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

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.

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.

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.

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

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

NASA Astrophysics Data System (ADS)

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

2009-02-01

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

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

PubMed

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

1998-06-01

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

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

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…

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.

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

PubMed

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

2018-02-01

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

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.

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.

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

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 ...

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.

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…

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.

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 ...

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/

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.

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.

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.

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.

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.

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...

Laxative-free CT colonography

PubMed Central

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

2012-01-01

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

Oil Spill Detection in Terma-Side-Looking Airborne Radar Images Using Image Features and Region Segmentation

PubMed Central

Alacid, Beatriz

2018-01-01

This work presents a method for oil-spill detection on Spanish coasts using aerial Side-Looking Airborne Radar (SLAR) images, which are captured using a Terma sensor. The proposed method uses grayscale image processing techniques to identify the dark spots that represent oil slicks on the sea. The approach is based on two steps. First, the noise regions caused by aircraft movements are detected and labeled in order to avoid the detection of false-positives. Second, a segmentation process guided by a map saliency technique is used to detect image regions that represent oil slicks. The results show that the proposed method is an improvement on the previous approaches for this task when employing SLAR images. PMID:29316716

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

DTIC Science & Technology

2006-10-01

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

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.

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

PubMed Central

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

2009-01-01

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

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.

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

PubMed

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

2018-06-12

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

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.

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

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.

Analyzing False Positives of Four Questions in the Force Concept Inventory

ERIC Educational Resources Information Center

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

2018-01-01

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

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.

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

PubMed Central

2014-01-01

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

The current limitations of in vitro genotoxicity testing and their relevance to the in vivo situation.

PubMed

Nesslany, Fabrice

2017-08-01

The standard regulatory core battery of genotoxicity tests generally includes 2 or 3 validated tests with at least one in vitro test in bacteria and one in vitro test on cell cultures. However, limitations in in vitro genotoxicity testing may exist at many levels. The knowledge of the underlying mechanisms of genotoxicity is particularly useful to assess the level of relevance for the in vivo situation. In order to avoid wrong conclusions regarding the actual genotoxicity status of any test substance, it appears very important to be aware of the various origins of related bias leading to 'false positives and negatives' by using in vitro methods. Among these, mention may be made on the metabolic activation system, experimental (extreme) conditions, specificities of the test systems implemented, cell type used etc. The knowledge of the actual 'limits' of the in vitro test systems used is clearly an advantage and may contribute to avoid some pitfalls in order to better assess the level of relevance for the in vivo situation. Copyright © 2016. Published by Elsevier Ltd.

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 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.

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

Evaluation of exome variants using the Ion Proton Platform to sequence error-prone regions.

PubMed

Seo, Heewon; Park, Yoomi; Min, Byung Joo; Seo, Myung Eui; Kim, Ju Han

2017-01-01

The Ion Proton sequencer from Thermo Fisher accurately determines sequence variants from target regions with a rapid turnaround time at a low cost. However, misleading variant-calling errors can occur. We performed a systematic evaluation and manual curation of read-level alignments for the 675 ultrarare variants reported by the Ion Proton sequencer from 27 whole-exome sequencing data but that are not present in either the 1000 Genomes Project and the Exome Aggregation Consortium. We classified positive variant calls into 393 highly likely false positives, 126 likely false positives, and 156 likely true positives, which comprised 58.2%, 18.7%, and 23.1% of the variants, respectively. We identified four distinct error patterns of variant calling that may be bioinformatically corrected when using different strategies: simplicity region, SNV cluster, peripheral sequence read, and base inversion. Local de novo assembly successfully corrected 201 (38.7%) of the 519 highly likely or likely false positives. We also demonstrate that the two sequencing kits from Thermo Fisher (the Ion PI Sequencing 200 kit V3 and the Ion PI Hi-Q kit) exhibit different error profiles across different error types. A refined calling algorithm with better polymerase may improve the performance of the Ion Proton sequencing platform.

Comparative evaluation of paired blood culture (aerobic/aerobic) and single blood culture, along with clinical importance in catheter versus peripheral line at a tertiary care hospital.

PubMed

Tarai, B; Das, P; Kumar, D; Budhiraja, S

2012-01-01

Paired blood culture (PBC) is uncommon practice in hospitals in India, leading to delayed and inadequate diagnosis. Also contamination remains a critical determinant in hampering the definitive diagnosis. To establish the need of PBC over single blood culture (SBC) along with the degree of contamination, this comparative retrospective study was initiated. We processed 2553 PBC and 4350 SBC in BacT/ALERT 3D (bioMerieux) between October 2010 and June 2011. The positive cultures were identified in VITEK 2 Compact (bioMerieux). True positivity and contaminants were also analyzed in 486 samples received from catheter and peripheral line. Out of 2553 PBC samples, positivity was seen in 350 (13.70%). In 4350 SBC samples, positivity was seen in 200 samples (4.59%). In PBC true pathogens were 267 (10.45%) and contaminants were 83 (3.25%), whereas in SBC 153 (3.51%) were true positives and contaminants were 47 (1.08%). Most of the blood cultures (99.27 %) grew within 72 h and 95.8% were isolated within 48 h. In 486 PBCs received from catheter/periphery (one each), catheter positivity was found in 85 (true positives were 48, false positives 37). In peripheral samples true positives were 50 and false positives were 8. Significantly higher positive rates were seen in PBCs compared with SBCs. Automated blood culture and identification methods significantly reduced the time required for processing of samples and also facilitated yield of diverse/rare organisms. Blood culture from catheter line had higher false positives than peripheral blood culture. Thus every positive result from a catheter must be correlated with clinical findings and requires further confirmation.

Reducing False Positives in Runtime Analysis of Deadlocks

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

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

ERIC Educational Resources Information Center

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

2010-01-01

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

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. Correction equations can be formulated using either a unit or ½ mass approach. The ½ mass correction approach does not suffer from the bias generated from polyatomic or end user based contamination at the unit mass but is limited by the abundance sensitivity of the adjacent mass. For instance, the use of m/z 78 in a unit mass correction of 156Gd on m/z 78 can be biased by residual 40Ar38Ar and 78Se while the ½ mass approach can use 77.5 or 78.5 and is limited by the abundance sensitivity issues from mass 77 and 78 or 78 and 79, respectively. This presentation will evaluate the use of both unit and ½ mass correction approaches as a means of addressing M+2 false positives within the context of updating US EPA Method 200.8. This evaluation will include the analysis of As and Se standards near the detection limit in the presence of low (2ppb) and high (50ppb) levels of REE with benchmark concentrations estimated using

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.

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.

Occurrence of CPPopt Values in Uncorrelated ICP and ABP Time Series.

PubMed

Cabeleira, M; Czosnyka, M; Liu, X; Donnelly, J; Smielewski, P

2018-01-01

Optimal cerebral perfusion pressure (CPPopt) is a concept that uses the pressure reactivity (PRx)-CPP relationship over a given period to find a value of CPP at which PRx shows best autoregulation. It has been proposed that this relationship be modelled by a U-shaped curve, where the minimum is interpreted as being the CPP value that corresponds to the strongest autoregulation. Owing to the nature of the calculation and the signals involved in it, the occurrence of CPPopt curves generated by non-physiological variations of intracranial pressure (ICP) and arterial blood pressure (ABP), termed here "false positives", is possible. Such random occurrences would artificially increase the yield of CPPopt values and decrease the reliability of the methodology.In this work, we studied the probability of the random occurrence of false-positives and we compared the effect of the parameters used for CPPopt calculation on this probability. To simulate the occurrence of false-positives, uncorrelated ICP and ABP time series were generated by destroying the relationship between the waves in real recordings. The CPPopt algorithm was then applied to these new series and the number of false-positives was counted for different values of the algorithm's parameters. The percentage of CPPopt curves generated from uncorrelated data was demonstrated to be 11.5%. This value can be minimised by tuning some of the calculation parameters, such as increasing the calculation window and increasing the minimum PRx span accepted on the curve.

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.

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.

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

PubMed Central

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

1983-01-01

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

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

Predicting radiologists' true and false positive decisions in reading mammograms by using gaze parameters and image-based features

NASA Astrophysics Data System (ADS)

Gandomkar, Ziba; Tay, Kevin; Ryder, Will; Brennan, Patrick C.; Mello-Thoms, Claudia

2016-03-01

Radiologists' gaze-related parameters combined with image-based features were utilized to classify suspicious mammographic areas ultimately scored as True Positives (TP) and False Positives (FP). Eight breast radiologists read 120 two-view digital mammograms of which 59 had biopsy proven cancer. Eye tracking data was collected and nearby fixations were clustered together. Suspicious areas on mammograms were independently identified based on thresholding an intensity saliency map followed by automatic segmentation and pruning steps. For each radiologist reported area, radiologist's fixation clusters in the area, as well as neighboring suspicious areas within 2.5° of the center of fixation, were found. A 45-dimensional feature vector containing gaze parameters of the corresponding cluster along with image-based characteristics was constructed. Gaze parameters included total number of fixations in the cluster, dwell time, time to hit the cluster for the first time, maximum number of consecutive fixations, and saccade magnitude of the first fixation in the cluster. Image-based features consisted of intensity, shape, and texture descriptors extracted from the region around the suspicious area, its surrounding tissue, and the entire breast. For each radiologist, a userspecific Support Vector Machine (SVM) model was built to classify the reported areas as TPs or FPs. Leave-one-out cross validation was utilized to avoid over-fitting. A feature selection step was embedded in the SVM training procedure by allowing radial basis function kernels to have 45 scaling factors. The proposed method was compared with the radiologists' performance using the jackknife alternative free-response receiver operating characteristic (JAFROC). The JAFROC figure of merit increased significantly for six radiologists.

Computerized scheme for vertebra detection in CT scout image

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

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

NASA Astrophysics Data System (ADS)

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

2006-03-01

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

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.

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.

Finding evolved stars in the inner Galactic disk with Gaia

NASA Astrophysics Data System (ADS)

Quiroga-Nuñez, L. H.; van Langevelde, H. J.; Pihlström, Y. M.; Sjouwerman, L. O.; Brown, A. G. A.

2018-04-01

The Bulge Asymmetries and Dynamical Evolution (BAaDE) survey will provide positions and line-of-sight velocities of ~20, 000 evolved, maser bearing stars in the Galactic plane. Although this Galactic region is affected by optical extinction, BAaDE targets may have Gaia cross-matches, eventually providing additional stellar information. In an initial attempt to cross-match BAaDE targets with Gaia, we have found more than 5,000 candidates. Of these, we may expect half to show SiO emission, which will allow us to obtain velocity information. The cross-match is being refined to avoid false positives using different criteria based on distance analysis, flux variability, and color assessment in the mid- and near-IR. Once the cross-matches can be confirmed, we will have a unique sample to characterize the stellar population of evolved stars in the Galactic bulge, which can be considered fossils of the Milky Way formation.

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.

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

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...

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

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

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.

Simultaneous hair testing for opiates, cocaine, and metabolites by GC-MS: a survey of applicants for driving licenses with a history of drug use.

