress for patients and place a financial burden on the health care system. A better way of screening is urgently needed. Performing additional spectral-domain optical coherence tomography scans on selected patients fulfils this need.

The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study.

PubMed

Karaceper, Maria D; Chakraborty, Pranesh; Coyle, Doug; Wilson, Kumanan; Kronick, Jonathan B; Hawken, Steven; Davies, Christine; Brownell, Marni; Dodds, Linda; Feigenbaum, Annette; Fell, Deshayne B; Grosse, Scott D; Guttmann, Astrid; Laberge, Anne-Marie; Mhanni, Aizeddin; Miller, Fiona A; Mitchell, John J; Nakhla, Meranda; Prasad, Chitra; Rockman-Greenberg, Cheryl; Sparkes, Rebecca; Wilson, Brenda J; Potter, Beth K

2016-02-03

There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings.

Deducing the Milky Way's Massive Cluster Population

NASA Astrophysics Data System (ADS)

Hanson, M. M.; Popescu, B.; Larsen, S. S.; Ivanov, V. D.

2010-11-01

Recent near-infrared surveys of the galactic plane have been used to identify new massive cluster candidates. Follow up study indicates about half are not true, gravitationally-bound clusters. These false positives are created by high density fields of unassociated stars, often due to a sight-line of reduced extinction. What is not so easy to estimate is the number of false negatives, clusters which exist but are not currently being detected by our surveys. In order to derive critical characteristics of the Milky Way's massive cluster population, such as cluster mass function and cluster lifetimes, one must be able to estimate the characteristics of these false negatives. Our group has taken on the daunting task of attempting such an estimate by first creating the stellar cluster imaging simulation program, MASSCLEAN. I will present our preliminary models and methods for deriving the biases of current searches.

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.

An intrapatient comparison of 99mTc-EDDA/HYNIC-TOC with 111In-DTPA-octreotide for diagnosis of somatostatin receptor-expressing tumors.

PubMed

Gabriel, Michael; Decristoforo, Clemens; Donnemiller, Eveline; Ulmer, Hanno; Watfah Rychlinski, Christine; Mather, Stephen J; Moncayo, Roy

2003-05-01

The aim of this study was to compare the imaging abilities of the recently developed somatostatin analog, (99m)Tc-hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC [(99m)Tc-TOC]), with (111)In-diethylenediaminepentaacetic acid-D-Phe(1)-octreotide ((111)In-OCT [Octreoscan]) in patients undergoing routine somatostatin receptor (SSTR) scintigraphy. Forty-one patients (20 men, 21 women; age range, 29-75 y; mean age, 56.7 y) with either histologically proven or biologically and clinically suspected endocrine tumors were enrolled in the study. Four groups were distinguished: (a) patients being evaluated for the detection and localization of neuroendocrine tumors (n = 6), (b) tumor staging (n = 19), (c) patients being investigated to determine the SSTR status of tumor lesions (n = 11), and (d) patient follow-up studies (n = 5). Each patient received a mean activity of 150 MBq (111)In-OCT and 350-400 MBq (99m)Tc-TOC. Scintigraphy with (99m)Tc-TOC was performed 4 h after injection and scintigraphy with (111)In-OCT was performed 4 and 24 h after injection. SPECT studies of areas of interest were performed 4 h after injection for both tracers as well as at 24 h after injection for (111)In-OCT. The time interval between the studies using each tracer ranged from 2 to 22 d (mean interval, 9.3 d). (111)In-OCT and (99m)Tc-TOC showed an equivalent scan result in 32 patients (78%), 9 cases showed discrepancies (22%), false-negative results with (111)In-OCT were seen in 6 cases (14.6%), whereas (99m)Tc-TOC was false-positive in 2 cases (4.9%). (111)In-OCT was true-negative in both cases. The false-positive findings of the (99m)Tc-TOC studies were caused by nonspecific uptake in the bowel. In 1 case, (99m)Tc-TOC correctly identified a metastasis in the lumbar spine but both scan results were false-positive because of an inflammatory process. In 21 patients with SSTR-expressing tumors, the semiquantitative region-of-interest analysis showed that (99m)Tc-TOC achieved higher tumor-to-normal tissue ratios than (111)In-OCT. This study revealed a higher sensitivity of (99m)Tc-TOC as compared with (111)In-OCT as an imaging agent for the localization of SSTR-expressing tumors. To avoid false-positive findings with (99m)Tc-OCT due to nonspecific tracer accumulation, additional scanning at 1-2 h after injection should be done.

[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.

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.

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.

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.

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.

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

Star tracker operation in a high density proton field

NASA Technical Reports Server (NTRS)

Miklus, Kenneth J.; Kissh, Frank; Flynn, David J.

1993-01-01

Algorithms that reject transient signals due to proton effects on charge coupled device (CCD) sensors have been implemented in the HDOS ASTRA-l Star Trackers to be flown on the TOPEX mission scheduled for launch in July 1992. A unique technique for simulating a proton-rich environment to test trackers is described, as well as the test results obtained. Solar flares or an orbit that passes through the South Atlantic Anomaly can subject the vehicle to very high proton flux levels. There are three ways in which spurious proton generated signals can impact tracker performance: the many false signals can prevent or extend the time to acquire a star; a proton-generated signal can compromise the accuracy of the star's reported magnitude and position; and the tracked star can be lost, requiring reacquisition. Tests simulating a proton-rich environment were performed on two ASTRA-1 Star Trackers utilizing these new algorithms. There were no false acquisitions, no lost stars, and a significant reduction in reported position errors due to these improvements.

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

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.

Effects of seven chemicals on DNA damage in the rat urinary bladder: a comet assay study.

PubMed

Wada, Kunio; Yoshida, Toshinori; Takahashi, Naofumi; Matsumoto, Kyomu

2014-07-15

The in vivo comet assay has been used for the evaluation of DNA damage and repair in various tissues of rodents. However, it can give false-positive results due to non-specific DNA damage associated with cell death. In this study, we examined whether the in vivo comet assay can distinguish between genotoxic and non-genotoxic DNA damage in urinary bladder cells, by using the following seven chemicals related to urinary bladder carcinogenesis in rodents: N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), glycidol, 2,2-bis(bromomethyl)-1,3-propanediol (BMP), 2-nitroanisole (2-NA), benzyl isothiocyanate (BITC), uracil, and melamine. BBN, glycidol, BMP, and 2-NA are known to be Ames test-positive and they are expected to produce DNA damage in the absence of cytotoxicity. BITC, uracil, and melamine are Ames test-negative with metabolic activation but have the potential to induce non-specific DNA damage due to cytotoxicity. The test chemicals were administered orally to male Sprague-Dawley rats (five per group) for each of two consecutive days. Urinary bladders were sampled 3h after the second administration and urothelial cells were analyzed by the comet assay and subjected to histopathological examination to evaluate cytotoxicity. In the urinary bladders of rats treated with BBN, glycidol, and BMP, DNA damage was detected. In contrast, 2-NA induced neither DNA damage nor cytotoxicity. The non-genotoxic chemicals (BITC, uracil, and melamine) did not induce DNA damage in the urinary bladders under conditions where some histopathological changes were observed. The results indicate that the comet assay could distinguish between genotoxic and non-genotoxic chemicals and that no false-positive responses were obtained. Copyright © 2014 Elsevier B.V. All rights reserved.

Outbreak or illusion: consequences of 'improved' diagnostics for gonorrhoea.

PubMed

Bennett, Amy; Jeffery, Katie; O'Neill, Eunan; Sherrard, Jackie

2017-06-01

The sexual health service in Oxford introduced gonorrhoea nucleic amplification acid testing using the BD Viper XTR™ System. For practical reasons, a confirmatory nucleic amplification acid testing using a different platform was not used initially. Following the introduction of nucleic amplification acid testing, the rates of gonorrhoea increased threefold. Concerns were raised that this increase represented an outbreak. A retrospective review of cases over six months suggested that there may have been a number of false-positive results. A prospective study was then undertaken over six months, where all gonorrhoea positive samples were sent for confirmatory testing. This evaluation of all gonorrhoea cases in an English county found that the overall presumptive false-positive rates for gonorrhoea nucleic amplification acid testing using BD Viper XTR™ in our population are significant at 27% of female samples, 13.2% of heterosexual male samples, 3.5% of anogenital multiple site men who have sex with men samples and 62.8% of pharyngeal only men who have sex with men samples. The data demonstrate the need for confirmatory testing using a second nucleic acid target, as per BASHH/Public Health England guidelines, especially in low-prevalence settings and extragenital sites, due to cross-reactivity with commensal Neisseria species and low positive predictive values.

Multiparameter double hole contrast detail phantom: Ability to detect image displacement due to off position anode stem

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

Pauzi, Nur Farahana; Majid, Zafri Azran Abdul; Sapuan, Abdul Halim

Contrast Detail phantom is a quality control tool to analyze the performance of imaging devices. Currently, its function is solely to evaluate the contrast detail characteristic of imaging system. It consists of drilled hole which gives effect to the penetration of x-ray beam divergence to pass through the base of each hole. This effect will lead to false appearance of image from its original location but it does not being visualized in the radiograph. In this study, a new design of Contrast Detail phantom’s hole which consists of double hole construction has been developed. It can detect the image displacementmore » which is due to off position of anode stem from its original location. The double hole differs from previous milled hole, whereby it consists of combination of different hole diameters. Small hole diameter (3 mm) is positioned on top of larger hole diameter (10 mm). The thickness of double hole acrylic blocks is 13 mm. Result revealed that Multiparameter Double Hole Contrast Detail phantom can visualize the shifted flaw image quality produced by x-ray machine due to improper position of the anode stem which is attached to rotor and stator. The effective focal spot of x-ray beam also has been shifted from the center of collimator as a result of off-position anode stem. As a conclusion, the new design of double hole Contrast Detail phantom able to measure those parameters in a well manner.« less

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening.

PubMed

Ibáñez-Sanz, Gemma; Garcia, Montse; Rodríguez-Moranta, Francisco; Binefa, Gemma; Gómez-Matas, Javier; Domènech, Xènia; Vidal, Carmen; Soriano, Antonio; Moreno, Víctor

2016-10-01

The most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. To identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). Cross-sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (≥20μg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. Women showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5-3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0-2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1-4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1-2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false-positive FIT. Concurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[Which initial tests should be performed to evaluate meno-metrorrhagias? A comparison of hysterography, transvaginal sonohysterography and hysteroscopy].

PubMed

Descargues, G; Lemercier, E; David, C; Genevois, A; Lemoine, J P; Marpeau, L

2001-02-01

Evaluate the feasibility and the value of hysterography, sonohysterography and hysteroscopy for investigation of abnormal uterine bleeding. Method. Longitudinal blind study of thirty-eight patients consulting for abnormal uterine bleeding during pre- and post menopause. All patients underwent an hysterography and transvaginal sonohysterography, in random order, followed by an hysteroscopy with histological sample. The results were compared with the histo-pathological examination that was used for reference diagnosis. Statistical study of sensitivity, specificity and Positive and Negative Predictive Value (PPV-NPV) of each investigation; rate of agreement by the coefficient of Kappa. The hysterography offers a PPV of 83% and a NPV of 100%. The interpretation errors were associated with the simple mucous hypertrophy interpreted as "hyperplasy". The limits correspond to a contrast agent allergy. The sonohysterography had a VPP of 89% and a VPN of 100%. The false positive is due to the difficulties of distinguishing the clots from the polyps. The limits correspond to the difficulties of cervix catheterization (13%). As regards the hysteroscopy, the VPP was 81.5% and the VPN of 75%. The interpretation mistakes were associated with mucous hypertrophy and the hyperplasy. The most useful examination for abnormal uterine bleeding, in the first instance, is transvaginal sonography with saline instillation. A complement by Doppler study would probably make it possible to limit the false positives.

Multimodal intraoperative neuromonitoring in corrective surgery for adolescent idiopathic scoliosis: Evaluation of 354 consecutive cases

PubMed Central

Kundnani, Vishal K; Zhu, Lisa; Tak, HH; Wong, HK

2010-01-01

Background: Multimodal intraoperative neuromonitoring is recommended during corrective spinal surgery, and has been widely used in surgery for spinal deformity with successful outcomes. Despite successful outcomes of corrective surgery due to increased safety of the patients with the usage of spinal cord monitoring in many large spine centers, this modality has not yet achieved widespread popularity. We report the analysis of prospectively collected intraoperative neurophysiological monitoring data of 354 consecutive patients undergoing corrective surgery for adolescent idiopathic scoliosis (AIS) to establish the efficacy of multimodal neuromonitoring and to evaluate comparative sensitivity and specificity. Materials and Methods: The study group consisted of 354 (female = 309; male = 45) patients undergoing spinal deformity corrective surgery between 2004 and 2008. Patients were monitored using electrophysiological methods including somatosensory-evoked potentials and motor-evoked potentials simultaneously. Results: Mean age of patients was 13.6 years (±2.3 years). The operative procedures involved were instrumented fusion of the thoracic/lumbar/both curves, Baseline somatosensory-evoked potentials (SSEP) and neurogenic motor-evoked potentials (NMEP) were recorded successfully in all cases. Thirteen cases expressed significant alert to prompt reversal of intervention. All these 13 cases with significant alert had detectable NMEP alerts, whereas significant SSEP alert was detected in 8 cases. Two patients awoke with new neurological deficit (0.56%) and had significant intraoperative SSEP + NMEP alerts. There were no false positives with SSEP (high specificity) but 5 patients with false negatives with SSEP (38%) reduced its sensitivity. There was no false negative with NMEP but 2 of 13 cases were false positive with NMEP (15%). The specificity of SSEP (100%) is higher than NMEP (96%); however, the sensitivity of NMEP (100%) is far better than SSEP (51%). Due to these results, the overall sensitivity, specificity and positive predictive value of combined multimodality neuromonitoring in this adult deformity series was 100, 98.5 and 85%, respectively. Conclusion: Neurogenic motor-evoked potential (NMEP) monitoring appears to be superior to conventional SSEP monitoring for identifying evolving spinal cord injury. Used in conjunction, the sensitivity and specificity of combined neuromonitoring may reach up to 100%. Multimodality monitoring with SSEP + NMEP should be the standard of care. PMID:20165679

Correction of autofluorescence intensity for epithelial scattering by optical coherence tomography: a phantom study

NASA Astrophysics Data System (ADS)

Pahlevaninezhad, H.; Lee, A. M. D.; Hyun, C.; Lam, S.; MacAulay, C.; Lane, P. M.

2013-03-01

In this paper, we conduct a phantom study for modeling the autofluorescence (AF) properties of tissue. A combined optical coherence tomography (OCT) and AF imaging system is proposed to measure the strength of the AF signal in terms of the scattering layer thickness and concentration. The combined AF-OCT system is capable of estimating the AF loss due to scattering in the epithelium using the thickness and scattering concentration calculated from the co-registered OCT images. We define a correction factor to account for scattering losses in the epithelium and calculate a scatteringcorrected AF signal. We believe the scattering-corrected AF will reduce the diagnostic false-positives rate in the early detection of airway lesions due to confounding factors such as increased epithelial thickness and inflammations.

[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.

Optimization approaches to ameliorate humidity and vibration related issues using the microAeth black carbon monitor for personal exposure measurement

PubMed Central

Cai, Jing; Yan, Beizhan; Kinney, Patrick L.; Perzanowski, Matthew S.; Jung, Kyung-Hwa; Li, Tiantian; Xiu, Guangli; Zhang, Danian; Olivo, Cosette; Ross, James; Miller, Rachel L.; Chillrud, Steven N.

2014-01-01

Exposure to ambient black carbon (BC) is associated with adverse health effects. Black carbon levels display large spatial and temporal variability in many settings, such as cities and rural households where fossil fuel and biomass, respectively, are commonly burned for transportation, heat and cooking. This paper addresses the optimization of the miniaturized personal BC monitor, the microAeth® for use in epidemiology studies. To address false positive and negative peaks in real time BC concentrations resulting from changes in temperature and humidity, an inlet with a diffusion drier was developed. In addition, we developed data cleaning algorithms to address occasional false positive and negative fluctuations in BC readings related to physical vibration, due in part to both dirt accumulations in the optical inserts and degraded components. These methods were successfully used to process real-time BC data generated from a cohort of 9-10 year old children (N= 54) in NYC, who wore 1 or 2 microAeth units for six 24hr time periods. Two hour and daily BC averages after data cleaning were consistent with averaged raw data (slopes near 1 with R =0.99, p<0.001; R= 0.95, p<0.001, respectively), strongly suggesting that the false positive and negative excursions balance each other out when averaged for at least 2 hrs. Data cleaning of identified suspect events allows more confidence in the interpretation of the real-time personal monitoring data generated in environmental exposure studies, with mean percent difference <10% for 19 duplicate deployments. PMID:25558122

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.

Needs for Professional Education to Optimize Cervical Cancer Screenings in Low-Income Countries: a Case Study from Tanzania.

PubMed

Lavelle, Anne E; Su, Dejun; Kahesa, Crispin; Soliman, Amr S

2017-09-11

Cervical cancer is a significant health problem in many developing countries. Due to limited treatment facilities for cancer in Tanzania, a screening referral program was developed between two urban clinics and Ocean Road Cancer Institute (ORCI), the only cancer treatment center in Tanzania. This study aimed to evaluate the effectiveness of the program and to identify opportunities for professional education. The study included 139 patients who were referred to ORCI from the screening clinics of Magomeni and Temeke between January 2015 and May 2016. Abstracted data from the medical records included patient age, screening results, and treatment. Eight nurses performing screening at the three locations were interviewed about their screening experience. Over half of the referrals (51.9%) were false positives. False positive diagnosis was more common among younger patients (35.68 ± 8.6 years) (p < 0.001) and those referred from Magomeni (59.8%) (p < 0.01) than referrals of older patients (42.46 ± 11.1 years) or those from Temeke (33.3%). Interviews of nurses showed differences among clinics, including resources, experience, and documentation of screening results. The high false positive rates and the variation of accuracy of screening between the two clinics showed a need for professional education of nurses and improvement in the health systems. Continuous education of nurses may increase the effectiveness of cervical screening. Health system enhancement of screening facilities such as provision of Lugol's iodine, more space for screening, and consistency and completion of screening records are needed to increase the accuracy of cervical screening and referrals in Tanzania and other similar low-income countries.

5 CFR 732.302 - Reporting to OPM.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Reporting to OPM. 732.302 Section 732.302 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.302 Reporting to OPM. (a) In accordance with...

5 CFR 732.302 - Reporting to OPM.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Reporting to OPM. 732.302 Section 732.302 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.302 Reporting to OPM. (a) In accordance with...

5 CFR 732.302 - Reporting to OPM.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Reporting to OPM. 732.302 Section 732.302 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.302 Reporting to OPM. (a) In accordance with...

5 CFR 732.302 - Reporting to OPM.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Reporting to OPM. 732.302 Section 732.302 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.302 Reporting to OPM. (a) In accordance with...

5 CFR 732.302 - Reporting to OPM.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Reporting to OPM. 732.302 Section 732.302 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.302 Reporting to OPM. (a) In accordance with...

A Nested PCR Assay to Avoid False Positive Detection of the Microsporidian Enterocytozoon hepatopenaei (EHP) in Environmental Samples in Shrimp Farms

PubMed Central

Jaroenlak, Pattana; Sanguanrut, Piyachat; Williams, Bryony A. P.; Stentiford, Grant D.; Flegel, Timothy W.; Sritunyalucksana, Kallaya

2016-01-01

Hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP) is an important disease of cultivated shrimp. Heavy infections may lead to retarded growth and unprofitable harvests. Existing PCR detection methods target the EHP small subunit ribosomal RNA (SSU rRNA) gene (SSU-PCR). However, we discovered that they can give false positive test results due to cross reactivity of the SSU-PCR primers with DNA from closely related microsporidia that infect other aquatic organisms. This is problematic for investigating and monitoring EHP infection pathways. To overcome this problem, a sensitive and specific nested PCR method was developed for detection of the spore wall protein (SWP) gene of EHP (SWP-PCR). The new SWP-PCR method did not produce false positive results from closely related microsporidia. The first PCR step of the SWP-PCR method was 100 times (104 plasmid copies per reaction vial) more sensitive than that of the existing SSU-PCR method (106 copies) but sensitivity was equal for both in the nested step (10 copies). Since the hepatopancreas of cultivated shrimp is not currently known to be infected with microsporidia other than EHP, the SSU-PCR methods are still valid for analyzing hepatopancreatic samples despite the lower sensitivity than the SWP-PCR method. However, due to its greater specificity and sensitivity, we recommend that the SWP-PCR method be used to screen for EHP in feces, feed and environmental samples for potential EHP carriers. PMID:27832178

A Nested PCR Assay to Avoid False Positive Detection of the Microsporidian Enterocytozoon hepatopenaei (EHP) in Environmental Samples in Shrimp Farms.

PubMed

Jaroenlak, Pattana; Sanguanrut, Piyachat; Williams, Bryony A P; Stentiford, Grant D; Flegel, Timothy W; Sritunyalucksana, Kallaya; Itsathitphaisarn, Ornchuma

2016-01-01

Hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP) is an important disease of cultivated shrimp. Heavy infections may lead to retarded growth and unprofitable harvests. Existing PCR detection methods target the EHP small subunit ribosomal RNA (SSU rRNA) gene (SSU-PCR). However, we discovered that they can give false positive test results due to cross reactivity of the SSU-PCR primers with DNA from closely related microsporidia that infect other aquatic organisms. This is problematic for investigating and monitoring EHP infection pathways. To overcome this problem, a sensitive and specific nested PCR method was developed for detection of the spore wall protein (SWP) gene of EHP (SWP-PCR). The new SWP-PCR method did not produce false positive results from closely related microsporidia. The first PCR step of the SWP-PCR method was 100 times (104 plasmid copies per reaction vial) more sensitive than that of the existing SSU-PCR method (106 copies) but sensitivity was equal for both in the nested step (10 copies). Since the hepatopancreas of cultivated shrimp is not currently known to be infected with microsporidia other than EHP, the SSU-PCR methods are still valid for analyzing hepatopancreatic samples despite the lower sensitivity than the SWP-PCR method. However, due to its greater specificity and sensitivity, we recommend that the SWP-PCR method be used to screen for EHP in feces, feed and environmental samples for potential EHP carriers.

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.

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

Transvaginal duplex ultrasonography appears to be the gold standard investigation for the haemodynamic evaluation of pelvic venous reflux in the ovarian and internal iliac veins in women.

PubMed

Whiteley, M S; Dos Santos, S J; Harrison, C C; Holdstock, J M; Lopez, A J

2015-12-01

To assess the suitability of transvaginal duplex ultrasonography to identify pathological reflux in the ovarian and internal iliac veins in women. A retrospective study of patients treated in 2011 and 2012 was performed in a specialised vein clinic. Diagnostic transvaginal duplex ultrasonography in women presenting with symptoms or signs of pelvic vein reflux were compared with the outcomes of treatment from pelvic vein embolisation. A repeat transvaginal duplex ultrasonography was performed 6 weeks later by a blinded observer and any residual reflux was identified. Results from 100 sequential patients were analysed. Mean age 44.2 years (32-69) with mode average parity of 3 (0-5 deliveries). Pre-treatment, 289/400 veins were refluxing (ovarian - 29 right, 81 left; internal iliac - 93 right, 86 left). Coil embolisation was successful in 86/100 patients and failed partially in 14/100 - 5 due to failure to cannulate the target vein. One false-positive diagnosis was made. Currently there is no accepted gold standard for pelvic vein incompetence. Comparing transvaginal duplex ultrasonography with the outcome from selectively treating the veins identified as having pathological reflux with coil embolisation, there were no false-negative diagnoses and only one false-positive. This study suggests that transvaginal duplex ultrasonography could be the gold standard in assessing pelvic vein reflux. © The Author(s) 2014.

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.

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.

Hypertension is strongly associated with false-positive bicycle exercise stress echocardiography testing results.

PubMed

Keller, Karsten; Stelzer, Kathrin; Munzel, Thomas; Ostad, Mir Abolfazl

2016-12-01

Exercise echocardiography is a reliable routine test in patients with known or suspected coronary artery disease. However, in ∼15% of all patients, stress echocardiography leads to false-positive stress echocardiography results. We aimed to investigate the impact of hypertension on stress echocardiographic results. We performed a retrospective study of patients with suspected or known stable coronary artery disease who underwent a bicycle exercise stress echocardiography. Patients with false-positive stress results were compared with those with appropriate results. 126 patients with suspected or known coronary artery disease were included in this retrospective study. 23 patients showed false-positive stress echocardiography results. Beside comparable age, gender distribution and coronary artery status, hypertension was more prevalent in patients with false-positive stress results (95.7% vs. 67.0%, p = 0.0410). Exercise peak load revealed a borderline-significance with lower loads in patients with false-positive results (100.0 (IQR 75.0/137.5) vs. 125.0 (100.0/150.0) W, p = 0.0601). Patients with false-positive stress results showed higher systolic (2.05 ± 0.69 vs. 1.67 ± 0.39 mmHg/W, p = 0.0193) and diastolic (1.03 ± 0.38 vs. 0.80 ± 0.28 mmHg/W, p = 0.0165) peak blood pressure (BP) per wattage. In a multivariate logistic regression test, hypertension (OR 17.6 [CI 95% 1.9-162.2], p = 0.0115), and systolic (OR 4.12 [1.56-10.89], p = 0.00430) and diastolic (OR 13.74 [2.46-76.83], p = 0.00285) peak BP per wattage, were associated with false-positive exercise results. ROC analysis for systolic and diastolic peak BP levels per wattage showed optimal cut-off values of 1.935mmHg/W and 0.823mmHg/W, indicating false-positive exercise echocardiographic results with AUCs of 0.660 and 0.664, respectively. Hypertension is a risk factor for false-positive stress exercise echocardiographic results in patients with known or suspected coronary artery disease. Presence of hypertension was associated with 17.6-fold elevated risk of false-positive results.

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

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.

Evaluation of fecal elastase and serum cholecystokinin in dogs with a false positive fecal elastase test.

PubMed

Steiner, J M; Rehfeld, J F; Pantchev, N

2010-01-01

An assay for the measurement of pancreatic elastase in dog feces has been introduced. The goal of this study was to evaluate the rate of false-positive fecal-elastase test results in dogs with suspected exocrine pancreatic insufficiency (EPI) and to assess serum cholecystokinin (CCK) concentrations in dogs with a false positive fecal elastase test result. Twenty-six fecal and serum samples from dogs suspected of EPI, for which samples had been submitted to a commercial laboratory (Vet Med Labor) for analysis. Prospective study. Serum trypsin-like immunoreactivity (TLI) was measured in 26 dogs with a decreased fecal elastase concentration of <10 microg/g feces. Serum CCK concentrations were measured in 21 of these dogs. Of 26 dogs with a decreased fecal elastase concentration, 6 (23%) had serum TLI concentrations within or above the reference range. Serum CCK concentrations were significantly higher in dogs with a true positive fecal elastase test result (median: 1.1 pmol/L; range: 0.1-3.3 pmol/L) than in those with a false positive fecal elastase test result (median: 0.1 pmol/L; range: 0.1-0.9 pmol/L; P value = .0163). The rate of false positive fecal elastase test results was high in this group of dogs, suggesting that diagnosis of EPI must be confirmed by other means. The decreased CCK concentration in dogs with a false positive fecal elastase test result could suggest that false positive results are because of decreased stimulation of exocrine pancreatic function caused by other conditions.

False-Positive Head-Impulse Test in Cerebellar Ataxia

PubMed Central

Kremmyda, Olympia; Kirchner, Hanni; Glasauer, Stefan; Brandt, Thomas; Jahn, Klaus; Strupp, Michael

2012-01-01

The objective of this study was to compare the findings of the bedside head-impulse test (HIT), passive head rotation gain, and caloric irrigation in patients with cerebellar ataxia (CA). In 16 patients with CA and bilaterally pathological bedside HIT, vestibuloocular reflex (VOR) gains were measured during HIT and passive head rotation by scleral search coil technique. Eight of the patients had pathologically reduced caloric responsiveness, while the other eight had normal caloric responses. Those with normal calorics showed a slightly reduced HIT gain (mean ± SD: 0.73 ± 0.15). In those with pathological calorics, gains 80 and 100 ms after the HIT as well as the passive rotation VOR gains were significantly lower. The corrective saccade after head turn occurred earlier in patients with pathological calorics (111 ± 62 ms after onset of the HIT) than in those with normal calorics (191 ± 17 ms, p = 0.0064). We identified two groups of patients with CA: those with an isolated moderate HIT deficit only, probably due to floccular dysfunction, and those with combined HIT, passive rotation, and caloric deficit, probably due to a peripheral vestibular deficit. From a clinical point of view, these results show that the bedside HIT alone can be false-positive for establishing a diagnosis of a bilateral peripheral vestibular deficit in patients with CA. PMID:23162531

Capture-ELISA for serum IgM antibody to respiratory syncytial virus.

PubMed Central

Cevenini, R.; Donati, M.; Bertini, S.; Moroni, A.; Sambri, V.

1986-01-01

A four-component solid-phase capture enzyme immunoassay was set up to test for serum IgM antibody to respiratory syncytial (RS) virus and was compared with immunofluorescence assay (IFA). A total of 128 young children with acute respiratory infections were studied. Thirty-six were shown to be RS virus-positive by the detection of RS virus in nasopharyngeal secretions and 92 were RS virus-negative. A serum specimen was collected after admission to the hospital (days 0-4) and a further specimen was obtained during days 10-14. Out of 36 RS virus-positive patients, 28 (77.7%) were found to be positive for IgM by both capture-ELISA and IFA. Out of 92 RS virus-negative patients 5 (5.4%) were IgM-positive. Four false-positive results were obtained by IFA due to the presence of rheumatoid factor. The capture-ELISA was shown to be a reliable technique in detecting specific IgM antibody to RS virus. PMID:3540115

[Systematic screening of deafness at a maternity ward using evoked otoacoustic emissions: practical aspects and parental attitudes].

PubMed

Moulin, A; Ferber-Viart, C; Berland, M; Dubreuil, C; Duclaux, R

2001-09-01

Evaluation of the feasibility and parental attitudes towards a hearing screening programme using evoked otoacoustic emissions, implemented in a maternity ward in France. A hearing screening test using transiently evoked otoacoustic emissions (TEOAE) was proposed to each baby, and an anonymous questionnaire was given to parents to assess their attitudes towards the screening procedure. Although the refusal of the test reached 16% (mainly during the first two weeks of the program), more than 92% of parents judged the test as being useful, and 65% wished it to be systematically done. However, nearly 35% of parents admitted to have a low level anxiety about being unnecessarily worried by the test results. One hundred and twenty-four babies were screened. Fifty three per cent of the tests have been performed in less than ten minutes, with an average of 12.2 minutes. This duration does not include delays due to programme and babies management. False positive rate (uni or bilateral fail) was 10.5% at the first stage. Repeating the test before discharge decreased the false positive rate to 6.5%. Although limited in time, this study shows that a systematic hearing screening programme using TEOAE is possible and should be done in France. False positive rate was below 7%, and the test was considered as useful by more than 90% of parents, although knowledge about deafness in childhood and its consequences were clearly insufficient.

Generating false negatives and false positives for As and Mo concentrations in groundwater due to well installation.

PubMed

Wallis, Ilka; Pichler, Thomas

2018-08-01

Groundwater monitoring relies on the acquisition of 'representative' groundwater samples, which should reflect the ambient water quality at a given location. However, drilling of a monitoring well for sample acquisition has the potential to perturb groundwater conditions to a point that may prove to be detrimental to the monitoring objective. Following installation of 20 monitoring wells in close geographic proximity in central Florida, opposing concentration trends for As and Mo were observed. In the first year after well installation As and Mo concentrations increased in some wells by a factor of 2, while in others As and Mo concentrations decreased by a factor of up to 100. Given this relatively short period of time, a natural change in groundwater composition of such magnitude is not expected, leaving well installation itself as the likely cause for the observed concentration changes. Hence, initial concentrations were identified as 'false negatives' if concentrations increased with time or as 'false positives' if concentrations decreased. False negatives were observed if concentrations were already high, i.e., the As or Mo were present at the time of drilling. False positives were observed if concentrations were relatively lower, i.e., As or Mo were present at low concentrations of approximately 1 to 2μg/L before drilling, but then released from the aquifer matrix as a result of drilling. Generally, As and Mo were present in the aquifer matrix in either pyrite or organic matter, both of which are susceptible to dissolution if redox conditions change due to the addition of oxygen. Thus, introduction of an oxidant into an anoxic aquifer through use of an oxygen saturated drilling fluid served as the conceptual model for the trends where concentrations decreased with time. Mixing between drilling fluid and groundwater (i.e., dilution) was used as the conceptual model for scenarios where increasing trends were observed. Conceptual models were successfully tested through formulation and application of data-driven reactive transport models, using the USGS code MODFLOW in conjunction with the reactive multicomponent transport code PHT3D. Copyright © 2018 Elsevier B.V. All rights reserved.

A search for life on earth at 100 meter resolution.

NASA Technical Reports Server (NTRS)

Sagan, C.; Wallace, D.

1971-01-01

Study of several thousand photos indicating that about 0.01 of Gemini and Apollo photographs of the earth at 100 m resolution reveal signs of life - rectangular arrays due to human agricultural and urban territoriality, roads, canals, jet contrails, and industrial pollution. Potential false positives - e.g., dunes, sand bars, jetstream clouds - abound. A curve is derived for the detectivity of contemporary life on earth, in a plot of ground resolution versus global coverage. A comparable biology on Mars would not have been detected by all observations of Mars through Mariner 7.

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

False positive 18FDG PET-CT results due to exogenous lipoid pneumonia secondary to oily drug inhalation: A case report.

PubMed

Chardin, David; Nivaggioni, Guillaume; Viau, Philippe; Butori, Caherine; Padovani, Bernard; Grangeaon, Caroline; Razzouk-Cadet, Micheline

2017-06-01

Exogenous lipoid pneumonia is a rare condition due to abnormal presence of oily substances in the lungs. It is a rarely known cause for false positive FDG PET-CT results and can sometimes lead to invasive investigations. Searching and finding the source of the oily substance is one of the keys to the diagnosis. Inhalation of oily drugs during snorting has rarely been described. A patient with well controlled HIV infection was referred for an FDG PET-CT to assess extension of Kaposi's disease, recently removed from his right foot. The patient had no particular symptoms. Abnormal uptake of FDG was found in a suspicious lung nodule. An experienced radiologist thought the nodule was due to lipoid pneumonia. Bronchoalveolar lavage fluid did not contain lipid-laden macrophages but bronchoscopy showed violet lesions resembling Kaposi's disease lesions. Lobectomy was performed after a multidisciplinary discussion. Anatomopathological analysis revealed the nodule was due to lipoid pneumonia. The patient's quality of life did not diminish after the operation and he is still in good health. The source of the oily substance causing lipoid pneumonia was found after the surgery: the patient used to snort oily drugs. The presence of a suspicious lung nodule possibly due to lipoid pneumonia in a patient with known Kaposi's disease was difficult to untangle and lead to invasive surgery. It is possible that if a source of exogenous lipoid pneumonia had been found beforehand, surgery could have been prevented.

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

False memories, but not false beliefs, affect implicit attitudes for food preferences.

PubMed

Howe, David; Anderson, Rachel J; Dewhurst, Stephen A

2017-09-01

Previous studies have found that false memories and false beliefs of childhood experiences can have attitudinal consequences. Previous studies have, however, focused exclusively on explicit attitude measures without exploring whether implicit attitudes are similarly affected. Using a false feedback/imagination inflation paradigm, false memories and beliefs of enjoying a certain food as a child were elicited in participants, and their effects were assessed using both explicit attitude measures (self-report questionnaires) and implicit measures (a Single-Target Implicit Association Test). Positive changes in explicit attitudes were observed both in participants with false memories and participants with false beliefs. In contrast, only participants with false memories exhibited more positive implicit attitudes. The findings are discussed in terms of theories of explicit and implicit attitudes. 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.

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.

Comparison of multiple methods for the determination of sulphite in Allium and Brassica vegetables

PubMed Central

Robbins Carlos, Katherine S.; de Jager, Lowri S.

2018-01-01

Sulphites are a family of additives regulated for use worldwide in food products. They must be declared on the label if they are present in concentrations greater than 10 mg kg−1, determined as sulphur dioxide (SO2). The current US regulatory method for sulphites, the optimised Monier–Williams method (OMW), produces false-positive results with vegetables from the Allium (garlic) and Brassica (cabbage) genera due to extraction conditions that are thought to cause endogenous sulphur compounds to release SO2. Recently, modifications to the OMW method (2× MW) were published that reportedly reduced this false-positive in garlic. However, no other vegetables from these genera have been investigated. In addition, an LC-MS/MS method was developed for sulphite analysis, but it has not yet been tested with these problematic matrices. Ten vegetable species were analysed using these sulphite methods (OMW titration, OMW gravimetric, 2× MW and LC-MS/MS) to determine the false-positive rate. Sulphite concentrations > 10 mg kg−1 SO2 were observed with the OMW analyses. The 2× MW method reduced the measured concentration in unsulphited samples to ≤ 10 mg kg−1 SO2 for all matrices analysed. The LC-MS/MS method showed concentrations < 10 mg kg−1 for the Brassica samples, but only displayed a slight reduction in the Allium matrices. Spiked recovery studies were conducted to determine if these methods can detect added sulphite. The 2× MW had recoveries of 17% and 42% for water and fresh garlic, respectively, and the LC-MS/MS had recoveries of 108%, 125%, 116% and 107% for water, fresh garlic, roasted garlic, and hummus, respectively. The low recoveries of the 2× MW may indicate that sulphur compounds cannot be properly quantified with this method. The ability to eliminate false-positives will enable accurate determination of added sulphite to ensure compliance with sulphite labelling requirements. PMID:27592824

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

PubMed

Bruijn, Merel M C; Hermans, Frederik J R; Vis, Jolande Y; Wilms, Femke F; Oudijk, Martijn A; Kwee, Anneke; Porath, Martina M; Oei, Guid; Scheepers, Hubertina C J; Spaanderman, Marc E A; Bloemenkamp, Kitty W M; Haak, Monique C; Bolte, Antoinette C; Vandenbussche, Frank P H A; Woiski, Mallory D; Bax, Caroline J; Cornette, Jérôme M J; Duvekot, Johannes J; Bijvank, Bas W A N I J; van Eyck, Jim; Franssen, Maureen T M; Sollie, Krystyna M; van der Post, Joris A M; Bossuyt, Patrick M M; Kok, Marjolein; Mol, Ben W J; van Baaren, Gert-Jan

2017-02-01

Objective  We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days. Methods  We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome. Results  Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12). Conclusion  The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Perfume dermatitis.

PubMed

Larsen, W G

1985-01-01

The most common reaction to fragrance materials seen by practicing dermatologists is allergic contact dermatitis. Photodermatitis is occasionally seen, as is contact urticaria, irritation, and depigmentation. Fragrances are the leading cause of allergic contact dermatitis due to cosmetics. The fragrance mixture can cause false-positive reactions; therefore, it is more desirable to test with a separate series of fragrance materials.

