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

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.

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

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.

Variants and pitfalls on radioiodine scans in pediatric patients with differentiated thyroid carcinoma.

PubMed

Mostafa, Mohamed; Vali, Reza; Chan, Jeffrey; Omarkhail, Yusuaf; Shammas, Amer

2016-10-01

Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data.

False Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease-Disinhibition or Amnesia?

PubMed

Flanagan, Emma C; Wong, Stephanie; Dutt, Aparna; Tu, Sicong; Bertoux, Maxime; Irish, Muireann; Piguet, Olivier; Rao, Sulakshana; Hodges, John R; Ghosh, Amitabha; Hornberger, Michael

2016-01-01

Episodic memory recall processes in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas recognition performance is more variable. A potential reason for this variability could be false-positive errors made on recognition trials and whether these errors are due to amnesia per se or a general over-endorsement of recognition items regardless of memory. The current study addressed this issue by analysing recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39 bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD patients were comparably impaired on delayed recall, bvFTD patients showed intact recognition performance in terms of the number of correct hits. However, both patient groups endorsed significantly more false-positives than controls, and bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits-false-positives). Furthermore, measures of disinhibition were significantly associated with false positives in both groups, with a stronger relationship with false-positives in bvFTD. Voxel-based morphometry analyses revealed similar neural correlates of false positive endorsement across bvFTD and AD, with both patient groups showing involvement of prefrontal and Papez circuitry regions, such as medial temporal and thalamic regions, and a DTI analysis detected an emerging but non-significant trend between false positives and decreased fornix integrity in bvFTD only. These findings suggest that false-positive errors on recognition tests relate to similar mechanisms in bvFTD and AD, reflecting deficits in episodic memory processes and disinhibition. These findings highlight that current memory tests are not sufficient to accurately distinguish between bvFTD and AD patients.

False positives in psychiatric diagnosis: implications for human freedom.

PubMed

Wakefield, Jerome C

2010-02-01

Current symptom-based DSM and ICD diagnostic criteria for mental disorders are prone to yielding false positives because they ignore the context of symptoms. This is often seen as a benign flaw because problems of living and emotional suffering, even if not true disorders, may benefit from support and treatment. However, diagnosis of a disorder in our society has many ramifications not only for treatment choice but for broader social reactions to the diagnosed individual. In particular, mental disorders impose a sick role on individuals and place a burden upon them to change; thus, disorders decrease the level of respect and acceptance generally accorded to those with even annoying normal variations in traits and features. Thus, minimizing false positives is important to a pluralistic society. The harmful dysfunction analysis of disorder is used to diagnose the sources of likely false positives, and propose potential remedies to the current weaknesses in the validity of diagnostic criteria.

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

PubMed

Bhattacharya, Rahul; Barton, Simon; Catalan, Jose

2008-05-01

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

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.

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.

PREDICTING ABUSE POTENTIAL OF STIMULANTS AND OTHER DOPAMINERGIC DRUGS: OVERVIEW AND RECOMMENDATIONS

PubMed Central

Huskinson, Sally L.; Naylor, Jennifer E.; Rowlett, James K.; Freeman, Kevin B.

2014-01-01

Examination of a drug’s abuse potential at multiple levels of analysis (molecular/cellular action, whole-organism behavior, epidemiological data) is an essential component to regulating controlled substances under the Controlled Substances Act (CSA). We reviewed studies that examined several central nervous system (CNS) stimulants, focusing on those with primarily dopaminergic actions, in drug self-administration, drug discrimination, and physical dependence. For drug self-administration and drug discrimination, we distinguished between experiments conducted with rats and nonhuman primates (NHP) to highlight the common and unique attributes of each model in the assessment of abuse potential. Our review of drug self-administration studies suggests that this procedure is important in predicting abuse potential of dopaminergic compounds, but there were many false positives. We recommended that tests to determine how reinforcing a drug is relative to a known drug of abuse may be more predictive of abuse potential than tests that yield a binary, yes-or-no classification. Several false positives also occurred with drug discrimination. With this procedure, we recommended that future research follow a standard decision-tree approach that may require examining the drug being tested for abuse potential as the training stimulus. This approach would also allow several known drugs of abuse to be tested for substitution, and this may reduce false positives. Finally, we reviewed evidence of physical dependence with stimulants and discussed the feasibility of modeling these phenomena in nonhuman animals in a rational and practical fashion. PMID:24662599

Predicting abuse potential of stimulants and other dopaminergic drugs: overview and recommendations.

PubMed

Huskinson, Sally L; Naylor, Jennifer E; Rowlett, James K; Freeman, Kevin B

2014-12-01

Examination of a drug's abuse potential at multiple levels of analysis (molecular/cellular action, whole-organism behavior, epidemiological data) is an essential component to regulating controlled substances under the Controlled Substances Act (CSA). We reviewed studies that examined several central nervous system (CNS) stimulants, focusing on those with primarily dopaminergic actions, in drug self-administration, drug discrimination, and physical dependence. For drug self-administration and drug discrimination, we distinguished between experiments conducted with rats and nonhuman primates (NHP) to highlight the common and unique attributes of each model in the assessment of abuse potential. Our review of drug self-administration studies suggests that this procedure is important in predicting abuse potential of dopaminergic compounds, but there were many false positives. We recommended that tests to determine how reinforcing a drug is relative to a known drug of abuse may be more predictive of abuse potential than tests that yield a binary, yes-or-no classification. Several false positives also occurred with drug discrimination. With this procedure, we recommended that future research follow a standard decision-tree approach that may require examining the drug being tested for abuse potential as the training stimulus. This approach would also allow several known drugs of abuse to be tested for substitution, and this may reduce false positives. Finally, we reviewed evidence of physical dependence with stimulants and discussed the feasibility of modeling these phenomena in nonhuman animals in a rational and practical fashion. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-12-01

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

Induction detection of concealed bulk banknotes

NASA Astrophysics Data System (ADS)

Fuller, Christopher; Chen, Antao

2012-06-01

The smuggling of bulk cash across borders is a serious issue that has increased in recent years. In an effort to curb the illegal transport of large numbers of paper bills, a detection scheme has been developed, based on the magnetic characteristics of bank notes. The results show that volumes of paper currency can be detected through common concealing materials such as plastics, cardboard, and fabrics making it a possible potential addition to border security methods. The detection scheme holds the potential of also reducing or eliminating false positives caused by metallic materials found in the vicinity, by observing the stark difference in received signals caused by metal and currency. The detection scheme holds the potential to detect for both the presence and number of concealed bulk notes, while maintaining the ability to reduce false positives caused by metal objects.

Transformation-aware Exploit Generation using a HI-CFG

DTIC Science & Technology

2013-05-16

testing has many limitations of its own: it can require significant target -specific setup to perform well; it is unlikely to trigger vulnerabilities...check fails represents a potential vulnerability, but a conservative analysis can produce false positives , so we can use exploit generation to find...warnings that correspond to true positives . We can also find potentially vulnerable instructions in the course of a manual binary- level security audit

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.

Dye-binding assays for evaluation of the effects of small molecule inhibitors on amyloid (aβ) self-assembly.

PubMed

Jameson, Laramie P; Smith, Nicholas W; Dzyuba, Sergei V

2012-11-21

Dye-binding assays, such as those utilizing Congo red and thioflavin T, are among the most widely used tools to probe the aggregation of amyloidogenic biomolecules and for the evaluation of small molecule inhibitors of amyloid aggregation and fibrillization. A number of recent reports have indicated that these dye-binding assays could be prone to false positive effects when assessing inhibitors' potential toward Aβ peptides, species involved in Alzheimer's disease. Specifically, this review focuses on the application of thioflavin T for determining the efficiency of small molecule inhibitors of Aβ aggregation and addresses potential reasons that might be associated with the false positive effects in an effort to increase reliability of dye-binding assays.

Dye-Binding Assays for Evaluation of the Effects of Small Molecule Inhibitors on Amyloid (Aβ) Self-Assembly

PubMed Central

2012-01-01

Dye-binding assays, such as those utilizing Congo red and thioflavin T, are among the most widely used tools to probe the aggregation of amyloidogenic biomolecules and for the evaluation of small molecule inhibitors of amyloid aggregation and fibrillization. A number of recent reports have indicated that these dye-binding assays could be prone to false positive effects when assessing inhibitors’ potential toward Aβ peptides, species involved in Alzheimer’s disease. Specifically, this review focuses on the application of thioflavin T for determining the efficiency of small molecule inhibitors of Aβ aggregation and addresses potential reasons that might be associated with the false positive effects in an effort to increase reliability of dye-binding assays. PMID:23173064

The local lymph node assay being too sensitive?

PubMed

Hans-Werner, Vohr; Jürgen, Ahr Hans

2005-12-01

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

Neural Network Target Identification System for False Alarm Reduction

NASA Technical Reports Server (NTRS)

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

2009-01-01

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

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.

Assessing conservation lands for forest birds in an exurban landscape

Treesearch

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

2017-01-01

Exurban development is the fastest growing type of land use in the United States and is prominent in the southern Appalachian region. A potential consequence of exurban development is the loss and fragmentation of wildlife habitat. We used a Bayesian model that accounts for false positive and false negative detections to make inferences about how the occupancy...

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

PubMed

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

2008-04-01

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

Avoiding false positives and optimizing identification of true negatives in estrogen receptor binding and agonist/antagonist assays

EPA Science Inventory

The potential for chemicals to affect endocrine signaling is commonly evaluated via in vitro receptor binding and gene activation, but these assays, especially antagonism assays, have potential artifacts that must be addressed for accurate interpretation. Results are presented fr...

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

Placing symptoms in context: the role of contextual criteria in reducing false positives in Diagnostic and Statistical Manual of Mental Disorders diagnoses.

PubMed

Wakefield, Jerome C; First, Michael B

2012-02-01

The Diagnostic and Statistical Manual of Mental Disorders (DSM) definition of mental disorder requires that symptoms be caused by a dysfunction in the individual; when dysfunction is absent, symptoms represent normal-range distress or eccentricity and, if diagnosed as a mental disorder, are false positives. We hypothesized that because of psychiatry's lack of direct laboratory tests to distinguish dysfunction from normal-range distress, the context in which symptoms occur (eg, lack of imminent danger in a panic attack) is often essential to determining whether symptoms are caused by a dysfunction. If this is right, then the DSM diagnostic criteria should include many contextual criteria added to symptom syndromes to prevent dysfunction false positives. Despite their potential importance, such contextual criteria have not been previously reviewed. We, thus, systematically reviewed DSM categories to establish the extent of such uses of contextual criteria and created a typology of such uses. Of 111 sampled categories, 68 (61%) used context to prevent dysfunction false positives. Contextual criteria fell into 7 types: (1) exclusion of specific false-positive scenarios; (2) requiring that patients experience preconditions for normal responses (eg, requiring that individuals experience adequate sexual stimulation before being diagnosed with sexual dysfunctions); (3) requiring that symptoms be disproportionate relative to circumstances; (4) for childhood disorders, requiring that symptoms be developmentally inappropriate; (5) requiring that symptoms occur in multiple contexts; (6) requiring a substantial discrepancy between beliefs and reality; and (7) a residual category. Most DSM categories include contextual criteria to eliminate false-positive diagnoses and increase validity of descriptive criteria. Future revisions should systematically evaluate each category's need for contextual criteria. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed

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

2007-01-01

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

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.

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 .

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.

Intraoperative monitoring of somatosensory (SSEPs) and transcranial electric motor-evoked potentials (tce-MEPs) during surgical correction of neuromuscular scoliosis in patients with central or peripheral nervous system diseases.

PubMed

Pastorelli, F; Di Silvestre, M; Vommaro, F; Maredi, E; Morigi, A; Bacchin, M R; Bonarelli, S; Plasmati, R; Michelucci, R; Greggi, T

2015-11-01

Combined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials (tce-MEPs) and somatosensory-evoked potentials (SSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, the literature data regarding the reliability of spinal cord monitoring in patients with neuromuscular scoliosis are conflicting and need to be confirmed. We reviewed IOM records of 40 consecutive patients with neuromuscular scoliosis related to central nervous system (CNS) (29 pts) or peripheral nervous system (PNS) (11 patients) diseases, who underwent posterior fusion with instrumentation surgery for spinal deformity. Multimodalitary IOM with SSEPs and tce-MEPs was performed. Spinal cord monitoring using at least one modality was attempted in 38/40 (95 %) patients. No false-negative results were present in either group, but a relatively high incidence of false-positive cases (4/29, 13.8 %) was noted in the CNS group. Two patients in the CNS group and one patient in the PNS group presented transient postoperative motor deficits (true positive), related to surgical manoeuvres in two cases and to malposition in the other one. Multimodalitary IOM is safe and effective to detect impending spinal cord and peripheral nerves dysfunction in neuromuscular scoliosis surgery. However, the interpretation of neurophysiological data may be challenging in such patients, and the rate of false-positive results is high when pre-operatory motor deficits are severe.

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.

Missed Lesions at CT Colonography: Lessons Learned

PubMed Central

Pickhardt, Perry J.

2017-01-01

Misinterpretation at CT colonography (CTC) can result in either a colorectal lesion being missed (false negative) or a false-positive diagnosis. This review will largely focus on potential missed lesions – and ways to avoid such misses. The general causes of false-negative interpretation at CTC can be broadly characterized and grouped into discrete categories related to suboptimal study technique, specific lesion characteristics, anatomic location, and imaging artifacts. Overlapping causes further increase the likelihood of missing a clinically relevant lesion. In the end, if the technical factors of bowel preparation, colonic distention, and robust CTC software are adequately addressed on a consistent basis, and the reader is aware of all the potential pitfalls at CTC, important lesions will seldom be missed. PMID:22539045

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2017-01-01

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

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

Reflectance-based skin detection in the short wave infrared band and its application to video

NASA Astrophysics Data System (ADS)

Langston, Tye

2016-10-01

Robust reflectance-based skin detection is a potentially powerful tool for security and search and rescue applications, especially when applied to video. However, to be useful it must be able to account for the variations of human skin, as well as other items in the environment that could cause false detections. This effort focused on identifying a robust skin detection scheme that is appropriate for video application. Skin reflectance was modeled to identify unique skin features and compare them to potential false positive materials. Based on these comparisons, specific wavelength bands were selected and different combinations of two and three optical filters were used for actively identifying skin, as well as identifying and removing potential false positive materials. One wavelength combination (1072/1250 nm) was applied to video using both single- and dual-camera configurations based on its still image performance, as well as its appropriateness for video application. There are several important factors regarding the extension of still image skin detection to video, including light available for detection (solar irradiance and reflectance intensity), overall intensity differences between different optical filters, optical component light loss, frame rate, time lag when switching between filters, image coregistration, and camera auto gain behavior.

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

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.

Event-related potential evidence suggesting voters remember political events that never happened

PubMed Central

Federmeier, Kara D.; Gonsalves, Brian D.

2014-01-01

Voters tend to misattribute issue positions to political candidates that are consistent with their partisan affiliation, even though these candidates have never explicitly stated or endorsed such stances. The prevailing explanation in political science is that voters misattribute candidates’ issue positions because they use their political knowledge to make educated but incorrect guesses. We suggest that voter errors can also stem from a different source: false memories. The current study examined event-related potential (ERP) responses to misattributed and accurately remembered candidate issue information. We report here that ERP responses to misattributed information can elicit memory signals similar to that of correctly remembered old information—a pattern consistent with a false memory rather than educated guessing interpretation of these misattributions. These results suggest that some types of voter misinformation about candidates may be harder to correct than previously thought. PMID:23202775

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.

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.

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.

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.

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.

Decision curve analysis as a framework to estimate the potential value of screening or other decision-making aids.

PubMed

Martin, Michael S; Wells, George A; Crocker, Anne G; Potter, Beth K; Colman, Ian

2018-03-01

There is an increasing debate about the impact of mental health screening. We illustrate the use of a decision making framework that can be applied when there is no sufficient data to support a traditional cost-benefit analysis. We conducted secondary analyses of data from 459 male prisoners who were screened upon intake. We compared the potential benefit of different approaches (screening, history taking, and universal interventions) to allocating treatment resources using decision curve analysis. Screening prisoners for distress at typical levels of sensitivity (75%) and specificity (71%) were estimated to provide the greatest net benefit if between 2 and 5 false positives per detected illness are tolerable. History taking and self-harm screening provide the largest net benefit when only 1 or 2 false positives per detected illness would be tolerable. The benefits of screening were less among those without a recent psychiatric history, ethnic minorities, and those with fewer psychosocial needs. Although screening has potential to increase detection of treatment, important subgroup differences exist. Greater consideration of responses to positive screens or alternatives to screening are needed to maximize the impact of efforts to improve detection and treatment of mental illness. Copyright © 2017 John Wiley & Sons, Ltd.

Visual and semi-automatic non-invasive detection of interictal fast ripples: A potential biomarker of epilepsy in children with tuberous sclerosis complex.

PubMed

Bernardo, Danilo; Nariai, Hiroki; Hussain, Shaun A; Sankar, Raman; Salamon, Noriko; Krueger, Darcy A; Sahin, Mustafa; Northrup, Hope; Bebin, E Martina; Wu, Joyce Y

2018-04-03

We aim to establish that interictal fast ripples (FR; 250-500 Hz) are detectable on scalp EEG, and to investigate their association to epilepsy. Scalp EEG recordings of a subset of children with tuberous sclerosis complex (TSC)-associated epilepsy from two large multicenter observational TSC studies were analyzed and compared to control children without epilepsy or any other brain-based diagnoses. FR were identified both by human visual review and compared with semi-automated review utilizing a deep learning-based FR detector. Seven out of 7 children with TSC-associated epilepsy had scalp FR compared to 0 out of 4 children in the control group (p = 0.003). The automatic detector has a sensitivity of 98% and false positive rate with average of 11.2 false positives per minute. Non-invasive detection of interictal scalp FR was feasible, by both visual and semi-automatic detection. Interictal scalp FR occurred exclusively in children with TSC-associated epilepsy and were absent in controls without epilepsy. The proposed detector achieves high sensitivity of FR detection; however, expert review of the results to reduce false positives is advised. Interictal FR are detectable on scalp EEG and may potentially serve as a biomarker of epilepsy in children with TSC. Copyright © 2018 International Federation of Clinical Neurophysiology. All rights reserved.

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 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.

BlackOPs: increasing confidence in variant detection through mappability filtering.

PubMed

Cabanski, Christopher R; Wilkerson, Matthew D; Soloway, Matthew; Parker, Joel S; Liu, Jinze; Prins, Jan F; Marron, J S; Perou, Charles M; Hayes, D Neil

2013-10-01

Identifying variants using high-throughput sequencing data is currently a challenge because true biological variants can be indistinguishable from technical artifacts. One source of technical artifact results from incorrectly aligning experimentally observed sequences to their true genomic origin ('mismapping') and inferring differences in mismapped sequences to be true variants. We developed BlackOPs, an open-source tool that simulates experimental RNA-seq and DNA whole exome sequences derived from the reference genome, aligns these sequences by custom parameters, detects variants and outputs a blacklist of positions and alleles caused by mismapping. Blacklists contain thousands of artifact variants that are indistinguishable from true variants and, for a given sample, are expected to be almost completely false positives. We show that these blacklist positions are specific to the alignment algorithm and read length used, and BlackOPs allows users to generate a blacklist specific to their experimental setup. We queried the dbSNP and COSMIC variant databases and found numerous variants indistinguishable from mapping errors. We demonstrate how filtering against blacklist positions reduces the number of potential false variants using an RNA-seq glioblastoma cell line data set. In summary, accounting for mapping-caused variants tuned to experimental setups reduces false positives and, therefore, improves genome characterization by high-throughput sequencing.

Dark energy, scalar singlet dark matter and the Higgs portal

NASA Astrophysics Data System (ADS)

Landim, Ricardo G.

2018-05-01

One of the simplest extensions of the Standard Model (SM) comprises the inclusion of a massive real scalar field, neutral under the SM gauge groups, to be a dark matter candidate. The addition of a dimension-six term into the potential of the scalar dark matter enables the appearance of a false vacuum that describes the cosmic acceleration. We show that the running of the singlet self-interaction and the Higgs portal coupling differs from the standard scalar singlet dark matter model. If we maintain a positive quartic coupling, it is also possible to describe the accelerated expansion of the Universe through a false vacuum with the addition of a dimension-eight interaction term. In this case, where the potential remains bounded from below at low energies, the false vacuum decay is highly suppressed.

Limitations of Rapid Diagnostic Testing in Patients with Suspected Malaria: A Diagnostic Accuracy Evaluation from Swaziland, a Low-Endemicity Country Aiming for Malaria Elimination

PubMed Central

Ranadive, Nikhil; Kunene, Simon; Darteh, Sarah; Ntshalintshali, Nyasatu; Nhlabathi, Nomcebo; Dlamini, Nomcebo; Chitundu, Stanley; Saini, Manik; Murphy, Maxwell; Soble, Adam; Schwartz, Alanna; Greenhouse, Bryan

2017-01-01

Abstract Background. The performance of Plasmodium falciparum–specific histidine-rich protein 2–based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Methods. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2–based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. Results. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. Conclusions. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts. PMID:28369268

Limitations of Rapid Diagnostic Testing in Patients with Suspected Malaria: A Diagnostic Accuracy Evaluation from Swaziland, a Low-Endemicity Country Aiming for Malaria Elimination.

PubMed

Ranadive, Nikhil; Kunene, Simon; Darteh, Sarah; Ntshalintshali, Nyasatu; Nhlabathi, Nomcebo; Dlamini, Nomcebo; Chitundu, Stanley; Saini, Manik; Murphy, Maxwell; Soble, Adam; Schwartz, Alanna; Greenhouse, Bryan; Hsiang, Michelle S

2017-05-01

The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized. Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards. To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors. From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing. Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively. After exclusion of samples with parasite densities <100/μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%. Deletions of pfhrp2 were not detected. False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation. In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects. The PPV was also low, requiring further investigation. A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Adaptive error detection for HDR/PDR brachytherapy: Guidance for decision making during real-time in vivo point dosimetry

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

Kertzscher, Gustavo, E-mail: guke@dtu.dk; Andersen, Claus E., E-mail: clan@dtu.dk; Tanderup, Kari, E-mail: karitand@rm.dk

Purpose: This study presents an adaptive error detection algorithm (AEDA) for real-timein vivo point dosimetry during high dose rate (HDR) or pulsed dose rate (PDR) brachytherapy (BT) where the error identification, in contrast to existing approaches, does not depend on an a priori reconstruction of the dosimeter position. Instead, the treatment is judged based on dose rate comparisons between measurements and calculations of the most viable dosimeter position provided by the AEDA in a data driven approach. As a result, the AEDA compensates for false error cases related to systematic effects of the dosimeter position reconstruction. Given its nearly exclusivemore » dependence on stable dosimeter positioning, the AEDA allows for a substantially simplified and time efficient real-time in vivo BT dosimetry implementation. Methods: In the event of a measured potential treatment error, the AEDA proposes the most viable dosimeter position out of alternatives to the original reconstruction by means of a data driven matching procedure between dose rate distributions. If measured dose rates do not differ significantly from the most viable alternative, the initial error indication may be attributed to a mispositioned or misreconstructed dosimeter (false error). However, if the error declaration persists, no viable dosimeter position can be found to explain the error, hence the discrepancy is more likely to originate from a misplaced or misreconstructed source applicator or from erroneously connected source guide tubes (true error). Results: The AEDA applied on twoin vivo dosimetry implementations for pulsed dose rate BT demonstrated that the AEDA correctly described effects responsible for initial error indications. The AEDA was able to correctly identify the major part of all permutations of simulated guide tube swap errors and simulated shifts of individual needles from the original reconstruction. Unidentified errors corresponded to scenarios where the dosimeter position was sufficiently symmetric with respect to error and no-error source position constellations. The AEDA was able to correctly identify all false errors represented by mispositioned dosimeters contrary to an error detection algorithm relying on the original reconstruction. Conclusions: The study demonstrates that the AEDA error identification during HDR/PDR BT relies on a stable dosimeter position rather than on an accurate dosimeter reconstruction, and the AEDA’s capacity to distinguish between true and false error scenarios. The study further shows that the AEDA can offer guidance in decision making in the event of potential errors detected with real-timein vivo point dosimetry.« less

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...

A national study of breast and colorectal cancer patients' decision-making for novel personalized medicine genomic diagnostics.

PubMed

Issa, Amalia M; Tufail, Waqas; Atehortua, Nelson; McKeever, John

2013-05-01

Molecular diagnostics are increasingly being used to help guide decision-making for personalized medical treatment of breast and colorectal cancer patients. The main aim of this study was to better understand and determine breast and colorectal cancer patients' decision-making strategies and the trade-offs they make in deciding about characteristics of molecular genomic diagnostics for breast and colorectal cancer. We surveyed a nationally representative sample of 300 breast and colorectal cancer patients using a previously developed web-administered instrument. Eligibility criteria included patients aged 18 years and older with either breast or colorectal cancer. We explored several attributes and attribute levels of molecular genomic diagnostics in 20 scenarios. Our analysis revealed that both breast and colorectal cancer patients weighted the capability of molecular genomic diagnostics to determine the probability of treatment efficacy as being of greater importance than information provided to detect adverse events. The probability of either false-positive or -negative results was ranked highly as a potential barrier by both breast and colorectal patients. However, 78.6% of breast cancer patients ranked the possibility of a 'false-negative test result leading to undertreatment' higher than the 'chance of a false positive, which may lead to overtreatment' (68%). This finding contrasted with the views of colorectal cancer patients who ranked the chance of a false positive as being of greater concern than a false negative (72.8 vs 63%). Overall, cancer patients exhibited a high willingness to accept and pay for genomic diagnostic tests, especially among breast cancer patients. Cancer patients seek a test accuracy rate of 90% or higher. Breast and colorectal cancer patients' decisions about genomic diagnostics are influenced more by the probability of being cured than by avoiding potential severe adverse events. This study provides insights into the relative weight that breast and colorectal cancer patients place on various aspects of molecular genomic diagnostics, and the trade-offs they are willing to make among attributes of such tests.

Automatic mouse ultrasound detector (A-MUD): A new tool for processing rodent vocalizations.

PubMed

Zala, Sarah M; Reitschmidt, Doris; Noll, Anton; Balazs, Peter; Penn, Dustin J

2017-01-01

House mice (Mus musculus) emit complex ultrasonic vocalizations (USVs) during social and sexual interactions, which have features similar to bird song (i.e., they are composed of several different types of syllables, uttered in succession over time to form a pattern of sequences). Manually processing complex vocalization data is time-consuming and potentially subjective, and therefore, we developed an algorithm that automatically detects mouse ultrasonic vocalizations (Automatic Mouse Ultrasound Detector or A-MUD). A-MUD is a script that runs on STx acoustic software (S_TOOLS-STx version 4.2.2), which is free for scientific use. This algorithm improved the efficiency of processing USV files, as it was 4-12 times faster than manual segmentation, depending upon the size of the file. We evaluated A-MUD error rates using manually segmented sound files as a 'gold standard' reference, and compared them to a commercially available program. A-MUD had lower error rates than the commercial software, as it detected significantly more correct positives, and fewer false positives and false negatives. The errors generated by A-MUD were mainly false negatives, rather than false positives. This study is the first to systematically compare error rates for automatic ultrasonic vocalization detection methods, and A-MUD and subsequent versions will be made available for the scientific community.

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

NASA Astrophysics Data System (ADS)

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

2009-02-01

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

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

Miller, James Christopher; Rennie, John Alan; Toevs, James Waldo

The introduction points out that radiation backgrounds fluctuate across very short distances: factors include geology, soil composition, altitude, building structures, topography, and other manmade structures; and asphalt and concrete can vary significantly over short distances. Brief descriptions are given of the detection system, experimental setup, and background variation measurements. It is concluded that positive and negative gradients can greatly reduce the detection sensitivity of an MDS: negative gradients create opportunities for false negatives (nondetection), and positive gradients create a potentially unacceptable FAR (above 1%); the location of use for mobile detection is important to understand; spectroscopic systems provide more informationmore » for screening out false alarms and may be preferred for mobile use; and mobile monitor testing at LANL accounts for expected variations in the background.« less

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

PubMed

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

2015-06-01

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

Azithromycin treatment failure for Chlamydia trachomatis among heterosexual men with nongonococcal urethritis

PubMed Central

Kissinger, Patricia; White, Scott; Manhart, Lisa E.; Schwebke, Jane; Taylor, Stephanie N; Mena, Leandro; Khosropour, Christine M; Wilcox, Larissa; Schmidt, Norine; Martin, David H

2016-01-01

Background Three recent prospective studies have suggested that the 1 g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%–22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to re-examine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. Methods Men who had sex with women, who received 1 g azithromycin under directly observed therapy (DOT) for presumptive treatment of nongonococcal urethritis (NGU) with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine and TOC screening was performed on urine using nucleic acid amplification tests (NAAT). Post-treatment vaginal sexual exposure was elicited at TOC. Data from the three studies was obtained and re-analyzed. Rates of Ct re-test positive were examined for all cases and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. Results The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). Conclusion In these samples of men who have sex with women with Ct-related NGU, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization’s target chlamydia treatment failure rate of < 5%. PMID:27631353

Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis.

PubMed

Kissinger, Patricia J; White, Scott; Manhart, Lisa E; Schwebke, Jane; Taylor, Stephanie N; Mena, Leandro; Khosropour, Christine M; Wilcox, Larissa; Schmidt, Norine; Martin, David H

2016-10-01

Three recent prospective studies have suggested that the 1-g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%-22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to reexamine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. Men who had sex with women, who received 1-g azithromycin under directly observed therapy for presumptive treatment of nongonococcal urethritis with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine, and TOC screening was performed on urine using nucleic acid amplification tests. Posttreatment vaginal sexual exposure was elicited at TOC. Data from the 3 studies were obtained and reanalyzed. Rates of Ct retest positive were examined for all cases, and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). In these samples of men who have sex with women with Ct-related nongonococcal urethritis, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization's target chlamydia treatment failure rate of < 5%.

Gene expression information improves reliability of receptor status in breast cancer patients

PubMed Central

Kenn, Michael; Schlangen, Karin; Castillo-Tong, Dan Cacsire; Singer, Christian F.; Cibena, Michael; Koelbl, Heinz; Schreiner, Wolfgang

2017-01-01

Immunohistochemical (IHC) determination of receptor status in breast cancer patients is frequently inaccurate. Since it directs the choice of systemic therapy, it is essential to increase its reliability. We increase the validity of IHC receptor expression by additionally considering gene expression (GE) measurements. Crisp therapeutic decisions are based on IHC estimates, even if they are borderline reliable. We further improve decision quality by a responsibility function, defining a critical domain for gene expression. Refined normalization is devised to file any newly diagnosed patient into existing data bases. Our approach renders receptor estimates more reliable by identifying patients with questionable receptor status. The approach is also more efficient since the rate of conclusive samples is increased. We have curated and evaluated gene expression data, together with clinical information, from 2880 breast cancer patients. Combining IHC with gene expression information yields a method more reliable and also more efficient as compared to common practice up to now. Several types of possibly suboptimal treatment allocations, based on IHC receptor status alone, are enumerated. A ‘therapy allocation check’ identifies patients possibly miss-classified. Estrogen: false negative 8%, false positive 6%. Progesterone: false negative 14%, false positive 11%. HER2: false negative 2%, false positive 50%. Possible implications are discussed. We propose an ‘expression look-up-plot’, allowing for a significant potential to improve the quality of precision medicine. Methods are developed and exemplified here for breast cancer patients, but they may readily be transferred to diagnostic data relevant for therapeutic decisions in other fields of oncology. PMID:29100391

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.

Detecting Seismic Events Using a Supervised Hidden Markov Model

NASA Astrophysics Data System (ADS)

Burks, L.; Forrest, R.; Ray, J.; Young, C.

2017-12-01

We explore the use of supervised hidden Markov models (HMMs) to detect seismic events in streaming seismogram data. Current methods for seismic event detection include simple triggering algorithms, such as STA/LTA and the Z-statistic, which can lead to large numbers of false positives that must be investigated by an analyst. The hypothesis of this study is that more advanced detection methods, such as HMMs, may decreases false positives while maintaining accuracy similar to current methods. We train a binary HMM classifier using 2 weeks of 3-component waveform data from the International Monitoring System (IMS) that was carefully reviewed by an expert analyst to pick all seismic events. Using an ensemble of simple and discrete features, such as the triggering of STA/LTA, the HMM predicts the time at which transition occurs from noise to signal. Compared to the STA/LTA detection algorithm, the HMM detects more true events, but the false positive rate remains unacceptably high. Future work to potentially decrease the false positive rate may include using continuous features, a Gaussian HMM, and multi-class HMMs to distinguish between types of seismic waves (e.g., P-waves and S-waves). Acknowledgement: Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA-0003525.SAND No: SAND2017-8154 A

False memory and level of processing effect: an event-related potential study.

PubMed

Beato, Maria Soledad; Boldini, Angela; Cadavid, Sara

2012-09-12

Event-related potentials (ERPs) were used to determine the effects of level of processing on true and false memory, using the Deese-Roediger-McDermott (DRM) paradigm. In the DRM paradigm, lists of words highly associated to a single nonpresented word (the 'critical lure') are studied and, in a subsequent memory test, critical lures are often falsely remembered. Lists with three critical lures per list were auditorily presented here to participants who studied them with either a shallow (saying whether the word contained the letter 'o') or a deep (creating a mental image of the word) processing task. Visual presentation modality was used on a final recognition test. True recognition of studied words was significantly higher after deep encoding, whereas false recognition of nonpresented critical lures was similar in both experimental groups. At the ERP level, true and false recognition showed similar patterns: no FN400 effect was found, whereas comparable left parietal and late right frontal old/new effects were found for true and false recognition in both experimental conditions. Items studied under shallow encoding conditions elicited more positive ERP than items studied under deep encoding conditions at a 1000-1500 ms interval. These ERP results suggest that true and false recognition share some common underlying processes. Differential effects of level of processing on true and false memory were found only at the behavioral level but not at the ERP level.

Rating the "Raters": Legal Exposure of Trustmark Authorities in the Context of Consumer Health Informatics

PubMed Central

Terry, Nicolas P

2000-01-01

There are three areas of potential legal exposure for an organization such as a trustmark authority involved in ehealth quality rating. First, an ehealth provider may make a complaint about negative or impliedly negative ratings rendered by the ratings body (false negative). Typically, a negative ratings complaint would rely on defamation or product disparagement causes of action. In some cases such complaints could be defended on the basis of absence of malice (US). Second, the rating body might render a positive rating on ehealth data that a third party allegedly relied upon and suffered injury (false positive). While the primary cause of action would be against the ehealth data provider, questions may arise as to possible liability of the trustmark authority. For example, some US liability exposure is possible based on cases involving the potential liability of product warrantors, trade associations and certifiers or endorsers. Third, a ratings body may face public law liability for its own web misfeasance. Several risk management approaches are possible and would not necessarily be mutually exclusive. These approaches will require careful investigation to assess their risk reduction potential and, in some cases, legislation.

Rating the Raters: Legal Exposure of Trustmark Authorities in the Context of Consumer Health Informatics

PubMed Central

2000-01-01

There are three areas of potential legal exposure for an organization such as a trustmark authority involved in e-health quality rating. First, an e-health provider may make a complaint about negative or impliedly negative ratings rendered by the ratings body (false negative). Typically, a negative ratings complaint would rely on defamation or product disparagement causes of action. In some cases such complaints could be defended on the basis of absence of malice (US). Second, the rating body might render a positive rating on e-health data that a third party allegedly relied upon and suffered injury (false positive). While the primary cause of action would be against the e-health data provider, questions may arise as to the possible liability of the trustmark authority. For example, some US liability exposure is possible based on cases involving the potential liability of product warrantors, trade associations, and certifiers or endorsers. Third, a ratings body may face public law liability for its own web misfeasance. Several risk management approaches are possible and would not necessarily be mutually exclusive. These approaches will require careful investigation to assess their risk reduction potential and, in some cases, the introduction of legislation. PMID:11720941

Computer-aided detection of breast lesions in DCE-MRI using region growing based on fuzzy C-means clustering and vesselness filter

NASA Astrophysics Data System (ADS)

B. Shokouhi, Shahriar; Fooladivanda, Aida; Ahmadinejad, Nasrin

2017-12-01

A computer-aided detection (CAD) system is introduced in this paper for detection of breast lesions in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The proposed CAD system firstly compensates motion artifacts and segments the breast region. Then, the potential lesion voxels are detected and used as the initial seed points for the seeded region-growing algorithm. A new and robust region-growing algorithm incorporating with Fuzzy C-means (FCM) clustering and vesselness filter is proposed to segment any potential lesion regions. Subsequently, the false positive detections are reduced by applying a discrimination step. This is based on 3D morphological characteristics of the potential lesion regions and kinetic features which are fed to the support vector machine (SVM) classifier. The performance of the proposed CAD system is evaluated using the free-response operating characteristic (FROC) curve. We introduce our collected dataset that includes 76 DCE-MRI studies, 63 malignant and 107 benign lesions. The prepared dataset has been used to verify the accuracy of the proposed CAD system. At 5.29 false positives per case, the CAD system accurately detects 94% of the breast lesions.

Rating the raters: legal exposure of trustmark authorities in the context of consumer health informatics.

PubMed

Terry, N P

2000-01-01

There are three areas of potential legal exposure for an organization such as a trustmark authority involved in e-health quality rating. First, an e-health provider may make a complaint about negative or impliedly negative ratings rendered by the ratings body (false negative). Typically, a negative ratings complaint would rely on defamation or product disparagement causes of action. In some cases such complaints could be defended on the basis of absence of malice (US). Second, the rating body might render a positive rating on e-health data that a third party allegedly relied upon and suffered injury (false positive). While the primary cause of action would be against the e-health data provider, questions may arise as to the possible liability of the trustmark authority. For example, some US liability exposure is possible based on cases involving the potential liability of product warrantors, trade associations, and certifiers or endorsers. Third, a ratings body may face public law liability for its own web misfeasance. Several risk management approaches are possible and would not necessarily be mutually exclusive. These approaches will require careful investigation to assess their risk reduction potential and, in some cases, the introduction of legislation.