PubMed

Montagna, M; Stramesi, C; Vignali, C; Groppi, A; Polettini, A

2000-01-10

A sensitive GC-MS method for the simultaneous determination of opiates, cocaine, and metabolites in hair at a cut-off level of 0.1 ng/mg was adopted to assess past exposure to these drugs in applicants for driving licenses with a history of drug use. The sampling protocol consisted of collection of one hair (sample A, 5-cm length) and one urine sample. When hair and urine (EMIT Syva, cut-off levels: 0.3 mg/l for opiates, 0.15 mg/l for cocaine, GC-MS confirmation of positives) were both positive or negative the protocol was concluded. In the other cases, the assessment of 'current exposure' to drugs was carried out, in order to avoid seriated random urinalysis, by collecting a second hair sample (sample B) 6 weeks later and analysing the proximal 1-cm segment. Out of the 214 'A' hair samples analyzed, 14 (6.5%) tested positive for morphine and/or 6-acetylmorphine (6AM), and 26 (12%) for cocaine and/or benzoylecgonine (BE), whereas none of the samples tested positive for both drugs. Levels between 0.1 and 1 ng/mg of the single analytes were found in eight out of the 14 morphine-6AM positives (57%) and in 18 out of the 26 cocaine-BE positives (69%). The time course of positive cases showed a progressive decrease of morphine-6AM positives and a corresponding increase of cocaine-BE positives within the study period September 1995-February 1999. No cases with positive urine and negative hair were observed. Among the 40 positive cases, seven (four and three for opiates and cocaine, respectively) were found to be 'currently exposed to drug', four by urinalysis (three and one) and three by analysis of the hair sample B (1 and 2).

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

PubMed

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

2015-10-15

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

p-hacking by post hoc selection with multiple opportunities: Detectability by skewness test?: Comment on Simonsohn, Nelson, and Simmons (2014).

PubMed

Ulrich, Rolf; Miller, Jeff

2015-12-01

Simonsohn, Nelson, and Simmons (2014) have suggested a novel test to detect p-hacking in research, that is, when researchers report excessive rates of "significant effects" that are truly false positives. Although this test is very useful for identifying true effects in some cases, it fails to identify false positives in several situations when researchers conduct multiple statistical tests (e.g., reporting the most significant result). In these cases, p-curves are right-skewed, thereby mimicking the existence of real effects even if no effect is actually present. (c) 2015 APA, all rights reserved).

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

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.

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

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.

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

Cardiac phase detection in intravascular ultrasound images

NASA Astrophysics Data System (ADS)

Matsumoto, Monica M. S.; Lemos, Pedro Alves; Yoneyama, Takashi; Furuie, Sergio Shiguemi

2008-03-01

Image gating is related to image modalities that involve quasi-periodic moving organs. Therefore, during intravascular ultrasound (IVUS) examination, there is cardiac movement interference. In this paper, we aim to obtain IVUS gated images based on the images themselves. This would allow the reconstruction of 3D coronaries with temporal accuracy for any cardiac phase, which is an advantage over the ECG-gated acquisition that shows a single one. It is also important for retrospective studies, as in existing IVUS databases there are no additional reference signals (ECG). From the images, we calculated signals based on average intensity (AI), and, from consecutive frames, average intensity difference (AID), cross-correlation coefficient (CC) and mutual information (MI). The process includes a wavelet-based filter step and ascendant zero-cross detection in order to obtain the phase information. Firstly, we tested 90 simulated sequences with 1025 frames each. Our method was able to achieve more than 95.0% of true positives and less than 2.3% of false positives ratio, for all signals. Afterwards, we tested in a real examination, with 897 frames and ECG as gold-standard. We achieved 97.4% of true positives (CC and MI), and 2.5% of false positives. For future works, methodology should be tested in wider range of IVUS examinations.

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" 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…

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.

Robotic CCD microscope for enhanced crystal recognition

DOEpatents

Segelke, Brent W.; Toppani, Dominique

2007-11-06

A robotic CCD microscope and procedures to automate crystal recognition. The robotic CCD microscope and procedures enables more accurate crystal recognition, leading to fewer false negative and fewer false positives, and enable detection of smaller crystals compared to other methods available today.

A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

PubMed

Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

Medico legal aspects on neuromonitoring in thyroid surgery: informed consent on malpractice claims

PubMed Central

DEMONTIS, R.; PITTAU, M.R.; MATURO, A.; PETRUZZO, P.; CALÒ, P.G.

2017-01-01

Aim The purpose of this paper is to provide a forensic profile framework of neuromonitoring in thyroid surgery, regarding the information given to the patient and its classification as part of professional liability in the event of recurrent injury. Method Evaluation and reflections on the required behaviour of the surgeon on providing details on the operation before the informed consent is given and to outline the possible legal implications regarding professional liability as a result of recurrent injury. In particular, if it is an obligation to inform the patient about using this method and if it is possible for the surgeon to freely choose whether to employ this method, which is still burdened by a certain percentage of error and for that reason it cannot be defined a “standard of care”. Results To recognize neuromonitoring the role of standard of care in surgery of the thyroid means attribute a role of method able to avoid the surgeon to cause iatrogenic damage to the laryngeal nerve. For the foregoing reasons that is not true, determining false positives and false negatives, and this can be a double edged sword for the surgeon. Conclusions Although the progress in the field of thyroid surgery made in the last decade, currently there is no scientific reassuring evidence to completely avoid the possibility of producing an iatrogenic lesion of the laryngeal nerve. Information given to the patient prior to surgery should respect the requirements of completeness, freedom and honesty in order to allow the patient to self-determination. PMID:29205147

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

Overcoming confounded controls in the analysis of gene expression data from microarray experiments.

PubMed

Bhattacharya, Soumyaroop; Long, Dang; Lyons-Weiler, James

2003-01-01

A potential limitation of data from microarray experiments exists when improper control samples are used. In cancer research, comparisons of tumour expression profiles to those from normal samples is challenging due to tissue heterogeneity (mixed cell populations). A specific example exists in a published colon cancer dataset, in which tissue heterogeneity was reported among the normal samples. In this paper, we show how to overcome or avoid the problem of using normal samples that do not derive from the same tissue of origin as the tumour. We advocate an exploratory unsupervised bootstrap analysis that can reveal unexpected and undesired, but strongly supported, clusters of samples that reflect tissue differences instead of tumour versus normal differences. All of the algorithms used in the analysis, including the maximum difference subset algorithm, unsupervised bootstrap analysis, pooled variance t-test for finding differentially expressed genes and the jackknife to reduce false positives, are incorporated into our online Gene Expression Data Analyzer ( http:// bioinformatics.upmc.edu/GE2/GEDA.html ).

A new QRT-PCR assay designed for the differentiation between elements provided from Agrobacterium sp. in GMOs plant events and natural Agrobacterium sp. bacteria.

PubMed

Nabi, Nesrine; Chaouachi, Maher; Zellama, Mohamed Salem; Ben Hafsa, Ahmed; Mrabet, Besma; Saïd, Khaled; Fathia, Harzallah Skhiri

2016-04-01

The question asked in the present work was how to differentiate between contamination of field samples with and GM plants contained sequences provided from this bacterium in order to avoid false positives in the frame of the detection and the quantification of GMO. For this, new set of primers and corresponding TaqMan Minor Groove Binder (MGB) probes were designed to target Agrobacterium sp. using the tumor-morphology-shooty gene (TMS1). Final standard curves were calculated for each pathogen by plotting the threshold cycle value against the bacterial number (log (colony forming units) per milliliter) via linear regression. The method designed was highly specific and sensitive, with a detection limit of 10CFU/ml. No significant cross-reaction was observed. Results from this study showed that TaqMan real-time PCR, is potentially an effective method for the rapid and reliable quantification of Agrobacterium sp. in samples containing GMO or non GMO samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

1998-01-01

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

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.

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.

Quantum Dot-Based Luminescent Oxygen Channeling Assay for Potential Application in Homogeneous Bioassays.

PubMed

Zhuang, Si-Hui; Guo, Xin-Xin; Wu, Ying-Song; Chen, Zhen-Hua; Chen, Yao; Ren, Zhi-Qi; Liu, Tian-Cai

2016-01-01

The unique photoproperties of quantum dots are promising for potential application in bioassays. In the present study, quantum dots were applied to a luminescent oxygen channeling assay. The reaction system developed in this study was based on interaction of biotin with streptavidin. Carboxyl-modified polystyrene microspheres doped with quantum dots were biotinylated and used as acceptors. Photosensitizer-doped carboxyl-modified polystyrene microspheres were conjugated with streptavidin and used as donors. The results indicated that the singlet oxygen that was released from the donor beads diffused into the acceptor beads. The acceptor beads were then exited via thioxene, and were subsequently fluoresced. To avoid generating false positives, a high concentration (0.01 mg/mL) of quantum dots is required for application in homogeneous immunoassays. Compared to a conventional luminescent oxygen channeling assay, this quantum dots-based technique requires less time, and would be easier to automate and miniaturize because it requires no washing to remove excess labels.

Veterans treatment courts: A case study of their efficacy for Veterans' needs.

PubMed

Erickson, John W

Veterans Treatment Courts (VTCs) were created to: (1) address issues unique to U.S. Military Veterans; and, (2) where possible, avoid punishing veterans for crimes that may have been committed as a direct result of their mental conditions (e.g., Posttraumatic Stress Disorder (PTSD) and/or Traumatic Brain Injury (TBI)). Little research has been undertaken to ascertain whether VTCs are accomplishing their intended goals. To that end, the present case study examined three operating VTCs in order to determine if they are meeting their objectives. The research provides further information about VTC operations and recidivism rates. The research further reveals that, while the three VTCs examined are arguably benefitting veterans, they are not reaching a greater part of the population due largely to the gatekeeping role of VTC prosecutors, and the rigid eligibility requirements established by the three VTCs for veteran participation. Consequently, it's possible that the low recidivism rates reported by the three VTCs examined are inflated or constitute false positives. Copyright © 2016 Elsevier Ltd. All rights reserved.

Practice Paper of the Academy of Nutrition and Dietetics: Role of the Registered Dietitian Nutritionist in the Diagnosis and Management of Food Allergies.

PubMed

Collins, Sherry Coleman

2016-10-01

Incidence of food allergy has increased significantly over the past decade and represents an important health issue for millions of Americans. Diagnosis of immunoglobulin E-mediated food allergies is sometimes difficult because blood and skin tests have high rates of false positives, and oral food challenges are uncommon due to the expense and potential for serious reactions. Accurate diagnosis is crucial to avoid unnecessary dietary restriction, especially in children. Because registered dietitian nutritionists often work independently, receiving referrals for dietary education and guidance for a patient who is followed by one or several other practitioners, navigating the data available and making the appropriate follow-up contact optimizes treatment. The purpose of this paper is to provide guidance to the registered dietitian nutritionists and nutrition and dietetics technician, registered on appropriate and evidence-based nutrition counseling for diagnosis and management of food allergies. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Extraction of advanced geospatial intelligence (AGI) from commercial synthetic aperture radar imagery

NASA Astrophysics Data System (ADS)

Kanberoglu, Berkay; Frakes, David

2017-04-01

The extraction of objects from advanced geospatial intelligence (AGI) products based on synthetic aperture radar (SAR) imagery is complicated by a number of factors. For example, accurate detection of temporal changes represented in two-color multiview (2CMV) AGI products can be challenging because of speckle noise susceptibility and false positives that result from small orientation differences between objects imaged at different times. These cases of apparent motion can result in 2CMV detection, but they obviously differ greatly in terms of significance. In investigating the state-of-the-art in SAR image processing, we have found that differentiating between these two general cases is a problem that has not been well addressed. We propose a framework of methods to address these problems. For the detection of the temporal changes while reducing the number of false positives, we propose using adaptive object intensity and area thresholding in conjunction with relaxed brightness optical flow algorithms that track the motion of objects across time in small regions of interest. The proposed framework for distinguishing between actual motion and misregistration can lead to more accurate and meaningful change detection and improve object extraction from a SAR AGI product. Results demonstrate the ability of our techniques to reduce false positives up to 60%.

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).

New Perspectives on the Diagnosis of Allergy to Anisakis spp.

PubMed

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

2017-05-01

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

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

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.

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...

Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison.