The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers

PubMed Central

Sahl, Jason W.; Vazquez, Adam J.; Hall, Carina M.; Busch, Joseph D.; Tuanyok, Apichai; Mayo, Mark; Schupp, James M.; Lummis, Madeline; Pearson, Talima; Shippy, Kenzie; Allender, Christopher J.; Theobald, Vanessa; Hutcheson, Alex; Korlach, Jonas; LiPuma, John J.; Ladner, Jason; Lovett, Sean; Koroleva, Galina; Palacios, Gustavo; Limmathurotsakul, Direk; Wuthiekanun, Vanaporn; Wongsuwan, Gumphol; Currie, Bart J.

2016-01-01

ABSTRACT Whole-genome sequence (WGS) data are commonly used to design diagnostic targets for the identification of bacterial pathogens. To do this effectively, genomics databases must be comprehensive to identify the strict core genome that is specific to the target pathogen. As additional genomes are analyzed, the core genome size is reduced and there is erosion of the target-specific regions due to commonality with related species, potentially resulting in the identification of false positives and/or false negatives. PMID:27651357

Predictors of pregnancy outcome in antiphospholipid syndrome: a review.

PubMed

De Carolis, Sara; Botta, Angela; Santucci, Stefania; Garofalo, Serafina; Martino, Carmelinda; Perrelli, Alessandra; Salvi, Silvia; Ferrazzani, Sergio; Caforio, Leonardo; Scambia, Giovanni

2010-04-01

In pregnant women, antiphospholipid syndrome (APS) is associated with an increased risk of preeclampsia, fetal intrauterine growth restriction, and other complications related to uteroplacental insufficiency. In the last two decades, several studies were performed to identify the predictive role of some parameters in relation to obstetric outcome in APS patients. Among these, the uterine velocimetry Doppler is the most studied. It provides a non-invasive method for the study of uteroplacental blood flow, being able to detect a condition of impaired placental perfusion, due to the presence of circulating antiphospholipid antibodies (aPL). To date, the uterine artery Doppler velocimetry resulted to be a useful tool to identify APS pregnancies at higher risk of adverse pregnancy outcome. False-positive IgM for toxoplasmosis, others, rubella, cytomegalovirus, herpes viruses (TORCH) complex is associated to a worse pregnancy outcome because it reflects a dysregulation of the immune system which may amplify placental autoimmune damage. Moreover low levels of complement components are related to an increased incidence of obstetrical complications, suggesting that placental deposition of immune complexes and activation of complement cascade may contribute to placental failure APS related. The abnormal uterine Doppler velocimetry, false-positive TORCH IgM and low levels of complement components can be considered prognostic indexes of poor pregnancy outcome in APS.

Optimization of the protocols for the use of contrast agents in PET/CT studies.

PubMed

Pelegrí Martínez, L; Kohan, A A; Vercher Conejero, J L

The introduction of PET/CT scanners in clinical practice in 1998 has improved care for oncologic patients throughout the clinical pathway, from the initial diagnosis of disease through the evaluation of the response to treatment to screening for possible recurrence. The CT component of a PET/CT study is used to correct the attenuation of PET studies; CT also provides anatomic information about the distribution of the radiotracer. CT is especially useful in situations where PET alone can lead to false positives and false negatives, and CT thereby improves the diagnostic performance of PET. The use of intravenous or oral contrast agents and optimal CT protocols have improved the detection and characterization of lesions. However, there are circumstances in which the systematic use of contrast agents is not justified. The standard acquisition in PET/CT scanners is the whole body protocol, but this can lead to artifacts due to the position of patients and respiratory movements between the CT and PET acquisitions. This article discusses these aspects from a constructive perspective with the aim of maximizing the diagnostic potential of PET/CT and providing better care for patients. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Validation of SmartRank: A likelihood ratio software for searching national DNA databases with complex DNA profiles.

PubMed

Benschop, Corina C G; van de Merwe, Linda; de Jong, Jeroen; Vanvooren, Vanessa; Kempenaers, Morgane; Kees van der Beek, C P; Barni, Filippo; Reyes, Eusebio López; Moulin, Léa; Pene, Laurent; Haned, Hinda; Sijen, Titia

2017-07-01

Searching a national DNA database with complex and incomplete profiles usually yields very large numbers of possible matches that can present many candidate suspects to be further investigated by the forensic scientist and/or police. Current practice in most forensic laboratories consists of ordering these 'hits' based on the number of matching alleles with the searched profile. Thus, candidate profiles that share the same number of matching alleles are not differentiated and due to the lack of other ranking criteria for the candidate list it may be difficult to discern a true match from the false positives or notice that all candidates are in fact false positives. SmartRank was developed to put forward only relevant candidates and rank them accordingly. The SmartRank software computes a likelihood ratio (LR) for the searched profile and each profile in the DNA database and ranks database entries above a defined LR threshold according to the calculated LR. In this study, we examined for mixed DNA profiles of variable complexity whether the true donors are retrieved, what the number of false positives above an LR threshold is and the ranking position of the true donors. Using 343 mixed DNA profiles over 750 SmartRank searches were performed. In addition, the performance of SmartRank and CODIS were compared regarding DNA database searches and SmartRank was found complementary to CODIS. We also describe the applicable domain of SmartRank and provide guidelines. The SmartRank software is open-source and freely available. Using the best practice guidelines, SmartRank enables obtaining investigative leads in criminal cases lacking a suspect. Copyright © 2017 Elsevier B.V. All rights reserved.

Automatic detection of lung vessel bifurcation in thoracic CT images

NASA Astrophysics Data System (ADS)

Maduskar, Pragnya; Vikal, Siddharth; Devarakota, Pandu

2011-03-01

Computer-aided diagnosis (CAD) systems for detection of lung nodules have been an active topic of research for last few years. It is desirable that a CAD system should generate very low false positives (FPs) while maintaining high sensitivity. This work aims to reduce the number of false positives occurring at vessel bifurcation point. FPs occur quite frequently on vessel branching point due to its shape which can appear locally spherical due to the intrinsic geometry of intersecting tubular vessel structures combined with partial volume effects and soft tissue attenuation appearance surrounded by parenchyma. We propose a model-based technique for detection of vessel branching points using skeletonization, followed by branch-point analysis. First we perform vessel structure enhancement using a multi-scale Hessian filter to accurately segment tubular structures of various sizes followed by thresholding to get binary vessel structure segmentation [6]. A modified Reebgraph [7] is applied next to extract the critical points of structure and these are joined by a nearest neighbor criterion to obtain complete skeletal model of vessel structure. Finally, the skeletal model is traversed to identify branch points, and extract metrics including individual branch length, number of branches and angle between various branches. Results on 80 sub-volumes consisting of 60 actual vessel-branching and 20 solitary solid nodules show that the algorithm identified correctly vessel branching points for 57 sub-volumes (95% sensitivity) and misclassified 2 nodules as vessel branch. Thus, this technique has potential in explicit identification of vessel branching points for general vessel analysis, and could be useful in false positive reduction in a lung CAD system.

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

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.

Laboratory and clinical evaluation of on-site urine drug testing.

PubMed

Beck, Olof; Carlsson, Sten; Tusic, Marinela; Olsson, Robert; Franzen, Lisa; Hulten, Peter

2014-11-01

Products for on-site urine drug testing offer the possibility to perform screening for drugs of abuse directly at the point-of-care. This is a well-established routine in emergency and dependency clinics but further evaluation of performance is needed due to inherent limitations with the available products. Urine drug testing by an on-site product was compared with routine laboratory methods. First, on-site testing was performed at the laboratory in addition to the routine method. Second, the on-site testing was performed at a dependency clinic and urine samples were subsequently sent to the laboratory for additional analytical investigation. The on-site testing products did not perform with assigned cut-off levels. The subjective reading between the presence of a spot (i.e. negative test result) being present or no spot (positive result) was difficult in 3.2% of the cases, and occurred for all parameters. The tests performed more accurately in drug negative samples (specificity 96%) but less accurately for detecting positives (sensitivity 79%). Of all incorrect results by the on-site test the proportion of false negatives was 42%. The overall agreement between on-site and laboratory testing was 95% in the laboratory study and 98% in the clinical study. Although a high degree of agreement was observed between on-site and routine laboratory urine drug testing, the performance of on-site testing was not acceptable due to significant number of false negative results. The limited sensitivity of on-site testing compared to laboratory testing reduces the applicability of these tests.

Neonatal respiratory distress syndrome: Chest X-ray or lung ultrasound? A systematic review

PubMed Central

Culpan, Anne-Marie; Watts, Catriona; Munyombwe, Theresa; Wolstenhulme, Stephen

2017-01-01

Background and aim Neonatal respiratory distress syndrome is a leading cause of morbidity in preterm new-born babies (<37 weeks gestation age). The current diagnostic reference standard includes clinical testing and chest radiography with associated exposure to ionising radiation. The aim of this review was to compare the diagnostic accuracy of lung ultrasound against the reference standard in symptomatic neonates of ≤42 weeks gestation age. Methods A systematic search of literature published between 1990 and 2016 identified 803 potentially relevant studies. Six studies met the review inclusion criteria and were retrieved for analysis. Quality assessment was performed before data extraction and meta-analysis. Results Four prospective cohort studies and two case control studies included 480 neonates. All studies were of moderate methodological quality although heterogeneity was evident across the studies. The pooled sensitivity and specificity of lung ultrasound were 97% (95% confidence interval [CI] 94–99%) and 91% (CI: 86–95%) respectively. False positive diagnoses were made in 16 cases due to pneumonia (n = 8), transient tachypnoea (n = 3), pneumothorax (n = 1) and meconium aspiration syndrome (n = 1); the diagnoses of the remaining three false positive results were not specified. False negatives diagnoses occurred in nine cases, only two were specified as air-leak syndromes. Conclusions Lung ultrasound was highly sensitive for the detection of neonatal respiratory distress syndrome although there is potential to miss co-morbid air-leak syndromes. Further research into lung ultrasound diagnostic accuracy for neonatal air-leak syndrome and economic modelling for service integration is required before lung ultrasound can replace chest radiography as the imaging component of the reference standard. PMID:28567102

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.

ROCS: a Reproducibility Index and Confidence Score for Interaction Proteomics Studies

PubMed Central

2012-01-01

Background Affinity-Purification Mass-Spectrometry (AP-MS) provides a powerful means of identifying protein complexes and interactions. Several important challenges exist in interpreting the results of AP-MS experiments. First, the reproducibility of AP-MS experimental replicates can be low, due both to technical variability and the dynamic nature of protein interactions in the cell. Second, the identification of true protein-protein interactions in AP-MS experiments is subject to inaccuracy due to high false negative and false positive rates. Several experimental approaches can be used to mitigate these drawbacks, including the use of replicated and control experiments and relative quantification to sensitively distinguish true interacting proteins from false ones. Methods To address the issues of reproducibility and accuracy of protein-protein interactions, we introduce a two-step method, called ROCS, which makes use of Indicator Prey Proteins to select reproducible AP-MS experiments, and of Confidence Scores to select specific protein-protein interactions. The Indicator Prey Proteins account for measures of protein identifiability as well as protein reproducibility, effectively allowing removal of outlier experiments that contribute noise and affect downstream inferences. The filtered set of experiments is then used in the Protein-Protein Interaction (PPI) scoring step. Prey protein scoring is done by computing a Confidence Score, which accounts for the probability of occurrence of prey proteins in the bait experiments relative to the control experiment, where the significance cutoff parameter is estimated by simultaneously controlling false positives and false negatives against metrics of false discovery rate and biological coherence respectively. In summary, the ROCS method relies on automatic objective criterions for parameter estimation and error-controlled procedures. Results We illustrate the performance of our method by applying it to five previously published AP-MS experiments, each containing well characterized protein interactions, allowing for systematic benchmarking of ROCS. We show that our method may be used on its own to make accurate identification of specific, biologically relevant protein-protein interactions, or in combination with other AP-MS scoring methods to significantly improve inferences. Conclusions Our method addresses important issues encountered in AP-MS datasets, making ROCS a very promising tool for this purpose, either on its own or in conjunction with other methods. We anticipate that our methodology may be used more generally in proteomics studies and databases, where experimental reproducibility issues arise. The method is implemented in the R language, and is available as an R package called “ROCS”, freely available from the CRAN repository http://cran.r-project.org/. PMID:22682516

[Early diagnosis of streptococcal pharyngitis in paediatric practice: Validity of a rapid antigen detection test].

PubMed

Flores Mateo, Gemma; Conejero, Jaume; Grenzner Martinel, Elisabet; Baba, Zeki; Dicono, Susana; Echasabal, Mildrey; Gonzalo Santos, Concepción; Aliaga, Arantxa; Barredo, María; Ruiz, Luis; Carrau, Montserrat

2010-07-01

To determine the validity of the rapid antigen test for the diagnoses of acute pharyngitis caused by group A beta-haemolytic Streptococcus (GABHS) compared with culture. Observational study of a consecutive sample of paediatric patients. Two primary care centres (PCC) from the metropolitan area of Barcelona. Children aged 1-14 years with sore throat of no more than 5 days duration were chosen at PCC. Oropharyngeal samples were collected from tonsillar bed and posterior pharynx. A rapid diagnostic test was performed, as well as a throat culture. A total of 211 patients were studied. The overall prevalence of pharyngitis due to Streptococcus was 34.1%. Compared with the throat culture, the sensitivity of the rapid test was 90.3% (95% CI: 81.0-96.0), the specificity was 78.4% (95% CI: 70.6-84.9). The percentage of false negatives was 9.7% and the false positives was 21.6%. Spectrum bias was present, inasmuch as the rapid test sensitivity increased with Centor scores. The diagnostic value of a rapid antigen test for the diagnosis of streptococcal pharyngitis in paediatric patients at PCC is high. However, the percentage of false positives and negatives is too high, and also the sensitivity is too low in patients with fewer symptoms to support the use of rapid antigenic test without culture confirmation and bacterial sensitivity test. 2009 Elsevier España, S.L. 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.

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

Screening for the presence of lipophilic marine biotoxins in shellfish samples using the neuro-2a bioassay.

PubMed

Bodero, Marcia; Bovee, Toine F H; Wang, Si; Hoogenboom, Ron L A P; Klijnstra, Mirjam D; Portier, Liza; Hendriksen, Peter J M; Gerssen, Arjen

2018-02-01

The neuro-2a bioassay is considered as one of the most promising cell-based in vitro bioassays for the broad screening of seafood products for the presence of marine biotoxins. The neuro-2a assay has been shown to detect a wide array of toxins like paralytic shellfish poisons (PSPs), ciguatoxins, and also lipophilic marine biotoxins (LMBs). However, the neuro-2a assay is rarely used for routine testing of samples due to matrix effects that, for example, lead to false positives when testing for LMBs. As a result there are only limited data on validation and evaluation of its performance on real samples. In the present study, the standard extraction procedure for LMBs was adjusted by introducing an additional clean-up step with n-hexane. Recovery losses due to this extra step were less than 10%. This wash step was a crucial addition in order to eliminate false-positive outcomes due to matrix effects. Next, the applicability of this assay was assessed by testing a broad range of shellfish samples contaminated with various LMBs, including diarrhetic shellfish toxins/poisons (DSPs). For comparison, the samples were also analysed by LC-MS/MS. Standards of all regulated LMBs were tested, including analogues of some of these toxins. The neuro-2a cells showed good sensitivity towards all compounds. Extracts of 87 samples, both blank and contaminated with various toxins, were tested. The neuro-2a outcomes were in line with those of LC-MS/MS analysis and support the applicability of this assay for the screening of samples for LMBs. However, for use in a daily routine setting, the test might be further improved and we discuss several recommended modifications which should be considered before a full validation is carried out.

Development and evaluation of IgY ImmunoCapture PCR ELISA for detection of Staphylococcus aureus enterotoxin A devoid of protein A interference.

PubMed

Reddy, Prakash; Ramlal, Shylaja; Sripathy, Murali Harishchandra; Batra, Harsh Vardhan

2014-06-01

In the present study, a sensitive and specific IgY mediated ImmunoCapture-PCR-ELISA (IC-PCR-ELISA) was developed for the detection of staphylococcal enterotoxin A (SEA) from culture supernatants and suspected contaminated samples. Due to the virtue of avian immunoglobulins (IgY) to have the least affinity towards staphylococcal protein A (SpA) responsible for false positives, we employed anti-SEA IgY for capture of SEA toxin and revealed with SEA specific rabbit antibodies conjugated to a 524bp DNA marker. Biotin-11-dUTP was incorporated during PCR amplification and post PCR analysis was performed by PCR-ELISA. Unlike IgG immunocapture, IgY mediated immunocapture of SEA was free from false positives due to protein A. The developed assay was specific to SEA except for minor cross reactivity with staphylococcal enterotoxin E (SEE). Several raw milk samples were evaluated for the presence of SEA with and without enrichment. Three samples were found to be positive for SEA after enrichment for 8h. Though IC-PCR-ELISA for SEA showed 100% correlation with PCR analysis for sea gene, the assay was unique in terms of sensitivity of detecting ~10pg/ml of SEA toxin from spiked milk samples. Result of IC-PCR-ELISA was further confirmed by conventional methods of isolation and characterization. The presented method can be very useful for rapid analysis of milk samples for SEA contamination and can be further extended for detection of multiple SE's in different wells of same PCR plate using common DNA substrate. Copyright © 2014 Elsevier B.V. All rights reserved.

Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific Immunoglobulin-E

PubMed Central

2012-01-01

Background Skin prick test (SPT) and fluorescence enzyme immunoassay (FEIA) are widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic disease. Basophil activation test (BAT) could obviate disadvantages of SPT and FEIA. However, it is not known whether BAT gives similar results as SPT or FEIA for aeroallergens. Objectives In this study, we compared the results of SPT, BAT and FEIA for different aeroallergens. Methods We performed BAT, SPT and FEIA in 41 atopic subjects (symptomatic and with positive SPT for at least 1 of 9 common aeroallergens) and 31 non-atopic subjects (asymptomatic and with negative SPT). Results Correlations between SPT and BAT, SPT and FEIA, and BAT and FEIA results were statistically significant but imperfect. Using SPT as the "gold standard", BAT and FEIA were similar in sensitivity. However, BAT had lower specificity than FEIA. False positive (BATposSPTneg) results were frequent in those atopic subjects who were allergic by SPT to a different allergen and rare in non-atopic subjects. The false positivity in atopic subjects was due in part to high levels of serum Total-IgE (T-IgE) levels in atopic individuals that lead to basophil activation upon staining with fluorochrome-labeled anti-IgE. Conclusion As an alternative to SPT in persons allergic to aeroallergens, BAT in its present form is useful for distinguishing atopic from non-atopic persons. However, BAT in its present form is less specific than FEIA when determining the allergen which a patient is allergic to. This is due to IgE staining-induced activation of atopic person's basophils and/or nonspecific hyperreactivity of atopic person's basophils. PMID:22264407

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.

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.

Repetition increases false recollection in older people.

PubMed

Pitarque, Alfonso; Sales, Alicia; Meléndez, Juan Carlos; Algarabel, Salvador

2015-02-01

Aging is accompanied by an increase in false alarms on recognition tasks, and these false alarms increase with repetition in older people (but not in young people). Traditionally, this increase was thought to be due to a greater use of familiarity in older people, but it was recently pointed out that false alarms also have a clear recollection component in these people. The main objective of our study is to analyze whether the expected increase in the rate of false alarms in older people due to stimulus repetition is produced by an inadequate use of familiarity, recollection, or both processes. To do so, we carried out an associative recognition experiment using pairs of words and pairs of images (faces associated with everyday contexts), in which we analyzed whether the repetition of some of the pairs increases the rate of false alarms in older people (compared to what was found in a sample of young people), and whether this increase is due to familiarity or recollection (using a remember-know paradigm). Our results show that the increase in false alarms in older people due to repetition is produced by false recollection, calling into question both dual and single-process models of recognition. Also, older people falsely recollect details of never studied stimuli, a clear case of perceptual illusions. These results are better explained in terms of source-monitoring errors, mediated by people's retrieval expectations. © 2014 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

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.

West Nile seroprevalence study in Bolivian horses, 2011.

PubMed

Mazzei, Maurizio; Savini, Giovanni; Di Gennaro, Annapia; Macchioni, Fabio; Prati, Maria Cristina; Guzmàn, Limberg Rojas; Tolari, Francesco

2013-12-01

West Nile virus (WNV) is a mosquito-borne virus belonging to the family Flaviviridae included in the Japanese encephalitis antigenic complex (JEAC). A seroepidemiological study was carried out in 2011 using 160 horse sera collected from different areas of Bolivia to investigate the presence of WNV antibody. A high proportion (59.4%) of the tested sera were positive to a commercially available WNV competitive enzyme-linked immunosorbent assay (C-ELISA). Sixty-six randomly selected C-ELISA-positive sera were further tested by WNV plaque reduction neutralization test (PRNT), virus neutralization (VN), and immunoglobulin M (IgM)-WNV ELISA to exclude false-positive results due to possible cross-reactions to other members of the JEAC and to investigate if the horses were recently infected. No WNV IgM was detected in these samples, whereas neutralizing antibodies were found in 21 and 18 samples by PRNT and VN, respectively. In conclusion, a high proportion of the Bolivian horses included in this study reacted serologically against viruses of the JEAC. WNV was partially responsible (31.8%) for these reactions, supporting the conclusion that WNV circulated in Bolivia.

Reflections on O2 as a Biosignature in Exoplanetary Atmospheres.

PubMed

Meadows, Victoria S

2017-10-01

Oxygenic photosynthesis is Earth's dominant metabolism, having evolved to harvest the largest expected energy source at the surface of most terrestrial habitable zone planets. Using CO 2 and H 2 O-molecules that are expected to be abundant and widespread on habitable terrestrial planets-oxygenic photosynthesis is plausible as a significant planetary process with a global impact. Photosynthetic O 2 has long been considered particularly robust as a sign of life on a habitable exoplanet, due to the lack of known "false positives"-geological or photochemical processes that could also produce large quantities of stable O 2 . O 2 has other advantages as a biosignature, including its high abundance and uniform distribution throughout the atmospheric column and its distinct, strong absorption in the visible and near-infrared. However, recent modeling work has shown that false positives for abundant oxygen or ozone could be produced by abiotic mechanisms, including photochemistry and atmospheric escape. Environmental factors for abiotic O 2 have been identified and will improve our ability to choose optimal targets and measurements to guard against false positives. Most of these false-positive mechanisms are dependent on properties of the host star and are often strongest for planets orbiting M dwarfs. In particular, selecting planets found within the conservative habitable zone and those orbiting host stars more massive than 0.4 M ⊙ (M3V and earlier) may help avoid planets with abundant abiotic O 2 generated by water loss. Searching for O 4 or CO in the planetary spectrum, or the lack of H 2 O or CH 4 , could help discriminate between abiotic and biological sources of O 2 or O 3 . In advance of the next generation of telescopes, thorough evaluation of potential biosignatures-including likely environmental context and factors that could produce false positives-ultimately works to increase our confidence in life detection. Key Words: Biosignatures-Exoplanets-Oxygen-Photosynthesis-Planetary spectra. Astrobiology 17, 1022-1052.

Reflections on O2 as a Biosignature in Exoplanetary Atmospheres

NASA Astrophysics Data System (ADS)

Meadows, Victoria S.

2017-10-01

Oxygenic photosynthesis is Earth's dominant metabolism, having evolved to harvest the largest expected energy source at the surface of most terrestrial habitable zone planets. Using CO2 and H2O - molecules that are expected to be abundant and widespread on habitable terrestrial planets - oxygenic photosynthesis is plausible as a significant planetary process with a global impact. Photosynthetic O2 has long been considered particularly robust as a sign of life on a habitable exoplanet, due to the lack of known "false positives" - geological or photochemical processes that could also produce large quantities of stable O2. O2 has other advantages as a biosignature, including its high abundance and uniform distribution throughout the atmospheric column and its distinct, strong absorption in the visible and near-infrared. However, recent modeling work has shown that false positives for abundant oxygen or ozone could be produced by abiotic mechanisms, including photochemistry and atmospheric escape. Environmental factors for abiotic O2 have been identified and will improve our ability to choose optimal targets and measurements to guard against false positives. Most of these false-positive mechanisms are dependent on properties of the host star and are often strongest for planets orbiting M dwarfs. In particular, selecting planets found within the conservative habitable zone and those orbiting host stars more massive than 0.4 M⊙ (M3V and earlier) may help avoid planets with abundant abiotic O2 generated by water loss. Searching for O4 or CO in the planetary spectrum, or the lack of H2O or CH4, could help discriminate between abiotic and biological sources of O2 or O3. In advance of the next generation of telescopes, thorough evaluation of potential biosignatures - including likely environmental context and factors that could produce false positives - ultimately works to increase our confidence in life detection.

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.

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.

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

Quality of malaria diagnosis and molecular confirmation of Plasmodium ovale curtisi in a rural area of the southeastern region of Ethiopia.

PubMed

Díaz, Pedro Berzosa; Lozano, Patricia Mula; Rincón, Jose Manuel Ramos; García, Luz; Reyes, Francisco; Llanes, Agustín Benito

2015-09-18

Approximately 50 million people (60 %) live in malaria risk areas in Ethiopia, at altitudes below 2000 m. According to official data, 60-70 % of malaria cases are due to Plasmodium falciparum, and 40-30 % by Plasmodium vivax. The species Plasmodium ovale was detected in 2013 in the northwest of the country, being the first report of the presence of this species in Ethiopia since the 60 s. The aim of this study was to assess the diagnosis by microscopy and PCR, and demonstrate the presence of other Plasmodium species in the country. The survey was conducted in Bulbula, situated in the Rift Valley (West Arsi Province, Oromia Region). From December 2010 to October 2011, 3060 samples were collected from patients with symptoms of malaria; the diagnosis of malaria was done by microscopy and confirmation by PCR. 736 samples were positive for malaria by microscopy. After removing the 260 samples (109 positives and 151 negatives) for which it was not possible to do PCR, there were a total of 2800 samples, 1209 are used for its confirmation by PCR and quality control (627 are positives and 582 negatives by microscopy). From the 627 positive samples, 604 were confirmed as positive by PCR, 23 false positives were detected, and the group of 582 negative samples, 184 were positive by PCR (false negatives), which added to the previous positive samples is a total of 788, positive samples for some species of Plasmodium sp. 13.3 % more positives were detected with the PCR than the microscopy. Importantly, 23 samples were detected by PCR as P. ovale, after the sequencing of these samples was determined as P. ovale curtisi. The PCR detected more positive samples than the microscopy; in addition, P. ovale and P. ovale/P. vivax were detected that had not been detected by microscopy, which can affect in the infection control.

Diagnostic tool for early detection of ovarian cancers using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Lieber, Chad A.; Molpus, Kelly; Brader, Kevin; Mahadevan-Jansen, Anita

2000-05-01

With an overall survival rate of about 35 percent, ovarian cancer claims more than 13,000 women in the US each year. It is estimated that roughly 1 in 70 women will develop ovarian cancer. Current screening techniques are challenged due to cost-effectiveness, variable false-positive results, and the asymptomatic nature of the early stages of ovarian cancer. The predominant screening method for ovarian cancers is transvaginal sonography (TVS). TVS is fairly accomplished at ovarian cancer detection, however it is inefficient in distinguishing between benign and malignant masses. Accurate diagnosis of the ovarian tumor relies on exploratory laparotomy, thus increasing the cost and hazard of false- positive screening methods. Raman spectroscopy has been sued successfully as a diagnostic tool in several organ systems in vitro. These studies have shown that Raman spectroscopy can be used to provide diagnosis of subtle changes in tissue pathology with high accuracy. Based on this success, we have developed a Raman spectroscopic system for application in the ovary. Using this system, the Raman signatures of normal and various types of non-normal human ovarian tissues were characterized in vitro. Raman spectra are being analyzed, and empirical as well as multivariate discriminatory algorithms developed. Based on the result of this study, a strategy for in vivo trials will be planned.

Fusion Imaging: A Novel Staging Modality in Testis Cancer

PubMed Central

Sterbis, Joseph R.; Rice, Kevin R.; Javitt, Marcia C.; Schenkman, Noah S.; Brassell, Stephen A.

2010-01-01

Objective: Computed tomography and chest radiographs provide the standard imaging for staging, treatment, and surveillance of testicular germ cell neoplasms. Positron emission tomography has recently been utilized for staging, but is somewhat limited in its ability to provide anatomic localization. Fusion imaging combines the metabolic information provided by positron emission tomography with the anatomic precision of computed tomography. To the best of our knowledge, this represents the first study of the effectiveness using fusion imaging in evaluation of patients with testis cancer. Methods: A prospective study of 49 patients presenting to Walter Reed Army Medical Center with testicular cancer from 2003 to 2009 was performed. Fusion imaging was compared with conventional imaging, tumor markers, pathologic results, and clinical follow-up. Results: There were 14 true positives, 33 true negatives, 1 false positive, and 1 false negative. Sensitivity, specificity, positive predictive value, and negative predictive value were 93.3, 97.0, 93.3, and 97.0% respectively. In 11 patient scenarios, fusion imaging differed from conventional imaging. Utility was found in superior lesion detection compared to helical computed tomography due to anatomical/functional image co-registration, detection of micrometastasis in lymph nodes (pathologic nodes < 1cm), surveillance for recurrence post-chemotherapy, differentiating fibrosis from active disease in nodes < 2.5cm, and acting as a quality assurance measure to computed tomography alone. Conclusions: In addition to demonstrating a sensitivity and specificity comparable or superior to conventional imaging, fusion imaging shows promise in providing additive data that may assist in clinical decision-making. PMID:21103077

Fusion imaging: a novel staging modality in testis cancer.

PubMed

Sterbis, Joseph R; Rice, Kevin R; Javitt, Marcia C; Schenkman, Noah S; Brassell, Stephen A

2010-11-05

Computed tomography and chest radiographs provide the standard imaging for staging, treatment, and surveillance of testicular germ cell neoplasms. Positron emission tomography has recently been utilized for staging, but is somewhat limited in its ability to provide anatomic localization. Fusion imaging combines the metabolic information provided by positron emission tomography with the anatomic precision of computed tomography. To the best of our knowledge, this represents the first study of the effectiveness using fusion imaging in evaluation of patients with testis cancer. A prospective study of 49 patients presenting to Walter Reed Army Medical Center with testicular cancer from 2003 to 2009 was performed. Fusion imaging was compared with conventional imaging, tumor markers, pathologic results, and clinical follow-up. There were 14 true positives, 33 true negatives, 1 false positive, and 1 false negative. Sensitivity, specificity, positive predictive value, and negative predictive value were 93.3, 97.0, 93.3, and 97.0% respectively. In 11 patient scenarios, fusion imaging differed from conventional imaging. Utility was found in superior lesion detection compared to helical computed tomography due to anatomical/functional image co-registration, detection of micrometastasis in lymph nodes (pathologic nodes < 1cm), surveillance for recurrence post-chemotherapy, differentiating fibrosis from active disease in nodes < 2.5cm, and acting as a quality assurance measure to computed tomography alone. In addition to demonstrating a sensitivity and specificity comparable or superior to conventional imaging, fusion imaging shows promise in providing additive data that may assist in clinical decision-making.

Can the Stockholm convention address the spectrum of chemicals currently under regulatory scrutiny? Advocating a more prominent role for modeling in POP screening assessment.

PubMed

McLachlan, Michael S

2018-01-24

Frameworks for chemical regulation are based on the science at the time they were written. Today some regulations are being applied to a much broader spectrum of chemicals than we had knowledge of when the regulations were written. This entails a risk that the regulations are being used outside of their chemical application domain. This question is explored using the POP screening assessment in the Stockholm convention, which was developed 20 years ago. Using perfluorinated alkyl acids (PFAAs) as an example, it is shown that the assessment can lead to false negative conclusions. A second case study using octamethylcyclotetrasiloxane (D4) illustrates that there is also a risk of false positives. The risk for false negative classification of PFAAs is due to the inclusion of a screening criterion - bioaccumulation - that is not a requirement for adverse effects of chemicals in remote regions. For D4 the risk of false positive classification stems from the four screening criteria (persistence, bioaccumulation, long-range transport, and adverse effects) applying to different environmental media/compartments. The major lesson is that applying the POP screening procedure to the broad spectrum of chemicals in modern commerce will require that we rely less on the individual screening criteria and more on the comparison of estimated exposure and the thresholds for effects stipulated in Annex D, paragraph 2 of the convention. Models have an important role to play in this context and should become more strongly integrated into the POP screening process.

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...

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).

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.

The Use of Dried Blood Spots: A Potential Tool for the Introduction of a Neonatal Screening Program for Sickle Cell Anemia in Zambia.

PubMed

Chindima, Nanjela; Nkhoma, Panji; Sinkala, Musalula; Zulu, Mildred; Kafita, Doris; Simakando, Marah; Mwaba, Florence; Mantina, Hamakwa; Mutale, Mubanga

2018-01-01

Sickle cell disease is a group of hemoglobin (Hb) disorders resulting from the inheritance of the sickle β-globin gene. It is the most common pathological Hb mutation worldwide with 75% being born in Sub-Saharan Africa. This study aims to determine if dried blood spots (DBSs) can be used for diagnosis of sickle cell in newborns. In Zambia, there is no neonatal screening program for sickle cell anemia (SCA), yet it has been proved that early diagnosis by newborn screening (NBS) using DBSs and access to comprehensive care results in survival to adulthood of over 96% of sickle cell patients. A cross-sectional study was carried out at the University Teaching Hospital to determine whether DBSs can be used to diagnose sickle cell using Hb electrophoresis. Results from DBSs stored for 2 weeks were then compared to those obtained using freshly collected whole blood. To evaluate performance characteristics, the following values were used: true positive, false positive, true negative, and false negative. Ninety-seven participants were included in this study. DBSs had a sensitivity of 100%, a specificity of 94.7%, positive predictive value of 96.7%, negative predictive value of 100%, overall efficiency of 97.9%, and a Kappa r 2 , P < 0.0001 in comparison to fresh whole blood which we used as the gold standard. The use of DBSs can be recommended for NBS of SCA in Zambia due to its high sensitivity, specificity, and stability of hemoglobin.

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.

Bone scintigraphy for neonatal osteomyelitis: simulation by extravasation of intravenous calcium

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

Balsam, D.; Goldfarb, C.R.; Stringer, B.

Intravenously administered calcium gluconate has become increasingly popular in the treatment of neonatal tetany. Occasionally, extravasation results in cellulitis, leading to a clinical diagnosis of superimposed osteomyelitis. Osseous scintigraphy, as the accepted modality in the early detection of osteomyelitis, would tend to be used in this circumstance. This case illustrates a false-positive result, probably due to soft-tissue calcification.

Evaluation of positive and false-positive results in syphilis screening of blood donors in Rio de Janeiro, Brazil.

PubMed

Sandes, V S; Silva, S G C; Motta, I J F; Velarde, L G C; de Castilho, S R

2017-06-01

We propose to analyse the positive and false-positive results of treponemal and nontreponemal tests in blood donors from Brazil and to evaluate possible factors associated with the results of treponemal tests. Treponemal tests have been used widely for syphilis screening in blood banks. The introduction of these tests in donor screening has caused an impact and a loss of donors who need to be assessed. This was a retrospective cross-sectional study of syphilis screening and confirmatory test results of blood donors that were obtained before and after adopting a chemiluminescent immunoassay (CLIA). A comparative analysis was performed using a second sample drawn from positive donors. The possible factors associated with CLIA-positive or CLIA-false-positive results were investigated in a subgroup. Statistical tests were used to compare the proportions and adjusted estimates of association. The reactivity rate increased from 1·01% (N = 28 158) to 2·66% (N = 25 577) after introducing the new test. Among Venereal Disease Research Laboratory (VDRL)- and CLIA-confirmed results, the false-positive rates were 40·5% (N = 180) and 37·4% (N = 359), respectively (P = 0·5266). Older donors (OR = 1·04; P = 0·0010) and donors with lower education levels (OR = 6·59; P = 0·0029) were associated with a higher risk of positivity for syphilis. CLIA represents an improvement in blood bank serological screening. However, its use in a healthy population appears to result in high rates of false positives. Identifying which characteristics can predict false positives, however, remains a challenge. © 2017 British Blood Transfusion Society.

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.

Alpha Elements' Effects on Planet Formation and the Hunt for Extragalactic Planets

NASA Astrophysics Data System (ADS)

Penny, Matthew; Rodriguez, Joseph E.; Beatty, Thomas; Zhou, George

2018-01-01

A star's likelihood of hosting a giant planet is well known to be strongly dependent on metallicity. However, little is known about what elements cause this correlation (e.g. bulk metals, iron, or alpha elements such as silicon and oxygen). This is likely because most planet searches target stars in the Galactic disk, and due to Galactic chemical evolution, alpha element abundances are themselves correlated with metallicity within a population. We investigate the feasibility of simultaneous transiting planet search towards the alpha-poor Sagittarius dwarf galaxy and alpha-rich Galactic bulge in a single field of view of DECam, that would enable a comparative study of planet frequency over an [alpha/Fe] baseline of ~0.4 dex. We show that a modestly sized survey could detect planet candidates in both populations, but that false positive rejection in Sgr Dwarf may be prohibitively expensive. Conversely, two-filter survey observations alone would be sufficient to rule out a large fraction of bulge false positives, enabling statistical validation of candidates with a modest follow-up investment. Although over a shorter [alpha/Fe] baseline, this survey would provide a test of whether it is alpha or iron that causes the planet metallicity correlation.

Evaluating remotely sensed plant count accuracy with differing unmanned aircraft system altitudes, physical canopy separations, and ground covers

NASA Astrophysics Data System (ADS)

Leiva, Josue Nahun; Robbins, James; Saraswat, Dharmendra; She, Ying; Ehsani, Reza

2017-07-01

This study evaluated the effect of flight altitude and canopy separation of container-grown Fire Chief™ arborvitae (Thuja occidentalis L.) on counting accuracy. Images were taken at 6, 12, and 22 m above the ground using unmanned aircraft systems. Plants were spaced to achieve three canopy separation treatments: 5 cm between canopy edges, canopy edges touching, and 5 cm of canopy edge overlap. Plants were placed on two different ground covers: black fabric and gravel. A counting algorithm was trained using Feature Analyst®. Total counting error, false positives, and unidentified plants were reported for images analyzed. In general, total counting error was smaller when plants were fully separated. The effect of ground cover on counting accuracy varied with the counting algorithm. Total counting error for plants placed on gravel (-8) was larger than for those on a black fabric (-2), however, false positive counts were similar for black fabric (6) and gravel (6). Nevertheless, output images of plants placed on gravel did not show a negative effect due to the ground cover but was impacted by differences in image spatial resolution.

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.

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

[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.

Breast cancer risk is increased in the years following false-positive breast cancer screening.