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.

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.

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.

Easy fix for clinical laboratories for the false-positive defect with the Abbott AxSym total beta-hCG test.

PubMed

Cole, Laurence A; Khanlian, Sarah A

2004-05-01

False-positive hCG results can lead to erroneous diagnoses and needless chemotherapy and surgery. In the last 2 years, eight publications described cases involving false-positive hCG tests; all eight involved the AxSym test. We investigated the source of this abundance of cases and a simple fix that may be used by clinical laboratories. False-positive hCG was primarily identified by absence of hCG in urine and varying or negative hCG results in alternative tests. Seventeen false-positive serum samples in the AxSym test were evaluated undiluted and at twofold dilution with diluent containing excess goat serum or immunoglobulin. We identified 58 patients with false-positive hCG, 47 of 58 due to the Abbott AxSym total hCGbeta test (81%). Sixteen of 17 of these "false-positive" results (mean 100 mIU/ml) became undetectable when tested again after twofold dilution. A simple twofold dilution with this diluent containing excess goat serum or immunoglobulin completely protected 16 of 17 samples from patients having false-positive results. It is recommended that laboratories using this test use twofold dilution as a minimum to prevent false-positive results.

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

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…

Comparison of false-negative/positive results of intraoperative evoked potential monitoring between no and partial neuromuscular blockade in patients receiving propofol/remifentanil-based anesthesia during cerebral aneurysm clipping surgery: A retrospective analysis of 685 patients.

PubMed

Kim, Sung-Hoon; Jin, Seok-Joon; Karm, Myong-Hwan; Moon, Young-Jin; Jeong, Hye-Won; Kim, Jae-Won; Ha, Seung-Il; Kim, Joung-Uk

2016-08-01

Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False-negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery.

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.

Assessing environmental DNA detection in controlled lentic systems.

PubMed

Moyer, Gregory R; Díaz-Ferguson, Edgardo; Hill, Jeffrey E; Shea, Colin

2014-01-01

Little consideration has been given to environmental DNA (eDNA) sampling strategies for rare species. The certainty of species detection relies on understanding false positive and false negative error rates. We used artificial ponds together with logistic regression models to assess the detection of African jewelfish eDNA at varying fish densities (0, 0.32, 1.75, and 5.25 fish/m3). Our objectives were to determine the most effective water stratum for eDNA detection, estimate true and false positive eDNA detection rates, and assess the number of water samples necessary to minimize the risk of false negatives. There were 28 eDNA detections in 324, 1-L, water samples collected from four experimental ponds. The best-approximating model indicated that the per-L-sample probability of eDNA detection was 4.86 times more likely for every 2.53 fish/m3 (1 SD) increase in fish density and 1.67 times less likely for every 1.02 C (1 SD) increase in water temperature. The best section of the water column to detect eDNA was the surface and to a lesser extent the bottom. Although no false positives were detected, the estimated likely number of false positives in samples from ponds that contained fish averaged 3.62. At high densities of African jewelfish, 3-5 L of water provided a >95% probability for the presence/absence of its eDNA. Conversely, at moderate and low densities, the number of water samples necessary to achieve a >95% probability of eDNA detection approximated 42-73 and >100 L, respectively. Potential biases associated with incomplete detection of eDNA could be alleviated via formal estimation of eDNA detection probabilities under an occupancy modeling framework; alternatively, the filtration of hundreds of liters of water may be required to achieve a high (e.g., 95%) level of certainty that African jewelfish eDNA will be detected at low densities (i.e., <0.32 fish/m3 or 1.75 g/m3).

Automatic mouse ultrasound detector (A-MUD): A new tool for processing rodent vocalizations

PubMed Central

Reitschmidt, Doris; Noll, Anton; Balazs, Peter; Penn, Dustin J.

2017-01-01

House mice (Mus musculus) emit complex ultrasonic vocalizations (USVs) during social and sexual interactions, which have features similar to bird song (i.e., they are composed of several different types of syllables, uttered in succession over time to form a pattern of sequences). Manually processing complex vocalization data is time-consuming and potentially subjective, and therefore, we developed an algorithm that automatically detects mouse ultrasonic vocalizations (Automatic Mouse Ultrasound Detector or A-MUD). A-MUD is a script that runs on STx acoustic software (S_TOOLS-STx version 4.2.2), which is free for scientific use. This algorithm improved the efficiency of processing USV files, as it was 4–12 times faster than manual segmentation, depending upon the size of the file. We evaluated A-MUD error rates using manually segmented sound files as a ‘gold standard’ reference, and compared them to a commercially available program. A-MUD had lower error rates than the commercial software, as it detected significantly more correct positives, and fewer false positives and false negatives. The errors generated by A-MUD were mainly false negatives, rather than false positives. This study is the first to systematically compare error rates for automatic ultrasonic vocalization detection methods, and A-MUD and subsequent versions will be made available for the scientific community. PMID:28727808

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

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.

Real-time hypoglycemia detection from continuous glucose monitoring data of subjects with type 1 diabetes.

PubMed

Jensen, Morten Hasselstrøm; Christensen, Toke Folke; Tarnow, Lise; Seto, Edmund; Dencker Johansen, Mette; Hejlesen, Ole Kristian

2013-07-01

Hypoglycemia is a potentially fatal condition. Continuous glucose monitoring (CGM) has the potential to detect hypoglycemia in real time and thereby reduce time in hypoglycemia and avoid any further decline in blood glucose level. However, CGM is inaccurate and shows a substantial number of cases in which the hypoglycemic event is not detected by the CGM. The aim of this study was to develop a pattern classification model to optimize real-time hypoglycemia detection. Features such as time since last insulin injection and linear regression, kurtosis, and skewness of the CGM signal in different time intervals were extracted from data of 10 male subjects experiencing 17 insulin-induced hypoglycemic events in an experimental setting. Nondiscriminative features were eliminated with SEPCOR and forward selection. The feature combinations were used in a Support Vector Machine model and the performance assessed by sample-based sensitivity and specificity and event-based sensitivity and number of false-positives. The best model was composed by using seven features and was able to detect 17 of 17 hypoglycemic events with one false-positive compared with 12 of 17 hypoglycemic events with zero false-positives for the CGM alone. Lead-time was 14 min and 0 min for the model and the CGM alone, respectively. This optimized real-time hypoglycemia detection provides a unique approach for the diabetes patient to reduce time in hypoglycemia and learn about patterns in glucose excursions. Although these results are promising, the model needs to be validated on CGM data from patients with spontaneous hypoglycemic events.

"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…

Do the benefits outweigh the side effects of colorectal cancer surveillance? A systematic review.

PubMed

Augestad, Knut Magne; Rose, Johnie; Crawshaw, Benjamin; Cooper, Gregory; Delaney, Conor

2014-05-15

Most patients treated with curative intent for colorectal cancer (CRC) are included in a follow-up program involving periodic evaluations. The survival benefits of a follow-up program are well delineated, and previous meta-analyses have suggested an overall survival improvement of 5%-10% by intensive follow-up. However, in a recent randomized trial, there was no survival benefit when a minimal vs an intensive follow-up program was compared. Less is known about the potential side effects of follow-up. Well-known side effects of preventive programs are those of somatic complications caused by testing, negative psychological consequences of follow-up itself, and the downstream impact of false positive or false negative tests. Accordingly, the potential survival benefits of CRC follow-up must be weighed against these potential negatives. The present review compares the benefits and side effects of CRC follow-up, and we propose future areas for research.

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

False positive acetaminophen concentrations in patients with liver injury.

PubMed

Polson, Julie; Wians, Frank H; Orsulak, Paul; Fuller, Dwain; Murray, Natalie G; Koff, Jonathan M; Khan, Adil I; Balko, Jody A; Hynan, Linda S; Lee, William M

2008-05-01

Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations >10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.

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.

Relative Accuracy of Nucleic Acid Amplification Tests and Culture in Detecting Chlamydia in Asymptomatic Men

PubMed Central

Cheng, Hong; Macaluso, Maurizio; Vermund, Sten H.; Hook, Edward W.

2001-01-01

Published estimates of the sensitivity and specificity of PCR and ligase chain reaction (LCR) for detecting Chlamydia trachomatis are potentially biased because of study design limitations (confirmation of test results was limited to subjects who were PCR or LCR positive but culture negative). Relative measures of test accuracy are less prone to bias in incomplete study designs. We estimated the relative sensitivity (RSN) and relative false-positive rate (RFP) for PCR and LCR versus cell culture among 1,138 asymptomatic men and evaluated the potential bias of RSN and RFP estimates. PCR and LCR testing in urine were compared to culture of urethral specimens. Discordant results (PCR or LCR positive, but culture negative) were confirmed by using a sequence including the other DNA amplification test, direct fluorescent antibody testing, and a DNA amplification test to detect chlamydial major outer membrane protein. The RSN estimates for PCR and LCR were 1.45 (95% confidence interval [CI] = 1.3 to 1.7) and 1.49 (95% CI = 1.3 to 1.7), respectively, indicating that both methods are more sensitive than culture. Very few false-positive results were found, indicating that the specificity levels of PCR, LCR, and culture are high. The potential bias in RSN and RFP estimates were <5 and <20%, respectively. The estimation of bias is based on the most likely and probably conservative parameter settings. If the sensitivity of culture is between 60 and 65%, then the true sensitivity of PCR and LCR is between 90 and 97%. Our findings indicate that PCR and LCR are significantly more sensitive than culture, while the three tests have similar specificities. PMID:11682509

Diverse convergent evidence in the genetic analysis of complex disease: coordinating omic, informatic, and experimental evidence to better identify and validate risk factors

PubMed Central

2014-01-01

In omic research, such as genome wide association studies, researchers seek to repeat their results in other datasets to reduce false positive findings and thus provide evidence for the existence of true associations. Unfortunately this standard validation approach cannot completely eliminate false positive conclusions, and it can also mask many true associations that might otherwise advance our understanding of pathology. These issues beg the question: How can we increase the amount of knowledge gained from high throughput genetic data? To address this challenge, we present an approach that complements standard statistical validation methods by drawing attention to both potential false negative and false positive conclusions, as well as providing broad information for directing future research. The Diverse Convergent Evidence approach (DiCE) we propose integrates information from multiple sources (omics, informatics, and laboratory experiments) to estimate the strength of the available corroborating evidence supporting a given association. This process is designed to yield an evidence metric that has utility when etiologic heterogeneity, variable risk factor frequencies, and a variety of observational data imperfections might lead to false conclusions. We provide proof of principle examples in which DiCE identified strong evidence for associations that have established biological importance, when standard validation methods alone did not provide support. If used as an adjunct to standard validation methods this approach can leverage multiple distinct data types to improve genetic risk factor discovery/validation, promote effective science communication, and guide future research directions. PMID:25071867

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

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.

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

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;

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.

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.

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.

False negative rates in Drosophila cell-based RNAi screens: a case study

PubMed Central

2011-01-01

Background High-throughput screening using RNAi is a powerful gene discovery method but is often complicated by false positive and false negative results. Whereas false positive results associated with RNAi reagents has been a matter of extensive study, the issue of false negatives has received less attention. Results We performed a meta-analysis of several genome-wide, cell-based Drosophila RNAi screens, together with a more focused RNAi screen, and conclude that the rate of false negative results is at least 8%. Further, we demonstrate how knowledge of the cell transcriptome can be used to resolve ambiguous results and how the number of false negative results can be reduced by using multiple, independently-tested RNAi reagents per gene. Conclusions RNAi reagents that target the same gene do not always yield consistent results due to false positives and weak or ineffective reagents. False positive results can be partially minimized by filtering with transcriptome data. RNAi libraries with multiple reagents per gene also reduce false positive and false negative outcomes when inconsistent results are disambiguated carefully. PMID:21251254

[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.

True- and false-belief reasoning in children and adults: an event-related potential study of theory of mind.

PubMed

Meinhardt, Jörg; Sodian, Beate; Thoermer, Claudia; Döhnel, Katrin; Sommer, Monika

2011-01-01

The understanding that another person's belief can differ from reality and that behaviour is guided by beliefs and not by reality reflects an important cornerstone in the development of a Theory of Mind. The present event-related potential (ERP) study had two aims: first, to reveal ERPs that distinguish between false- and true-belief reasoning and second, to investigate the neural changes in the development of false- and true-belief reasoning from childhood to adulthood. True- and false-belief cartoon stories were presented to adults and 6-8-year-old children. Results revealed two waveforms that differentiated between the two conditions: a late positive complex (LPC) associated with the reorientation from external stimuli to internal mental representations and a late anterior slow wave (LSW) associated with stimulus-independent processing of internal mental representations, a process that might be centrally involved in the decoupling mechanism. Additionally, we found developmental effects at an ERP level. Children showed a more posterior localization of the LPC and a broader frontal distribution of the LSW. The results may reflect developmental progress in conceptualizing the mental domain and support the idea that the cortical mentalizing network continues to develop even after children are able to master false beliefs. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

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.

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

PubMed

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

2007-02-01

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

Evaluation of culture- and PCR-based detection methods for Escherichia coli O157:H7 in inoculated ground beeft.

PubMed

Arthur, Terrance M; Bosilevac, Joseph M; Nou, Xiangwu; Koohmaraie, Mohammad

2005-08-01

Currently, several beef processors employ test-and-hold systems for increased quality control of ground beef. In such programs, each lot of product must be tested and found negative for Escherichia coli O157:H7 prior to release of the product into commerce. Optimization of three testing attributes (detection time, specificity, and sensitivity) is critical to the success of such strategies. Because ground beef is a highly perishable product, the testing methodology used must be as rapid as possible. The test also must have a low false-positive result rate so product is not needlessly discarded. False-negative results cannot be tolerated because they would allow contaminated product to be released and potentially cause disease. In this study, two culture-based and three PCR-based methods for detecting E. coli O157:H7 in ground beef were compared for their abilities to meet the above criteria. Ground beef samples were individually spiked with five genetically distinct strains of E. coli O157: H7 at concentrations of 17 and 1.7 CFU/65 g and then subjected to the various testing methodologies. There was no difference (P > 0.05) in the abilities of the PCR-based methods to detect E. coli O157:H7 inoculated in ground beef at 1.7 CFU/65 g. The culture-based systems detected more positive samples than did the PCR-based systems, but the detection times (21 to 48 h) were at least 9 h longer than those for the PCR-based methods (7.5 to 12 h). Ground beef samples were also spiked with potentially cross-reactive strains. The PCR-based systems that employed an immunomagnetic separation step prior to detection produced fewer false-positive results.

Urine drug screens: Considerations for the psychiatric pharmacist

PubMed Central

Hale, Genevieve M.; Ross, Clint

2016-01-01

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

A novel ECG detector performance metric and its relationship with missing and false heart rate limit alarms.

PubMed

Daluwatte, Chathuri; Vicente, Jose; Galeotti, Loriano; Johannesen, Lars; Strauss, David G; Scully, Christopher G

Performance of ECG beat detectors is traditionally assessed on long intervals (e.g.: 30min), but only incorrect detections within a short interval (e.g.: 10s) may cause incorrect (i.e., missed+false) heart rate limit alarms (tachycardia and bradycardia). We propose a novel performance metric based on distribution of incorrect beat detection over a short interval and assess its relationship with incorrect heart rate limit alarm rates. Six ECG beat detectors were assessed using performance metrics over long interval (sensitivity and positive predictive value over 30min) and short interval (Area Under empirical cumulative distribution function (AUecdf) for short interval (i.e., 10s) sensitivity and positive predictive value) on two ECG databases. False heart rate limit and asystole alarm rates calculated using a third ECG database were then correlated (Spearman's rank correlation) with each calculated performance metric. False alarm rates correlated with sensitivity calculated on long interval (i.e., 30min) (ρ=-0.8 and p<0.05) and AUecdf for sensitivity (ρ=0.9 and p<0.05) in all assessed ECG databases. Sensitivity over 30min grouped the two detectors with lowest false alarm rates while AUecdf for sensitivity provided further information to identify the two beat detectors with highest false alarm rates as well, which was inseparable with sensitivity over 30min. Short interval performance metrics can provide insights on the potential of a beat detector to generate incorrect heart rate limit alarms. Published by Elsevier Inc.

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.

Frequency of false positive rapid HIV serologic tests in African men and women receiving PrEP for HIV prevention: implications for programmatic roll-out of biomedical interventions.

PubMed

Ndase, Patrick; Celum, Connie; Kidoguchi, Lara; Ronald, Allan; Fife, Kenneth H; Bukusi, Elizabeth; Donnell, Deborah; Baeten, Jared M

2015-01-01

Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results. We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests. A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits. When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.

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.

Substances that interfere with guaiac card tests: implications for gastric aspirate testing.

PubMed

Gogel, H K; Tandberg, D; Strickland, R G

1989-09-01

Previous studies have shown that acidic pH and several ingestible substances can cause misleading guaiac tests of gastric aspirates. In this in vitro study, over 100 foods, beverages, and drugs were diluted to concentrations potentially present in the stomachs of outpatients being evaluated for gastrointestinal bleeding. These were mixed with known concentrations of blood and tested with different brands of guaiac cards. Decreased guaiac test sensitivity was associated with activated charcoal, dimethylaminoethanol, red chile, N-acetylcysteine, rifampin, red Jell-O (General Foods Corp, White Plains, NY), orange juice, Pepto-Bismol (Norwich Eaton Pharmaceuticals, Norwich, NY), simethicone, spaghetti sauce, and several red wines. Chlorophyll and methylene blue-containing tablets produced false-positive results, but other blue and blue-green colored tablets did not, except at high concentrations. Previously described false-negative results with vitamin C, bile, and certain antacids were confirmed, as were false-positive results with iodide, bromide, cupric sulfate, iron salts, and hypochlorite. Physicians should exercise caution when interpreting guaiac card tests of gastric aspirates, especially in the outpatient setting.

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.

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).

Early Disseminated Lyme Disease Masquerading as Mononucleosis: A Case Report.

PubMed

Tumminello, Richard; Glaspey, Lindsey; Bhamidipati, Anita; Sheehan, Patrick; Patel, Sundip

2017-12-01

Disseminated Lyme disease can be difficult to diagnose, as it begins with nonspecific signs and symptoms, which, if not treated correctly, can lead to atrioventricular conduction blocks and meningitis. In addition, the diagnosis can be further complicated by potentially false-positive test results. We report a case of early-disseminated Lyme disease presenting with Borrelia meningitis and concomitant Lyme carditis, which was misdiagnosed as mononucleosis. A young, previously healthy patient had been hiking in the woods of upstate New York and 4 weeks later developed fever, night sweats, and myalgias. He was diagnosed with mononucleosis via a positive rapid heterophile agglutination antibody test to the Epstein-Barr virus at a walk-in clinic and was started on medications, but then subsequently developed left hip pain, a facial droop, and a very long first-degree atrioventricular conduction block. He went to the Emergency Department, where he had testing that confirmed disseminated Lyme disease. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the difficulty in early diagnosis of disseminated Lyme disease and how a potentially false-positive laboratory test can lead to the complications of Borrelia meningitis and Lyme carditis in untreated young healthy patients. Emergency physicians need to consider Lyme disease in patients with nonspecific signs and symptoms, especially if they have been outdoors for prolonged periods of time in Lyme-endemic areas. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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.

Field testing Diorhabda elongata (Coleoptera:Chrysomelidae) from Crete, Greece to assess potential impact to non-target native California plants in the genus Frankenia

USDA-ARS?s Scientific Manuscript database

When laboratory host specificity tests on weed biological control agents produce ambiguous results or are suspected of producing false positives, field cage or open field tests can be utilized in an attempt to determine the true ecological host range of the agent. The leaf beetle Diorhabda elongata ...

Development of size-selective sampling of Bacillus anthracis surrogate spores from simulated building air intake mixtures for analysis via laser-induced breakdown spectroscopy.

PubMed

Gibb-Snyder, Emily; Gullett, Brian; Ryan, Shawn; Oudejans, Lukas; Touati, Abderrahmane

2006-08-01

Size-selective sampling of Bacillus anthracis surrogate spores from realistic, common aerosol mixtures was developed for analysis by laser-induced breakdown spectroscopy (LIBS). A two-stage impactor was found to be the preferential sampling technique for LIBS analysis because it was able to concentrate the spores in the mixtures while decreasing the collection of potentially interfering aerosols. Three common spore/aerosol scenarios were evaluated, diesel truck exhaust (to simulate a truck running outside of a building air intake), urban outdoor aerosol (to simulate common building air), and finally a protein aerosol (to simulate either an agent mixture (ricin/anthrax) or a contaminated anthrax sample). Two statistical methods, linear correlation and principal component analysis, were assessed for differentiation of surrogate spore spectra from other common aerosols. Criteria for determining percentages of false positives and false negatives via correlation analysis were evaluated. A single laser shot analysis of approximately 4 percent of the spores in a mixture of 0.75 m(3) urban outdoor air doped with approximately 1.1 x 10(5) spores resulted in a 0.04 proportion of false negatives. For that same sample volume of urban air without spores, the proportion of false positives was 0.08.

Sentinel lymph node mapping in melanoma: the issue of false-negative findings.

PubMed

Manca, Gianpiero; Rubello, Domenico; Romanini, Antonella; Boni, Giuseppe; Chiacchio, Serena; Tredici, Manuel; Mazzarri, Sara; Duce, Valerio; Colletti, Patrick M; Volterrani, Duccio; Mariani, Giuliano

2014-07-01

Management of cutaneous melanoma has changed after introduction in the clinical routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the nodal basin status, SLNB provides a powerful prognostic information. Nevertheless, some debate still surrounds the accuracy of this procedure in terms of false-negative rate. 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. In this review, we identified all the technical aspects that the nuclear medicine physician, the surgeon, and the pathologist should take into account to improve accuracy of the procedure and minimize the false-negative rate. In particular, SPECT/CT imaging detects more SLNs than those found by planar lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a consensus on the radioactive counting rate threshold to better guide the surgeon in identifying the lymph nodes with the highest likelihood of housing metastases ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques is also a further potential source for error. More accurate SLN analysis (eg, molecular analysis by reverse transcriptase-polymerase chain reaction) and more extensive SLN sampling identify more positive nodes, thus reducing the false-negative rate.The clinical factors identifying patients at higher-risk local recurrence after a negative SLNB include older age at diagnosis, deeper lesions, histological ulceration, and head-neck anatomic location of the primary lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma patients remains controversial, because the majority of studies have failed to demonstrate overall statistically significant disadvantage in melanoma-specific survival for false-negative SLNB patients compared with true-positive SLNB patients.When new more effective drugs will be available in the adjuvant setting for stage III melanoma patients, the implication of an accurate staging procedure for the sentinel lymph nodes will be crucial for both patients and clinicians. Standardization and accuracy of SLN identification, removal, and analysis are required.

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.

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.

A Cross-Reactivity of Fenofibric Acid With MDMA DRI Assay.

PubMed

Bugier, Sarah; Garcia-Hejl, Carine; Vest, Philippe; Plantamura, Julie; Chianea, Denis; Renard, Christophe

2016-09-01

Within the framework of routine fitness examinations, French Air Force military crew underwent urine testing for 3,4 methylenedioxymetamphetamine (MDMA [ecstasy]). The cross-reactivity of a dyslipidemic drug, fenofibrate, with an MDMA immunoassay was studied and confirmed on a large population sample. A 3-year retrospective study was performed on the MDMA DRI Ecstasy Assay on the Unicel DXC 600. In the event of positive test result, a confirmatory testing was carried out by gas chromatography/mass spectrometry (GC/MS) to establish the presence of MDMA. When analysis by GC/MS did not confirm the presence of MDMA, a false-positive result was suspected and the samples were analyzed by high-performance liquid chromatography-mass spectrometry to identify a potential interfering substance. A total of 15,169 urine samples, from 7,803 patients, were tested for 3 years. Of the tested samples, 22 (0.15%) were positive by DRI Ecstasy Assay. None of them were positive by GC/MS. A cross-reactivity of fenofibrate's metabolite with MDMA using this assay was systematically found. Fenofibrate's interference with MDMA immunoassay was confirmed. Fenofibrate being widely prescribed, physicians had to be alerted that this treatment could lead to false-positive results. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

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.

Chemical applicability domain of the local lymph node assay (LLNA) for skin sensitisation potency. Part 4. Quantitative correlation of LLNA potency with human potency.

PubMed

Roberts, David W; Api, Anne Marie

2018-07-01

Prediction of skin sensitisation potential and potency by non-animal methods is the target of many active research programmes. Although the aim is to predict sensitisation potential and potency in humans, data from the murine local lymph node assay (LLNA) constitute much the largest source of quantitative data on in vivo skin sensitisation. The LLNA has been the preferred in vivo method for identification of skin sensitising chemicals and as such is potentially valuable as a benchmark for assessment of non-animal approaches. However, in common with all predictive test methods, the LLNA is subject to false positives and false negatives with an overall level of accuracy said variously to be approximately 80% or 90%. It is also necessary to consider the extent to which, for true positives, LLNA potency correlates with human potency. In this paper LLNA potency and human potency are compared so as to express quantitatively the correlation between them, and reasons for non-agreement between LLNA and human potency are analysed. This leads to a better definition of the applicability domain of the LLNA, within which LLNA data can be used confidently to predict human potency and as a benchmark to assess the performance of non-animal approaches. Copyright © 2018. Published by Elsevier Inc.

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.

Detection of cytomegalovirus DNA in fecal samples as a method for CMV enterocolitis diagnosis after allogeneic stem cell transplantation.

PubMed

Zavrelova, Alzbeta; Radocha, Jakub; Pliskova, Lenka; Paterova, Pavla; Vejrazkova, Eva; Cyrany, Jiri; Gabalec, Filip; Podhola, Miroslav; Zak, Pavel

2018-05-16

Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.

An investigation into false-negative transthoracic fine needle aspiration and core biopsy specimens.

PubMed

Minot, Douglas M; Gilman, Elizabeth A; Aubry, Marie-Christine; Voss, Jesse S; Van Epps, Sarah G; Tuve, Delores J; Sciallis, Andrew P; Henry, Michael R; Salomao, Diva R; Lee, Peter; Carlson, Stephanie K; Clayton, Amy C

2014-12-01

Transthoracic fine needle aspiration (TFNA)/core needle biopsy (CNB) under computed tomography (CT) guidance has proved useful in the assessment of pulmonary nodules. We sought to determine the TFNA false-negative (FN) rate at our institution and identify potential causes of FN diagnoses. Medical records were reviewed from 1,043 consecutive patients who underwent CT-guided TFNA with or without CNB of lung nodules over a 5-year time period (2003-2007). Thirty-seven FN cases of "negative" TFNA/CNB with malignant outcome were identified with 36 cases available for review, of which 35 had a corresponding CNB. Cases were reviewed independently (blinded to original diagnosis) by three pathologists with 15 age- and sex-matched positive and negative controls. Diagnosis (i.e., nondiagnostic, negative or positive for malignancy, atypical or suspicious) and qualitative assessments were recorded. Consensus diagnosis was suspicious or positive in 10 (28%) of 36 TFNA cases and suspicious in 1 (3%) of 35 CNB cases, indicating potential interpretive errors. Of the 11 interpretive errors (including both suspicious and positive cases), 8 were adenocarcinomas, 1 squamous cell carcinoma, 1 metastatic renal cell carcinoma, and 1 lymphoma. The remaining 25 FN cases (69.4%) were considered sampling errors and consisted of 7 adenocarcinomas, 3 nonsmall cell carcinomas, 3 lymphomas, 2 squamous cell carcinomas, and 2 renal cell carcinomas. Interpretive and sampling error cases were more likely to abut the pleura, while histopathologically, they tended to be necrotic and air-dried. The overall FN rate in this patient cohort is 3.5% (1.1% interpretive and 2.4% sampling errors). © 2014 Wiley Periodicals, Inc.

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.

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.

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.

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

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.

Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

PubMed

Herbert, Cornelia; Kübler, Andrea

2011-01-01

The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences), target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay.

PubMed

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi

2015-12-01

The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was < 10%. Therefore, these chemicals were classified as moderate skin sensitizers in the LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE.

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed Central

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

2015-01-01

Background Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Methodology/Principal Findings Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). Conclusion The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study. PMID:26161864

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed

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

2015-01-01

Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

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.

No Influence of Positive Emotion on Orbitofrontal Reality Filtering: Relevance for Confabulation

PubMed Central

Liverani, Maria Chiara; Manuel, Aurélie L.; Guggisberg, Adrian G.; Nahum, Louis; Schnider, Armin

2016-01-01

Orbitofrontal reality filtering (ORFi) is a mechanism that allows us to keep thought and behavior in phase with reality. Its failure induces reality confusion with confabulation and disorientation. Confabulations have been claimed to have a positive emotional bias, suggesting that they emanate from a tendency to embellish the situation of a handicap. Here we tested the influence of positive emotion on ORFi in healthy subjects using a paradigm validated in reality confusing patients and with a known electrophysiological signature, a frontal positivity at 200–300 ms after memory evocation. Subjects made two continuous recognition tasks (“two runs”), composed of the same set of neutral and positive pictures, but arranged in different order. In both runs, participants had to indicate picture repetitions within, and only within, the ongoing run. The first run measures learning and recognition. The second run, where all items are familiar, requires ORFi to avoid false positive responses. High-density evoked potentials were recorded from 19 healthy subjects during completion of the task. Performance was more accurate and faster on neutral than positive pictures in both runs and for all conditions. Evoked potential correlates of emotion and reality filtering occurred at 260–350 ms but dissociated in terms of amplitude and topography. In both runs, positive stimuli evoked a more negative frontal potential than neutral ones. In the second run, the frontal positivity characteristic of reality filtering was separately, and to the same degree, expressed for positive and neutral stimuli. We conclude that ORFi, the ability to place oneself correctly in time and space, is not influenced by emotional positivity of the processed material. PMID:27303276

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.

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

Consensus-based identification of factors related to false-positives in ultrasound scanning of synovitis and tenosynovitis.

PubMed

Ikeda, Kei; Narita, Akihiro; Ogasawara, Michihiro; Ohno, Shigeru; Kawahito, Yutaka; Kawakami, Atsushi; Ito, Hiromu; Matsushita, Isao; Suzuki, Takeshi; Misaki, Kenta; Ogura, Takehisa; Kamishima, Tamotsu; Seto, Yohei; Nakahara, Ryuichi; Kaneko, Atsushi; Nakamura, Takayuki; Henmi, Mihoko; Fukae, Jun; Nishida, Keiichiro; Sumida, Takayuki; Koike, Takao

2016-01-01

We aimed to identify causes of false-positives in ultrasound scanning of synovial/tenosynovial/bursal inflammation and provide corresponding imaging examples. We first performed systematic literature review to identify previously reported causes of false-positives. We next determined causes of false-positives and corresponding example images for educational material through Delphi exercises and discussion by 15 experts who were an instructor and/or a lecturer in the 2013 advanced course for musculoskeletal ultrasound organized by Japan College of Rheumatology Committee for the Standardization of Musculoskeletal Ultrasonography. Systematic literature review identified 11 articles relevant to sonographic false-positives of synovial/tenosynovial inflammation. Based on these studies, 21 candidate causes of false-positives were identified in the consensus meeting. Of these items, 11 achieved a predefined consensus (≥ 80%) in Delphi exercise and were classified as follows: (I) Gray-scale assessment [(A) non-specific synovial findings and (B) normal anatomical structures which can mimic synovial lesions due to either their low echogenicity or anisotropy]; (II) Doppler assessment [(A) Intra-articular normal vessels and (B) reverberation)]. Twenty-four corresponding examples with 49 still and 23 video images also achieved consensus. Our study provides a set of representative images that can help sonographers to understand false-positives in ultrasound scanning of synovitis and tenosynovitis.

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.

Application of the LDM algorithm to identify small lung nodules on low-dose MSCT scans

NASA Astrophysics Data System (ADS)

Zhao, Binsheng; Ginsberg, Michelle S.; Lefkowitz, Robert A.; Jiang, Li; Cooper, Cathleen; Schwartz, Lawrence H.

2004-05-01

In this work, we present a computer-aided detection (CAD) algorithm for small lung nodules on low-dose MSCT images. With this technique, identification of potential lung nodules is carried out with a local density maximum (LDM) algorithm, followed by reduction of false positives from the nodule candidates using task-specific 2-D/3-D features along with a knowledge-based nodule inclusion/exclusion strategy. Twenty-eight MSCT scans (40/80mAs, 120kVp, 5mm collimation/2.5mm reconstruction) from our lung cancer screening program that included at least one lung nodule were selected for this study. Two radiologists independently interpreted these cases. Subsequently, a consensus reading by both radiologists and CAD was generated to define a "gold standard". In total, 165 nodules were considered as the "gold standard" (average: 5.9 nodules/case; range: 1-22 nodules/case). The two radiologists detected 146 nodules (88.5%) and CAD detected 100 nodules (60.6%) with 8.7 false-positives/case. CAD detected an additional 19 nodules (6 nodules > 3mm and 13 nodules < 3mm) that had been missed by both radiologists. Preliminary results show that the CAD is capable of detecting small lung nodules with acceptable number of false-positives on low-dose MSCT scans and it can detect nodules that are otherwise missed by radiologists, though a majority are small nodules (< 3mm).

Revisiting Recombination Signal in the Tick-Borne Encephalitis Virus: A Simulation Approach

PubMed Central

Johansson, Magnus; Norberg, Peter

2016-01-01

The hypothesis of wide spread reticulate evolution in Tick-Borne Encephalitis virus (TBEV) has recently gained momentum with several publications describing past recombination events involving various TBEV clades. Despite a large body of work, no consensus has yet emerged on TBEV evolutionary dynamics. Understanding the occurrence and frequency of recombination in TBEV bears significant impact on epidemiology, evolution, and vaccination with live vaccines. In this study, we investigated the possibility of detecting recombination events in TBEV by simulating recombinations at several locations on the virus’ phylogenetic tree and for different lengths of recombining fragments. We derived estimations of rates of true and false positive for the detection of past recombination events for seven recombination detection algorithms. Our analytical framework can be applied to any investigation dealing with the difficult task of distinguishing genuine recombination signal from background noise. Our results suggest that the problem of false positives associated with low detection P-values in TBEV, is more insidious than generally acknowledged. We reappraised the recombination signals present in the empirical data, and showed that reliable signals could only be obtained in a few cases when highly genetically divergent strains were involved, whereas false positives were common among genetically similar strains. We thus conclude that recombination among wild-type TBEV strains may occur, which has potential implications for vaccination with live vaccines, but that these events are surprisingly rare. PMID:27760182

Autonomic responses to correct outcomes and interaction errors during single-switch scanning among children with severe spastic quadriplegic cerebral palsy

PubMed Central

2014-01-01

Background The combination of single-switch access technology and scanning is the most promising means of augmentative and alternative communication for many children with severe physical disabilities. However, the physical impairment of the child and the technology’s limited ability to interpret the child’s intentions often lead to false positives and negatives (corresponding to accidental and missed selections, respectively) occurring at rates that frustrate the user and preclude functional communication. Multiple psychophysiological studies have associated cardiac deceleration and increased phasic electrodermal activity with self-realization of errors among able-bodied individuals. Thus, physiological measurements have potential utility at enhancing single-switch access, provided that such prototypical autonomic responses exist in persons with profound disabilities. Methods The present case series investigated the autonomic responses of three pediatric single-switch users with severe spastic quadriplegic cerebral palsy, in the context of a single-switch letter matching activity. Each participant exhibited distinct autonomic responses to activity engagement. Results Our analysis confirmed the presence of the autonomic response pattern of cardiac deceleration and increased phasic electrodermal activity following true positives, false positives and false negatives errors, but not subsequent to true negative outcomes. Conclusions These findings suggest that there may be merit in complementing single-switch input with autonomic measurements to improve augmentative and alternative communications for pediatric access technology users. PMID:24607065

Autonomic responses to correct outcomes and interaction errors during single-switch scanning among children with severe spastic quadriplegic cerebral palsy.

PubMed

Leung, Brian; Chau, Tom

2014-03-08

The combination of single-switch access technology and scanning is the most promising means of augmentative and alternative communication for many children with severe physical disabilities. However, the physical impairment of the child and the technology's limited ability to interpret the child's intentions often lead to false positives and negatives (corresponding to accidental and missed selections, respectively) occurring at rates that frustrate the user and preclude functional communication. Multiple psychophysiological studies have associated cardiac deceleration and increased phasic electrodermal activity with self-realization of errors among able-bodied individuals. Thus, physiological measurements have potential utility at enhancing single-switch access, provided that such prototypical autonomic responses exist in persons with profound disabilities. The present case series investigated the autonomic responses of three pediatric single-switch users with severe spastic quadriplegic cerebral palsy, in the context of a single-switch letter matching activity. Each participant exhibited distinct autonomic responses to activity engagement. Our analysis confirmed the presence of the autonomic response pattern of cardiac deceleration and increased phasic electrodermal activity following true positives, false positives and false negatives errors, but not subsequent to true negative outcomes. These findings suggest that there may be merit in complementing single-switch input with autonomic measurements to improve augmentative and alternative communications for pediatric access technology users.

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

PubMed

Tenore, Peter L

2012-01-01

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

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

PubMed

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.

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

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

Biological false-positive venereal disease research laboratory test in cerebrospinal fluid in the diagnosis of neurosyphilis - a case-control study.