PubMed

Den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evert-Jan P A; Milles, Julien; Schilham, Arnold M R; Lammers, Jan-Willem; de Jong, Pim A; Leiner, Tim; Budde, Ricardo P J

2016-02-01

To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules. In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity. Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level. CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

The utility of a handheld metal detector in detection and localization of pediatric metallic foreign body ingestion.

PubMed

Nation, Javan; Jiang, Wen

2017-01-01

To test the ability of a handheld metal detector (HHMD) to identify the presence and location of ingested metallic foreign bodies (MFBs) in children. Prospective case series enrolling children suspected of metallic foreign body ingestion presenting to the Emergency Department. Thirty-eight children were enrolled and the HHMD was used to detect the presence and location of a MFB. Results were compared to standard radiographic studies. Thirty-seven of the 38 ingested foreign bodies were MFBs. Of the 37 MFBs, the HHMD positively identified 33, and 4 were missed by HHMD but identified on radiography. When positive, the location indicated by HHMD correlated 100% with radiograph. There were 33 true positives, 0 false positives, 4 false negatives, and 1 true negative. This resulted in a sensitivity of 89% (95% CI of 75%-96%) and specificity of 100% (95% CI of 2.5%-100%). Our study demonstrates the accuracy of HHMD in the identification and localization of metallic foreign bodies. We propose an emergency room foreign body protocol that uses HHMD as an early screening tool in triage in order to expedite the process of obtaining Otolaryngology consultation and potentially shorten the wait time to the operating room or discharge. In instances were outside films are previously performed, HHMD use may be able to minimize the overall radiation exposure to children by obviating the need for repeat radiographs. As the sensitivity is not 100%, a negative HHMD screening does not negate the need for a standard radiograph in order to avoid missed MFBs. HHMD is best suited for detection of coins, which accounts for the majority of the MFB ingestions, and may not be suitable for all metallic objects since the amount of metal may decrease its sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Direct Imaging Search for Earth 2.0: Quantifying Biases and Planetary False Positives

NASA Astrophysics Data System (ADS)

Guimond, Claire Marie; Cowan, Nicolas B.

2018-06-01

Direct imaging is likely the best way to characterize the atmospheres of Earth-sized exoplanets in the habitable zone of Sun-like stars. Previously, Stark et al. estimated the Earth twin yield of future direct imaging missions, such as LUVOIR and HabEx. We extend this analysis to other types of planets, which will act as false positives for Earth twins. We define an Earth twin as any exoplanet within half an e-folding of 1 au in semimajor axis and 1 {R}\\oplus in planetary radius, orbiting a G-dwarf. Using Monte Carlo analyses, we quantify the biases and planetary false-positive rates of Earth searches. That is, given a pale dot at the correct projected separation and brightness to be a candidate Earth, what are the odds that it is, in fact, an Earth twin? Our notional telescope has a diameter of 10 m, an inner working angle of 3λ/D, and an outer working angle of 10λ/D (62 mas and 206 mas at 1.0 μm). With no precursor knowledge and one visit per star, 77% of detected candidate Earths are actually un-Earths; their mean radius is 2.3 {R}\\oplus , a sub-Neptune. The odds improve if we image every planet at its optimal orbital phase, either by relying on precursor knowledge, or by performing multi-epoch direct imaging. In such a targeted search, 47% of detected Earth twin candidates are false positives, and they have a mean radius of 1.7 {R}\\oplus . The false-positive rate is insensitive to stellar spectral type and the assumption of circular orbits.

Neural Network Target Identification System for False Alarm Reduction

NASA Technical Reports Server (NTRS)

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

2009-01-01

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

A computerized scheme for lung nodule detection in multiprojection chest radiography

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

Guo Wei; Li Qiang; Boyce, Sarah J.

2012-04-15

Purpose: Our previous study indicated that multiprojection chest radiography could significantly improve radiologists' performance for lung nodule detection in clinical practice. In this study, the authors further verify that multiprojection chest radiography can greatly improve the performance of a computer-aided diagnostic (CAD) scheme. Methods: Our database consisted of 59 subjects, including 43 subjects with 45 nodules and 16 subjects without nodules. The 45 nodules included 7 real and 38 simulated ones. The authors developed a conventional CAD scheme and a new fusion CAD scheme to detect lung nodules. The conventional CAD scheme consisted of four steps for (1) identification ofmore » initial nodule candidates inside lungs, (2) nodule candidate segmentation based on dynamic programming, (3) extraction of 33 features from nodule candidates, and (4) false positive reduction using a piecewise linear classifier. The conventional CAD scheme processed each of the three projection images of a subject independently and discarded the correlation information between the three images. The fusion CAD scheme included the four steps in the conventional CAD scheme and two additional steps for (5) registration of all candidates in the three images of a subject, and (6) integration of correlation information between the registered candidates in the three images. The integration step retained all candidates detected at least twice in the three images of a subject and removed those detected only once in the three images as false positives. A leave-one-subject-out testing method was used for evaluation of the performance levels of the two CAD schemes. Results: At the sensitivities of 70%, 65%, and 60%, our conventional CAD scheme reported 14.7, 11.3, and 8.6 false positives per image, respectively, whereas our fusion CAD scheme reported 3.9, 1.9, and 1.2 false positives per image, and 5.5, 2.8, and 1.7 false positives per patient, respectively. The low performance of the conventional CAD scheme may be attributed to the high noise level in chest radiography, and the small size and low contrast of most nodules. Conclusions: This study indicated that the fusion of correlation information in multiprojection chest radiography can markedly improve the performance of CAD scheme for lung nodule detection.« less

CHROMOSPHERIC EMISSION OF PLANET CANDIDATE HOST STARS: A WAY TO IDENTIFY FALSE POSITIVES

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

Karoff, Christoffer; Knudsen, Mads Faurschou; Albrecht, Simon

2016-10-10

It has been hypothesized that the presence of closely orbiting giant planets is associated with enhanced chromospheric emission of their host stars. The main cause for such a relation would likely be enhanced dynamo action induced by the planet. We present measurements of chromospheric emission in 234 planet candidate systems from the Kepler mission. This ensemble includes 37 systems with giant-planet candidates, which show a clear emission enhancement. The enhancement, however, disappears when systems that are also identified as eclipsing binary candidates are removed from the ensemble. This suggests that a large fraction of the giant-planet candidate systems with chromosphericmore » emission stronger than the Sun are not giant-planet systems, but false positives. Such false-positive systems could be tidally interacting binaries with strong chromospheric emission. This hypothesis is supported by an analysis of 188 eclipsing binary candidates that show increasing chromospheric emission as function of decreasing orbital period.« less

Challenges associated with post-deployment screening for mild traumatic brain injury in military personnel.

PubMed

Iverson, Grant L; Langlois, Jean A; McCrea, Michael A; Kelly, James P

2009-11-01

There is ongoing debate regarding the epidemiology of mild traumatic brain injury (MTBI) in military personnel. Accurate and timely estimates of the incidence of brain injury and the prevalence of long-term problems associated with brain injuries among active duty service members and veterans are essential for (a) operational planning, and (b) to allocate sufficient resources for rehabilitation and ongoing services and supports. The purpose of this article is to discuss challenges associated with post-deployment screening for MTBI. Multiple screening methods have been used in military, Veterans Affairs, and independent studies, which complicate cross-study comparisons of the resulting epidemiological data. We believe that post-deployment screening is important and necessary--but no screening methodology will be flawless, and false positives and false negatives are inevitable. Additional research is necessary to refine the sequential screening methodology, with the goal of minimizing false negatives during initial post-deployment screening and minimizing false positives during follow-up evaluations.

LOD significance thresholds for QTL analysis in experimental populations of diploid species

PubMed

Van Ooijen JW

1999-11-01

Linkage analysis with molecular genetic markers is a very powerful tool in the biological research of quantitative traits. The lack of an easy way to know what areas of the genome can be designated as statistically significant for containing a gene affecting the quantitative trait of interest hampers the important prediction of the rate of false positives. In this paper four tables, obtained by large-scale simulations, are presented that can be used with a simple formula to get the false-positives rate for analyses of the standard types of experimental populations with diploid species with any size of genome. A new definition of the term 'suggestive linkage' is proposed that allows a more objective comparison of results across species.

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.

The performance of non-NAAT point-of-care (POC) tests and rapid NAAT tests for chlamydia and gonorrhoea infections. An assessment of currently available assays.

PubMed

Brook, Gary

2015-12-01

To identify point-of-care (POC) and rapid nucleic acid amplification techniques (NAATs) for the diagnosis of chlamydia and gonorrhoea and assess their utility. Literature search for available POC and rapid NAATs. The performance from the best-performing assays were applied hypothetically to patients in the clinic in which 100 consecutive patients with chlamydia and 100 with gonorrhoea were diagnosed in 1737 and 4575 patients respectively, with 44/100 and 54/100 treated at first attendance, respectively. 11 POC and 1 rapid NAAT were identified. Published performances for the best POC for chlamydia (CRT) were: sensitivity 41%-87%, specificity 89%-99.6%. Our data suggest that if this assay was used instead of our current NAAT, for every 100 patients diagnosed currently, 23-46 extra patients would be treated at first attendance; 10-35 would go undiagnosed with 7-191 false-positives. Best chlamydia rapid NAAT (GeneXpert): sensitivity 97.5%-98.7%, specificity 99.4%-99.9%. Anticipated performance for every 100 patients diagnosed currently: 0 extra patients treated at first attendance, 1-3 undiagnosed, 0-2 false-positives. Best POC for gonorrhoea (GC Check): sensitivity 54%-70%, specificity 97%-98%. Anticipated performance for every 100 patients diagnosed currently: 14-18 extra patients treated at first attendance, 28-32 undiagnosed, 92-137 false-positives. Best rapid NAAT for gonorrhoea (GeneXpert): sensitivity 96%-100%, specificity 99.9%-100%. Anticipated performance for every 100 patients diagnosed currently: 0 extra patients treated at first attendance, 0-4 undiagnosed, 0-5 false-positives. Rapid NAAT would reduce time to treatment by 4 days for initially untreated patients. POC assays would need to be used in conjunction with a NAAT, increasing early treatment rates expense and false-positive results. The rapid NAAT could be used alone, with a reduction in average time-to-treat and a small reduction in sensitivity and specificity. 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/

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

Automatic detection of apical roots in oral radiographs

NASA Astrophysics Data System (ADS)

Wu, Yi; Xie, Fangfang; Yang, Jie; Cheng, Erkang; Megalooikonomou, Vasileios; Ling, Haibin

2012-03-01

The apical root regions play an important role in analysis and diagnosis of many oral diseases. Automatic detection of such regions is consequently the first step toward computer-aided diagnosis of these diseases. In this paper we propose an automatic method for periapical root region detection by using the state-of-theart machine learning approaches. Specifically, we have adapted the AdaBoost classifier for apical root detection. One challenge in the task is the lack of training cases especially for diseased ones. To handle this problem, we boost the training set by including more root regions that are close to the annotated ones and decompose the original images to randomly generate negative samples. Based on these training samples, the Adaboost algorithm in combination with Haar wavelets is utilized in this task to train an apical root detector. The learned detector usually generates a large amount of true and false positives. In order to reduce the number of false positives, a confidence score for each candidate detection result is calculated for further purification. We first merge the detected regions by combining tightly overlapped detected candidate regions and then we use the confidence scores from the Adaboost detector to eliminate the false positives. The proposed method is evaluated on a dataset containing 39 annotated digitized oral X-Ray images from 21 patients. The experimental results show that our approach can achieve promising detection accuracy.