PubMed

Goossens, Mathijs C; De Brabander, Isabel; De Greve, Jacques; Vaes, Evelien; Van Ongeval, Chantal; Van Herck, Koen; Kellen, Eliane

2017-09-01

A small number of studies have investigated breast cancer (BC) risk among women with a history of false-positive recall (FPR) in BC screening, but none of them has used time-to-event analysis while at the same time quantifying the effect of false-negative diagnostic assessment (FNDA). FNDA occurs when screening detects BC, but this BC is missed on diagnostic assessment (DA). As a result of FNDA, screenings that detected cancer are incorrectly classified as FPR. Our study linked data recorded in the Flemish BC screening program (women aged 50-69 years) to data from the national cancer registry. We used Cox proportional hazards models on a retrospective cohort of 298 738 women to assess the association between FPR and subsequent BC, while adjusting for potential confounders. The mean follow-up was 6.9 years. Compared with women without recall, women with a history of FPR were at an increased risk of developing BC [hazard ratio=2.10 (95% confidence interval: 1.92-2.31)]. However, 22% of BC after FPR was due to FNDA. The hazard ratio dropped to 1.69 (95% confidence interval: 1.52-1.87) when FNDA was excluded. Women with FPR have a subsequently increased BC risk compared with women without recall. The risk is higher for women who have a FPR BI-RADS 4 or 5 compared with FPR BI-RADS 3. There is room for improvement of diagnostic assessment: 41% of the excess risk is explained by FNDA after baseline screening.

High resolution microendoscopy for early detection of esophageal cancer in low-resource settings (Conference Presentation)

NASA Astrophysics Data System (ADS)

Richards-Kortum, Rebecca

2016-03-01

Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide. Most deaths due to ESCN occur in developing countries, with highest risk areas in northern China. Lugol's chromoendoscopy (LCE) is the gold-standard for ESCN screening; while the sensitivity of LCE for ESCN is >95%, LCE suffers poor specificity (< 65%) due to false positive findings from inflammatory lesions. High resolution microendoscopy (HRME) uses a low-cost, fiber-optic fluorescence microscope to image morphology of the surface epithelium without need for biopsy. We developed a tablet-interfaced HRME with automated, real-time image analysis. In an in vivo study of 177 patients referred for endoscopy in China, use of the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91% compared to the gold standard of histology.

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.

Degrees of Freedom in Planning, Running, Analyzing, and Reporting Psychological Studies: A Checklist to Avoid p-Hacking

PubMed Central

Wicherts, Jelte M.; Veldkamp, Coosje L. S.; Augusteijn, Hilde E. M.; Bakker, Marjan; van Aert, Robbie C. M.; van Assen, Marcel A. L. M.

2016-01-01

The designing, collecting, analyzing, and reporting of psychological studies entail many choices that are often arbitrary. The opportunistic use of these so-called researcher degrees of freedom aimed at obtaining statistically significant results is problematic because it enhances the chances of false positive results and may inflate effect size estimates. In this review article, we present an extensive list of 34 degrees of freedom that researchers have in formulating hypotheses, and in designing, running, analyzing, and reporting of psychological research. The list can be used in research methods education, and as a checklist to assess the quality of preregistrations and to determine the potential for bias due to (arbitrary) choices in unregistered studies. PMID:27933012

Degrees of Freedom in Planning, Running, Analyzing, and Reporting Psychological Studies: A Checklist to Avoid p-Hacking.

PubMed

Wicherts, Jelte M; Veldkamp, Coosje L S; Augusteijn, Hilde E M; Bakker, Marjan; van Aert, Robbie C M; van Assen, Marcel A L M

2016-01-01

The designing, collecting, analyzing, and reporting of psychological studies entail many choices that are often arbitrary. The opportunistic use of these so-called researcher degrees of freedom aimed at obtaining statistically significant results is problematic because it enhances the chances of false positive results and may inflate effect size estimates. In this review article, we present an extensive list of 34 degrees of freedom that researchers have in formulating hypotheses, and in designing, running, analyzing, and reporting of psychological research. The list can be used in research methods education, and as a checklist to assess the quality of preregistrations and to determine the potential for bias due to (arbitrary) choices in unregistered studies.

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.

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.

Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.

PubMed

de Haas, Masja; Thurik, Florentine F; van der Ploeg, Catharina P B; Veldhuisen, Barbera; Hirschberg, Hoang; Soussan, Aicha Ait; Woortmeijer, Heleen; Abbink, Frithjofna; Page-Christiaens, Godelieve C M L; Scheffer, Peter G; Ellen van der Schoot, C

2016-11-07

 To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.  Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting.  25 789 RhD negative pregnant women.  Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme.  A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme.  Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Systematic detection of physical child abuse at emergency rooms].

PubMed

Sittig, J S; Uiterwaal, C S P M; Moons, K G M; Russel, I M B; Nievelstein, R A J; Nieuwenhuis, E E S; van de Putte, E M

2016-01-01

The aim of our diagnostic accuracy study Child Abuse Inventory at Emergency Rooms (CHAIN-ER) was to establish whether a widely used checklist accurately detects or excludes physical abuse among children presenting to ERs with physical injury. A large multicentre study with a 6-month follow-up in 4 ERs in The Netherlands. Participants were 4290 children aged 0-7 years, attending the ER because of physical injury. All children were systematically tested with an easy-to-use child abuse checklist (index test). A national expert panel (reference standard) retrospectively assessed all children with positive screens and a 15% random sample of the children with negative screens for physical abuse, using additional information, namely, an injury history taken by a paediatrician, information provided by the general practitioner, youth doctor and social services by structured questionnaires, and 6-month follow-up information. Our main outcome measure was physical child abuse; secondary outcome measure was injury due to neglect and need for help. 4253/4290 (99%) parents agreed to follow-up. At a prevalence of 0.07% (3/4253) for inflicted injury by expert panel decision, the positive predictive value of the checklist was 0.03 (95% CI 0.006 to 0.085), and the negative predictive value 1.0 (0.994 to 1.0). There was 100% (93 to 100) agreement about inflicted injury in children, with positive screens between the expert panel and child abuse experts. Rare cases of inflicted injury among preschool children presenting at ERs for injury are very likely captured by easy-to-use checklists, but at very high false-positive rates. Subsequent assessment by child abuse experts can be safely restricted to children with positive screens at very low risk of missing cases of inflicted injury. Because of the high false positive rate, we do advise careful prior consideration of cost-effectiveness and clinical and societal implications before de novo implementation.

[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.

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.

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.

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/

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.

Relationship between echocardiographic LV mass and ECG based left ventricular voltages in an adolescent population: related or random?

PubMed

Czosek, Richard J; Cnota, James F; Knilans, Timothy K; Pratt, Jesse; Guerrier, Karine; Anderson, Jeffrey B

2014-09-01

In attempts to detect diseases that may place adolescents at risk for sudden death, some have advocated for population-based screening. Controversy exists over electrocardiography (ECG) screening due to the lack of specificity, cost, and detrimental effects of false positive or extraneous outcomes. Analyze the relationship between precordial lead voltage on ECG and left ventricle (LV) mass by echocardiogram in adolescent athletes. Retrospective cohort analysis of a prospectively obtained population of self-identified adolescent athletes during sports screening with ECG and echocardiogram. Correlation between ECG LV voltages (R wave in V6 [RV6] and S wave in lead V1 [SV1]) was compared to echocardiogram-based measurements of left ventricular mass. Potential effects on ECG voltages by body anthropometrics, including weight, body mass index (BMI), and body surface area were analyzed, and ECG voltages indexed to BMI were compared to LV mass indices to analyze for improved correlation. A total of 659 adolescents enrolled in this study (64% male). The mean age was 15.4 years (14-18). The correlations between LV mass and RV6, SV1, and RV6 + SV1 were all less than 0.20. The false positive rate for abnormal voltages was relatively high (5.5%) but improved if abnormal voltages in both RV6 and SV1 were mandated simultaneously (0%). Indexing ECG voltages to BMI significantly improved correlation to LV mass, though false positive findings were increased (12.9%). There is poor correlation between ECG precordial voltages and echocardiographic LV mass. This relationship is modified by BMI. This finding may contribute to the poor ECG screening characteristics. ©2014 Wiley Periodicals, Inc.

Quantification of false positive reduction in nucleic acid purification on hemorrhagic fever DNA.

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

James, Conrad D.; Pohl, Kenneth Roy; Derzon, Mark Steven

2006-11-01

Columbia University has developed a sensitive highly multiplexed system for genetic identification of nucleic acid targets. The primary obstacle to implementing this technology is the high rate of false positives due to high levels of unbound reporters that remain within the system after hybridization. The ability to distinguish between free reporters and reporters bound to targets limits the use of this technology. We previously demonstrated a new electrokinetic method for binary separation of kb pair long DNA molecules and oligonucleotides. The purpose of this project 99864 is to take these previous demonstrations and further develop the technique and hardware formore » field use. Specifically, our objective was to implement separation in a heterogeneous sample (containing target DNA and background oligo), to perform the separation in a flow-based device, and to develop all of the components necessary for field testing a breadboard prototype system.« less

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).

Breaking through the false coincidence barrier in electron–ion coincidence experiments

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

Osborn, David L.; Hayden, Carl C.; Hemberger, Patrick

Photoelectron Photoion Coincidence (PEPICO) spectroscopy holds the promise of a universal, isomer-selective, and sensitive analytical technique for time-resolved quantitative analysis of bimolecular chemical reactions. Unfortunately, its low dynamic range of ~10 3 has largely precluded its use for this purpose, where a dynamic range of at least 10 5 is generally required. This limitation is due to the false coincidence background common to all coincidence experiments, especially at high count rates. Electron/ion pairs emanating from separate ionization events but arriving within the ion time of flight (TOF) range of interest constitute the false coincidence background. Although this background has uniformmore » intensity at every m/z value, the Poisson scatter in the false coincidence background obscures small signals. In this paper, temporal ion deflection coupled with a position-sensitive ion detector enables suppression of the false coincidence background, increasing the dynamic range in the PEPICO TOF mass spectrum by 2–3 orders of magnitude. The ions experience a time-dependent electric deflection field at a well-defined fraction of their time of flight. This deflection defines an m/z- and ionization-time dependent ion impact position for true coincidences, whereas false coincidences appear randomly outside this region and can be efficiently suppressed. When cold argon clusters are ionized, false coincidence suppression allows us to observe species up to Ar 9 +, whereas Ar 4 + is the largest observable cluster under traditional operation. As a result, this advance provides mass-selected photoelectron spectra for fast, high sensitivity quantitative analysis of reacting systems.« less

Breaking through the false coincidence barrier in electron–ion coincidence experiments

DOE PAGES

Osborn, David L.; Hayden, Carl C.; Hemberger, Patrick; ...

2016-10-31

Photoelectron Photoion Coincidence (PEPICO) spectroscopy holds the promise of a universal, isomer-selective, and sensitive analytical technique for time-resolved quantitative analysis of bimolecular chemical reactions. Unfortunately, its low dynamic range of ~10 3 has largely precluded its use for this purpose, where a dynamic range of at least 10 5 is generally required. This limitation is due to the false coincidence background common to all coincidence experiments, especially at high count rates. Electron/ion pairs emanating from separate ionization events but arriving within the ion time of flight (TOF) range of interest constitute the false coincidence background. Although this background has uniformmore » intensity at every m/z value, the Poisson scatter in the false coincidence background obscures small signals. In this paper, temporal ion deflection coupled with a position-sensitive ion detector enables suppression of the false coincidence background, increasing the dynamic range in the PEPICO TOF mass spectrum by 2–3 orders of magnitude. The ions experience a time-dependent electric deflection field at a well-defined fraction of their time of flight. This deflection defines an m/z- and ionization-time dependent ion impact position for true coincidences, whereas false coincidences appear randomly outside this region and can be efficiently suppressed. When cold argon clusters are ionized, false coincidence suppression allows us to observe species up to Ar 9 +, whereas Ar 4 + is the largest observable cluster under traditional operation. As a result, this advance provides mass-selected photoelectron spectra for fast, high sensitivity quantitative analysis of reacting systems.« less

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

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.

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.

Determining Occurrence Dynamics when False Positives Occur: Estimating the Range Dynamics of Wolves from Public Survey Data.

PubMed

Miller, David A W; Nichols, James D; Gude, Justin A; Rich, Lindsey N; Podruzny, Kevin M; Hines, James E; Mitchell, Michael S

2013-01-01

Large-scale presence-absence monitoring programs have great promise for many conservation applications. Their value can be limited by potential incorrect inferences owing to observational errors, especially when data are collected by the public. To combat this, previous analytical methods have focused on addressing non-detection from public survey data. Misclassification errors have received less attention but are also likely to be a common component of public surveys, as well as many other data types. We derive estimators for dynamic occupancy parameters (extinction and colonization), focusing on the case where certainty can be assumed for a subset of detections. We demonstrate how to simultaneously account for non-detection (false negatives) and misclassification (false positives) when estimating occurrence parameters for gray wolves in northern Montana from 2007-2010. Our primary data source for the analysis was observations by deer and elk hunters, reported as part of the state's annual hunter survey. This data was supplemented with data from known locations of radio-collared wolves. We found that occupancy was relatively stable during the years of the study and wolves were largely restricted to the highest quality habitats in the study area. Transitions in the occupancy status of sites were rare, as occupied sites almost always remained occupied and unoccupied sites remained unoccupied. Failing to account for false positives led to over estimation of both the area inhabited by wolves and the frequency of turnover. The ability to properly account for both false negatives and false positives is an important step to improve inferences for conservation from large-scale public surveys. The approach we propose will improve our understanding of the status of wolf populations and is relevant to many other data types where false positives are a component of observations.

Best research practices in psychology: Illustrating epistemological and pragmatic considerations with the case of relationship science.

PubMed

Finkel, Eli J; Eastwick, Paul W; Reis, Harry T

2015-02-01

In recent years, a robust movement has emerged within psychology to increase the evidentiary value of our science. This movement, which has analogs throughout the empirical sciences, is broad and diverse, but its primary emphasis has been on the reduction of statistical false positives. The present article addresses epistemological and pragmatic issues that we, as a field, must consider as we seek to maximize the scientific value of this movement. Regarding epistemology, this article contrasts the false-positives-reduction (FPR) approach with an alternative, the error balance (EB) approach, which argues that any serious consideration of optimal scientific practice must contend simultaneously with both false-positive and false-negative errors. Regarding pragmatics, the movement has devoted a great deal of attention to issues that frequently arise in laboratory experiments and one-shot survey studies, but it has devoted less attention to issues that frequently arise in intensive and/or longitudinal studies. We illustrate these epistemological and pragmatic considerations with the case of relationship science, one of the many research domains that frequently employ intensive and/or longitudinal methods. Specifically, we examine 6 research prescriptions that can help to reduce false-positive rates: preregistration, prepublication sharing of materials, postpublication sharing of data, close replication, avoiding piecemeal publication, and increasing sample size. For each, we offer concrete guidance not only regarding how researchers can improve their research practices and balance the risk of false-positive and false-negative errors, but also how the movement can capitalize upon insights from research practices within relationship science to make the movement stronger and more inclusive. PsycINFO Database Record (c) 2015 APA, all rights reserved.

High-frequency (8 to 16 kHz) reference thresholds and intrasubject threshold variability relative to ototoxicity criteria using a Sennheiser HDA 200 earphone.

PubMed

Frank, T

2001-04-01

The first purpose of this study was to determine high-frequency (8 to 16 kHz) thresholds for standardizing reference equivalent threshold sound pressure levels (RETSPLs) for a Sennheiser HDA 200 earphone. The second and perhaps more important purpose of this study was to determine whether repeated high-frequency thresholds using a Sennheiser HDA 200 earphone had a lower intrasubject threshold variability than the ASHA 1994 significant threshold shift criteria for ototoxicity. High-frequency thresholds (8 to 16 kHz) were obtained for 100 (50 male, 50 female) normally hearing (0.25 to 8 kHz) young adults (mean age of 21.2 yr) in four separate test sessions using a Sennheiser HDA 200 earphone. The mean and median high-frequency thresholds were similar for each test session and increased as frequency increased. At each frequency, the high-frequency thresholds were not significantly (p > 0.05) different for gender, test ear, or test session. The median thresholds at each frequency were similar to the 1998 interim ISO RETSPLs; however, large standard deviations and wide threshold distributions indicated very high intersubject threshold variability, especially at 14 and 16 kHz. Threshold repeatability was determined by finding the threshold differences between each possible test session comparison (N = 6). About 98% of all of the threshold differences were within a clinically acceptable range of +/-10 dB from 8 to 14 kHz. The threshold differences between each subject's second, third, and fourth minus their first test session were also found to determine whether intrasubject threshold variability was less than the ASHA 1994 criteria for determining a significant threshold shift due to ototoxicity. The results indicated a false-positive rate of 0% for a threshold shift > or = 20 dB at any frequency and a false-positive rate of 2% for a threshold shift >10 dB at two consecutive frequencies. This study verified that the output of high-frequency audiometers at 0 dB HL using Sennheiser HDA 200 earphones should equal the 1998 interim ISO RETSPLs from 8 to 16 kHz. Further, because the differences between repeated thresholds were well within +/-10 dB and had an extremely low false-positive rate in reference to the ASHA 1994 criteria for a significant threshold shift due to ototoxicity, a Sennheiser HDA 200 earphone can be used for serial monitoring to determine whether significant high-frequency threshold shifts have occurred for patients receiving potentially ototoxic drug therapy.

An immunoblotting diagnostic assay for heartwater based on the immunodominant 32-kilodalton protein of Cowdria ruminantium detects false positives in field sera.

PubMed Central

Mahan, S M; Tebele, N; Mukwedeya, D; Semu, S; Nyathi, C B; Wassink, L A; Kelly, P J; Peter, T; Barbet, A F

1993-01-01

Heartwater, a major constraint to improved livestock production in Zimbabwe, threatens to invade areas which have been previously unaffected. To monitor its spread in Zimbabwe, an immunoblotting diagnostic assay based on the responses of animals to the immunodominant, conserved 32-kDa protein of Cowdria ruminantium was evaluated. In this assay, no false reactions were detected with sera known to be positive and negative, but sera from some cattle, sheep, and goats from heartwater-free areas of Zimbabwe reacted strongly with the 32-kDa protein, suggesting that either these animals had previous exposure to heartwater or they were false positives. To investigate the possibility of previous exposure to heartwater, 11 immunoblot-positive and 6 immunoblot-negative sheep from heartwater-free areas of Zimbabwe were compared regarding their susceptibilities to challenge with C. ruminantium. Prior to challenge, C. ruminantium could not be detected in any sheep by transmission to Amblyomma hebraeum ticks or by the polymerase chain reaction (PCR) conducted with plasma samples. All sheep were equally susceptible to the challenge, and infection was confirmed by brain biopsy, necropsy, PCR, and transmission of C. ruminantium to ticks. Our data suggest that the immunoblot-positive reactions of sera from heartwater-free areas were due not to previous C. ruminantium infection but rather to antigenic cross-reactivity between C. ruminantium and another agent(s) such as Ehrlichia species. In conclusion, the immunodominant 32-kDa protein is not antigenically specific to C. ruminantium and its use in serological diagnosis of heartwater requires reevaluation. Images PMID:8253974

About egophony.

PubMed

Sapira, J D

1995-09-01

Egophony is a change in timbre (Ee to A) but not pitch or volume. It is due to a decrease in the amplitude and an increase in the frequency [corrected] of the second formant, produced by solid (including compressed lung) interposed between the resonator and the stethoscope head. This explains certain difficulties in learning this valuable but currently neglected sign as well as in understanding certain physiologic false-positive occurrences.

Significance chasing in research practice: causes, consequences and possible solutions.

PubMed

Ware, Jennifer J; Munafò, Marcus R

2015-01-01

The low reproducibility of findings within the scientific literature is a growing concern. This may be due to many findings being false positives which, in turn, can misdirect research effort and waste money. We review factors that may contribute to poor study reproducibility and an excess of 'significant' findings within the published literature. Specifically, we consider the influence of current incentive structures and the impact of these on research practices. The prevalence of false positives within the literature may be attributable to a number of questionable research practices, ranging from the relatively innocent and minor (e.g. unplanned post-hoc tests) to the calculated and serious (e.g. fabrication of data). These practices may be driven by current incentive structures (e.g. pressure to publish), alongside the preferential emphasis placed by journals on novelty over veracity. There are a number of potential solutions to poor reproducibility, such as new publishing formats that emphasize the research question and study design, rather than the results obtained. This has the potential to minimize significance chasing and non-publication of null findings. Significance chasing, questionable research practices and poor study reproducibility are the unfortunate consequence of a 'publish or perish' culture and a preference among journals for novel findings. It is likely that top-down change implemented by those with the ability to modify current incentive structure (e.g. funders and journals) will be required to address problems of poor reproducibility. © 2014 Society for the Study of Addiction.

CT Colonography with Computer-aided Detection: Recognizing the Causes of False-Positive Reader Results

PubMed Central

Dachman, Abraham H.; Wroblewski, Kristen; Vannier, Michael W.; Horne, John M.

2014-01-01

Computed tomography (CT) colonography is a screening modality used to detect colonic polyps before they progress to colorectal cancer. Computer-aided detection (CAD) is designed to decrease errors of detection by finding and displaying polyp candidates for evaluation by the reader. CT colonography CAD false-positive results are common and have numerous causes. The relative frequency of CAD false-positive results and their effect on reader performance on the basis of a 19-reader, 100-case trial shows that the vast majority of CAD false-positive results were dismissed by readers. Many CAD false-positive results are easily disregarded, including those that result from coarse mucosa, reconstruction, peristalsis, motion, streak artifacts, diverticulum, rectal tubes, and lipomas. CAD false-positive results caused by haustral folds, extracolonic candidates, diminutive lesions (<6 mm), anal papillae, internal hemorrhoids, varices, extrinsic compression, and flexural pseudotumors are almost always recognized and disregarded. The ileocecal valve and tagged stool are common sources of CAD false-positive results associated with reader false-positive results. Nondismissable CAD soft-tissue polyp candidates larger than 6 mm are another common cause of reader false-positive results that may lead to further evaluation with follow-up CT colonography or optical colonoscopy. Strategies for correctly evaluating CAD polyp candidates are important to avoid pitfalls from common sources of CAD false-positive results. ©RSNA, 2014 PMID:25384290

Diagnostic and prognostic value of additional SPECT/CT in sentinel lymph node mapping in breast cancer patients.

PubMed

Stanzel, Susanne; Pernthaler, Birgit; Schwarz, Thomas; Bjelic-Radisic, Vesna; Kerschbaumer, Stefan; Aigner, Reingard M

2018-06-01

of the study was to demonstrate the diagnostic and prognostic value of SPECT/CT in sentinel lymph node mapping (SLNM) in patients with invasive breast cancer. 114 patients with invasive breast cancer with clinically negative lymph nodes were included in this retrospective study as they were referred for SLNM with 99m Tc-nanocolloid. Planar image acquisition was accomplished in a one-day or two-day protocol depending on the schedule of the surgical procedure. Low dose SPECT/CT was performed after the planar images. The sentinel lymph node biopsy (SLNB) was considered false negative if a primary recurrence developed within 12 months after SLNB in the axilla from which a tumor-free SLN had been removed. Between December 2009 and December 2011, 114 patients (pts.) underwent SLNM with additional SPECT/CT. Planar imaging identified in 109 pts. 139 SLNs, which were tumor-positive in 42 nodes (n = 41 pts.). SPECT/CT identified in 81 pts. 151 additional SLNs, of which 19 were tumor-positive and led to therapy change (axillary lymph node dissection) in 11 pts. (9.6 %). Of overall 61 tumor-positive SLNs (n = 52 pts.) SPECT/CT detected all, whereas planar imaging detected only 42 of 61 ( P < 0.0001). No patient had lymph node metastasis within 12 months after SLNB in the axilla from which a tumor-free SLN had been removed resulting in a false-negative rate of 0 %. The local relapse rate was 1.8 % leading to a 4-year disease-free survival rate of 90 %. Among patients with breast cancer, the use of SPECT/CT-aided SLNM correlated due to a better anatomical localization and identification of planar not visible SLNs with a higher detection rate of SLNs. This led to therapeutic consequences and an excellent false-negative and 4-year disease-free survival rate. Schattauer GmbH.

Detecting and avoiding likely false-positive findings - a practical guide.

PubMed

Forstmeier, Wolfgang; Wagenmakers, Eric-Jan; Parker, Timothy H

2017-11-01

Recently there has been a growing concern that many published research findings do not hold up in attempts to replicate them. We argue that this problem may originate from a culture of 'you can publish if you found a significant effect'. This culture creates a systematic bias against the null hypothesis which renders meta-analyses questionable and may even lead to a situation where hypotheses become difficult to falsify. In order to pinpoint the sources of error and possible solutions, we review current scientific practices with regard to their effect on the probability of drawing a false-positive conclusion. We explain why the proportion of published false-positive findings is expected to increase with (i) decreasing sample size, (ii) increasing pursuit of novelty, (iii) various forms of multiple testing and researcher flexibility, and (iv) incorrect P-values, especially due to unaccounted pseudoreplication, i.e. the non-independence of data points (clustered data). We provide examples showing how statistical pitfalls and psychological traps lead to conclusions that are biased and unreliable, and we show how these mistakes can be avoided. Ultimately, we hope to contribute to a culture of 'you can publish if your study is rigorous'. To this end, we highlight promising strategies towards making science more objective. Specifically, we enthusiastically encourage scientists to preregister their studies (including a priori hypotheses and complete analysis plans), to blind observers to treatment groups during data collection and analysis, and unconditionally to report all results. Also, we advocate reallocating some efforts away from seeking novelty and discovery and towards replicating important research findings of one's own and of others for the benefit of the scientific community as a whole. We believe these efforts will be aided by a shift in evaluation criteria away from the current system which values metrics of 'impact' almost exclusively and towards a system which explicitly values indices of scientific rigour. © 2016 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.

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.

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.

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.

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

Lack of Utility of the Lysis-Centrifugation Blood Culture Method for Detection of Fungemia in Immunocompromised Cancer Patients

PubMed Central

Creger, Richard J.; Weeman, Kisa E.; Jacobs, Michael R.; Morrissey, Anne; Parker, Pamela; Fox, Robert M.; Lazarus, Hillard M.

1998-01-01

We retrospectively compared the utility of a fungal isolation device (Isolator) versus conventional techniques for recovering fungal organisms from blood cultures obtained from neutropenic cancer patients. Positive cultures were deemed true pathogens, possible pathogens, or contaminants according to laboratory and clinical criteria. Fifty-three patients had 66 positive blood cultures for fungi, nine on multiple occasions. In 20 episodes true pathogens were recovered, 6 from broth medium alone, 4 from the Isolator system alone, and 10 from both systems. False-negative cultures were noted in 4 of 20 (20%) cases in which broth medium was used and in 6 of 20 (30%) cases in which the Isolator system was used. Possible pathogens were detected in 4 of 66 blood culture-positive cases. Forty-two positive cultures were considered contaminants, 1 collected from standard medium and 41 of 42 (98%) which grew only in Isolators. Eleven of 18 patients with true fungal infections expired as a result of infection, while 4 of 33 patients with a contaminant expired, none from a fungal cause. We do not advocate the routine use of Isolator tubes in the evaluation of the febrile, neutropenic patient due to the high rates of false positives and of contamination. PMID:9431970

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…

Fine needle aspiration cytology of oral and oropharyngeal lesions with an emphasis on the diagnostic utility and pitfalls.

PubMed

Gupta, Nalini; Banik, Tarak; Rajwanshi, Arvind; Radotra, Bishan D; Panda, Naresh; Dey, Pranab; Srinivasan, Radhika; Nijhawan, Raje

2012-01-01

This study was undertaken to evaluate the diagnostic utility and pitfalls of fine needle aspiration cytology (FNAC) in oral and oropharyngeal lesions. This was a retrospective audit of oral and oropharyngeal lesions diagnosed with FNAC over a period of six years (2005-2010). Oral/oropharyngeal lesions [n=157] comprised 0.35% of the total FNAC load. The age ranged 1-80 years with the male: female ratio being 1.4:1. Aspirates were inadequate in 7% cases. Histopathology was available in 73/157 (46.5%) cases. Palate was the most common site of involvement [n=66] followed by tongue [n=35], buccal mucosa [n=18], floor of the mouth [n=17], tonsil [n=10], alveolus [n=5], retromolar trigone [n=3], and posterior pharyngeal wall [n=3]. Cytodiagnoses were categorized into infective/inflammatory lesions and benign cysts, and benign and malignant tumours. Uncommon lesions included ectopic lingual thyroid and adult rhabdomyoma of tongue, and solitary fibrous tumor (SFT), and leiomyosarcoma in buccal mucosa. A single false-positive case was dense inflammation with squamous cells misinterpreted as squamous cell carcinoma (SCC) on cytology. There were eight false-negative cases mainly due to sampling error. One false-negative case due to interpretation error was in a salivary gland tumor. The sensitivity of FNAC in diagnosing oral/oropharyngeal lesions was 71.4%; specificity was 97.8% with diagnostic accuracy of 87.7%. Salivary gland tumors and squamous cell carcinoma (SCC) are the most common lesions seen in the oral cavity. FNAC proves to be highly effective in diagnosing the spectrum of different lesions in this region. Sampling error is the main cause of false-negative cases in this region.

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.

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.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-07-03

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

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

Pathway analysis with next-generation sequencing data.

PubMed

Zhao, Jinying; Zhu, Yun; Boerwinkle, Eric; Xiong, Momiao

2015-04-01

Although pathway analysis methods have been developed and successfully applied to association studies of common variants, the statistical methods for pathway-based association analysis of rare variants have not been well developed. Many investigators observed highly inflated false-positive rates and low power in pathway-based tests of association of rare variants. The inflated false-positive rates and low true-positive rates of the current methods are mainly due to their lack of ability to account for gametic phase disequilibrium. To overcome these serious limitations, we develop a novel statistic that is based on the smoothed functional principal component analysis (SFPCA) for pathway association tests with next-generation sequencing data. The developed statistic has the ability to capture position-level variant information and account for gametic phase disequilibrium. By intensive simulations, we demonstrate that the SFPCA-based statistic for testing pathway association with either rare or common or both rare and common variants has the correct type 1 error rates. Also the power of the SFPCA-based statistic and 22 additional existing statistics are evaluated. We found that the SFPCA-based statistic has a much higher power than other existing statistics in all the scenarios considered. To further evaluate its performance, the SFPCA-based statistic is applied to pathway analysis of exome sequencing data in the early-onset myocardial infarction (EOMI) project. We identify three pathways significantly associated with EOMI after the Bonferroni correction. In addition, our preliminary results show that the SFPCA-based statistic has much smaller P-values to identify pathway association than other existing methods.

"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…

Risk of breast cancer after false-positive results in mammographic screening.

PubMed

Román, Marta; Castells, Xavier; Hofvind, Solveig; von Euler-Chelpin, My

2016-06-01

Women with false-positive results are commonly referred back to routine screening. Questions remain regarding their long-term outcome of breast cancer. We assessed the risk of screen-detected breast cancer in women with false-positive results. We conducted a joint analysis using individual level data from the population-based screening programs in Copenhagen and Funen in Denmark, Norway, and Spain. Overall, 150,383 screened women from Denmark (1991-2008), 612,138 from Norway (1996-2010), and 1,172,572 from Spain (1990-2006) were included. Poisson regression was used to estimate the relative risk (RR) of screen-detected cancer for women with false-positive versus negative results. We analyzed information from 1,935,093 women 50-69 years who underwent 6,094,515 screening exams. During an average 5.8 years of follow-up, 230,609 (11.9%) women received a false-positive result and 27,849 (1.4%) were diagnosed with screen-detected cancer. The adjusted RR of screen-detected cancer after a false-positive result was 2.01 (95% CI: 1.93-2.09). Women who tested false-positive at first screen had a RR of 1.86 (95% CI: 1.77-1.96), whereas those who tested false-positive at third screening had a RR of 2.42 (95% CI: 2.21-2.64). The RR of breast cancer at the screening test after the false-positive result was 3.95 (95% CI: 3.71-4.21), whereas it decreased to 1.25 (95% CI: 1.17-1.34) three or more screens after the false-positive result. Women with false-positive results had a twofold risk of screen-detected breast cancer compared to women with negative tests. The risk remained significantly higher three or more screens after the false-positive result. The increased risk should be considered when discussing stratified screening strategies. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

US women's attitudes to false positive mammography results and detection of ductal carcinoma in situ: cross sectional survey

PubMed Central

Schwartz, Lisa M; Woloshin, Steven; Sox, Harold C; Fischhoff, Baruch; Welch, H Gilbert

2000-01-01

Objective To determine women's attitudes to and knowledge of both false positive mammography results and the detection of ductal carcinoma in situ after screening mammography. Design Cross sectional survey. Setting United States. Participants 479 women aged 18-97 years who did not report a history of breast cancer. Main outcome measures Attitudes to and knowledge of false positive results and the detection of ductal carcinoma in situ after screening mammography. Results Women were aware that false positive results do occur. Their median estimate of the false positive rate for 10 years of annual screening was 20% (25th percentile estimate, 10%; 75th percentile estimate, 45%). The women were highly tolerant of false positives: 63% thought that 500 or more false positives per life saved was reasonable and 37% would tolerate 10 000 or more. Women who had had a false positive result (n=76) expressed the same high tolerance: 39% would tolerate 10 000 or more false positives. 62% of women did not want to take false positive results into account when deciding about screening. Only 8% of women thought that mammography could harm a woman without breast cancer, and 94% doubted the possibility of non-progressive breast cancers. Few had heard about ductal carcinoma in situ, a cancer that may not progress, but when informed, 60% of women wanted to take into account the possibility of it being detected when deciding about screening. Conclusions Women are aware of false positives and seem to view them as an acceptable consequence of screening mammography. In contrast, most women are unaware that screening can detect cancers that may never progress but feel that such information would be relevant. Education should perhaps focus less on false positives and more on the less familiar outcome of detection of ductal carcinoma in situ. PMID:10856064

Extreme Algal Bloom Detection with MERIS

NASA Astrophysics Data System (ADS)

Amin, R.; Gilerson, A.; Gould, R.; Arnone, R.; Ahmed, S.

2009-05-01

Harmful Algal Blooms (HAB's) are a major concern all over the world due to their negative impacts on the marine environment, human health, and the economy. Their detection from space still remains a challenge particularly in turbid coastal waters. In this study we propose a simple reflectance band difference approach for use with Medium Resolution Imaging Spectrometer (MERIS) data to detect intense plankton blooms. For convenience we label this approach as the Extreme Bloom Index (EBI) which is defined as EBI = Rrs (709) - Rrs (665). Our initial analysis shows that this band difference approach has some advantages over the band ratio approaches, particularly in reducing errors due to imperfect atmospheric corrections. We also do a comparison between the proposed EBI technique and the Maximum Chlorophyll Index (MCI) Gower technique. Our preliminary result shows that both the EBI and MCI indeces detect intense plankton blooms, however, MCI is more vulnerable in highly scattering waters, giving more positive false alarms than EBI.

Moving target parameter estimation of SAR after two looks cancellation

NASA Astrophysics Data System (ADS)

Gan, Rongbing; Wang, Jianguo; Gao, Xiang

2005-11-01

Moving target detection of synthetic aperture radar (SAR) by two looks cancellation is studied. First, two looks are got by the first and second half of the synthetic aperture. After two looks cancellation, the moving targets are reserved and stationary targets are removed. After that, a Constant False Alarm Rate (CFAR) detector detects moving targets. The ground range velocity and cross-range velocity of moving target can be got by the position shift between the two looks. We developed a method to estimate the cross-range shift due to slant range moving. we estimate cross-range shift by Doppler frequency center. Wigner-Ville Distribution (WVD) is used to estimate the Doppler frequency center (DFC). Because the range position and cross range before correction is known, estimation of DFC is much easier and efficient. Finally experiments results show that our algorithms have good performance. With the algorithms we can estimate the moving target parameter accurately.

A mega-analysis of memory reports from eight peer-reviewed false memory implantation studies.

PubMed

Scoboria, Alan; Wade, Kimberley A; Lindsay, D Stephen; Azad, Tanjeem; Strange, Deryn; Ost, James; Hyman, Ira E

2017-02-01

Understanding that suggestive practices can promote false beliefs and false memories for childhood events is important in many settings (e.g., psychotherapeutic, medical, and legal). The generalisability of findings from memory implantation studies has been questioned due to variability in estimates across studies. Such variability is partly due to false memories having been operationalised differently across studies and to differences in memory induction techniques. We explored ways of defining false memory based on memory science and developed a reliable coding system that we applied to reports from eight published implantation studies (N = 423). Independent raters coded transcripts using seven criteria: accepting the suggestion, elaboration beyond the suggestion, imagery, coherence, emotion, memory statements, and not rejecting the suggestion. Using this scheme, 30.4% of cases were classified as false memories and another 23% were classified as having accepted the event to some degree. When the suggestion included self-relevant information, an imagination procedure, and was not accompanied by a photo depicting the event, the memory formation rate was 46.1%. Our research demonstrates a useful procedure for systematically combining data that are not amenable to meta-analysis, and provides the most valid estimate of false memory formation and associated moderating factors within the implantation literature to date.

Influence of education and diagnostic modes on glaucoma assessment by optometrists.

PubMed

Yoshioka, Nayuta; Wong, Elizabeth; Kalloniatis, Michael; Yapp, Michael; Hennessy, Michael P; Agar, Ashish; Healey, Paul R; Hayen, Andrew; Zangerl, Barbara

2015-11-01

To evaluate the influence of different clinical examination techniques, including optic nerve head (ONH) photography, visual field tests, and adjunct imaging on the diagnosis of glaucoma by Australian and New Zealand optometrists. The effect of a short-term, didactic teaching module on these is also explored. Clinical data of 30 patients previously seen at the Centre for Eye Health was collected and compiled into glaucoma diagnostic assessment modules. Each of six modules contained different combinations of clinical examination results and required a classification of the cases as normal, suspicious or glaucoma. A cohort of 54 Australian and New Zealand optometrists were recruited for the study and allocated into two cohorts. The intervention group completed a glaucoma training course prior to the assessment while the control group completed the assessment without additional training. Diagnostic accuracy was compared between modules and optometrist groups. High false negative rates were observed with ONH photography, which were drastically reduced with the addition of visual field, albeit at the cost of increased false positive rates. Addition of adjunct imaging techniques partially compensated for the increase in the false positive rate from the visual field, but had limited effect on false negative rate. Educational intervention resulted in larger improvement in the diagnostic ability when multiple imaging modalities were provided. The study highlighted the importance of combining both structural and functional assessments in glaucoma. Current imaging technology demonstrated limited usefulness for event diagnosis due to the persistent difficulties of defining structural and functional loss in glaucoma, thus highlighting the need for new glaucoma assessment techniques. Short-term didactic teaching programs may only result in limited improvement of glaucoma diagnostic ability in optometrists, and hence, it may need to be combined with long-term and/or non-didactic training components to obtain a greater effect. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Gencrypt: one-way cryptographic hashes to detect overlapping individuals across samples

PubMed Central

Turchin, Michael C.; Hirschhorn, Joel N.

2012-01-01

Summary: Meta-analysis across genome-wide association studies is a common approach for discovering genetic associations. However, in some meta-analysis efforts, individual-level data cannot be broadly shared by study investigators due to privacy and Institutional Review Board concerns. In such cases, researchers cannot confirm that each study represents a unique group of people, leading to potentially inflated test statistics and false positives. To resolve this problem, we created a software tool, Gencrypt, which utilizes a security protocol known as one-way cryptographic hashes to allow overlapping participants to be identified without sharing individual-level data. Availability: Gencrypt is freely available under the GNU general public license v3 at http://www.broadinstitute.org/software/gencrypt/ Contact: joelh@broadinstitute.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:22302573

A correlated meta-analysis strategy for data mining "OMIC" scans.