PubMed

Zheng, S; Lin, R J; Chan, Y H; Ngan, C C L

2018-03-01

There is no clear consensus on the diagnosis of neurosyphilis. The Venereal Disease Research Laboratory (VDRL) test from cerebrospinal fluid (CSF) has traditionally been considered the gold standard for diagnosing neurosyphilis but is widely known to be insensitive. In this study, we compared the clinical and laboratory characteristics of true-positive VDRL-CSF cases with biological false-positive VDRL-CSF cases. We retrospectively identified cases of true and false-positive VDRL-CSF across a 3-year period received by the Immunology and Serology Laboratory, Singapore General Hospital. A biological false-positive VDRL-CSF is defined as a reactive VDRL-CSF with a non-reactive Treponema pallidum particle agglutination (TPPA)-CSF and/or negative Line Immuno Assay (LIA)-CSF IgG. A true-positive VDRL-CSF is a reactive VDRL-CSF with a concordant reactive TPPA-CSF and/or positive LIA-CSF IgG. During the study period, a total of 1254 specimens underwent VDRL-CSF examination. Amongst these, 60 specimens from 53 patients tested positive for VDRL-CSF. Of the 53 patients, 42 (79.2%) were true-positive cases and 11 (20.8%) were false-positive cases. In our setting, a positive non-treponemal serology has 97.6% sensitivity, 100% specificity, 100% positive predictive value and 91.7% negative predictive value for a true-positive VDRL-CSF based on our laboratory definition. HIV seropositivity was an independent predictor of a true-positive VDRL-CSF. Biological false-positive VDRL-CSF is common in a setting where patients are tested without first establishing a serological diagnosis of syphilis. Serological testing should be performed prior to CSF evaluation for neurosyphilis. © 2017 European Academy of Dermatology and Venereology.

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

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

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...

A safe and effective management strategy for blunt cerebrovascular injury: Avoiding unnecessary anticoagulation and eliminating stroke.

PubMed

Shahan, Charles P; Magnotti, Louis J; Stickley, Shaun M; Weinberg, Jordan A; Hendrick, Leah E; Uhlmann, Rebecca A; Schroeppel, Thomas J; Hoit, Daniel A; Croce, Martin A; Fabian, Timothy C

2016-06-01

Few injuries have produced as much debate with respect to management as have blunt cerebrovascular injuries (BCVIs). Recent work (American Association for the Surgery of Trauma 2013) from our institution suggested that 64-channel multidetector computed tomographic angiography (CTA) could be the primary screening tool for BCVI. Consequently, our screening algorithm changed from digital subtraction angiography (DSA) to CTA, with DSA reserved for definitive diagnosis of BCVI following CTA-positive study results or unexplained neurologic findings. The current study was performed to evaluate outcomes, including the potential for missed clinically significant BCVI, since this new management algorithm was adopted. Patients who underwent DSA (positive CTA finding or unexplained neurologic finding) over an 18-month period subsequent to the previous study were identified. Screening and confirmatory test results, complications, and BCVI-related strokes were reviewed and compared. A total of 228 patients underwent DSA: 64% were male, with mean age and Injury Severity Score (ISS) of 43 years and 22, respectively. A total of 189 patients (83%) had a positive screening CTA result. Of these, DSA confirmed injury in 104 patients (55%); the remaining 85 patients (45%) (false-positive results) were found to have no injury on DSA. Five patients (4.8%) experienced BCVI-related strokes, unchanged from the previous study (3.9%, p = 0.756); two were symptomatic at trauma center presentation, and three occurred while receiving appropriate therapy. No patient with a negative screening CTA result experienced a stroke. This management scheme using 64-channel CTA for screening coupled with DSA for definitive diagnosis was proven to be safe and effective in identifying clinically significant BCVIs and maintaining a low stroke rate. Definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients (false-positive results). No strokes resulted from injuries missed by CTA. Diagnostic study, level III.

Finding strong lenses in CFHTLS using convolutional neural networks

NASA Astrophysics Data System (ADS)

Jacobs, C.; Glazebrook, K.; Collett, T.; More, A.; McCarthy, C.

2017-10-01

We train and apply convolutional neural networks, a machine learning technique developed to learn from and classify image data, to Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) imaging for the identification of potential strong lensing systems. An ensemble of four convolutional neural networks was trained on images of simulated galaxy-galaxy lenses. The training sets consisted of a total of 62 406 simulated lenses and 64 673 non-lens negative examples generated with two different methodologies. An ensemble of trained networks was applied to all of the 171 deg2 of the CFHTLS wide field image data, identifying 18 861 candidates including 63 known and 139 other potential lens candidates. A second search of 1.4 million early-type galaxies selected from the survey catalogue as potential deflectors, identified 2465 candidates including 117 previously known lens candidates, 29 confirmed lenses/high-quality lens candidates, 266 novel probable or potential lenses and 2097 candidates we classify as false positives. For the catalogue-based search we estimate a completeness of 21-28 per cent with respect to detectable lenses and a purity of 15 per cent, with a false-positive rate of 1 in 671 images tested. We predict a human astronomer reviewing candidates produced by the system would identify 20 probable lenses and 100 possible lenses per hour in a sample selected by the robot. Convolutional neural networks are therefore a promising tool for use in the search for lenses in current and forthcoming surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope.

Social influences on adaptive criterion learning.

PubMed

Cassidy, Brittany S; Dubé, Chad; Gutchess, Angela H

2015-07-01

People adaptively shift decision criteria when given biased feedback encouraging specific types of errors. Given that work on this topic has been conducted in nonsocial contexts, we extended the literature by examining adaptive criterion learning in both social and nonsocial contexts. Specifically, we compared potential differences in criterion shifting given performance feedback from social sources varying in reliability and from a nonsocial source. Participants became lax when given false positive feedback for false alarms, and became conservative when given false positive feedback for misses, replicating prior work. In terms of a social influence on adaptive criterion learning, people became more lax in response style over time if feedback was provided by a nonsocial source or by a social source meant to be perceived as unreliable and low-achieving. In contrast, people adopted a more conservative response style over time if performance feedback came from a high-achieving and reliable source. Awareness that a reliable and high-achieving person had not provided their feedback reduced the tendency to become more conservative, relative to those unaware of the source manipulation. Because teaching and learning often occur in a social context, these findings may have important implications for many scenarios in which people fine-tune their behaviors, given cues from others.

Human versus automation in responding to failures: an expected-value analysis

NASA Technical Reports Server (NTRS)

Sheridan, T. B.; Parasuraman, R.

2000-01-01

A simple analytical criterion is provided for deciding whether a human or automation is best for a failure detection task. The method is based on expected-value decision theory in much the same way as is signal detection. It requires specification of the probabilities of misses (false negatives) and false alarms (false positives) for both human and automation being considered, as well as factors independent of the choice--namely, costs and benefits of incorrect and correct decisions as well as the prior probability of failure. The method can also serve as a basis for comparing different modes of automation. Some limiting cases of application are discussed, as are some decision criteria other than expected value. Actual or potential applications include the design and evaluation of any system in which either humans or automation are being considered.

Inflammatory disorders mimicking periprosthetic joint infections may result in false positive α-defensin.

PubMed

Plate, Andreas; Stadler, Laura; Sutter, Reto; Anagnostopoulos, Alexia; Frustaci, Dario; Zbinden, Reinhard; Fucentese, Sandro F; Zinkernagel, Annelies S; Zingg, Patrick O; Achermann, Yvonne

2018-02-26

The antimicrobial peptide α-defensin has recently been introduced as potential "single" biomarker with a high sensitivity and specificity for the preoperative diagnosis of periprosthetic joint infections (PJIs). However, most studies assessed the benefits of the test with exclusion of patients with rheumatic diseases. We aimed to evaluate the α-defensin test in a cohort study without exclusion of cases with inflammatory diseases. Between June 2016 and June 2017, we prospectively included cases with a suspected PJI and an available lateral flow test α-defensin (Synovasure®) in synovial fluid. We compared the test result to the diagnostic criteria for PJIs published by an International Consensus Group in 2013. We included 109 cases (49 hips, 60 knees) in which preoperative α-defensin tests had been performed. Thereof, 20 PJIs (16 hips, 4 knees) were diagnosed. Preoperative α-defensin tests were positive in 25 cases (22.9%) with a test sensitivity and specificity of 90% and 92.1% (95% confidence interval [CI], 68.3 - 98.8% and 84.5 - 96.8%, respectively), and a high negative predictive value of 97.6% (95% CI, 91.7 - 99.4%). We interpreted seven α-defensin tests as false positive, mainly in cases with inflammatory rheumatic diseases, including crystal deposition diseases. A negative synovial α-defensin test can reliably rule out a PJI. However, the test can be false positive in conjunction with an underlying non-infectious inflammatory disease. We therefore propose to use the α-defensin test only in addition to MSIS criteria and assessment for crystals in synovial aspirates. Copyright © 2018. Published by Elsevier Ltd.

Way forward in case of a false positive in vitro genotoxicity result for a cosmetic substance?

PubMed

Doktorova, Tatyana Y; Ates, Gamze; Vinken, Mathieu; Vanhaecke, Tamara; Rogiers, Vera

2014-02-01

The currently used regulatory in vitro mutagenicity/genotoxicity test battery has a high sensitivity for detecting genotoxicants, but it suffers from a large number of irrelevant positive results (i.e. low specificity) thereby imposing the need for additional follow-up by in vitro and/or in vivo genotoxicity tests. This could have a major impact on the cosmetic industry in Europe, seen the imposed animal testing and marketing bans on cosmetics and their ingredients. Afflicted, but safe substances could therefore be lost. Using the example of triclosan, a cosmetic preservative, we describe here the potential applicability of a human toxicogenomics-based in vitro assay as a potential mechanistically based follow-up test for positive in vitro genotoxicity results. Triclosan shows a positive in vitro chromosomal aberration test, but is negative during in vivo follow-up tests. Toxicogenomics analysis unequivocally shows that triclosan is identified as a compound acting through non-DNA reactive mechanisms. This proof-of-principle study illustrates the potential of genome-wide transcriptomics data in combination with in vitro experimentation as a possible weight-of-evidence follow-up approach for de-risking a positive outcome in a standard mutagenicity/genotoxicity battery. As such a substantial number of cosmetic compounds wrongly identified as genotoxicants could be saved for the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-03-01

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

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.

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 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.

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.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

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

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

The efficacy and cost of alternative strategies for systematic screening for type 2 diabetes in the U.S. population 45-74 years of age.

PubMed

Johnson, Susan L; Tabaei, Bahman P; Herman, William H

2005-02-01

To simulate the outcomes of alternative strategies for screening the U.S. population 45-74 years of age for type 2 diabetes. We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs. At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion. Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.

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.

Detecting and characterizing coal mine related seismicity in the Western U.S. using subspace methods

NASA Astrophysics Data System (ADS)

Chambers, Derrick J. A.; Koper, Keith D.; Pankow, Kristine L.; McCarter, Michael K.

2015-11-01

We present an approach for subspace detection of small seismic events that includes methods for estimating magnitudes and associating detections from multiple stations into unique events. The process is used to identify mining related seismicity from a surface coal mine and an underground coal mining district, both located in the Western U.S. Using a blasting log and a locally derived seismic catalogue as ground truth, we assess detector performance in terms of verified detections, false positives and failed detections. We are able to correctly identify over 95 per cent of the surface coal mine blasts and about 33 per cent of the events from the underground mining district, while keeping the number of potential false positives relatively low by requiring all detections to occur on two stations. We find that most of the potential false detections for the underground coal district are genuine events missed by the local seismic network, demonstrating the usefulness of regional subspace detectors in augmenting local catalogues. We note a trade-off in detection performance between stations at smaller source-receiver distances, which have increased signal-to-noise ratio, and stations at larger distances, which have greater waveform similarity. We also explore the increased detection capabilities of a single higher dimension subspace detector, compared to multiple lower dimension detectors, in identifying events that can be described as linear combinations of training events. We find, in our data set, that such an advantage can be significant, justifying the use of a subspace detection scheme over conventional correlation methods.

Online information about risks and benefits of screening mammography in 10 European countries: An observational Web sites analysis.

PubMed

Spagnoli, Laura; Navaro, Monica; Ferrara, Pietro; Del Prete, Viola; Attena, Francesco

2018-06-01

Most publications about breast cancer do not provide accurate and comprehensive information, giving few or no data about risk/benefit ratios. We conducted a comparative study among 10 European countries about health information on breast cancer screening, assessing the first 10 Web sites addressing the general public that appeared following an Internet search.With the help of medical residents involved in the EuroNet MRPH Association, we analyzed the first 30 results of an Internet search in 10 European countries to determine the first 10 sites that offered screening mammography. We searched for the following information: source of information, general information on mammography and breast cancer screening, potential harms and risks (false positives, false positives after biopsy, false negatives, interval cancer, overdiagnosis, lead-time bias, and radiation exposure), and potential benefits (reduced mortality and increased survival).The United Kingdom provided the most information: 39 of all 70 possible identified risks (56%) were reported on its sites. Five nations presented over 35% of the possible information (United Kingdom, Spain, France, Ireland, and Italy); the others were under 30% (Portugal, Poland, Slovenia, Netherlands, and Croatia). Regarding the benefits, sites offering the most complete information were those in France (95%) and Poland (90%).Our results suggest that, despite consensus in the scientific community about providing better information to citizens, further efforts are needed to improve information about breast cancer screening. That conclusion also applies to countries showing better results. We believe that there should be greater coordination in this regard throughout Europe.

INFRARED- BASED BLINK DETECTING GLASSES FOR FACIAL PACING: TOWARDS A BIONIC BLINK

PubMed Central

Frigerio, Alice; Hadlock, Tessa A; Murray, Elizabeth H; Heaton, James T

2015-01-01

IMPORTANCE Facial paralysis remains one of the most challenging conditions to effectively manage, often causing life-altering deficits in both function and appearance. Facial rehabilitation via pacing and robotic technology has great yet unmet potential. A critical first step towards reanimating symmetrical facial movement in cases of unilateral paralysis is the detection of healthy movement to use as a trigger for stimulated movement. OBJECTIVE To test a blink detection system that can be attached to standard eyeglasses and used as part of a closed-loop facial pacing system. DESIGN Standard safety glasses were equipped with an infrared (IR) emitter/detector pair oriented horizontally across the palpebral fissure, creating a monitored IR beam that became interrupted when the eyelids closed. SETTING Tertiary care Facial Nerve Center. PARTICIPANTS 24 healthy volunteers. MAIN OUTCOME MEASURE Video-quantified blinking was compared with both IR sensor signal magnitude and rate of change in healthy participants with their gaze in repose, while they shifted gaze from central to far peripheral positions, and during the production of particular facial expressions. RESULTS Blink detection based on signal magnitude achieved 100% sensitivity in forward gaze, but generated false-detections on downward gaze. Calculations of peak rate of signal change (first derivative) typically distinguished blinks from gaze-related lid movements. During forward gaze, 87% of detected blink events were true positives, 11% were false positives, and 2% false negatives. Of the 11% false positives, 6% were associated with partial eyelid closures. During gaze changes, false blink detection occurred 6.3% of the time during lateral eye movements, 10.4% during upward movements, 46.5% during downward movements, and 5.6% for movements from an upward or downward gaze back to the primary gaze. Facial expressions disrupted sensor output if they caused substantial squinting or shifted the glasses. CONCLUSION AND RELEVANCE Our blink detection system provides a reliable, non-invasive indication of eyelid closure using an invisible light beam passing in front of the eye. Future versions will aim to mitigate detection errors by using multiple IR emitter/detector pairs mounted on the glasses, and alternative frame designs may reduce shifting of the sensors relative to the eye during facial movements. PMID:24699708

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012–2013

PubMed Central

Zucker, Jane R.; Giancotti, Francesca R.; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L.; Rosen, Jennifer B.

2017-01-01

ABSTRACT The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. PMID:28701468

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.

Static Analysis of Mobile Programs

DTIC Science & Technology

2017-02-01

information flow analysis has the potential to significantly aid human auditors , but it is handicapped by high false positive rates. Instead, auditors ...presents these specifications to a human auditor for validation. We have implemented this framework for a taint analysis of An- droid apps that relies on...of queries to a human auditor . 6.4 Inferring Library Information Flow Specifications Using Dynamic Anal- ysis In [15], we present a technique to mine

An Assessment of Normalized Difference Skin Index Robustness in Aquatic Environments

DTIC Science & Technology

2014-03-27

Index NDSI Normalized Difference Skin Index NDVI Normalized Difference Vegetation Index NIR Near-Infrared SAR Search and Rescue SERG Sensors... Vegetation and water-bearing objects with high scatter tend to have NDSI values similar to human skin , potentially causing false positives in certain...AN ASSESSMENT OF NORMALIZED DIFFERENCE SKIN INDEX ROBUSTNESS IN AQUATIC ENVIRONMENTS THESIS Alice W. Chan, First Lieutenant, USAF AFIT-ENG-14-M-17

Mapping of Synaptic-Neuronal Impairment on the Brain Surface through Fluctuation Analysis

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

Musha, Toshimitsu; Kurachi, Takayoshi; Suzuki, Naohoro

2005-08-25

Increase of demented population year by year is becoming a serious social problem to be solved urgently. The most effective way to block this increase is in its early detection by means of an inexpensive, non-invasive, sensitive, reliable and easy-to-operate diagnosis method. We have developed a method satisfying these requirements by using scalp potential fluctuations. We have collected 21ch EEG and SPECT data of 25 very mild Alzheimer's disease (AD) (MMSE=26{+-}1.8), moderately severe AD (MMSE=15.3{+-}6.4) and age-matched normal controls. As AD progresses, local synaptic-neuronal activity becomes abnormal, either more unstable or more inactive than in normal state. Such abnormality ismore » detected in terms of normalized power variance (NPV) of a scalp potential recorded with a scalp electrode. The z-score is defined by z = ((NPV of a subject) - (mean NPV of normal subjects))/(standard deviation of NPV of normal subjects). Correlation of a measured z-score map with the mean z-score map for AD patients characterizes likelihood to AD, in terms of which AD is discriminated from normal with 75% of true positive and 25% false negative probability. By introducing two thresholds, we have 90% of true positive and 10% of false negative discrimination.« less

A preliminary investigation into the use of biosensors to screen stomach contents for selected poisons and drugs.

PubMed

Redshaw, Natalie; Dickson, Stuart J; Ambrose, Vikki; Horswell, Jacqui

2007-10-25

The bioluminescence response of two genetically modified (lux-marked) bacteria to potentially toxic compounds (PTCs) in stomach contents was monitored using an in vitro assay. Cells of Escherichia coli HB101 and Salmonella typhimurium both carrying the lux light producing gene on a plasmid (pUDC607) were added to stomach contents containing various concentrations of organic and inorganic compounds. There was some variability in the response of the two biosensors, but both were sensitive to the herbicides glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T); pentachlorophenol (PCP), and inorganic poisons arsenic and mercury at a concentration range likely to be found in stomach contents samples submitted for toxicological analysis. This study demonstrates that biosensor bioassays could be a useful preliminary screening tool in forensic toxicology and that such a toxicological screening should include more than one test organism to maximise the number of PTC's detected. The probability of false positive results from samples containing compounds that may interfere with the assay such as over-the-counter (OTC) drugs and caffeine in tea and coffee was also investigated. Of the substances tested only coffee has the potential to cause false positive results.

High-resolution multi-band imaging for validation and characterization of small Kepler planets

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

Everett, Mark E.; Silva, David R.; Barclay, Thomas

2015-02-01

High-resolution ground-based optical speckle and near-infrared adaptive optics images are taken to search for stars in close angular proximity to host stars of candidate planets identified by the NASA Kepler Mission. Neighboring stars are a potential source of false positive signals. These stars also blend into Kepler light curves, affecting estimated planet properties, and are important for an understanding of planets in multiple star systems. Deep images with high angular resolution help to validate candidate planets by excluding potential background eclipsing binaries as the source of the transit signals. A study of 18 Kepler Object of Interest stars hosting amore » total of 28 candidate and validated planets is presented. Validation levels are determined for 18 planets against the likelihood of a false positive from a background eclipsing binary. Most of these are validated at the 99% level or higher, including five newly validated planets in two systems: Kepler-430 and Kepler-431. The stellar properties of the candidate host stars are determined by supplementing existing literature values with new spectroscopic characterizations. Close neighbors of seven of these stars are examined using multi-wavelength photometry to determine their nature and influence on the candidate planet properties. Most of the close neighbors appear to be gravitationally bound secondaries, while a few are best explained as closely co-aligned field stars. Revised planet properties are derived for each candidate and validated planet, including cases where the close neighbors are the potential host stars.« less

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

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.

False recollection of emotional pictures in Alzheimer's disease.

PubMed

Gallo, David A; Foster, Katherine T; Wong, Jessica T; Bennett, David A

2010-10-01

Alzheimer's Disease (AD) can reduce the effects of emotional content on memory for studied pictures, but less is known about false memory. In healthy adults, emotionally arousing pictures can be more susceptible to false memory effects than neutral pictures, potentially because emotional pictures share conceptual similarities that cause memory confusions. We investigated these effects in AD patients and healthy controls. Participants studied pictures and their verbal labels, and then picture recollection was tested using verbal labels as retrieval cues. Some of the test labels had been associated with a picture at study, whereas other had not. On this picture recollection test, we found that both AD patients and controls incorrectly endorsed some of the test labels that had not been studied with pictures. These errors were associated with medium to high levels of confidence, indicating some degree of false recollection. Critically, these false recollection judgments were greater for emotional compared to neutral items, especially for positively valenced items, in both AD patients and controls. Dysfunction of the amygdala and hippocampus in early AD may impair recollection, but AD did not disrupt the effect of emotion on false recollection judgments. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

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.

False-positive defects on exercise 99mTc-sestamibi SPECT imaging, but not on dipyridamole 99mTc-sestamibi SPECT imaging, in a patient with right bundle branch block (RBBB).

PubMed

Javadi, Hamid; Jallalat, Sara; Semnani, Shahriar; Mogharrabi, Mehdi; Nabipour, Iraj; Abbaszadeh, Moloud; Assadi, Majid

2013-01-01

False-positive findings with myocardial perfusion imaging (MPI) have frequently been identified in the presence of left bundle branch block (LBBB) and tend to lower the accuracy of MPI in individuals with normal coronary angiographs. Pharmacologic stress is recognized as the preferred method for MPI in patients with LBBB. In contrast, very few studies have evaluated the effect of right bundle branch block (RBBB) on MPI, and there is no consensus regarding the selection of pharmacologic versus exercise stress during MPI for the RBBB patient. In this study, we present a 45-year-old man with RBBB, who has a normal coronary artery angiography, but who showed abnormal myocardial perfusion with exercise MPI, and normal perfusion on dipyridamole MPI. The aim of the study is to stimulate awareness that the stress method selected for patients with RBBB can potentially interfere with the accuracy of the data.

PROSPECT improves cis-acting regulatory element prediction by integrating expression profile data with consensus pattern searches

PubMed Central

Fujibuchi, Wataru; Anderson, John S. J.; Landsman, David

2001-01-01

Consensus pattern and matrix-based searches designed to predict cis-acting transcriptional regulatory sequences have historically been subject to large numbers of false positives. We sought to decrease false positives by incorporating expression profile data into a consensus pattern-based search method. We have systematically analyzed the expression phenotypes of over 6000 yeast genes, across 121 expression profile experiments, and correlated them with the distribution of 14 known regulatory elements over sequences upstream of the genes. Our method is based on a metric we term probabilistic element assessment (PEA), which is a ranking of potential sites based on sequence similarity in the upstream regions of genes with similar expression phenotypes. For eight of the 14 known elements that we examined, our method had a much higher selectivity than a naïve consensus pattern search. Based on our analysis, we have developed a web-based tool called PROSPECT, which allows consensus pattern-based searching of gene clusters obtained from microarray data. PMID:11574681

Automated detection of retinal nerve fiber layer defects on fundus images: false positive reduction based on vessel likelihood

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Ishida, Kyoko; Sawada, Akira; Hatanaka, Yuji; Yamamoto, Tetsuya; Fujita, Hiroshi

2016-03-01

Early detection of glaucoma is important to slow down or cease progression of the disease and for preventing total blindness. We have previously proposed an automated scheme for detection of retinal nerve fiber layer defect (NFLD), which is one of the early signs of glaucoma observed on retinal fundus images. In this study, a new multi-step detection scheme was included to improve detection of subtle and narrow NFLDs. In addition, new features were added to distinguish between NFLDs and blood vessels, which are frequent sites of false positives (FPs). The result was evaluated with a new test dataset consisted of 261 cases, including 130 cases with NFLDs. Using the proposed method, the initial detection rate was improved from 82% to 98%. At the sensitivity of 80%, the number of FPs per image was reduced from 4.25 to 1.36. The result indicates the potential usefulness of the proposed method for early detection of glaucoma.

Detection of miRNA using a double-strand displacement biosensor with a self-complementary fluorescent reporter.

PubMed

Larkey, Nicholas E; Almlie, C Kyle; Tran, Victoria; Egan, Marianne; Burrows, Sean M

2014-02-04

Design of rapid, selective, and sensitive DNA and ribonucleic acid (RNA) biosensors capable of minimizing false positives from nuclease degradation is crucial for translational research and clinical diagnostics. We present proof-of-principle studies of an innovative micro-ribonucleic acid (miRNA) reporter-probe biosensor that displaces a self-complementary reporter, while target miRNA binds to the probe. The freed reporter folds into a hairpin structure to induce a decrease in the fluorescent signal. The self-complementarity of the reporter facilitates the reduction of false positives from nuclease degradation. Nanomolar limits of detection and quantitation were capable with this proof-of-principle design. Detection of miRNA occurs within 10 min and does not require any additional hybridization, labeling, or rinsing steps. The potential for medical applications of the reporter-probe biosensor is demonstrated by selective detection of a cancer regulating microRNA, Lethal-7 (Let-7a). Mechanisms for transporting the biosensor across the cell membrane will be the focus of future work.

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.

Detection of human enteric viruses in stream water with RT-PCR and cell culture.

USGS Publications Warehouse

Denis-Mize, K.; Fout, G.S.; Dahling, D.R.; Francy, D.S.

2004-01-01

A multiplex RT-PCR method was used to measure virus occurrence at five stream water sites that span a range of hydroclimatic, water-quality, and land-use characteristics. The performance of the molecular method was evaluated in comparison with traditional cell culture and Escherichia coli membrane filtration assays. The study incorporated multiple quality controls and included a control for virus recovery during the sampling procedure as well as controls to detect potentially false-negative and false-positive data. Poliovirus recovery ranged from 16 to 65% and was variable, even in samples collected within the same stream. All five sites were positive for viruses by both molecular and cell culture-based virus assays. Enteroviruses, reoviruses, rotaviruses, and hepatitis A viruses were detected, but the use of the quality controls proved critical for interpretation of the molecular data. All sites showed evidence of faecal contamination, and culturable viruses were detected in four samples that would have met the US Environmental Protection Agency's recommended E. coli guideline for safe recreational water.

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.

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

Correlation of final evoked potential amplitudes on intraoperative electromyography of the recurrent laryngeal nerve with immediate postoperative vocal fold function after thyroid and parathyroid surgery.

PubMed

Genther, Dane J; Kandil, Emad H; Noureldine, Salem I; Tufano, Ralph P

2014-02-01

Thyroid and parathyroid surgery are among the most common operations in the United States. Recurrent laryngeal nerve (RLN) injury is an infrequent but potentially detrimental complication. To correlate the final evoked potential amplitudes on intraoperative electromyography (EMG) after stimulation of the RLN with immediate postoperative vocal fold function after thyroid and parathyroid surgery. Retrospective observational study at a tertiary academic medical center. We included 674 patients (with 1000 nerves at risk) undergoing thyroid or parathyroid surgery from July 1, 2008, through June 30, 2012. Thyroid and parathyroid surgery. The association of final evoked potential amplitudes on EMG after thyroid and parathyroid surgery with vocal fold function as determined by postoperative fiberoptic laryngoscopy. Three patients experienced permanent vocal fold paresis (VFP) secondary to intraoperative RLN transection. Of the remaining 997 RLNs at risk, 22 (2.2%) in 20 patients exhibited temporary VFP on fiberoptic laryngoscopy after extubation. Eighteen patients experienced unilateral temporary VFP, and 2 experienced bilateral VFP without the need for tracheostomy or reintubation. Of the 22 RLNs, postdissection EMG amplitudes were less than 200 µV (true-positive findings) in 21 and at least 200 µV (false-negative finding) in 1. Of the 975 RLNs (97.5%) with normal function, postdissection EMG amplitudes were at least 200 µV (true-negative findings) in 967 and less than 200 µV (false-positive findings) in 8. In regard to immediate postoperative VFP, sensitivity, specificity, positive and negative predictive values, and accuracy of postdissection EMG amplitudes of less than 200 µV were 95.5%, 99.2%, 72.4%, 99.9%, and 99.1%, respectively. Intraoperative nerve monitoring of the RLN with EMG provides real-time information regarding neurophysiologic function of the RLN and can predict immediate postoperative VFP reliably when a cutoff of 200 µV is used. The high negative predictive value means that the surgeon can presume with confidence that the RLN has not been injured in the presence of a potential of at least 200 µV. This information would be useful in patients for whom bilateral thyroid surgery is being considered.

Sherlock Holmes and child psychopathology assessment approaches: the case of the false-positive.

PubMed

Jensen, P S; Watanabe, H

1999-02-01

To explore the relative value of various methods of assessing childhood psychopathology, the authors compared 4 groups of children: those who met criteria for one or more DSM diagnoses and scored high on parent symptom checklists, those who met psychopathology criteria on either one of these two assessment approaches alone, and those who met no psychopathology assessment criterion. Parents of 201 children completed the Child Behavior Checklist (CBCL), after which children and parents were administered the Diagnostic Interview Schedule for Children (version 2.1). Children and parents also completed other survey measures and symptom report inventories. The 4 groups of children were compared against "external validators" to examine the merits of "false-positive" and "false-negative" cases. True-positive cases (those that met DSM criteria and scored high on the CBCL) differed significantly from the true-negative cases on most external validators. "False-positive" and "false-negative" cases had intermediate levels of most risk factors and external validators. "False-positive" cases were not normal per se because they scored significantly above the true-negative group on a number of risk factors and external validators. A similar but less marked pattern was noted for "false-negatives." Findings call into question whether cases with high symptom checklist scores despite no formal diagnoses should be considered "false-positive." Pending the availability of robust markers for mental illness, researchers and clinicians must resist the tendency to reify diagnostic categories or to engage in arcane debates about the superiority of one assessment approach over another.

Retrospective imaging study on the diagnosis of pathological false positive iodine-131 scans in patients with thyroid cancer.

PubMed

Jia, Qiang; Meng, Zhaowei; Tan, Jian; Zhang, Guizhi; He, Yajing; Sun, Haoran; Yu, Chunshui; Li, Dong; Zheng, Wei; Wang, Renfei; Wang, Shen; Li, Xue; Zhang, Jianping; Hu, Tianpeng; Liu, N A; Upadhyaya, Arun

2015-11-01

Iodine-131 (I-131) therapy and post-therapy I-131 scanning are essential in the management of differentiated thyroid cancer (DTC). However, pathological false positive I-131 scans can lead to misdiagnosis and inappropriate I-131 treatment. This retrospective study aimed to investigate the best imaging modality for the diagnosis of pathological false positive I-131 scans in a DTC patient cohort, and to determine its incidence. DTC patient data archived from January 2008 to January 2010 was retrieved. Post-therapeutic I-131 scans were conducted and interpreted. The imaging modalities of magnetic resonance imaging (MRI), computed tomography and ultrasonography were applied and compared to check all suspected lesions. Biopsy or needle aspiration was conducted for patients who consented to the acquisition of histopathological confirmation. Data for 156 DTC patients were retrieved. Only 6 cases of pathological false-positives were found among these (incidence, 3.85%), which included 3 cases of thymic hyperplasia in the mediastinum, 1 case of pleomorphic adenoma in the parapharyngeal space and 1 case of thyroglossal duct cyst in the neck. MRI was demonstrated as the best imaging modality for diagnosis due to its superior soft tissue resolution. However, no imaging modality was able to identify the abdominal false positive-lesions observed in 2 cases, one of whom also had thymic hyperplasia. In conclusion, pathological false positive I-131 scans occurred with an incidence of 3.85%. MRI was the best imaging modality for diagnosing these pathological false-positives.

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

PubMed

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

2006-12-01

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

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.

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/

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.

Comparison of acridine orange and Gram stains for detection of microorganisms in cerebrospinal fluid and other clinical specimens.

PubMed Central

Lauer, B A; Reller, L B; Mirrett, S

1981-01-01

Acridine orange, a fluorochrome strain, is potentially superior to the Gram stain in the direct microscopic examination of clinical specimens because it gives striking differential staining between bacteria and background cells and debris. Its value in clinical laboratories was evaluated by testing 209 cerebrospinal fluids and 288 other body fluids, tissues, and exudates by both techniques. Smears were made in duplicate, fixed with methanol, stained, and examined without knowledge of the result of the companion smear or culture. Overall, acridine orange was slightly more sensitive than the Gram stain (acridine orange, 59.9%; Gram stain, 55.8%) and equally specific in detecting microorganisms. One smear was falsely positive by the Gram stain; none was falsely positive by the acridine orange stain. We conclude that acridine orange staining is a sensitive method for screening clinical specimens and reviewing selected specimens that are purulent, but negative by the Gram stain. Bloody fluids, thick exudates, and other normally difficult-to-read specimens were easily and quickly examined. We recommend, however, that positive smears be reexamined with the Gram stain to confirm the result and determine the Gram reaction of the microorganisms. PMID:6168652

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.

DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study

PubMed Central

Palomaki, Glenn E.; Deciu, Cosmin; Kloza, Edward M.; Lambert-Messerlian, Geralyn M.; Haddow, James E.; Neveux, Louis M.; Ehrich, Mathias; van den Boom, Dirk; Bombard, Allan T.; Grody, Wayne W.; Nelson, Stanley F.; Canick, Jacob A.

2012-01-01

Purpose: To determine whether maternal plasma cell–free DNA sequencing can effectively identify trisomy 18 and 13. Methods: Sixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias. Results: Among the 99.1% of samples interpreted (1,971/1,988), observed trisomy 18 and 13 detection rates were 100% (59/59) and 91.7% (11/12) at false-positive rates of 0.28% and 0.97%, respectively. Among the 17 samples without an interpretation, three were trisomy 18. If z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies. An independent academic laboratory confirmed performance in a subset. Conclusion: Among high-risk pregnancies, sequencing circulating cell–free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies. PMID:22281937

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.

Novel shifts in memory research and their impact on the legal process: introduction to the special issue on memory formation and suggestibility in the legal process.

PubMed

Otgaar, Henry; Sauerland, Melanie; Petrila, John P

2013-01-01

The functioning and frailties of memory are frequently at the centerpiece of much expert testimony about the reliability of eyewitness accounts. Although we have much knowledge about how false memories and suggestibility can affect testimonies, the contributions in this special issue show that when using a sound theoretical framework, novel directions in this field can surface. The papers in this issue can broadly be divided into contributions that are related to: (1) the exact determinants of false memory and suggestibility; (2) new paradigms in legal psychology; (3) positive consequences of memory illusions; and (4) developmental false memory research. Collectively, these contributions have the potential to provide novel shifts in memory research and push this field beyond its current boundaries. Copyright © 2013 John Wiley & Sons, Ltd.

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.

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

Exoplanet Biosignatures: Understanding Oxygen as a Biosignature in the Context of Its Environment.

PubMed

Meadows, Victoria S; Reinhard, Christopher T; Arney, Giada N; Parenteau, Mary N; Schwieterman, Edward W; Domagal-Goldman, Shawn D; Lincowski, Andrew P; Stapelfeldt, Karl R; Rauer, Heike; DasSarma, Shiladitya; Hegde, Siddharth; Narita, Norio; Deitrick, Russell; Lustig-Yaeger, Jacob; Lyons, Timothy W; Siegler, Nicholas; Grenfell, J Lee

2018-06-01

We describe how environmental context can help determine whether oxygen (O 2 ) detected in extrasolar planetary observations is more likely to have a biological source. Here we provide an in-depth, interdisciplinary example of O 2 biosignature identification and observation, which serves as the prototype for the development of a general framework for biosignature assessment. Photosynthetically generated O 2 is a potentially strong biosignature, and at high abundance, it was originally thought to be an unambiguous indicator for life. However, as a biosignature, O 2 faces two major challenges: (1) it was only present at high abundance for a relatively short period of Earth's history and (2) we now know of several potential planetary mechanisms that can generate abundant O 2 without life being present. Consequently, our ability to interpret both the presence and absence of O 2 in an exoplanetary spectrum relies on understanding the environmental context. Here we examine the coevolution of life with the early Earth's environment to identify how the interplay of sources and sinks may have suppressed O 2 release into the atmosphere for several billion years, producing a false negative for biologically generated O 2 . These studies suggest that planetary characteristics that may enhance false negatives should be considered when selecting targets for biosignature searches. We review the most recent knowledge of false positives for O 2 , planetary processes that may generate abundant atmospheric O 2 without a biosphere. We provide examples of how future photometric, spectroscopic, and time-dependent observations of O 2 and other aspects of the planetary environment can be used to rule out false positives and thereby increase our confidence that any observed O 2 is indeed a biosignature. These insights will guide and inform the development of future exoplanet characterization missions. Key Words: Biosignatures-Oxygenic photosynthesis-Exoplanets-Planetary atmospheres. Astrobiology 18, 630-662.

Exoplanet Biosignatures: Understanding Oxygen as a Biosignature in the Context of Its Environment

PubMed Central

Reinhard, Christopher T.; Arney, Giada N.; Parenteau, Mary N.; Schwieterman, Edward W.; Domagal-Goldman, Shawn D.; Lincowski, Andrew P.; Stapelfeldt, Karl R.; Rauer, Heike; DasSarma, Shiladitya; Hegde, Siddharth; Narita, Norio; Deitrick, Russell; Lustig-Yaeger, Jacob; Lyons, Timothy W.; Siegler, Nicholas; Grenfell, J. Lee

2018-01-01

Abstract We describe how environmental context can help determine whether oxygen (O2) detected in extrasolar planetary observations is more likely to have a biological source. Here we provide an in-depth, interdisciplinary example of O2 biosignature identification and observation, which serves as the prototype for the development of a general framework for biosignature assessment. Photosynthetically generated O2 is a potentially strong biosignature, and at high abundance, it was originally thought to be an unambiguous indicator for life. However, as a biosignature, O2 faces two major challenges: (1) it was only present at high abundance for a relatively short period of Earth's history and (2) we now know of several potential planetary mechanisms that can generate abundant O2 without life being present. Consequently, our ability to interpret both the presence and absence of O2 in an exoplanetary spectrum relies on understanding the environmental context. Here we examine the coevolution of life with the early Earth's environment to identify how the interplay of sources and sinks may have suppressed O2 release into the atmosphere for several billion years, producing a false negative for biologically generated O2. These studies suggest that planetary characteristics that may enhance false negatives should be considered when selecting targets for biosignature searches. We review the most recent knowledge of false positives for O2, planetary processes that may generate abundant atmospheric O2 without a biosphere. We provide examples of how future photometric, spectroscopic, and time-dependent observations of O2 and other aspects of the planetary environment can be used to rule out false positives and thereby increase our confidence that any observed O2 is indeed a biosignature. These insights will guide and inform the development of future exoplanet characterization missions. Key Words: Biosignatures—Oxygenic photosynthesis—Exoplanets—Planetary atmospheres. Astrobiology 18, 630–662. PMID:29746149

Handheld echocardiographic screening for rheumatic heart disease by non-experts.