Overview of Five-Years of Experience Performing Non-Invasive Fetal Sex Assessment in Maternal Blood

PubMed Central

Perlado-Marina, Sara; Bustamante-Aragones, Ana; Horcajada, Laura; Trujillo-Tiebas, Maria Jose; Lorda-Sanchez, Isabel; Ruiz Ramos, Marta; Plaza, Javier; Rodriguez de Alba, Marta

2013-01-01

Since the discovery of the presence of fetal DNA in maternal blood, non-invasive fetal sex determination has been the test most widely translated into clinical practice. To date there is no agreement between the different laboratories performing such tests in relation to which is the best protocol. As a consequence there are almost as many protocols as laboratories offering the service, using different methodologies and thus obtaining different diagnostic accuracies. By the end of 2007, after a validation study performed in 316 maternal samples collected between the 5th and 12th week of gestation, the fetal sex determination was incorporated into clinical practice in our Service. The test is performed in the first trimester of pregnancy, and it is offered as part of the genetic counseling process for couples at risk of X-linked disorders. As a general rule and in order to avoid misdiagnosis, two samples at different gestational ages are tested per patient. The analysis is performed by the study of the SRY gene by RT-PCR. Two hundred and twenty six pregnancies have been tested so far in these 5 years. Neither false positives nor false negatives diagnoses have been registered, thus giving a diagnostic accuracy of 100%. PMID:26835681

Improving sensitivity in proteome studies by analysis of false discovery rates for multiple search engines

PubMed Central

Jones, Andrew R.; Siepen, Jennifer A.; Hubbard, Simon J.; Paton, Norman W.

2010-01-01

Tandem mass spectrometry, run in combination with liquid chromatography (LC-MS/MS), can generate large numbers of peptide and protein identifications, for which a variety of database search engines are available. Distinguishing correct identifications from false positives is far from trivial because all data sets are noisy, and tend to be too large for manual inspection, therefore probabilistic methods must be employed to balance the trade-off between sensitivity and specificity. Decoy databases are becoming widely used to place statistical confidence in results sets, allowing the false discovery rate (FDR) to be estimated. It has previously been demonstrated that different MS search engines produce different peptide identification sets, and as such, employing more than one search engine could result in an increased number of peptides being identified. However, such efforts are hindered by the lack of a single scoring framework employed by all search engines. We have developed a search engine independent scoring framework based on FDR which allows peptide identifications from different search engines to be combined, called the FDRScore. We observe that peptide identifications made by three search engines are infrequently false positives, and identifications made by only a single search engine, even with a strong score from the source search engine, are significantly more likely to be false positives. We have developed a second score based on the FDR within peptide identifications grouped according to the set of search engines that have made the identification, called the combined FDRScore. We demonstrate by searching large publicly available data sets that the combined FDRScore can differentiate between between correct and incorrect peptide identifications with high accuracy, allowing on average 35% more peptide identifications to be made at a fixed FDR than using a single search engine. PMID:19253293

Development of a quantitative loop-mediated isothermal amplification assay for the field detection of Erysiphe necator

USDA-ARS?s Scientific Manuscript database

Plant pathogen detection systems have been useful tools to monitor inoculum presence and initiate management schedules. More recently, a LAMP assay was successfully designed for field use in the grape powdery mildew pathosystem; however, false negatives or false positives were prevalent in grower-co...

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.

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.

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

PubMed

Bansal, Ravi; Peterson, Bradley S

2018-06-01

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

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 Plantation Mapping in Indonesia Using Remote Sensing Data

NASA Astrophysics Data System (ADS)

Karpatne, A.; Jia, X.; Khandelwal, A.; Kumar, V.

2017-12-01

Plantation mapping is critical for understanding and addressing deforestation, a key driver of climate change and ecosystem degradation. Unfortunately, most plantation maps are limited to small areas for specific years because they rely on visual inspection of imagery. In this work, we propose a data-driven approach which automatically generates yearly plantation maps for large regions using MODIS multi-spectral data. While traditional machine learning algorithms face manifold challenges in this task, e.g. imperfect training labels, spatio-temporal data heterogeneity, noisy and high-dimensional data, lack of evaluation data, etc., we introduce a novel deep learning-based framework that combines existing imperfect plantation products as training labels and models the spatio-temporal relationships of land covers. We also explores the post-processing steps based on Hidden Markov Model that further improve the detection accuracy. Then we conduct extensive evaluation of the generated plantation maps. Specifically, by randomly sampling and comparing with high-resolution Digital Globe imagery, we demonstrate that the generated plantation maps achieve both high precision and high recall. When compared with existing plantation mapping products, our detection can avoid both false positives and false negatives. Finally, we utilize the generated plantation maps in analyzing the relationship between forest fires and growth of plantations, which assists in better understanding the cause of deforestation in Indonesia.

Using principal component analysis for selecting network behavioral anomaly metrics

NASA Astrophysics Data System (ADS)

Gregorio-de Souza, Ian; Berk, Vincent; Barsamian, Alex

2010-04-01

This work addresses new approaches to behavioral analysis of networks and hosts for the purposes of security monitoring and anomaly detection. Most commonly used approaches simply implement anomaly detectors for one, or a few, simple metrics and those metrics can exhibit unacceptable false alarm rates. For instance, the anomaly score of network communication is defined as the reciprocal of the likelihood that a given host uses a particular protocol (or destination);this definition may result in an unrealistically high threshold for alerting to avoid being flooded by false positives. We demonstrate that selecting and adapting the metrics and thresholds, on a host-by-host or protocol-by-protocol basis can be done by established multivariate analyses such as PCA. We will show how to determine one or more metrics, for each network host, that records the highest available amount of information regarding the baseline behavior, and shows relevant deviances reliably. We describe the methodology used to pick from a large selection of available metrics, and illustrate a method for comparing the resulting classifiers. Using our approach we are able to reduce the resources required to properly identify misbehaving hosts, protocols, or networks, by dedicating system resources to only those metrics that actually matter in detecting network deviations.

Comparison of body mass index, waist circumference, and waist to height ratio in the prediction of hypertension and diabetes mellitus: Filipino-American women cardiovascular study.

PubMed

Battie, Cynthia A; Borja-Hart, Nancy; Ancheta, Irma B; Flores, Rene; Rao, Goutham; Palaniappan, Latha

2016-12-01

The relative ability of three obesity indices to predict hypertension (HTN) and diabetes (DM) and the validity of using Asian-specific thresholds of these indices were examined in Filipino-American women (FAW). Filipino-American women ( n  = 382), 40-65 years of age were screened for hypertension (HTN) and diabetes (DM) in four major US cities. Body mass index (BMI), waist circumference (WC) and waist circumference to height ratio (WHtR) were measured. ROC analyses determined that the three obesity measurements were similar in predicting HTN and DM (AUC: 0.6-0.7). The universal WC threshold of ≥ 35 in. missed 13% of the hypertensive patients and 12% of the diabetic patients. The Asian WC threshold of ≥ 31.5 in. increased detection of HTN and DM but with a high rate of false positives. The traditional BMI ≥ 25 kg/m 2 threshold missed 35% of those with hypertension and 24% of those with diabetes. The Asian BMI threshold improved detection but resulted in a high rate of false positives. The suggested WHtR cut-off of ≥ 0.5 missed only 1% of those with HTN and 0% of those with DM. The three obesity measurements had similar but modest ability to predict HTN and DM in FAW. Using Asian-specific thresholds increased accuracy but with a high rate of false positives. Whether FAW, especially at older ages, should be encouraged to reach these lower thresholds needs further investigation because of the high false positive rates.

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.

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

PubMed

Basketter, David A; Kimber, Ian

2011-10-01

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

Model Selection in the Analysis of Photoproduction Data

NASA Astrophysics Data System (ADS)

Landay, Justin

2017-01-01

Scattering experiments provide one of the most powerful and useful tools for probing matter to better understand its fundamental properties governed by the strong interaction. As the spectroscopy of the excited states of nucleons enters a new era of precision ushered in by improved experiments at Jefferson Lab and other facilities around the world, traditional partial-wave analysis methods must be adjusted accordingly. In this poster, we present a rigorous set of statistical tools and techniques that we implemented; most notably, the LASSO method, which serves for the selection of the simplest model, allowing us to avoid over fitting. In the case of establishing the spectrum of exited baryons, it avoids overpopulation of the spectrum and thus the occurrence of false-positives. This is a prerequisite to reliably compare theories like lattice QCD or quark models to experiments. Here, we demonstrate the principle by simultaneously fitting three observables in neutral pion photo-production, such as the differential cross section, beam asymmetry and target polarization across thousands of data points. Other authors include Michael Doring, Bin Hu, and Raquel Molina.

Application of Chemical Genomics to Plant-Bacteria Communication: A High-Throughput System to Identify Novel Molecules Modulating the Induction of Bacterial Virulence Genes by Plant Signals.

PubMed

Vandelle, Elodie; Puttilli, Maria Rita; Chini, Andrea; Devescovi, Giulia; Venturi, Vittorio; Polverari, Annalisa

2017-01-01

The life cycle of bacterial phytopathogens consists of a benign epiphytic phase, during which the bacteria grow in the soil or on the plant surface, and a virulent endophytic phase involving the penetration of host defenses and the colonization of plant tissues. Innovative strategies are urgently required to integrate copper treatments that control the epiphytic phase with complementary tools that control the virulent endophytic phase, thus reducing the quantity of chemicals applied to economically and ecologically acceptable levels. Such strategies include targeted treatments that weaken bacterial pathogens, particularly those inhibiting early infection steps rather than tackling established infections. This chapter describes a reporter gene-based chemical genomic high-throughput screen for the induction of bacterial virulence by plant molecules. Specifically, we describe a chemical genomic screening method to identify agonist and antagonist molecules for the induction of targeted bacterial virulence genes by plant extracts, focusing on the experimental controls required to avoid false positives and thus ensuring the results are reliable and reproducible.

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.

Automatic abdominal lymph node detection method based on local intensity structure analysis from 3D x-ray CT images

NASA Astrophysics Data System (ADS)

Nakamura, Yoshihiko; Nimura, Yukitaka; Kitasaka, Takayuki; Mizuno, Shinji; Furukawa, Kazuhiro; Goto, Hidemi; Fujiwara, Michitaka; Misawa, Kazunari; Ito, Masaaki; Nawano, Shigeru; Mori, Kensaku

2013-03-01

This paper presents an automated method of abdominal lymph node detection to aid the preoperative diagnosis of abdominal cancer surgery. In abdominal cancer surgery, surgeons must resect not only tumors and metastases but also lymph nodes that might have a metastasis. This procedure is called lymphadenectomy or lymph node dissection. Insufficient lymphadenectomy carries a high risk for relapse. However, excessive resection decreases a patient's quality of life. Therefore, it is important to identify the location and the structure of lymph nodes to make a suitable surgical plan. The proposed method consists of candidate lymph node detection and false positive reduction. Candidate lymph nodes are detected using a multi-scale blob-like enhancement filter based on local intensity structure analysis. To reduce false positives, the proposed method uses a classifier based on support vector machine with the texture and shape information. The experimental results reveal that it detects 70.5% of the lymph nodes with 13.0 false positives per case.

Automated detection of microcalcification clusters in mammograms

NASA Astrophysics Data System (ADS)

Karale, Vikrant A.; Mukhopadhyay, Sudipta; Singh, Tulika; Khandelwal, Niranjan; Sadhu, Anup

2017-03-01

Mammography is the most efficient modality for detection of breast cancer at early stage. Microcalcifications are tiny bright spots in mammograms and can often get missed by the radiologist during diagnosis. The presence of microcalcification clusters in mammograms can act as an early sign of breast cancer. This paper presents a completely automated computer-aided detection (CAD) system for detection of microcalcification clusters in mammograms. Unsharp masking is used as a preprocessing step which enhances the contrast between microcalcifications and the background. The preprocessed image is thresholded and various shape and intensity based features are extracted. Support vector machine (SVM) classifier is used to reduce the false positives while preserving the true microcalcification clusters. The proposed technique is applied on two different databases i.e DDSM and private database. The proposed technique shows good sensitivity with moderate false positives (FPs) per image on both databases.