PubMed

Province, Michael A; Borecki, Ingrid B

2013-01-01

Meta-analysis is becoming an increasingly popular and powerful tool to integrate findings across studies and OMIC dimensions. But there is the danger that hidden dependencies between putatively "independent" studies can cause inflation of type I error, due to reinforcement of the evidence from false-positive findings. We present here a simple method for conducting meta-analyses that automatically estimates the degree of any such non-independence between OMIC scans and corrects the inference for it, retaining the proper type I error structure. The method does not require the original data from the source studies, but operates only on summary analysis results from these in OMIC scans. The method is applicable in a wide variety of situations including combining GWAS and or sequencing scan results across studies with dependencies due to overlapping subjects, as well as to scans of correlated traits, in a meta-analysis scan for pleiotropic genetic effects. The method correctly detects which scans are actually independent in which case it yields the traditional meta-analysis, so it may safely be used in all cases, when there is even a suspicion of correlation amongst scans.

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

Short RNA indicator sequences are not completely degraded by autoclaving

PubMed Central

Unnithan, Veena V.; Unc, Adrian; Joe, Valerisa; Smith, Geoffrey B.

2014-01-01

Short indicator RNA sequences (<100 bp) persist after autoclaving and are recovered intact by molecular amplification. Primers targeting longer sequences are most likely to produce false positives due to amplification errors easily verified by melting curves analyses. If short indicator RNA sequences are used for virus identification and quantification then post autoclave RNA degradation methodology should be employed, which may include further autoclaving. PMID:24518856

Comparative assessment of methods for the fusion transcripts detection from RNA-Seq data

PubMed Central

Kumar, Shailesh; Vo, Angie Duy; Qin, Fujun; Li, Hui

2016-01-01

RNA-Seq made possible the global identification of fusion transcripts, i.e. “chimeric RNAs”. Even though various software packages have been developed to serve this purpose, they behave differently in different datasets provided by different developers. It is important for both users, and developers to have an unbiased assessment of the performance of existing fusion detection tools. Toward this goal, we compared the performance of 12 well-known fusion detection software packages. We evaluated the sensitivity, false discovery rate, computing time, and memory usage of these tools in four different datasets (positive, negative, mixed, and test). We conclude that some tools are better than others in terms of sensitivity, positive prediction value, time consumption and memory usage. We also observed small overlaps of the fusions detected by different tools in the real dataset (test dataset). This could be due to false discoveries by various tools, but could also be due to the reason that none of the tools are inclusive. We have found that the performance of the tools depends on the quality, read length, and number of reads of the RNA-Seq data. We recommend that users choose the proper tools for their purpose based on the properties of their RNA-Seq data. PMID:26862001

Accuracy and reliability of forensic latent fingerprint decisions

PubMed Central

Ulery, Bradford T.; Hicklin, R. Austin; Buscaglia, JoAnn; Roberts, Maria Antonia

2011-01-01

The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. The National Research Council of the National Academies and the legal and forensic sciences communities have called for research to measure the accuracy and reliability of latent print examiners’ decisions, a challenging and complex problem in need of systematic analysis. Our research is focused on the development of empirical approaches to studying this problem. Here, we report on the first large-scale study of the accuracy and reliability of latent print examiners’ decisions, in which 169 latent print examiners each compared approximately 100 pairs of latent and exemplar fingerprints from a pool of 744 pairs. The fingerprints were selected to include a range of attributes and quality encountered in forensic casework, and to be comparable to searches of an automated fingerprint identification system containing more than 58 million subjects. This study evaluated examiners on key decision points in the fingerprint examination process; procedures used operationally include additional safeguards designed to minimize errors. Five examiners made false positive errors for an overall false positive rate of 0.1%. Eighty-five percent of examiners made at least one false negative error for an overall false negative rate of 7.5%. Independent examination of the same comparisons by different participants (analogous to blind verification) was found to detect all false positive errors and the majority of false negative errors in this study. Examiners frequently differed on whether fingerprints were suitable for reaching a conclusion. PMID:21518906

Accuracy and reliability of forensic latent fingerprint decisions.

PubMed

Ulery, Bradford T; Hicklin, R Austin; Buscaglia, Joann; Roberts, Maria Antonia

2011-05-10

The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. The National Research Council of the National Academies and the legal and forensic sciences communities have called for research to measure the accuracy and reliability of latent print examiners' decisions, a challenging and complex problem in need of systematic analysis. Our research is focused on the development of empirical approaches to studying this problem. Here, we report on the first large-scale study of the accuracy and reliability of latent print examiners' decisions, in which 169 latent print examiners each compared approximately 100 pairs of latent and exemplar fingerprints from a pool of 744 pairs. The fingerprints were selected to include a range of attributes and quality encountered in forensic casework, and to be comparable to searches of an automated fingerprint identification system containing more than 58 million subjects. This study evaluated examiners on key decision points in the fingerprint examination process; procedures used operationally include additional safeguards designed to minimize errors. Five examiners made false positive errors for an overall false positive rate of 0.1%. Eighty-five percent of examiners made at least one false negative error for an overall false negative rate of 7.5%. Independent examination of the same comparisons by different participants (analogous to blind verification) was found to detect all false positive errors and the majority of false negative errors in this study. Examiners frequently differed on whether fingerprints were suitable for reaching a conclusion.

Significance chasing in research practice: Causes, consequences, and possible solutions

PubMed Central

Ware, Jennifer J.; Munafò, Marcus R.

2016-01-01

Background and Aims The low reproducibility of findings within the scientific literature is a growing concern. This may be due to many findings being false positives, which in turn can misdirect research effort and waste money. Methods We review factors that may contribute to poor study reproducibility and an excess of ‘significant’ findings within the published literature. Specifically, we consider the influence of current incentive structures, and the impact of these on research practices. Results The prevalence of false positives within the literature may be attributable to a number of questionable research practices, ranging from the relatively innocent and minor (e.g., unplanned post hoc tests), to the calculated and serious (e.g., fabrication of data). These practices may be driven by current incentive structures (e.g. pressure to publish), alongside the preferential emphasis placed by journals on novelty over veracity. There are a number of potential solutions to poor reproducibility, such as new publishing formats that emphasise the research question and study design, rather than the results obtained. This has the potential to minimise significance chasing and non-publication of null findings. Conclusions Significance chasing, questionable research practices, and poor study reproducibility are the unfortunate consequence of a “publish or perish” culture and a preference among journals for novel findings. It is likely that top-down change implemented by those with the ability to modify current incentive structure (e.g., funders and journals) will be required to address problems of poor reproducibility. PMID:25040652

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

Improved method to visualize lipid distribution within arterial vessel walls by 1.7 μm spectroscopic spectral-domain optical coherence tomography

NASA Astrophysics Data System (ADS)

Hirano, Mitsuharu; Tonosaki, Shozo; Ueno, Takahiro; Tanaka, Masato; Hasegawa, Takemi

2014-02-01

We report an improved method to visualize lipid distribution in axial and lateral direction within arterial vessel walls by spectroscopic spectral-domain Optical Coherence Tomography (OCT) at 1.7μm wavelength for identification of lipidrich plaque that is suspected to cause coronary events. In our previous method, an extended InGaAs-based line camera detects an OCT interferometric spectrum from 1607 to 1766 nm, which is then divided into twenty subbands, and A-scan OCT profile is calculated for each subband, resulting in a tomographic spectrum. This tomographic spectrum is decomposed into lipid spectrum having an attenuation peak at 1730 nm and non-lipid spectrum independent of wavelength, and the weight of each spectrum, that is, lipid and non-lipid score is calculated. In this paper, we present an improved algorithm, in which we have combined the lipid score and the non-lipid score to derive a corrected lipid score. We have found that the corrected lipid score is better than the raw lipid score in that the former is more robust against false positive occurring due to abrupt change in reflectivity at vessel surface. In addition, we have optimized spatial smoothing filter and reduced false positive and false negative due to detection noise and speckle. We have verified this improved algorithm by the use of measuring data of normal porcine coronary artery and lard as a model of lipid-rich plaque and confirmed that both the sensitivity and the specificity of lard are 92%.

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.

[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.

Evaluation of a quantitative H2S MPN test for fecal microbes analysis of water using biochemical and molecular identification.

PubMed

McMahan, Lanakila; Grunden, Amy M; Devine, Anthony A; Sobsey, Mark D

2012-04-15

The sensitivity and specificity of the H(2)S test to detect fecal bacteria in water has been variable and uncertain in previous studies, partly due to its presence-absence results. Furthermore, in groundwater samples false-positive results have been reported, with H(2)S-positive samples containing no fecal coliforms or Escherichia coli. False-negative results also have been reported in other studies, with H(2)S-negative samples found to contain E. coli. Using biochemical and molecular methods and a novel quantitative test format, this research identified the types and numbers of microbial community members present in natural water samples, including fecal indicators and pathogens as well as other bacteria. Representative water sources tested in this study included cistern rainwater, a protected lake, and wells in agricultural and forest settings. Samples from quantitative H(2)S tests of water were further cultured for fecal bacteria by spread plating onto the selective media for detection and isolation of Aeromonas spp., E. coli, Clostridium spp., H(2)S-producers, and species of Salmonella and Shigella. Isolates were then tested for H(2)S production, and identified to the genus and species level using biochemical methods. Terminal Restriction Fragment Length Polymorphisms (TRFLP) was the molecular method employed to quantitatively characterize microbial community diversity. Overall, it was shown that water samples testing positive for H(2)S bacteria also had bacteria of likely fecal origin and waters containing fecal pathogens also were positive for H(2)S bacteria. Of the microorganisms isolated from natural water, greater than 70 percent were identified using TRFLP analysis to reveal a relatively stable group of organisms whose community composition differed with water source and over time. These results further document the validity of the H(2)S test for detecting and quantifying fecal contamination of water. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detecting false positives in multielement designs: implications for brief assessments.

PubMed

Bartlett, Sara M; Rapp, John T; Henrickson, Marissa L

2011-11-01

The authors assessed the extent to which multielement designs produced false positives using continuous duration recording (CDR) and interval recording with 10-s and 1-min interval sizes. Specifically, they created 6,000 graphs with multielement designs that varied in the number of data paths, and the number of data points per data path, using a random number generator. In Experiment 1, the authors visually analyzed the graphs for the occurrence of false positives. Results indicated that graphs depicting only two sessions for each condition (e.g., a control condition plotted with multiple test conditions) produced the highest percentage of false positives for CDR and interval recording with 10-s and 1-min intervals. Conversely, graphs with four or five sessions for each condition produced the lowest percentage of false positives for each method. In Experiment 2, they applied two new rules, which were intended to decrease false positives, to each graph that depicted a false positive in Experiment 1. Results showed that application of new rules decreased false positives to less than 5% for all of the graphs except for those with two data paths and two data points per data path. Implications for brief assessments are discussed.

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.

Reliability and Normative Reference Values for the Vestibular/Ocular Motor Screening (VOMS) Tool in Youth Athletes.

PubMed

Moran, Ryan N; Covassin, Tracey; Elbin, R J; Gould, Dan; Nogle, Sally

2018-05-01

The Vestibular/Ocular Motor Screening (VOMS) measure is a newly developed vestibular and ocular motor symptom provocation screening tool for sport-related concussions. Baseline data, psychometric properties, and reliability of the VOMS are needed to further understand the applications of this tool, especially in the youth population, where research is scarce. To establish normative data and document the internal consistency and false-positive rate of the VOMS in a sample of nonconcussed youth athletes. Cross-sectional study; Level of evidence, 3. A total of 423 youth athletes (male = 278, female = 145) between the ages of 8 and 14 years completed baseline VOMS screening before the start of their respective sport seasons. Internal consistency was measured with Cronbach α and inter-item correlations. Approximately 60% of youth athletes reported no symptom provocation on baseline VOMS assessment, with 9% to 13% scoring over the cutoff levels (score of ≥2 for any individual VOMS symptom, near point convergence distance of ≥5 cm). The VOMS displayed a high internal consistency (Cronbach α = .97) at baseline among youth athletes. The current findings provide preliminary support for the implementation of VOMS baseline assessment into clinical practice, due to a high internal consistency, strong relationships between VOMS items, and a low false-positive rate at baseline in youth athletes.

Cross-reactivity of antibodies with phenolic compounds in pistachios during quantification of ochratoxin A by commercial enzyme-linked immunosorbent assay kits.

PubMed

Lee, Hyun Jung; Meldrum, Alexander D; Rivera, Nicholas; Ryu, Dojin

2014-10-01

Ochratoxin A (OTA), a nephrotoxic mycotoxin, naturally occurs in wide range of agricultural commodities. Typical screening of OTA involves various enzyme-linked immunosorbent assay (ELISA) methods. Pistachio (Pistacia vera L.) is a rich source of phenolic compounds that may result in a false positive due to structural similarities to OTA. The present study investigated the cross-reactivity profiles of phenolic compounds using two commercial ELISA test kits. High-performance liquid chromatography was used to confirm the concentration of OTA in the pistachio samples and compared with the results obtained from ELISA. When the degree of interaction and 50 % inhibitory concentration of phenolic compounds were determined, the cross-reactivity showed a pattern similar to that observed with the commercial ELSIA kits, although quantitatively different. In addition, the degree of interaction increased with the increasing concentration of phenolic compounds. The ELISA value had stronger correlations with the content of total phenolic compound, gallic acid, and catechin (R(2) = 0.757, 0.732, and 0.729, respectively) compared with epicatechin (R(2) = 0.590). These results suggest that phenolic compounds in pistachio skins may cross-react with the OTA antibody and lead to a false positive or to an overestimation of OTA concentration in ELISA-based tests.

Focal Cortical Dysplasia (FCD) lesion analysis with complex diffusion approach.

PubMed

Rajan, Jeny; Kannan, K; Kesavadas, C; Thomas, Bejoy

2009-10-01

Identification of Focal Cortical Dysplasia (FCD) can be difficult due to the subtle MRI changes. Though sequences like FLAIR (fluid attenuated inversion recovery) can detect a large majority of these lesions, there are smaller lesions without signal changes that can easily go unnoticed by the naked eye. The aim of this study is to improve the visibility of focal cortical dysplasia lesions in the T1 weighted brain MRI images. In the proposed method, we used a complex diffusion based approach for calculating the FCD affected areas. Based on the diffused image and thickness map, a complex map is created. From this complex map; FCD areas can be easily identified. MRI brains of 48 subjects selected by neuroradiologists were given to computer scientists who developed the complex map for identifying the cortical dysplasia. The scientists were blinded to the MRI interpretation result of the neuroradiologist. The FCD could be identified in all the patients in whom surgery was done, however three patients had false positive lesions. More lesions were identified in patients in whom surgery was not performed and lesions were seen in few of the controls. These were considered as false positive. This computer aided detection technique using complex diffusion approach can help detect focal cortical dysplasia in patients with epilepsy.

Rapid and reliable determination of illegal adulterant in herbal medicines and dietary supplements by LC/MS/MS.

PubMed

Liang, Qionglin; Qu, Jun; Luo, Guoan; Wang, Yiming

2006-02-13

In recent years, dietary supplements and herbal medicines are increasing in popularity all over the world. However, it is problematic that some manufacturers illegally included synthetic drugs in their products. Due to the extremely complex matrices of those products, most existing methods for screening illegal adulterations are time-consuming and liable to false positive. In this paper, a robust LC/MS/MS method for the high-throughput, sensitive and reliable determination of illegal adulterations from herbal medicines and dietary supplements was established. Minimal LC separation was employed and MRM was used to simultaneously monitor the three transitions under their respective optimal collision energy for each compound. Positive results were determined only if well-defined peaks appeared at all of the three transitions and the ratios among the peak areas were within given threshold. In this study, the method had been applied for the screening of nine most commonly adulterated therapeutic substances, such as sildenafil (Viagra) and famotidine, and the lower limits of detection of these compounds ranged from 0.05 to 1.5 ng/ml. Little sample preparation was needed for this method and the analysis time was less than 5 min/sample. The reliability has been demonstrated by the test with blank matrix. Over 200 products that were under suspicion by SDA of China had been assayed and till now no false negative or positive result was found. This method is rapid, simple, reliable and capable of screening multiple adulterants in one run.

Are the memories of older adults positively biased?

PubMed

Fernandes, Myra; Ross, Michael; Wiegand, Melanie; Schryer, Emily

2008-06-01

There is disagreement in the literature about whether a "positivity effect" in memory performance exists in older adults. To assess the generalizability of the effect, the authors examined memory for autobiographical, picture, and word information in a group of younger (17-29 years old) and older (60-84 years old) adults. For the autobiographical memory task, the authors asked participants to produce 4 positive, 4 negative, and 4 neutral recent autobiographical memories and to recall these a week later. For the picture and word tasks, participants studied photos or words of different valences (positive, negative, neutral) and later remembered them on a free-recall test. The authors found significant correlations in memory performance, across task material, for recall of both positive and neutral valence autobiographical events, pictures, and words. When the authors examined accurate memories, they failed to find consistent evidence, across the different types of material, of a positivity effect in either age group. However, the false memory findings offer more consistent support for a positivity effect in older adults. During recall of all 3 types of material, older participants recalled more false positive than false negative memories.

Clinical impact of reducing routine blood culture incubation time from 7 to 5 days.

PubMed

Marginson, Michael J; Daveson, Kathryn L; Kennedy, Karina J

2014-12-01

The aim of this study was to determine the clinical impact of reducing the blood culture incubation protocol from 7 to 5 days.A laboratory data extraction identified positive blood cultures occurring after 5 or more days of incubation at Canberra Hospital, Australia between 1 January 2001 and 31 August 2011. Isolates were identified as clinically significant using a pre-existing prospective bacteraemia database. Medical records review determined whether the positive result affected clinical management.Positive blood cultures after 5 or more days of incubation accounted for 2.65% (423/15979) of all positive blood cultures, although the majority were false positives or contaminants. Eighty-five were significant/indeterminate, representing an average of eight cases per year or 0.47% (85/15979) of all positive blood cultures sets. Forty-three were isolated for the first time, representing 1.1% of all significant/indeterminate blood culture episodes. Fungi and anaerobic bacteria compromised over 50% of isolates. In 26 cases (2.4 cases per year), the culture result led to a change in patient management.A 7 day incubation protocol is preferable due to late isolation of organisms; however, if space is required to accommodate increasing blood culture numbers, reducing to a 5 or 6 day protocol would miss only a small percentage of clinically significant isolates.

Detection by hyperspectral imaging of shiga toxin-producing Escherichia coli serogroups O26, O45, O103, O111, O121, and O145 on rainbow agar.

PubMed

Windham, William R; Yoon, Seung-Chul; Ladely, Scott R; Haley, Jennifer A; Heitschmidt, Jerry W; Lawrence, Kurt C; Park, Bosoon; Narrang, Neelam; Cray, William C

2013-07-01

The U.S. Department of Agriculture, Food Safety Inspection Service has determined that six non-O157 Shiga toxin-producing Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, and O145) are adulterants in raw beef. Isolate and phenotypic discrimination of non-O157 STEC is problematic due to the lack of suitable agar media. The lack of distinct phenotypic color variation among non-O157serogroups cultured on chromogenic agar poses a challenge in selecting colonies for confirmation. In this study, visible and near-infrared hyperspectral imaging and chemometrics were used to detect and classify non-O157 STEC serogroups grown on Rainbow agar O157. The method was first developed by building spectral libraries for each serogroup obtained from ground-truth regions of interest representing the true identity of each pixel and thus each pure culture colony in the hyperspectral agar-plate image. The spectral library for the pure-culture non-O157 STEC consisted of 2,171 colonies, with spectra derived from 124,347 of pixels. The classification models for each serogroup were developed with a k nearest-neighbor classifier. The overall classification training accuracy at the colony level was 99%. The classifier was validated with ground beef enrichments artificially inoculated with 10, 50, and 100 CFU/ml STEC. The validation ground-truth regions of interest of the STEC target colonies consisted of 606 colonies, with 3,030 pixels of spectra. The overall classification accuracy was 98%. The average specificity of the method was 98% due to the low false-positive rate of 1.2%. The sensitivity ranged from 78 to 100% due to the false-negative rates of 22, 7, and 8% for O145, O45, and O26, respectively. This study showed the potential of visible and near-infrared hyperspectral imaging for detecting and classifying colonies of the six non-O157 STEC serogroups. The technique needs to be validated with bacterial cultures directly extracted from meat products and positive identification of colonies by using confirmatory tests such as latex agglutination tests or PCR.

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.

Screening for subclinical Cushing's syndrome in type 2 diabetes mellitus: low false-positive rates with nocturnal salivary cortisol.

PubMed

Gagliardi, L; Chapman, I M; O'Loughlin, P; Torpy, D J

2010-04-01

The diagnosis of subclinical Cushing's syndrome (SCS) is important, but its relative rarity amongst patients with common metabolic disorders requires a simple test with a low false-positive rate. Using nocturnal salivary cortisol (NSC), which we first validated in patients with suspected and proven Cushing's syndrome, we screened 106 overweight patients with type 2 diabetes mellitus, a group at high risk of SCS and nontumoral hypothalamic-pituitary-adrenal axis perturbations. Our hypothesis was that a lower false-positive rate with NSC was likely, compared with that reported with the dexamethasone suppression test (DST) (10-20%), currently the foundation of diagnosis of SCS. No participant had clinically apparent Cushing's syndrome. Three participants had an elevated NSC but further testing excluded SCS. In this study, NSC had a lower false-positive rate (3%) than previously reported for the DST. Given the reported excellent performance of NSC in detection of hypercortisolism, the low false-positive rate in SCS suggests NSC may be superior to the DST for SCS screening. The NSC and DST should be compared directly in metabolic disorder patients; although our data suggest the patient group will need to be substantially larger to definitively determine the optimal screening test. Georg Thieme Verlag KG Stuttgart New York.

A New Way to Confirm Planet Candidates

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2016-05-01

What was the big deal behind the Kepler news conference yesterday? Its not just that the number of confirmed planets found by Kepler has more than doubled (though thats certainly exciting news!). Whats especially interesting is the way in which these new planets were confirmed.Number of planet discoveries by year since 1995, including previous non-Kepler discoveries (blue), previous Kepler discoveries (light blue) and the newly validated Kepler planets (orange). [NASA Ames/W. Stenzel; Princeton University/T. Morton]No Need for Follow-UpBefore Kepler, the way we confirmed planet candidates was with follow-up observations. The candidate could be validated either by directly imaging (which is rare) or obtaining a large number radial-velocity measurements of the wobble of the planets host star due to the planets orbit. But once Kepler started producing planet candidates, these approaches to validation became less feasible. A lot of Kepler candidates are small and orbit faint stars, making follow-up observations difficult or impossible.This problem is what inspired the development of whats known as probabilistic validation, an analysis technique that involves assessing the likelihood that the candidates signal is caused by various false-positive scenarios. Using this technique allows astronomers to estimate the likelihood of a candidate signal being a true planet detection; if that likelihood is high enough, the planet candidate can be confirmed without the need for follow-up observations.A breakdown of the catalog of Kepler Objects of Interest. Just over half had previously been identified as false positives or confirmed as candidates. 1284 are newly validated, and another 455 have FPP of1090%. [Morton et al. 2016]Probabilistic validation has been used in the past to confirm individual planet candidates in Kepler data, but now Timothy Morton (Princeton University) and collaborators have taken this to a new level: they developed the first code thats designed to do fully automated batch processing of a large number of candidates.In a recently published study the results of which were announced yesterday the teamapplied their code to the entire catalog of 7,470 Kepler objects of interest.New Planets and False PositivesThe teams code was able to successfully evaluate the total false-positive probability (FPP) for 7,056 of the objects of interest. Of these, 428 objects previously identified as candidates were found to have FPP of more than 90%, suggesting that they are most likely false positives.Periods and radii of candidate and confirmed planets in the Kepler Objects of Interest catalog. Blue circles have previously been identified as confirmed planets. Candidates (orange) are shaded by false positive probability; more transparent means more likely to be a false positive. [Morton et al. 2016]In contrast, 1,935 candidates were found to have FPP of less than 1%, and were therefore declared validated planets. Of these confirmations, 1,284 were previously unconfirmed, more than doubling Keplers previous catalog of 1,041 confirmed planets. Morton and collaborators believe that 9 of these newly confirmed planets may fall within the habitable zone of their host stars.While the announcement of 1,284 newly confirmed planets is huge, the analysis presented in this study is the real news. The code used is publicly available and can be applied to any transiting exoplanet candidate. This means that this analysis technique can be used to find batches of exoplanets in data from the extended Kepler mission (K2) or from the future TESS and PLATO transit missions.CitationTimothy D. Morton et al 2016 ApJ 822 86. doi:10.3847/0004-637X/822/2/86

Hydrogen breath test in schoolchildren.

PubMed Central

Douwes, A C; Schaap, C; van der Klei-van Moorsel, J M

1985-01-01

The frequency of negative hydrogen breath tests due to colonic bacterial flora which are unable to produce hydrogen was determined after oral lactulose challenge in 98 healthy Dutch schoolchildren. There was a negative result in 9.2%. The probability of a false normal lactose breath test (1:77) was calculated from these results together with those from a separate group of children with lactose malabsorption (also determined by hydrogen breath test). A study of siblings and mothers of subjects with a negative breath test did not show familial clustering of this condition. Faecal incubation tests with various sugars showed an increase in breath hydrogen greater than 100 parts per million in those with a positive breath test while subjects with a negative breath test also had a negative faecal incubation test. The frequency of a false negative hydrogen breath test was higher than previously reported, but this does not affect the superiority of this method of testing over the conventional blood glucose determination. PMID:4004310

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.

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.

Rapid Identification and Susceptibility Testing of Candida spp. from Positive Blood Cultures by Combination of Direct MALDI-TOF Mass Spectrometry and Direct Inoculation of Vitek 2

PubMed Central

Idelevich, Evgeny A.; Grunewald, Camilla M.; Wüllenweber, Jörg; Becker, Karsten

2014-01-01

Fungaemia is associated with high mortality rates and early appropriate antifungal therapy is essential for patient management. However, classical diagnostic workflow takes up to several days due to the slow growth of yeasts. Therefore, an approach for direct species identification and direct antifungal susceptibility testing (AFST) without prior time-consuming sub-culturing of yeasts from positive blood cultures (BCs) is urgently needed. Yeast cell pellets prepared using Sepsityper kit were used for direct identification by MALDI-TOF mass spectrometry (MS) and for direct inoculation of Vitek 2 AST-YS07 card for AFST. For comparison, MALDI-TOF MS and Vitek 2 testing were performed from yeast subculture. A total of twenty four positive BCs including twelve C. glabrata, nine C. albicans, two C. dubliniensis and one C. krusei isolate were processed. Applying modified thresholds for species identification (score ≥1.5 with two identical consecutive propositions), 62.5% of BCs were identified by direct MALDI-TOF MS. AFST results were generated for 72.7% of BCs directly tested by Vitek 2 and for 100% of standardized suspensions from 24 h cultures. Thus, AFST comparison was possible for 70 isolate-antifungal combinations. Essential agreement (minimum inhibitory concentration difference ≤1 double dilution step) was 88.6%. Very major errors (VMEs) (false-susceptibility), major errors (false-resistance) and minor errors (false categorization involving intermediate result) amounted to 33.3% (of resistant isolates), 1.9% (of susceptible isolates) and 1.4% providing 90.0% categorical agreement. All VMEs were due to fluconazole or voriconazole. This direct method saved on average 23.5 h for identification and 15.1 h for AFST, compared to routine procedures. However, performance for azole susceptibility testing was suboptimal and testing from subculture remains indispensable to validate the direct finding. PMID:25489741

Rapid identification and susceptibility testing of Candida spp. from positive blood cultures by combination of direct MALDI-TOF mass spectrometry and direct inoculation of Vitek 2.

PubMed

Idelevich, Evgeny A; Grunewald, Camilla M; Wüllenweber, Jörg; Becker, Karsten

2014-01-01

Fungaemia is associated with high mortality rates and early appropriate antifungal therapy is essential for patient management. However, classical diagnostic workflow takes up to several days due to the slow growth of yeasts. Therefore, an approach for direct species identification and direct antifungal susceptibility testing (AFST) without prior time-consuming sub-culturing of yeasts from positive blood cultures (BCs) is urgently needed. Yeast cell pellets prepared using Sepsityper kit were used for direct identification by MALDI-TOF mass spectrometry (MS) and for direct inoculation of Vitek 2 AST-YS07 card for AFST. For comparison, MALDI-TOF MS and Vitek 2 testing were performed from yeast subculture. A total of twenty four positive BCs including twelve C. glabrata, nine C. albicans, two C. dubliniensis and one C. krusei isolate were processed. Applying modified thresholds for species identification (score ≥ 1.5 with two identical consecutive propositions), 62.5% of BCs were identified by direct MALDI-TOF MS. AFST results were generated for 72.7% of BCs directly tested by Vitek 2 and for 100% of standardized suspensions from 24 h cultures. Thus, AFST comparison was possible for 70 isolate-antifungal combinations. Essential agreement (minimum inhibitory concentration difference ≤ 1 double dilution step) was 88.6%. Very major errors (VMEs) (false-susceptibility), major errors (false-resistance) and minor errors (false categorization involving intermediate result) amounted to 33.3% (of resistant isolates), 1.9% (of susceptible isolates) and 1.4% providing 90.0% categorical agreement. All VMEs were due to fluconazole or voriconazole. This direct method saved on average 23.5 h for identification and 15.1 h for AFST, compared to routine procedures. However, performance for azole susceptibility testing was suboptimal and testing from subculture remains indispensable to validate the direct finding.

Determination of cyclic volatile methylsiloxanes in personal care products by gas chromatography.

PubMed

Brothers, H M; Boehmer, T; Campbell, R A; Dorn, S; Kerbleski, J J; Lewis, S; Mund, C; Pero, D; Saito, K; Wieser, M; Zoller, W

2017-12-01

Organosiloxanes are prevalent in personal care products (PCPs) due to the desired properties they impart in the usage and application of such products. However, the European Chemical Agency (ECHA) has recently published restriction proposals on the amount of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclotetrasiloxane (D5), allowed in wash off products such as shampoos and conditioners which are discharged down the drain during consumer use. This legislation will require that reliable analytical methods are available for manufacturers and government agencies to use in documenting compliance with the restrictions. This article proposes a simple analytical method to enable accurate measurement of these compounds down to the circa 0.1 weight per cent level in PCPs. Although gas chromatography methods are reported in the literature for quantitation of D4 and D5 in several matrices including PCPs, the potential for generation of false positives due to contamination, co-elution and in situ generation of cyclic volatile methylsiloxanes (cVMS) is always present and needs to be controlled. This report demonstrates the applicability of using a combination of emulsion break, liquid-liquid extraction and silylation sample preparation followed by GC-FID analysis as a suitable means of analysing PCPs for specific cVMS. The reliability and limitations of such methodology were demonstrated through several round-robin studies conducted in the laboratories of a consortium of silicone manufacturers. In addition, this report presents examples of false positives encountered during development of the method and presents a comparative analysis between this method and a published QuEChERS sample preparation procedure to illustrate the potential for generation of false positives when an inappropriate approach is applied to determination of cVMS in personal care products. This report demonstrates that an approach to determine cVMS levels in personal care products is to perform an emulsion break on the sample, isolate the non-polar phase from the emulsion break and treat with a silylation reagent to abate potential in situ formation of cyclics during the course of GC-FID analysis. Round-robin studies conducted in laboratories representing multiple siloxane manufacturers demonstrated the reliability of the GC-FID method when measuring cVMS in PCPs down to circa 0.1%. © 2017 CES - Silicones Europe. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and the Société Française de Cosmétologie.

[Roaming through methodology. XXXII. False test results].

PubMed

van der Weijden, T; van den Akker, M

2001-05-12

The number of requests for diagnostic tests is rising. This leads to a higher chance of false test results. The false-negative proportion of a test is the proportion of negative test results among the diseased subjects. The false-positive proportion is the proportion of positive test results among the healthy subjects. The calculation of the false-positive proportion is often incorrect. For example, instead of 1 minus the specificity it is calculated as 1 minus the positive predictive value. This can lead to incorrect decision-making with respect to the application of the test. Physicians must apply diagnostic tests in such a way that the risk of false test results is minimal. The patient should be aware that a perfectly conclusive diagnostic test is rare in medical practice, and should more often be informed of the implications of false-positive and false-negative test results.

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.

Further Evidence for Nonspecificity of Theory of Mind in Preschoolers: Training and Transferability in the Understanding of False Beliefs and False Signs

ERIC Educational Resources Information Center

Iao, Lai-Sang; Leekam, Susan; Perner, Josef; McConachie, Helen

2011-01-01

In a training study, the authors addressed whether or not preschoolers' difficulty with false belief is due to a domain-specific problem with mental states. Following Slaughter's (1998) design, 57 children who failed a false-belief (FB) pretest received two sessions of training on either an FB, false sign (FS), or control task. All children were…

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

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.

Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology.

PubMed

Grandjean, P

2015-12-01

A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication. © The Author(s) 2015.

Meningiomas, dicentric chromosomes, gliomas, and telomerase activity.

PubMed

Carroll, T; Maltby, E; Brock, I; Royds, J; Timperley, W; Jellinek, D

1999-08-01

Lack of telomere maintenance during cell replication leads to telomere erosion and loss of function. This can result in telomere associations which probably cause the dicentric chromosomes seen in some tumour cells. One mechanism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening during cell division. Over 90 per cent of extracranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity. Telomerase activity was measured on 25 meningiomas and 29 gliomas. Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty-five of 29 gliomas were glioblastoma multiforme tumours. Measures were taken to ensure absence of false positives due to primer-dimer interaction and false negatives due to protein degradation or the presence of Taq polymerase inhibitors. All 25 meningiomas and the four low-grade gliomas (WHO grade II) were telomerase activity-negative. Seven (28 per cent) of the 25 glioblastoma multiforme tumours showed telomerase activity. The absence of telomerase activity in meningiomas and the high frequency of telomere associations support the hypothesis that these tumours are benign, transformed but pre-crisis. The relatively low frequency of telomerase activity in the malignant glioblastoma multiforme suggests that most of these tumours may have other mechanisms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the majority of patients suffering from these tumours. Copyright 1999 John Wiley & Sons, Ltd.

Analyzing False Positives of Four Questions in the Force Concept Inventory

ERIC Educational Resources Information Center

Yasuda, Jun-ichro; Mae, Naohiro; Hull, Michael M.; Taniguchi, Masa-aki

2018-01-01

In this study, we analyze the systematic error from false positives of the Force Concept Inventory (FCI). We compare the systematic errors of question 6 (Q.6), Q.7, and Q.16, for which clearly erroneous reasoning has been found, with Q.5, for which clearly erroneous reasoning has not been found. We determine whether or not a correct response to a…

Assessment of rates of recanting and hair testing as a biological measure of drug use in a general population sample of young people.

PubMed

Taylor, Michelle; Sullivan, John; Ring, Susan M; Macleod, John; Hickman, Matthew

2017-03-01

We investigate the extent of and factors associated with denial of previously reported cannabis and other illicit drug use, and assess the potential of hair testing for measuring substance use in general population samples. Birth cohort study. United Kingdom, 1991-present. A total of 3643 participants who provided hair and self-report measures of cannabis and other illicit drug use in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18 years. Denial of ever use of cannabis and other illicit drugs at age 18 following previously reported use. Positive hair drug tests for cannabis and other illicit drugs, and expected numbers of false positives and false negatives based on expected sensitivity and specificity. Cannabis and other illicit drug use was reported by 1223 and 393 individuals, respectively, before age 18 years. Of these 176 (14.4%) and 99 (25.2%), respectively, denied use at age 18. Denial of cannabis use decreased with the reporting of other substances and antisocial behaviour. Cannabis and other illicit drug use at age 18 was reported by 547 (22.5%) and 203 (8.4%) individuals, respectively. Of these, 111 (20.3%) and 13 (6.4%) were hair-positive for cannabis and other illicit drugs, respectively. Based on hair testing for cannabis use we expect 0 [95% confidence interval (CI) = 0-169] false positives and 394 (95% CI = 323-449) false negatives compared to observed 362 potential false positives and 436 potential false negatives based on self-report. In hair-positive individuals, reporting the use of other substances and antisocial behaviour decreased the odds of a negative self-report. Hair analysis provides an unreliable marker of substance use in general population samples. People who report more frequent substance use before age 18 are less likely to later deny previous substance use at age 18 than people who report occasional use. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Limits of intravascular contrast extravasation on computed tomography scan to define the need for pelvic angioembolization in pelvic blunt trauma: a specific assessment on the risk of false-positives.

PubMed

Ramin, Séverin; Hermida, Margaux; Millet, Ingrid; Murez, Thibault; Monnin, Valérie; Hamoui, Mazen; Capdevila, Xavier; Charbit, Jonathan

2018-06-12

The objective was to assess the predictive performance of different intravascular contrast extravasation (ICE) characteristics for need for pelvic transarterial embolization (TAE) to determine the risk factors of false-positives. A retrospective study was performed in our trauma center between 2010 and 2015. All severe trauma patients with pelvic fracture were included. Pelvic ICE characteristics on computed tomography (CT) scan were studied: arterial (aSICE), portal surface (pSICE), and extension (exSICE) anatomic relationships. The overall predictive performance of ICE surfaces for pelvic TAE was analyzed using receiver operating characteristic curves. The analysis focused on risk factors for false-positives. Among 311 severe trauma patients with pelvic ring fracture (mean age, 42 ± 19 years, mean Injury Severity Score, 27 ± 19), 94 (30%) had at least one pelvic ICE on the initial CT scan. Patients requiring pelvic TAE had significantly larger aSICE and pSICE than others (P=0.001 and P=0.035, respectively). The overall ability of ICE surfaces to predict pelvic TAE was modest (aSICE AUC, 0.76 [95% CI, 0.64-0.90]; P=0.011) or non-significant (pSICE and exSICE). The high-sensitivity threshold was defined as aSICE ≥20 mm. Using this threshold, 76% of patients were false-positives. Risk factors for false-positives were: admission systolic blood pressure ≥90 mmHg (63% versus 20%; P=0.03) and low transfusion needs (63% versus 10%; P=0.009), extravasation in contact with complex bone fracture (78% versus 30%; P=0.008) or the absence of a direct relationship between extravasation and a large retroperitoneal hematoma (100% versus 38%; P<0.001). A significant pelvic ICE during the arterial phase does not guarantee the need for pelvic TAE. Three-quarter of patients with aSICE ≥20 mm did not need pelvic TAE. Several complementary CT scan criteria will help to identify this risk of false-positives to determine adequate hemostatic pelvic procedures.This work is an original article, retrospective study Level II of evidence, Therapeutic/Critical Care management.

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.

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.

Modeling false positive detections in species occurrence data under different study designs.