PubMed

Ploutz, Michelle; Lu, Jimmy C; Scheel, Janet; Webb, Catherine; Ensing, Greg J; Aliku, Twalib; Lwabi, Peter; Sable, Craig; Beaton, Andrea

2016-01-01

Handheld echocardiography (HAND) has good sensitivity and specificity for rheumatic heart disease (RHD) when performed by cardiologists. However, physician shortages in RHD-endemic areas demand less-skilled users to make RHD screening practical. We examine nurse performance and interpretation of HAND using a simplified approach for RHD screening. Two nurses received training on HAND and a simplified screening approach. Consented students at two schools in Uganda were eligible for participation. A simplified approach (HAND performed and interpreted by a non-expert) was compared with the reference standard (standard portable echocardiography, performed and interpreted by experts according to the 2012 World Heart Federation guidelines). Reasons for false-positive and false-negative HAND studies were identified. A total of 1002 children were consented, with 956 (11.1 years, 41.8% male) having complete data for review. Diagnoses included: 913 (95.5%) children were classified normal, 32 (3.3%) borderline RHD and 11 (1.2%) definite RHD. The simplified approach had a sensitivity of 74.4% (58.8% to 86.5%) and a specificity of 78.8% (76.0% to 81.4%) for any RHD (borderline and definite). Sensitivity improved to 90.9% (58.7% to 98.5%) for definite RHD. Identification and measurement of erroneous colour jets was the most common reason for false-positive studies (n=164/194), while missed mitral regurgitation and shorter regurgitant jet lengths with HAND were the most common reasons for false-negative studies (n=10/11). Non-expert-led HAND screening programmes offer a potential solution to financial and workforce barriers that limit widespread RHD screening. Nurses trained on HAND using a simplified approach had reasonable sensitivity and specificity for RHD screening. Information on reasons for false-negative and false-positive screening studies should be used to inform future training protocols, which could lead to improved screening performance. 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/

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.

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.

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.

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.

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.

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.

Optimization of visual evoked potential (VEP) recording systems.

PubMed

Karanjia, Rustum; Brunet, Donald G; ten Hove, Martin W

2009-01-01

To explore the influence of environmental conditions on pattern visual evoked potential (VEP) recordings. Fourteen subjects with no known ocular pathology were recruited for the study. In an attempt to optimize the recording conditions, VEP recordings were performed in both the seated and recumbent positions. Comparisons were made between recordings using either LCD or CRT displays and recordings obtained in silence or with quiet background music. Paired recordings (in which only one variable was changed) were analyzed for changes in P100 latency, RMS noise, and variability. Baseline RMS noise demonstrated a significant decrease in the variability during the first 50msec accompanied by a 73% decrease in recording time for recumbent position when compared to the seated position (p<0.05). Visual evoked potentials recorded using LCD monitors demonstrated a significant increase in the P100 latency when compared to CRT recordings in the same subjects. The addition of background music did not affect the amount of RMS noise during the first 50msec of the recordings. This study demonstrates that the use of the recumbent position increases patient comfort and improves the signal to noise ratio. In contrast, the addition of background music to relax the patient did not improve the recording signal. Furthermore, the study illustrates the importance of avoiding low-contrast visual stimulation patterns obtained with LCD as they lead to higher latencies resulting in false positive recordings. These findings are important when establishing or modifying a pattern VEP recording protocol.

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

Consensus model for identification of novel PI3K inhibitors in large chemical library.

PubMed

Liew, Chin Yee; Ma, Xiao Hua; Yap, Chun Wei

2010-02-01

Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non-inhibitors) and 64,078 generated putative negatives was developed for predicting compounds with PI3K inhibitory activity of IC(50) < or = 10 microM. The consensus model has an estimated false positive rate of 0.75%. Nine novel potential inhibitors were identified using the consensus model and several of these contain structural features that are consistent with those found to be important for PI3K inhibitory activities. An advantage of the current model is that it does not require knowledge of 3D structural information of the various PI3K isoforms, which is not readily available for all isoforms.

Consensus model for identification of novel PI3K inhibitors in large chemical library

NASA Astrophysics Data System (ADS)

Liew, Chin Yee; Ma, Xiao Hua; Yap, Chun Wei

2010-02-01

Phosphoinositide 3-kinases (PI3Ks) inhibitors have treatment potential for cancer, diabetes, cardiovascular disease, chronic inflammation and asthma. A consensus model consisting of three base classifiers (AODE, kNN, and SVM) trained with 1,283 positive compounds (PI3K inhibitors), 16 negative compounds (PI3K non-inhibitors) and 64,078 generated putative negatives was developed for predicting compounds with PI3K inhibitory activity of IC50 ≤ 10 μM. The consensus model has an estimated false positive rate of 0.75%. Nine novel potential inhibitors were identified using the consensus model and several of these contain structural features that are consistent with those found to be important for PI3K inhibitory activities. An advantage of the current model is that it does not require knowledge of 3D structural information of the various PI3K isoforms, which is not readily available for all isoforms.

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.

Designing occupancy studies when false-positive detections occur

USGS Publications Warehouse

Clement, Matthew

2016-01-01

1.Recently, estimators have been developed to estimate occupancy probabilities when false-positive detections occur during presence-absence surveys. Some of these estimators combine different types of survey data to improve estimates of occupancy. With these estimators, there is a tradeoff between the number of sample units surveyed, and the number and type of surveys at each sample unit. Guidance on efficient design of studies when false positives occur is unavailable. 2.For a range of scenarios, I identified survey designs that minimized the mean square error of the estimate of occupancy. I considered an approach that uses one survey method and two observation states and an approach that uses two survey methods. For each approach, I used numerical methods to identify optimal survey designs when model assumptions were met and parameter values were correctly anticipated, when parameter values were not correctly anticipated, and when the assumption of no unmodelled detection heterogeneity was violated. 3.Under the approach with two observation states, false positive detections increased the number of recommended surveys, relative to standard occupancy models. If parameter values could not be anticipated, pessimism about detection probabilities avoided poor designs. Detection heterogeneity could require more or fewer repeat surveys, depending on parameter values. If model assumptions were met, the approach with two survey methods was inefficient. However, with poor anticipation of parameter values, with detection heterogeneity, or with removal sampling schemes, combining two survey methods could improve estimates of occupancy. 4.Ignoring false positives can yield biased parameter estimates, yet false positives greatly complicate the design of occupancy studies. Specific guidance for major types of false-positive occupancy models, and for two assumption violations common in field data, can conserve survey resources. This guidance can be used to design efficient monitoring programs and studies of species occurrence, species distribution, or habitat selection, when false positives occur during surveys.

A statistical model of false negative and false positive detection of phase singularities.

PubMed

Jacquemet, Vincent

2017-10-01

The complexity of cardiac fibrillation dynamics can be assessed by analyzing the distribution of phase singularities (PSs) observed using mapping systems. Interelectrode distance, however, limits the accuracy of PS detection. To investigate in a theoretical framework the PS false negative and false positive rates in relation to the characteristics of the mapping system and fibrillation dynamics, we propose a statistical model of phase maps with controllable number and locations of PSs. In this model, phase maps are generated from randomly distributed PSs with physiologically-plausible directions of rotation. Noise and distortion of the phase are added. PSs are detected using topological charge contour integrals on regular grids of varying resolutions. Over 100 × 10 6 realizations of the random field process are used to estimate average false negative and false positive rates using a Monte-Carlo approach. The false detection rates are shown to depend on the average distance between neighboring PSs expressed in units of interelectrode distance, following approximately a power law with exponents in the range of 1.14 to 2 for false negatives and around 2.8 for false positives. In the presence of noise or distortion of phase, false detection rates at high resolution tend to a non-zero noise-dependent lower bound. This model provides an easy-to-implement tool for benchmarking PS detection algorithms over a broad range of configurations with multiple PSs.

Automatic recognition of coronal type II radio bursts: The ARBIS 2 method and first observations

NASA Astrophysics Data System (ADS)

Lobzin, Vasili; Cairns, Iver; Robinson, Peter; Steward, Graham; Patterson, Garth

Major space weather events such as solar flares and coronal mass ejections are usually accompa-nied by solar radio bursts, which can potentially be used for real-time space weather forecasts. Type II radio bursts are produced near the local plasma frequency and its harmonic by fast electrons accelerated by a shock wave moving through the corona and solar wind with a typi-cal speed of 1000 km s-1 . The coronal bursts have dynamic spectra with frequency gradually falling with time and durations of several minutes. We present a new method developed to de-tect type II coronal radio bursts automatically and describe its implementation in an extended Automated Radio Burst Identification System (ARBIS 2). Preliminary tests of the method with spectra obtained in 2002 show that the performance of the current implementation is quite high, ˜ 80%, while the probability of false positives is reasonably low, with one false positive per 100-200 hr for high solar activity and less than one false event per 10000 hr for low solar activity periods. The first automatically detected coronal type II radio bursts are also presented. ARBIS 2 is now operational with IPS Radio and Space Services, providing email alerts and event lists internationally.

[Computed tomography with computer-assisted detection of pulmonary nodules in dogs and cats].

PubMed

Niesterok, C; Piesnack, S; Köhler, C; Ludewig, E; Alef, M; Kiefer, I

2015-01-01

The aim of this study was to assess the potential benefit of computer-assisted detection (CAD) of pulmonary nodules in veterinary medicine. Therefore, the CAD rate was compared to the detection rates of two individual examiners in terms of its sensitivity and false-positive findings. We included 51 dogs and 16 cats with pulmonary nodules previously diagnosed by computed tomography. First, the number of nodules ≥ 3 mm was recorded for each patient by two independent examiners. Subsequently, each examiner used the CAD software for automated nodule detection. With the knowledge of the CAD results, a final consensus decision on the number of nodules was achieved. The software used was a commercially available CAD program. The sensitivity of examiner 1 was 89.2%, while that of examiner 2 reached 87.4%. CAD had a sensitivity of 69.4%. With CAD, the sensitivity of examiner 1 increased to 94.7% and that of examiner 2 to 90.8%. The CAD-system, which we used in our study, had a moderate sensitivity of 69.4%. Despite its severe limitations, with a high level of false-positive and false-negative results, CAD increased the examiners' sensitivity. Therefore, its supportive role in diagnostics appears to be evident.

More than just T₄: diagnostic testing for hyperthyroidism in cats.

PubMed

Peterson, Mark E

2013-09-01

In older cats presenting with clinical features of hyperthyroidism, confirmation of a diagnosis of thyroid disease is usually straightforward. However, the potential for false-negative and false-positive results exists with all thyroid function tests (especially in the context of routine screening of asymptomatic cats) and leads to clinical dilemmas. For example, a high serum T₄ value may be found in a cat that lacks clinical signs of hyperthyroidism, or hyperthyroidism may be suspected in a cat with normal total T₄ concentrations. To avoid unnecessary treatment and potentially adverse effects in a euthyroid cat, thyroid function tests must always be interpreted in the light of the cat's history, clinical signs, physical examination findings and other laboratory findings. In this article the author reviews the use of commonly recommended thyroid function tests, focusing on clinical scenarios that present diagnostic difficulties. In doing so, he draws on the veterinary and comparative literature, his own clinical experience, and data, unpublished to date, obtained from a series of 100 hyperthyroid cats consecutively diagnosed at his clinic.

EuGI: a novel resource for studying genomic islands to facilitate horizontal gene transfer detection in eukaryotes.

PubMed

Clasen, Frederick Johannes; Pierneef, Rian Ewald; Slippers, Bernard; Reva, Oleg

2018-05-03

Genomic islands (GIs) are inserts of foreign DNA that have potentially arisen through horizontal gene transfer (HGT). There are evidences that GIs can contribute significantly to the evolution of prokaryotes. The acquisition of GIs through HGT in eukaryotes has, however, been largely unexplored. In this study, the previously developed GI prediction tool, SeqWord Gene Island Sniffer (SWGIS), is modified to predict GIs in eukaryotic chromosomes. Artificial simulations are used to estimate ratios of predicting false positive and false negative GIs by inserting GIs into different test chromosomes and performing the SWGIS v2.0 algorithm. Using SWGIS v2.0, GIs are then identified in 36 fungal, 22 protozoan and 8 invertebrate genomes. SWGIS v2.0 predicts GIs in large eukaryotic chromosomes based on the atypical nucleotide composition of these regions. Averages for predicting false negative and false positive GIs were 20.1% and 11.01% respectively. A total of 10,550 GIs were identified in 66 eukaryotic species with 5299 of these GIs coding for at least one functional protein. The EuGI web-resource, freely accessible at http://eugi.bi.up.ac.za , was developed that allows browsing the database created from identified GIs and genes within GIs through an interactive and visual interface. SWGIS v2.0 along with the EuGI database, which houses GIs identified in 66 different eukaryotic species, and the EuGI web-resource, provide the first comprehensive resource for studying HGT in eukaryotes.

Belief and sign, true and false: the unique of false belief reasoning.

PubMed

Zhang, Ting; Zhang, Qin; Li, Yiyuan; Long, Changquan; Li, Hong

2013-11-01

For a long time, a controversy has been proposed that whether the process of theory of mind is a result of domain-specific or domain-general changes (Wellman in The handbook of childhood cognitive development. Blackwell Publication, New Jersey, 2011). This event-related potential study explored the neural time course of domain-general and domain-specific components in belief reasoning. Fourteen participants completed location transfer false belief (FB), true belief (TB), false sign (FS) and true sign (TS) tasks, in which two pictures told a story related to a dog that ran from a green into a red box. In the TB and FB tasks, a boy saw or did not see the transfer of the dog, respectively. In the FS and TS tasks, an arrow that pointed to the green box either altered its direction to the red box or did not alter following the transfer of the dog. Participants then inferred where the boy thought of, or the arrow indicated the location of the dog. FB and TB reasoning elicited lower N2 amplitudes than FS and TS reasoning, which is associated with domain-general components, the detection, and classification. The late slow wave (LSW) for FB was more positive at frontal, central, and parietal sites than FS because of the domain-specific component involved in FB reasoning. However, the LSW was less positive for TB than for FB but did not differ from the TS condition, which implies that mental representation might not be involved in TB reasoning.

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.

[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.

In-office diagnostic arthroscopy for knee and shoulder intra-articular injuries its potential impact on cost savings in the United States

PubMed Central

2014-01-01

Background The purpose of this analysis was to determine whether in office diagnostic needle arthroscopy (Visionscope Imaging System [VSI]) can provide for improved diagnostic assessment and; more cost effective care. Methods Data on arthroscopy procedures in the US for deep seated pathology in the knee and shoulder were used (Calendar Year 2012). These procedures represent approximately 25-30% of all arthroscopic procedures performed annually. Sensitivities, specificities, positive predictive, and negative predictive values for MRI analysis of this deep seated pathology from systematic reviews and meta-analyses were used in assessing for false positive and false negative MRI findings. The costs of performing diagnostic and surgical arthroscopy procedures (using 2013 Medicare reimbursement amounts); costs associated with false negative findings; and the costs for treating associated complications arising from diagnostic and therapeutic arthroscopy procedures were then assessed. Results In patients presenting with medial meniscal pathology (ICD9CM diagnosis 836.0 over 540,000 procedures in CY 2012); use of the VSI system in place of MRI assessment (standard of care) resulted in a net cost savings to the system of $151 million. In patients presenting with rotator cuff pathology (ICD9CM 840.4 over 165,000 procedures in CY2012); use of VSI in place of MRI similarly saved $59 million. These savings were realized along with more appropriate care as; fewer patients were exposed to higher risk surgical arthroscopic procedures. Conclusions The use of an in-office arthroscopy system can: possibly save the US healthcare system money; shorten the diagnostic odyssey for patients; potentially better prepare clinicians for arthroscopic surgery (when needed) and; eliminate unnecessary outpatient arthroscopy procedures, which commonly result in surgical intervention. PMID:24885678

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

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 ...

Crystal Genetics, Inc.

PubMed

Kermani, Bahram G

2016-07-01

Crystal Genetics, Inc. is an early-stage genetic test company, focused on achieving the highest possible clinical-grade accuracy and comprehensiveness for detecting germline (e.g., in hereditary cancer) and somatic (e.g., in early cancer detection) mutations. Crystal's mission is to significantly improve the health status of the population, by providing high accuracy, comprehensive, flexible and affordable genetic tests, primarily in cancer. Crystal's philosophy is that when it comes to detecting mutations that are strongly correlated with life-threatening diseases, the detection accuracy of every single mutation counts: a single false-positive error could cause severe anxiety for the patient. And, more importantly, a single false-negative error could potentially cost the patient's life. Crystal's objective is to eliminate both of these error types.

Feline focus: Diagnostic testing for feline thyroid disease: hyperthyroidism.

PubMed

Peterson, Mark E

2013-08-01

In older cats presenting with clinical features of hyperthyroidism, confirming the diagnosis of thyroid disease is usually straightforward. However, the potential for false-negative and false-positive results exists with all thyroid function tests, especially when used for routine screening of large numbers of asymptomatic cats. Therefore, all thyroid function test results must be interpreted in light of the cat's history, clinical signs, and other laboratory findings. If a high serum thyroxine (T4) value is found in a cat that lacks clinical signs of hyperthyroidism, or if hyperthyroidism is suspected in a cat with normal total T4 concentrations, repeating the total T4 analysis, determining the free T4 concentration, or performing thyroid scintigraphy may be needed to confirm the diagnosis.

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.

[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.

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012-2013.

PubMed

Isaac, Beth M; Zucker, Jane R; Giancotti, Francesca R; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L; Rosen, Jennifer B

2017-09-01

The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. Copyright © 2017 American Society for Microbiology.

Implications of false-positive results for future cancer screenings.

PubMed

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

2018-06-01

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

False-Positive 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.

The effect of sample storage on the performance and reproducibility of the galactomannan EIA test.

PubMed

Kimpton, George; White, P Lewis; Barnes, Rosemary A

2014-08-01

Galactomannan enzyme immune assay (GM EIA) is a nonculture test for detecting invasive aspergillosis (IA) forming a key part of diagnosis and management. Recent reports have questioned the reproducibility of indices after sample storage. To investigate this, 198 serum samples (72 from cases and 126 from controls) and 61 plasma samples (24 from cases and 37 from controls), initially tested between 2010 and 2013, were retested to determine any change in index. Data were also collected on circulatory protein levels for false-positive serum samples. Serum indices significantly declined on retesting (median: initial, 0.50, retest, 0.23; P < 0.0001). This was shown to be diagnosis dependent as the decline was apparent on retesting of control samples (median: initial 0.50, retest 0.12; P < 0.0001), but was not evident with case samples (median: initial, 0.80, retest, 0.80; P = 0.724). Plasma samples showed little change on reanalysis after long-term storage at 4°C. Retesting after freezing showed a decrease in index values for controls (median: initial 0.40, retest 0.26; P = 0.0505), but no significant change in cases. Circulatory proteins showed a correlation between serum albumin concentration and difference in index value on retesting. Overall, this study suggests that a lack of reproducibility in GM EIA positivity is only significant when disease is absent. Retesting after freezing helps to differentiate false-positive GM EIA results and, with consecutive positivity, could help to improve accuracy in predicting disease status. The freezing of samples prior to testing could potentially reduce false-positivity rates and the need to retest. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Event-related brain potential correlates of two states of conscious awareness in memory

PubMed Central

Düzel, Emrah; Yonelinas, Andrew P.; Mangun, George R.; Heinze, Hans-Jochen; Tulving, Endel

1997-01-01

We report an event-related potential (ERP) experiment of human recognition memory that explored the relation between conscious awareness and electrophysiological activity of the brain. We recorded ERPs from healthy adults while they made “remember” and “know” recognition judgments about previously seen words. These two kinds of judgments reflect “autonoetic” and “noetic” awareness, respectively. The ERP effects differed between the two kinds of awareness while they were similar for “true” and “false” recognition. Noetic awareness was associated with a temporoparietal positivity in the N400 range (325–600 ms) and a late (600–1,000 ms) frontocentral negativity, whereas autonoetic awareness was associated with a widespread, late, bifrontal and left parietotemporal (600–1000 ms) positivity. In the very late (1,300–1,900 ms) time window, a right frontal positivity was observed for both remember and know judgments of both true and false targets. These results provide physiological evidence for two types of conscious awareness in episodic memory retrieval. PMID:9159185

Prediction of Protein-Protein Interaction Sites with Machine-Learning-Based Data-Cleaning and Post-Filtering Procedures.

PubMed

Liu, Guang-Hui; Shen, Hong-Bin; Yu, Dong-Jun

2016-04-01

Accurately predicting protein-protein interaction sites (PPIs) is currently a hot topic because it has been demonstrated to be very useful for understanding disease mechanisms and designing drugs. Machine-learning-based computational approaches have been broadly utilized and demonstrated to be useful for PPI prediction. However, directly applying traditional machine learning algorithms, which often assume that samples in different classes are balanced, often leads to poor performance because of the severe class imbalance that exists in the PPI prediction problem. In this study, we propose a novel method for improving PPI prediction performance by relieving the severity of class imbalance using a data-cleaning procedure and reducing predicted false positives with a post-filtering procedure: First, a machine-learning-based data-cleaning procedure is applied to remove those marginal targets, which may potentially have a negative effect on training a model with a clear classification boundary, from the majority samples to relieve the severity of class imbalance in the original training dataset; then, a prediction model is trained on the cleaned dataset; finally, an effective post-filtering procedure is further used to reduce potential false positive predictions. Stringent cross-validation and independent validation tests on benchmark datasets demonstrated the efficacy of the proposed method, which exhibits highly competitive performance compared with existing state-of-the-art sequence-based PPIs predictors and should supplement existing PPI prediction methods.

Improved detection of overrepresentation of Gene-Ontology annotations with parent child analysis.

PubMed

Grossmann, Steffen; Bauer, Sebastian; Robinson, Peter N; Vingron, Martin

2007-11-15

High-throughput experiments such as microarray hybridizations often yield long lists of genes found to share a certain characteristic such as differential expression. Exploring Gene Ontology (GO) annotations for such lists of genes has become a widespread practice to get first insights into the potential biological meaning of the experiment. The standard statistical approach to measuring overrepresentation of GO terms cannot cope with the dependencies resulting from the structure of GO because they analyze each term in isolation. Especially the fact that annotations are inherited from more specific descendant terms can result in certain types of false-positive results with potentially misleading biological interpretation, a phenomenon which we term the inheritance problem. We present here a novel approach to analysis of GO term overrepresentation that determines overrepresentation of terms in the context of annotations to the term's parents. This approach reduces the dependencies between the individual term's measurements, and thereby avoids producing false-positive results owing to the inheritance problem. ROC analysis using study sets with overrepresented GO terms showed a clear advantage for our approach over the standard algorithm with respect to the inheritance problem. Although there can be no gold standard for exploratory methods such as analysis of GO term overrepresentation, analysis of biological datasets suggests that our algorithm tends to identify the core GO terms that are most characteristic of the dataset being analyzed.

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

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.

Using machine learning algorithms to guide rehabilitation planning for home care clients.

PubMed

Zhu, Mu; Zhang, Zhanyang; Hirdes, John P; Stolee, Paul

2007-12-20

Targeting older clients for rehabilitation is a clinical challenge and a research priority. We investigate the potential of machine learning algorithms - Support Vector Machine (SVM) and K-Nearest Neighbors (KNN) - to guide rehabilitation planning for home care clients. This study is a secondary analysis of data on 24,724 longer-term clients from eight home care programs in Ontario. Data were collected with the RAI-HC assessment system, in which the Activities of Daily Living Clinical Assessment Protocol (ADLCAP) is used to identify clients with rehabilitation potential. For study purposes, a client is defined as having rehabilitation potential if there was: i) improvement in ADL functioning, or ii) discharge home. SVM and KNN results are compared with those obtained using the ADLCAP. For comparison, the machine learning algorithms use the same functional and health status indicators as the ADLCAP. The KNN and SVM algorithms achieved similar substantially improved performance over the ADLCAP, although false positive and false negative rates were still fairly high (FP > .18, FN > .34 versus FP > .29, FN. > .58 for ADLCAP). Results are used to suggest potential revisions to the ADLCAP. Machine learning algorithms achieved superior predictions than the current protocol. Machine learning results are less readily interpretable, but can also be used to guide development of improved clinical protocols.

An Evaluation of Unit and ½ Mass Correction Approaches as a Means of Minimizing the False Positives Produced by M+2 species in US EPA Method 200.8 using ICP-MS (webinar presentation)

EPA Science Inventory

Rare earth elements (REE) and certain alkaline earths can produce M+2 interferences in ICP-MS because they have sufficiently low second ionization energies. Four REEs (150Sm, 150Nd, 156Gd and 156Dy) produce false positives on 75As and 78Se and 132Ba can produce a false positive ...

Finite mixture modeling for vehicle crash data with application to hotspot identification.

PubMed

Park, Byung-Jung; Lord, Dominique; Lee, Chungwon

2014-10-01

The application of finite mixture regression models has recently gained an interest from highway safety researchers because of its considerable potential for addressing unobserved heterogeneity. Finite mixture models assume that the observations of a sample arise from two or more unobserved components with unknown proportions. Both fixed and varying weight parameter models have been shown to be useful for explaining the heterogeneity and the nature of the dispersion in crash data. Given the superior performance of the finite mixture model, this study, using observed and simulated data, investigated the relative performance of the finite mixture model and the traditional negative binomial (NB) model in terms of hotspot identification. For the observed data, rural multilane segment crash data for divided highways in California and Texas were used. The results showed that the difference measured by the percentage deviation in ranking orders was relatively small for this dataset. Nevertheless, the ranking results from the finite mixture model were considered more reliable than the NB model because of the better model specification. This finding was also supported by the simulation study which produced a high number of false positives and negatives when a mis-specified model was used for hotspot identification. Regarding an optimal threshold value for identifying hotspots, another simulation analysis indicated that there is a discrepancy between false discovery (increasing) and false negative rates (decreasing). Since the costs associated with false positives and false negatives are different, it is suggested that the selected optimal threshold value should be decided by considering the trade-offs between these two costs so that unnecessary expenses are minimized. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

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

PubMed

Tsakanikos, Elias; Reed, Phil

2005-12-01

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

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.

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

PubMed Central

2013-01-01

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

Performing IgE serum testing due to bioinformatics matches in the allergenicity assessment of GM crops.

PubMed

Goodman, Richard E

2008-10-01

Proteins introduced into genetically modified (GM) organisms through genetic engineering must be evaluated for their potential to cause allergic disease under various national laws and regulations. The Codex Alimentarius Commission guidance document (2003) calls for testing of serum IgE binding to the introduced protein if the gene was from an allergenic source, or the sequence of the transferred protein has >35% identity in any segment of 80 or more amino acids to a known allergen or shares significant short amino acid identities. The Codex guidance recognized that the assessment will evolve based on new scientific knowledge. Arguably, the current criteria are too conservative as discussed in this paper and they do not provide practical guidance on serum testing. The goals of this paper are: (1) to summarize evidence supporting the level of identity that indicates potential risk of cross-reactivity for those with existing allergies; (2) to provide example bioinformatics results and discuss their interpretation using published examples of proteins expressed in transgenic crops; and (3) to discuss key factors of experimental design and methodology for serum IgE tests to minimize the rate of false negative and false positive identification of potential allergens and cross-reactive proteins.

Prevalence and associated risk factors of latent tuberculosis infection among undergraduate and postgraduate dental students: A retrospective study.

PubMed

Lamberti, Monica; Muoio, Maria Rosaria; Westermann, Claudia; Nienhaus, Albert; Arnese, Antonio; Ribeiro Sobrinho, Antônio Paulino; Di Giuseppe, Gabriella; Garzillo, Elpidio Maria; Crispino, Vincenzo; Coppola, Nicola; De Rosa, Alfredo

2017-03-04

To estimate the prevalence of latent tuberculosis (TB) infection (LTBI) in Italian dental students exposed to the same occupational risks as dental health care personnel and to evaluate potential risk factors, a cross-sectional study was conducted on undergraduate and postgraduate students. After clinical evaluation, students were given a tuberculin skin test; in those found positive, an interferon-γ release assay (IGRA) was conducted. Of the 281 students enrolled, 10 were only TST positive; 8 were TST or/and IGRA positive. We found that participants testing positive at TST and/or IGRA, a group in which the risk of false LTBI positives is minimal, were older and had been studying longer. Although the prevalence of LTBI among dental students in our study was low, a risk of acquiring a work-related infection exists even in a country with a low incidence of TB. Thus, dental students should be screened to catch LTBI early on.

Observer training for computer-aided detection of pulmonary nodules in chest radiography.

PubMed

De Boo, Diederick W; van Hoorn, François; van Schuppen, Joost; Schijf, Laura; Scheerder, Maeke J; Freling, Nicole J; Mets, Onno; Weber, Michael; Schaefer-Prokop, Cornelia M

2012-08-01

To assess whether short-term feedback helps readers to increase their performance using computer-aided detection (CAD) for nodule detection in chest radiography. The 140 CXRs (56 with a solitary CT-proven nodules and 84 negative controls) were divided into four subsets of 35; each were read in a different order by six readers. Lesion presence, location and diagnostic confidence were scored without and with CAD (IQQA-Chest, EDDA Technology) as second reader. Readers received individual feedback after each subset. Sensitivity, specificity and area under the receiver-operating characteristics curve (AUC) were calculated for readings with and without CAD with respect to change over time and impact of CAD. CAD stand-alone sensitivity was 59 % with 1.9 false-positives per image. Mean AUC slightly increased over time with and without CAD (0.78 vs. 0.84 with and 0.76 vs. 0.82 without CAD) but differences did not reach significance. The sensitivity increased (65 % vs. 70 % and 66 % vs. 70 %) and specificity decreased over time (79 % vs. 74 % and 80 % vs. 77 %) but no significant impact of CAD was found. Short-term feedback does not increase the ability of readers to differentiate true- from false-positive candidate lesions and to use CAD more effectively. • Computer-aided detection (CAD) is increasingly used as an adjunct for many radiological techniques. • Short-term feedback does not improve reader performance with CAD in chest radiography. • Differentiation between true- and false-positive CAD for low conspicious possible lesions proves difficult. • CAD can potentially increase reader performance for nodule detection in chest radiography.

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.

A comparative evaluation of in vitro skin sensitisation tests: the human cell-line activation test (h-CLAT) versus the local lymph node assay (LLNA).

PubMed

Ashikaga, Takao; Sakaguchi, Hitoshi; Sono, Sakiko; Kosaka, Nanae; Ishikawa, Makie; Nukada, Yuko; Miyazawa, Masaaki; Ito, Yuichi; Nishiyama, Naohiro; Itagaki, Hiroshi

2010-08-01

We previously developed the human cell-line activation test (h-CLAT) in vitro skin sensitisation test, based on our reported finding that a 24-hour exposure of THP-1 cells (a human monocytic leukaemia cell line) to sensitisers is sufficient to induce the augmented expression of CD86 and CD54. The aim of this study is to confirm the predictive value of h-CLAT for skin sensitisation activity by employing a larger number of test chemicals. One hundred chemicals were selected, according to their categorisation in the local lymph node assay (LLNA), as being: extreme, strong, moderate and weak sensitisers, and non-sensitisers. The correlation of the h-CLAT results with the LLNA results was 84%. There were some false negatives (e.g. benzoyl peroxide, hexyl cinnamic aldehyde) and some false positives (e.g. 1-bromobutane, diethylphthalate). Eight out of the 9 false negatives (89%) were water-insoluble chemicals. The h-CLAT could positively predict not only extreme and strong sensitisers, but also moderate and weak sensitisers, though the detection rates of weak sensitisers and non-sensitisers were comparatively low. Some sensitisers enhanced both CD86 and CD54 levels, and some enhanced the level of only one of them. The use of the combination of CD86 and CD54 induction as a positive indicator, improved the accuracy of the test. In conclusion, the h-CLAT is expected to be a useful cell-based in vitro method for predicting skin sensitisation potential. 2010 FRAME.

Automating cell detection and classification in human brain fluorescent microscopy images using dictionary learning and sparse coding.

PubMed

Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M; Grinberg, Lea T

2017-04-15

Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

Convolutional neural network based deep-learning architecture for prostate cancer detection on multiparametric magnetic resonance images

NASA Astrophysics Data System (ADS)

Tsehay, Yohannes K.; Lay, Nathan S.; Roth, Holger R.; Wang, Xiaosong; Kwak, Jin Tae; Turkbey, Baris I.; Pinto, Peter A.; Wood, Brad J.; Summers, Ronald M.

2017-03-01

Prostate cancer (PCa) is the second most common cause of cancer related deaths in men. Multiparametric MRI (mpMRI) is the most accurate imaging method for PCa detection; however, it requires the expertise of experienced radiologists leading to inconsistency across readers of varying experience. To increase inter-reader agreement and sensitivity, we developed a computer-aided detection (CAD) system that can automatically detect lesions on mpMRI that readers can use as a reference. We investigated a convolutional neural network based deep-learing (DCNN) architecture to find an improved solution for PCa detection on mpMRI. We adopted a network architecture from a state-of-the-art edge detector that takes an image as an input and produces an image probability map. Two-fold cross validation along with a receiver operating characteristic (ROC) analysis and free-response ROC (FROC) were used to determine our deep-learning based prostate-CAD's (CADDL) performance. The efficacy was compared to an existing prostate CAD system that is based on hand-crafted features, which was evaluated on the same test-set. CADDL had an 86% detection rate at 20% false-positive rate while the top-down learning CAD had 80% detection rate at the same false-positive rate, which translated to 94% and 85% detection rate at 10 false-positives per patient on the FROC. A CNN based CAD is able to detect cancerous lesions on mpMRI of the prostate with results comparable to an existing prostate-CAD showing potential for further development.

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.

Sustained Performance of a "Physicianless" System of Automated Prehospital STEMI Diagnosis and Catheterization Laboratory Activation.

PubMed

Potter, Brian J; Matteau, Alexis; Mansour, Samer; Naim, Charbel; Riahi, Mounir; Essiambre, Richard; Montigny, Martine; Sareault, Isabelle; Gobeil, François

2017-01-01

Treatment times for primary percutaneous coronary intervention frequently exceed the recommended maximum delay. Automated "physicianless" systems of prehospital cardiac catheterization laboratory (CCL) activation show promise, but have been met with resistance over concerns regarding the potential for false positive and inappropriate activations (IAs). From 2010 to 2015, first responders performed electrocardiograms (ECGs) in the field for all patients with a complaint of chest pain or dyspnea. An automated machine diagnosis of "acute myocardial infarction" resulted in immediate CCL activation and direct transfer without transmission or human reinterpretation of the ECG prior to patient arrival. Any activation resulting from a nondiagnostic ECG (no ST-elevation) was deemed an IA, whereas activations resulting from ECG's compatible with ST-elevation myocardial infarction but without angiographic evidence of a coronary event were deemed false positive. In 2012, the referral algorithm was modified to exclude supraventricular tachycardia and left bundle branch block. There were 155 activations in the early cohort (2010-2012; prior to algorithm modification) and 313 in the late cohort (2012-2015). Algorithm modification resulted in a 42% relative decrease in the rate of IAs (12% vs 7%; P < 0.01) without a significant effect on treatment delay. A combination of prehospital automated ST-elevation myocardial infarction diagnosis and "physicianless" CCL activation is safe and effective in improving treatment delay and these results are sustainable over time. The performance of the referral algorithm in terms of IA and false positive is at least on par with systems that ensure real-time human oversight. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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).

Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases.

PubMed

Pavletic, Adriana J; Marques, Adriana R

2017-07-15

False-positive serology for Lyme disease was reported in patients with acute infectious mononucleosis. Here we describe 2 patients with early disseminated Lyme disease who were misdiagnosed with infectious mononucleosis based on false-positive tests for primary Epstein-Barr virus infection. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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

PubMed

Sephton, Mark A; Carter, Jonathan N

2014-08-01

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

Intraoperative imprint cytology for evaluation of sentinel lymph nodes from Merkel cell carcinoma.

PubMed

Wong, S Lindsey; Young, Yorke D; Geisinger, Kim R; Shen, Perry; Stewart, John H; Sangueza, Omar; Pichardo-Geisinger, Rita; Levine, Edward A

2009-07-01

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy. Intraoperative imprint cytology (IIC) can potentially avoid second operations for completion lymphadenectomy when nodal metastases are found during nodal staging with sentinel lymph node biopsy (SLN). This represents the first series of IIC for MCC we are aware of and our initial experience. Patients with biopsy-proven MCC underwent SLN (at the time of wide excision) using a double indicator technique with 99technetium sulfur colloid and isosulfan blue. SLN were identified and bisected and touch imprints of each half were made. One half was air-dried and stained with Diff-Quick and the other was fixed with 95 per cent alcohol and stained with hematoxylin and eosin (H&E). Paraffin-embedded sections were examined by H&E. Eighteen patients underwent successful SLN mapping procedures. IIC was negative in 84.2 per cent (16) cases. Three false-negatives occurred with IIC, but there were no false-positives, making the sensitivity 33 per cent and the specificity 100 per cent. Two of four patients with positive pathology-confirmed SLN also had positive IIC. SLN mapping has usefulness in patients with MCC. IIC is feasible and accurate in evaluating the SLN. IIC is a practical diagnostic tool when intraoperative analysis of SLN biopsy is desired for MCC.