Performance and process in collective and individual memory: the role of social decision schemes and memory bias in collective memory.

PubMed

Van Swol, Lyn M

2008-04-01

To assess performance and processes in collective and individual memory, participants watched two job candidates on video. Beforehand, half the participants were told they would be tested on their memory of the interviews, and the other half were asked to make a decision to hire one of the candidates. Afterwards, participants completed a recognition memory task in either a group or individual condition. Groups had better recognition memory than individuals. Individuals made more false positives than false negatives and groups exaggerated this. Post-hoc analysis found that groups only exaggerated the tendency towards false positives on items that reflected negatively on the job candidate. There was no significant difference between instruction conditions. When reaching consensus on the recognition task, groups tended to choose the correct answer if at least two members had the correct answer. This method of consensus is discussed as a factor in groups' superior memory performance.

Methodological basis for the optimization of a marine sea-urchin embryo test (SET) for the ecological assessment of coastal water quality.

PubMed

Saco-Alvarez, Liliana; Durán, Iria; Ignacio Lorenzo, J; Beiras, Ricardo

2010-05-01

The sea-urchin embryo test (SET) has been frequently used as a rapid, sensitive, and cost-effective biological tool for marine monitoring worldwide, but the selection of a sensitive, objective, and automatically readable endpoint, a stricter quality control to guarantee optimum handling and biological material, and the identification of confounding factors that interfere with the response have hampered its widespread routine use. Size increase in a minimum of n=30 individuals per replicate, either normal larvae or earlier developmental stages, was preferred to observer-dependent, discontinuous responses as test endpoint. Control size increase after 48 h incubation at 20 degrees C must meet an acceptability criterion of 218 microm. In order to avoid false positives minimums of 32 per thousand salinity, 7 pH and 2mg/L oxygen, and a maximum of 40 microg/L NH(3) (NOEC) are required in the incubation media. For in situ testing size increase rates must be corrected on a degree-day basis using 12 degrees C as the developmental threshold. Copyright 2010 Elsevier Inc. All rights reserved.

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.

Preliminary road alinement through the Great Kavir in Iran by repetitive ERTS-1 coverage

NASA Technical Reports Server (NTRS)

Krinsley, D. B.

1974-01-01

Access to the Great Kavir is generally limited to the period August through October when some salt crusts will support limited vehicular movement. The condition of the salt crusts and their parent sediments during the long wet season have been unknown. This absence of information about the surface of the Great Kavir has prevented an intensive study of a possible road alinement which could shorten the present route between northern and central Iran by 760 km. False color diazo composites of bands 4, 5, and 7 were prepared from positives of ERTS-1 MSS images taken of the Great Kavir. These scenes presented a record of the seasonal hydrologic changes that occurred from the dry to the wet season. During the period of maximum inundation and lowest bearing strengths, as inferred from the image of May 12, 1973, it was possible to select a preliminary road alinement that would avoid the wettest or roughest areas and take advantage of the best terrain and shortest distance. The eventual road alinement should be based on a longer record of observation and on-site investigations.

An Automatic Detection System of Lung Nodule Based on Multi-Group Patch-Based Deep Learning Network.

PubMed

Jiang, Hongyang; Ma, He; Qian, Wei; Gao, Mengdi; Li, Yan

2017-07-14

High-efficiency lung nodule detection dramatically contributes to the risk assessment of lung cancer. It is a significant and challenging task to quickly locate the exact positions of lung nodules. Extensive work has been done by researchers around this domain for approximately two decades. However, previous computer aided detection (CADe) schemes are mostly intricate and time-consuming since they may require more image processing modules, such as the computed tomography (CT) image transformation, the lung nodule segmentation and the feature extraction, to construct a whole CADe system. It is difficult for those schemes to process and analyze enormous data when the medical images continue to increase. Besides, some state of the art deep learning schemes may be strict in the standard of database. This study proposes an effective lung nodule detection scheme based on multi-group patches cut out from the lung images, which are enhanced by the Frangi filter. Through combining two groups of images, a four-channel convolution neural networks (CNN) model is designed to learn the knowledge of radiologists for detecting nodules of four levels. This CADe scheme can acquire the sensitivity of 80.06% with 4.7 false positives per scan and the sensitivity of 94% with 15.1 false positives per scan. The results demonstrate that the multi-group patch-based learning system is efficient to improve the performance of lung nodule detection and greatly reduce the false positives under a huge amount of image data.

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

PubMed

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

2016-10-01

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

Putting a New Filter On Cancer Screening.

PubMed

Huff, Charlotte

2016-10-01

Experts are rethinking routine cancer screening. Genetic tests could be the answer. They may add upfront expense, but might eventually lead to savings by winnowing out unnecessary screening. Concern about false positives helps push this movement along.

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

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

PubMed

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

2017-10-01

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

False Positives in Multiple Regression: Unanticipated Consequences of Measurement Error in the Predictor Variables

ERIC Educational Resources Information Center

Shear, Benjamin R.; Zumbo, Bruno D.

2013-01-01

Type I error rates in multiple regression, and hence the chance for false positive research findings, can be drastically inflated when multiple regression models are used to analyze data that contain random measurement error. This article shows the potential for inflated Type I error rates in commonly encountered scenarios and provides new…

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

USGS Publications Warehouse

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

2015-01-01

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

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.

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

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

Benefits, harms, and costs for breast cancer screening after US implementation of digital mammography.

PubMed

Stout, Natasha K; Lee, Sandra J; Schechter, Clyde B; Kerlikowske, Karla; Alagoz, Oguzhan; Berry, Donald; Buist, Diana S M; Cevik, Mucahit; Chisholm, Gary; de Koning, Harry J; Huang, Hui; Hubbard, Rebecca A; Miglioretti, Diana L; Munsell, Mark F; Trentham-Dietz, Amy; van Ravesteyn, Nicolien T; Tosteson, Anna N A; Mandelblatt, Jeanne S

2014-06-01

Compared with film, digital mammography has superior sensitivity but lower specificity for women aged 40 to 49 years and women with dense breasts. Digital has replaced film in virtually all US facilities, but overall population health and cost from use of this technology are unclear. Using five independent models, we compared digital screening strategies starting at age 40 or 50 years applied annually, biennially, or based on density with biennial film screening from ages 50 to 74 years and with no screening. Common data elements included cancer incidence and test performance, both modified by breast density. Lifetime outcomes included mortality, quality-adjusted life-years, and screening and treatment costs. For every 1000 women screened biennially from age 50 to 74 years, switching to digital from film yielded a median within-model improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false-positive results, and $0.35 million more in costs. For an individual woman, this translates to a health gain of 0.73 days. Extending biennial digital screening to women ages 40 to 49 years was cost-effective, although results were sensitive to quality-of-life decrements related to screening and false positives. Targeting annual screening by density yielded similar outcomes to targeting by age. Annual screening approaches could increase costs to $5.26 million per 1000 women, in part because of higher numbers of screens and false positives, and were not efficient or cost-effective. The transition to digital breast cancer screening in the United States increased total costs for small added health benefits. The value of digital mammography screening among women aged 40 to 49 years depends on women's preferences regarding false positives. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Using gas chromatography with ion mobility spectrometry to resolve explosive compounds in the presence of interferents.

PubMed

Cook, Greg W; LaPuma, Peter T; Hook, Gary L; Eckenrode, Brian A

2010-11-01

Ion mobility spectrometry (IMS) is a valued field detection technology because of its speed and high sensitivity, but IMS cannot easily resolve analytes of interest within mixtures. Coupling gas chromatography (GC) to IMS adds a separation capability to resolve complex matrices. A GC-IONSCAN® operated in IMS and GC⁄ IMS modes was evaluated with combinations of five explosives and four interferents. In 100 explosive/interferent combinations, IMS yielded 21 false positives while GC⁄ IMS substantially reduced the occurrence of false positives to one. In addition, the results indicate that through redesign or modification of the preconcentrator there would be significant advantages to using GC⁄ IMS, such as enhancement of the linear dynamic range (LDR) in some situations. By balancing sensitivity with LDR, GC⁄ IMS could prove to be a very advantageous tool when addressing real world complex mixture situations.

Improving face image extraction by using deep learning technique

NASA Astrophysics Data System (ADS)

Xue, Zhiyun; Antani, Sameer; Long, L. R.; Demner-Fushman, Dina; Thoma, George R.

2016-03-01

The National Library of Medicine (NLM) has made a collection of over a 1.2 million research articles containing 3.2 million figure images searchable using the Open-iSM multimodal (text+image) search engine. Many images are visible light photographs, some of which are images containing faces ("face images"). Some of these face images are acquired in unconstrained settings, while others are studio photos. To extract the face regions in the images, we first applied one of the most widely-used face detectors, a pre-trained Viola-Jones detector implemented in Matlab and OpenCV. The Viola-Jones detector was trained for unconstrained face image detection, but the results for the NLM database included many false positives, which resulted in a very low precision. To improve this performance, we applied a deep learning technique, which reduced the number of false positives and as a result, the detection precision was improved significantly. (For example, the classification accuracy for identifying whether the face regions output by this Viola- Jones detector are true positives or not in a test set is about 96%.) By combining these two techniques (Viola-Jones and deep learning) we were able to increase the system precision considerably, while avoiding the need to manually construct a large training set by manual delineation of the face regions.

Methods for consistent forewarning of critical events across multiple data channels

DOEpatents

Hively, Lee M.

2006-11-21

This invention teaches further method improvements to forewarn of critical events via phase-space dissimilarity analysis of data from biomedical equipment, mechanical devices, and other physical processes. One improvement involves conversion of time-serial data into equiprobable symbols. A second improvement is a method to maximize the channel-consistent total-true rate of forewarning from a plurality of data channels over multiple data sets from the same patient or process. This total-true rate requires resolution of the forewarning indications into true positives, true negatives, false positives and false negatives. A third improvement is the use of various objective functions, as derived from the phase-space dissimilarity measures, to give the best forewarning indication. A fourth improvement uses various search strategies over the phase-space analysis parameters to maximize said objective functions. A fifth improvement shows the usefulness of the method for various biomedical and machine applications.

The Final Kepler Planet Candidate Catalog (DR25)

NASA Astrophysics Data System (ADS)

Coughlin, Jeffrey; Thompson, Susan E.; Kepler Team

2017-06-01

We present Kepler's final planet candidate catalog, which is based on the Q1--Q17 DR25 data release and was created to allow for accurate calculations of planetary occurrence rates. We discuss improvements made to our fully automated candidate vetting procedure, which yields specific categories of false positives and a disposition score value to indicate decision confidence. We present the use of light curve inversion and scrambling, in addition to our continued use of pixel-level transit injection, to produce artificial planet candidates and false positives. Since these simulated data sets were subjected to the same automated vetting procedure as the real data set, we are able to measure both the completeness and reliability of the catalog. The DR25 catalog, source code, and a multitude of completeness and reliability data products are available at the Exoplanet Archive (http://exoplanetarchive.ipac.caltech.edu). The DR25 light curves and pixel-level data are available at MAST (http://archive.stsci.edu/kepler).