PubMed

Chambert, Thierry; Miller, David A W; Nichols, James D

2015-02-01

The occurrence of false positive detections in presence-absence data, even when they occur infrequently, can lead to severe bias when estimating species occupancy patterns. Building upon previous efforts to account for this source of observational error, we established a general framework to model false positives in occupancy studies and extend existing modeling approaches to encompass a broader range of sampling designs. Specifically, we identified three common sampling designs that are likely to cover most scenarios encountered by researchers. The different designs all included ambiguous detections, as well as some known-truth data, but their modeling differed in the level of the model hierarchy at which the known-truth information was incorporated (site level or observation level). For each model, we provide the likelihood, as well as R and BUGS code needed for implementation. We also establish a clear terminology and provide guidance to help choosing the most appropriate design and modeling approach.

A misleading false-negative result using Neisseria gonorrhoeae opa MGB multiplex PCR assay in patient's rectal sample due to partial mutations of the opa gene.

PubMed

Vahidnia, Ali; van Empel, Pieter Jan; Costa, Sandra; Oud, Rob T N; van der Straaten, Tahar; Bliekendaal, Harry; Spaargaren, Joke

2015-07-01

A 53-year-old homosexual man presented at his general practitioner (GP) practice with a suspicion of sexually transmitted infection. Initial NAAT screening was performed for Chlamydia trachomatis and Neisseria gonorrhoeae. The patient was positive for Neisseria gonorrhoeae both for his urine and rectal sample. The subsequent confirmation test for Neisseria gonorrhoeae by a second laboratory was only confirmed for the urine sample and the rectal sample was negative. We report a case of a potential false-negative diagnosis of Neisseria gonorrhoeae due to mutations of DNA sequence in the probe region of opa-MGB assay of the rectal sample. The patient did not suffer any discomfort as diagnosis of Neisseria gonorrhoeae in his urine sample had already led to treatment by prescribing the patient with Ceftriaxone 500 mg IV dissolved in 1 ml lidocaine 2% and 4 mL saline. The patient also received a prescription for Azithromycin (2x500 mg).

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

Optimizing the TESS Planet Finding Pipeline

NASA Astrophysics Data System (ADS)

Chitamitara, Aerbwong; Smith, Jeffrey C.; Tenenbaum, Peter; TESS Science Processing Operations Center

2017-10-01

The Transiting Exoplanet Survey Satellite (TESS) is a new NASA planet finding all-sky survey that will observe stars within 200 light years and 10-100 times brighter than that of the highly successful Kepler mission. TESS is expected to detect ~1000 planets smaller than Neptune and dozens of Earth size planets. As in the Kepler mission, the Science Processing Operations Center (SPOC) processing pipeline at NASA Ames Research center is tasked with calibrating the raw pixel data, generating systematic error corrected light curves and then detecting and validating transit signals. The Transiting Planet Search (TPS) component of the pipeline must be modified and tuned for the new data characteristics in TESS. For example, due to each sector being viewed for as little as 28 days, the pipeline will be identifying transiting planets based on a minimum of two transit signals rather than three, as in the Kepler mission. This may result in a significantly higher false positive rate. The study presented here is to measure the detection efficiency of the TESS pipeline using simulated data. Transiting planets identified by TPS are compared to transiting planets from the simulated transit model using the measured epochs, periods, transit durations and the expected detection statistic of injected transit signals (expected MES). From the comparisons, the recovery and false positive rates of TPS is measured. Measurements of recovery in TPS are then used to adjust TPS configuration parameters to maximize the planet recovery rate and minimize false detections. The improvements in recovery rate between initial TPS conditions and after various adjustments will be presented and discussed.

Approach for detecting mutagenicity of biodegraded and ozonated pharmaceuticals, metabolites and transformation products from a drinking water perspective.

PubMed

Gartiser, Stefan; Hafner, Christoph; Kronenberger-Schäfer, Kerstin; Happel, Oliver; Trautwein, Christoph; Kümmerer, Klaus

2012-09-01

Many pharmaceuticals and related metabolites are not efficiently removed in sewage treatment plants and enter into surface water. There, they might be subject of drinking water abstraction and treatment by ozonation. In this study, a systematic approach for producing and effect-based testing of transformation products (TPs) during the drinking water ozonation process is proposed. For this, two pharmaceutical parent substances, three metabolites and one environmental degradation product were investigated with respect to their biodegradability and fate during drinking water ozonation. The Ames test (TA98, TA100) was used for the identification of mutagenic activity present in the solutions after testing inherent biodegradability and/or after ozonation of the samples. Suspicious results were complemented with the umu test. Due to the low substrate concentration required for ozonation, all ozonated samples were concentrated via solid phase extraction (SPE) before performing the Ames test. With the exception of piracetam, all substances were only incompletely biodegradable, suggesting the formation of stable TPs. Metformin, piracetam and guanylurea could not be removed completely by the ozonation process. We received some evidence that technical TPs are formed by ozonation of metformin and piracetam, whereas all tested metabolites were not detectable by analytical means after ozonation. In the case of guanylurea, one ozonation TP was identified by LC/MS. None of the experiments showed an increase of mutagenic effects in the Ames test. However, the SPE concentration procedure might lead to false-positive results due to the generation of mutagenic artefacts or might lead to false-negative results by missing adequate recovery efficiency. Thus, these investigations should always be accompanied by process blank controls that are carried out along the whole ozonation and SPE procedure. The study presented here is a first attempt to investigate the significance of transformation products by a systematic approach. However, the adequacy and sensitivity of the methodology need to be further investigated. The approach of combining biodegradation and ozonation with effect-based assays is a promising tool for the early detection of potential hazards from TPs as drinking water contaminants. It can support the strategy for the evaluation of substances and metabolites in drinking water. A multitude of possible factors which influence the results have to be carefully considered, among them the selectivity and sensibility of the mutagenicity test applied, the extraction method for concentrating the relevant compounds and the biocompatibility of the solvent. Therefore, the results have to be carefully interpreted, and possible false-negative and false-positive results should be considered.

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.

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.

Point-of-care urine tests for smoking status and isoniazid treatment monitoring in adult patients.

PubMed

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference.

Point-of-Care Urine Tests for Smoking Status and Isoniazid Treatment Monitoring in Adult Patients

PubMed Central

Nicolau, Ioana; Tian, Lulu; Menzies, Dick; Ostiguy, Gaston; Pai, Madhukar

2012-01-01

Background Poor adherence to isoniazid (INH) preventive therapy (IPT) is an impediment to effective control of latent tuberculosis (TB) infection. TB patients who smoke are at higher risk of latent TB infection, active disease, and TB mortality, and may have lower adherence to their TB medications. The objective of our study was to validate IsoScreen and SmokeScreen (GFC Diagnostics, UK), two point-of-care tests for monitoring INH intake and determining smoking status. The tests could be used together in the same individual to help identify patients with a high-risk profile and provide a tailored treatment plan that includes medication management, adherence interventions, and smoking cessation programs. Methodology/Principal Findings 200 adult outpatients attending the TB and/or the smoking cessation clinic were recruited at the Montreal Chest Institute. Sensitivity and specificity were measured for each test against the corresponding composite reference standard. Test reliability was measured using kappa statistic for intra-rater and inter-rater agreement. Univariate and multivariate logistic regression models were used to explore possible covariates that might be related to false-positive and false-negative test results. IsoScreen had a sensitivity of 93.2% (95% confidence interval [CI] 80.3, 98.2) and specificity of 98.7% (94.8, 99.8). IsoScreen had intra-rater agreement (kappa) of 0.75 (0.48, 0.94) and inter-rater agreement of 0.61 (0.27, 0.90). SmokeScreen had a sensitivity of 69.2% (56.4, 79.8), specificity of 81.6% (73.0, 88.0), intra-rater agreement of 0.77 (0.56, 0.94), and inter-rater agreement of 0.66 (0.42, 0.88). False-positive SmokeScreen tests were strongly associated with INH treatment. Conclusions IsoScreen had high validity and reliability, whereas SmokeScreen had modest validity and reliability. SmokeScreen tests did not perform well in a population receiving INH due to the association between INH treatment and false-positive SmokeScreen test results. Development of the next generation SmokeScreen assay should account for this potential interference. PMID:23029310

Evaluation of immunohematologic routine methods using the new erythrocyte-magnetized technology on the QWALYS 2 system.

PubMed

Schoenfeld, Helge; Bulling, Katia; von Heymann, Christian; Neuner, Bruno; Kalus, Ulrich; Kiesewetter, Holger; Pruss, Axel

2009-07-01

QWALYS 2 is a fully automated system for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte-magnetized technology (EMT) is based on the use of magnetic nanoparticles and avoids centrifugation and washing steps. Overall 499 blood samples were tested with our routine blood bank methods for ABO/D grouping, 313 samples for Rh phenotyping and K typing (microtiter plates; Olympus PK 7200), and 478 samples for ABS (gel centrifugation technique, DiaMed). All samples were tested in parallel with the EMT. In 496 of 499 samples (99.4%), a complete concordance between the observed (QWALYS 2) and the expected results for ABO/D grouping was found. One sample with a weak A in an AB blood group and 2 samples with a weak D were not detected by the QWALYS system. Rh phenotyping and K tests revealed a 100% concordance. In the two ABS techniques, 427 samples were negative in both and 15 samples showed the same antibody specificity in both. Three immunoglobulin M antibodies were as expected negative in EMT and positive by DiaMed. In 32 cases (6.7%), false-positive reactions were observed by EMT due to 22 unspecific reactions (4.6%) and 10 lipemic or fibrinic plasmas (2.1%). One autoantibody was found by EMT only. The EMT is reliably suited to ABO/D grouping, Rh phenotyping, and K testing and is suitable to detect immunoglobulin G red blood cell alloantibodies as well. The rate of false-positive reactions in ABS due to lipemic and fibrinic samples needs to be reduced.

Dengue Virus Seroconversion in Travelers to Dengue-Endemic Areas

PubMed Central

Olivero, Rosemary M.; Hamer, Davidson H.; MacLeod, William B.; Benoit, Christine M.; Sanchez-Vegas, Carolina; Jentes, Emily S.; Chen, Lin H.; Wilson, Mary E.; Marano, Nina; Yanni, Emad A.; Ooi, Winnie W.; Karchmer, Adolf W.; Kogelman, Laura; Barnett, Elizabeth D.

2016-01-01

We conducted a prospective study to measure dengue virus (DENV) antibody seroconversion in travelers to dengue-endemic areas. Travelers seen in the Boston Area Travel Medicine Network planning to visit dengue-endemic countries for ≥ 2 weeks were enrolled from 2009 to 2010. Pre- and post-travel blood samples and questionnaires were collected. Post-travel sera were tested for anti-DENV IgG by indirect IgG enzyme-linked immunosorbent assay (ELISA) and anti-DENV IgM by capture IgM ELISA. Participants with positive post-travel anti-DENV IgG or IgM were tested for pre-travel anti-DENV IgG and IgM; they were excluded from the seroconversion calculation if either pre-travel anti-DENV IgG or IgM were positive. Paired sera and questionnaires were collected for 62% (589/955) of enrolled travelers. Most participants were 19–64 years of age, female, and white. The most common purposes of travel were tourism and visiting friends and relatives; most trips were to Asia or Africa. Median length of travel was 21 days. DENV antibody seroconversion by either anti-DENV IgM or IgG ELISA was 2.9–6.8%; lower range percent excluded potential false-positive anti-DENV IgG due to receipt of yellow fever or Japanese encephalitis vaccines at enrollment; upper range percent excluded proven false-positive anti-DENV IgM. Eighteen percent of those with seroconversion reported dengue-like symptoms. Seroconversion was documented for travel to Africa as well as countries and regions known to be highly dengue endemic (India, Brazil, southeast Asia). Given widespread risk of dengue, travel medicine counseling should include information on risk of dengue in endemic areas and advice on preventing insect bites and seeking prompt medical attention for febrile illness. PMID:27573631

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.

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.

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

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.

Low hospital referral rates of school scoliosis screening positives in an urban district of mainland China.

PubMed

Guo, Yawen; Jiang, Qingwu; Tanimoto, Tetsuya; Kami, Masahiro; Luo, Chunyan; Leppold, Claire; Nishimura, Koichi; He, Yongpin; Kato, Shigeaki; Ding, Xiaocang

2017-04-01

Significant prevalence rates of adolescent scoliosis in China were suggested in previous studies. However, school screenings for adolescent scoliosis have been suspended due to low rates of positive detection under the past screening system in China. The present study was undertaken to screen for adolescent scoliosis in middle school students under a modern assessment system in a district of Shanghai. We performed a population-based, cross-sectional study of a middle school scoliosis screening program in the Jingan district. In 2015, schoolchildren were initially screened by visual inspection of clinical signs and the forward-bending test. Suspected cases were referred for radiography in hospital for scoliosis diagnosis. A total of 5327 middle school students (grades 6-8) were screened with 520 (9.76%) positives (the positive rates of girls and boys at 15.28% and 4.59%, respectively) and no statistically significant difference among grades. Only 301 positives (57.9%) followed the referral for hospital radiography. There were 102 cases (33.9%) that were diagnosed with scoliosis by radiography criteria (Cobb angle ≥10°) including mild scoliosis (Cobb 10-25) for 94 cases and moderate scoliosis (Cobb 25-40) for 8 cases, and false-positives (Cobb 0) for 39 cases. The putative prevalence rate was estimated as 1.9% from the referred students. Under an accurate and modern assessment system, school screenings can detect scoliosis at a significant rate, but awareness of scoliosis risks is needed for residents in China to take up referrals for hospital diagnosis after school screenings.

Explorative analyses on the value of interim PET for prediction of response in pediatric and adolescent non-Hodgkin lymphoma patients

PubMed Central

2013-01-01

Background This study is to evaluate the predictive value of FDG-PET (PET) in pediatric and adolescent patients suffering from non-Hodgkin lymphoma (pNHL) in comparison to information provided by conventional imaging methods (CIM). Methods Imaging was performed at baseline and at interim (after 2 cycles of chemotherapy). The response assessment in PET was carried out visually and semi-quantitatively, the latter one by use of percentage decrease in SUVmax from baseline to interim (ΔSUVmax). The PET-based results were compared to the findings by CIM. Progression-free survival (PFS) was analyzed using Kaplan-Meier curves (KM) and log-rank test. Results The final study included 16 patients (mean follow-up time, 60.2 months (range, 4.0 to 85.7 months)). Relapse occurred in four patients. Visual PET compared to CIM revealed higher sensitivity (3/4 vs 1/4) and NPV (6/7 vs 10/13), and equal PPV (3/9 vs 1/3), but lower specificity (6/12 vs 10/12) and accuracy (9/16 vs 11/16). False-positive findings in PET at interim were predominantly observed in patients presenting bulky disease (5/6), whereas CIM was true-negative in all of these cases. KM analyses revealed no significant differences in 5-year PFS neither for CIM (76.9% vs 66.7%; p = 0.67) nor for visual PET (85.7% vs 66.7%; p = 0.34) nor for ΔSUVmax (88.9% vs 57.1%; p = 0.12). Conclusions The predictive value of iPET in pediatric patients suffering from NHL was limited due to considerably high amount of false-positive findings, especially in patients suffering from bulky disease. However, due to our limited sample size, final conclusions cannot be drawn and, thus, call for further evaluation of PET in pNHL in larger and more homogenous patient series. PMID:24139528

Expectancy Effects on Self-Reported Attention-Deficit/Hyperactivity Disorder Symptoms in Simulated Neurofeedback: A Pilot Study.

PubMed

Lee, Grace J; Suhr, Julie A

2018-03-31

Expectancy is a psychological factor that can impact treatment effectiveness. Research on neurofeedback for attention-deficit/hyperactivity disorder (ADHD) suggests expectancy may contribute to treatment outcomes, though evidence for expectancy as an explanatory factor is sparse. This pilot study investigated the effects of expectancies on self-reported ADHD symptoms in simulated neurofeedback. Forty-six adults who were concerned that they had ADHD expected to receive active neurofeedback, but were randomly assigned to receive a placebo with false feedback indicating attentive (positive false feedback) or inattentive (negative false feedback) states. Effects of the expectancy manipulation were measured on an ADHD self-report scale. Large expectancy effects were found, such that individuals who received positive false feedback reported significant decreases in ADHD symptoms, whereas individuals who received negative false feedback reported significant increases in ADHD symptoms. Findings suggest that expectancy should be considered as an explanatory mechanism for ADHD symptom change in response to neurofeedback.

Testing the effectiveness of automated acoustic sensors for monitoring vocal activity of Marbled Murrelets Brachyramphus marmoratus

USGS Publications Warehouse

Cragg, Jenna L.; Burger, Alan E.; Piatt, John F.

2015-01-01

Cryptic nest sites and secretive breeding behavior make population estimates and monitoring of Marbled Murrelets Brachyramphus marmoratus difficult and expensive. Standard audio-visual and radar protocols have been refined but require intensive field time by trained personnel. We examined the detection range of automated sound recorders (Song Meters; Wildlife Acoustics Inc.) and the reliability of automated recognition models (“recognizers”) for identifying and quantifying Marbled Murrelet vocalizations during the 2011 and 2012 breeding seasons at Kodiak Island, Alaska. The detection range of murrelet calls by Song Meters was estimated to be 60 m. Recognizers detected 20 632 murrelet calls (keer and keheer) from a sample of 268 h of recordings, yielding 5 870 call series, which compared favorably with human scanning of spectrograms (on average detecting 95% of the number of call series identified by a human observer, but not necessarily the same call series). The false-negative rate (percentage of murrelet call series that the recognizers failed to detect) was 32%, mainly involving weak calls and short call series. False-positives (other sounds included by recognizers as murrelet calls) were primarily due to complex songs of other bird species, wind and rain. False-positives were lower in forest nesting habitat (48%) and highest in shrubby vegetation where calls of other birds were common (97%–99%). Acoustic recorders tracked spatial and seasonal trends in vocal activity, with higher call detections in high-quality forested habitat and during late July/early August. Automated acoustic monitoring of Marbled Murrelet calls could provide cost-effective, valuable information for assessing habitat use and temporal and spatial trends in nesting activity; reliability is dependent on careful placement of sensors to minimize false-positives and on prudent application of digital recognizers with visual checking of spectrograms.

False-positive cancer screens and health-related quality of life.

PubMed

McGovern, Patricia M; Gross, Cynthia R; Krueger, Richard A; Engelhard, Deborah A; Cordes, Jill E; Church, Timothy R

2004-01-01

By design, screening tests are imperfect-unresponsive to some cancers (false negatives) while occasionally raising suspicion of cancer where none exists (false positives). This pilot study describes patients' responses to having a false-positive screening test for cancer, and identifies screening effects on health-related quality of life (HRQoL). The pilot findings suggest issues important for incorporation in future evaluations of the impact of screening for prostate, lung, colon, or ovarian (PLCO) cancers. Seven focus groups were conducted to identify the nature and meaning of all phases of PLCO screening. Minnesota participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial who had completed screening, with at least 1 false-positive screen, participated (N = 47). Participants' reactions to abnormal screens and diagnostic work-ups were primarily emotional (eg, anxiety and distress), not physical, and ultimately positive for the majority. Health distress and fear of cancer and death were the major negative aspects of HRQoL identified. These concepts are not typically included in generic HRQoL questionnaires like the SF-36, but are highly relevant to PLCO screening. Clinicians were regarded as underestimating the discomfort of follow-up diagnostic testing. However, relief and assurance appeared to eventually outweigh the negative emotions for most participants. Implications for oncology nurses include the need to consider the emotional consequences of screening in association with screen reliability and validity.

Utility of galactomannan antigen detection in bronchoalveolar lavage fluid in immunocompromised patients.

PubMed

Brownback, Kyle R; Pitts, Lucas R; Simpson, Steven Q

2013-09-01

Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme-linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin-tazobactam and 11 were receiving an alternative beta-lactam antibiotic. BAL GM assay shows excellent sensitivity for diagnosing IPA. There was a significant number of false positive BAL GM assays and several of those patients were receiving beta-lactam antibiotics at the time of bronchoscopy. © 2013 Blackwell Verlag GmbH.

Female False Positive Exercise Stress ECG Testing - Fact Verses Fiction.

PubMed

Fitzgerald, Benjamin T; Scalia, William M; Scalia, Gregory M

2018-03-07

Exercise stress testing is a well validated cardiovascular investigation. Accuracy for treadmill stress electrocardiograph (ECG) testing has been documented at 60%. False positive stress ECGs (exercise ECG changes with non-obstructive disease on anatomical testing) are common, especially in women, limiting the effectiveness of the test. This study investigates the incidence and predictors of false positive stress ECG findings, referenced against stress echocardiography (SE) as a standard. Stress echocardiography was performed using the Bruce treadmill protocol. False positive stress ECG tests were defined as greater than 1mm of ST depression on ECG during exertion, without pain, with a normal SE. Potential causes for false positive tests were recorded before the test. Three thousand consecutive negative stress echocardiograms (1036 females, 34.5%) were analysed (age 59+/-14 years. False positive (F+) stress ECGs were documented in 565/3000 tests (18.8%). F+ stress ECGs were equally prevalent in females (194/1036, 18.7%) and males (371/1964, 18.9%, p=0.85 for the difference). Potential causes (hypertension, left ventricular hypertrophy, known coronary disease, arrhythmia, diabetes mellitus, valvular heart disease) were recorded in 36/194 (18.6%) of the female F+ ECG tests and 249/371 (68.2%) of the male F+ ECG tests (p<0.0001 for the difference). These data suggest that F+ stress ECG tests are frequent and equally common in women and men. However, most F+ stress ECGs in men can be predicted before the test, while most in women cannot. Being female may be a risk factor in itself. These data reinforce the value of stress imaging, particularly in women. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Analyzing false positives of four questions in the Force Concept Inventory

NASA Astrophysics Data System (ADS)

Yasuda, Jun-ichiro; Mae, Naohiro; Hull, Michael M.; Taniguchi, Masa-aki

2018-06-01

In this study, we analyze the systematic error from false positives of the Force Concept Inventory (FCI). We compare the systematic errors of question 6 (Q.6), Q.7, and Q.16, for which clearly erroneous reasoning has been found, with Q.5, for which clearly erroneous reasoning has not been found. We determine whether or not a correct response to a given FCI question is a false positive using subquestions. In addition to the 30 original questions, subquestions were introduced for Q.5, Q.6, Q.7, and Q.16. This modified version of the FCI was administered to 1145 university students in Japan from 2015 to 2017. In this paper, we discuss our finding that the systematic errors of Q.6, Q.7, and Q.16 are much larger than that of Q.5 for students with mid-level FCI scores. Furthermore, we find that, averaged over the data sample, the sum of the false positives from Q.5, Q.6, Q.7, and Q.16 is about 10% of the FCI score of a midlevel student.

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.

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.

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).

Reflections on O2 as a Biosignature in Exoplanetary Atmospheres

PubMed Central

2017-01-01

Abstract Oxygenic photosynthesis is Earth's dominant metabolism, having evolved to harvest the largest expected energy source at the surface of most terrestrial habitable zone planets. Using CO2 and H2O—molecules that are expected to be abundant and widespread on habitable terrestrial planets—oxygenic photosynthesis is plausible as a significant planetary process with a global impact. Photosynthetic O2 has long been considered particularly robust as a sign of life on a habitable exoplanet, due to the lack of known “false positives”—geological or photochemical processes that could also produce large quantities of stable O2. O2 has other advantages as a biosignature, including its high abundance and uniform distribution throughout the atmospheric column and its distinct, strong absorption in the visible and near-infrared. However, recent modeling work has shown that false positives for abundant oxygen or ozone could be produced by abiotic mechanisms, including photochemistry and atmospheric escape. Environmental factors for abiotic O2 have been identified and will improve our ability to choose optimal targets and measurements to guard against false positives. Most of these false-positive mechanisms are dependent on properties of the host star and are often strongest for planets orbiting M dwarfs. In particular, selecting planets found within the conservative habitable zone and those orbiting host stars more massive than 0.4 M⊙ (M3V and earlier) may help avoid planets with abundant abiotic O2 generated by water loss. Searching for O4 or CO in the planetary spectrum, or the lack of H2O or CH4, could help discriminate between abiotic and biological sources of O2 or O3. In advance of the next generation of telescopes, thorough evaluation of potential biosignatures—including likely environmental context and factors that could produce false positives—ultimately works to increase our confidence in life detection. Key Words: Biosignatures—Exoplanets—Oxygen—Photosynthesis—Planetary spectra. Astrobiology 17, 1022–1052. PMID:28443722

An evaluation of the Monosticon rapid slide test diagnosis of infectious mononucleosis

PubMed Central

Scott, G. L.; Priest, C. J.

1972-01-01

A new rapid slide test for the detection of infectious mononucleosis heterophile antibody has been compared with the Paul-Bunnell absorption test. Out of 200 sera, 46 were seropositive for infectious mononucleosis by the Paul-Bunnell test and 43 of these were detected by the Monosticon test; the three Monosticon-negative sera were of low titre. There was no problem with false positive reactions due to heterophile antibody not specific for infectious mononucleosis. PMID:4678188

Diagnostic classification of macular ganglion cell and retinal nerve fiber layer analysis: differentiation of false-positives from glaucoma.

PubMed

Kim, Ko Eun; Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2015-03-01

To investigate the rate and associated factors of false-positive diagnostic classification of ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) maps, and characteristic false-positive patterns on optical coherence tomography (OCT) deviation maps. Prospective, cross-sectional study. A total of 104 healthy eyes of 104 normal participants. All participants underwent peripapillary and macular spectral-domain (Cirrus-HD, Carl Zeiss Meditec Inc, Dublin, CA) OCT scans. False-positive diagnostic classification was defined as yellow or red color-coded areas for GCA and RNFL maps. Univariate and multivariate logistic regression analyses were used to determine associated factors. Eyes with abnormal OCT deviation maps were categorized on the basis of the shape and location of abnormal color-coded area. Differences in clinical characteristics among the subgroups were compared. (1) The rate and associated factors of false-positive OCT maps; (2) patterns of false-positive, color-coded areas on the GCA deviation map and associated clinical characteristics. Of the 104 healthy eyes, 42 (40.4%) and 32 (30.8%) showed abnormal diagnostic classifications on any of the GCA and RNFL maps, respectively. Multivariate analysis revealed that false-positive GCA diagnostic classification was associated with longer axial length and larger fovea-disc angle, whereas longer axial length and smaller disc area were associated with abnormal RNFL maps. Eyes with abnormal GCA deviation map were categorized as group A (donut-shaped round area around the inner annulus), group B (island-like isolated area), and group C (diffuse, circular area with an irregular inner margin in either). The axial length showed a significant increasing trend from group A to C (P=0.001), and likewise, the refractive error was more myopic in group C than in groups A (P=0.015) and B (P=0.014). Group C had thinner average ganglion cell-inner plexiform layer thickness compared with other groups (group A=B>C, P=0.004). Abnormal OCT diagnostic classification should be interpreted with caution, especially in eyes with long axial lengths, large fovea-disc angles, and small optic discs. Our findings suggest that the characteristic patterns of OCT deviation map can provide useful clues to distinguish glaucomatous changes from false-positive findings. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Applying a 2D based CAD scheme for detecting micro-calcification clusters using digital breast tomosynthesis images: an assessment

NASA Astrophysics Data System (ADS)

Park, Sang Cheol; Zheng, Bin; Wang, Xiao-Hui; Gur, David

2008-03-01

Digital breast tomosynthesis (DBT) has emerged as a promising imaging modality for screening mammography. However, visually detecting micro-calcification clusters depicted on DBT images is a difficult task. Computer-aided detection (CAD) schemes for detecting micro-calcification clusters depicted on mammograms can achieve high performance and the use of CAD results can assist radiologists in detecting subtle micro-calcification clusters. In this study, we compared the performance of an available 2D based CAD scheme with one that includes a new grouping and scoring method when applied to both projection and reconstructed DBT images. We selected a dataset involving 96 DBT examinations acquired on 45 women. Each DBT image set included 11 low dose projection images and a varying number of reconstructed image slices ranging from 18 to 87. In this dataset 20 true-positive micro-calcification clusters were visually detected on the projection images and 40 were visually detected on the reconstructed images, respectively. We first applied the CAD scheme that was previously developed in our laboratory to the DBT dataset. We then tested a new grouping method that defines an independent cluster by grouping the same cluster detected on different projection or reconstructed images. We then compared four scoring methods to assess the CAD performance. The maximum sensitivity level observed for the different grouping and scoring methods were 70% and 88% for the projection and reconstructed images with a maximum false-positive rate of 4.0 and 15.9 per examination, respectively. This preliminary study demonstrates that (1) among the maximum, the minimum or the average CAD generated scores, using the maximum score of the grouped cluster regions achieved the highest performance level, (2) the histogram based scoring method is reasonably effective in reducing false-positive detections on the projection images but the overall CAD sensitivity is lower due to lower signal-to-noise ratio, and (3) CAD achieved higher sensitivity and higher false-positive rate (per examination) on the reconstructed images. We concluded that without changing the detection threshold or performing pre-filtering to possibly increase detection sensitivity, current CAD schemes developed and optimized for 2D mammograms perform relatively poorly and need to be re-optimized using DBT datasets and new grouping and scoring methods need to be incorporated into the schemes if these are to be used on the DBT examinations.

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

PubMed

Torres-Mejía, Gabriela; Smith, Robert A; Carranza-Flores, María de la Luz; Bogart, Andy; Martínez-Matsushita, Louis; Miglioretti, Diana L; Kerlikowske, Karla; Ortega-Olvera, Carolina; Montemayor-Varela, Ernesto; Angeles-Llerenas, Angélica; Bautista-Arredondo, Sergio; Sánchez-González, Gilberto; Martínez-Montañez, Olga G; Uscanga-Sánchez, Santos R; Lazcano-Ponce, Eduardo; Hernández-Ávila, Mauricio

2015-05-16

An alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries. We evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed. Radiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms. Given the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography.

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.

Tile-Based Fisher-Ratio Software for Improved Feature Selection Analysis of Comprehensive Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry Data

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

Marney, Luke C.; Siegler, William C.; Parsons, Brendon A.

Two-dimensional (2D) gas chromatography coupled with time-of-flight mass spectrometry (GC × GC – TOFMS) is a highly capable instrumental platform that produces complex and information-rich multi-dimensional chemical data. The complex data can be overwhelming, especially when many samples (of various sample classes) are analyzed with multiple injections for each sample. Thus, the data must be analyzed in such a way to extract the most meaningful information. The pixel-based and peak table-based algorithmic use of Fisher ratios has been used successfully in the past to reduce the multi-dimensional data down to those chemical compounds that are changing between classes relative tomore » those that are not (i.e., chemical feature selection). We report on the initial development of a computationally fast novel tile-based Fisher-ratio software that addresses challenges due to 2D retention time misalignment without explicitly aligning the data, which is a problem for both pixel-based and peak table- based methods. Concurrently, the tile-based Fisher-ratio software maximizes the sensitivity contrast of true positives against a background of potential false positives and noise. To study this software, eight compounds, plus one internal standard, were spiked into diesel at various concentrations. The tile-based F-ratio software was able to discover all spiked analytes, within the complex diesel sample matrix with thousands of potential false positives, in each possible concentration comparison, even at the lowest absolute spiked analyte concentration ratio of 1.06.« less

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.

Modeling malaria and typhoid fever co-infection dynamics.

PubMed

Mutua, Jones M; Wang, Feng-Bin; Vaidya, Naveen K

2015-06-01

Malaria and typhoid are among the most endemic diseases, and thus, of major public health concerns in tropical developing countries. In addition to true co-infection of malaria and typhoid, false diagnoses due to similar signs and symptoms and false positive results in testing methods, leading to improper controls, are the major challenges on managing these diseases. In this study, we develop novel mathematical models describing the co-infection dynamics of malaria and typhoid. Through mathematical analyses of our models, we identify distinct features of typhoid and malaria infection dynamics as well as relationships associated to their co-infection. The global dynamics of typhoid can be determined by a single threshold (the typhoid basic reproduction number, R0(T)) while two thresholds (the malaria basic reproduction number, R0(M), and the extinction index, R0(MM)) are needed to determine the global dynamics of malaria. We demonstrate that by using efficient simultaneous prevention programs, the co-infection basic reproduction number, R0, can be brought down to below one, thereby eradicating the diseases. Using our model, we present illustrative numerical results with a case study in the Eastern Province of Kenya to quantify the possible false diagnosis resulting from this co-infection. In Kenya, despite having higher prevalence of typhoid, malaria is more problematic in terms of new infections and disease deaths. We find that false diagnosis-with higher possible cases for typhoid than malaria-cause significant devastating impacts on Kenyan societies. Our results demonstrate that both diseases need to be simultaneously managed for successful control of co-epidemics. Copyright © 2015 Elsevier Inc. All rights reserved.

The (in)famous GWAS P-value threshold revisited and updated for low-frequency variants.

PubMed

Fadista, João; Manning, Alisa K; Florez, Jose C; Groop, Leif

2016-08-01

Genome-wide association studies (GWAS) have long relied on proposed statistical significance thresholds to be able to differentiate true positives from false positives. Although the genome-wide significance P-value threshold of 5 × 10(-8) has become a standard for common-variant GWAS, it has not been updated to cope with the lower allele frequency spectrum used in many recent array-based GWAS studies and sequencing studies. Using a whole-genome- and -exome-sequencing data set of 2875 individuals of European ancestry from the Genetics of Type 2 Diabetes (GoT2D) project and a whole-exome-sequencing data set of 13 000 individuals from five ancestries from the GoT2D and T2D-GENES (Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples) projects, we describe guidelines for genome- and exome-wide association P-value thresholds needed to correct for multiple testing, explaining the impact of linkage disequilibrium thresholds for distinguishing independent variants, minor allele frequency and ancestry characteristics. We emphasize the advantage of studying recent genetic isolate populations when performing rare and low-frequency genetic association analyses, as the multiple testing burden is diminished due to higher genetic homogeneity.

Studies on the detection and identification of the explosives in the terahertz range

NASA Astrophysics Data System (ADS)

Zhou, Qing-li; Zhang, Cun-lin; Li, Wei-Wei; Mu, Kai-jun; Feng, Rui-shu

2008-03-01

The sensing of the explosives and the related compounds is very important for homeland security and defense. Based on the non-invasive terahertz (THz) technology, we have studied some pure and mixed explosives by using the THz time-domain spectroscopy and have obtained the absorption spectra of those samples. The obtained results show that those explosives can be identified due to their different characterized finger-prints in the terahertz frequency region of 0.2-2.5 THz. Furthermore, the spectra analyses indicate that the shape and peak positions of the spectra for these mixed explosive are mainly determined by their explosive components. In order to identify those different kinds of explosives, we have applied the artificial neural network, which is a mathematical device for modeling complex and non-linear functionalities, to our present work. After the repetitive modeling and adequate training with the known input-output data, the identification of the explosive is realized roughly on a multi-hidden-layers model. It is shown that the neural network analyses of the THz spectra would positively identify the explosives and reduce false alarm rates.

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.

A search for life on earth at 100 meter resolution

NASA Technical Reports Server (NTRS)

Sagan, C.; Wallace, D.

1970-01-01

A study of several thousand photos indicated approximately 1% of Gemini and Apollo photographs of the earth at 100 m resolution revealed signs of life; rectangular arrays due to human agricultural and urban territoriality, roads, canals, jet contrails, and industrial pollution. Potential false positives such as dunes, sand bars, and jet stream clouds abound. A curve was derived for the detectivity of contemporary life on earth, in a plot of ground resolution versus global coverage. A comparable biology on Mars would not have been detected by all observations of Mars through Mariner 7. Forthcoming Mars orbiter and lander imaging experiments hold significant promise of detecting life on Mars of contemporary terrestrial extent and advancement, should such life exist.

Genome-wide signals of positive selection in human evolution

PubMed Central

Enard, David; Messer, Philipp W.; Petrov, Dmitri A.

2014-01-01

The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci, and the genome-wide patterns of polymorphism show signatures consistent with frequent positive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1000 Genomes Project and detect signatures of positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to argue that the observed signatures require a high rate of strongly adaptive substitutions near amino acid changes. We further demonstrate that the observed signatures of positive selection correlate better with the presence of regulatory sequences, as predicted by the ENCODE Project Consortium, than with the positions of amino acid substitutions. Our results suggest that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson that adaptive divergence is primarily driven by regulatory changes. PMID:24619126

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.

The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

PubMed

la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

2014-01-01

Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09μmol/L, adenosine <1.61μmol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result. In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of the Third Wave Invader Human Papillomavirus (HPV) Assay and the Digene HPV Hybrid Capture 2 Assay for Detection of High-Risk HPV DNA▿

PubMed Central

Ginocchio, C. C.; Barth, D.; Zhang, F.

2008-01-01

This study compared the clinical performance of the Digene Hybrid Capture 2 (HC2) assay to that of a prototype Third Wave Invader human papillomavirus (HPV) (IHPV) analyte-specific reagent-based assay for the detection of oncogenic or “high-risk” (HR) HPV DNA using liquid-based cytology specimens. In total, 821 ThinPrep vials were tested using both assays. In accordance with the type-specific probes contained within each test, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the IHPV assay were 95.9%, 97.6%, 97.5%, and 96.1%, respectively, and those for the HC2 assay were 98.1%, 86.2%, 87.1%, and 97.9%. Overall, the sensitivity and NPV were comparable between the assays, but the IHPV assay demonstrated a better specificity and PPV, since the IHPV assay had fewer false-positive HR HPV results. The incorporation of an internal control to evaluate the cellularity of the test material is an important feature of the IHPV assay and should reduce the risk of false-negative results due to insufficient sample collection rather than the lack of HR HPV DNA. An additional benefit of the IHPV assay was the smaller sample volume required (1 ml versus 4 ml for the HC2 assay). PMID:18367578

Cluster-level statistical inference in fMRI datasets: The unexpected behavior of random fields in high dimensions.