Automated detection of masses on whole breast volume ultrasound scanner: false positive reduction using deep convolutional neural network

NASA Astrophysics Data System (ADS)

Hiramatsu, Yuya; Muramatsu, Chisako; Kobayashi, Hironobu; Hara, Takeshi; Fujita, Hiroshi

2017-03-01

Breast cancer screening with mammography and ultrasonography is expected to improve sensitivity compared with mammography alone, especially for women with dense breast. An automated breast volume scanner (ABVS) provides the operator-independent whole breast data which facilitate double reading and comparison with past exams, contralateral breast, and multimodality images. However, large volumetric data in screening practice increase radiologists' workload. Therefore, our goal is to develop a computer-aided detection scheme of breast masses in ABVS data for assisting radiologists' diagnosis and comparison with mammographic findings. In this study, false positive (FP) reduction scheme using deep convolutional neural network (DCNN) was investigated. For training DCNN, true positive and FP samples were obtained from the result of our initial mass detection scheme using the vector convergence filter. Regions of interest including the detected regions were extracted from the multiplanar reconstraction slices. We investigated methods to select effective FP samples for training the DCNN. Based on the free response receiver operating characteristic analysis, simple random sampling from the entire candidates was most effective in this study. Using DCNN, the number of FPs could be reduced by 60%, while retaining 90% of true masses. The result indicates the potential usefulness of DCNN for FP reduction in automated mass detection on ABVS images.

Lymphadenopathy resulting from acute toxoplasmosis mimicking relapse of non-Hodgkin's lymphoma on fluorodeoxyglucose positron emission tomography/computed tomography.

PubMed

Joshi, Prathamesh; Lele, Vikram; Mahajan, Pravin

2012-01-01

We report a case documenting fluorodeoxyglucose (FDG) accumulation in cervical, supraclavicular and axillary lymph nodes resulting from acute toxoplasmosis. A 50-year-old Indian female with history of non-Hodgkin's lymphoma (NHL) of left breast, postchemotherapy status, was found to have hypermetabolic right cervical, supraclavicular and axillary lymph nodes on a surveillance FDG positron emission tomography/computed tomography (PET/CT) scan. Her previous two PET/CT scans were unremarkable with no evidence of metabolically active disease. Therefore, a differential diagnosis of relapse of NHL versus infectious/inflammatory pathology was raised in the report. Biopsy of axillary lymph node demonstrated features characteristic of toxoplasmosis. The serological test results were also compatible with acute toxoplasmosis infection. Infective and inflammatory diseases are known to accumulate FDG, resulting in false positives for malignancy. This case demonstrates lymph nodal toxoplasmosis as a potential cause of false positive FDG PET/CT findings in patients with known malignancy and highlights the importance of histopathological and laboratory correlation for the accurate interpretation of FDG PET/CT scans.

Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

PubMed

Favaloro, Emmanuel J

2018-02-01

Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ("anti-PF4-heparin"). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ("screening"), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow, and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief article overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. © 2017 Wiley Periodicals, Inc.

Mantis: A Fast, Small, and Exact Large-Scale Sequence-Search Index.

PubMed

Pandey, Prashant; Almodaresi, Fatemeh; Bender, Michael A; Ferdman, Michael; Johnson, Rob; Patro, Rob

2018-06-18

Sequence-level searches on large collections of RNA sequencing experiments, such as the NCBI Sequence Read Archive (SRA), would enable one to ask many questions about the expression or variation of a given transcript in a population. Existing approaches, such as the sequence Bloom tree, suffer from fundamental limitations of the Bloom filter, resulting in slow build and query times, less-than-optimal space usage, and potentially large numbers of false-positives. This paper introduces Mantis, a space-efficient system that uses new data structures to index thousands of raw-read experiments and facilitates large-scale sequence searches. In our evaluation, index construction with Mantis is 6× faster and yields a 20% smaller index than the state-of-the-art split sequence Bloom tree (SSBT). For queries, Mantis is 6-108× faster than SSBT and has no false-positives or -negatives. For example, Mantis was able to search for all 200,400 known human transcripts in an index of 2,652 RNA sequencing experiments in 82 min; SSBT took close to 4 days. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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

PubMed

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

2012-11-01

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

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

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

PubMed

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

2014-01-01

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

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

PubMed

Larrabee, Glenn J

2014-01-01

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

An Evaluation of Unit and ½ Mass Correction Approaches as a ...

EPA Pesticide Factsheets

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 on 66Zn. Currently, US EPA Method 200.8 does not address these as sources of false positives. Additionally, these M+2 false positives are typically enhanced if collision cell technology is utilized to reduce polyatomic interferences associated with ICP-MS detection. A preliminary evaluation indicates that instrumental tuning conditions can impact the observed M+2/M+1 ratio and in turn the false positives generated on Zn, As and Se. Both unit and ½ mass approaches will be evaluated to correct for these false positives relative to the benchmark concentrations estimates from a triple quadrupole ICP-MS using standard solutions. The impact of matrix on these M+2 corrections will be evaluated over multiple analysis days with a focus on evaluating internal standards that mirror the matrix induced shifts in the M+2 ion transmission. The goal of this evaluation is to move away from fixed M+2 corrective approaches and move towards sample specific approaches that mimic the sample matrix induced variability while attempting to address intra-day variability of the M+2 correction factors through the use of internal standards. Oral Presentation via webinar for EPA Laboratory Technical Informati

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

PubMed

Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

PubMed Central

Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

2016-01-01

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

All That Glisters Is Not Gold: Sampling-Process Uncertainty in Disease-Vector Surveys with False-Negative and False-Positive Detections

PubMed Central

Abad-Franch, Fernando; Valença-Barbosa, Carolina; Sarquis, Otília; Lima, Marli M.

2014-01-01

Background Vector-borne diseases are major public health concerns worldwide. For many of them, vector control is still key to primary prevention, with control actions planned and evaluated using vector occurrence records. Yet vectors can be difficult to detect, and vector occurrence indices will be biased whenever spurious detection/non-detection records arise during surveys. Here, we investigate the process of Chagas disease vector detection, assessing the performance of the surveillance method used in most control programs – active triatomine-bug searches by trained health agents. Methodology/Principal Findings Control agents conducted triplicate vector searches in 414 man-made ecotopes of two rural localities. Ecotope-specific ‘detection histories’ (vectors or their traces detected or not in each individual search) were analyzed using ordinary methods that disregard detection failures and multiple detection-state site-occupancy models that accommodate false-negative and false-positive detections. Mean (±SE) vector-search sensitivity was ∼0.283±0.057. Vector-detection odds increased as bug colonies grew denser, and were lower in houses than in most peridomestic structures, particularly woodpiles. False-positive detections (non-vector fecal streaks misidentified as signs of vector presence) occurred with probability ∼0.011±0.008. The model-averaged estimate of infestation (44.5±6.4%) was ∼2.4–3.9 times higher than naïve indices computed assuming perfect detection after single vector searches (11.4–18.8%); about 106–137 infestation foci went undetected during such standard searches. Conclusions/Significance We illustrate a relatively straightforward approach to addressing vector detection uncertainty under realistic field survey conditions. Standard vector searches had low sensitivity except in certain singular circumstances. Our findings suggest that many infestation foci may go undetected during routine surveys, especially when vector density is low. Undetected foci can cause control failures and induce bias in entomological indices; this may confound disease risk assessment and mislead program managers into flawed decision making. By helping correct bias in naïve indices, the approach we illustrate has potential to critically strengthen vector-borne disease control-surveillance systems. PMID:25233352

Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism.

PubMed

Peterson, Mark E

2013-08-01

Although naturally occurring hypothyroidism is very rare in cats, iatrogenic hypothyroidism is a recognized complication of treatment for hyperthyroidism. However, confirming the diagnosis of hypothyroidism in cats is not generally straightforward. The potential for false-negative and false-positive results exists with all thyroid function tests, especially in older cats that may have concurrent nonthyroidal illness. Therefore, all thyroid function test results must be interpreted in light of the cat's history, clinical signs, and other laboratory findings. If a low to low-normal serum thyroxine (T4) value is found in a cat that has been treated for hyperthyroidism, repeating the total T4 analysis, determining free T4 and thyroid stimulating hormone (TSH) concentrations, or performing a TSH stimulation test or thyroid scintigraphy may be needed to confirm the diagnosis.

Predictive performance of the Vitrigel-eye irritancy test method using 118 chemicals.

PubMed

Yamaguchi, Hiroyuki; Kojima, Hajime; Takezawa, Toshiaki

2016-08-01

We recently developed a novel Vitrigel-eye irritancy test (EIT) method. The Vitrigel-EIT method is composed of two parts, i.e., the construction of a human corneal epithelium (HCE) model in a collagen vitrigel membrane chamber and the prediction of eye irritancy by analyzing the time-dependent profile of transepithelial electrical resistance values for 3 min after exposing a chemical to the HCE model. In this study, we estimated the predictive performance of Vitrigel-EIT method by testing a total of 118 chemicals. The category determined by the Vitrigel-EIT method in comparison to the globally harmonized system classification revealed that the sensitivity, specificity and accuracy were 90.1%, 65.9% and 80.5%, respectively. Here, five of seven false-negative chemicals were acidic chemicals inducing the irregular rising of transepithelial electrical resistance values. In case of eliminating the test chemical solutions showing pH 5 or lower, the sensitivity, specificity and accuracy were improved to 96.8%, 67.4% and 84.4%, respectively. Meanwhile, nine of 16 false-positive chemicals were classified irritant by the US Environmental Protection Agency. In addition, the disappearance of ZO-1, a tight junction-associated protein and MUC1, a cell membrane-spanning mucin was immunohistologically confirmed in the HCE models after exposing not only eye irritant chemicals but also false-positive chemicals, suggesting that such false-positive chemicals have an eye irritant potential. These data demonstrated that the Vitrigel-EIT method could provide excellent predictive performance to judge the widespread eye irritancy, including very mild irritant chemicals. We hope that the Vitrigel-EIT method contributes to the development of safe commodity chemicals. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Extended focused assessment with sonography for trauma (EFAST) in the diagnosis of pneumothorax: experience at a community based level I trauma center.

PubMed

Nandipati, Kalyana C; Allamaneni, Shyam; Kakarla, Ravindra; Wong, Alfredo; Richards, Neil; Satterfield, James; Turner, James W; Sung, Kae-Jae

2011-05-01

Early identification of pneumothorax is crucial to reduce the mortality in critically injured patients. The objective of our study is to investigate the utility of surgeon performed extended focused assessment with sonography for trauma (EFAST) in the diagnosis of pneumothorax. We prospectively analysed 204 trauma patients in our level I trauma center over a period of 12 (06/2007-05/2008) months in whom EFAST was performed. The patients' demographics, type of injury, clinical examination findings (decreased air entry), CXR, EFAST and CT scan findings were entered into the data base. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated. Of 204 patients (mean age--43.01+/-19.5 years, sex--male 152, female 52) 21 (10.3%) patients had pneumothorax. Of 21 patients who had pneumothorax 12 were due to blunt trauma and 9 were due to penetrating trauma. The diagnosis of pneumothorax in 204 patients demonstrated the following: clinical examination was positive in 17 patients (true positive in 13/21, 62%; 4 were false positive and 8 were false negative), CXR was positive in 16 (true positive in 15/19, 79%; 1 false positive, 4 missed and 2 CXR not performed before chest tube) patients and EFAST was positive in 21 patients (20 were true positive [95.2%], 1 false positive and 1 false negative). In diagnosing pneumothorax EFAST has significantly higher sensitivity compared to the CXR (P=0.02). Surgeon performed trauma room extended FAST is simple and has higher sensitivity compared to the chest X-ray and clinical examination in detecting pneumothorax. Published by Elsevier Ltd.

HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia.

PubMed

Favaloro, Emmanuel J; McCaughan, Georgia; Mohammed, Soma; Lau, Kun Kan Edwin; Gemmell, Rosalie; Cavanaugh, Lauren; Donikian, Dea; Kondo, Mayuko; Brighton, Timothy; Pasalic, Leonardo

2018-04-17

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy, which in a proportion of patients causes platelet activation and thrombosis. Initial clinical assessment of the likelihood of HIT is facilitated by laboratory testing to confirm or exclude HIT. This prospective investigation was performed over an 18-month period, and has involved testing of over 300 test samples from over 100 consecutive patients. Clinical assessment by 4T score was supplemented by laboratory tests that comprised both immunological [lateral flow ('STiC'), chemiluminescence (AcuStar; HIT-IgG (PF4-H) ), ELISA (Asserachrom HPIA IgG)] and functional assays [SRA, platelet aggregation using whole blood ('Multiplate') and platelet rich plasma ('LTA')]. We observed both false positive and false negative test findings with most assays. Overall, the whole blood aggregation method provided a reasonable alternative to SRA for identifying functional HIT. STiC, AcuStar and ELISA procedures were fairly comparable in terms of screening for HIT, although STiC and AcuStar both yielded false negatives, albeit also resulting in fewer false positives than ELISA. The 4T score had less utility in our patient cohort than we were expecting, although there was an association with the likelihood of HIT. Nevertheless, we accept that our observations are based on limited test numbers. In conclusion, no single approach (clinical or laboratory) was associated with optimal sensitivity or specificity of HIT exclusion or identification, and thus, a combination of clinical evaluation and laboratory testing will best ensure the accuracy of diagnosis. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Are there financial savings associated with supplementing current diagnostic practice for preeclampsia with a novel test? Learnings from a modeling analysis from a German payer perspective.

PubMed

Hadker, Nandini; Garg, Suchita; Costanzo, Cory; van der Helm, Wim; Creeden, James

2013-05-01

To quantify the financial impact of adding a novel serum test to the current diagnostic toolkit for preeclampsia (PE) detection in Germany. A decision-analytic model was created to quantify the economic impact of adding a recently developed novel diagnostic test for PE (Roche Diagnostics, Rotkreuz, Switzerland) to current diagnostic practice in Germany. The model simulated a cohort of 1000 pregnant patients receiving obstetric care and quantified the budget impact of adding the novel test to current German PE detection and management practices. The model estimates that the costs associated with managing a typical pregnancy in Germany are €941 when the novel test is used versus €1579 with standard practice. This represents savings of €637 per pregnant woman, even when the test is used as a supplementary diagnostic tool. The savings are attributed to the novel test's ability to better classify patients relative to current practice, specifically, its ability to reduce false negatives by 67% and false positives by 71%. The novel PE test has the potential to provide substantial cost savings to German healthcare payers, even when used as an addition to standard practice. Better classification of patients at risk for developing PE and declassification of those that are not compared to current practice leads to economic savings for the healthcare system. Furthermore, by reducing the rates of false-positive and false-negative classification relative to current standard of care, the test helps better target healthcare spending and lowers overall costs associated with PE care.

False-positive iodine-131 whole-body scan findings in patients with differentiated thyroid carcinoma: report of 11 cases and review of the literature.

PubMed

Buton, Leckzinscka; Morel, Olivier; Gault, Patricia; Illouz, Frédéric; Rodien, Patrice; Rohmer, Vincent

2013-07-01

Iodine-131 (I-131) whole-body scan (WBS) plays an important role in the management of patients with differentiated thyroid carcinoma (DTC), to detect normal thyroid remnants and recurrent or metastatic disease. A focus of I-131 accumulation outside the thyroid bed and the areas of physiological uptake is strongly suggestive of a distant functioning metastasis. However, many false-positive I-131 WBS findings have been reported in the literature. We describe a series of 11 personal cases of patients with DTC, collected from 1992 to 2011, in whom diagnostic or post-treatment WBS showed false-positive retention of I-131 in various locations. False-positive accumulations of I-131 on WBS may be classified according to the underlying pathophysiological mechanisms: external and internal contaminations by body secretions, ectopic normal thyroid and gastric tissues, inflammatory and infectious diseases, benign and malignant tumors, cysts and effusions of serous cavities, thymic uptake, and other non classified causes. Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Comparing diagnostic tests on benefit-risk.

PubMed

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

2016-01-01

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

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

PubMed Central

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

2012-01-01

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

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.

False-positive psychology: undisclosed flexibility in data collection and analysis allows presenting anything as significant.

PubMed

Simmons, Joseph P; Nelson, Leif D; Simonsohn, Uri

2011-11-01

In this article, we accomplish two things. First, we show that despite empirical psychologists' nominal endorsement of a low rate of false-positive findings (≤ .05), flexibility in data collection, analysis, and reporting dramatically increases actual false-positive rates. In many cases, a researcher is more likely to falsely find evidence that an effect exists than to correctly find evidence that it does not. We present computer simulations and a pair of actual experiments that demonstrate how unacceptably easy it is to accumulate (and report) statistically significant evidence for a false hypothesis. Second, we suggest a simple, low-cost, and straightforwardly effective disclosure-based solution to this problem. The solution involves six concrete requirements for authors and four guidelines for reviewers, all of which impose a minimal burden on the publication process.

Evaluation of recombinant proteins of Burkholderia mallei for serodiagnosis of glanders.

PubMed

Pal, Vijai; Kumar, Subodh; Malik, Praveen; Rai, Ganga Prasad

2012-08-01

Glanders is a contagious disease caused by the Gram-negative bacillus Burkholderia mallei. The number of equine glanders outbreaks has increased steadily during the last decade. The disease must be reported to the Office International des Epizooties, Paris, France. Glanders serodiagnosis is hampered by the considerable number of false positives and negatives of the internationally prescribed tests. The major problem leading to the low sensitivity and specificity of the complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) has been linked to the test antigens currently used, i.e., crude preparations of whole cells. False-positive results obtained from other diagnostic tests utilizing crude antigens lead to financial losses to animal owners, and false-negative results can turn a risk into a possible threat. In this study, we report on the identification of diagnostic targets using bioinformatics tools for serodiagnosis of glanders. The identified gene sequences were cloned and expressed as recombinant proteins. The purified recombinant proteins of B. mallei were used in an indirect ELISA format for serodiagnosis of glanders. Two recombinant proteins, 0375H and 0375TH, exhibited 100% sensitivity and specificity for glanders diagnosis. The proteins also did not cross-react with sera from patients with the closely related disease melioidosis. The results of this investigation highlight the potential of recombinant 0375H and 0375TH proteins in specific and sensitive diagnosis of glanders.

Evaluation of Recombinant Proteins of Burkholderia mallei for Serodiagnosis of Glanders

PubMed Central

Kumar, Subodh; Malik, Praveen

2012-01-01

Glanders is a contagious disease caused by the Gram-negative bacillus Burkholderia mallei. The number of equine glanders outbreaks has increased steadily during the last decade. The disease must be reported to the Office International des Epizooties, Paris, France. Glanders serodiagnosis is hampered by the considerable number of false positives and negatives of the internationally prescribed tests. The major problem leading to the low sensitivity and specificity of the complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) has been linked to the test antigens currently used, i.e., crude preparations of whole cells. False-positive results obtained from other diagnostic tests utilizing crude antigens lead to financial losses to animal owners, and false-negative results can turn a risk into a possible threat. In this study, we report on the identification of diagnostic targets using bioinformatics tools for serodiagnosis of glanders. The identified gene sequences were cloned and expressed as recombinant proteins. The purified recombinant proteins of B. mallei were used in an indirect ELISA format for serodiagnosis of glanders. Two recombinant proteins, 0375H and 0375TH, exhibited 100% sensitivity and specificity for glanders diagnosis. The proteins also did not cross-react with sera from patients with the closely related disease melioidosis. The results of this investigation highlight the potential of recombinant 0375H and 0375TH proteins in specific and sensitive diagnosis of glanders. PMID:22695165

The Effect Of Digital Unsharp Masking On The Detectability Of Interstitial Infiltrates And Pneumothoraces

NASA Astrophysics Data System (ADS)

MacMahon, Heber; Vyborny, Carl; Sabeti, Victoria; Metz, Charles; Doi, Kunio

1985-09-01

A potential advantage of digital radiographic systems is their ability to enhance images by various types of processing. Digital unsharp masking is one of the simplest and potentially most useful forms of enhancement. The efficacy of unsharp masking in clinical radiologic diagnosis has not been investigated systematically, however. The effect of digital unsharp masking on the detectability of two types of subtle abnormalities, pneumothorax and interstitial infiltrate, was studied in an observer performance test. An ROC analysis of this preliminary data suggests that unsharp masking may improve diagnostic accuracy for pneumothorax. Radiologists' performance in identifying interstitial infiltrates was degraded by the image processing, however, and false positive diagnoses tended to be more frequent.

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.

Generic, scalable and decentralized fault detection for robot swarms.

PubMed

Tarapore, Danesh; Christensen, Anders Lyhne; Timmis, Jon

2017-01-01

Robot swarms are large-scale multirobot systems with decentralized control which means that each robot acts based only on local perception and on local coordination with neighboring robots. The decentralized approach to control confers number of potential benefits. In particular, inherent scalability and robustness are often highlighted as key distinguishing features of robot swarms compared with systems that rely on traditional approaches to multirobot coordination. It has, however, been shown that swarm robotics systems are not always fault tolerant. To realize the robustness potential of robot swarms, it is thus essential to give systems the capacity to actively detect and accommodate faults. In this paper, we present a generic fault-detection system for robot swarms. We show how robots with limited and imperfect sensing capabilities are able to observe and classify the behavior of one another. In order to achieve this, the underlying classifier is an immune system-inspired algorithm that learns to distinguish between normal behavior and abnormal behavior online. Through a series of experiments, we systematically assess the performance of our approach in a detailed simulation environment. In particular, we analyze our system's capacity to correctly detect robots with faults, false positive rates, performance in a foraging task in which each robot exhibits a composite behavior, and performance under perturbations of the task environment. Results show that our generic fault-detection system is robust, that it is able to detect faults in a timely manner, and that it achieves a low false positive rate. The developed fault-detection system has the potential to enable long-term autonomy for robust multirobot systems, thus increasing the usefulness of robots for a diverse repertoire of upcoming applications in the area of distributed intelligent automation.

Generic, scalable and decentralized fault detection for robot swarms

PubMed Central

Christensen, Anders Lyhne; Timmis, Jon

2017-01-01

Robot swarms are large-scale multirobot systems with decentralized control which means that each robot acts based only on local perception and on local coordination with neighboring robots. The decentralized approach to control confers number of potential benefits. In particular, inherent scalability and robustness are often highlighted as key distinguishing features of robot swarms compared with systems that rely on traditional approaches to multirobot coordination. It has, however, been shown that swarm robotics systems are not always fault tolerant. To realize the robustness potential of robot swarms, it is thus essential to give systems the capacity to actively detect and accommodate faults. In this paper, we present a generic fault-detection system for robot swarms. We show how robots with limited and imperfect sensing capabilities are able to observe and classify the behavior of one another. In order to achieve this, the underlying classifier is an immune system-inspired algorithm that learns to distinguish between normal behavior and abnormal behavior online. Through a series of experiments, we systematically assess the performance of our approach in a detailed simulation environment. In particular, we analyze our system’s capacity to correctly detect robots with faults, false positive rates, performance in a foraging task in which each robot exhibits a composite behavior, and performance under perturbations of the task environment. Results show that our generic fault-detection system is robust, that it is able to detect faults in a timely manner, and that it achieves a low false positive rate. The developed fault-detection system has the potential to enable long-term autonomy for robust multirobot systems, thus increasing the usefulness of robots for a diverse repertoire of upcoming applications in the area of distributed intelligent automation. PMID:28806756

Colocalization recognition-activated cascade signal amplification strategy for ultrasensitive detection of transcription factors.

PubMed

Zhu, Desong; Wang, Lei; Xu, Xiaowen; Jiang, Wei

2017-03-15

Transcription factors (TFs) bind to specific double-stranded DNA (dsDNA) sequences in the regulatory regions of genes to regulate the process of gene transcription. Their expression levels sensitively reflect cell developmental situation and disease state. TFs have become potential diagnostic markers and therapeutic targets of cancers and some other diseases. Hence, high sensitive detection of TFs is of vital importance for early diagnosis of diseases and drugs development. The traditional exonucleases-assisted signal amplification methods suffered from the false positives caused by incomplete digestion of excess recognition probes. Herein, based on a new recognition way-colocalization recognition (CR)-activated dual signal amplification, an ultrasensitive fluorescent detection strategy for TFs was developed. TFs-induced the colocalization of three split recognition components resulted in noticeable increases of local effective concentrations and hybridization of three split components, which activated the subsequent cascade signal amplification including strand displacement amplification (SDA) and exponential rolling circle amplification (ERCA). This strategy eliminated the false positive influence and achieved ultra-high sensitivity towards the purified NF-κB p50 with detection limit of 2.0×10 -13 M. Moreover, NF-κB p50 can be detected in as low as 0.21ngμL -1 HeLa cell nuclear extracts. In addition, this proposed strategy could be used for the screening of NF-κB p50 activity inhibitors and potential anti-NF-κB p50 drugs. Finally, our proposed strategy offered a potential method for reliable detection of TFs in medical diagnosis and treatment research of cancers and other related diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of fecal occult blood tests for colorectal cancer screening in an Alaska Native population with high prevalence of Helicobacter pylori infection, 2008-2012.

PubMed

Redwood, Diana; Provost, Ellen; Asay, Elvin; Roberts, Diana; Haverkamp, Donald; Perdue, David; Bruce, Michael G; Sacco, Frank; Espey, David

2014-04-10

Alaska Native colorectal cancer (CRC) incidence and mortality rates are the highest of any ethnic/racial group in the United States. CRC screening using guaiac-based fecal occult blood tests (gFOBT) are not recommended for Alaska Native people because of false-positive results associated with a high prevalence of Helicobacter pylori-associated hemorrhagic gastritis. This study evaluated whether the newer immunochemical FOBT (iFOBT) resulted in a lower false-positive rate and higher specificity for detecting advanced colorectal neoplasia than gFOBT in a population with elevated prevalence of H. pylori infection. We used a population-based sample of 304 asymptomatic Alaska Native adults aged 40 years or older undergoing screening or surveillance colonoscopy (April 2008-January 2012). Specificity differed significantly (P < .001) between gFOBT (76%; 95% CI, 71%-81%) and iFOBT (92%; 95% CI, 89%-96%). Among H. pylori-positive participants (54%), specificity of iFOBT was even higher (93% vs 69%). Overall, sensitivity did not differ significantly (P = .73) between gFOBT (29%) and iFOBT (36%). Positive predictive value was 11% for gFOBT and 32% for iFOBT. The iFOBT had a significantly higher specificity than gFOBT, especially in participants with current H. pylori infection. The iFOBT represents a potential strategy for expanding CRC screening among Alaska Native and other populations with elevated prevalence of H. pylori, especially where access to screening endoscopy is limited.

DEWS (DEep White matter hyperintensity Segmentation framework): A fully automated pipeline for detecting small deep white matter hyperintensities in migraineurs.

PubMed

Park, Bo-Yong; Lee, Mi Ji; Lee, Seung-Hak; Cha, Jihoon; Chung, Chin-Sang; Kim, Sung Tae; Park, Hyunjin

2018-01-01

Migraineurs show an increased load of white matter hyperintensities (WMHs) and more rapid deep WMH progression. Previous methods for WMH segmentation have limited efficacy to detect small deep WMHs. We developed a new fully automated detection pipeline, DEWS (DEep White matter hyperintensity Segmentation framework), for small and superficially-located deep WMHs. A total of 148 non-elderly subjects with migraine were included in this study. The pipeline consists of three components: 1) white matter (WM) extraction, 2) WMH detection, and 3) false positive reduction. In WM extraction, we adjusted the WM mask to re-assign misclassified WMHs back to WM using many sequential low-level image processing steps. In WMH detection, the potential WMH clusters were detected using an intensity based threshold and region growing approach. For false positive reduction, the detected WMH clusters were classified into final WMHs and non-WMHs using the random forest (RF) classifier. Size, texture, and multi-scale deep features were used to train the RF classifier. DEWS successfully detected small deep WMHs with a high positive predictive value (PPV) of 0.98 and true positive rate (TPR) of 0.70 in the training and test sets. Similar performance of PPV (0.96) and TPR (0.68) was attained in the validation set. DEWS showed a superior performance in comparison with other methods. Our proposed pipeline is freely available online to help the research community in quantifying deep WMHs in non-elderly adults.

Detection of reactive metabolites using isotope-labeled glutathione trapping and simultaneous neutral loss and precursor ion scanning with ultra-high-pressure liquid chromatography triple quadruple mass spectrometry.

PubMed

Huang, Ke; Huang, Lingyi; van Breemen, Richard B

2015-04-07

Metabolic activation of drugs to electrophilic species is responsible for over 60% of black box warnings and drug withdrawals from the market place in the United States. Reactive metabolite trapping using glutathione (GSH) and analysis using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) or HPLC with high resolution mass spectrometry (mass defect filtering) have enabled screening for metabolic activation to become routine during drug development. However, current MS-based approaches cannot detect all GSH conjugates present in complex mixtures, especially those present in extracts of botanical dietary supplements. To overcome these limitations, a fast triple quadrupole mass spectrometer-based approach was developed that can detect positively and negatively charged GSH conjugates in a single analysis without the need for advanced knowledge of the elemental compositions of potential conjugates and while avoiding false positives. This approach utilized UHPLC instead of HPLC to shorten separation time and enhance sensitivity, incorporated stable-isotope labeled GSH to avoid false positives, and used fast polarity switching electrospray MS/MS to detect GSH conjugates that form positive and/or negative ions. The general new method was then used to test the licorice dietary supplement Glycyrrhiza glabra, which was found to form multiple GSH conjugates upon metabolic activation. Among the GSH conjugates found in the licorice assay were conjugates with isoliquiritigenin and glabridin, which is an irreversible inhibitor of cytochrome P450 enzymes.

Automatic lung nodule graph cuts segmentation with deep learning false positive reduction

NASA Astrophysics Data System (ADS)

Sun, Wenqing; Huang, Xia; Tseng, Tzu-Liang Bill; Qian, Wei

2017-03-01

To automatic detect lung nodules from CT images, we designed a two stage computer aided detection (CAD) system. The first stage is graph cuts segmentation to identify and segment the nodule candidates, and the second stage is convolutional neural network for false positive reduction. The dataset contains 595 CT cases randomly selected from Lung Image Database Consortium and Image Database Resource Initiative (LIDC/IDRI) and the 305 pulmonary nodules achieved diagnosis consensus by all four experienced radiologists were our detection targets. Consider each slice as an individual sample, 2844 nodules were included in our database. The graph cuts segmentation was conducted in a two-dimension manner, 2733 lung nodule ROIs are successfully identified and segmented. With a false positive reduction by a seven-layer convolutional neural network, 2535 nodules remain detected while the false positive dropped to 31.6%. The average F-measure of segmented lung nodule tissue is 0.8501.

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

PubMed

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

2004-01-01

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

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

PubMed

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

2014-07-09

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

Memory Distortion and Its Avoidance: An Event-Related Potentials Study on False Recognition and Correct Rejection

PubMed Central

Beato, Maria Soledad

2016-01-01

Memory researchers have long been captivated by the nature of memory distortions and have made efforts to identify the neural correlates of true and false memories. However, the underlying mechanisms of avoiding false memories by correctly rejecting related lures remains underexplored. In this study, we employed a variant of the Deese/Roediger-McDermott paradigm to explore neural signatures of committing and avoiding false memories. ERP were obtained for True recognition, False recognition, Correct rejection of new items, and, more importantly, Correct rejection of related lures. With these ERP data, early-frontal, left-parietal, and late right-frontal old/new effects (associated with familiarity, recollection, and monitoring processes, respectively) were analysed. Results indicated that there were similar patterns for True and False recognition in all three old/new effects analysed in our study. Also, False recognition and Correct rejection of related lures activities seemed to share common underlying familiarity-based processes. The ERP similarities between False recognition and Correct rejection of related lures disappeared when recollection processes were examined because only False recognition presented a parietal old/new effect. This finding supported the view that actual false recollections underlie false memories, providing evidence consistent with previous behavioural research and with most ERP and neuroimaging studies. Later, with the onset of monitoring processes, False recognition and Correct rejection of related lures waveforms presented, again, clearly dissociated patterns. Specifically, False recognition and True recognition showed more positive going patterns than Correct rejection of related lures signal and Correct rejection of new items signature. Since False recognition and Correct rejection of related lures triggered familiarity-recognition processes, our results suggest that deciding which items are studied is based more on recollection processes, which are later supported by monitoring processes. Results are discussed in terms of Activation-Monitoring Framework and Fuzzy Trace-Theory, the most prominent explanatory theories of false memory raised with the Deese/Roediger-McDermott paradigm. PMID:27711125

Memory Distortion and Its Avoidance: An Event-Related Potentials Study on False Recognition and Correct Rejection.

PubMed

Cadavid, Sara; Beato, Maria Soledad

2016-01-01

Memory researchers have long been captivated by the nature of memory distortions and have made efforts to identify the neural correlates of true and false memories. However, the underlying mechanisms of avoiding false memories by correctly rejecting related lures remains underexplored. In this study, we employed a variant of the Deese/Roediger-McDermott paradigm to explore neural signatures of committing and avoiding false memories. ERP were obtained for True recognition, False recognition, Correct rejection of new items, and, more importantly, Correct rejection of related lures. With these ERP data, early-frontal, left-parietal, and late right-frontal old/new effects (associated with familiarity, recollection, and monitoring processes, respectively) were analysed. Results indicated that there were similar patterns for True and False recognition in all three old/new effects analysed in our study. Also, False recognition and Correct rejection of related lures activities seemed to share common underlying familiarity-based processes. The ERP similarities between False recognition and Correct rejection of related lures disappeared when recollection processes were examined because only False recognition presented a parietal old/new effect. This finding supported the view that actual false recollections underlie false memories, providing evidence consistent with previous behavioural research and with most ERP and neuroimaging studies. Later, with the onset of monitoring processes, False recognition and Correct rejection of related lures waveforms presented, again, clearly dissociated patterns. Specifically, False recognition and True recognition showed more positive going patterns than Correct rejection of related lures signal and Correct rejection of new items signature. Since False recognition and Correct rejection of related lures triggered familiarity-recognition processes, our results suggest that deciding which items are studied is based more on recollection processes, which are later supported by monitoring processes. Results are discussed in terms of Activation-Monitoring Framework and Fuzzy Trace-Theory, the most prominent explanatory theories of false memory raised with the Deese/Roediger-McDermott paradigm.

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

PubMed

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

2010-01-31

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

Negative affect promotes encoding of and memory for details at the expense of the gist: affect, encoding, and false memories.

PubMed

Storbeck, Justin

2013-01-01

I investigated whether negative affective states enhance encoding of and memory for item-specific information reducing false memories. Positive, negative, and neutral moods were induced, and participants then completed a Deese-Roediger-McDermott (DRM) false-memory task. List items were presented in unique spatial locations or unique fonts to serve as measures for item-specific encoding. The negative mood conditions had more accurate memories for item-specific information, and they also had fewer false memories. The final experiment used a manipulation that drew attention to distinctive information, which aided learning for DRM words, but also promoted item-specific encoding. For the condition that promoted item-specific encoding, false memories were reduced for positive and neutral mood conditions to a rate similar to that of the negative mood condition. These experiments demonstrated that negative affective cues promote item-specific processing reducing false memories. People in positive and negative moods encode events differently creating different memories for the same event.

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

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-11-01

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

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

PubMed

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

2016-01-01

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

RESPECT-ED: Rates of Pulmonary Emboli (PE) and Sub-Segmental PE with Modern Computed Tomographic Pulmonary Angiograms in Emergency Departments: A Multi-Center Observational Study Finds Significant Yield Variation, Uncorrelated with Use or Small PE Rates.

PubMed

Mountain, David; Keijzers, Gerben; Chu, Kevin; Joseph, Anthony; Read, Catherine; Blecher, Gabriel; Furyk, Jeremy; Bharat, Chrianna; Velusamy, Karthik; Munro, Andrew; Baker, Kylie; Kinnear, Frances; Mukherjee, Ahses; Watkins, Gina; Buntine, Paul; Livesay, Georgia; Fatovich, Daniel

2016-01-01

Overuse of CT Pulmonary Angiograms (CTPA) for diagnosing pulmonary embolism (PE), particularly in Emergency Departments (ED), is considered problematic. Marked variations in positive CTPA rates are reported, with American 4-10% yields driving most concerns. Higher resolution CTPA may increase sub-segmental PE (SSPE) diagnoses, which may be up to 40% false positive. Excessive use and false positives could increase harm vs. benefit. These issues have not been systematically examined outside America. To describe current yield variation and CTPA utilisation in Australasian ED, exploring potential factors correlated with variation. A retrospective multi-centre review of consecutive ED-ordered CTPA using standard radiology reports. ED CTPA report data were inputted onto preformatted data-sheets. The primary outcome was site level yield, analysed both intra-site and against a nominated 15.3% yield. Factors potentially associated with yield were assessed for correlation. Fourteen radiology departments (15 ED) provided 7077 CTPA data (94% ≥64-slice CT); PE were reported in 1028 (yield 14.6% (95%CI 13.8-15.4%; range 9.3-25.3%; site variation p <0.0001) with four sites significantly below and one above the 15.3% target. Admissions, CTPA usage, PE diagnosis rates and size of PE were uncorrelated with yield. Large PE (≥lobar) were 55% (CI: 52.1-58.2%) and SSPE 8.8% (CI: 7.1-10.5%) of positive scans. CTPA usage (0.2-1.5% adult attendances) was correlated (p<0.006) with PE diagnosis but not SSPE: large PE proportions. We found significant intra-site CTPA yield variation within Australasia. Yield was not clearly correlated with CTPA usage or increased small PE rates. Both SSPE and large PE rates were similar to higher yield historical cohorts. CTPA use was considerably below USA 2.5-3% rates. Higher CTPA utilisation was positively correlated with PE diagnoses, but without evidence of increased proportions of small PE. This suggests that increased diagnoses seem to be of clinically relevant sized PE.

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

PubMed

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

2010-01-01

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

Wavelet method for CT colonography computer-aided polyp detection.