Predicting protein functions from redundancies in large-scale protein interaction networks

NASA Technical Reports Server (NTRS)

Samanta, Manoj Pratim; Liang, Shoudan

2003-01-01

Interpreting data from large-scale protein interaction experiments has been a challenging task because of the widespread presence of random false positives. Here, we present a network-based statistical algorithm that overcomes this difficulty and allows us to derive functions of unannotated proteins from large-scale interaction data. Our algorithm uses the insight that if two proteins share significantly larger number of common interaction partners than random, they have close functional associations. Analysis of publicly available data from Saccharomyces cerevisiae reveals >2,800 reliable functional associations, 29% of which involve at least one unannotated protein. By further analyzing these associations, we derive tentative functions for 81 unannotated proteins with high certainty. Our method is not overly sensitive to the false positives present in the data. Even after adding 50% randomly generated interactions to the measured data set, we are able to recover almost all (approximately 89%) of the original associations.

Detection of Fundus Lesions Using Classifier Selection

NASA Astrophysics Data System (ADS)

Nagayoshi, Hiroto; Hiramatsu, Yoshitaka; Sako, Hiroshi; Himaga, Mitsutoshi; Kato, Satoshi

A system for detecting fundus lesions caused by diabetic retinopathy from fundus images is being developed. The system can screen the images in advance in order to reduce the inspection workload on doctors. One of the difficulties that must be addressed in completing this system is how to remove false positives (which tend to arise near blood vessels) without decreasing the detection rate of lesions in other areas. To overcome this difficulty, we developed classifier selection according to the position of a candidate lesion, and we introduced new features that can distinguish true lesions from false positives. A system incorporating classifier selection and these new features was tested in experiments using 55 fundus images with some lesions and 223 images without lesions. The results of the experiments confirm the effectiveness of the proposed system, namely, degrees of sensitivity and specificity of 98% and 81%, respectively.

Texture-based CAD improves diagnosis for low-dose CT colonography

NASA Astrophysics Data System (ADS)

Liang, Zhengrong; Cohen, Harris; Posniak, Erica; Fiore, Eddie; Wang, Zigang; Li, Bin; Andersen, Joseph; Harrington, Donald

2008-03-01

Computed tomography (CT)-based virtual colonoscopy or CT colonography (CTC) currently utilizes oral contrast solutions to tag the colonic fluid and possibly residual stool for differentiation from the colon wall and polyps. The enhanced image density of the tagged colonic materials causes a significant partial volume (PV) effect into the colon wall as well as the lumen space (filled with air or CO II). The PV effect on the colon wall can "bury" polyps of size as large as 5mm by increasing their image densities to a noticeable level, resulting in false negatives. It can also create false positives when PV effect goes into the lumen space. We have been modeling the PV effect for mixture-based image segmentation and developing text-based computer-aided detection of polyp (CADpolyp) by utilizing the PV mixture-based image segmentation. This work presents some preliminary results of developing and applying texture-based CADpolyp technique to low-dose CTC studies. A total of 114 studies of asymptomatic patients older than 50, who underwent CTC and then optical colonoscopy (OC) on the same day, were selected from a database, which was accumulated in the past decade and contains various bowel preparations and CT scanning protocols. The participating radiologists found ten polyps of greater than 5 mm from a total of 16 OC proved polyps, i.e., a detection sensitivity of 63%. They scored 23 false positives from the database, i.e., a 20% false positive rate. Approximately 70% of the datasets were marked as imperfect bowel cleansing and/or presence of image artifacts. The impact of imperfect bowel cleansing and image artifacts on VC performance is significant. The texture-based CADpolyp detected all the polyps with an average of 2.68 false positives per patient. This indicates that texture-based CADpolyp can improve the CTC performance in the cases of imperfect cleansed bowels and presence of image artifacts.

Imaging in gynaecology: How good are we in identifying endometriomas?

PubMed Central

Van Holsbeke, C.; Van Calster, B.; Guerriero, S.; Savelli, L.; Leone, F.; Fischerova, D; Czekierdowski, A.; Fruscio, R.; Veldman, J.; Van de Putte, G.; Testa, A.C.; Bourne, T.; Valentin, L.; Timmerman, D.

2009-01-01

Aim: To evaluate the performance of subjective evaluation of ultrasound findings (pattern recognition) to discriminate endometriomas from other types of adnexal masses and to compare the demographic and ultrasound characteristics of the true positive cases with those cases that were presumed to be an endometrioma but proved to have a different histology (false positive cases) and the endometriomas missed by pattern recognition (false negative cases). Methods: All patients in the International Ovarian Tumor Analysis (IOTA ) studies were included for analysis. In the IOTA studies, patients with an adnexal mass that were preoperatively examined by expert sonologists following the same standardized ultrasound protocol were prospectively included in 21 international centres. Sensitivity and specificity to discriminate endometriomas from other types of adnexal masses using pattern recognition were calculated. Ultrasound and some demographic variables of the masses presumed to be an endometrioma were analysed (true positives and false positives) and compared with the variables of the endometriomas missed by pattern recognition (false negatives) as well as the true negatives. Results: IOTA phase 1, 1b and 2 included 3511 patients of which 2560 were benign (73%) and 951 malignant (27%). The dataset included 713 endometriomas. Sensitivity and specificity for pattern recognition were 81% (577/713) and 97% (2723/2798). The true positives were more often unilocular with ground glass echogenicity than the masses in any other category. Among the 75 false positive cases, 66 were benign but 9 were malignant (5 borderline tumours, 1 rare primary invasive tumour and 3 endometrioid adenocarcinomas). The presumed diagnosis suggested by the sonologist in case of a missed endometrioma was mostly functional cyst or cystadenoma. Conclusion: Expert sonologists can quite accurately discriminate endometriomas from other types of adnexal masses, but in this dataset 1% of the masses that were classified as endometrioma by pattern recognition proved to be malignancies. PMID:25478066

A new pooling strategy for high-throughput screening: the Shifted Transversal Design

PubMed Central

Thierry-Mieg, Nicolas

2006-01-01

Background In binary high-throughput screening projects where the goal is the identification of low-frequency events, beyond the obvious issue of efficiency, false positives and false negatives are a major concern. Pooling constitutes a natural solution: it reduces the number of tests, while providing critical duplication of the individual experiments, thereby correcting for experimental noise. The main difficulty consists in designing the pools in a manner that is both efficient and robust: few pools should be necessary to correct the errors and identify the positives, yet the experiment should not be too vulnerable to biological shakiness. For example, some information should still be obtained even if there are slightly more positives or errors than expected. This is known as the group testing problem, or pooling problem. Results In this paper, we present a new non-adaptive combinatorial pooling design: the "shifted transversal design" (STD). It relies on arithmetics, and rests on two intuitive ideas: minimizing the co-occurrence of objects, and constructing pools of constant-sized intersections. We prove that it allows unambiguous decoding of noisy experimental observations. This design is highly flexible, and can be tailored to function robustly in a wide range of experimental settings (i.e., numbers of objects, fractions of positives, and expected error-rates). Furthermore, we show that our design compares favorably, in terms of efficiency, to the previously described non-adaptive combinatorial pooling designs. Conclusion This method is currently being validated by field-testing in the context of yeast-two-hybrid interactome mapping, in collaboration with Marc Vidal's lab at the Dana Farber Cancer Institute. Many similar projects could benefit from using the Shifted Transversal Design. PMID:16423300

LS-CAP: an algorithm for identifying cytogenetic aberrations in hepatocellular carcinoma using microarray data.

PubMed

He, Xianmin; Wei, Qing; Sun, Meiqian; Fu, Xuping; Fan, Sichang; Li, Yao

2006-05-01

Biological techniques such as Array-Comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH) and affymetrix single nucleotide pleomorphism (SNP) array have been used to detect cytogenetic aberrations. However, on genomic scale, these techniques are labor intensive and time consuming. Comparative genomic microarray analysis (CGMA) has been used to identify cytogenetic changes in hepatocellular carcinoma (HCC) using gene expression microarray data. However, CGMA algorithm can not give precise localization of aberrations, fails to identify small cytogenetic changes, and exhibits false negatives and positives. Locally un-weighted smoothing cytogenetic aberrations prediction (LS-CAP) based on local smoothing and binomial distribution can be expected to address these problems. LS-CAP algorithm was built and used on HCC microarray profiles. Eighteen cytogenetic abnormalities were identified, among them 5 were reported previously, and 12 were proven by CGH studies. LS-CAP effectively reduced the false negatives and positives, and precisely located small fragments with cytogenetic aberrations.

Overhead longwave infrared hyperspectral material identification using radiometric models

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

Zelinski, M. E.

Material detection algorithms used in hyperspectral data processing are computationally efficient but can produce relatively high numbers of false positives. Material identification performed as a secondary processing step on detected pixels can help separate true and false positives. This paper presents a material identification processing chain for longwave infrared hyperspectral data of solid materials collected from airborne platforms. The algorithms utilize unwhitened radiance data and an iterative algorithm that determines the temperature, humidity, and ozone of the atmospheric profile. Pixel unmixing is done using constrained linear regression and Bayesian Information Criteria for model selection. The resulting product includes an optimalmore » atmospheric profile and full radiance material model that includes material temperature, abundance values, and several fit statistics. A logistic regression method utilizing all model parameters to improve identification is also presented. This paper details the processing chain and provides justification for the algorithms used. Several examples are provided using modeled data at different noise levels.« less

Tests for a disease-susceptibility locus allowing for an inbreeding coefficient (F).

PubMed

Song, Kijoung; Elston, Robert C

2003-11-01

We begin by discussing the false positive test results that arise because of cryptic relatedness and population substructure when testing a disease susceptibility locus. We extend and evaluate the Hardy-Weinberg disequilibrium (HWD) method, allowing for an inbreeding coefficient (F) in a similar way that Devlin and Roeder (1999) allowed for inbreeding in a case-control study. Then we compare the HWD measure and the common direct measure of linkage disequilibrium, both when there is no population substructure (F = 0) and when there is population substructure (F not = 0), for a single marker. The HWD test statistic gives rise to false positives caused by population stratification. These false positives can be controlled by adjusting the test statistic for the amount of variance inflation caused by the inbreeding coefficient (F). The power loss for the HWD test that arises when controlling for population structure is much less than that which arises for the common direct measure of linkage disequilibrium. However, in the multiplicative model, the HWD test has virtually no power even when allowing for non-zero F.

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%.

A deep learning framework for the automated inspection of complex dual-energy x-ray cargo imagery

NASA Astrophysics Data System (ADS)

Rogers, Thomas W.; Jaccard, Nicolas; Griffin, Lewis D.

2017-05-01

Previously, we investigated the use of Convolutional Neural Networks (CNNs) to detect so-called Small Metallic Threats (SMTs) hidden amongst legitimate goods inside a cargo container. We trained a CNN from scratch on data produced by a Threat Image Projection (TIP) framework that generates images with realistic variation to robustify performance. The system achieved 90% detection of containers that contained a single SMT, while raising 6% false positives on benign containers. The best CNN architecture used the raw high energy image (single-energy) and its logarithm as input channels. Use of the logarithm improved performance, thus echoing studies on human operator performance. However, it is an unexpected result with CNNs. In this work, we (i) investigate methods to exploit material information captured in dual-energy images, and (ii) introduce a new CNN training scheme that generates `spot-the-difference' benign and threat pairs on-the-fly. To the best of our knowledge, this is the first time that CNNs have been applied directly to raw dual-energy X-ray imagery, in any field. To exploit dual-energy, we experiment with adapting several physics-derived approaches to material discrimination from the cargo literature, and introduce three novel variants. We hypothesise that CNNs can implicitly learn about the material characteristics of objects from the raw dual-energy images, and use this to suppress false positives. The best performing method is able to detect 95% of containers containing a single SMT, while raising 0.4% false positives on benign containers. This is a step change improvement in performance over our prior work

Extensive testing or focused testing of patients with elevated liver enzymes.