PubMed

Bansal, Ravi; Peterson, Bradley S

2018-06-01

Identifying regional effects of interest in MRI datasets usually entails testing a priori hypotheses across many thousands of brain voxels, requiring control for false positive findings in these multiple hypotheses testing. Recent studies have suggested that parametric statistical methods may have incorrectly modeled functional MRI data, thereby leading to higher false positive rates than their nominal rates. Nonparametric methods for statistical inference when conducting multiple statistical tests, in contrast, are thought to produce false positives at the nominal rate, which has thus led to the suggestion that previously reported studies should reanalyze their fMRI data using nonparametric tools. To understand better why parametric methods may yield excessive false positives, we assessed their performance when applied both to simulated datasets of 1D, 2D, and 3D Gaussian Random Fields (GRFs) and to 710 real-world, resting-state fMRI datasets. We showed that both the simulated 2D and 3D GRFs and the real-world data contain a small percentage (<6%) of very large clusters (on average 60 times larger than the average cluster size), which were not present in 1D GRFs. These unexpectedly large clusters were deemed statistically significant using parametric methods, leading to empirical familywise error rates (FWERs) as high as 65%: the high empirical FWERs were not a consequence of parametric methods failing to model spatial smoothness accurately, but rather of these very large clusters that are inherently present in smooth, high-dimensional random fields. In fact, when discounting these very large clusters, the empirical FWER for parametric methods was 3.24%. Furthermore, even an empirical FWER of 65% would yield on average less than one of those very large clusters in each brain-wide analysis. Nonparametric methods, in contrast, estimated distributions from those large clusters, and therefore, by construct rejected the large clusters as false positives at the nominal FWERs. Those rejected clusters were outlying values in the distribution of cluster size but cannot be distinguished from true positive findings without further analyses, including assessing whether fMRI signal in those regions correlates with other clinical, behavioral, or cognitive measures. Rejecting the large clusters, however, significantly reduced the statistical power of nonparametric methods in detecting true findings compared with parametric methods, which would have detected most true findings that are essential for making valid biological inferences in MRI data. Parametric analyses, in contrast, detected most true findings while generating relatively few false positives: on average, less than one of those very large clusters would be deemed a true finding in each brain-wide analysis. We therefore recommend the continued use of parametric methods that model nonstationary smoothness for cluster-level, familywise control of false positives, particularly when using a Cluster Defining Threshold of 2.5 or higher, and subsequently assessing rigorously the biological plausibility of the findings, even for large clusters. Finally, because nonparametric methods yielded a large reduction in statistical power to detect true positive findings, we conclude that the modest reduction in false positive findings that nonparametric analyses afford does not warrant a re-analysis of previously published fMRI studies using nonparametric techniques. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessment of rates of recanting and hair testing as a biological measure of drug use in a general population sample of young people

PubMed Central

Sullivan, John; Ring, Susan M.; Macleod, John; Hickman, Matthew

2016-01-01

Abstract Aims We investigate the extent of and factors associated with denial of previously reported cannabis and other illicit drug use, and assess the potential of hair testing for measuring substance use in general population samples. Design Birth cohort study. Setting United Kingdom, 1991–present. Participants A total of 3643 participants who provided hair and self‐report measures of cannabis and other illicit drug use in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18 years. Measurements Denial of ever use of cannabis and other illicit drugs at age 18 following previously reported use. Positive hair drug tests for cannabis and other illicit drugs, and expected numbers of false positives and false negatives based on expected sensitivity and specificity. Findings Cannabis and other illicit drug use was reported by 1223 and 393 individuals, respectively, before age 18 years. Of these 176 (14.4%) and 99 (25.2%), respectively, denied use at age 18. Denial of cannabis use decreased with the reporting of other substances and antisocial behaviour. Cannabis and other illicit drug use at age 18 was reported by 547 (22.5%) and 203 (8.4%) individuals, respectively. Of these, 111 (20.3%) and 13 (6.4%) were hair‐positive for cannabis and other illicit drugs, respectively. Based on hair testing for cannabis use we expect 0 [95% confidence interval (CI) = 0–169] false positives and 394 (95% CI = 323–449) false negatives compared to observed 362 potential false positives and 436 potential false negatives based on self‐report. In hair‐positive individuals, reporting the use of other substances and antisocial behaviour decreased the odds of a negative self‐report. Conclusions Hair analysis provides an unreliable marker of substance use in general population samples. People who report more frequent substance use before age 18 are less likely to later deny previous substance use at age 18 than people who report occasional use. PMID:27743424

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.

MRI criteria for MS in patients with clinically isolated syndromes.

PubMed

Montalban, X; Tintoré, M; Swanton, J; Barkhof, F; Fazekas, F; Filippi, M; Frederiksen, J; Kappos, L; Palace, J; Polman, C; Rovaris, M; de Stefano, N; Thompson, A; Yousry, T; Rovira, A; Miller, D H

2010-02-02

In recent years, criteria for the diagnosis of multiple sclerosis (MS) have changed, mainly due to the incorporation of new MRI criteria. While the new criteria are a logical step forward, they are complex and-not surprisingly-a good working knowledge of them is not always evident among neurologists and neuroradiologists. In some circumstances, several MRI examinations are needed to achieve an accurate and prompt diagnosis. This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome. Within the European multicenter collaborative research network that studies MRI in MS (MAGNIMS), a workshop was held in London in November 2007 to review information that may simplify the existing MS diagnostic criteria, while maintaining a high specificity that is essential to minimize false positive diagnoses. New data that are now published were reviewed and discussed and together with a new proposal are integrated in this position paper.

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

Tinel's sign or percussion test? Developing a better method of evoking a Tinel's sign.

PubMed

Monsivais, J J; Sun, Y

1997-01-01

Clinicians elicit a Tinel's sign by tapping over a nerve site with their fingertips. No standard force has been established, and overzealous tapping can produce a false-positive "Tinel's sign" that is actually a positive percussion test. The purpose of our study was to determine a threshold force that produces a positive percussion test in each of seven nerve locations in the upper extremities of subjects with no known nerve injuries and in subjects with nerve injuries. These data suggest limits for the amount of force necessary to elicit a Tinel's sign. If these limits are adhered to, the incidence of false-positive responses may be kept low.

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.

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.

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.

Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays

PubMed Central

Sozhamannan, Shanmuga; Holland, Mitchell Y.; Hall, Adrienne T.; Negrón, Daniel A.; Ivancich, Mychal; Koehler, Jeffrey W.; Minogue, Timothy D.; Campbell, Catherine E.; Berger, Walter J.; Christopher, George W.; Goodwin, Bruce G.; Smith, Michael A.

2015-01-01

Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes. PMID:26090727

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.

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.

Laxative-free CT colonography.

PubMed

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

2012-08-01

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. 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. 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). Switching from Picolax to Gastrografin as a CTC preparation technique produced less diarrhoea, but did not reduce the number of false-positives.

Selecting At-Risk First-Grade Readers for Early Intervention: Eliminating False Positives and Exploring the Promise of a Two-Stage Gated Screening Process

ERIC Educational Resources Information Center

Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Bouton, Bobette; Gilbert, Jennifer K.; Barquero, Laura A.; Cho, Eunsoo; Crouch, Robert C.

2010-01-01

The purposes of this study were (a) to identify measures that when added to a base 1st-grade screening battery help eliminate false positives and (b) to investigate gains in efficiency associated with a 2-stage gated screening procedure. We tested 355 children in the fall of 1st grade and assessed for reading difficulty at the end of 2nd grade.…

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.

Deep multi-scale location-aware 3D convolutional neural networks for automated detection of lacunes of presumed vascular origin.

PubMed

Ghafoorian, Mohsen; Karssemeijer, Nico; Heskes, Tom; Bergkamp, Mayra; Wissink, Joost; Obels, Jiri; Keizer, Karlijn; de Leeuw, Frank-Erik; Ginneken, Bram van; Marchiori, Elena; Platel, Bram

2017-01-01

Lacunes of presumed vascular origin (lacunes) are associated with an increased risk of stroke, gait impairment, and dementia and are a primary imaging feature of the small vessel disease. Quantification of lacunes may be of great importance to elucidate the mechanisms behind neuro-degenerative disorders and is recommended as part of study standards for small vessel disease research. However, due to the different appearance of lacunes in various brain regions and the existence of other similar-looking structures, such as perivascular spaces, manual annotation is a difficult, elaborative and subjective task, which can potentially be greatly improved by reliable and consistent computer-aided detection (CAD) routines. In this paper, we propose an automated two-stage method using deep convolutional neural networks (CNN). We show that this method has good performance and can considerably benefit readers. We first use a fully convolutional neural network to detect initial candidates. In the second step, we employ a 3D CNN as a false positive reduction tool. As the location information is important to the analysis of candidate structures, we further equip the network with contextual information using multi-scale analysis and integration of explicit location features. We trained, validated and tested our networks on a large dataset of 1075 cases obtained from two different studies. Subsequently, we conducted an observer study with four trained observers and compared our method with them using a free-response operating characteristic analysis. Shown on a test set of 111 cases, the resulting CAD system exhibits performance similar to the trained human observers and achieves a sensitivity of 0.974 with 0.13 false positives per slice. A feasibility study also showed that a trained human observer would considerably benefit once aided by the CAD system.

Pepper, chili (Capsicum annuum).

PubMed

Min, Jung; Shin, Sun Hee; Jeon, En Mi; Park, Jung Mi; Hyun, Ji Young; Harn, Chee Hark

2015-01-01

Pepper is a recalcitrant plant for Agrobacterium-mediated genetic transformation. Several obstacles to genetic transformation remain such as extremely low transformation rates; the choice of correct genotype is critical; and there is a high frequency of false positives due to direct shoot formation. Here, we report a useful protocol with a suitable selection method. The most important aspect of the pepper transformation protocol is selecting shoots growing from the callus, which is referred to as callus-mediated shoot formation. This protocol is a reproducible and reliable system for pepper transformation.

Children's False Memory and True Disclosure in the Face of Repeated Questions

ERIC Educational Resources Information Center

Schaaf, Jennifer M.; Alexander, Kristen Weede; Goodman, Gail S.

2008-01-01

The current study was designed to investigate children's memory and suggestibility for events differing in valence (positive or negative) and veracity (true or false). A total of 82 3- and 5-year-olds were asked repeated questions about true and false events, either in a grouped order (i.e., all questions about a certain event asked consecutively)…

Value of a Single-Tube Widal Test in Diagnosis of Typhoid Fever in Vietnam

PubMed Central

Parry, Christopher M.; Hoa, Nguyen Thi Tuyet; Diep, To Song; Wain, John; Chinh, Nguyen Tran; Vinh, Ha; Hien, Tran Tinh; White, Nicholas J.; Farrar, Jeremy J.

1999-01-01

The diagnostic value of an acute-phase single-tube Widal test for suspected typhoid fever was evaluated with 2,000 Vietnamese patients admitted to an infectious disease referral hospital between 1993 and 1998. Test patients had suspected typhoid fever and a blood culture positive for Salmonella typhi (n= 1,400) or Salmonella paratyphi A (n = 45). Control patients had a febrile illness for which another cause was confirmed (malaria [n = 103], dengue [n = 76], or bacteremia due to another microorganism [n = 156] or tetanus (n = 265). An O-agglutinin titer of ≥100 was found in 18% of the febrile controls and 7% of the tetanus patients. Corresponding values for H agglutinins were 8 and 1%, respectively. The O-agglutinin titer was ≥100 in 83% of the blood culture-positive typhoid fever cases, and the H-agglutinin titer was ≥100 in 67%. The disease prevalence in investigated patients in this hospital was 30.8% (95% confidence interval, 26.8 to 35.1%); at this prevalence, an elevated level of H agglutinins gave better positive predictive values for typhoid fever than did O agglutinins. With a cutoff titer of ≥200 for O agglutinin or ≥100 for H agglutinin, the Widal test would diagnose correctly 74% of the blood culture-positive cases of typhoid fever. However, 14% of the positive results would be false-positive, and 10% of the negative results would be false-negative. The Widal test can be helpful in the laboratory diagnosis of typhoid fever in Vietnam if interpreted with care. PMID:10449469

Motivated reconstruction: The effect of brand commitment on false memories.

PubMed

Montgomery, Nicole Votolato; Rajagopal, Priyali

2018-06-01

Across 5 studies, we examine the effect of prior brand commitment on the creation of false memories about product experience after reading online product reviews. We find that brand commitment and the valence of reviews to which consumers are exposed, interact to affect the incidence of false memories. Thus, highly committed consumers are more susceptible to the creation of false experience memories on exposure to positive versus negative reviews, whereas low commitment consumers exhibit similar levels of false memories in response to both positive and negative reviews. Further, these differences across brand commitment are attenuated when respondents are primed with an accuracy motivation, suggesting that the biasing effects of commitment are likely because of the motivation to defend the committed brand. Finally, we find that differences in false memories subsequently lead to differences in intentions to spread word-of-mouth (e.g., recommend the product to friends), suggesting that the consequences of false product experience memories can be significant for marketers and consumers. Our findings contribute to the literatures in false memory and marketing by documenting a motivated bias in false memories because of brand commitment. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

Reducing false-positive detections by combining two stage-1 computer-aided mass detection algorithms

NASA Astrophysics Data System (ADS)

Bedard, Noah D.; Sampat, Mehul P.; Stokes, Patrick A.; Markey, Mia K.

2006-03-01

In this paper we present a strategy for reducing the number of false-positives in computer-aided mass detection. Our approach is to only mark "consensus" detections from among the suspicious sites identified by different "stage-1" detection algorithms. By "stage-1" we mean that each of the Computer-aided Detection (CADe) algorithms is designed to operate with high sensitivity, allowing for a large number of false positives. In this study, two mass detection methods were used: (1) Heath and Bowyer's algorithm based on the average fraction under the minimum filter (AFUM) and (2) a low-threshold bi-lateral subtraction algorithm. The two methods were applied separately to a set of images from the Digital Database for Screening Mammography (DDSM) to obtain paired sets of mass candidates. The consensus mass candidates for each image were identified by a logical "and" operation of the two CADe algorithms so as to eliminate regions of suspicion that were not independently identified by both techniques. It was shown that by combining the evidence from the AFUM filter method with that obtained from bi-lateral subtraction, the same sensitivity could be reached with fewer false-positives per image relative to using the AFUM filter alone.

Value of the BI-RADS classification in MR-Mammography for diagnosis of benign and malignant breast tumors.

PubMed

Sohns, Christian; Scherrer, Martin; Staab, Wieland; Obenauer, Silvia

2011-12-01

To assess whether the BI-RADS classification in MR-Mammography (MRM) can distinguish between benign and malignant lesions. 207 MRM investigations were categorised according to BI-RADS. The results were compared to histology. All MRM studies were interpreted by two examiners. Statistical significance for the accuracy of MRM was calculated. A significant correlation between specific histology and MRM-tumour-morphology could not be reported. Mass (68%) was significant for malignancy. Significance raised with irregular shape (88%), spiculated margin (97%), rim enhancement (98%), fast initial increase (90%), post initial plateau (65%), and intermediate T2 result (82%). Highly significant for benignity was an oval mass (79%), slow initial increase (94%) and a hyperintense T2 result (77%), also an inconspicuous MRM result (77%) was often seen in benign histology. Symmetry (90%) and further post initial increase (90%) were significant, whereas a regional distribution (74%) was lowly significant for benignity. On basis of the BI-RADS classification an objective comparability and statement of diagnosis could be made highly significant. Due to the fact of false-negative and false-positive MRM-results, histology is necessary.

IgM rheumatoid factor removal and performance of the FTA-ABS (IgM) test in congenital syphilis.

PubMed

Meyer, M P; Roditi, D; Louw, S

1992-08-01

To determine the performance of the FTA-ABS (IgM) test in congenital syphilis after eliminating interference by IgM rheumatoid factor (RF) and preventing competitive inhibition by IgG. The FTA-ABS (IgM) test was carried out before and after RF removal (achieved by immunoprecipitation of the IgG) in infants with congenital syphilis and controls. Newborns delivered in the Peninsula Maternal and Neonatal Services in Cape Town and infants presenting at Red Cross War Memorial Children's Hospital. Infants with congenital syphilis aged 0-4 months were divided into those with clinical signs at presentation and those who were asymptomatic at delivery. In addition, patients without congenital syphilis but with similar clinical signs at presentation were investigated as were control infants. The diagnosis of congenital syphilis was based on the criteria suggested by Kaufman et al (1977). Amongst symptomatic infants with congenital syphilis the FTA-ABS (IgM) test was positive in 34 (92%) of 37 cases prior to abolishing the RF effect and in 29 (78.4%) of 37 cases afterwards (p = 0.19). In 12 cases of congenital syphilis who were asymptomatic at birth, 10 had positive FTA-ABS (IgM) tests before RF removal and only three had positive tests afterwards (p = 0.006). False positive tests were not found amongst 15 symptomatic infants whose clinical features mimicked those of the infants with congenital syphilis. Among 51 healthy infants the test had a false-positive rate of 2% in newborns and 13% in older infants. The false positive reactions were eradicated by IgG precipitation. Following IgG and RF removal there was an improvement in the specificity of the FTA-ABS (IgM) test but this was at the expense of a loss of sensitivity, particularly in asymptomatic newborns. For newborns, if the FTA-ABS (IgM) test was positive, the patient was likely to require treatment for congenital syphilis, regardless of whether the result was due to the presence of RF or specific IgM.

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...

Anti-HCV immunoblot indeterminate results in blood donors: non-specific reactivity or past exposure to HCV?

PubMed

Kiely, P; Styles, C

2017-08-01

The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results. © 2017 International Society of Blood Transfusion.

Accuracy of vaginal symptom self-diagnosis algorithms for deployed military women.

PubMed

Ryan-Wenger, Nancy A; Neal, Jeremy L; Jones, Ashley S; Lowe, Nancy K

2010-01-01

Deployed military women have an increased risk for development of vaginitis due to extreme temperatures, primitive sanitation, hygiene and laundry facilities, and unavailable or unacceptable healthcare resources. The Women in the Military Self-Diagnosis (WMSD) and treatment kit was developed as a field-expedient solution to this problem. The primary study aims were to evaluate the accuracy of women's self-diagnosis of vaginal symptoms and eight diagnostic algorithms and to predict potential self-medication omission and commission error rates. Participants included 546 active duty, deployable Army (43.3%) and Navy (53.6%) women with vaginal symptoms who sought healthcare at troop medical clinics on base.In the clinic lavatory, women conducted a self-diagnosis using a sterile cotton swab to obtain vaginal fluid, a FemExam card to measure positive or negative pH and amines, and the investigator-developed WMSD Decision-Making Guide. Potential self-diagnoses were "bacterial infection" (bacterial vaginosis [BV] and/or trichomonas vaginitis [TV]), "yeast infection" (candida vaginitis [CV]), "no infection/normal," or "unclear." The Affirm VPIII laboratory reference standard was used to detect clinically significant amounts of vaginal fluid DNA for organisms associated with BV, TV, and CV. Women's self-diagnostic accuracy was 56% for BV/TV and 69.2% for CV. False-positives would have led to a self-medication commission error rate of 20.3% for BV/TV and 8% for CV. Potential self-medication omission error rates due to false-negatives were 23.7% for BV/TV and 24.8% for CV. The positive predictive value of diagnostic algorithms ranged from 0% to 78.1% for BV/TV and 41.7% for CV. The algorithms were based on clinical diagnostic standards. The nonspecific nature of vaginal symptoms, mixed infections, and a faulty device intended to measure vaginal pH and amines explain why none of the algorithms reached the goal of 95% accuracy. The next prototype of the WMSD kit will not include nonspecific vaginal signs and symptoms in favor of recently available point-of-care devices that identify antigens or enzymes of the causative BV, TV, and CV organisms.

A crisis of visibility: The psychological consequences of false-positive screening mammograms, an interview study.

PubMed

Bond, Mary; Garside, Ruth; Hyde, Christopher

2015-11-01

To understand the meaning of having a false-positive screening mammogram. Qualitative interview study. Twenty-one women, who had experienced false-positive screening mammograms, took part in semi-structured interviews that were analysed with Interpretive Phenomenological Analysis. This research took place in the United Kingdom. The analysis revealed a wide range of response to having a false-positive mammogram, from nonchalance to extreme fear. These reactions come from the potential for the belief that one is healthy to be challenged by being recalled, as the worst is frequently assumed. For most, the image of the lesion on the X-ray brought the reality of this challenge into sharp focus, as they might soon discover they had breast cancer. Waiting, whether for the appointment, at the clinic or for biopsy results was considered the worst aspect of being recalled. Generally, the uncertainty was quickly resolved with the pronouncement of the 'all-clear', which brought considerable relief and the restoration of belief in the healthy self. However, for some, lack of information, contradictory information, or poor interpersonal communication meant that uncertainty about their health status lingered at least until their next normal screening mammogram. Mammography screening related anxiety lasted for up to 12 years. Breast cancer screening produces a 'crisis of visibility'. Accepting the screening invitation is taking a risk that you may experience unnecessary stress, uncertainty, fear, anxiety, and physical pain. Not accepting the invitation is taking a risk that malignant disease will remain invisible. Statement of contribution What is already known on this subject? More than 50,000 women a year in England have a false-positive mammogram (FPM). Having an FPM can cause anxiety compared with a normal mammogram. The anxiety can last up to 35 months. What does this study add? Refocuses attention from the average response found in quantitative studies to the wide range of individual response. Gives insight into the nature of the anxiety of having FPMs. Highlights the role of uncertainty in provoking distress from an FPM. © 2015 The British Psychological Society.

Intellectual factors in false memories of patients with schizophrenia.

PubMed

Zhu, Bi; Chen, Chuansheng; Loftus, Elizabeth F; Dong, Qi; Lin, Chongde; Li, Jun

2018-07-01

The current study explored the intellectual factors in false memories of 139 patients with schizophrenia, using a recognition task and an IQ test. The full-scale IQ score of the participants ranged from 57 to 144 (M = 100, SD = 14). The full IQ score had a negative correlation with false recognition in patients with schizophrenia, and positive correlations with high-confidence true recognition and discrimination rates. Further analyses with the subtests' scores revealed that false recognition was negatively correlated with scores of performance IQ (and one of its subtests: picture arrangement), whereas true recognition was positively correlated with scores of verbal IQ (and two of its subtests: information and digit span). High-IQ patients had less false recognition (overall or high-confidence false recognition), more high-confidence true recognition, and higher discrimination abilities than those with low IQ. These findings contribute to a better understanding of the cognitive mechanism in false memory of patients with schizophrenia, and are of practical relevance to the evaluation of memory reliability in patients with different intellectual levels. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

THE POSSIBLE MOON OF KEPLER-90g IS A FALSE POSITIVE

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

Kipping, D. M.; Torres, G.; Buchhave, L. A.

2015-01-20

The discovery of an exomoon would provide deep insights into planet formation and the habitability of planetary systems, with transiting examples being particularly sought after. Of the hundreds of Kepler planets now discovered, the seven-planet system Kepler-90 is unusual for exhibiting an unidentified transit-like signal in close proximity to one of the transits of the long-period gas-giant Kepler-90g, as noted by Cabrera et al. As part of the ''Hunt for Exomoons with Kepler'' project, we investigate this possible exomoon signal and find it passes all conventional photometric, dynamical, and centroid diagnostic tests. However, pixel-level light curves indicate that the moon-like signalmore » occurs on nearly all of the target's pixels, which we confirm using a novel way of examining pixel-level data which we dub the ''transit centroid''. This test reveals that the possible exomoon to Kepler-90g is likely a false positive, perhaps due to a cosmic ray induced sudden pixel sensitivity dropout. This work highlights the extreme care required for seeking non-periodic low-amplitude transit signals, such as exomoons.« less

Cerebral microbleed detection in traumatic brain injury patients using 3D convolutional neural networks

NASA Astrophysics Data System (ADS)

Standvoss, K.; Crijns, T.; Goerke, L.; Janssen, D.; Kern, S.; van Niedek, T.; van Vugt, J.; Alfonso Burgos, N.; Gerritse, E. J.; Mol, J.; van de Vooren, D.; Ghafoorian, M.; van den Heuvel, T. L. A.; Manniesing, R.

2018-02-01

The number and location of cerebral microbleeds (CMBs) in patients with traumatic brain injury (TBI) is important to determine the severity of trauma and may hold prognostic value for patient outcome. However, manual assessment is subjective and time-consuming due to the resemblance of CMBs to blood vessels, the possible presence of imaging artifacts, and the typical heterogeneity of trauma imaging data. In this work, we present a computer aided detection system based on 3D convolutional neural networks for detecting CMBs in 3D susceptibility weighted images. Network architectures with varying depth were evaluated. Data augmentation techniques were employed to improve the networks' generalization ability and selective sampling was implemented to handle class imbalance. The predictions of the models were clustered using a connected component analysis. The system was trained on ten annotated scans and evaluated on an independent test set of eight scans. Despite this limited data set, the system reached a sensitivity of 0.87 at 16.75 false positives per scan (2.5 false positives per CMB), outperforming related work on CMB detection in TBI patients.

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.

The human false-negative rate of rescreening Pap tests. Measured in a two-arm prospective clinical trial.

PubMed

Renshaw, A A; Lezon, K M; Wilbur, D C

2001-04-25

Routine quality control rescreening often is used to calculate the false-negative rate (FNR) of gynecologic cytology. Theoretic analysis suggests that this is not appropriate, due to the high FNR of rescreening and the inability to actually measure it. The authors sought to determine the FNR of manual rescreening in a large, prospective, two-arm clinical trial using an analytic instrument in the evaluation. The results of the Autopap System Clinical Trial, encompassing 25,124 analyzed slides, were reviewed. The false-negative and false-positive rates at various thresholds were determined for routine primary screening, routine rescreening, Autopap primary screening, and Autopap rescreening by using a simple, standard methodology. The FNR of routine manual rescreening at the level of atypical squamous cells of undetermined significance (ASCUS) was 73%, more than 3 times the FNR of primary screening; 11 cases were detected. The FNR of Autopap rescreening was 34%; 80 cases were detected. Routine manual rescreening decreased the laboratory FNR by less than 1%; Autopap rescreening reduced the overall laboratory FNR by 5.7%. At the same time, the false-positive rate for Autopap screening was significantly less than that of routine manual screening at the ASCUS level (4.7% vs. 5.6%; P < 0.0001). Rescreening with the Autopap system remained more sensitive than manual rescreening at the low grade squamous intraepithelial lesions threshold (FNR of 58.8% vs. 100%, respectively), although the number of cases rescreened was low. Routine manual rescreening cannot be used to calculate the FNR of primary screening. Routine rescreening is an extremely ineffective method to detect error and thereby decrease a laboratory's FNR. The Autopap system is a much more effective way of detecting errors within a laboratory and reduces the laboratory's FNR by greater than 25%.

Kepler Reliability and Occurrence Rates

NASA Astrophysics Data System (ADS)

Bryson, Steve

2016-10-01

The Kepler mission has produced tables of exoplanet candidates (``KOI table''), as well as tables of transit detections (``TCE table''), hosted at the Exoplanet Archive (http://exoplanetarchive.ipac.caltech.edu). Transit detections in the TCE table that are plausibly due to a transiting object are selected for inclusion in the KOI table. KOI table entries that have not been identified as false positives (FPs) or false alarms (FAs) are classified as planet candidates (PCs, Mullally et al. 2015). A subset of PCs have been confirmed as planetary transits with greater than 99% probability, but most PCs have <99% probability of being true planets. The fraction of PCs that are true transiting planets is the PC reliability rate. The overall PC population is believed to have a reliability rate >90% (Morton & Johnson 2011).

The memorial consequences of multiple-choice testing.

PubMed

Marsh, Elizabeth J; Roediger, Henry L; Bjork, Robert A; Bjork, Elizabeth L

2007-04-01

The present article addresses whether multiple-choice tests may change knowledge even as they attempt to measure it. Overall, taking a multiple-choice test boosts performance on later tests, as compared with non-tested control conditions. This benefit is not limited to simple definitional questions, but holds true for SAT II questions and for items designed to tap concepts at a higher level in Bloom's (1956) taxonomy of educational objectives. Students, however, can also learn false facts from multiple-choice tests; testing leads to persistence of some multiple-choice lures on later general knowledge tests. Such persistence appears due to faulty reasoning rather than to an increase in the familiarity of lures. Even though students may learn false facts from multiple-choice tests, the positive effects of testing outweigh this cost.

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.

Reducing False Positives in Runtime Analysis of Deadlocks

NASA Technical Reports Server (NTRS)

Bensalem, Saddek; Havelund, Klaus; Clancy, Daniel (Technical Monitor)

2002-01-01

This paper presents an improvement of a standard algorithm for detecting dead-lock potentials in multi-threaded programs, in that it reduces the number of false positives. The standard algorithm works as follows. The multi-threaded program under observation is executed, while lock and unlock events are observed. A graph of locks is built, with edges between locks symbolizing locking orders. Any cycle in the graph signifies a potential for a deadlock. The typical standard example is the group of dining philosophers sharing forks. The algorithm is interesting because it can catch deadlock potentials even though no deadlocks occur in the examined trace, and at the same time it scales very well in contrast t o more formal approaches to deadlock detection. The algorithm, however, can yield false positives (as well as false negatives). The extension of the algorithm described in this paper reduces the amount of false positives for three particular cases: when a gate lock protects a cycle, when a single thread introduces a cycle, and when the code segments in different threads that cause the cycle can actually not execute in parallel. The paper formalizes a theory for dynamic deadlock detection and compares it to model checking and static analysis techniques. It furthermore describes an implementation for analyzing Java programs and its application to two case studies: a planetary rover and a space craft altitude control system.

Exploring effective multiplicity in multichannel functional near-infrared spectroscopy using eigenvalues of correlation matrices

PubMed Central

Uga, Minako; Dan, Ippeita; Dan, Haruka; Kyutoku, Yasushi; Taguchi, Y-h; Watanabe, Eiju

2015-01-01

Abstract. Recent advances in multichannel functional near-infrared spectroscopy (fNIRS) allow wide coverage of cortical areas while entailing the necessity to control family-wise errors (FWEs) due to increased multiplicity. Conventionally, the Bonferroni method has been used to control FWE. While Type I errors (false positives) can be strictly controlled, the application of a large number of channel settings may inflate the chance of Type II errors (false negatives). The Bonferroni-based methods are especially stringent in controlling Type I errors of the most activated channel with the smallest p value. To maintain a balance between Types I and II errors, effective multiplicity (Meff) derived from the eigenvalues of correlation matrices is a method that has been introduced in genetic studies. Thus, we explored its feasibility in multichannel fNIRS studies. Applying the Meff method to three kinds of experimental data with different activation profiles, we performed resampling simulations and found that Meff was controlled at 10 to 15 in a 44-channel setting. Consequently, the number of significantly activated channels remained almost constant regardless of the number of measured channels. We demonstrated that the Meff approach can be an effective alternative to Bonferroni-based methods for multichannel fNIRS studies. PMID:26157982

Language and False Belief: Evidence for General, Not Specific, Effects in Cantonese-Speaking Preschoolers

ERIC Educational Resources Information Center

Tardif, Twila; So, Catherine Wing-Chee; Kaciroti, Niko

2007-01-01

Two studies were conducted with Cantonese-speaking preschoolers examining J. de Villiers's (1995) hypothesis that syntactic complements play a unique role in the acquisition of false belief (FB). In Study 1, the authors found a positive correlation between FB and syntactic complements in 72 four- to six-year-old Cantonese-speaking preschoolers.…

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.

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.

Perspective: Innocence and due diligence: managing unfounded allegations of scientific misconduct.

PubMed

Goldenring, James R

2010-03-01

While the incidence of fraud in science is well documented, issues related to the establishment of innocence in cases of fallacious allegations remain unaddressed. In this article, the author uses his own experience to examine issues that arise when investigators are falsely accused of scientific fraud. Investigators must understand the processes in place to protect themselves against false accusations. The present system takes a position of guilty until proven innocent, a concept that is antithetical to American principles of jurisprudence. Yet this stance is acceptable as a requirement for membership in the scientific community, more reflective of the rules within a guild organization. The necessity for proof of innocence by members of the scientific community carries obligations that transcend normal legal assumptions. Scientists must safeguard their reputations by organizing and maintaining all original image files and data relevant to publications and grant proposals. Investigators must be able to provide clear documentation rapidly whenever concerns are raised during the review process. Moreover, peer-reviewed journals must be diligent not only in the identification of fraud but also in providing rapid due process for adjudication of allegations. The success of the scientific guild rules of conduct lies in the practice of due diligence by both scientists and journal editors in questions of scientific misconduct.

Challenging a bioinformatic tool's ability to detect microbial contaminants using in silico whole genome sequencing data.

PubMed

Olson, Nathan D; Zook, Justin M; Morrow, Jayne B; Lin, Nancy J

2017-01-01

High sensitivity methods such as next generation sequencing and polymerase chain reaction (PCR) are adversely impacted by organismal and DNA contaminants. Current methods for detecting contaminants in microbial materials (genomic DNA and cultures) are not sensitive enough and require either a known or culturable contaminant. Whole genome sequencing (WGS) is a promising approach for detecting contaminants due to its sensitivity and lack of need for a priori assumptions about the contaminant. Prior to applying WGS, we must first understand its limitations for detecting contaminants and potential for false positives. Herein we demonstrate and characterize a WGS-based approach to detect organismal contaminants using an existing metagenomic taxonomic classification algorithm. Simulated WGS datasets from ten genera as individuals and binary mixtures of eight organisms at varying ratios were analyzed to evaluate the role of contaminant concentration and taxonomy on detection. For the individual genomes the false positive contaminants reported depended on the genus, with Staphylococcus , Escherichia , and Shigella having the highest proportion of false positives. For nearly all binary mixtures the contaminant was detected in the in-silico datasets at the equivalent of 1 in 1,000 cells, though F. tularensis was not detected in any of the simulated contaminant mixtures and Y. pestis was only detected at the equivalent of one in 10 cells. Once a WGS method for detecting contaminants is characterized, it can be applied to evaluate microbial material purity, in efforts to ensure that contaminants are characterized in microbial materials used to validate pathogen detection assays, generate genome assemblies for database submission, and benchmark sequencing methods.

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.

Characterisation of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

PubMed Central

Maratou, Klio; Behmoaras, Jacques; Fewings, Chris; Srivastava, Prashant; D’Souza, Zelpha; Smith, Jennifer; Game, Laurence; Cook, Terence; Aitman, Tim

2010-01-01

Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity. PMID:21179115

Differences in tuberculin reactivity as determined in a veterans administration employee health screening program.

PubMed

Mehta, Sanjay R; MacGruder, Cathy; Looney, David; Johns, Scott; Smith, Davey M

2009-04-01

In response to a difference in pricing, the San Diego Veterans Administration Medical Center changed its tuberculin preparation from Tubersol to Aplisol in the fall of 2006. Following the change, an increased number of employee skin test conversions was noted. Employee tuberculin skin test converters from 2006 were screened with the QuantiFERON Gold (QFT-G) gamma interferon release assay. Those employees who tested negative by QFT-G were asked to repeat their skin test with both Tubersol and Aplisol tuberculin preparations. Of the new purified protein derivative converters, 12 of 14 returned for repeat testing with QFT-G, and the assay was negative for 83% (10/12), positive for 8% (1/12), and indeterminate for 8% (1/12) of the individuals. Nine of the individuals who were QFT-G negative agreed to repeat skin testing with both tuberculin preparations, and 7/8 (87.5%) demonstrated reactivity with the Aplisol preparation, while 0/8 (0%) reacted to the Tubersol preparation. A change from Tubersol to Aplisol resulted in elevated tuberculin skin test conversion rates that may be due to false-positive reactions. The differences in skin test reactivity between preparations support CDC guidelines that recommend that institutions should not change tuberculin preparations, as doing so may falsely increase the number of positive reactions.

False-Positive Rate of AKI Using Consensus Creatinine-Based Criteria.

PubMed

Lin, Jennie; Fernandez, Hilda; Shashaty, Michael G S; Negoianu, Dan; Testani, Jeffrey M; Berns, Jeffrey S; Parikh, Chirag R; Wilson, F Perry

2015-10-07

Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false-positive rates because of inherent laboratory and biologic variabilities of creatinine. We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false-positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient's true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria. Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false-positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%-8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false-positive AKI diagnosis rate of 30.5% (interquartile range =30.1%-30.9%) versus 2.0% (interquartile range =1.9%-2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001). Use of small serum creatinine changes to diagnose AKI is limited by high false-positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies. Copyright © 2015 by the American Society of Nephrology.

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.

Randomly auditing research labs could be an affordable way to improve research quality: A simulation study

PubMed Central

Zardo, Pauline; Graves, Nicholas

2018-01-01

The “publish or perish” incentive drives many researchers to increase the quantity of their papers at the cost of quality. Lowering quality increases the number of false positive errors which is a key cause of the reproducibility crisis. We adapted a previously published simulation of the research world where labs that produce many papers are more likely to have “child” labs that inherit their characteristics. This selection creates a competitive spiral that favours quantity over quality. To try to halt the competitive spiral we added random audits that could detect and remove labs with a high proportion of false positives, and also improved the behaviour of “child” and “parent” labs who increased their effort and so lowered their probability of making a false positive error. Without auditing, only 0.2% of simulations did not experience the competitive spiral, defined by a convergence to the highest possible false positive probability. Auditing 1.35% of papers avoided the competitive spiral in 71% of simulations, and auditing 1.94% of papers in 95% of simulations. Audits worked best when they were only applied to established labs with 50 or more papers compared with labs with 25 or more papers. Adding a ±20% random error to the number of false positives to simulate peer reviewer error did not reduce the audits’ efficacy. The main benefit of the audits was via the increase in effort in “child” and “parent” labs. Audits improved the literature by reducing the number of false positives from 30.2 per 100 papers to 12.3 per 100 papers. Auditing 1.94% of papers would cost an estimated $15.9 million per year if applied to papers produced by National Institutes of Health funding. Our simulation greatly simplifies the research world and there are many unanswered questions about if and how audits would work that can only be addressed by a trial of an audit. PMID:29649314

Randomly auditing research labs could be an affordable way to improve research quality: A simulation study.

PubMed

Barnett, Adrian G; Zardo, Pauline; Graves, Nicholas

2018-01-01

The "publish or perish" incentive drives many researchers to increase the quantity of their papers at the cost of quality. Lowering quality increases the number of false positive errors which is a key cause of the reproducibility crisis. We adapted a previously published simulation of the research world where labs that produce many papers are more likely to have "child" labs that inherit their characteristics. This selection creates a competitive spiral that favours quantity over quality. To try to halt the competitive spiral we added random audits that could detect and remove labs with a high proportion of false positives, and also improved the behaviour of "child" and "parent" labs who increased their effort and so lowered their probability of making a false positive error. Without auditing, only 0.2% of simulations did not experience the competitive spiral, defined by a convergence to the highest possible false positive probability. Auditing 1.35% of papers avoided the competitive spiral in 71% of simulations, and auditing 1.94% of papers in 95% of simulations. Audits worked best when they were only applied to established labs with 50 or more papers compared with labs with 25 or more papers. Adding a ±20% random error to the number of false positives to simulate peer reviewer error did not reduce the audits' efficacy. The main benefit of the audits was via the increase in effort in "child" and "parent" labs. Audits improved the literature by reducing the number of false positives from 30.2 per 100 papers to 12.3 per 100 papers. Auditing 1.94% of papers would cost an estimated $15.9 million per year if applied to papers produced by National Institutes of Health funding. Our simulation greatly simplifies the research world and there are many unanswered questions about if and how audits would work that can only be addressed by a trial of an audit.

Diagnostic performance of semi-quantitative and quantitative stress CMR perfusion analysis: a meta-analysis.