PubMed

Li, Jiang; Van Uitert, Robert; Yao, Jianhua; Petrick, Nicholas; Franaszek, Marek; Huang, Adam; Summers, Ronald M

2008-08-01

Computed tomographic colonography (CTC) computer aided detection (CAD) is a new method to detect colon polyps. Colonic polyps are abnormal growths that may become cancerous. Detection and removal of colonic polyps, particularly larger ones, has been shown to reduce the incidence of colorectal cancer. While high sensitivities and low false positive rates are consistently achieved for the detection of polyps sized 1 cm or larger, lower sensitivities and higher false positive rates occur when the goal of CAD is to identify "medium"-sized polyps, 6-9 mm in diameter. Such medium-sized polyps may be important for clinical patient management. We have developed a wavelet-based postprocessor to reduce false positives for this polyp size range. We applied the wavelet-based postprocessor to CTC CAD findings from 44 patients in whom 45 polyps with sizes of 6-9 mm were found at segmentally unblinded optical colonoscopy and visible on retrospective review of the CT colonography images. Prior to the application of the wavelet-based postprocessor, the CTC CAD system detected 33 of the polyps (sensitivity 73.33%) with 12.4 false positives per patient, a sensitivity comparable to that of expert radiologists. Fourfold cross validation with 5000 bootstraps showed that the wavelet-based postprocessor could reduce the false positives by 56.61% (p <0.001), to 5.38 per patient (95% confidence interval [4.41, 6.34]), without significant sensitivity degradation (32/45, 71.11%, 95% confidence interval [66.39%, 75.74%], p=0.1713). We conclude that this wavelet-based postprocessor can substantially reduce the false positive rate of our CTC CAD for this important polyp size range.

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.

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

Automatic detection of axillary lymphadenopathy on CT scans of untreated chronic lymphocytic leukemia patients

NASA Astrophysics Data System (ADS)

Liu, Jiamin; Hua, Jeremy; Chellappa, Vivek; Petrick, Nicholas; Sahiner, Berkman; Farooqui, Mohammed; Marti, Gerald; Wiestner, Adrian; Summers, Ronald M.

2012-03-01

Patients with chronic lymphocytic leukemia (CLL) have an increased frequency of axillary lymphadenopathy. Pretreatment CT scans can be used to upstage patients at the time of presentation and post-treatment CT scans can reduce the number of complete responses. In the current clinical workflow, the detection and diagnosis of lymph nodes is usually performed manually by examining all slices of CT images, which can be time consuming and highly dependent on the observer's experience. A system for automatic lymph node detection and measurement is desired. We propose a computer aided detection (CAD) system for axillary lymph nodes on CT scans in CLL patients. The lung is first automatically segmented and the patient's body in lung region is extracted to set the search region for lymph nodes. Multi-scale Hessian based blob detection is then applied to detect potential lymph nodes within the search region. Next, the detected potential candidates are segmented by fast level set method. Finally, features are calculated from the segmented candidates and support vector machine (SVM) classification is utilized for false positive reduction. Two blobness features, Frangi's and Li's, are tested and their free-response receiver operating characteristic (FROC) curves are generated to assess system performance. We applied our detection system to 12 patients with 168 axillary lymph nodes measuring greater than 10 mm. All lymph nodes are manually labeled as ground truth. The system achieved sensitivities of 81% and 85% at 2 false positives per patient for Frangi's and Li's blobness, respectively.

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

Measuring the psychosocial consequences of screening

PubMed Central

Brodersen, John; McKenna, Stephen P; Doward, Lynda C; Thorsen, Hanne

2007-01-01

The last three decades have seen a dramatic rise in the implementation of screening programmes for cancer in industrialised countries. However, in contrast to screening for infectious diseases, most cancer screening programmes only have the potential to reduce mortality; they cannot lower the incidence of cancer in a population. In fact, most cancer screening programmes have been shown to increase the incidence of the disease as a consequence of over-diagnosis. A further dilemma of cancer screening programmes is that they do not distinguish between healthy people and those with disease. Rather, they identify a continuum of disease severity. Consequently, many healthy people who have abnormal screening tests are wrongly diagnosed. Indeed, studies have demonstrated that for each screening-prevented death from cancer, at least 200 false-positive results are given. Therefore, screening has the potential to be harmful as well as beneficial. The psychosocial consequences of false-positive screening results cannot be determined by diagnostic tests or by other technical means. Instead, patient reported outcome measures must be employed. To measure the outcomes of screening accurately and comprehensively patient reported outcome measures have to capture; the nature and extent of the psychosocial consequences and how these change over time. The outcome measures used must have high content validity and their psychometric properties should be determined prior to their use in the specific population. In particular it is important to establish unidimensionality, additivity and item ordering through the application of Item Response Theory. PMID:17210071

Exoplanet Biosignatures: A Framework for Their Assessment.

PubMed

Catling, David C; Krissansen-Totton, Joshua; Kiang, Nancy Y; Crisp, David; Robinson, Tyler D; DasSarma, Shiladitya; Rushby, Andrew J; Del Genio, Anthony; Bains, William; Domagal-Goldman, Shawn

2018-04-20

Finding life on exoplanets from telescopic observations is an ultimate goal of exoplanet science. Life produces gases and other substances, such as pigments, which can have distinct spectral or photometric signatures. Whether or not life is found with future data must be expressed with probabilities, requiring a framework of biosignature assessment. We present a framework in which we advocate using biogeochemical "Exo-Earth System" models to simulate potential biosignatures in spectra or photometry. Given actual observations, simulations are used to find the Bayesian likelihoods of those data occurring for scenarios with and without life. The latter includes "false positives" wherein abiotic sources mimic biosignatures. Prior knowledge of factors influencing planetary inhabitation, including previous observations, is combined with the likelihoods to give the Bayesian posterior probability of life existing on a given exoplanet. Four components of observation and analysis are necessary. (1) Characterization of stellar (e.g., age and spectrum) and exoplanetary system properties, including "external" exoplanet parameters (e.g., mass and radius), to determine an exoplanet's suitability for life. (2) Characterization of "internal" exoplanet parameters (e.g., climate) to evaluate habitability. (3) Assessment of potential biosignatures within the environmental context (components 1-2), including corroborating evidence. (4) Exclusion of false positives. We propose that resulting posterior Bayesian probabilities of life's existence map to five confidence levels, ranging from "very likely" (90-100%) to "very unlikely" (<10%) inhabited. Key Words: Bayesian statistics-Biosignatures-Drake equation-Exoplanets-Habitability-Planetary science. Astrobiology 18, xxx-xxx.

Acid-fast Smear and Histopathology Results Provide Guidance for the Appropriate Use of Broad-Range Polymerase Chain Reaction and Sequencing for Mycobacteria.

PubMed

Miller, Kennon; Harrington, Susan M; Procop, Gary W

2015-08-01

New molecular diagnostic tests are attractive because of the potential they hold for improving diagnostics in microbiology. The value of these tests, which is often assumed, should be investigated to determine the best use of these potentially powerful tools. To investigate the usefulness of broad-range polymerase chain reaction (PCR), followed by sequencing, in mycobacterial infections. We reviewed the test performance of acid-fast bacilli (AFB) PCR and traditional diagnostic methods (histopathology, AFB smear, and culture). We assessed the diagnostic effect and cost of the unrestricted ordering of broad-range PCR for the detection and identification of mycobacteria in clinical specimens. The AFB PCR was less sensitive than culture and histopathology and was less specific than culture, AFB smear, and histopathology. During 18 months, $93 063 was spent on 183 patient specimens for broad-range PCR and DNA sequencing for mycobacteria to confirm one culture-proven Mycobacterium tuberculosis infection that was also known to be positive by AFB smear and histopathology. In this cohort, there was a false-negative AFB PCR for M tuberculosis and a false-positive AFB PCR for Mycobacterium lentiflavum . Testing of AFB smear-negative specimens from patients without an inflammatory response supportive of a mycobacterial infection is costly and has not been proven to improve patient care. Traditional diagnostics (histopathology, AFB smear, and culture) should remain the primary methods for the detection of mycobacteria in clinical specimens.

Direct-to-consumer online genetic testing and the four principles: an analysis of the ethical issues.

PubMed

Wasson, Katherine; Cook, E David; Helzlsouer, Kathy

2006-01-01

The development of genetic tests marketed and sold direct-to-consumers (DTC) via the internet raises moral concerns and debate about their appropriateness and ethical and clinical significance. These tests are offered for a wide range of diseases and conditions, and the mutations have variable penetrance and associated risk. A number of these tests lack data on their accuracy and reliability, making interpretation of results difficult. DTC genetic testing is undertaken outside the context of the physician-patient relationship and may lack appropriate individual and family genetic counseling, leaving the consumer vulnerable to potential harms, such as misinterpretation of results, including false positive or false reassurance, with limited or no benefits. Beauchamp and Childress's four principles of biomedical ethics provide a framework for analyzing the ethical issues raised by DTC genetic testing. We argue that the potential harms outweigh the potential benefits of such tests, that respect for autonomy should be limited in light of potential harm from DTC testing, and that the availability of genetic testing over the internet may be considered unfair and unjust and affect resource allocation by placing an unfair burden on primary care physicians. In light of the moral issues posed by these tests, practical responses are suggested in the areas of consumer education, medical education, and interaction with commercial companies.

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.

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.

Automating Cell Detection and Classification in Human Brain Fluorescent Microscopy Images Using Dictionary Learning and Sparse Coding

PubMed Central

Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A.; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M.

2017-01-01

Background Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. New method Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Results Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. Comparison with existing methods We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. Conclusion The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. PMID:28267565

Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology.

PubMed

Bianchi, Diana W; Parsa, Saba; Bhatt, Sucheta; Halks-Miller, Meredith; Kurtzman, Kathryn; Sehnert, Amy J; Swanson, Amy

2015-02-01

To describe the clinical experience with noninvasive prenatal testing for fetal sex chromosomes using sequencing of maternal plasma cell-free DNA in a commercial laboratory. A noninvasive prenatal testing laboratory data set was examined for samples in which fetal sex chromosomes were reported. Available clinical outcomes were reviewed. Of 18,161 samples with sex chromosome results, no sex chromosome aneuploidy was detected in 98.9% and the fetal sex was reported as XY (9,236) or XX (8,721). In 4 of 32 cases in which the fetal sex was reportedly discordant between noninvasive prenatal testing and karyotype or ultrasonogram, a potential biological reason for the discordance exists, including two cases of documented co-twin demise, one case of a maternal kidney transplant from a male donor, and one case of fetal ambiguous genitalia. In the remaining 204 samples (1.1%), one of four sex chromosome aneuploidies (monosomy X, XXX, XXY, or XYY) was detected. The frequency of false positive results for sex chromosome aneuploidies is a minimum of 0.26% and a maximum of 1.05%. All but one of the discordant sex chromosome aneuploidy results involved the X chromosome. In two putative false-positive XXX cases, maternal XXX was confirmed by karyotype. For the false-positive cases, mean maternal age was significantly higher in monosomy X (P<.001) and lower in XXX (P=.008). Noninvasive prenatal testing results for sex chromosome aneuploidy can be confounded by maternal or fetal biological phenomena. When a discordant noninvasive prenatal testing result is encountered, resolution requires additional maternal history, detailed fetal ultrasonography, and determination of fetal and possibly maternal karyotypes.

A coevolution analysis for identifying protein-protein interactions by Fourier transform.

PubMed

Yin, Changchuan; Yau, Stephen S-T

2017-01-01

Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees. The existing coevolution methods depend on multiple sequence alignments (MSA); however, the MSA-based coevolution methods often produce high false positive interactions. In this paper, we present a computational method using an alignment-free approach to accurately detect PPIs and reduce false positives. In the method, protein sequences are numerically represented by biochemical properties of amino acids, which reflect the structural and functional differences of proteins. Fourier transform is applied to the numerical representation of protein sequences to capture the dissimilarities of protein sequences in biophysical context. The method is assessed for predicting PPIs in Ebola virus. The results indicate strong coevolution between the protein pairs (NP-VP24, NP-VP30, NP-VP40, VP24-VP30, VP24-VP40, and VP30-VP40). The method is also validated for PPIs in influenza and E.coli genomes. Since our method can reduce false positive and increase the specificity of PPI prediction, it offers an effective tool to understand mechanisms of disease pathogens and find potential targets for drug design. The Python programs in this study are available to public at URL (https://github.com/cyinbox/PPI).

Presence of Cross-Reactions with Other Viral Encephalitides in the Indirect Fluorescent-Antibody Test for Diagnosis of Rabies

PubMed Central

Appler, Kim A.; Wong, Susan J.

2013-01-01

The antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. A combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. Modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. However, medical intervention efforts require a rapid and accurate diagnosis as early in the course of clinical disease as possible. Indirect fluorescent-antibody (IFA) testing on cerebrospinal fluid and serum specimens provides rapid results, but the specificity of the assay has not been well studied. Because false-positive IFA results could significantly affect patient treatment and outcomes, it is critical to understand the specificity of this assay. In this study, IFA testing was performed on 135 cerebrospinal fluid and serum specimens taken from patients with viral encephalitis or a presumed viral infection involving an agent other than rabies virus. Results indicate that false-positive results can occur in interpreting the rabies IFA test. Staining patterns morphologically similar to antirabies staining were observed in 7 of the 135 cerebrospinal fluid specimens examined. In addition, a majority of the cerebrospinal fluid specimens tested from patients with encephalitis presented immunoglobulin that bound to antigens present in the cell culture substrate. Of marked concern was the frequent presence of cross-reactive antibodies in encephalitis cases associated with West Nile and Powassan flaviviruses. Because IFA testing for rabies on human specimens may result in false-positive results, it should not be used as the sole basis for initiating antirabies treatment. PMID:24088851

Replacing Alpha-Fetoprotein With Alpha-Fetoprotein-L3 Increases the Sensitivity of Prenatal Screening for Trisomy 21.

PubMed

Huai, Lei; Leng, Jianhang; Ma, Shenglin; Huang, Fang; Shen, Junya; Ding, Yu

This study aimed to investigate the serum concentration of alpha-fetoprotein (AFP)-L3 in midterm pregnancies and its potential application in prenatal trisomy screening. The serum samples from 27 women with trisomy 21 fetuses and 800 women with normal fetuses were examined to measure the concentrations of AFP, AFP-L3, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and inhibin-A. The screening results of various tests consisting of these markers were analyzed. In normal pregnancies within 15-20 weeks of gestation, the medians of serum AFP-L3 were 4.63, 5.70, 5.78, 6.58, 7.03, and 7.25 pg/mL. The median of AFP-L3 MoM in the trisomy 21 group was 0.46, which was significantly lower than the value of 1 in the normal group (P < 0.05). When using a cutoff value of 1/270, the sensitivity of the triple marker test (AFP, hCG, uE3) was improved from 74% to 81% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 5.4% to 6.8%. Similarly, the sensitivity of the quad marker test (AFP, hCG, uE3, inhibin-A) was improved from 81% to 89% by replacing AFP with AFP-L3, with the false-positive rate slightly increased from 4.6% to 5.6%. Serum AFP-L3 concentration increases along with more weeks of gestation in the midterm pregnancies. Trisomy 21 screening tests with AFP replaced by AFP-L3 have higher sensitivities at the expense of slightly increased false-positive rates. This improvement in screening may help to better prepare the parents and caregivers for the special needs of newborns with trisomy 21.

Computer-aided detection system for lung cancer in computed tomography scans: Review and future prospects

PubMed Central

2014-01-01

Introduction The goal of this paper is to present a critical review of major Computer-Aided Detection systems (CADe) for lung cancer in order to identify challenges for future research. CADe systems must meet the following requirements: improve the performance of radiologists providing high sensitivity in the diagnosis, a low number of false positives (FP), have high processing speed, present high level of automation, low cost (of implementation, training, support and maintenance), the ability to detect different types and shapes of nodules, and software security assurance. Methods The relevant literature related to “CADe for lung cancer” was obtained from PubMed, IEEEXplore and Science Direct database. Articles published from 2009 to 2013, and some articles previously published, were used. A systemic analysis was made on these articles and the results were summarized. Discussion Based on literature search, it was observed that many if not all systems described in this survey have the potential to be important in clinical practice. However, no significant improvement was observed in sensitivity, number of false positives, level of automation and ability to detect different types and shapes of nodules in the studied period. Challenges were presented for future research. Conclusions Further research is needed to improve existing systems and propose new solutions. For this, we believe that collaborative efforts through the creation of open source software communities are necessary to develop a CADe system with all the requirements mentioned and with a short development cycle. In addition, future CADe systems should improve the level of automation, through integration with picture archiving and communication systems (PACS) and the electronic record of the patient, decrease the number of false positives, measure the evolution of tumors, evaluate the evolution of the oncological treatment, and its possible prognosis. PMID:24713067

Levels of Office Blood Pressure and Their Operating Characteristics for Detecting Masked Hypertension Based on Ambulatory Blood Pressure Monitoring

PubMed Central

Lin, Feng-Chang; Tuttle, Laura A.; Shimbo, Daichi; Diaz, Keith M.; Olsson, Emily; Stankevitz, Kristin; Hinderliter, Alan L.

2015-01-01

BACKGROUND Masked hypertension (MH)—nonelevated office blood pressure (BP) with elevated out-of-office BP average—conveys cardiovascular risk similar to or approaching sustained hypertension, making its detection of potential clinical importance. However, it may not be feasible or cost-effective to perform ambulatory BP monitoring (ABPM) on all patients with a nonelevated office BP. There likely exists a level of office BP below which ABPM is not warranted because the probability of MH is low. METHODS We analyzed data from 294 adults aged ≥30 years not on BP-lowering medication with office BP <140/90mm Hg, all of whom underwent 24-hour ABPM. We calculated sensitivity, false-positive rate, and likelihood ratios (LRs) for the range of office BP cutoffs from 110 to 138mm Hg systolic and from 68 to 88mm Hg diastolic for detecting MH. RESULTS The systolic BP cutoff with the highest +LR for detecting MH (1.8) was 120mm Hg, and the diastolic cutoff with the highest +LR (2.4) was 82mm Hg. However, the systolic level of 120mm Hg had a false-positive rate of 42%, and the diastolic level of 82mm Hg had a sensitivity of only 39%. CONCLUSIONS The cutoff of office BP with the best overall operating characteristics for diagnosing MH is approximately 120/82mm Hg. However, this cutoff may have an unacceptably high false-positive rate. Clinical risk tools to identify patients with nonelevated office BP for whom ABPM should be considered will likely need to include factors in addition to office BP. PMID:24898379

Presence of cross-reactions with other viral encephalitides in the indirect fluorescent-antibody test for diagnosis of rabies.

PubMed

Rudd, Robert J; Appler, Kim A; Wong, Susan J

2013-12-01

The antemortem diagnosis of rabies in humans employs techniques that require accuracy, speed, and sensitivity. A combination of histochemical analysis, in vitro virus isolation, immunological methods, and molecular amplification procedures are utilized in efforts to diagnose the disease. Modern medicine now offers potentially life-saving treatment for a disease that was considered invariably fatal once clinical signs develop. However, medical intervention efforts require a rapid and accurate diagnosis as early in the course of clinical disease as possible. Indirect fluorescent-antibody (IFA) testing on cerebrospinal fluid and serum specimens provides rapid results, but the specificity of the assay has not been well studied. Because false-positive IFA results could significantly affect patient treatment and outcomes, it is critical to understand the specificity of this assay. In this study, IFA testing was performed on 135 cerebrospinal fluid and serum specimens taken from patients with viral encephalitis or a presumed viral infection involving an agent other than rabies virus. Results indicate that false-positive results can occur in interpreting the rabies IFA test. Staining patterns morphologically similar to antirabies staining were observed in 7 of the 135 cerebrospinal fluid specimens examined. In addition, a majority of the cerebrospinal fluid specimens tested from patients with encephalitis presented immunoglobulin that bound to antigens present in the cell culture substrate. Of marked concern was the frequent presence of cross-reactive antibodies in encephalitis cases associated with West Nile and Powassan flaviviruses. Because IFA testing for rabies on human specimens may result in false-positive results, it should not be used as the sole basis for initiating antirabies treatment.

A coevolution analysis for identifying protein-protein interactions by Fourier transform

PubMed Central

Yin, Changchuan; Yau, Stephen S. -T.

2017-01-01

Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees. The existing coevolution methods depend on multiple sequence alignments (MSA); however, the MSA-based coevolution methods often produce high false positive interactions. In this paper, we present a computational method using an alignment-free approach to accurately detect PPIs and reduce false positives. In the method, protein sequences are numerically represented by biochemical properties of amino acids, which reflect the structural and functional differences of proteins. Fourier transform is applied to the numerical representation of protein sequences to capture the dissimilarities of protein sequences in biophysical context. The method is assessed for predicting PPIs in Ebola virus. The results indicate strong coevolution between the protein pairs (NP-VP24, NP-VP30, NP-VP40, VP24-VP30, VP24-VP40, and VP30-VP40). The method is also validated for PPIs in influenza and E.coli genomes. Since our method can reduce false positive and increase the specificity of PPI prediction, it offers an effective tool to understand mechanisms of disease pathogens and find potential targets for drug design. The Python programs in this study are available to public at URL (https://github.com/cyinbox/PPI). PMID:28430779

Computer-aided detection system for lung cancer in computed tomography scans: review and future prospects.

PubMed

Firmino, Macedo; Morais, Antônio H; Mendoça, Roberto M; Dantas, Marcel R; Hekis, Helio R; Valentim, Ricardo

2014-04-08

The goal of this paper is to present a critical review of major Computer-Aided Detection systems (CADe) for lung cancer in order to identify challenges for future research. CADe systems must meet the following requirements: improve the performance of radiologists providing high sensitivity in the diagnosis, a low number of false positives (FP), have high processing speed, present high level of automation, low cost (of implementation, training, support and maintenance), the ability to detect different types and shapes of nodules, and software security assurance. The relevant literature related to "CADe for lung cancer" was obtained from PubMed, IEEEXplore and Science Direct database. Articles published from 2009 to 2013, and some articles previously published, were used. A systemic analysis was made on these articles and the results were summarized. Based on literature search, it was observed that many if not all systems described in this survey have the potential to be important in clinical practice. However, no significant improvement was observed in sensitivity, number of false positives, level of automation and ability to detect different types and shapes of nodules in the studied period. Challenges were presented for future research. Further research is needed to improve existing systems and propose new solutions. For this, we believe that collaborative efforts through the creation of open source software communities are necessary to develop a CADe system with all the requirements mentioned and with a short development cycle. In addition, future CADe systems should improve the level of automation, through integration with picture archiving and communication systems (PACS) and the electronic record of the patient, decrease the number of false positives, measure the evolution of tumors, evaluate the evolution of the oncological treatment, and its possible prognosis.

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

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.

DSM-5: proposed changes to depressive disorders.

PubMed

Wakefield, Jerome C

2012-03-01

The Diagnostic and Statistical Manual of Mental Disorders (DSM) is currently undergoing a revision that will lead to a fifth edition in 2013. Proposed changes for DSM-5 include the creation of several new categories of depressive disorder. Some nosologists have expressed concern that the proposed changes could yield many 'false-positive diagnoses' in which normal distress is mislabeled as a mental disorder. Such confusion of normal distress and mental disorder undermines the interpretability of clinical trials and etiological research, causes inefficient allocation of resources, and incurs risks of unnecessary treatment. To evaluate these concerns, I critically examine five proposed DSM-5 expansions in the scope of depressive and grief disorders: (1) a new mixed anxiety/depression category; (2) a new premenstrual dysphoric disorder category; (3) elimination of the major depression bereavement exclusion; (4) elimination of the adjustment disorder bereavement exclusion, thus allowing the diagnosis of subsyndromal depressive symptoms during bereavement as adjustment disorders; and (5) a new category of adjustment disorder related to bereavement for diagnosing pathological non-depressive grief. I examine each proposal's face validity and conceptual coherence as well as empirical support where relevant, with special attention to potential implications for false-positive diagnoses. I conclude that mixed anxiety/depression and premenstrual dysphoric disorder are needed categories, but are too broadly drawn and will yield substantial false positives; that the elimination of the bereavement exclusion is not supported by the evidence; and that the proposed elimination of the adjustment-disorder bereavement exclusion, as well as the new category of grief-related adjustment disorder, are inconsistent with recent grief research, which suggests that these proposals would massively pathologize normal grief responses.

Modelling science trustworthiness under publish or perish pressure

PubMed Central

Ioannidis, John P. A.

2018-01-01

Scientific publication is immensely important to the scientific endeavour. There is, however, concern that rewarding scientists chiefly on publication creates a perverse incentive, allowing careless and fraudulent conduct to thrive, compounded by the predisposition of top-tier journals towards novel, positive findings rather than investigations confirming null hypothesis. This potentially compounds a reproducibility crisis in several fields, and risks undermining science and public trust in scientific findings. To date, there has been comparatively little modelling on factors that influence science trustworthiness, despite the importance of quantifying the problem. We present a simple phenomenological model with cohorts of diligent, careless and unethical scientists, with funding allocated by published outputs. This analysis suggests that trustworthiness of published science in a given field is influenced by false positive rate, and pressures for positive results. We find decreasing available funding has negative consequences for resulting trustworthiness, and examine strategies to combat propagation of irreproducible science. PMID:29410855

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.

Evaluation of Double-Disk Potentiation and Disk Potentiation Tests Using Dipicolinic Acid for Detection of Metallo-β-Lactamase-Producing Pseudomonas spp. and Acinetobacter spp.

PubMed Central

Yong, Dongeun; Lee, Yangsoon; Jeong, Seok Hoon; Lee, Kyungwon

2012-01-01

Accurate detection of metallo-β-lactamase (MBL)-producing Pseudomonas spp. and Acinetobacter spp. became very important with the increasing prevalence of carbapenem-nonsusceptible clinical isolates. The performance of phenotypic MBL detection methods may depend on the types of MBL and the characteristics of the isolates. A high false-positive rate is a problem with EDTA-based MBL detection methods. We evaluated the performance of double-disk potentiation tests (DDPTs) and disk potentiation tests (DPTs) with dipicolinic acid (DPA) using 44 isolates of Pseudomonas spp. and Acinetobacter spp. producing IMP-1-like, VIM-2-like, and SIM-1 type MBLs. Also, we characterized P. aeruginosa isolates with positive imipenem (IPM)-DPA DDPT, but negative meropenem (MEM)-DPA DDPT, and determined possibility of improving a DDPT by using MacConkey agar. Among five different DDPT methods, the IPM-DPA 250-μg method showed the highest sensitivity (97.7%) and specificity (100%). Among four DPT tests, the highest sensitivity (100%) was shown by the IPM-EDTA 1,900-μg disk method, but the specificity was very low (11.4%). Five of six P. aeruginosa isolates with false-negative DDPTs with MEM-DPA 250-μg disks carried blaIMP-6, and the high level resistance to MEM (MIC ≥ 512 μg/ml) was reduced by the presence of phenylalanine arginine β-naphtylamide. Improvement of DDPTs was observed when MacConkey agar was used instead of Mueller-Hinton agar. In conclusion, DPA is a better MBL inhibitor than EDTA for detection of Pseudomonas spp. and Acinetobacter spp. with IMP-1-like, VIM-2-like, and SIM-1-type MBLs. In DPA DDPTs, IPM disks perform better than MEM disks when the isolates are highly resistant to MEM due to the overexpression of efflux pumps. PMID:22837321

Potential microbial risk factors related to soil amendments and irrigation water of potato crops.

PubMed

Selma, M V; Allende, A; López-Gálvez, F; Elizaquível, P; Aznar, R; Gil, M I

2007-12-01

This study assesses the potential microbial risk factors related to the use of soil amendments and irrigation water on potato crops, cultivated in one traditional and two intensive farms during two harvest seasons. The natural microbiota and potentially pathogenic micro-organisms were evaluated in the soil amendment, irrigation water, soil and produce. Uncomposted amendments and residual and creek water samples showed the highest microbial counts. The microbial load of potatoes harvested in spring was similar among the tested farms despite the diverse microbial levels of Listeria spp. and faecal coliforms in the potential risk sources. However, differences in total coliform load of potato were found between farms cultivated in the autumn. Immunochromatographic rapid tests and the BAM's reference method (Bacteriological Analytical Manual; AOAC International) were used to detect Escherichia coli O157:H7 from the potential risk sources and produce. Confirmation of the positive results by polymerase chain reaction procedures showed that the immunochromatographic assay was not reliable as it led to false-positive results. The potentially pathogenic micro-organisms of soil amendment, irrigation water and soil samples changed with the harvest seasons and the use of different agricultural practices. However, the microbial load of the produce was not always influenced by these risk sources. Improvements in environmental sample preparation are needed to avoid interferences in the use of immunochromatographic rapid tests. The potential microbial risk sources of fresh produce should be regularly controlled using reliable detection methods to guarantee their microbial safety.

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.

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.

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.

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.

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

PubMed

Tetteh, Ato Kwamena; Agyarko, Edward

2017-01-01

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

Comparative Measurement of Microcystins in Diverse Surface ...

EPA Pesticide Factsheets

The measurement of microcystins, cyanotoxins associated with cyanobacterial blooms which are increasingly prevalent in inland waters, is complicated by the diversity of congeners which have been observed in the environment. At present, more than 150 microcystin congeners have been identified, and this poses a significant challenge to analytical methods intended to assess human health risks in surface and drinking water systems. The most widely employed analytical method at present is the ADDA-ELISA technique which is potentially sensitive to all microcystins, but it is primarily intended as a semi-quantitative method, and questions have been raised regarding the potential for cross-reactivity and false positives. LC-MS/MS methods targeting specific congeners, such as US EPA Method 544, are intended for use as a secondary confirmation following a positive ELISA response, but these techniques can target only those congeners for which commercial standards are available. Accordingly, they are not suitable for ascertaining the safety of a given water sample, given the potential for omitting unknown microcystin congeners which might be present.An alternative approach involves oxidative transformation of microcystins to a common product, 2-methyl-3-methoxy-4-phenylbutyric acid, or MMPB. Measuring MMPB by LC-MS/MS can potentially provide a metric for the sum of all microcystin congeners present in a sample, subject to the efficiency and overall yield of conversion. The

Comparative measurement of microcystins in diverse surface ...

EPA Pesticide Factsheets

The measurement of microcystins, cyanotoxins associated with cyanobacterial blooms which are increasingly prevalent in inland waters, is complicated by the diversity of congeners which have been observed in the environment. At present, more than 150 microcystin congeners have been identified, and this poses a significant challenge to analytical methods intended to assess human health risks in surface and drinking water systems. The most widely employed analytical method at present is the ADDA-ELISA technique which is potentially sensitive to all microcystins, but it is primarily intended as a semi-quantitative method, and questions have been raised regarding the potential for cross-reactivity and false positives. LC-MS/MS methods targeting specific congeners, such as US EPA Method 544, are intended for use as a secondary confirmation following a positive ELISA response, but these techniques can target only those congeners for which commercial standards are available. Accordingly, they not suitable for ascertaining the safety of a given water sample, given the potential for omitting unknown microcystin congeners which might be present.An alternative approach involves oxidative transformation of microcystins to a common product, 2-methyl-3-methoxy-4-phenylbutyric acid, or MMPB. Measuring MMPB by LC-MS/MS can potentially provide a metric for the sum of all microcystin congeners present in a sample, subject to the efficiency and overall yield of conversion. The pres

Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.

PubMed

Zhong, Zhandong Don; Clements-Egan, Adrienne; Gorovits, Boris; Maia, Mauricio; Sumner, Giane; Theobald, Valerie; Wu, Yuling; Rajadhyaksha, Manoj

2017-11-01

Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided.

[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.

Usefulness and limitations of various guinea-pig test methods in detecting human skin sensitizers-validation of guinea-pig tests for skin hypersensitivity.

PubMed

Marzulli, F; Maguire, H C

1982-02-01

Several guinea-pig predictive test methods were evaluated by comparison of results with those obtained with human predictive tests, using ten compounds that have been used in cosmetics. The method involves the statistical analysis of the frequency with which guinea-pig tests agree with the findings of tests in humans. In addition, the frequencies of false positive and false negative predictive findings are considered and statistically analysed. The results clearly demonstrate the superiority of adjuvant tests (complete Freund's adjuvant) in determining skin sensitizers and the overall superiority of the guinea-pig maximization test in providing results similar to those obtained by human testing. A procedure is suggested for utilizing adjuvant and non-adjuvant test methods for characterizing compounds as of weak, moderate or strong sensitizing potential.

How early ferns became trees.

PubMed

Galtier, J; Hueber, F M

2001-09-22

A new anatomically preserved fern, discovered from the basalmost Carboniferous of Australia, shows a unique combination of very primitive anatomical characters (solid centrarch cauline protostele) with the elaboration of an original model of the arborescent habit. This plant possessed a false trunk composed of a repetitive branching system of very small stems, which established it as the oldest tree-fern known to date. The potential of this primitive zygopterid fern to produce such an unusual growth form-without real equivalent among living plants-is related to the possession of two kinds of roots that have complementary functional roles: (i) large roots produced by stems with immediate positive geotropism, strongly adapted to mechanical support and water uptake from the soil; and (ii) small roots borne either on large roots or on petiole bases for absorbing humidity inside the false trunk.

Intraoperative Evaluation of Breast Tumor Margins with Optical Coherence Tomography

PubMed Central

Nguyen, Freddy T.; Zysk, Adam M.; Chaney, Eric J.; Kotynek, Jan G.; Oliphant, Uretz J.; Bellafiore, Frank J.; Rowland, Kendrith M.; Johnson, Patricia A.; Boppart, Stephen A.

2009-01-01

As breast cancer screening rates increase, smaller and more numerous lesions are being identified earlier, leading to more breast-conserving surgical procedures. Achieving a clean surgical margin represents a technical challenge with important clinical implications. Optical coherence tomography (OCT) is introduced as an intraoperative high-resolution imaging technique that assesses surgical breast tumor margins by providing real-time microscopic images up to 2 mm beneath the tissue surface. In a study of 37 patients split between training and study groups, OCT images covering 1 cm2 regions were acquired from surgical margins of lumpectomy specimens, registered with ink, and correlated with corresponding histological sections. A 17 patient training set used to establish standard imaging protocols and OCT evaluation criteria demonstrated that areas of higher scattering tissue with a heterogeneous pattern were indicative of tumor cells and tumor tissue, in contrast to lower scattering adipocytes found in normal breast tissue. The remaining 20 patients were enrolled into the feasibility study. Of these lumpectomy specimens, 11 were identified with a positive or close surgical margin and 9 were identified with a negative margin under OCT. Based on histological findings, 9 true positives, 9 true negatives, 2 false positives, and 0 false negatives were found, yielding a sensitivity of 100% and specificity of 82%. These results demonstrate the potential of OCT as a real-time method for intraoperative margin assessment in breast conserving surgeries. PMID:19910294

Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

PubMed

Abbas, A; Smith, A; Cecelja, M; Waltham, M

2012-02-01

AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Multispectra CWT-based algorithm (MCWT) in mass spectra for peak extraction.

PubMed

Hsueh, Huey-Miin; Kuo, Hsun-Chih; Tsai, Chen-An

2008-01-01

An important objective in mass spectrometry (MS) is to identify a set of biomarkers that can be used to potentially distinguish patients between distinct treatments (or conditions) from tens or hundreds of spectra. A common two-step approach involving peak extraction and quantification is employed to identify the features of scientific interest. The selected features are then used for further investigation to understand underlying biological mechanism of individual protein or for development of genomic biomarkers to early diagnosis. However, the use of inadequate or ineffective peak detection and peak alignment algorithms in peak extraction step may lead to a high rate of false positives. Also, it is crucial to reduce the false positive rate in detecting biomarkers from ten or hundreds of spectra. Here a new procedure is introduced for feature extraction in mass spectrometry data that extends the continuous wavelet transform-based (CWT-based) algorithm to multiple spectra. The proposed multispectra CWT-based algorithm (MCWT) not only can perform peak detection for multiple spectra but also carry out peak alignment at the same time. The author' MCWT algorithm constructs a reference, which integrates information of multiple raw spectra, for feature extraction. The algorithm is applied to a SELDI-TOF mass spectra data set provided by CAMDA 2006 with known polypeptide m/z positions. This new approach is easy to implement and it outperforms the existing peak extraction method from the Bioconductor PROcess package.

Efficient detection of human circulating tumor cells without significant production of false-positive cells by a novel conditionally replicating adenovirus

PubMed Central

Sakurai, Fuminori; Narii, Nobuhiro; Tomita, Kyoko; Togo, Shinsaku; Takahashi, Kazuhisa; Machitani, Mitsuhiro; Tachibana, Masashi; Ouchi, Masaaki; Katagiri, Nobuyoshi; Urata, Yasuo; Fujiwara, Toshiyoshi; Mizuguchi, Hiroyuki

2016-01-01

Circulating tumor cells (CTCs) are promising biomarkers in several cancers, and thus methods and apparatuses for their detection and quantification in the blood have been actively pursued. A novel CTC detection system using a green fluorescence protein (GFP)–expressing conditionally replicating adenovirus (Ad) (rAd-GFP) was recently developed; however, there is concern about the production of false-positive cells (GFP-positive normal blood cells) when using rAd-GFP, particularly at high titers. In addition, CTCs lacking or expressing low levels of coxsackievirus–adenovirus receptor (CAR) cannot be detected by rAd-GFP, because rAd-GFP is constructed based on Ad serotype 5, which recognizes CAR. In order to suppress the production of false-positive cells, sequences perfectly complementary to blood cell–specific microRNA, miR-142-3p, were incorporated into the 3′-untranslated region of the E1B and GFP genes. In addition, the fiber protein was replaced with that of Ad serotype 35, which recognizes human CD46, creating rAdF35-142T-GFP. rAdF35-142T-GFP efficiently labeled not only CAR-positive tumor cells but also CAR-negative tumor cells with GFP. The numbers of false-positive cells were dramatically lower for rAdF35-142T-GFP than for rAd-GFP. CTCs in the blood of cancer patients were detected by rAdF35-142T-GFP with a large reduction in false-positive cells. PMID:26966699

Factors affecting urine reagent strip blood results in dogs and nonhuman primates and interpretation of urinalysis in preclinical toxicology studies: a Multi-Institution Contract Research Organization and BioPharmaceutical Company Perspective.