PubMed

Tapper, Elliot B; Saini, Sameer D; Sengupta, Neil

2017-02-01

Many patients have elevated serum aminotransferases reflecting many underlying conditions, both common and rare. Clinicians generally apply one of two evaluative strategies: testing for all diseases at once (extensive) or just common diseases first (focused). We simulated the evaluation of 10,000 adult outpatients with elevated with alanine aminotransferase to compare both testing strategies. Model inputs employed population-based data from the US (National Health and Nutrition Examination Survey) and Britain (Birmingham and Lambeth Liver Evaluation Testing Strategies). Patients were followed until a diagnosis was provided or a diagnostic liver biopsy was considered. The primary outcome was US dollars per diagnosis. Secondary outcomes included doctor visits per diagnosis, false-positives per diagnosis and confirmatory liver biopsies ordered. The extensive testing strategy required the lowest monetary cost, yielding diagnoses for 54% of patients at $448/patient compared to 53% for $502 under the focused strategy. The extensive strategy also required fewer doctor visits (1.35 vs. 1.61 visits/patient). However, the focused strategy generated fewer false-positives (0.1 vs. 0.19/patient) and more biopsies (0.04 vs. 0.08/patient). Focused testing becomes the most cost-effective strategy when accounting for pre-test probabilities and prior evaluations performed. This includes when the respective prevalence of alcoholic, non-alcoholic and drug-induced liver disease exceeds 51.1%, 53.0% and 13.0%. Focused testing is also the most cost-effective strategy in the referral setting where assessments for viral hepatitis, alcoholic and non-alcoholic fatty liver disease have already been performed. Testing for elevated liver enzymes should be deliberate and focused to account for pre-test probabilities if possible. Many patients have elevated liver enzymes reflecting one of many possible liver diseases, some of which are very common and some of which are rare. Tests are widely available for most causes but it is unclear whether clinicians should order them all at once or direct testing based on how likely a given disease may be given the patient's history and physical exam. The tradeoffs of both approaches involve the money spent on testing, number of office visits needed, and false positive results generated. This study shows that if there are no clues available at the time of evaluation, testing all at once saves time and money while causing more false positives. However, if there are strong clues regarding the likelihood of a particular disease, limited testing saves time, money and prevents false positives. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Evaluation of Second-Level Inference in fMRI Analysis

PubMed Central

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

2016-01-01

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

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

PubMed Central

2017-01-01

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

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

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

Grana, Justin; Wolpert, David; Neil, Joshua

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

Effect of segmentation algorithms on the performance of computerized detection of lung nodules in CT

PubMed Central

Guo, Wei; Li, Qiang

2014-01-01

Purpose: The purpose of this study is to reveal how the performance of lung nodule segmentation algorithm impacts the performance of lung nodule detection, and to provide guidelines for choosing an appropriate segmentation algorithm with appropriate parameters in a computer-aided detection (CAD) scheme. Methods: The database consisted of 85 CT scans with 111 nodules of 3 mm or larger in diameter from the standard CT lung nodule database created by the Lung Image Database Consortium. The initial nodule candidates were identified as those with strong response to a selective nodule enhancement filter. A uniform viewpoint reformation technique was applied to a three-dimensional nodule candidate to generate 24 two-dimensional (2D) reformatted images, which would be used to effectively distinguish between true nodules and false positives. Six different algorithms were employed to segment the initial nodule candidates in the 2D reformatted images. Finally, 2D features from the segmented areas in the 24 reformatted images were determined, selected, and classified for removal of false positives. Therefore, there were six similar CAD schemes, in which only the segmentation algorithms were different. The six segmentation algorithms included the fixed thresholding (FT), Otsu thresholding (OTSU), fuzzy C-means (FCM), Gaussian mixture model (GMM), Chan and Vese model (CV), and local binary fitting (LBF). The mean Jaccard index and the mean absolute distance (Dmean) were employed to evaluate the performance of segmentation algorithms, and the number of false positives at a fixed sensitivity was employed to evaluate the performance of the CAD schemes. Results: For the segmentation algorithms of FT, OTSU, FCM, GMM, CV, and LBF, the highest mean Jaccard index between the segmented nodule and the ground truth were 0.601, 0.586, 0.588, 0.563, 0.543, and 0.553, respectively, and the corresponding Dmean were 1.74, 1.80, 2.32, 2.80, 3.48, and 3.18 pixels, respectively. With these segmentation results of the six segmentation algorithms, the six CAD schemes reported 4.4, 8.8, 3.4, 9.2, 13.6, and 10.4 false positives per CT scan at a sensitivity of 80%. Conclusions: When multiple algorithms are available for segmenting nodule candidates in a CAD scheme, the “optimal” segmentation algorithm did not necessarily lead to the “optimal” CAD detection performance. PMID:25186393

An effect size filter improves the reproducibility in spectral counting-based comparative proteomics.

PubMed

Gregori, Josep; Villarreal, Laura; Sánchez, Alex; Baselga, José; Villanueva, Josep

2013-12-16

The microarray community has shown that the low reproducibility observed in gene expression-based biomarker discovery studies is partially due to relying solely on p-values to get the lists of differentially expressed genes. Their conclusions recommended complementing the p-value cutoff with the use of effect-size criteria. The aim of this work was to evaluate the influence of such an effect-size filter on spectral counting-based comparative proteomic analysis. The results proved that the filter increased the number of true positives and decreased the number of false positives and the false discovery rate of the dataset. These results were confirmed by simulation experiments where the effect size filter was used to evaluate systematically variable fractions of differentially expressed proteins. Our results suggest that relaxing the p-value cut-off followed by a post-test filter based on effect size and signal level thresholds can increase the reproducibility of statistical results obtained in comparative proteomic analysis. Based on our work, we recommend using a filter consisting of a minimum absolute log2 fold change of 0.8 and a minimum signal of 2-4 SpC on the most abundant condition for the general practice of comparative proteomics. The implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of the results obtained among independent laboratories and MS platforms. Quality control analysis of microarray-based gene expression studies pointed out that the low reproducibility observed in the lists of differentially expressed genes could be partially attributed to the fact that these lists are generated relying solely on p-values. Our study has established that the implementation of an effect size post-test filter improves the statistical results of spectral count-based quantitative proteomics. The results proved that the filter increased the number of true positives whereas decreased the false positives and the false discovery rate of the datasets. The results presented here prove that a post-test filter applying a reasonable effect size and signal level thresholds helps to increase the reproducibility of statistical results in comparative proteomic analysis. Furthermore, the implementation of feature filtering approaches could improve proteomic biomarker discovery initiatives by increasing the reproducibility of results obtained among independent laboratories and MS platforms. This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

A New Concept for Counter-Checking of Assumed CPM Pairs

NASA Astrophysics Data System (ADS)

Knapp, Wilfried; Nanson, John

2017-01-01

The inflation of “newly discovered” CPM pairs makes it necessary to develop an approach for a solid concept for counter-checking assumed CPM pairs with the target to identify false positives. Such a concept is presented in this report.

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

DOE PAGES

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

2016-03-11

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

Enrichment of statistical power for genome-wide association studies

USDA-ARS?s Scientific Manuscript database

The inheritance of most human diseases and agriculturally important traits is controlled by many genes with small effects. Identifying these genes, while simultaneously controlling false positives, is challenging. Among available statistical methods, the mixed linear model (MLM) has been the most fl...

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.

Application of Template Matching for Improving Classification of Urban Railroad Point Clouds

PubMed Central

Arastounia, Mostafa; Oude Elberink, Sander

2016-01-01

This study develops an integrated data-driven and model-driven approach (template matching) that clusters the urban railroad point clouds into three classes of rail track, contact cable, and catenary cable. The employed dataset covers 630 m of the Dutch urban railroad corridors in which there are four rail tracks, two contact cables, and two catenary cables. The dataset includes only geometrical information (three dimensional (3D) coordinates of the points) with no intensity data and no RGB data. The obtained results indicate that all objects of interest are successfully classified at the object level with no false positives and no false negatives. The results also show that an average 97.3% precision and an average 97.7% accuracy at the point cloud level are achieved. The high precision and high accuracy of the rail track classification (both greater than 96%) at the point cloud level stems from the great impact of the employed template matching method on excluding the false positives. The cables also achieve quite high average precision (96.8%) and accuracy (98.4%) due to their high sampling and isolated position in the railroad corridor. PMID:27973452

Cytokines in pleural liquid for diagnosis of tuberculous pleurisy.

PubMed

Yamada, Y; Nakamura, A; Hosoda, M; Kato, T; Asano, T; Tonegawa, K; Itoh, M

2001-07-01

An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNFalpha and IFNgamma levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0.770, 0.875, 0.892 and 0.987, respectively for IL-8, TNFalpha, ADA and IFNgamma. No false-positives were encountered with IFNgamma and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFNgamma is a very reliable marker of tuberculous pleurisy.

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).

Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease.

PubMed

Cardona, Diana M; Detweiler, Claire J; Shealy, Michael J; Sung, Anthony D; Wild, Daniel M; Poleski, Martin H; Balmadrid, Bryan L; Cirrincione, Constance T; Howell, David N; Sullivan, Keith M

2018-04-26

- Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical record from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

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

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

Morphological biosignatures and the search for life on Mars.

PubMed

Cady, Sherry L; Farmer, Jack D; Grotzinger, John P; Schopf, J William; Steele, Andrew

2003-01-01

This report provides a rationale for the advances in instrumentation and understanding needed to assess claims of ancient and extraterrestrial life made on the basis of morphological biosignatures. Morphological biosignatures consist of bona fide microbial fossils as well as microbially influenced sedimentary structures. To be recognized as evidence of life, microbial fossils must contain chemical and structural attributes uniquely indicative of microbial cells or cellular or extracellular processes. When combined with various research strategies, high-resolution instruments can reveal such attributes and elucidate how morphological fossils form and become altered, thereby improving the ability to recognize them in the geological record on Earth or other planets. Also, before fossilized microbially influenced sedimentary structures can provide evidence of life, criteria to distinguish their biogenic from non-biogenic attributes must be established. This topic can be advanced by developing process-based models. A database of images and spectroscopic data that distinguish the suite of bona fide morphological biosignatures from their abiotic mimics will avoid detection of false-positives for life. The use of high-resolution imaging and spectroscopic instruments, in conjunction with an improved knowledge base of the attributes that demonstrate life, will maximize our ability to recognize and assess the biogenicity of extraterrestrial and ancient terrestrial life.

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

Poor effectiveness of antenatal detection of fetal growth restriction and consequences for obstetric management and neonatal outcomes: a French national study.

PubMed

Monier, I; Blondel, B; Ego, A; Kaminiski, M; Goffinet, F; Zeitlin, J

2015-03-01

To assess the proportion of small for gestational age (SGA) and normal birthweight infants suspected of fetal growth restriction (FGR) during pregnancy, and to investigate obstetric and neonatal outcomes by suspicion of FGR and SGA status at birth. Population-based study. All French maternity units in 2010. Representative sample of singleton births (n = 14,100). We compared SGA infants with a birthweight of less than the 10th percentile suspected of FGR, defined as mention of FGR in medical charts (true positives), non-SGA infants suspected of FGR (false positives), SGA infants without suspicion of FGR (false negatives) and non-SGA infants without suspicion of FGR (true negatives). Multivariable analyses were adjusted for maternal and neonatal characteristics hypothesised to affect closer surveillance for FGR and our outcomes. Obstetric management (caesarean, provider-initiated preterm and early term delivery) and neonatal outcomes (late fetal death, preterm birth, Apgar score, resuscitation at birth). 21.7% of SGA infants (n = 265) and 2.1% of non-SGA infants (n = 271) were suspected of FGR during pregnancy. Compared with true negatives, provider-initiated preterm deliveries were higher for true and false positives (adjusted risk ratio [aRR], 6.1 [95% CI, 3.8-9.8] and 4.6 [95% CI, 3.2-6.7]), but not for false negatives (aRR, 1.1 [95% CI, 0.6-1.9]). Neonatal outcomes were not better for SGA infants if FGR was suspected. Antenatal suspicion of FGR among SGA infants was low and one-half of infants suspected of FGR were not SGA. The increased risk of provider-initiated delivery observed in non-SGA infants suspected of FGR raises concerns about the iatrogenic consequences of screening. © 2014 The Authors BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Comparison of 3 Methods to Assess Urine Specific Gravity in Collegiate Wrestlers

PubMed Central

Drury, Daniel G.