PubMed

van Dijk, R; van Assen, M; Vliegenthart, R; de Bock, G H; van der Harst, P; Oudkerk, M

2017-11-27

Stress cardiovascular magnetic resonance (CMR) perfusion imaging is a promising modality for the evaluation of coronary artery disease (CAD) due to high spatial resolution and absence of radiation. Semi-quantitative and quantitative analysis of CMR perfusion are based on signal-intensity curves produced during the first-pass of gadolinium contrast. Multiple semi-quantitative and quantitative parameters have been introduced. Diagnostic performance of these parameters varies extensively among studies and standardized protocols are lacking. This study aims to determine the diagnostic accuracy of semi- quantitative and quantitative CMR perfusion parameters, compared to multiple reference standards. Pubmed, WebOfScience, and Embase were systematically searched using predefined criteria (3272 articles). A check for duplicates was performed (1967 articles). Eligibility and relevance of the articles was determined by two reviewers using pre-defined criteria. The primary data extraction was performed independently by two researchers with the use of a predefined template. Differences in extracted data were resolved by discussion between the two researchers. The quality of the included studies was assessed using the 'Quality Assessment of Diagnostic Accuracy Studies Tool' (QUADAS-2). True positives, false positives, true negatives, and false negatives were subtracted/calculated from the articles. The principal summary measures used to assess diagnostic accuracy were sensitivity, specificity, andarea under the receiver operating curve (AUC). Data was pooled according to analysis territory, reference standard and perfusion parameter. Twenty-two articles were eligible based on the predefined study eligibility criteria. The pooled diagnostic accuracy for segment-, territory- and patient-based analyses showed good diagnostic performance with sensitivity of 0.88, 0.82, and 0.83, specificity of 0.72, 0.83, and 0.76 and AUC of 0.90, 0.84, and 0.87, respectively. In per territory analysis our results show similar diagnostic accuracy comparing anatomical (AUC 0.86(0.83-0.89)) and functional reference standards (AUC 0.88(0.84-0.90)). Only the per territory analysis sensitivity did not show significant heterogeneity. None of the groups showed signs of publication bias. The clinical value of semi-quantitative and quantitative CMR perfusion analysis remains uncertain due to extensive inter-study heterogeneity and large differences in CMR perfusion acquisition protocols, reference standards, and methods of assessment of myocardial perfusion parameters. For wide spread implementation, standardization of CMR perfusion techniques is essential. CRD42016040176 .

Utility and limitations of a peptide reactivity assay to predict fragrance allergens in vitro.

PubMed

Natsch, A; Gfeller, H; Rothaupt, M; Ellis, G

2007-10-01

A key step in the skin sensitization process is the formation of a covalent adduct between the skin sensitizer and endogenous proteins and/or peptides in the skin. A published peptide depletion assay was used to relate the in vitro reactivity of fragrance molecules to LLNA data. Using the classical assay, 22 of 28 tested moderate to strong sensitizers were positive. The prediction of weak sensitizers proved to be more difficult with only 50% of weak sensitizers giving a positive response, but for some compounds this could also be due to false-positive results from the LLNA. LC-MS analysis yielded the expected mass of the peptide adducts in several cases, whereas in other cases putative oxidation reactions led to adducts of unexpected molecular weight. Several moderately sensitizing aldehydes were correctly predicted by the depletion assay, but no adducts were found and the depletion appears to be due to an oxidation of the parent peptide catalyzed by the test compound. Finally, alternative test peptides derived from a physiological reactive protein with enhanced sensitivity for weak Michael acceptors were found, further increasing the sensitivity of the assay.

Vestibular-Evoked Myogenic Potentials in Bilateral Vestibulopathy

PubMed Central

Rosengren, Sally M.; Welgampola, Miriam S.; Taylor, Rachael L.

2018-01-01

Bilateral vestibulopathy (BVP) is a chronic condition in which patients have a reduction or absence of vestibular function in both ears. BVP is characterized by bilateral reduction of horizontal canal responses; however, there is increasing evidence that otolith function can also be affected. Cervical and ocular vestibular-evoked myogenic potentials (cVEMPs/oVEMPs) are relatively new tests of otolith function that can be used to test the saccule and utricle of both ears independently. Studies to date show that cVEMPs and oVEMPs are often small or absent in BVP but are in the normal range in a significant proportion of patients. The variability in otolith function is partly due to the heterogeneous nature of BVP but is also due to false negative and positive responses that occur because of the large range of normal VEMP amplitudes. Due to their variability, VEMPs are not part of the diagnosis of BVP; however, they are helpful complementary tests that can provide information about the extent of disease within the labyrinth. This article is a review of the use of VEMPs in BVP, summarizing the available data on VEMP abnormalities in patients and discussing the limitations of VEMPs in diagnosing bilateral loss of otolith function. PMID:29719527

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.

Bacillus cereus bacteremia outbreak due to contaminated hospital linens.

PubMed

Sasahara, T; Hayashi, S; Morisawa, Y; Sakihama, T; Yoshimura, A; Hirai, Y

2011-02-01

We describe an outbreak of Bacillus cereus bacteremia that occurred at Jichi Medical University Hospital in 2006. This study aimed to identify the source of this outbreak and to implement appropriate control measures. We reviewed the charts of patients with blood cultures positive for B. cereus, and investigated B. cereus contamination within the hospital environment. Genetic relationships among B. cereus isolates were analyzed. Eleven patients developed B. cereus bacteremia between January and August 2006. The hospital linens and the washing machine were highly contaminated with B. cereus, which was also isolated from the intravenous fluid. All of the contaminated linens were autoclaved, the washing machine was cleaned with a detergent, and hand hygiene was promoted among the hospital staff. The number of patients per month that developed new B. cereus bacteremia rapidly decreased after implementing these measures. The source of this outbreak was B. cereus contamination of hospital linens, and B. cereus was transmitted from the linens to patients via catheter infection. Our findings demonstrated that bacterial contamination of hospital linens can cause nosocomial bacteremia. Thus, blood cultures that are positive for B. cereus should not be regarded as false positives in the clinical setting.

Comparison of the diuretic renogram and the pressure perfusion study in children

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

Kass, E.J.; Majd, M.; Belman, A.B.

1985-07-01

The authors evaluated 42 hydronephrotic kidneys with diuretic renography and pressure perfusion studies to diagnose or exclude the presence of obstruction. Both studies were highly accurate but a small number of false positive and false negative studies were observed with each testing modality. The advantages, disadvantages and potential sources of inaccuracy of each study are discussed, and a protocol for the evaluation of hydronephrosis incorporating both studies is proposed.

Conditional reasoning with false premises facilitates the transition between familiar and abstract reasoning.

PubMed

Markovits, Henry; Lortie-Forgues, Hugues

2011-01-01

Abstract reasoning is critical for science and mathematics, but is very difficult. In 3 studies, the hypothesis that alternatives generation required for conditional reasoning with false premises facilitates abstract reasoning is examined. Study 1 (n = 372) found that reasoning with false premises improved abstract reasoning in 12- to 15-year-olds. Study 2 (n = 366) found a positive effect of simply generating alternatives, but only in 19-year-olds. Study 3 (n = 92) found that 9- to 11-year-olds were able to respond logically with false premises, whereas no such ability was observed in 6- to 7-year-olds. Reasoning with false premises was found to improve reasoning with semiabstract premises in the older children. These results support the idea that alternatives generation with false premises facilitates abstract reasoning. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

[Systematic review of the validity of urine cultures collected by sterile perineal bags].

PubMed

Ochoa Sangrador, C; Pascual Terrazas, A

2016-02-01

The perineal adhesive bag is the most used method in our country for urine culture collection in infants, despite having a high risk of contamination and false-positive results. We aim to quantify both types of risks through a systematic review. Search updated in May 2014 in PUBMED, SCOPUS (includes EMBASE), IBECS; CINAHL, LILACS AND CUIDEN, without language or time limits. Percentages of contaminated urines, false positives, sensitivity and specificity (with respect to catheterization or bladder puncture) were recorded. A total of 21 studies of medium quality (7,659 samples) were selected. The pooled percentage of contaminated urines was 46.6% (15 studies; 6856 samples; 95% confidence interval [95% CI]: 35.6 to 57.8%; I(2): 97.3%). The pooled percentage of false positives was 61.1% (12 studies; 575 samples; 95% CI: 37.9 to 82.2%; I(2): 96.2%). Sensitivity (88%; 95% CI: 81-93%; I(2): 55.2%), and specificity (82%; 95% CI: 75-89%; I(2): 41.3%) were estimated in five studies, but without including contaminated urines. The perineal adhesive bag is not a valid enough method for urine culture collection, because almost half are contaminated and, if they are positive, two out of three are false. Although these estimates are imprecise, because of their great heterogeneity, they should be considered when choosing the method of urine collection. The estimates of sensitivity and specificity are not applicable because they do not take into account the risk of contamination. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

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.

HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status.

PubMed

Richardson, Lyndsay Ann; El-Zein, Mariam; Ramanakumar, Agnihotram V; Ratnam, Samuel; Sangwa-Lugoma, Ghislain; Longatto-Filho, Adhemar; Cardoso, Marly Augusto; Coutlée, Francois; Franco, Eduardo L

2015-12-01

Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. © 2015 American Cancer Society.

High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients.

PubMed

Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

2015-08-01

Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

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.

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.

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.

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

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 study of the shortest-period planets found with Kepler

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

Sanchis-Ojeda, Roberto; Rappaport, Saul; Winn, Joshua N.

2014-05-20

We present the results of a survey aimed at discovering and studying transiting planets with orbital periods shorter than one day (ultra-short-period, or USP, planets), using data from the Kepler spacecraft. We computed Fourier transforms of the photometric time series for all 200,000 target stars, and detected transit signals based on the presence of regularly spaced sharp peaks in the Fourier spectrum. We present a list of 106 USP candidates, of which 18 have not previously been described in the literature. This list of candidates increases the number of planet candidates with orbital periods shorter than about six hours frommore » two to seven. In addition, among the objects we studied, there are 26 USP candidates that had been previously reported in the literature which do not pass our various tests. All 106 of our candidates have passed several standard tests to rule out false positives due to eclipsing stellar systems. A low false positive rate is also implied by the relatively high fraction of candidates for which more than one transiting planet signal was detected. By assuming these multi-transit candidates represent coplanar multi-planet systems, we are able to infer that the USP planets are typically accompanied by other planets with periods in the range 1-50 days, in contrast with hot Jupiters which very rarely have companions in that same period range. Another clear pattern is that almost all USP planets are smaller than 2 R {sub ⊕}, possibly because gas giants in very tight orbits would lose their atmospheres by photoevaporation when subject to extremely strong stellar irradiation. Based on our survey statistics, USP planets exist around approximately (0.51 ± 0.07)% of G-dwarf stars, and (0.83 ± 0.18)% of K-dwarf stars.« less

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.

Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: split-sample study.

PubMed

Preisler, Sarah; Rebolj, Matejka; Ejegod, Ditte Møller; Lynge, Elsebeth; Rygaard, Carsten; Bonde, Jesper

2016-07-20

High-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays. Consecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months. Cross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224. Despite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes.

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.

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

A statistical method for the detection of variants from next-generation resequencing of DNA pools.

PubMed

Bansal, Vikas

2010-06-15

Next-generation sequencing technologies have enabled the sequencing of several human genomes in their entirety. However, the routine resequencing of complete genomes remains infeasible. The massive capacity of next-generation sequencers can be harnessed for sequencing specific genomic regions in hundreds to thousands of individuals. Sequencing-based association studies are currently limited by the low level of multiplexing offered by sequencing platforms. Pooled sequencing represents a cost-effective approach for studying rare variants in large populations. To utilize the power of DNA pooling, it is important to accurately identify sequence variants from pooled sequencing data. Detection of rare variants from pooled sequencing represents a different challenge than detection of variants from individual sequencing. We describe a novel statistical approach, CRISP [Comprehensive Read analysis for Identification of Single Nucleotide Polymorphisms (SNPs) from Pooled sequencing] that is able to identify both rare and common variants by using two approaches: (i) comparing the distribution of allele counts across multiple pools using contingency tables and (ii) evaluating the probability of observing multiple non-reference base calls due to sequencing errors alone. Information about the distribution of reads between the forward and reverse strands and the size of the pools is also incorporated within this framework to filter out false variants. Validation of CRISP on two separate pooled sequencing datasets generated using the Illumina Genome Analyzer demonstrates that it can detect 80-85% of SNPs identified using individual sequencing while achieving a low false discovery rate (3-5%). Comparison with previous methods for pooled SNP detection demonstrates the significantly lower false positive and false negative rates for CRISP. Implementation of this method is available at http://polymorphism.scripps.edu/~vbansal/software/CRISP/.

Positive Psychology and Adolescent Mental Health: False Promise or True Breakthrough?

ERIC Educational Resources Information Center

Kelley, Thomas M.

2004-01-01

The emerging field of positive psychology has pledged to improve the mental health of American adolescents. Yet, without a principle-based conceptual foundation to guide its study of optimal youth functioning, positive psychology will ultimately fail to keep its promise. This paper suggests that the principles of Mind, Thought and Consciousness…

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.

Kepler Planet Detection Metrics: Robovetter Completeness and Effectiveness for Data Release 25

NASA Technical Reports Server (NTRS)

Coughlin, Jeffrey L.

2017-01-01

In general, the Kepler pipeline identifies a list of Threshold Crossing Events (TCEs), which are periodic flux decrements meeting certain criteria (Jenkins, 2017). These TCEs are reviewed and those that appear consistent with astrophysically transiting or eclipsing systems are classified as Kepler Objects of Interest (KOIs). Further review is given to KOIs, which are then dispositioned as Planet Candidates (PCs) or False Positive (FPs). FPs are further denoted by four major flags that indicate if the signal is Not Transit-Like (NTL), due to a Stellar Eclipse (SS; previously referred to as Significant Secondary), and/or due to contamination from a source other than the target as evidenced by a Centroid Offset (CO) oran Ephemeris Match (EM) with another object. This entire TCE review process is known as dispositioning or vetting.In the first five Kepler mission planet candidate catalogs (Borucki et al., 2011a,b; Batalha et al., 2013; Burke et al., 2014; Rowe et al., 2015), TCEs were manually examined on an individual basis and dispositioned using various plots and quantitative diagnostic tests (see e.g., Coughlin, 2017). In the sixth catalog, Mullally et al. (2015a) employed partial automation via simple parameter cuts to automatically disposition a large fraction of TCEs as not transit-like. Mullally et al. (2015a) also used an automated technique known as the centroid Robovetter (Mullally, 2017) to automatically identify some FP KOIs due to centroid offsets - a telltale signature of light contamination from another target. The remaining targets were manually dispositioned. In the seventh catalog, Coughlin et al. (2016) automated theentire dispositioning process using what is collectively known simply as the Robovetter.In the eighth and final mission catalog, Thompson et al. (2017) use a revised Robovetter to automate the dispositioning of all TCEs with an emphasis on creating a catalog suitable for accurately determining planet occurrence rates. In order to calculate accurate occurrence rates, the completeness and effectiveness of the Robovetter must be characterized. We define these terms as applied to the Robovetter, following Thompson et al. (2017), as:1. Completeness: The fraction of transiting planets detected by the pipeline that are classified as planet candidates by the Robovetter.2. Effectiveness: The fraction of false positives detected by the pipeline that are classified as false positives by the Robovetter.The remainder of this document describes products that can be used to quantitatively assess Robovetter completeness and effectiveness for an arbitrary set of Kepler stars.

Do doctors understand the test characteristics of lung cancer screening?

PubMed

Schmidt, Richard; Breyer, Marie; Breyer-Kohansal, Robab; Urban, Matthias; Funk, Georg-Christian

2018-04-01

Screening for lung cancer with a low-dose computed tomography (CT) scan is estimated to prevent 3 deaths per 1000 individuals at high risk; however, false positive results and radiation exposure are relevant harms and deserve careful consideration. Screening candidates can only make an autonomous decision if doctors correctly inform them of the pros and cons of the method; therefore, this study aimed to evaluate whether doctors understand the test characteristics of lung cancer screening. In a randomized trial 556 doctors (members of the Austrian Respiratory Society) were invited to answer questions regarding lung cancer screening based on online case vignettes. Half of the participants were randomized to the group 'solutions provided' and received the correct solutions in advance. The group 'solutions withheld' had to rely on prior knowledge or estimates. The primary endpoint was the between-group difference in the estimated number of deaths preventable by screening. Secondary endpoints were the between-group differences in the prevalence of lung cancer, prevalence of a positive screening results, sensitivity, specificity, positive predictive value, and false negative rate. Estimations were also compared with current data from the literature. The response rate was 29% in both groups. The reduction in the number of deaths due to screening was overestimated six-fold (95% confidence interval CI: 4-8) compared with the actual data, and there was no effect of group allocation. Providing the correct solutions to doctors had no systematic effect on their answers. Doctors poorly understand the test characteristics of lung cancer screening. Providing the correct solutions in advance did not improve the answers. Continuing education regarding lung cancer screening and the interpretation of test characteristics may be a simple remedy. Clinical trial registered with www.clinicaltrials.gov (NCT02542332).

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

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.

Experimental Null Method to Guide the Development of Technical Procedures and to Control False-Positive Discovery in Quantitative Proteomics.

PubMed

Shen, Xiaomeng; Hu, Qiang; Li, Jun; Wang, Jianmin; Qu, Jun

2015-10-02

Comprehensive and accurate evaluation of data quality and false-positive biomarker discovery is critical to direct the method development/optimization for quantitative proteomics, which nonetheless remains challenging largely due to the high complexity and unique features of proteomic data. Here we describe an experimental null (EN) method to address this need. Because the method experimentally measures the null distribution (either technical or biological replicates) using the same proteomic samples, the same procedures and the same batch as the case-vs-contol experiment, it correctly reflects the collective effects of technical variability (e.g., variation/bias in sample preparation, LC-MS analysis, and data processing) and project-specific features (e.g., characteristics of the proteome and biological variation) on the performances of quantitative analysis. To show a proof of concept, we employed the EN method to assess the quantitative accuracy and precision and the ability to quantify subtle ratio changes between groups using different experimental and data-processing approaches and in various cellular and tissue proteomes. It was found that choices of quantitative features, sample size, experimental design, data-processing strategies, and quality of chromatographic separation can profoundly affect quantitative precision and accuracy of label-free quantification. The EN method was also demonstrated as a practical tool to determine the optimal experimental parameters and rational ratio cutoff for reliable protein quantification in specific proteomic experiments, for example, to identify the necessary number of technical/biological replicates per group that affords sufficient power for discovery. Furthermore, we assessed the ability of EN method to estimate levels of false-positives in the discovery of altered proteins, using two concocted sample sets mimicking proteomic profiling using technical and biological replicates, respectively, where the true-positives/negatives are known and span a wide concentration range. It was observed that the EN method correctly reflects the null distribution in a proteomic system and accurately measures false altered proteins discovery rate (FADR). In summary, the EN method provides a straightforward, practical, and accurate alternative to statistics-based approaches for the development and evaluation of proteomic experiments and can be universally adapted to various types of quantitative techniques.

LOW FALSE POSITIVE RATE OF KEPLER CANDIDATES ESTIMATED FROM A COMBINATION OF SPITZER AND FOLLOW-UP OBSERVATIONS

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

Désert, Jean-Michel; Brown, Timothy M.; Charbonneau, David

NASA’s Kepler mission has provided several thousand transiting planet candidates during the 4 yr of its nominal mission, yet only a small subset of these candidates have been confirmed as true planets. Therefore, the most fundamental question about these candidates is the fraction of bona fide planets. Estimating the rate of false positives of the overall Kepler sample is necessary to derive the planet occurrence rate. We present the results from two large observational campaigns that were conducted with the Spitzer Space Telescope during the the Kepler mission. These observations are dedicated to estimating the false positive rate (FPR) amongmore » the Kepler candidates. We select a sub-sample of 51 candidates, spanning wide ranges in stellar, orbital, and planetary parameter space, and we observe their transits with Spitzer at 4.5 μm. We use these observations to measures the candidate’s transit depths and infrared magnitudes. An authentic planet produces an achromatic transit depth (neglecting the modest effect of limb darkening). Conversely a bandpass-dependent depth alerts us to the potential presence of a blending star that could be the source of the observed eclipse: a false positive scenario. For most of the candidates (85%), the transit depths measured with Kepler are consistent with the transit depths measured with Spitzer as expected for planetary objects, while we find that the most discrepant measurements are due to the presence of unresolved stars that dilute the photometry. The Spitzer constraints on their own yield FPRs between 5% and depending on the Kepler Objects of Interest. By considering the population of the Kepler field stars, and by combining follow-up observations (imaging) when available, we find that the overall FPR of our sample is low. The measured upper limit on the FPR of our sample is 8.8% at a confidence level of 3σ. This observational result, which uses the achromatic property of planetary transit signals that is not investigated by the Kepler observations, provides an independent indication that Kepler’s FPR is low.« less

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.

Parametric vs. non-parametric statistics of low resolution electromagnetic tomography (LORETA).

PubMed

Thatcher, R W; North, D; Biver, C

2005-01-01

This study compared the relative statistical sensitivity of non-parametric and parametric statistics of 3-dimensional current sources as estimated by the EEG inverse solution Low Resolution Electromagnetic Tomography (LORETA). One would expect approximately 5% false positives (classification of a normal as abnormal) at the P < .025 level of probability (two tailed test) and approximately 1% false positives at the P < .005 level. EEG digital samples (2 second intervals sampled 128 Hz, 1 to 2 minutes eyes closed) from 43 normal adult subjects were imported into the Key Institute's LORETA program. We then used the Key Institute's cross-spectrum and the Key Institute's LORETA output files (*.lor) as the 2,394 gray matter pixel representation of 3-dimensional currents at different frequencies. The mean and standard deviation *.lor files were computed for each of the 2,394 gray matter pixels for each of the 43 subjects. Tests of Gaussianity and different transforms were computed in order to best approximate a normal distribution for each frequency and gray matter pixel. The relative sensitivity of parametric vs. non-parametric statistics were compared using a "leave-one-out" cross validation method in which individual normal subjects were withdrawn and then statistically classified as being either normal or abnormal based on the remaining subjects. Log10 transforms approximated Gaussian distribution in the range of 95% to 99% accuracy. Parametric Z score tests at P < .05 cross-validation demonstrated an average misclassification rate of approximately 4.25%, and range over the 2,394 gray matter pixels was 27.66% to 0.11%. At P < .01 parametric Z score cross-validation false positives were 0.26% and ranged from 6.65% to 0% false positives. The non-parametric Key Institute's t-max statistic at P < .05 had an average misclassification error rate of 7.64% and ranged from 43.37% to 0.04% false positives. The nonparametric t-max at P < .01 had an average misclassification rate of 6.67% and ranged from 41.34% to 0% false positives of the 2,394 gray matter pixels for any cross-validated normal subject. In conclusion, adequate approximation to Gaussian distribution and high cross-validation can be achieved by the Key Institute's LORETA programs by using a log10 transform and parametric statistics, and parametric normative comparisons had lower false positive rates than the non-parametric tests.

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.

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.

Maximum number of children per sperm donor based on false paternity rate.

PubMed

Sánchez-Castelló, Isabel M; Gonzalvo, María C; Clavero, Ana; López-Regalado, María L; Mozas, Juan; Martínez-Granados, Luis; Navas, Purificación; Castilla, José A

2017-03-01

The aim of this study is to estimate the weight of each relevant factor in such unions of inadvertent consanguinity and to determine a "reasonable" limit for the number of children per donor, matching the probability of inadvertent consanguinity arising from the use of sperm donor in assisted reproduction with that of such a union arising from false paternity. In this study, we applied to Spanish data a mathematical model of consanguineous unions, taking into account the following factors: maximum number of live births/donor, fertility rate, average number of births per donor in a pregnancy, donor success rate, matings per phenotype, number of newborns/year, and number of donors needed in the population/year and births by false paternity. In Spain, the number of inadvertent unions between descendants of the same donor in Spain has been estimated at 0.4/year (one every two and a half years), although this frequency decreases as the reference population increases. On the other hand, the frequency of unions between family members due to false paternity has been estimated at 6.1/year. Thus, only 6% of such unions are due to the use of donor sperm. A total of 25 children per sperm donor are needed to align the probability of inadvertant consanguinity arising from the use of assisted reproduction with that due to false paternity. Therefore, we consider this number to be the maximum "reasonable" number of children born per donor in Spain.

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.

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).

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.

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

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

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

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

Inflammatory myofibroblastic tumor of the mesentery associated with high fever and positive Widal test.

PubMed

Chouairy, Camil J; Bechara, Elie A; Gebran, Sleiman J; Ghabril, Ramy H

2008-12-01

Inflammatory myofibroblastic tumor (IMT) is associated in 15-30% of cases with systemic symptomatology, such as prolonged fever, weight loss, elevated erythrocyte sedimentation rate (ESR), anemia, thrombocytosis, and leukocytosis. We report the case of a 4-year-old Lebanese boy who presented with high-grade fever of long duration, and a single (unpaired) positive Widal agglutination test. Blood culture was negative. A diagnosis of typhoid fever was made. An abdominal (mesenteric) IMT was incidentally discovered, 30 days after the fever had appeared. After surgery, the fever disappeared immediately, and the ESR returned to normal. We strongly favor the possibility of a false positive Widal test, due to polyclonal increase in serum immunoglobulins, which often occurs in IMT. We also think that IMT might be a mimicker of typhoid fever, both clinically and serologically. Physicians, especially pediatricians practicing in endemic areas, should probably be aware of this mimicry.

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

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 Simplexa HSV 1 & 2 PCR with culture, immunofluorescence, and laboratory-developed TaqMan PCR for detection of herpes simplex virus in swab specimens.

PubMed

Gitman, Melissa R; Ferguson, David; Landry, Marie L

2013-11-01

The Simplexa HSV 1 & 2 direct PCR assay was compared with conventional cell culture, cytospin-enhanced direct fluorescent antibody (DFA), and a laboratory-developed real-time TaqMan PCR (LDT HSV PCR) using extracted nucleic acid for the detection of herpes simplex virus (HSV) in dermal, genital, mouth, ocular, and other swab samples. One hundred seventy-one swabs were tested prospectively, and 58 were positive for HSV (34 HSV-1 and 24 HSV-2). Cytospin-DFA detected 50 (86.2%), conventional cell culture 51 (87.9%), Simplexa direct 55 (94.8%), and LDT HSV PCR 57 (98.3%) of 58 true positives. Simplexa direct detected more positives than DFA and culture, but the differences were not significant (P = 0.0736 and P = 0.3711, respectively, by the McNemar test). Samples that were positive by all methods (n = 48) were strong positives (LDT cycle threshold [CT] value, 14.4 to 26.1). One strongly positive sample was falsely negative by LDT HSV PCR due to a failure of TaqMan probe binding. Three samples falsely negative by Simplexa direct had high CT values by LDT HSV PCR (LDT CT, 35.8 to 38.2). Omission of the DNA extraction step by Simplexa direct led to a drop in sensitivity compared to the sensitivity of LDT HSV PCR using extracted samples (94.8% versus 98.3%, respectively), but the difference was not significant (P = 0.6171). Simplexa HSV 1 & 2 direct PCR was the most expensive but required the least training of the assays used, had the lowest hands-on time and fastest assay time (75 min, versus 3 h by LDT HSV PCR), and provided the HSV type.

Comparison of Simplexa HSV 1 & 2 PCR with Culture, Immunofluorescence, and Laboratory-Developed TaqMan PCR for Detection of Herpes Simplex Virus in Swab Specimens

PubMed Central

Gitman, Melissa R.; Ferguson, David

2013-01-01

The Simplexa HSV 1 & 2 direct PCR assay was compared with conventional cell culture, cytospin-enhanced direct fluorescent antibody (DFA), and a laboratory-developed real-time TaqMan PCR (LDT HSV PCR) using extracted nucleic acid for the detection of herpes simplex virus (HSV) in dermal, genital, mouth, ocular, and other swab samples. One hundred seventy-one swabs were tested prospectively, and 58 were positive for HSV (34 HSV-1 and 24 HSV-2). Cytospin-DFA detected 50 (86.2%), conventional cell culture 51 (87.9%), Simplexa direct 55 (94.8%), and LDT HSV PCR 57 (98.3%) of 58 true positives. Simplexa direct detected more positives than DFA and culture, but the differences were not significant (P = 0.0736 and P = 0.3711, respectively, by the McNemar test). Samples that were positive by all methods (n = 48) were strong positives (LDT cycle threshold [CT] value, 14.4 to 26.1). One strongly positive sample was falsely negative by LDT HSV PCR due to a failure of TaqMan probe binding. Three samples falsely negative by Simplexa direct had high CT values by LDT HSV PCR (LDT CT, 35.8 to 38.2). Omission of the DNA extraction step by Simplexa direct led to a drop in sensitivity compared to the sensitivity of LDT HSV PCR using extracted samples (94.8% versus 98.3%, respectively), but the difference was not significant (P = 0.6171). Simplexa HSV 1 & 2 direct PCR was the most expensive but required the least training of the assays used, had the lowest hands-on time and fastest assay time (75 min, versus 3 h by LDT HSV PCR), and provided the HSV type. PMID:24006008

Reduction of false-positive recalls using a computerized mammographic image feature analysis scheme

NASA Astrophysics Data System (ADS)

Tan, Maxine; Pu, Jiantao; Zheng, Bin

2014-08-01

The high false-positive recall rate is one of the major dilemmas that significantly reduce the efficacy of screening mammography, which harms a large fraction of women and increases healthcare cost. This study aims to investigate the feasibility of helping reduce false-positive recalls by developing a new computer-aided diagnosis (CAD) scheme based on the analysis of global mammographic texture and density features computed from four-view images. Our database includes full-field digital mammography (FFDM) images acquired from 1052 recalled women (669 positive for cancer and 383 benign). Each case has four images: two craniocaudal (CC) and two mediolateral oblique (MLO) views. Our CAD scheme first computed global texture features related to the mammographic density distribution on the segmented breast regions of four images. Second, the computed features were given to two artificial neural network (ANN) classifiers that were separately trained and tested in a ten-fold cross-validation scheme on CC and MLO view images, respectively. Finally, two ANN classification scores were combined using a new adaptive scoring fusion method that automatically determined the optimal weights to assign to both views. CAD performance was tested using the area under a receiver operating characteristic curve (AUC). The AUC = 0.793  ±  0.026 was obtained for this four-view CAD scheme, which was significantly higher at the 5% significance level than the AUCs achieved when using only CC (p = 0.025) or MLO (p = 0.0004) view images, respectively. This study demonstrates that a quantitative assessment of global mammographic image texture and density features could provide useful and/or supplementary information to classify between malignant and benign cases among the recalled cases, which may eventually help reduce the false-positive recall rate in screening mammography.

Genovar: a detection and visualization tool for genomic variants.

PubMed

Jung, Kwang Su; Moon, Sanghoon; Kim, Young Jin; Kim, Bong-Jo; Park, Kiejung

2012-05-08

Along with single nucleotide polymorphisms (SNPs), copy number variation (CNV) is considered an important source of genetic variation associated with disease susceptibility. Despite the importance of CNV, the tools currently available for its analysis often produce false positive results due to limitations such as low resolution of array platforms, platform specificity, and the type of CNV. To resolve this problem, spurious signals must be separated from true signals by visual inspection. None of the previously reported CNV analysis tools support this function and the simultaneous visualization of comparative genomic hybridization arrays (aCGH) and sequence alignment. The purpose of the present study was to develop a useful program for the efficient detection and visualization of CNV regions that enables the manual exclusion of erroneous signals. A JAVA-based stand-alone program called Genovar was developed. To ascertain whether a detected CNV region is a novel variant, Genovar compares the detected CNV regions with previously reported CNV regions using the Database of Genomic Variants (DGV, http://projects.tcag.ca/variation) and the Single Nucleotide Polymorphism Database (dbSNP). The current version of Genovar is capable of visualizing genomic data from sources such as the aCGH data file and sequence alignment format files. Genovar is freely accessible and provides a user-friendly graphic user interface (GUI) to facilitate the detection of CNV regions. The program also provides comprehensive information to help in the elimination of spurious signals by visual inspection, making Genovar a valuable tool for reducing false positive CNV results. http://genovar.sourceforge.net/.

Multimodal intraoperative monitoring (MIOM) during cervical spine surgical procedures in 246 patients

PubMed Central

Sutter, Martin A.; Grob, Dieter; Jeszenszky, Dezsö; Porchet, François; Dvorak, Jiri

2007-01-01

A prospective study of 246 patients who received multimodal intraoperative monitoring during cervical spine surgery between March 2000 and December 2005. To determine the sensitivity and specificity of MIOM techniques used to monitor spinal cord and nerve root function during cervical spine surgery. It is appreciated that complication rate of cervical spine surgery is low, however, there is a significant risk of neurological injury. The combination of monitoring of ascending and descending pathways may provide more sensitive and specific results giving immediate feedback information and/or alert regarding any neurological changes during the operation to the surgeon. Intraoperative somatosensory spinal and cerebral evoked potentials combined with continuous EMG and motor-evoked potentials of the spinal cord and muscles were evaluated and compared with postoperative clinical neurological changes. A total of 246 consecutive patients with cervical pathologies, majority spinal stenosis due to degenerative changes of cervical spine were monitored by means of MIOM during the surgical procedure. About 232 patients presented true negative while 2 patients false negative responses. About ten patients presented true positive responses where neurological deficit after the operation was predicted and two patients presented false positive findings. The sensitivity of MIOM applied during cervical spine procedure (anterior and/or posterior) was 83.3% and specificity of 99.2%. MIOM is an effective method of monitoring the spinal cord functional integrity during cervical spine surgery and can help to reduce the risk of neurological deficit by alerting the surgeon when monitoring changes are observed. PMID:17610090

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

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.

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.

Quantitative Value of Aldosterone-Renin Ratio for Detection of Aldosterone-Producing Adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) Study.

PubMed

Maiolino, Giuseppe; Rossitto, Giacomo; Bisogni, Valeria; Cesari, Maurizio; Seccia, Teresa Maria; Plebani, Mario; Rossi, Gian Paolo

2017-05-21

Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false-positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone-producing adenoma as reference index. We also assessed whether the post-captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false-positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post-captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between-area under the curve difference, 0.005; 95% CI, -0.031 to 0.040; P =0.7 for comparison, and 0.05; 95% CI, -0.061 to 0.064; P =0.051 for comparison, respectively). These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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.

Soft Salt-Mannitol Agar–Cloxacillin Test: a Highly Specific Bedside Screening Test for Detection of Colonization with Methicillin-Resistant Staphylococcus aureus

PubMed Central

Mir, Nuria; Sánchez, Miguel; Baquero, Fernando; López, Blanca; Calderón, Celia; Cantón, Rafael

1998-01-01

The early detection of colonization with methicillin-resistant Staphylococcus aureus (MRSA) of patients in intensive-care units is an essential step in the strategy for preventing MRSA epidemics. In this study, tubes containing soft salt-mannitol agar with cloxacillin (6 μg/ml) (SSMAC) were prepared for inoculation of clinical samples at patients’ bedsides by personnel of an intensive-care unit. A total of 1,914 swabs from different sample sites of 81 patients were dipped into SSMAC tubes, and after 24 h of incubation (in an incubator located near the intensive-care unit), an evident color change was considered by the intensive-care-unit personnel to be an MRSA alarm. Sixty-three (3.3%) SSMAC tubes were considered positive for MRSA, 1,827 (95.4%) were considered negative, and 24 (1.2%) were considered intermediate. Compared with values for parallel conventional surveillance cultures for MRSA, excluding tubes with intermediate results, the SSMAC test had a sensitivity of 72.7%, a specificity of 99.2%, a positive predictive value of 76.2%, and a negative predictive value of 99.0%. When intermediate tubes were considered positive, the corresponding values were 75.3, 98.2, 63.2, and 99.0%, respectively. The sensitivity and specificity values of the test to identify MRSA-colonized patients were 89.4 and 100%, respectively. Oropharyngeal and naris specimens were the most reliable samples for MRSA detection. False-negative results were frequent in bronchial aspirates with low (<103 to 106 CFU/ml) MRSA counts. False-positive results were mainly due to methicillin-resistant Staphylococcus haemolyticus. The SSMAC tube is a useful, rapid, and inexpensive tool for the early identification of MRSA-colonized patients and, consequently, for the implementation of measures to prevent the spread of MRSA. PMID:9542922

Multi-site evaluation of the LN34 pan-lyssavirus real-time RT-PCR assay for post-mortem rabies diagnostics

PubMed Central

Dettinger, Lisa; Powell, James W.; Seiders, Melanie; Condori, Rene Edgar Condori; Griesser, Richard; Okogi, Kenneth; Carlos, Maria; Pesko, Kendra; Breckenridge, Mike; Simon, Edson Michael M.; Chu, Maria Yna Joyce V.; Davis, April D.; Brunt, Scott J.; Orciari, Lillian; Yager, Pamela; Carson, William C.; Hartloge, Claire; Saliki, Jeremiah T.; Deldari, Mojgan; Hsieh, Kristina; Wadhwa, Ashutosh; Wilkins, Kimberly; Rabideau, Patricia; Gruhn, Nina; Cadet, Rolain; Isloor, Shrikrishna; Nath, Sujith S.; Joseph, Tomy; Gao, Jinxin; Wallace, Ryan; Reynolds, Mary; Olson, Victoria A.

2018-01-01

Rabies is a fatal zoonotic disease that requires fast, accurate diagnosis to prevent disease in an exposed individual. The current gold standard for post-mortem diagnosis of human and animal rabies is the direct fluorescent antibody (DFA) test. While the DFA test has proven sensitive and reliable, it requires high quality antibody conjugates, a skilled technician, a fluorescence microscope and diagnostic specimen of sufficient quality. The LN34 pan-lyssavirus real-time RT-PCR assay represents a strong candidate for rabies post-mortem diagnostics due to its ability to detect RNA across the diverse Lyssavirus genus, its high sensitivity, its potential for use with deteriorated tissues, and its simple, easy to implement design. Here, we present data from a multi-site evaluation of the LN34 assay in 14 laboratories. A total of 2,978 samples (1,049 DFA positive) from Africa, the Americas, Asia, Europe, and the Middle East were tested. The LN34 assay exhibited low variability in repeatability and reproducibility studies and was capable of detecting viral RNA in fresh, frozen, archived, deteriorated and formalin-fixed brain tissue. The LN34 assay displayed high diagnostic specificity (99.68%) and sensitivity (99.90%) when compared to the DFA test, and no DFA positive samples were negative by the LN34 assay. The LN34 assay produced definitive findings for 80 samples that were inconclusive or untestable by DFA; 29 were positive. Five samples were inconclusive by the LN34 assay, and only one sample was inconclusive by both tests. Furthermore, use of the LN34 assay led to the identification of one false negative and 11 false positive DFA results. Together, these results demonstrate the reliability and robustness of the LN34 assay and support a role for the LN34 assay in improving rabies diagnostics and surveillance. PMID:29768505

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.

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.

Detection of antibodies against classical swine fever virus in fecal samples from wild boar.

PubMed

Seo, Sang won; Sunwoo, Sun young; Hyun, Bang hoon; Lyoo, Young S

2012-12-28

Classical swine fever (CSF) is a contagious viral disease that affects pigs. Wild boars can play an important epidemiological role in CSF outbreaks. In the past decades, studies conducted in many countries have reported that the CSF virus (CSFV) may persist in wild boar populations. The existence of CSFV in the free-ranging wild boar populations was indirectly confirmed by determining the prevalence of antibodies against CSFV in the serum of hunted wild boars. However, analyzing sero-prevalence in hunted wild boars to study the risk of CSF outbreaks is difficult due to insufficient number of samples, limitation of hunting area and biased age distribution of hunted wild boars. To improve this survey method, we collected feces of wild boars from their habitat and tested them using CSFV antibody enzyme-linked immunosorbent assay (ELISA) and CSF virus neutralization (VN) test. In this study, ELISA was found to be highly sensitive for detecting antibodies against CSFV in fecal samples. Most of doubtful or positive results obtained in CSFV ELISA were confirmed by VN tests. Despite the high coincidence rate of antibody-positive samples between CSFV ELISA and VN test, the possibility of false positive reaction should be considered. In the regional distribution, a fact that antibody-positive fecal and serum samples were found in geographically close area was shown. Hence, presence of antibodies in fecal samples may provide vital information regarding the risk of CSF outbreaks in wild boar groups in geographical proximity. Copyright © 2012 Elsevier B.V. All rights reserved.

Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system.

PubMed

Curvers, W L; Singh, R; Song, L-M Wong-Kee; Wolfsen, H C; Ragunath, K; Wang, K; Wallace, M B; Fockens, P; Bergman, J J G H M

2008-02-01

To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett's oesophagus. Prospective multi-centre study. Tertiary referral centres. 84 Patients with Barrett's oesophagus. The Barrett's oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett's oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.

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.

The role of ethics in shale gas policies.

PubMed

de Melo-Martín, Inmaculada; Hays, Jake; Finkel, Madelon L

2014-02-01

The United States has experienced a boom in natural gas production due to recent technological innovations that have enabled natural gas to be produced from unconventional sources, such as shale. There has been much discussion about the costs and benefits of developing shale gas among scientists, policy makers, and the general public. The debate has typically revolved around potential gains in economics, employment, energy independence, and national security as well as potential harms to the environment, the climate, and public health. In the face of scientific uncertainty, national and international governments must make decisions on how to proceed. So far, the results have been varied, with some governments banning the process, others enacting moratoria until it is better understood, and others explicitly sanctioning shale gas development. These policies reflect legislature's preferences to avoid false negative errors or false positive ones. Here we argue that policy makers have a prima facie duty to minimize false negatives based on three considerations: (1) protection from serious harm generally takes precedence over the enhancement of welfare; (2) minimizing false negatives in this case is more respectful to people's autonomy; and (3) alternative solutions exist that may provide many of the same benefits while minimizing many of the harms. © 2013.

Ancestry estimation and control of population stratification for sequence-based association studies.

PubMed

Wang, Chaolong; Zhan, Xiaowei; Bragg-Gresham, Jennifer; Kang, Hyun Min; Stambolian, Dwight; Chew, Emily Y; Branham, Kari E; Heckenlively, John; Fulton, Robert; Wilson, Richard K; Mardis, Elaine R; Lin, Xihong; Swaroop, Anand; Zöllner, Sebastian; Abecasis, Gonçalo R

2014-04-01

Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.

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.

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.

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.

The HTS barcode checker pipeline, a tool for automated detection of illegally traded species from high-throughput sequencing data.

PubMed

Lammers, Youri; Peelen, Tamara; Vos, Rutger A; Gravendeel, Barbara

2014-02-06

Mixtures of internationally traded organic substances can contain parts of species protected by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). These mixtures often raise the suspicion of border control and customs offices, which can lead to confiscation, for example in the case of Traditional Chinese medicines (TCMs). High-throughput sequencing of DNA barcoding markers obtained from such samples provides insight into species constituents of mixtures, but manual cross-referencing of results against the CITES appendices is labor intensive. Matching DNA barcodes against NCBI GenBank using BLAST may yield misleading results both as false positives, due to incorrectly annotated sequences, and false negatives, due to spurious taxonomic re-assignment. Incongruence between the taxonomies of CITES and NCBI GenBank can result in erroneous estimates of illegal trade. The HTS barcode checker pipeline is an application for automated processing of sets of 'next generation' barcode sequences to determine whether these contain DNA barcodes obtained from species listed on the CITES appendices. This analytical pipeline builds upon and extends existing open-source applications for BLAST matching against the NCBI GenBank reference database and for taxonomic name reconciliation. In a single operation, reads are converted into taxonomic identifications matched with names on the CITES appendices. By inclusion of a blacklist and additional names databases, the HTS barcode checker pipeline prevents false positives and resolves taxonomic heterogeneity. The HTS barcode checker pipeline can detect and correctly identify DNA barcodes of CITES-protected species from reads obtained from TCM samples in just a few minutes. The pipeline facilitates and improves molecular monitoring of trade in endangered species, and can aid in safeguarding these species from extinction in the wild. The HTS barcode checker pipeline is available at https://github.com/naturalis/HTS-barcode-checker.

The HTS barcode checker pipeline, a tool for automated detection of illegally traded species from high-throughput sequencing data

PubMed Central

2014-01-01

Background Mixtures of internationally traded organic substances can contain parts of species protected by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). These mixtures often raise the suspicion of border control and customs offices, which can lead to confiscation, for example in the case of Traditional Chinese medicines (TCMs). High-throughput sequencing of DNA barcoding markers obtained from such samples provides insight into species constituents of mixtures, but manual cross-referencing of results against the CITES appendices is labor intensive. Matching DNA barcodes against NCBI GenBank using BLAST may yield misleading results both as false positives, due to incorrectly annotated sequences, and false negatives, due to spurious taxonomic re-assignment. Incongruence between the taxonomies of CITES and NCBI GenBank can result in erroneous estimates of illegal trade. Results The HTS barcode checker pipeline is an application for automated processing of sets of 'next generation’ barcode sequences to determine whether these contain DNA barcodes obtained from species listed on the CITES appendices. This analytical pipeline builds upon and extends existing open-source applications for BLAST matching against the NCBI GenBank reference database and for taxonomic name reconciliation. In a single operation, reads are converted into taxonomic identifications matched with names on the CITES appendices. By inclusion of a blacklist and additional names databases, the HTS barcode checker pipeline prevents false positives and resolves taxonomic heterogeneity. Conclusions The HTS barcode checker pipeline can detect and correctly identify DNA barcodes of CITES-protected species from reads obtained from TCM samples in just a few minutes. The pipeline facilitates and improves molecular monitoring of trade in endangered species, and can aid in safeguarding these species from extinction in the wild. The HTS barcode checker pipeline is available at https://github.com/naturalis/HTS-barcode-checker. PMID:24502833

Impact of magnetic resonance imaging on preoperative planning for breast cancer surgery.

PubMed

Law, Y; Cheung, Polly S Y; Lau, Silvia; Lo, Gladys G

2013-08-01

To review the impact of preoperative breast magnetic resonance imaging on the management of planned surgery, and the appropriateness of any resulting alterations. Retrospective review. A private hospital in Hong Kong. PATIENTS; For the 147 consecutive biopsy-proven breast cancer patients who underwent preoperative magnetic resonance imaging to determine tumour extent undergoing operation by a single surgeon between 1 January 2006 and 31 December 2009, the impact of magnetic resonance imaging findings was reviewed in terms of management alterations and their appropriateness. The most common indication for breast magnetic resonance imaging was the presence of multiple indeterminate shadows on ultrasound scans (53%), followed by ill-defined border of the main tumour on ultrasound scans (19%). In 66% (97 out of 147) of the patients, the extent of the operation was upgraded. Upgrading entailed: lumpectomy to wider lumpectomy (23 out of 97), lumpectomy to mastectomy (47 out of 97), lumpectomy to bilateral lumpectomy (15 out of 97), and other (12 out of 97). Mostly, these management changes were because magnetic resonance imaging showed more extensive disease (n=29), additional cancer foci (n=39), or contralateral disease (n=24). In five instances, upgrading was due to patient preference. In 34% (50 out of 147) of the patients, there was no change in the planned operation. Regarding 97 of the patients having altered management, in 12 the changes were considered inappropriately extensive (due to false-positive magnetic resonance imaging findings). In terms of magnetic resonance imaging detection of more extensive, multifocal, multicentric, or contralateral disease, the false-positive rate was 13% and false-negative rate 7%. Corresponding rates for sensitivity and specificity were 95% and 81%, using the final pathology as the gold standard. Preoperative magnetic resonance imaging had a clinically significant and mostly correct impact on management plans. Magnetic resonance imaging should be included as part of the preoperative investigation in patients planned for breast-conserving surgery, in whom there are doubts about the extent of the tumours based on conventional assessment.

Defining Smallness for Gestational Age in the Early Years of the Danish Medical Birth Registry

PubMed Central

Rogvi, Rasmus á.; Mathiasen, Rene; Greisen, Gorm

2011-01-01

Background Being born small for gestational age (SGA) is associated with decreased insulin sensitivity and increased blood pressure in childhood, but the association with clinical disease in early adulthood is less certain. The Danish Medical Birth Registry has registered all births in Denmark since 1973, but due to variable data quality, data is most often used only from 1981 onwards, and birth registers in other countries may have similar problems for the early years. We wanted to examine whether the data can be used for identification of children born SGA and used in future research. Methodology/Principal Findings All persons born between 1974 and 1996 were identified in the Danish Medical Birth Registry (n = 1.704.890). Immigrants and children without data on gestational age and birth weight were excluded, and a total of 1.348.106 children were included in the analysis. The difference between the different variables used in the history of the registry were examined, and the quality of data in the birth registry from 1974-1981 was examined and compared to subsequent years. Data on birth weight and gestational age in the early years of the registry is inconsistent, and the identification of children born SGA is inaccurate, with 49% false-positives. The biggest source of error is due to the rough and inaccurate intervals used for gestational age. By using –3 standard deviations as a cut-off for the identification of children born SGA, the number of false-positives was reduced to 9%, while the amount of false-negatives were increased. Conclusion Choosing –3 standard deviations for identifying children born SGA is a viable, though not optimal solution for identifying children born SGA. Overall the data in the registry is of sufficient quality to be used in further medical research. PMID:21304958

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

PubMed

Paixão, Enny S; Harron, Katie; Andrade, Kleydson; Teixeira, Maria Glória; Fiaccone, Rosemeire L; Costa, Maria da Conceição N; Rodrigues, Laura C

2017-07-17

Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes.

Consensus QSAR model for identifying novel H5N1 inhibitors.

PubMed

Sharma, Nitin; Yap, Chun Wei

2012-08-01

Due to the importance of neuraminidase in the pathogenesis of influenza virus infection, it has been regarded as the most important drug target for the treatment of influenza. Resistance to currently available drugs and new findings related to structure of the protein requires novel neuraminidase 1 (N1) inhibitors. In this study, a consensus QSAR model with defined applicability domain (AD) was developed using published N1 inhibitors. The consensus model was validated using an external validation set. The model achieved high sensitivity, specificity, and overall accuracy along with low false positive rate (FPR) and false discovery rate (FDR). The performance of model on the external validation set and training set were comparable, thus it was unlikely to be overfitted. The low FPR and low FDR will increase its accuracy in screening large chemical libraries. Screening of ZINC library resulted in 64,772 compounds as probable N1 inhibitors, while 173,674 compounds were defined to be outside the AD of the consensus model. The advantage of the current model is that it was developed using a large and diverse dataset and has a defined AD which prevents its use on compounds that it is not capable of predicting. The consensus model developed in this study is made available via the free software, PaDEL-DDPredictor.

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.

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.

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.

TU-G-204-09: The Effects of Reduced- Dose Lung Cancer Screening CT On Lung Nodule Detection Using a CAD Algorithm

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

Young, S; Lo, P; Kim, G

2015-06-15

Purpose: While Lung Cancer Screening CT is being performed at low doses, the purpose of this study was to investigate the effects of further reducing dose on the performance of a CAD nodule-detection algorithm. Methods: We selected 50 cases from our local database of National Lung Screening Trial (NLST) patients for which we had both the image series and the raw CT data from the original scans. All scans were acquired with fixed mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare). All images were reconstructed with 1-mm slice thickness, B50 kernel.more » 10 of the cases had at least one nodule reported on the NLST reader forms. Based on a previously-published technique, we added noise to the raw data to simulate reduced-dose versions of each case at 50% and 25% of the original NLST dose (i.e. approximately 1.0 and 0.5 mGy CTDIvol). For each case at each dose level, the CAD detection algorithm was run and nodules greater than 4 mm in diameter were reported. These CAD results were compared to “truth”, defined as the approximate nodule centroids from the NLST reports. Subject-level mean sensitivities and false-positive rates were calculated for each dose level. Results: The mean sensitivities of the CAD algorithm were 35% at the original dose, 20% at 50% dose, and 42.5% at 25% dose. The false-positive rates, in decreasing-dose order, were 3.7, 2.9, and 10 per case. In certain cases, particularly in larger patients, there were severe photon-starvation artifacts, especially in the apical region due to the high-attenuating shoulders. Conclusion: The detection task was challenging for the CAD algorithm at all dose levels, including the original NLST dose. However, the false-positive rate at 25% dose approximately tripled, suggesting a loss of CAD robustness somewhere between 0.5 and 1.0 mGy. NCI grant U01 CA181156 (Quantitative Imaging Network); Tobacco Related Disease Research Project grant 22RT-0131.« less

Challenging a bioinformatic tool’s ability to detect microbial contaminants using in silico whole genome sequencing data

PubMed Central

Zook, Justin M.; Morrow, Jayne B.; Lin, Nancy J.

2017-01-01

High sensitivity methods such as next generation sequencing and polymerase chain reaction (PCR) are adversely impacted by organismal and DNA contaminants. Current methods for detecting contaminants in microbial materials (genomic DNA and cultures) are not sensitive enough and require either a known or culturable contaminant. Whole genome sequencing (WGS) is a promising approach for detecting contaminants due to its sensitivity and lack of need for a priori assumptions about the contaminant. Prior to applying WGS, we must first understand its limitations for detecting contaminants and potential for false positives. Herein we demonstrate and characterize a WGS-based approach to detect organismal contaminants using an existing metagenomic taxonomic classification algorithm. Simulated WGS datasets from ten genera as individuals and binary mixtures of eight organisms at varying ratios were analyzed to evaluate the role of contaminant concentration and taxonomy on detection. For the individual genomes the false positive contaminants reported depended on the genus, with Staphylococcus, Escherichia, and Shigella having the highest proportion of false positives. For nearly all binary mixtures the contaminant was detected in the in-silico datasets at the equivalent of 1 in 1,000 cells, though F. tularensis was not detected in any of the simulated contaminant mixtures and Y. pestis was only detected at the equivalent of one in 10 cells. Once a WGS method for detecting contaminants is characterized, it can be applied to evaluate microbial material purity, in efforts to ensure that contaminants are characterized in microbial materials used to validate pathogen detection assays, generate genome assemblies for database submission, and benchmark sequencing methods. PMID:28924496

Comparative diagnostic value of 18F-fluoride PET-CT versus MRI for skull-base bone invasion in nasopharyngeal carcinoma.

PubMed

Le, Yali; Chen, Yu; Zhou, Fan; Liu, Guangfu; Huang, Zhanwen; Chen, Yue

2016-10-01

This study compared the diagnostic value of F-fluoride PET-computed tomography (PET-CT) and MRI in skull-base bone erosion in nasopharyngeal carcinoma (NPC) patients. A total of 93 patients with biopsy-confirmed NPC were enrolled, including 68 men and 25 women between 23 and 74 years of age. All patients were evaluated by both F-fluoride PET-CT and MRI, and the interval between the two imaging examinations was less than 20 days. The patients received no treatment either before or between scans. The studies were interpreted by two nuclear medicine physicians or two radiologists with more than 10 years of professional experience who were blinded to both the diagnosis and the results of the other imaging studies. The reference standard was skull-base bone erosion at a 20-week follow-up imaging study. On the basis of the results of the follow-up imaging studies, 52 patients showed skull-base bone erosion. The numbers of true positives, false positives, true negatives, and false negatives with F-fluoride PET-CT were 49, 4, 37, and 3, respectively. The numbers of true positives, false positives, true negatives, and false negatives with MRI were 46, 5, 36, and 6, respectively. The sensitivity, specificity, and crude accuracy of F-fluoride PET-CT were 94.23, 90.24, and 92.47%, respectively; for MRI, these values were 88.46, 87.80, and 88.17%. Of the 52 patients, 43 showed positive findings both on F-fluoride PET-CT and on MRI. Within the patient cohort, F-fluoride PET-CT and MRI detected 178 and 135 bone lesions, respectively. Both F-fluoride PET-CT and MRI have high sensitivity, specificity, and crude accuracy for detecting skull-base bone invasion in patients with NPC. F-fluoride PET-CT detected more lesions than did MRI in the skull-base bone. This suggests that F-fluoride PET-CT has a certain advantage in evaluating the skull-base bone of NPC patients. Combining the two methods could improve the diagnostic accuracy of skull-base bone invasion for NPC.

Microvascular autonomic dysfunction may justify false-positive stress myocardial perfusion imaging in patients with liver cirrhosis undergoing liver transplantation.

PubMed

Senzolo, M; Bassanello, M; Graziotto, A; Zucchetta, P; Cillo, U; Maraglino, G; Loreno, M; Bellotto, F; Davià, G; Burra, P

2008-01-01

Up to 15% of liver transplant candidates have asymptomatic coronary artery diseases, which increase the risk of cardiac complications during and after transplantation. The aim of this study was to prospectively investigate the usefulness of an integrated cardiological approach in cirrhotic patients undergoing liver transplantation. Twenty-four consecutive patients undergoing evaluation for liver transplantation were studied by assessing risk factors for coronary artery diseases, electrocardiogram with QTc interval determination, chest X-ray, echocardiography, 24-hour Holter monitor, myocardial perfusion scintigraphy (99mTc)MIBI-GSPECT at rest and after dipyridamole infusion. Cardiac (123)I-metaiodobenzylguanidine (MIBG) scan and coronarography were performed in patients with myocardial perfusion defects. Twenty three of 24 patients underwent successful liver transplantation; one patient died on the waiting list. Before liver transplantation, 29% of patients were diabetic and 41% were smokers. Eleven of 24 patients had a prolonged QTc interval, and 3/24 had positive myocardioscintigraphy after dipyridamole infusion: in two coronarography was negative, while the (123)I-MIBG washout was altered. No cardiac events were recorded during the short-and long-term follow-up after surgery. Predictive value of positive cardiac (99mTc)MIBI-GSPECT in patients with liver cirrhosis is low, and this may be due to alterations of cardiac microvascular tone as showed by cardiac (123)I-MIBG scan.

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.

Evaluation of Natural Language Processing (NLP) Systems to Annotate Drug Product Labeling with MedDRA Terminology.

PubMed

Ly, Thomas; Pamer, Carol; Dang, Oanh; Brajovic, Sonja; Haider, Shahrukh; Botsis, Taxiarchis; Milward, David; Winter, Andrew; Lu, Susan; Ball, Robert

2018-05-31

The FDA Adverse Event Reporting System (FAERS) is a primary data source for identifying unlabeled adverse events (AEs) in a drug or biologic drug product's postmarketing phase. Many AE reports must be reviewed by drug safety experts to identify unlabeled AEs, even if the reported AEs are previously identified, labeled AEs. Integrating the labeling status of drug product AEs into FAERS could increase report triage and review efficiency. Medical Dictionary for Regulatory Activities (MedDRA) is the standard for coding AE terms in FAERS cases. However, drug manufacturers are not required to use MedDRA to describe AEs in product labels. We hypothesized that natural language processing (NLP) tools could assist in automating the extraction and MedDRA mapping of AE terms in drug product labels. We evaluated the performance of three NLP systems, (ETHER, I2E, MetaMap) for their ability to extract AE terms from drug labels and translate the terms to MedDRA Preferred Terms (PTs). Pharmacovigilance-based annotation guidelines for extracting AE terms from drug labels were developed for this study. We compared each system's output to MedDRA PT AE lists, manually mapped by FDA pharmacovigilance experts using the guidelines, for ten drug product labels known as the "gold standard AE list" (GSL) dataset. Strict time and configuration conditions were imposed in order to test each system's capabilities under conditions of no human intervention and minimal system configuration. Each NLP system's output was evaluated for precision, recall and F measure in comparison to the GSL. A qualitative error analysis (QEA) was conducted to categorize a random sample of each NLP system's false positive and false negative errors. A total of 417, 278, and 250 false positive errors occurred in the ETHER, I2E, and MetaMap outputs, respectively. A total of 100, 80, and 187 false negative errors occurred in ETHER, I2E, and MetaMap outputs, respectively. Precision ranged from 64% to 77%, recall from 64% to 83% and F measure from 67% to 79%. I2E had the highest precision (77%), recall (83%) and F measure (79%). ETHER had the lowest precision (64%). MetaMap had the lowest recall (64%). The QEA found that the most prevalent false positive errors were context errors such as "Context error/General term", "Context error/Instructions or monitoring parameters", "Context error/Medical history preexisting condition underlying condition risk factor or contraindication", and "Context error/AE manifestations or secondary complication". The most prevalent false negative errors were in the "Incomplete or missed extraction" error category. Missing AE terms were typically due to long terms, or terms containing non-contiguous words which do not correspond exactly to MedDRA synonyms. MedDRA mapping errors were a minority of errors for ETHER and I2E but were the most prevalent false positive errors for MetaMap. The results demonstrate that it may be feasible to use NLP tools to extract and map AE terms to MedDRA PTs. However, the NLP tools we tested would need to be modified or reconfigured to lower the error rates to support their use in a regulatory setting. Tools specific for extracting AE terms from drug labels and mapping the terms to MedDRA PTs may need to be developed to support pharmacovigilance. Conducting research using additional NLP systems on a larger, diverse GSL would also be informative. Copyright © 2018. Published by Elsevier Inc.

A Metric for Reducing False Positives in the Computer-Aided Detection of Breast Cancer from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Based Screening Examinations of High-Risk Women.

PubMed

Levman, Jacob E D; Gallego-Ortiz, Cristina; Warner, Ellen; Causer, Petrina; Martel, Anne L

2016-02-01

Magnetic resonance imaging (MRI)-enabled cancer screening has been shown to be a highly sensitive method for the early detection of breast cancer. Computer-aided detection systems have the potential to improve the screening process by standardizing radiologists to a high level of diagnostic accuracy. This retrospective study was approved by the institutional review board of Sunnybrook Health Sciences Centre. This study compares the performance of a proposed method for computer-aided detection (based on the second-order spatial derivative of the relative signal intensity) with the signal enhancement ratio (SER) on MRI-based breast screening examinations. Comparison is performed using receiver operating characteristic (ROC) curve analysis as well as free-response receiver operating characteristic (FROC) curve analysis. A modified computer-aided detection system combining the proposed approach with the SER method is also presented. The proposed method provides improvements in the rates of false positive markings over the SER method in the detection of breast cancer (as assessed by FROC analysis). The modified computer-aided detection system that incorporates both the proposed method and the SER method yields ROC results equal to that produced by SER while simultaneously providing improvements over the SER method in terms of false positives per noncancerous exam. The proposed method for identifying malignancies outperforms the SER method in terms of false positives on a challenging dataset containing many small lesions and may play a useful role in breast cancer screening by MRI as part of a computer-aided detection system.

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.

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.

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.

A critical reappraisal of false negative sentinel lymph node biopsy in melanoma.

PubMed

Manca, G; Romanini, A; Rubello, D; Mazzarri, S; Boni, G; Chiacchio, S; Tredici, M; Duce, V; Tardelli, E; Volterrani, D; Mariani, G

2014-06-01

Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. Several large-scale studies have reported a relatively high false-negative rate (5.6-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the prognosis of melanoma patients. Indeed, most studies have failed to show that there is worse melanoma-specific survival for false-negative compared to true-positive SLNB patients.

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.

Further evidence of the cross-reactivity of the Binax NOW® Filariasis ICT cards to non-Wuchereria bancrofti filariae: experimental studies with Loa loa and Onchocerca ochengi.

PubMed

Wanji, Samuel; Amvongo-Adjia, Nathalie; Njouendou, Abdel Jelil; Kengne-Ouafo, Jonas Arnaud; Ndongmo, Winston Patrick Chounna; Fombad, Fanny Fri; Koudou, Benjamin; Enyong, Peter A; Bockarie, Moses

2016-05-05

The immunochromatographic test (ICT) for lymphatic filariasis is a serological test designed for unequivocal detection of circulating Wuchereria bancrofti antigen. It was validated and promoted by WHO as the primary diagnostic tool for mapping and impact monitoring for disease elimination following interventions. The initial tests for specificity and sensitivity were based on samples collected in areas free of loiasis and the results suggested a near 100% specificity for W. bancrofti. The possibility of cross-reactivity with non-Wuchereria bancrofti antigens was not investigated until recently, when false positive results were observed in three independent studies carried out in Central Africa. Associations were demonstrated between ICT positivity and Loa loa microfilaraemia, but it was not clearly established if these false positive results were due to L. loa or can be extended to other filarial nematodes. This study brought further evidences of the cross-reactivity of ICT card with L. loa and Onchocerca ochengi (related to O. volvulus parasite) using in vivo and in vitro systems. Two filarial/host experimental systems (L. loa-baboon and O. ochengi-cattle) and the in vitro maintenance of different stages (microfilariae, infective larvae and adult worm) of the two filariae were used in three experiments per filarial species. First, whole blood and sera samples were prepared from venous blood of patent baboons and cattle, and applied on ICT cards to detect circulating filarial antigens. Secondly, larval stages of L. loa and O. ochengi as well as O. ochengi adult males were maintained in vitro. Culture supernatants were collected and applied on ICT cards after 6, 12 and 24 h of in vitro maintenance. Finally, total worm extracts (TWE) were prepared using L. loa microfilariae (Mf) and O. ochengi microfilariae, infective larvae and adult male worms. TWE were also tested on ICT cards. For each experiment, control assays (whole blood and sera from uninfected babon/cattle, culture medium and extraction buffer) were performed. Positive ICT results were obtained with whole blood and sera of L. loa microfilaremic baboons, culture supernatants of L. loa Mf and infective larvae as well as with L. loa Mf protein extracts. In contrast, negative ICT results were observed with whole blood and sera from the O. ochengi-cattle system. Surprisingly, culture supernatant of O. ochengi adult males and total worm extracts (Mf, infective larvae and adult worm) were positive to the test. This study has provided further evidence of L. loa cross-reactivity for the ICT card. All stages of L. loa seem capable of inducing the cross-reactivity. Onchocerca ochengi. can also induce cross-reactivity in vitro, but this is less likely in vivo due to the location of parasite. The availability of the parasite proteins in the blood stream determines the magnitude of the cross-reactivity. The cross-reactivity of the ICT card to these non-W. bancrofti filariae poses some doubts to the reliability and validity of the current map of LF of Central Africa that was generated using this diagnostic tool.

Can missed breast cancer be recognized by regular peer auditing on screening mammography?

PubMed

Pan, Huay-Ben; Yang, Tsung-Lung; Hsu, Giu-Cheng; Chiang, Chia-Ling; Huang, Jer-Shyung; Chou, Chen-Pin; Wang, Yen-Chi; Liang, Huei-Lung; Lee, San-Kan; Chou, Yi-Hong; Wong, Kam-Fai

2012-09-01

This study was conducted to investigate whether detectable missed breast cancers could be distinguished from truly false negative images in a mammographic screening by a regular peer auditing. Between 2004 and 2007, a total of 311,193 free nationwide biennial mammographic screenings were performed for 50- to 69-year-old women in Taiwan. Retrospectively comparing the records in Taiwan's Cancer registry, 1283 cancers were detected (4.1 per 1000). Of the total, 176 (0.6 per 1000) initial mammographic negative assessments were reported to have cancers (128 traditional films and 48 laser-printed digital images). We selected 186 true negative films (138 traditional films and 48 laser-printed ones) as control group. These were seeded into 4815 films of 2008 images to be audited in 2009. Thirty-four auditors interpreted all the films in a single-blind, randomized, pair-control study. The performance of 34 auditors was analyzed by chi-square test. A p value of < 0.05 was considered significant. Eight (6 traditional and 2 digital films) of the 176 false negative films were not reported by the auditors (missing rate of 4.5%). Of this total, 87 false negatives were reassessed as positive, while 29 of the 186 true negatives were reassessed as positive, making the overall performance of the 34 auditors in interpreting the false negatives and true negatives a specificity of 84.4% and sensitivity of 51.8%. The specificity and sensitivity in traditional films and laser-printed films were 98.6% versus 43.8% and 41.8% versus 78.3%, respectively. Almost 42% of the traditional false negative films had positive reassessment by the auditors, showing a significant difference from the initial screeners (p < 0.001). The specificity of their reinterpretation of laser-printed films was obviously low. Almost 42% of the false negative traditional films were judged as missed cancers in this study. A peer auditing should reduce the probability of missed cancers. 2012 Published by Elsevier B.V

A likelihood ratio anomaly detector for identifying within-perimeter computer network attacks

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

Grana, Justin; Wolpert, David; Neil, Joshua

The rapid detection of attackers within firewalls of enterprise computer networks is of paramount importance. Anomaly detectors address this problem by quantifying deviations from baseline statistical models of normal network behavior and signaling an intrusion when the observed data deviates significantly from the baseline model. But, many anomaly detectors do not take into account plausible attacker behavior. As a result, anomaly detectors are prone to a large number of false positives due to unusual but benign activity. Our paper first introduces a stochastic model of attacker behavior which is motivated by real world attacker traversal. Then, we develop a likelihoodmore » ratio detector that compares the probability of observed network behavior under normal conditions against the case when an attacker has possibly compromised a subset of hosts within the network. Since the likelihood ratio detector requires integrating over the time each host becomes compromised, we illustrate how to use Monte Carlo methods to compute the requisite integral. We then present Receiver Operating Characteristic (ROC) curves for various network parameterizations that show for any rate of true positives, the rate of false positives for the likelihood ratio detector is no higher than that of a simple anomaly detector and is often lower. Finally, we demonstrate the superiority of the proposed likelihood ratio detector when the network topologies and parameterizations are extracted from real-world networks.« less

A likelihood ratio anomaly detector for identifying within-perimeter computer network attacks

DOE PAGES

Grana, Justin; Wolpert, David; Neil, Joshua; ...

2016-03-11

The rapid detection of attackers within firewalls of enterprise computer networks is of paramount importance. Anomaly detectors address this problem by quantifying deviations from baseline statistical models of normal network behavior and signaling an intrusion when the observed data deviates significantly from the baseline model. But, many anomaly detectors do not take into account plausible attacker behavior. As a result, anomaly detectors are prone to a large number of false positives due to unusual but benign activity. Our paper first introduces a stochastic model of attacker behavior which is motivated by real world attacker traversal. Then, we develop a likelihoodmore » ratio detector that compares the probability of observed network behavior under normal conditions against the case when an attacker has possibly compromised a subset of hosts within the network. Since the likelihood ratio detector requires integrating over the time each host becomes compromised, we illustrate how to use Monte Carlo methods to compute the requisite integral. We then present Receiver Operating Characteristic (ROC) curves for various network parameterizations that show for any rate of true positives, the rate of false positives for the likelihood ratio detector is no higher than that of a simple anomaly detector and is often lower. Finally, we demonstrate the superiority of the proposed likelihood ratio detector when the network topologies and parameterizations are extracted from real-world networks.« less

[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.

Chromosome 9p21 In Ischemic Stroke: Population Structure and Meta-Analysis

PubMed Central

Anderson, CD; Biffi, A; Rost, NS; Cortellini, L; Furie, KL; Rosand, J

2011-01-01

Background and Purpose Sequence variants on chromosome 9p21.3 are implicated in coronary artery disease (CAD) and myocardial infarction (MI), but studies in ischemic stroke have produced inconsistent results. We investigated whether these conflicting findings were due to false positive studies confounded by population stratification, or false negative studies that failed to account for effects specific to certain stroke subtypes. Methods After assessing for population stratification at 9p21.3 using genome-wide data, we meta-analyzed 8 ischemic stroke studies. This analysis focused on two single nucleotide polymorphisms (SNPs), rs1537378 and rs10757278, as these variants are in strong linkage disequilibrium with most SNPs analyzed in prior studies of the region. Results Principal component analysis of the genome-wide data showed no evidence of population stratification at that locus. Meta-analysis confirmed that both rs1537378 and rs10757278 are risk factors for ischemic stroke (odds ratios 1.09, [p = 0.0014], and 1.11, [p = 0.001] respectively). Subtype analysis revealed a substantial increase in the effect of each SNP for risk of large artery (LA) stroke, achieving an effect size similar to that seen in CAD/MI. Conclusions Variants on 9p21.3 are associated with ischemic stroke, and restriction of analysis to LA stroke increases effect size towards that observed in prior association studies of CAD/MI. Previous inconsistent findings are best explained by this subtype-specificity rather than any unmeasured confounding by population stratification. PMID:20395606

[A case of systemic lupus erythematosus discovered from left heart failure due to lupus induced mitral regurgitation].

PubMed

Ueno, K; Fujimoto, S; Fujimoto, T; Nakano, H; Nakajima, T; Yamano, S; Shiiki, H; Hashimoto, T; Imoto, K; Miyagawa, S; Dohi, K

1999-10-01

A 50-year-old female was admitted to a local hospital because of dyspnea, and diagnosed as having left heart failure secondary to mitral regurgitation. After the improvement of congestive heart failure, polyarthralgia, fever, and positive anti-nuclear antibody were pointed out. She was referred to our hospital for the further evaluation. Serological test showed anti-double stranded DNA antibodies, anti-SS-A antibodies, anti-beta 2-GPI antibodies and biological false positive for syphilis. The diagnosis of SLE has been made from the clinical signs and the serology. Therefore mitral valvular lesion of this patient was considered to be one of the symptoms of SLE. We reported a rare case in which left heart failure was a initial clinical manifestation of SLE.

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.

Massive-training artificial neural network (MTANN) for reduction of false positives in computer-aided detection of polyps: Suppression of rectal tubes

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

Suzuki, Kenji; Yoshida, Hiroyuki; Naeppi, Janne

2006-10-15

One of the limitations of the current computer-aided detection (CAD) of polyps in CT colonography (CTC) is a relatively large number of false-positive (FP) detections. Rectal tubes (RTs) are one of the typical sources of FPs because a portion of a RT, especially a portion of a bulbous tip, often exhibits a cap-like shape that closely mimics the appearance of a small polyp. Radiologists can easily recognize and dismiss RT-induced FPs; thus, they may lose their confidence in CAD as an effective tool if the CAD scheme generates such ''obvious'' FPs due to RTs consistently. In addition, RT-induced FPs maymore » distract radiologists from less common true positives in the rectum. Therefore, removal RT-induced FPs as well as other types of FPs is desirable while maintaining a high sensitivity in the detection of polyps. We developed a three-dimensional (3D) massive-training artificial neural network (MTANN) for distinction between polyps and RTs in 3D CTC volumetric data. The 3D MTANN is a supervised volume-processing technique which is trained with input CTC volumes and the corresponding ''teaching'' volumes. The teaching volume for a polyp contains a 3D Gaussian distribution, and that for a RT contains zeros for enhancement of polyps and suppression of RTs, respectively. For distinction between polyps and nonpolyps including RTs, a 3D scoring method based on a 3D Gaussian weighting function is applied to the output of the trained 3D MTANN. Our database consisted of CTC examinations of 73 patients, scanned in both supine and prone positions (146 CTC data sets in total), with optical colonoscopy as a reference standard for the presence of polyps. Fifteen patients had 28 polyps, 15 of which were 5-9 mm and 13 were 10-25 mm in size. These CTC cases were subjected to our previously reported CAD scheme that included centerline-based segmentation of the colon, shape-based detection of polyps, and reduction of FPs by use of a Bayesian neural network based on geometric and texture features. Application of this CAD scheme yielded 96.4% (27/28) by-polyp sensitivity with 3.1 (224/73) FPs per patient, among which 20 FPs were caused by RTs. To eliminate the FPs due to RTs and possibly other normal structures, we trained a 3D MTANN with ten representative polyps and ten RTs, and applied the trained 3D MTANN to the above CAD true- and false-positive detections. In the output volumes of the 3D MTANN, polyps were represented by distributions of bright voxels, whereas RTs and other normal structures partly similar to RTs appeared as darker voxels, indicating the ability of the 3D MTANN to suppress RTs as well as other normal structures effectively. Application of the 3D MTANN to the CAD detections showed that the 3D MTANN eliminated all RT-induced 20 FPs, as well as 53 FPs due to other causes, without removal of any true positives. Overall, the 3D MTANN was able to reduce the FP rate of the CAD scheme from 3.1 to 2.1 FPs per patient (33% reduction), while the original by-polyp sensitivity of 96.4% was maintained.« less

Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance.

PubMed

Bevilacqua, Elisa; Ordóñez, Elena; Hurtado, Ivan; Rueda, Laura; Mazzone, Eléonora; Cirigliano, Vincenzo; Jani, Jacques C

2017-08-23

To study patient choice regarding testing for sex chromosome aneuploidy (SCA) and the performance of cell-free DNA (cfDNA) screening for SCA. Patient choice regarding screening for SCA and factors influencing this choice were evaluated in a single center. In a subsequent two-center study, cases that screened positive for SCA were analyzed to determine the positive predictive value (PPV) for each SCA. In all, 1,957 (61.9%) of the 3,162 patients undergoing cfDNA testing opted for SCA screening. Regression analysis demonstrated that independent predictors of a patient's decision for SCA were earlier gestational age, spontaneous conception, and cfDNA chosen as a primary method of screening. A total of 161 cases screened positive for SCA and follow-up data were available for 118 (73.3%). Forty-six of the 61 cases of 45,X were false-positive results and 15 were concordant with the fetal karyotype (PPV = 24.6%). Seventeen of the 22 cases of 47,XXX were false positive and 5 concordant (PPV = 22.7%). Eleven of the 30 cases of 47,XXY were false positive and 19 concordant (PPV = 63.3%). All 5 cases of 47,XYY were correctly identified, thus yielding a PPV of 100%. More than half of the patients undergoing cfDNA aneuploidy screening also opted for SCA testing, but they were less likely to do so in the presence of an increased risk of trisomy. SCAs involving the X chromosome had a lower PPV than those involving the Y chromosome. © 2017 S. Karger AG, Basel.

Increased perceived self-efficacy facilitates the extinction of fear in healthy participants

PubMed Central

Zlomuzica, Armin; Preusser, Friederike; Schneider, Silvia; Margraf, Jürgen

2015-01-01

Self-efficacy has been proposed as an important element of a successful cognitive behavioral treatment (CBT). Positive changes in perceived self-efficacy have been linked to an improved adaptive emotional and behavioral responding in the context of anxiety-provoking situations. Furthermore, a positive influence of increased self-efficacy on cognitive functions has been confirmed. The present study examined the effect of verbal persuasion on perceived self-efficacy and fear extinction. Healthy participants were subjected to a standardized differential fear conditioning paradigm. After fear acquisition, half of the participants received a verbal persuasion aimed at increasing perceived self-efficacy. The extinction of fear was assessed immediately thereafter on both the implicit and explicit level. Our results suggest that an increased perceived self-efficacy was associated with enhanced extinction, evidenced on the psychophysiological level and accompanied by more pronounced decrements in conditioned negative valence. Changes in extinction were not due to a decrease in overall emotional reactivity to conditioned stimuli (CS). In addition, debriefing participants about the false positive feedback did not affect the processing of already extinguished conditioned responses during a subsequent continued extinction phase. Our results suggest that positive changes in perceived self-efficacy can be beneficial for emotional learning. Findings are discussed with respect to strategies aimed at increasing extinction learning in the course of exposure-based treatments. PMID:26528152