PubMed

Aulbach, Adam D; Schultze, Eric; Tripathi, Niraj K; Hall, Robert L; Logan, Michael R; Meyer, Denny J

2015-06-01

Urinalysis data in preclinical toxicology studies can be influenced by preanalytic and analytic factors which have the potential to confound interpretation. There is a paucity of information regarding positive reagent strip urinary blood reactions in healthy nonhuman primates (NHP) and Beagle dogs used in preclinical toxicology studies. The objectives were (1) to establish historical control data for reagent strip urinary blood reactions in healthy NHP and Beagle dogs, (2) to determine the incidence of positive urinary blood reactions during predose and dosing phases, and (3) to determine if collection practice was a relevant parameter. Historical control data from 2 institutions in the biopharmaceutical industry were retrospectively analyzed for reagent strip urinary blood reactions in healthy NHP and Beagles. The incidence of positive results between the 2 institutions with different urine collection practices and between males and females was compared. The incidence of positive urinary blood reactions in NHP was comparable between institutions (≤ 14% in males; ≤ 33% in females), while the incidence of positive urinary blood reactions in Beagles was more variable (≤ 77% in males; ≤ 69% in females), and higher in females during the dosing phase. Positive urinary blood results that could potentially be misinterpreted as toxicologically relevant were identified in healthy NHP and Beagles during predose and dosing phases. Different incidences of positive results between the 2 institutions were likely related to collection practices. Strategies to reduce feces and food contamination of collected urine samples should help minimize false-positive urinary blood reactions. © 2015 American Society for Veterinary Clinical Pathology.

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

PubMed Central

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

2009-01-01

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

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

PubMed

Wiwanitkit, Viroj; Udomsantisuk, Nibhond; Boonchalermvichian, Chaiyaporn

2005-06-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

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.

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.

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.

Cost Analysis of Cot-Side Screening Methods for Neonatal Hypoglycaemia.

PubMed

Glasgow, Matthew J; Harding, Jane E; Edlin, Richard

2018-06-12

Babies at risk of neonatal hypoglycaemia are often screened using cot-side glucometers, but non-enzymatic glucometers are inaccurate, potentially resulting in over-treatment and under-treatment, and low values require laboratory confirmation. More accurate enzymatic glucometers are available but at apparently higher costs. Our objective was to compare the cost of screening for neonatal hypoglycaemia using point-of-care enzymatic and non-enzymatic glucometers. We used a decision tree to model costs, including consumables and staff time. Sensitivity analyses assessed the impact of staff time, staff costs, probability that low results are confirmed via laboratory testing, false-positive and false-negative rates of non-enzymatic glucometers, and the blood glucose concentration threshold. In the primary analysis, screening using an enzymatic glucometer cost NZD 86.94 (USD 63.47) while using a non-enzymatic glucometer cost NZD 97.08 (USD 70.87) per baby. Sensitivity analyses showed that using an enzymatic glucometer is cost saving with wide variations in staff time and costs, irrespective of the false-positive level of non-enzymatic glucometers, and where ≥78% of low values are laboratory confirmed. Where non-enzymatic glucometers may be less costly (e.g., false-negative rate exceeds 15%), instances of hypoglycaemia will be missed. Reducing the blood glucose concentration threshold to 1.94 mmol/L reduced the incidence of hypoglycaemia from 52 to 13%, and the cost of screening using a non-enzymatic glucometer to NZD 47.71 (USD 34.83). In view of their lower cost in most circumstances and greater accuracy, enzymatic glucometers should be routinely utilised for point-of-care screening for neonatal hypoglycaemia. © 2018 S. Karger AG, Basel.

Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design

PubMed Central

2012-01-01

The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads. PMID:24900472

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.

Peripheral Synucleinopathy in Early Parkinson’s Disease: Submandibular Gland Needle Biopsy Findings

PubMed Central

Adler, Charles H.; Dugger, Brittany N.; Hentz, Joseph G.; Hinni, Michael L.; Lott, David G.; Driver-Dunckley, Erika; Mehta, Shyamal; Serrano, Geidy; Sue, Lucia I.; Duffy, Amy; Intorcia, Anthony; Filon, Jessica; Pullen, Joel; Walker, Douglas G.; Beach, Thomas G.

2015-01-01

Background Finding a peripheral tissue biopsy site to diagnose early Parkinson’s disease would be of value for clinical care, biomarker validation, and as research enrollment criteria. While autopsy and advanced Parkinson’s disease studies suggest submandibular gland is an important biopsy site, there are no studies in early Parkinson’s disease. Objectives Determine whether needle biopsy of the submandibular gland reveals Lewy type α-synucleinopathy in early Parkinson’s disease. Methods Twenty-five early Parkinson’s disease (duration < 5 years) and 10 controls underwent transcutaneous needle core biopsies of the submandibular gland. Tissue was stained for phosphorylated α-synuclein, reviewed blind to clinical diagnosis, and only nerve element staining was considered positive. Results Mean (Standard Deviation) age 69.5 (8.3) for Parkinson’s disease group, 64.8 (8.0) years for controls, and disease duration 2.6 (1.1) years. Six Parkinson’s disease and one control subject had inadequate glandular tissue. Positive staining was found in 14/19 (74%) Parkinson’s disease and 2/9 (22%) control subjects. Parkinson’s disease positive and negative cases did not differ clinically. Adverse events (mainly swelling and bruising) were common (77% of cases), but were minor and transient. Conclusions Submandibular gland needle biopsies identified phosphorylated α-synuclein staining in 74% of early Parkinson’s disease subjects. False positives may be true false positives or may represent prodromal Parkinson’s disease. If confirmed in larger studies with eventual autopsy confirmation, the potential value of submandibular gland biopsies for early Parkinson’s disease may be to aid in clinical trial inclusion/exclusion and eventually serve as a gold standard for biomarker studies short of autopsy confirmation. PMID:26799362

Rapid HIV Testing in Dental Practices

PubMed Central

Abel, Stephen N.; Pereyra, Margaret; Liguori, Terri; Pollack, Harold A.; Metsch, Lisa R.

2012-01-01

Despite increasing discussion about the dental care setting as a logical, potentially fruitful venue for rapid HIV testing, dentists’ willingness to take on this task is unclear. Semistructured interviews with 40 private practice dentists revealed their principal concerns regarding offering patients HIV testing were false results, offending patients, viewing HIV testing as outside the scope of licensure, anticipating low patient acceptance of HIV testing in a dental setting, expecting inadequate reimbursement, and potential negative impact on the practice. Dentists were typically not concerned about transmission risks, staff opposition to testing, or making referrals for follow-up after a positive result. A larger cultural change may be required to engage dentists more actively in primary prevention and population-based HIV screening. PMID:22397342

From the RSNA refresher courses: US of the rotator cuff: pitfalls, limitations, and artifacts.

PubMed

Rutten, Matthieu J C M; Jager, Gerrit J; Blickman, Johan G

2006-01-01

High-resolution ultrasonography (US) has gained increasing popularity as a diagnostic tool for assessment of the soft tissues in shoulder impingement syndrome. US is a powerful and accurate method for diagnosis of rotator cuff tears and other rotator cuff abnormalities, provided the examiner has a detailed knowledge of shoulder anatomy, uses a standardized examination technique, and has a thorough understanding of the potential pitfalls, limitations, and artifacts. False-positive sonographic findings of rotator cuff tears can be caused by the technique (anisotropy, transducer positioning, acoustic shadowing by the deltoid septum), by the anatomy (rotator cuff interval, supraspinatus-infraspinatus interface, musculotendinous junction, fibrocartilaginous insertion), or by disease (criteria for diagnosis of rotator cuff tears, tendon inhomogeneity, acoustic shadowing by scar tissue or calcification, rotator cuff thinning). False-negative sonographic findings of rotator cuff tears can be caused by the technique (transducer frequency, suboptimal focusing, imaging protocol, transducer handling), by the anatomy (nondiastasis of the ruptured tendon fibers, posttraumatic obscuration of landmarks), by disease (tendinosis, calcifications, synovial proliferation, granulation or scar tissue, bursal thickening, massive rotator cuff tears), or by patient factors (obesity, muscularity, limited shoulder motion). (c) RSNA, 2006.

Analysis of audiometric notch as a noise-induced hearing loss phenotype in US youth: data from the National Health And Nutrition Examination Survey, 2005-2010.

PubMed

Bhatt, Ishan S; Guthrie, O'neil

2017-06-01

Bilateral audiometric notch (BN) at 4000-6000 Hz was identified as a noise-induced hearing loss (NIHL) phenotype for genetic association analysis in college-aged musicians. This study analysed BN in a sample of US youth. Prevalence of the BN within the study sample was determined and logistic-regression analyses were performed to identify audiologic and other demographic factors associated with BN. Computer-simulated "flat" audiograms were used to estimate potential influence of false-positive rates in estimating the prevalence of the BN. 2348 participants (12-19 years) following the inclusion criteria were selected from the National Health and Nutrition Examination Survey data (2005-2010). The prevalence of BN was 16.6%. Almost 55.6% of the participants showed notch in at least one ear. Noise exposure, gender, ethnicity and age showed significant relationship with the BN. Computer simulation revealed that 5.5% of simulated participants with "flat" audiograms showed BN. Association of noise exposure with BN suggests that it is a useful NIHL phenotype for genetic association analyses. However, further research is necessary to reduce false-positive rates in notch identification.

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

Trypanosoma cruzi (Agent of Chagas Disease) in Sympatric Human and Dog Populations in "Colonias" of the Lower Rio Grande Valley of Texas.

PubMed

Curtis-Robles, Rachel; Zecca, Italo B; Roman-Cruz, Valery; Carbajal, Ester S; Auckland, Lisa D; Flores, Isidore; Millard, Ann V; Hamer, Sarah A

2017-04-01

AbstractThe zoonotic, vector-borne parasite Trypanosoma cruzi causes Chagas disease throughout the Americas, but human and veterinary health burdens in the United States are unknown. We conducted a cross-sectional prevalence study in indigent, medically underserved human and cohabiting canine populations of seven south Texas border communities, known as colonias. Defining positivity as those samples that were positive on two or more independent tests, we found 1.3% seroprevalence in 233 humans, including one child born in the United States with only short-duration travel to Mexico. Additionally, a single child with no travel outside south Texas was positive on only a single test. Among 209 dogs, seroprevalence was 19.6%, but adjusted to 31.6% when including those dogs positive on only one test and extrapolating potential false negatives. Parasite DNA was detected in five dogs, indicating potential parasitemia. Seropositive dogs lived in all sampled colonias with no difference in odds of positivity across age, sex, or breed. Colonia residents collected two adult Triatoma gerstaeckeri and one nymph triatomine from around their homes; one of three bugs was infected with T. cruzi , and blood meal hosts were molecularly determined to include dog, human, and raccoon. Dogs and the infected vector all harbored T. cruzi discrete typing unit I, which has previously been implicated in human disease in the United States. Colonias harbor active T. cruzi transmission cycles and should be a priority in outreach and vector control initiatives.

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.

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.

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

PubMed

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

2015-09-01

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

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.

How does negative emotion cause false memories?

PubMed

Brainerd, C J; Stein, L M; Silveira, R A; Rohenkohl, G; Reyna, V F

2008-09-01

Remembering negative events can stimulate high levels of false memory, relative to remembering neutral events. In experiments in which the emotional valence of encoded materials was manipulated with their arousal levels controlled, valence produced a continuum of memory falsification. Falsification was highest for negative materials, intermediate for neutral materials, and lowest for positive materials. Conjoint-recognition analysis produced a simple process-level explanation: As one progresses from positive to neutral to negative valence, false memory increases because (a) the perceived meaning resemblance between false and true items increases and (b) subjects are less able to use verbatim memories of true items to suppress errors.

A new retrospective, multi-evidence veterinary drug screening method using drift tube ion mobility mass spectrometry.

PubMed

Xu, Zhenzhen; Li, Jianzhong; Chen, Ailiang; Ma, Xin; Yang, Shuming

2018-05-03

The retrospectivity (the ability to retrospect to a previously unknown compound in raw data) is very meaningful for food safety and risk assessment when facing new emerging drugs. Accurate mass and retention time based screening may lead false positive and false negative results so new retrospective, reliable platform is desirable. Different concentration levels of standards with and without matrix were analyzed using ion mobility (IM)-quadrupole-time-of-flight (Q-TOF) for collecting retrospective accurate mass, retention time, drift time and tandem MS evidence for identification in a single experiment. The isomer separation ability of IM and the four-dimensional (4D) feature abundance quantification abilities were evaluated for veterinary drugs for the first time. The sensitivity of the IM-Q-TOF workflow was obviously higher than that of the traditional database searching algorithm [find by formula (FbF) function] for Q-TOF. In addition, the IM-Q-TOF workflow contained most of the results from FbF and removed the false positive results. Some isomers were separated by IM and the 4D feature abundance quantitation removed interference with similar accurate mass and showed good linearity. A new retrospective, multi-evidence platform was built for veterinary drug screening in a single experiment. The sensitivity was significantly improved and the data can be used for quantification. The platform showed its potential to be used for food safety and risk assessment. This article is protected by copyright. All rights reserved.

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

Kipping, David M.; Chen, Jingjing; Sandford, Emily

The analysis of Proxima Centauri’s radial velocities recently led Anglada-Escudé et al. to claim the presence of a low-mass planet orbiting the Sun’s nearest star once every 11.2 days. Although the a priori probability that Proxima b transits its parent star is just 1.5%, the potential impact of such a discovery would be considerable. Independent of recent radial velocity efforts, we observed Proxima Centauri for 12.5 days in 2014 and 31 days in 2015 with the Microwave and Oscillations of Stars space telescope. We report here that we cannot make a compelling case that Proxima b transits in our precisemore » photometric time series. Imposing an informative prior on the period and phase, we do detect a candidate signal with the expected depth. However, perturbing the phase prior across 100 evenly spaced intervals reveals one strong false positive and one weaker instance. We estimate a false-positive rate of at least a few percent and a much higher false-negative rate of 20%–40%, likely caused by the very high flare rate of Proxima Centauri. Comparing our candidate signal to HATSouth ground-based photometry reveals that the signal is somewhat, but not conclusively, disfavored (1 σ –2 σ ), leading us to argue that the signal is most likely spurious. We expect that infrared photometric follow-up could more conclusively test the existence of this candidate signal, owing to the suppression of flare activity and the impressive infrared brightness of the parent star.« less

No Conclusive Evidence for Transits of Proxima b in MOST Photometry

NASA Astrophysics Data System (ADS)

Kipping, David M.; Cameron, Chris; Hartman, Joel D.; Davenport, James R. A.; Matthews, Jaymie M.; Sasselov, Dimitar; Rowe, Jason; Siverd, Robert J.; Chen, Jingjing; Sandford, Emily; Bakos, Gáspár Á.; Jordán, Andrés; Bayliss, Daniel; Henning, Thomas; Mancini, Luigi; Penev, Kaloyan; Csubry, Zoltan; Bhatti, Waqas; Da Silva Bento, Joao; Guenther, David B.; Kuschnig, Rainer; Moffat, Anthony F. J.; Rucinski, Slavek M.; Weiss, Werner W.

2017-03-01

The analysis of Proxima Centauri’s radial velocities recently led Anglada-Escudé et al. to claim the presence of a low-mass planet orbiting the Sun’s nearest star once every 11.2 days. Although the a priori probability that Proxima b transits its parent star is just 1.5%, the potential impact of such a discovery would be considerable. Independent of recent radial velocity efforts, we observed Proxima Centauri for 12.5 days in 2014 and 31 days in 2015 with the Microwave and Oscillations of Stars space telescope. We report here that we cannot make a compelling case that Proxima b transits in our precise photometric time series. Imposing an informative prior on the period and phase, we do detect a candidate signal with the expected depth. However, perturbing the phase prior across 100 evenly spaced intervals reveals one strong false positive and one weaker instance. We estimate a false-positive rate of at least a few percent and a much higher false-negative rate of 20%-40%, likely caused by the very high flare rate of Proxima Centauri. Comparing our candidate signal to HATSouth ground-based photometry reveals that the signal is somewhat, but not conclusively, disfavored (1σ-2σ), leading us to argue that the signal is most likely spurious. We expect that infrared photometric follow-up could more conclusively test the existence of this candidate signal, owing to the suppression of flare activity and the impressive infrared brightness of the parent star.

Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

PubMed

Saeed, Mohammad

2017-05-01

Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

A panel of ancestry informative markers to estimate and correct potential effects of population stratification in Han Chinese.

PubMed

Qin, Pengfei; Li, Zhiqiang; Jin, Wenfei; Lu, Dongsheng; Lou, Haiyi; Shen, Jiawei; Jin, Li; Shi, Yongyong; Xu, Shuhua

2014-02-01

Population stratification acts as a confounding factor in genetic association studies and may lead to false-positive or false-negative results. Previous studies have analyzed the genetic substructures in Han Chinese population, the largest ethnic group in the world comprising ∼20% of the global human population. In this study, we examined 5540 Han Chinese individuals with about 1 million single-nucleotide polymorphisms (SNPs) and screened a panel of ancestry informative markers (AIMs) to facilitate the discerning and controlling of population structure in future association studies on Han Chinese. Based on genome-wide data, we first confirmed our previous observation of the north-south differentiation in Han Chinese population. Second, we developed a panel of 150 validated SNP AIMs to determine the northern or southern origin of each Han Chinese individual. We further evaluated the performance of our AIMs panel in association studies in simulation analysis. Our results showed that this AIMs panel had sufficient power to discern and control population stratification in Han Chinese, which could significantly reduce false-positive rates in both genome-wide association studies (GWAS) and candidate gene association studies (CGAS). We suggest this AIMs panel be genotyped and used to control and correct population stratification in the study design or data analysis of future association studies, especially in CGAS which is the most popular approach to validate previous reports on genetic associations of diseases in post-GWAS era.

Amplitude/frequency differences in a supine resting single-lead electrocardiogram of normal versus coronary heart diseased males.

DOT National Transportation Integrated Search

1974-05-01

A resting 'normal' ECG can coexist with known angina pectoris, positive angiocardiography and previous myocardial infarction. In contemporary exercise ECG tests, a false positive/false negative total error of 10% is not unusual. Research aimed at imp...

Finkelstein's test: a descriptive error that can produce a false positive.

PubMed

Elliott, B G

1992-08-01

Over the last three decades an error in performing Finkelstein's test has crept into the English literature in both text books and journals. This error can produce a false-positive, and if relied upon, a wrong diagnosis can be made, leading to inappropriate surgery.

A Demonstration of Regression False Positive Selection in Data Mining

ERIC Educational Resources Information Center

Pinder, Jonathan P.

2014-01-01

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

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.

Evaluation of an inhouse rapid ELISA test for detection of giardia in domestic sheep (Ovis aries).

PubMed

Wilson, Jolaine M; Hankenson, F Claire

2010-11-01

Sheep (Ovis aries) are increasingly used at our institution as models of human disease. Within the research environment, routine husbandry and handling of sheep has potential for transmission of zoonotic agents, including Giardia. The prevalence of Giardia in sheep may approach 68%. Classic diagnostic testing involves microscopic examination for fecal cysts or trophozoites; however, limitations of microscopy include time, labor, and potential false-negative results due to intermittent shedding. We wished to determine whether a commercial rapid ELISA used for Giardia detection in dogs and cats could be used in sheep. Fecal samples collected from sheep (n = 93) were tested with a combination of 6 methods: reference laboratory fecal flotation, reference laboratory ELISA, inhouse fecal flotation, and commercially available tests (enzyme immunoassay, direct fluorescence antibody assay, and rapid ELISA). Prevalence of Giardia infection in facility sheep was 11.8% (11 of 93 animals). Of the 11 samples considered positive, 3 were confirmed by multiple testing methods, and 5 were positive by microscopy alone. Inhouse fecal flotation for 8 samples was positive on only 1 of 2 consecutive testing days. The rapid ELISA test exhibited 0% sensitivity for sheep giardiasis. Overall, the examined methods had low sensitivities and low positive predictive values. Despite limitations, microscopic analysis of repeat fecal samples remained the most accurate diagnostic method for ovine giardiasis among the methods tested.

The effect of mood on false memory for emotional DRM word lists.

PubMed

Zhang, Weiwei; Gross, Julien; Hayne, Harlene

2017-04-01

In the present study, we investigated the effect of participants' mood on true and false memories of emotional word lists in the Deese-Roediger-McDermott (DRM) paradigm. In Experiment 1, we constructed DRM word lists in which all the studied words and corresponding critical lures reflected a specified emotional valence. In Experiment 2, we used these lists to assess mood-congruent true and false memory. Participants were randomly assigned to one of three induced-mood conditions (positive, negative, or neutral) and were presented with word lists comprised of positive, negative, or neutral words. For both true and false memory, there was a mood-congruent effect in the negative mood condition; this effect was due to a decrease in true and false recognition of the positive and neutral words. These findings are consistent with both spreading-activation and fuzzy-trace theories of DRM performance and have practical implications for our understanding of the effect of mood on memory.

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

PubMed

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

2008-03-01

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

Evaluation of Immunoassays and General Biological Indicator Tests for Field Screening of Bacillus anthracis and Ricin

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

Bartholomew, Rachel A.; Ozanich, Richard M.; Arce, Jennifer S.

2017-02-01

The goal of this testing was to evaluate the ability of currently available commercial off-the-shelf (COTS) biological indicator tests and immunoassays to detect Bacillus anthracis (Ba) spores and ricin. In general, immunoassays provide more specific identification of biological threats as compared to indicator tests [3]. Many of these detection products are widely used by first responders and other end users. In most cases, performance data for these instruments are supplied directly from the manufacturer, but have not been verified by an external, independent assessment [1]. Our test plan modules included assessments of inclusivity (ability to generate true positive results), commonlymore » encountered hoax powders (which can cause potential interferences or false positives), and estimation of limit of detection (LOD) (sensitivity) testing.« less

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

PubMed

Schlauch, Robert S; Carney, Edward

2011-04-01

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

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.

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

PubMed

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

2005-08-01

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

An investigation of causes of false positive single nucleotide polymorphisms using simulated reads from a small eukaryote genome.

PubMed

Ribeiro, Antonio; Golicz, Agnieszka; Hackett, Christine Anne; Milne, Iain; Stephen, Gordon; Marshall, David; Flavell, Andrew J; Bayer, Micha

2015-11-11

Single Nucleotide Polymorphisms (SNPs) are widely used molecular markers, and their use has increased massively since the inception of Next Generation Sequencing (NGS) technologies, which allow detection of large numbers of SNPs at low cost. However, both NGS data and their analysis are error-prone, which can lead to the generation of false positive (FP) SNPs. We explored the relationship between FP SNPs and seven factors involved in mapping-based variant calling - quality of the reference sequence, read length, choice of mapper and variant caller, mapping stringency and filtering of SNPs by read mapping quality and read depth. This resulted in 576 possible factor level combinations. We used error- and variant-free simulated reads to ensure that every SNP found was indeed a false positive. The variation in the number of FP SNPs generated ranged from 0 to 36,621 for the 120 million base pairs (Mbp) genome. All of the experimental factors tested had statistically significant effects on the number of FP SNPs generated and there was a considerable amount of interaction between the different factors. Using a fragmented reference sequence led to a dramatic increase in the number of FP SNPs generated, as did relaxed read mapping and a lack of SNP filtering. The choice of reference assembler, mapper and variant caller also significantly affected the outcome. The effect of read length was more complex and suggests a possible interaction between mapping specificity and the potential for contributing more false positives as read length increases. The choice of tools and parameters involved in variant calling can have a dramatic effect on the number of FP SNPs produced, with particularly poor combinations of software and/or parameter settings yielding tens of thousands in this experiment. Between-factor interactions make simple recommendations difficult for a SNP discovery pipeline but the quality of the reference sequence is clearly of paramount importance. Our findings are also a stark reminder that it can be unwise to use the relaxed mismatch settings provided as defaults by some read mappers when reads are being mapped to a relatively unfinished reference sequence from e.g. a non-model organism in its early stages of genomic exploration.

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.

Reconsidering Cluster Bias in Multilevel Data: A Monte Carlo Comparison of Free and Constrained Baseline Approaches.

PubMed

Guenole, Nigel

2018-01-01

The test for item level cluster bias examines the improvement in model fit that results from freeing an item's between level residual variance from a baseline model with equal within and between level factor loadings and between level residual variances fixed at zero. A potential problem is that this approach may include a misspecified unrestricted model if any non-invariance is present, but the log-likelihood difference test requires that the unrestricted model is correctly specified. A free baseline approach where the unrestricted model includes only the restrictions needed for model identification should lead to better decision accuracy, but no studies have examined this yet. We ran a Monte Carlo study to investigate this issue. When the referent item is unbiased, compared to the free baseline approach, the constrained baseline approach led to similar true positive (power) rates but much higher false positive (Type I error) rates. The free baseline approach should be preferred when the referent indicator is unbiased. When the referent assumption is violated, the false positive rate was unacceptably high for both free and constrained baseline approaches, and the true positive rate was poor regardless of whether the free or constrained baseline approach was used. Neither the free or constrained baseline approach can be recommended when the referent indicator is biased. We recommend paying close attention to ensuring the referent indicator is unbiased in tests of cluster bias. All Mplus input and output files, R, and short Python scripts used to execute this simulation study are uploaded to an open access repository.

Automatic brain tumor detection in MRI: methodology and statistical validation

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Islam, Mohammad A.; Shaik, Jahangheer; Parra, Carlos; Ogg, Robert

2005-04-01

Automated brain tumor segmentation and detection are immensely important in medical diagnostics because it provides information associated to anatomical structures as well as potential abnormal tissue necessary to delineate appropriate surgical planning. In this work, we propose a novel automated brain tumor segmentation technique based on multiresolution texture information that combines fractal Brownian motion (fBm) and wavelet multiresolution analysis. Our wavelet-fractal technique combines the excellent multiresolution localization property of wavelets to texture extraction of fractal. We prove the efficacy of our technique by successfully segmenting pediatric brain MR images (MRIs) from St. Jude Children"s Research Hospital. We use self-organizing map (SOM) as our clustering tool wherein we exploit both pixel intensity and multiresolution texture features to obtain segmented tumor. Our test results show that our technique successfully segments abnormal brain tissues in a set of T1 images. In the next step, we design a classifier using Feed-Forward (FF) neural network to statistically validate the presence of tumor in MRI using both the multiresolution texture and the pixel intensity features. We estimate the corresponding receiver operating curve (ROC) based on the findings of true positive fractions and false positive fractions estimated from our classifier at different threshold values. An ROC, which can be considered as a gold standard to prove the competence of a classifier, is obtained to ascertain the sensitivity and specificity of our classifier. We observe that at threshold 0.4 we achieve true positive value of 1.0 (100%) sacrificing only 0.16 (16%) false positive value for the set of 50 T1 MRI analyzed in this experiment.

Reconsidering Cluster Bias in Multilevel Data: A Monte Carlo Comparison of Free and Constrained Baseline Approaches

PubMed Central

Guenole, Nigel

2018-01-01

The test for item level cluster bias examines the improvement in model fit that results from freeing an item's between level residual variance from a baseline model with equal within and between level factor loadings and between level residual variances fixed at zero. A potential problem is that this approach may include a misspecified unrestricted model if any non-invariance is present, but the log-likelihood difference test requires that the unrestricted model is correctly specified. A free baseline approach where the unrestricted model includes only the restrictions needed for model identification should lead to better decision accuracy, but no studies have examined this yet. We ran a Monte Carlo study to investigate this issue. When the referent item is unbiased, compared to the free baseline approach, the constrained baseline approach led to similar true positive (power) rates but much higher false positive (Type I error) rates. The free baseline approach should be preferred when the referent indicator is unbiased. When the referent assumption is violated, the false positive rate was unacceptably high for both free and constrained baseline approaches, and the true positive rate was poor regardless of whether the free or constrained baseline approach was used. Neither the free or constrained baseline approach can be recommended when the referent indicator is biased. We recommend paying close attention to ensuring the referent indicator is unbiased in tests of cluster bias. All Mplus input and output files, R, and short Python scripts used to execute this simulation study are uploaded to an open access repository. PMID:29551985

Aortic stiffness improves the prediction of both diagnosis and severity of coronary artery disease.

PubMed

Yannoutsos, Alexandra; Ahouah, Mathieu; Dreyfuss Tubiana, Céline; Topouchian, Jirar; Safar, Michel E; Blacher, Jacques

2018-02-01

Elective coronography has low diagnostic yield for obstructive coronary artery disease (CAD). We aim to determine whether non-invasive aortic stiffness assessment improves diagnostic accuracy of CAD screening by reducing the number of false-positive results from the cardiac stress test. A cross-sectional study was conducted from January 2013 to September 2014 in our medical center. Electrocardiogram (ECG) stress test coupled with nuclear imaging was performed in 367 consecutive patients routinely followed for myocardial ischemia screening. Aortic pulse wave velocity (PWV) was assessed by applanation tonometry in the overall population. Forty-two patients underwent elective coronography because of ischemia. Theoretical PWV was calculated according to age, blood pressure and gender. The results were expressed as an index ((measured PWV-theoretical PWV)/theoretical PWV) for each patient. Ten patients presented with obstructive CAD, 16 patients had non-obstructive CAD and 16 patients had normal coronary angiography. PWV index and severity of CAD were positively correlated (P=0.001). All patients with obstructive CAD had a positive PWV index. When considering the PWV index retrospectively, the false positive results of cardiac stress test were significantly reduced (P<0.001). Twenty-three procedures may have been avoided in the present study cohort. The salient finding of this study was that in patients with known or suspected CAD, routinely followed aortic PWV index may be considered clinically useful for reducing the rate of unnecessary invasive angiographies. The clinical relevance of this individualized decision approach should be confirmed in a large-scale study. Prospective studies have the potential to evaluate the PWV index as a marker of CAD.

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.

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.

Psychosomatic disorders of gravida status: false and denied pregnancies.

PubMed

Kenner, William D; Nicolson, Stephen E

2015-01-01

The authors review the literature on two dramatic psychosomatic disorders of reproduction and offer a potential classification of pregnancy denial. Information on false and denied pregnancies is summarized by comparing the descriptions, differential diagnoses, epidemiology, patient characteristics, psychological factors, abdominal tone, and neuroendocrinology. Pregnancy denial's association with neonaticide is reviewed. False and denied pregnancies have fooled women, families, and doctors for centuries as the body obscures her true condition. Improvements in pregnancy testing have decreased reports of false pregnancy. However, recent data suggests 1/475 pregnancies are denied to 20 weeks, and 1/2455 may go undiagnosed to delivery. Factors that may contribute to the unconscious deception include abdominal muscle tone, persistent corpus luteum function, and reduced availability of biogenic amines in false pregnancy, and posture, fetal position, and corpus luteum insufficiency in denied pregnancy. For each condition, there are multiple reports in which the body reveals her true pregnancy status as soon as the woman is convinced of her diagnosis. Forensic literature on denied pregnancy focused on the woman's rejection of motherhood, while psychiatric studies have revealed that trauma and dissociation drive her denial. False pregnancy has firm grounding as a classic psychosomatic disorder. Pregnancy denial's association with neonaticide has led to misleading forensic data, which obscures the central role of trauma and dissociation. A reappraisal of pregnancy denial confirms it as the somatic inverse of false pregnancy. With that perspective, clinicians can help women understand their pregnancy status to avoid unexpected deliveries with tragic outcomes. Copyright © 2015 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

False Memories for Affective Information in Schizophrenia.

PubMed

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

2016-01-01

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

False Memories for Affective Information in Schizophrenia

PubMed Central

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

2016-01-01

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

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

PubMed

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

2015-12-01

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

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.

Looking for Childhood Schizophrenia: Case Series of False Positives.

ERIC Educational Resources Information Center

Stayer, Catherine; Sporn, Alexandra; Gogtay, Nitin; Tossell, Julia; Lenane, Marge; Gochman, Peter; Rapoport, Judith L.

2004-01-01

Extensive experience with the diagnosis of childhood-onset schizophrenia indicates a high rate of false positives. Most mislabeled patients have chronic disabling, affective, or behavioral disorders. The authors report the cases of three children who passed stringent initial childhood-onset schizophrenia "screens" but had no chronic psychotic…

Current methodological issues in the economic assessment of personalized medicine.

PubMed

Annemans, Lieven; Redekop, Ken; Payne, Katherine

2013-01-01

There is a need for methodological scrutiny in the economic assessment of personalized medicine. In this article, we present a list of 10 specific issues that we argue pose specific methodological challenges that require careful consideration when designing and conducting robust model-based economic evaluations in the context of personalized medicine. Key issues are related to the correct framing of the research question, interpretation of test results, data collection of medical management options after obtaining test results, and expressing the value of tests. The need to formulate the research question clearly and be explicit and specific about the technology being evaluated is essential because various test kits can have the same purpose and yet differ in predictive value, costs, and relevance to practice and patient populations. The correct reporting of sensitivity/specificity, and especially the false negatives and false positives (which are population dependent), of the investigated tests is also considered as a key element. This requires additional structural complexity to establish the relationship between the test result and the consecutive treatment changes and outcomes. This process involves translating the test characteristics into clinical utility, and therefore outlining the clinical and economic consequences of true and false positives and true and false negatives. Information on treatment patterns and on their costs and outcomes, however, is often lacking, especially for false-positive and false-negative test results. The analysis can even become very complex if different tests are combined or sequentially used. This potential complexity can be handled by explicitly showing how these tests are going to be used in practice and then working with the combined sensitivities and specificities of the tests. Each of these issues leads to a higher degree of uncertainty in economic models designed to assess the added value of personalized medicine compared with their simple pharmaceutical counterparts. To some extent, these problems can be overcome by performing early population-level simulations, which can lead to the identification and collection of data on critical input parameters. Finally, it is important to understand that a test strategy does not necessarily lead to more quality-adjusted life-years (QALYs). It is possible that the test will lead to not only fewer QALYs but also fewer costs, which can be defined as "decremental" cost per QALYs. Different decision criteria are needed to interpret such results. © 2013 Published by Elsevier Inc. on behalf of International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

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

PubMed

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

2008-08-01

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

The 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

Real-Time Detection of Infusion Site Failures in a Closed-Loop Artificial Pancreas.

PubMed

Howsmon, Daniel P; Baysal, Nihat; Buckingham, Bruce A; Forlenza, Gregory P; Ly, Trang T; Maahs, David M; Marcal, Tatiana; Towers, Lindsey; Mauritzen, Eric; Deshpande, Sunil; Huyett, Lauren M; Pinsker, Jordan E; Gondhalekar, Ravi; Doyle, Francis J; Dassau, Eyal; Hahn, Juergen; Bequette, B Wayne

2018-05-01

As evidence emerges that artificial pancreas systems improve clinical outcomes for patients with type 1 diabetes, the burden of this disease will hopefully begin to be alleviated for many patients and caregivers. However, reliance on automated insulin delivery potentially means patients will be slower to act when devices stop functioning appropriately. One such scenario involves an insulin infusion site failure, where the insulin that is recorded as delivered fails to affect the patient's glucose as expected. Alerting patients to these events in real time would potentially reduce hyperglycemia and ketosis associated with infusion site failures. An infusion site failure detection algorithm was deployed in a randomized crossover study with artificial pancreas and sensor-augmented pump arms in an outpatient setting. Each arm lasted two weeks. Nineteen participants wore infusion sets for up to 7 days. Clinicians contacted patients to confirm infusion site failures detected by the algorithm and instructed on set replacement if failure was confirmed. In real time and under zone model predictive control, the infusion site failure detection algorithm achieved a sensitivity of 88.0% (n = 25) while issuing only 0.22 false positives per day, compared with a sensitivity of 73.3% (n = 15) and 0.27 false positives per day in the SAP arm (as indicated by retrospective analysis). No association between intervention strategy and duration of infusion sets was observed ( P = .58). As patient burden is reduced by each generation of advanced diabetes technology, fault detection algorithms will help ensure that patients are alerted when they need to manually intervene. Clinical Trial Identifier: www.clinicaltrials.gov,NCT02773875.

Evaluation of a direct high-capacity target screening approach for urine drug testing using liquid chromatography-time-of-flight mass spectrometry.

PubMed

Saleh, Aljona; Stephanson, Niclas Nikolai; Granelli, Ingrid; Villén, Tomas; Beck, Olof

2012-11-15

In this study a rapid liquid chromatography-time-of-flight mass spectrometry method was developed, validated and applied in order to evaluate the potential of this technique for routine urine drug testing. Approximately 800 authentic patient samples were analyzed for amphetamines (amphetamine and methamphetamine), opiates (morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine and codeine-6-glucuronide) and buprenorphines (buprenorphine and buprenorphine-glucuronide) using immunochemical screening assays and mass spectrometry confirmation methods for comparison. The chromatographic application utilized a rapid gradient with high flow and a reversed phase column with 1.8 μm particles. Total analysis time was 4 min. The mass spectrometer operated with an electrospray interface in positive mode with a resolution power of >10,000 at m/z 956. The applied reporting limits were 100 ng/mL for amphetamines and opiates, and 5 ng/mL for buprenorphines, with lower limits of quantification were 2.8-41 ng/mL. Calibration curves showed a linear response with coefficients of correlation of 0.97-0.99. The intra- and interday imprecision in quantification at the reporting limits were <10% for all analytes but for buprenorphines <20%. Method validation data met performance criteria for a qualitative and quantitative method. The liquid chromatography-time-of-flight mass spectrometry method was found to be more selective than the immunochemical method by producing lower rates of false positives (0% for amphetamines and opiates; 3.2% for buprenorphines) and negatives (1.8% for amphetamines; 0.6% for opiates; 0% for buprenorphines). The overall agreement between the two screening methods was between 94.2 and 97.4%. Comparison of data with the confirmation (LC-MS) results for all individual 9 analytes showed that most deviating results were produced in samples with low levels of analytes. False negatives were mainly related to failure of detected peak to meet mass accuracy criteria (±20 mDa). False positives was related to presence of interfering peaks meeting mass accuracy and retention time criteria and occurred mainly at low levels. It is concluded that liquid chromatography-time-of-flight mass spectrometry has potential both as a complement and as replacement of immunochemical screening assays. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel Handheld Magnetometer Probe Based on Magnetic Tunnelling Junction Sensors for Intraoperative Sentinel Lymph Node Identification

PubMed Central

Cousins, A.; Balalis, G. L.; Thompson, S. K.; Forero Morales, D.; Mohtar, A.; Wedding, A. B.; Thierry, B.

2015-01-01

Using magnetic tunnelling junction sensors, a novel magnetometer probe for the identification of the sentinel lymph node using magnetic tracers was developed. Probe performance was characterised in vitro and validated in a preclinical swine model. Compared to conventional gamma probes, the magnetometer probe showed excellent spatial resolution of 4.0 mm, and the potential to detect as few as 5 μg of magnetic tracer. Due to the high sensitivity of the magnetometer, all first-tier nodes were identified in the preclinical experiments, and there were no instances of false positive or false negative detection. Furthermore, these preliminary data encourage the application of the magnetometer probe for use in more complex lymphatic environments, such as in gastrointestinal cancers, where the sentinel node is often in close proximity to other non-sentinel nodes, and high spatial resolution detection is required. PMID:26038833

Identification and Discrimination of Brands of Fuels by Gas Chromatography and Neural Networks Algorithm in Forensic Research

PubMed Central

Ugena, L.; Moncayo, S.; Manzoor, S.; Rosales, D.

2016-01-01

The detection of adulteration of fuels and its use in criminal scenes like arson has a high interest in forensic investigations. In this work, a method based on gas chromatography (GC) and neural networks (NN) has been developed and applied to the identification and discrimination of brands of fuels such as gasoline and diesel without the necessity to determine the composition of the samples. The study included five main brands of fuels from Spain, collected from fifteen different local petrol stations. The methodology allowed the identification of the gasoline and diesel brands with a high accuracy close to 100%, without any false positives or false negatives. A success rate of three blind samples was obtained as 73.3%, 80%, and 100%, respectively. The results obtained demonstrate the potential of this methodology to help in resolving criminal situations. PMID:27375919

Development and Implementation of Metrics for Identifying Military Impulse Noise

DTIC Science & Technology

2010-09-01

False Negative Rate FP False Positive FPR False Positive Rate FtC Fort Carson, CO GIS Geographic Information System GMM Gaussian mixture model Hz...60 70 80 90 100 110 Bin Number B in N um be r N um ber of D ata Points M apped to B in 14 Figure 8. Plot of typical neuron activation...signal metrics and waveform itself were saved and transmitted to the home base. There is also a provision to download the entire recorded waveform

Why overestimate or underestimate chronic kidney disease when correct estimation is possible?

PubMed

De Broe, Marc E; Gharbi, Mohamed Benghanem; Zamd, Mohamed; Elseviers, Monique

2017-04-01

There is no doubt that the introduction of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 14 years ago, and their subsequent updates, have substantially contributed to the early detection of different stages of chronic kidney disease (CKD). Several recent studies from different parts of the world mention a CKD prevalence of 8-13%. However, some editorials and reviews have begun to describe the weaknesses of a substantial number of studies. Maremar (maladies rénales chroniques au Maroc) is a recently published prevalence study of CKD, hypertension, diabetes and obesity in a randomized, representative and high response rate (85%) sample of the adult population of Morocco that strictly applied the KDIGO guidelines. When adjusted to the actual adult population of Morocco (2015), a rather low prevalence of CKD (2.9%) was found. Several reasons for this low prevalence were identified; the tagine-like population pyramid of the Maremar population was a factor, but even more important were the confirmation of proteinuria found at first screening and the proof of chronicity of decreased estimated glomerular filtration rate (eGFR), eliminating false positive results. In addition, it was found that when an arbitrary single threshold of eGFR (<60 mL/min/1.73 m2) was used to classify CKD stages 3, 4 and 5, it lead to substantial 'overdiagnosis' (false positives) in the elderly (>55 years of age), particularly in those without proteinuria, haematuria or hypertension. It also resulted in a significant 'underdiagnosis' (false negatives) in younger individuals with an eGFR >60 mL/min/1.73 m2 and below the third percentile of their age-/gender-category. The use of the third percentile eGFR level as a cut-off, based on age-gender-specific reference values of eGFR, allows the detection of these false positives and negatives. There is an urgent need for additional quality studies of the prevalence of CKD using the recent KDIGO guidelines in the correct way, to avoid overestimation of the true disease state of CKD by ≥50% with potentially dramatic consequences. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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

Exploring the cause of initially reactive bovine brains on rapid tests for BSE

PubMed Central

Dudas, Sandor; James, Jace; Anderson, Renee; Czub, Stefanie

2015-01-01

ABSTRACT Bovine spongiform encephalopathy (BSE) is an invariably fatal prion disease of cattle. The identification of the zoonotic potential of BSE prompted safety officials to initiate surveillance testing for this disease. In Canada, BSE surveillance is primarily focused on high risk cattle including animals which are dead, down and unable to rise, diseased or distressed. This targeted surveillance results in the submission of brain samples with a wide range of tissue autolysis and associated contaminants. These contaminants have the potential to interfere with important steps of surveillance tests resulting in initially positive test results requiring additional testing to confirm the disease status of the animal. The current tests used for BSE screening in Canada utilize the relative protease resistance of the prion protein gained when it misfolds from PrPC to PrPSc as part of the disease process. Proteinase K completely digests PrPC in normal brains, but leaves most of the PrPSc in BSE positive brains intact which is detected using anti-prion antibodies. These tests are highly reliable but occasionally give rise to initially reactive/false positive results. Test results for these reactive samples were close to the positive/negative cut-off on a sub set of test platforms. This is in contrast to all of the previous Canadian positive samples whose numeric values on these same test platforms were 10 to 100 fold greater than the test positive/negative cut-off. Here we explore the potential reason why a sample is repeatedly positive on a sub-set of rapid surveillance tests, but negative on other test platforms. In order to better understand and identify what might cause these initial reactions, we have conducted a variety of rapid and confirmatory assays as well as bacterial isolation and identification on BSE positive, negative and initially reactive samples. We observed high levels of viable bacterial contamination in initially reactive samples suggesting that the reactivity may be related to bacterial factors. Several bacteria isolated from the initially reactive samples have characteristics of biofilm forming bacteria and this extracellular matrix might play a role in preventing complete digestion of PrPC in these samples. PMID:26689488

Two cases of false-positive dengue non-structural protein 1 (NS1) antigen in patients with hematological malignancies and a review of the literature on the use of NS1 for the detection of Dengue infection.

PubMed

Chung, Shimin J; Krishnan, Prabha U; Leo, Yee Sin

2015-02-01

Early diagnosis of dengue has been made easier in recent years owing to the advancement in diagnostic technologies. The rapid non-structural protein 1 (NS1) test strip is widely used in many developed and developing regions at risk of dengue. Despite the relatively high specificity of this test, we recently encountered two cases of false-positive dengue NS1 antigen in patients with underlying hematological malignancies. We reviewed the literature for causes of false-positive dengue NS1. © The American Society of Tropical Medicine and Hygiene.

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

PubMed Central

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

1987-01-01

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

Risk management and precaution: insights on the cautious use of evidence.

PubMed Central

Hrudey, Steve E; Leiss, William

2003-01-01

Risk management, done well, should be inherently precautionary. Adopting an appropriate degree of precaution with respect to feared health and environmental hazards is fundamental to risk management. The real problem is in deciding how precautionary to be in the face of inevitable uncertainties, demanding that we understand the equally inevitable false positives and false negatives from screening evidence. We consider a framework for detection and judgment of evidence of well-characterized hazards, using the concepts of sensitivity, specificity, positive predictive value, and negative predictive value that are well established for medical diagnosis. Our confidence in predicting the likelihood of a true danger inevitably will be poor for rare hazards because of the predominance of false positives; failing to detect a true danger is less likely because false negatives must be rarer than the danger itself. Because most controversial environmental hazards arise infrequently, this truth poses a dilemma for risk management. PMID:14527835

Emotion and false memory: How goal-irrelevance can be relevant for what people remember.

PubMed

Van Damme, Ilse; Kaplan, Robin L; Levine, Linda J; Loftus, Elizabeth F

2017-02-01

Elaborating on misleading information concerning emotional events can lead people to form false memories. The present experiment compared participants' susceptibility to false memories when they elaborated on information associated with positive versus negative emotion and pregoal versus postgoal emotion. Pregoal emotion reflects appraisals that goal attainment or failure is anticipated but has not yet occurred (e.g., hope and fear). Postgoal emotion reflects appraisals that goal attainment or failure has already occurred (e.g., happiness and devastation). Participants watched a slideshow depicting an interaction between a couple and were asked to empathise with the protagonist's feelings of hope (positive pregoal), happiness (positive postgoal), fear (negative pregoal), or devastation (negative postgoal); in control conditions, no emotion was mentioned. Participants were then asked to reflect on details of the interaction that had occurred (true) or had not occurred (false), and that were relevant or irrelevant to the protagonist's goal. Irrespective of emotional valence, participants in the pregoal conditions were more susceptible to false memories concerning goal-irrelevant details than were participants in the other conditions. These findings support the view that pregoal emotions narrow attention to information relevant to goal pursuit, increasing susceptibility to false memories for irrelevant information.

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

PubMed

Benigni, Romualdo

2014-09-01

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

Automated asteroseismic peak detections

NASA Astrophysics Data System (ADS)

García Saravia Ortiz de Montellano, Andrés; Hekker, S.; Themeßl, N.

2018-05-01

Space observatories such as Kepler have provided data that can potentially revolutionize our understanding of stars. Through detailed asteroseismic analyses we are capable of determining fundamental stellar parameters and reveal the stellar internal structure with unprecedented accuracy. However, such detailed analyses, known as peak bagging, have so far been obtained for only a small percentage of the observed stars while most of the scientific potential of the available data remains unexplored. One of the major challenges in peak bagging is identifying how many solar-like oscillation modes are visible in a power density spectrum. Identification of oscillation modes is usually done by visual inspection that is time-consuming and has a degree of subjectivity. Here, we present a peak-detection algorithm especially suited for the detection of solar-like oscillations. It reliably characterizes the solar-like oscillations in a power density spectrum and estimates their parameters without human intervention. Furthermore, we provide a metric to characterize the false positive and false negative rates to provide further information about the reliability of a detected oscillation mode or the significance of a lack of detected oscillation modes. The algorithm presented here opens the possibility for detailed and automated peak bagging of the thousands of solar-like oscillators observed by Kepler.

Comparisons of false negative rates from a trend test alone and from a trend test jointly with a control-high groups pairwise test in the determination of the carcinogenicity of new drugs.

PubMed

Lin, Karl K; Rahman, Mohammad A

2018-05-21

Interest has been expressed in using a joint test procedure that requires that the results of both a trend test and a pairwise comparison test between the control and the high groups be statistically significant simultaneously at the levels of significance recommended in the FDA 2001 draft guidance for industry document for the separate tests in order for the drug effect on the development of an individual tumor type to be considered as statistically significant. Results of our simulation studies show that there is a serious consequence of large inflations of the false negative rate through large decreases of false positive rate in the use of the above joint test procedure in the final interpretation of the carcinogenicity potential of a new drug if the levels of significance recommended for separate tests are used. The inflation can be as high as 204.5% of the false negative rate when the trend test alone is required to test if the effect is statistically significant. To correct the problem, new sets of levels of significance have also been developed for those who want to use the joint test in reviews of carcinogenicity studies.

RBM10-TFE3 Renal Cell Carcinoma: A Potential Diagnostic Pitfall Due to Cryptic Intrachromosomal Xp11.2 Inversion Resulting in False-negative TFE3 FISH.

PubMed

Argani, Pedram; Zhang, Lei; Reuter, Victor E; Tickoo, Satish K; Antonescu, Cristina R

2017-05-01

Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion. TFE3 rearrangement was not detected by conventional TFE3 break-apart FISH, but was suggested by strong diffuse TFE3 immunoreactivity in a clean background. We then developed novel fosmid probes to detect the RBM10-TFE3 gene fusion in archival material. These cases validate RBM10-TFE3 as a recurrent gene fusion in Xp11 translocation RCC, illustrate a source of false-negative TFE3 break-apart FISH, and highlight the complementary role of TFE3 IHC and TFE3 FISH.

Dynamic thresholds and a summary ROC curve: Assessing prognostic accuracy of longitudinal markers.

PubMed

Saha-Chaudhuri, P; Heagerty, P J

2018-04-19

Cancer patients, chronic kidney disease patients, and subjects infected with HIV are routinely monitored over time using biomarkers that represent key health status indicators. Furthermore, biomarkers are frequently used to guide initiation of new treatments or to inform changes in intervention strategies. Since key medical decisions can be made on the basis of a longitudinal biomarker, it is important to evaluate the potential accuracy associated with longitudinal monitoring. To characterize the overall accuracy of a time-dependent marker, we introduce a summary ROC curve that displays the overall sensitivity associated with a time-dependent threshold that controls time-varying specificity. The proposed statistical methods are similar to concepts considered in disease screening, yet our methods are novel in choosing a potentially time-dependent threshold to define a positive test, and our methods allow time-specific control of the false-positive rate. The proposed summary ROC curve is a natural averaging of time-dependent incident/dynamic ROC curves and therefore provides a single summary of net error rates that can be achieved in the longitudinal setting. Copyright © 2018 John Wiley & Sons, Ltd.

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.

Machine-learning-based real-bogus system for the HSC-SSP moving object detection pipeline

NASA Astrophysics Data System (ADS)

Lin, Hsing-Wen; Chen, Ying-Tung; Wang, Jen-Hung; Wang, Shiang-Yu; Yoshida, Fumi; Ip, Wing-Huen; Miyazaki, Satoshi; Terai, Tsuyoshi

2018-01-01

Machine-learning techniques are widely applied in many modern optical sky surveys, e.g., Pan-STARRS1, PTF/iPTF, and the Subaru/Hyper Suprime-Cam survey, to reduce human intervention in data verification. In this study, we have established a machine-learning-based real-bogus system to reject false detections in the Subaru/Hyper-Suprime-Cam Strategic Survey Program (HSC-SSP) source catalog. Therefore, the HSC-SSP moving object detection pipeline can operate more effectively due to the reduction of false positives. To train the real-bogus system, we use stationary sources as the real training set and "flagged" data as the bogus set. The training set contains 47 features, most of which are photometric measurements and shape moments generated from the HSC image reduction pipeline (hscPipe). Our system can reach a true positive rate (tpr) ˜96% with a false positive rate (fpr) ˜1% or tpr ˜99% at fpr ˜5%. Therefore, we conclude that stationary sources are decent real training samples, and using photometry measurements and shape moments can reject false positives effectively.

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

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

PubMed Central

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

2017-01-01

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

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.

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.

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.

Prediction of phospholipidosis-inducing potential of drugs by in vitro biochemical and physicochemical assays followed by multivariate analysis.

PubMed

Kuroda, Yukihiro; Saito, Madoka

2010-03-01

An in vitro method to predict phospholipidosis-inducing potential of cationic amphiphilic drugs (CADs) was developed using biochemical and physicochemical assays. The following parameters were applied to principal component analysis, as well as physicochemical parameters: pK(a) and clogP; dissociation constant of CADs from phospholipid, inhibition of enzymatic phospholipid degradation, and metabolic stability of CADs. In the score plot, phospholipidosis-inducing drugs (amiodarone, propranolol, imipramine, chloroquine) were plotted locally forming the subspace for positive CADs; while non-inducing drugs (chlorpromazine, chloramphenicol, disopyramide, lidocaine) were placed scattering out of the subspace, allowing a clear discrimination between both classes of CADs. CADs that often produce false results by conventional physicochemical or cell-based assay methods were accurately determined by our method. Basic and lipophilic disopyramide could be accurately predicted as a nonphospholipidogenic drug. Moreover, chlorpromazine, which is often falsely predicted as a phospholipidosis-inducing drug by in vitro methods, could be accurately determined. Because this method uses the pharmacokinetic parameters pK(a), clogP, and metabolic stability, which are usually obtained in the early stages of drug development, the method newly requires only the two parameters, binding to phospholipid, and inhibition of lipid degradation enzyme. Therefore, this method provides a cost-effective approach to predict phospholipidosis-inducing potential of a drug. Copyright (c) 2009 Elsevier Ltd. 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 reproducibility of research and the misinterpretation of p-values

PubMed Central

2017-01-01

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

RESPECT-ED: Rates of Pulmonary Emboli (PE) and Sub-Segmental PE with Modern Computed Tomographic Pulmonary Angiograms in Emergency Departments: A Multi-Center Observational Study Finds Significant Yield Variation, Uncorrelated with Use or Small PE Rates

PubMed Central

Chu, Kevin; Joseph, Anthony; Read, Catherine; Blecher, Gabriel; Furyk, Jeremy; Bharat, Chrianna; Velusamy, Karthik; Munro, Andrew; Baker, Kylie; Kinnear, Frances; Mukherjee, Ahses; Watkins, Gina; Buntine, Paul; Livesay, Georgia

2016-01-01

Introduction Overuse of CT Pulmonary Angiograms (CTPA) for diagnosing pulmonary embolism (PE), particularly in Emergency Departments (ED), is considered problematic. Marked variations in positive CTPA rates are reported, with American 4–10% yields driving most concerns. Higher resolution CTPA may increase sub-segmental PE (SSPE) diagnoses, which may be up to 40% false positive. Excessive use and false positives could increase harm vs. benefit. These issues have not been systematically examined outside America. Aims To describe current yield variation and CTPA utilisation in Australasian ED, exploring potential factors correlated with variation. Methods A retrospective multi-centre review of consecutive ED-ordered CTPA using standard radiology reports. ED CTPA report data were inputted onto preformatted data-sheets. The primary outcome was site level yield, analysed both intra-site and against a nominated 15.3% yield. Factors potentially associated with yield were assessed for correlation. Results Fourteen radiology departments (15 ED) provided 7077 CTPA data (94% ≥64-slice CT); PE were reported in 1028 (yield 14.6% (95%CI 13.8–15.4%; range 9.3–25.3%; site variation p <0.0001) with four sites significantly below and one above the 15.3% target. Admissions, CTPA usage, PE diagnosis rates and size of PE were uncorrelated with yield. Large PE (≥lobar) were 55% (CI: 52.1–58.2%) and SSPE 8.8% (CI: 7.1–10.5%) of positive scans. CTPA usage (0.2–1.5% adult attendances) was correlated (p<0.006) with PE diagnosis but not SSPE: large PE proportions. Discussion/ Conclusions We found significant intra-site CTPA yield variation within Australasia. Yield was not clearly correlated with CTPA usage or increased small PE rates. Both SSPE and large PE rates were similar to higher yield historical cohorts. CTPA use was considerably below USA 2.5–3% rates. Higher CTPA utilisation was positively correlated with PE diagnoses, but without evidence of increased proportions of small PE. This suggests that increased diagnoses seem to be of clinically relevant sized PE. PMID:27918576

The potential of liquid-based cytology in lymph node cytological evaluation: the role of morphology and the aid of ancillary techniques.

PubMed

Rossi, E D; Martini, M; Straccia, P; Bizzarro, T; Fadda, G; Larocca, L M

2016-02-01

Our aim was to evaluate the feasibility and diagnostic accuracy of liquid-based cytology (LBC) on lymph node fine needle aspiration (FNA). FNA may fulfil a challenging role in the evaluation of the majority of primary (benign and malignant) diagnoses as well as metastatic lymph node lesions. Although the morphological features may be quite easily recognized, cytological samples with a scant cellular component may raise some issues. We appraised 263 cytological lymph nodes from different body regions analysed between January and December 2013, including 137 male and 126 female patients, and processed with LBC. The cytological diagnoses included 160 benign and 103 malignant lesions. We reported 35 benign and 73 malignant lesions from 108 with surgical follow-up. The latter malignant series included 68 metastatic lesions, four suspicious for malignancy and one inadequate sample. The cytological diagnoses were supported by 62 conclusive immunocytochemical and 28 molecular analyses. Of the 108 cases, we documented 35 true negatives, 72 true positives, one false negative and no false positives, resulting in 98.6% sensitivity, 100% specificity, 99% diagnostic accuracy, 97.2% negative predictive value and 100% positive predictive value. FNA represents the first diagnostic tool in lymph node management and a reliable approach in order to avoid an excision biopsy. Furthermore, LBC is a feasible method for ancillary tests for which methanol-fixed samples are suitable, such as immunocytochemistry and molecular analysis. © 2014 John Wiley & Sons Ltd.

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.

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

PubMed

Frederick, R I

2000-01-01

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

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

Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease.

PubMed

Nelson, Christina; Hojvat, Sally; Johnson, Barbara; Petersen, Jeannine; Schriefer, Marty; Beard, C Ben; Petersen, Lyle; Mead, Paul

2014-04-18

In 2005, CDC and the Food and Drug Administration (FDA) issued a warning regarding the use of Lyme disease tests whose accuracy and clinical usefulness have not been adequately established. Often these are laboratory-developed tests (also known as "home brew" tests) that are manufactured and used within a single laboratory and have not been cleared or approved by FDA. Recently, CDC has received inquiries regarding a laboratory-developed test that uses a novel culture method to identify Borrelia burgdorferi, the spirochete that causes Lyme disease. Patient specimens reportedly are incubated using a two-step pre-enrichment process, followed by immunostaining with or without polymerase chain reaction (PCR) analysis. Specimens that test positive by immunostaining or PCR are deemed "culture positive". Published methods and results for this laboratory-developed test have been reviewed by CDC. The review raised serious concerns about false-positive results caused by laboratory contamination and the potential for misdiagnosis.

Dual-stage deep learning framework for pigment epithelium detachment segmentation in polypoidal choroidal vasculopathy

PubMed Central

Xu, Yupeng; Yan, Ke; Kim, Jinman; Wang, Xiuying; Li, Changyang; Su, Li; Yu, Suqin; Xu, Xun; Feng, Dagan David

2017-01-01

Worldwide, polypoidal choroidal vasculopathy (PCV) is a common vision-threatening exudative maculopathy, and pigment epithelium detachment (PED) is an important clinical characteristic. Thus, precise and efficient PED segmentation is necessary for PCV clinical diagnosis and treatment. We propose a dual-stage learning framework via deep neural networks (DNN) for automated PED segmentation in PCV patients to avoid issues associated with manual PED segmentation (subjectivity, manual segmentation errors, and high time consumption).The optical coherence tomography scans of fifty patients were quantitatively evaluated with different algorithms and clinicians. Dual-stage DNN outperformed existing PED segmentation methods for all segmentation accuracy parameters, including true positive volume fraction (85.74 ± 8.69%), dice similarity coefficient (85.69 ± 8.08%), positive predictive value (86.02 ± 8.99%) and false positive volume fraction (0.38 ± 0.18%). Dual-stage DNN achieves accurate PED quantitative information, works with multiple types of PEDs and agrees well with manual delineation, suggesting that it is a potential automated assistant for PCV management. PMID:28966847

Dual-stage deep learning framework for pigment epithelium detachment segmentation in polypoidal choroidal vasculopathy.

PubMed

Xu, Yupeng; Yan, Ke; Kim, Jinman; Wang, Xiuying; Li, Changyang; Su, Li; Yu, Suqin; Xu, Xun; Feng, Dagan David

2017-09-01

Worldwide, polypoidal choroidal vasculopathy (PCV) is a common vision-threatening exudative maculopathy, and pigment epithelium detachment (PED) is an important clinical characteristic. Thus, precise and efficient PED segmentation is necessary for PCV clinical diagnosis and treatment. We propose a dual-stage learning framework via deep neural networks (DNN) for automated PED segmentation in PCV patients to avoid issues associated with manual PED segmentation (subjectivity, manual segmentation errors, and high time consumption).The optical coherence tomography scans of fifty patients were quantitatively evaluated with different algorithms and clinicians. Dual-stage DNN outperformed existing PED segmentation methods for all segmentation accuracy parameters, including true positive volume fraction (85.74 ± 8.69%), dice similarity coefficient (85.69 ± 8.08%), positive predictive value (86.02 ± 8.99%) and false positive volume fraction (0.38 ± 0.18%). Dual-stage DNN achieves accurate PED quantitative information, works with multiple types of PEDs and agrees well with manual delineation, suggesting that it is a potential automated assistant for PCV management.

Combining multiple positive training sets to generate confidence scores for protein-protein interactions.

PubMed

Yu, Jingkai; Finley, Russell L

2009-01-01

High-throughput experimental and computational methods are generating a wealth of protein-protein interaction data for a variety of organisms. However, data produced by current state-of-the-art methods include many false positives, which can hinder the analyses needed to derive biological insights. One way to address this problem is to assign confidence scores that reflect the reliability and biological significance of each interaction. Most previously described scoring methods use a set of likely true positives to train a model to score all interactions in a dataset. A single positive training set, however, may be biased and not representative of true interaction space. We demonstrate a method to score protein interactions by utilizing multiple independent sets of training positives to reduce the potential bias inherent in using a single training set. We used a set of benchmark yeast protein interactions to show that our approach outperforms other scoring methods. Our approach can also score interactions across data types, which makes it more widely applicable than many previously proposed methods. We applied the method to protein interaction data from both Drosophila melanogaster and Homo sapiens. Independent evaluations show that the resulting confidence scores accurately reflect the biological significance of the interactions.

Streptomycin interference in Jaffe reaction - possible false positive creatinine estimation in excessive dose exposure.

PubMed

Syal, Kirtimaan; Srinivasan, Anand; Banerjee, Dibyajyoti

2013-01-01

To study the potential of commonly used aminoglycoside antibiotics to form non-creatinine chromogen with alkaline picrate reagent. We studied the non-creatinine chromogen formation of various concentrations of streptomycin, amikacin, kanamycin, netilmicin, gentamicin and tobramycin added to known creatinine concentrations by the Jaffe reaction based creatinine estimation. Only streptomycin above therapeutic concentrations of 10mg/mL interfered in the Jaffe reaction and acted as non-creatinine chromogen. Therapeutic doses of the aminoglycosides do not form non-creatinine chromogens. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2005-02-01

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

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

PubMed

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

2007-09-01

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

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

Efficient structure from motion on large scenes using UAV with position and pose information

NASA Astrophysics Data System (ADS)

Teng, Xichao; Yu, Qifeng; Shang, Yang; Luo, Jing; Wang, Gang

2018-04-01

In this paper, we exploit prior information from global positioning systems and inertial measurement units to speed up the process of large scene reconstruction from images acquired by Unmanned Aerial Vehicles. We utilize weak pose information and intrinsic parameter to obtain the projection matrix for each view. As compared to unmanned aerial vehicles' flight altitude, topographic relief can usually be ignored, we assume that the scene is flat and use weak perspective camera to get projective transformations between two views. Furthermore, we propose an overlap criterion and select potentially matching view pairs between projective transformed views. A robust global structure from motion method is used for image based reconstruction. Our real world experiments show that the approach is accurate, scalable and computationally efficient. Moreover, projective transformations between views can also be used to eliminate false matching.

Current state of knowledge, beliefs, and attitudes toward organ transplantation among academic students in Poland and the potential means for altering them.

PubMed

Nowak, E; Pfitzner, R; Koźlik, P; Kozynacka, A; Durajski, L; Przybyłowski, P

2014-10-01

Students manifest a high level of social commitment. Improving their knowledge and developing more positive attitudes toward organ transplantation may increase the number of organ donations. This study was an assessment of the knowledge and attitudes toward organ transplantation among young people in Poland, with an overview of current beliefs and potential methods for improving transplantology awareness. The study included 400 medical students and 400 nonmedical students from public universities in Kraków, Poland. Data were collected by using an anonymous questionnaire examining demographic factors and transplantology issues. Despite the overall positive attitude toward transplantology among academic students in Poland, the state of knowledge of the nonmedical population remains relatively low. The most important issues for social education to focus on are the role of presumed consent and brain death diagnosis, actual hazards of living donations, recipient qualification criteria, and the attitudes of religious authorities. The overall level of knowledge and the number of positive attitudes were significantly higher among medical students than among nonmedical students, proving that formal educational programs are more efficient than the more accessible but less reliable sources of knowledge. Introduction of transplantology issues in schools and churches, promoting the positive outcomes of organ transplantation rather than negating false beliefs, and eliminating misleading information from the media may significantly increase young people's knowledge and result in more positive attitudes toward transplantology in a society-wide fashion. This outcome could create a favorable background for introducing an opt-in system of consent for organ donation.

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).

Detecting False Positives in Multielement Designs: Implications for Brief Assessments

ERIC Educational Resources Information Center

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

2011-01-01

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…

IS HCI THAT IS USED AS A PRESERVATIVE CREATING FALSE POSITIVES FOR TBA IN GROUND WATER

EPA Science Inventory

Will hydrochloric acid produce false positives for TBA? Yes, if you heat the sample to get a lower detection limit for TBA. Conventional purge and trap methods at ambient temperature have a reporting limit for TBA between 50 and 100 g/liter. This is higher than the provisiona...

Are False-Positive Rates Leading to an Overestimation of Noise-Induced Hearing Loss?

ERIC Educational Resources Information Center

Schlauch, Robert S.; Carney, Edward

2011-01-01

Purpose: To estimate false-positive rates for rules proposed to identify early noise-induced hearing loss (NIHL) using the presence of notches in audiograms. Method: Audiograms collected from school-age children in a national survey of health and nutrition (the Third National Health and Nutrition Examination Survey [NHANES III]; National Center…

False-Positive Cases of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomographic Scans in Metastasis of Esophageal Cancer

PubMed Central

Yamatsuji, Tomoki; Ishida, Naomasa; Takaoka, Munenori; Hayashi, Jiro; Yoshida, Kazuhiro; Shigemitsu, Kaori; Urakami, Atsushi; Haisa, Minoru; Naomoto, Yoshio

2017-01-01

Of 129 esophagectomies at our institute from June 2010 to March 2015, we experienced three preoperative positron emission tomography-computed tomographic (PET/CT) false positives. Bone metastasis was originally suspected in 2 cases, but they were later found to be bone metastasis negative after a preoperative bone biopsy and clinical course observation. The other cases suspected of mediastinal lymph node metastasis were diagnosed as inflammatory lymphadenopathy by a pathological examination of the removed lymph nodes. Conducting a PET/CT is useful when diagnosing esophageal cancer metastasis, but we need to be aware of the possibility of false positives. Therapeutic decisions should be made based on appropriate and accurate diagnoses, with pathological diagnosis actively introduced if necessary. PMID:28469502

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.

Chlamydia and gonorrhoea contamination of clinic surfaces.

PubMed

Lewis, Natasha; Dube, Gail; Carter, Christine; Pitt, Rachel; Alexander, Sarah; Ison, Catherine A; Harding, Jan; Brown, Louise; Fryer, John; Hodson, James; Ross, Jonathan

2012-10-01

Nucleic acid amplification tests, with their ability to detect very small amounts of nucleic acid, have become the principle diagnostic tests for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in many sexual health clinics. The aim of this study was to investigate the extent of surface contamination with CT and GC within a city centre sexual health clinic and to evaluate the potential for contamination of containers used for the collection of self-taken swabs. Surface contamination with CT and GC was assessed by systematically sampling 154 different sites within one clinic using transcription-mediated amplification (TMA), quantitative PCR and culture. The caps of containers used by patients to collect self-taken samples were also tested for CT and GC using TMA. Of the 154 sites sampled, 20 (13.0%) tested positive on TMA. Of these, five (3.2%) were positive for CT alone, 11 (7.1%) for GC alone and four (2.6%) for both CT and GC. The proportion of GC TMA-positive test results differed by gender, with 11 (18.3%) positive results from the male patient clinic area compared with one (1.6%) from the female area (p=0.002). Positive samples were obtained from a variety of locations in the clinic, but the patient toilets were more likely to be contaminated than examination rooms (p=0.015). Quantitative PCR and culture assays were negative for all samples. 46 caps of the containers used for self-taken swabs were negative for both CT and GC on TMA testing. Surface contamination with chlamydial and gonococcal rRNA can occur within sexual health clinics, but the quantity of nucleic acid detected is low and infection risk to patients and staff is small. There remains a potential risk of contamination of patient samples leading to false-positive results.

Alarm setting for the critically ill patient: a descriptive pilot survey of nurses' perceptions of current practice in an Australian Regional Critical Care Unit.

PubMed

Christensen, Martin; Dodds, Andrew; Sauer, Josh; Watts, Nigel

2014-08-01

The aim of this survey was to assess registered nurse's perceptions of alarm setting and management in an Australian Regional Critical Care Unit. The setting and management of alarms within the critical care environment is one of the key responsibilities of the nurse in this area. However, with up to 99% of alarms potentially being false-positives it is easy for the nurse to become desensitised or fatigued by incessant alarms; in some cases up to 400 per patient per day. Inadvertently ignoring, silencing or disabling alarms can have deleterious implications for the patient and nurse. A total population sample of 48 nursing staff from a 13 bedded ICU/HDU/CCU within regional Australia were asked to participate. A 10 item open-ended and multiple choice questionnaire was distributed to determine their perceptions and attitudes of alarm setting and management within this clinical area. Two key themes were identified from the open-ended questions: attitudes towards inappropriate alarm settings and annoyance at delayed responses to alarms. A significant number of respondents (93%) agreed that alarm fatigue can result in alarm desensitisation and the disabling of alarms, whilst 81% suggested the key factors are those associated with false-positive alarms and inappropriately set alarms. This study contributes to what is known about alarm fatigue, setting and management within a critical care environment. In addition it gives an insight as to what nurses' within a regional context consider the key factors which contribute to alarm fatigue. Clearly nursing burnout and potential patient harm are important considerations for practice especially when confronted with alarm fatigue and desensitisation. Therefore, promoting and maintaining an environment of ongoing intra-professional communication and alarm surveillance are crucial in alleviating these potential problems. Copyright © 2014. Published by Elsevier Ltd.

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

Validation of a Syndromic Case Definition for Detecting Emergency Department Visits Potentially Related to Marijuana.

PubMed

DeYoung, Kathryn; Chen, Yushiuan; Beum, Robert; Askenazi, Michele; Zimmerman, Cali; Davidson, Arthur J

Reliable methods are needed to monitor the public health impact of changing laws and perceptions about marijuana. Structured and free-text emergency department (ED) visit data offer an opportunity to monitor the impact of these changes in near-real time. Our objectives were to (1) generate and validate a syndromic case definition for ED visits potentially related to marijuana and (2) describe a method for doing so that was less resource intensive than traditional methods. We developed a syndromic case definition for ED visits potentially related to marijuana, applied it to BioSense 2.0 data from 15 hospitals in the Denver, Colorado, metropolitan area for the period September through October 2015, and manually reviewed each case to determine true positives and false positives. We used the number of visits identified by and the positive predictive value (PPV) for each search term and field to refine the definition for the second round of validation on data from February through March 2016. Of 126 646 ED visits during the first period, terms in 524 ED visit records matched ≥1 search term in the initial case definition (PPV, 92.7%). Of 140 932 ED visits during the second period, terms in 698 ED visit records matched ≥1 search term in the revised case definition (PPV, 95.7%). After another revision, the final case definition contained 6 keywords for marijuana or derivatives and 5 diagnosis codes for cannabis use, abuse, dependence, poisoning, and lung disease. Our syndromic case definition and validation method for ED visits potentially related to marijuana could be used by other public health jurisdictions to monitor local trends and for other emerging concerns.

False positive fecal coliform in biosolid samples assayed using A-1 medium.

PubMed

Baker, Katherine H; Redmond, Brady; Herson, Diane S

2005-01-01

Two most probable number (MPN) methods-lauryl tryptose broth with Escherichia coli broth confirmation and direct A-1 broth incubation (A-1)--were compared for the enumeration of fecal coliform in lime-treated biosolid. Fecal coliform numbers were significantly higher using the A-1 method. Analysis of positive A-1 tubes, however, indicated that a high percentage of these were false positives. Therefore, the use of A-1 broth for 40 CFR Part 503 Pathogen Reduction (CFR, 1993) compliance testing is not recommended.

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

The Precautionary Principle and Electric and Magnetic Fields

PubMed Central

Jamieson, Dale; Wartenberg, Daniel

2001-01-01

Current environmental regulation represents a paternalistic policy, more concerned to avoid false positives than false negatives, limiting opportunities for individuals to make choices between risk-avoidance and risk-taking alternatives. For example, many exposures to magnetic fields could be reduced at little or no cost but are not considered seriously, owing to the uncertainty of risk and the concern to avoid false positives. Even though precautionary approaches that focus on avoiding false negatives often do not lead to adverse economic consequences or irrational choices, such approaches usually are not taken. The value of autonomy and the proper role of governmental paternalism with respect to environmental policy need to be considered more carefully in environmental decision making. PMID:11527754

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.

A three-year follow-up of congenital adrenal hyperplasia newborn screening.

PubMed

Pezzuti, Isabela L; Barra, Cristina B; Mantovani, Rafael M; Januário, José N; Silva, Ivani N

2014-01-01

congenital adrenal hyperplasia (CAH) newborn screening can prevent neonatal mortality in children with the salt-wasting form of the disease and prevent incorrect gender assignments, which can occur in females. However, the occurrence of false-positive results in preterm or low-birth-weight newborns creates some diagnostic difficulties, with consequent therapeutic implications. This study aimed to report the results of a pilot project for neonatal CAH screening conducted in the state of Minas Gerais, Brazil from 09/2007 to 05/2008 with a three-year follow-up. dried blood specimens were collected on filter paper cards three to seven days after birth of all newborns in the period. Samples were analyzed for 17-hydroxyprogesterone using an enzyme-linked immunosorbent assay (ELISA). a total of 159,415 children were screened. The apparent incidence of the classic variant of the disease was 1:9,963, based on initial diagnoses following newborn screening. During the follow-up period, eight of 16 children initially diagnosed with CAH were reclassified as unaffected, resulting in a revised incidence of 1:19,927. The false-positive rate was 0.31%, and the positive predictive value was 2.1%. Sensitivity and specificity were 100% and 99.7%, respectively. newborn screening is an important public health policy in developing countries such as Brazil, where CAH remains underdiagnosed. It has great potential to identify children with the disease who otherwise cannot be diagnosed earlier. Long-term follow-up and monitoring of all children with positive screening results are crucial to ensure a correct diagnosis and to calculate a reliable incidence ratio of the disease. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.