2003-01-01

Objective: To investigate the reliability and validity of refractometry, hydrometry, and reagent strips in assessing urine specific gravity in collegiate wrestlers. Design and Setting: We assessed the reliability of refractometry, hydrometry, and reagent strips between 2 trials and among 4 testers. The validity of hydrometry and reagent strips was assessed by comparison with refractometry, the criterion measure for urine specific gravity. Subjects: Twenty-one National Collegiate Athletic Association Division III collegiate wrestlers provided fresh urine samples. Measurements: Four testers measured the specific gravity of each urine sample 6 times: twice by refractometry, twice by hydrometry, and twice by reagent strips. Results: Refractometer measurements were consistent between trials (R = .998) and among testers; hydrometer measurements were consistent between trials (R = .987) but not among testers; and reagent-strip measurements were not consistent between trials or among testers. Hydrometer (1.018 ± 0.006) and reagent-strip (1.017 ± 0.007) measurements were significantly higher than refractometer (1.015 ± 0.006) measurements. Intraclass correlation coefficients were moderate between refractometry and hydrometry (R = .869) and low between refractometry and reagent strips (R = .573). The hydrometer produced 28% false positives and 2% false negatives, and reagent strips produced 15% false positives and 9% false negatives. Conclusions: Only the refractometer should be used to determine urine specific gravity in collegiate wrestlers during the weight-certification process. PMID:14737213

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

PubMed

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

2012-10-07

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

Evaluation of the on-site immunoassay drug-screening device Triage-TOX in routine forensic autopsy.

PubMed

Tominaga, Mariko; Michiue, Tomomi; Maeda, Hitoshi

2015-11-01

Instrumental identification of drugs with quantification is essential in forensic toxicology, while on-site immunoassay urinalysis drug-screening devices conveniently provide preliminary information when adequately used. However, suitable or sufficient urine specimens are not always available. The present study evaluated the efficacy of a new on-site immunoassay drug-screening device Triage-TOX (Alere Inc., San Diego, CA, USA), which has recently been developed to provide objective data on the one-step automated processor, using 51 urine and 19 pericardial fluid samples from 66 forensic autopsy cases, compared with Triage-Drug of Abuse (DOA) and Monitect-9. For benzodiazepines, the positive predictive value and specificity of Triage-TOX were higher than those of Triage-DOA; however, sensitivity was higher with Monitect-9, despite frequent false-positives. The results for the other drugs with the three devices also included a few false-negatives and false-positives. These observations indicate the applicability of Triage-TOX in preliminary drug screening using urine or alternative materials in routine forensic autopsy, when a possible false-negative is considered, especially for benzodiazepines, providing objective information; however, the combined use of another device such as Monitect-9 can help minimize misinterpretation prior to instrumental analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Using the genome aggregation database, computational pathogenicity prediction tools, and patch clamp heterologous expression studies to demote previously published long QT syndrome type 1 mutations from pathogenic to benign.

PubMed

Clemens, Daniel J; Lentino, Anne R; Kapplinger, Jamie D; Ye, Dan; Zhou, Wei; Tester, David J; Ackerman, Michael J

2018-04-01

Mutations in the KCNQ1-encoded Kv7.1 potassium channel cause long QT syndrome (LQTS) type 1 (LQT1). It has been suggested that ∼10%-20% of rare LQTS case-derived variants in the literature may have been published erroneously as LQT1-causative mutations and may be "false positives." The purpose of this study was to determine which previously published KCNQ1 case variants are likely false positives. A list of all published, case-derived KCNQ1 missense variants (MVs) was compiled. The occurrence of each MV within the Genome Aggregation Database (gnomAD) was assessed. Eight in silico tools were used to predict each variant's pathogenicity. Case-derived variants that were either (1) too frequently found in gnomAD or (2) absent in gnomAD but predicted to be pathogenic by ≤2 tools were considered potential false positives. Three of these variants were characterized functionally using whole-cell patch clamp technique. Overall, there were 244 KCNQ1 case-derived MVs. Of these, 29 (12%) were seen in ≥10 individuals in gnomAD and are demotable. However, 157 of 244 MVs (64%) were absent in gnomAD. Of these, 7 (4%) were predicted to be pathogenic by ≤2 tools, 3 of which we characterized functionally. There was no significant difference in current density between heterozygous KCNQ1-F127L, -P477L, or -L619M variant-containing channels compared to KCNQ1-WT. This study offers preliminary evidence for the demotion of 32 (13%) previously published LQT1 MVs. Of these, 29 were demoted because of their frequent sighting in gnomAD. Additionally, in silico analysis and in vitro functional studies have facilitated the demotion of 3 ultra-rare MVs (F127L, P477L, L619M). Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening.

PubMed

Chien, Yin-Hsiu; Chiang, Shu-Chuan; Weng, Wen-Chin; Lee, Ni-Chung; Lin, Ching-Jie; Hsieh, Wu-Shiun; Lee, Wang-Tso; Jong, Yuh-Jyh; Ko, Tsang-Ming; Hwu, Wuh-Liang

2017-11-01

To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS). We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c.888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c.840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample. Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2. Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives. ClinicalTrials.gov NCT02123186. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

PubMed

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

2017-07-01

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

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

EPA Science Inventory

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

Consortium for Imaging and Biomarkers (CIB) | Division of Cancer Prevention

Cancer.gov

Overdiagnosis and false positives present significant clinical problems in the prevention, detection and treatment of | 8 lead investigators combining imaging methods for the visualization of lesions with biomarkers to improve the accuracy of screening, early cancer detection, and the diagnosis of early stage cancers.

Adaptive Image Processing Methods for Improving Contaminant Detection Accuracy on Poultry Carcasses

USDA-ARS?s Scientific Manuscript database

Technical Abstract A real-time multispectral imaging system has demonstrated a science-based tool for fecal and ingesta contaminant detection during poultry processing. In order to implement this imaging system at commercial poultry processing industry, the false positives must be removed. For doi...

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

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.

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.

Global Sensitivity Analysis with Small Sample Sizes: Ordinary Least Squares Approach

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

Davis, Michael J.; Liu, Wei; Sivaramakrishnan, Raghu

2016-12-21

A new version of global sensitivity analysis is developed in this paper. This new version coupled with tools from statistics, machine learning, and optimization can devise small sample sizes that allow for the accurate ordering of sensitivity coefficients for the first 10-30 most sensitive chemical reactions in complex chemical-kinetic mechanisms, and is particularly useful for studying the chemistry in realistic devices. A key part of the paper is calibration of these small samples. Because these small sample sizes are developed for use in realistic combustion devices, the calibration is done over the ranges of conditions in such devices, with amore » test case being the operating conditions of a compression ignition engine studied earlier. Compression ignition engines operate under low-temperature combustion conditions with quite complicated chemistry making this calibration difficult, leading to the possibility of false positives and false negatives in the ordering of the reactions. So an important aspect of the paper is showing how to handle the trade-off between false positives and false negatives using ideas from the multiobjective optimization literature. The combination of the new global sensitivity method and the calibration are sample sizes a factor of approximately 10 times smaller than were available with our previous algorithm.« less

Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

USDA-ARS?s Scientific Manuscript database

A genome-wide association study (GWAS) is the foremost strategy used for finding genes that control human diseases and agriculturally important traits, but it often reports false positives. In contrast, its complementary method, linkage analysis, provides direct genetic confirmation, but with limite...

[Prospective performance evaluation of first trimester screenings in Germany for risk calculation through http://www.firsttrimester.net].

PubMed

Kleinsorge, F; Smetanay, K; Rom, J; Hörmansdörfer, C; Hörmannsdörfer, C; Scharf, A; Schmidt, P

2010-12-01

In 2008, 2 351 first trimester screenings were calculated by a newly developed internet database ( http:// www.firsttrimester.net ) to evaluate the risk for the presence of Down's syndrome. All data were evaluated by the conventional first trimester screening according to Nicolaides (FTS), based on the previous JOY Software, and by the advanced first trimester screening (AFS). After receiving the feedback of the karyotype as well as the rates of the correct positives, correct negatives, false positives, false negatives, the sensitivity and specificity were calculated and compared. Overall 255 cases were investigated which were analysed by both methods. These included 2 cases of Down's syndrome and one case of trisomy 18. The FTS and the AFS had a sensitivity of 100%. The specificity was 88.5% for the FTS and 93.0% for the AFS. As already shown in former studies, the higher specificity of the AFS is a result of a reduction of the false positive rate (28 to 17 cases). As a consequence of the AFS with a detection rate of 100% the rate of further invasive diagnostics in pregnant women is decreased by having 39% fewer positive tested women. © Georg Thieme Verlag KG Stuttgart · New York.

Enhancement of a culture-based bacterial detection system (eBDS) for platelet products based on measurement of oxygen consumption.

PubMed

Holme, Stein; McAlister, Morven B; Ortolano, Girolamo A; Chong, Chiyong; Cortus, Mary Anne; Jacobs, Michael R; Yomtovian, Roslyn; Freundlich, Lawrence F; Wenz, Barry

2005-06-01

An enhanced bacterial detection system (Pall eBDS) was developed that distinguishes itself from its predecessor (Pall BDS) by removal of the platelet (PLT)-retaining filter allowing for optimal bacterial transfer, modification of the culture tablet to reduce the confounding effects of respiring PLTs while enhancing bacterial growth, and facilitation of nutrients and gas exchange by agitating the sample pouch during incubation at 35 degrees C. The objective was to evaluate the performance of the new eBDS. Leukoreduced whole blood-derived PLT concentrates (LR-PCs) and LR single-donor PLTs (LR-SDPs) were inoculated with 1 to 15 colony-forming units (CFUs) of bacteria per mL in studies of each of 10 bacterial species associated with fatal transfusion-transmitted bacterial infection. Immediately after inoculation and after 24 hours of storage at 22 degrees C, samples of inoculated LR-PCs were aseptically transferred into the eBDS pouches. Pouches were then incubated for 24 hours at 35 degrees C with agitation and oxygen concentration was then measured. Median inoculation levels ranged from 5 to 13 CFUs per mL for each species studied. No significant differences in oxygen concentration were found when comparing LR-PCs with LR-SDPs. When sampling occurred from the PLTs 24 hours after inoculation, all 280 cases (24-33 replicates of each species) were detected as contaminated by the device (100% sensitivity). No false-positives were obtained with 713 uninoculated PLT units. The eBDS demonstrated improved detection sensitivity in the range of 1 to 15 CFUs per mL with no observed false-positives compared to the original BDS (detection range 100 to 500 CFUs/mL) with no false-positives.

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.

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.

Tile-based Fisher ratio analysis of comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS) data using a null distribution approach.

PubMed

Parsons, Brendon A; Marney, Luke C; Siegler, W Christopher; Hoggard, Jamin C; Wright, Bob W; Synovec, Robert E

2015-04-07

Comprehensive two-dimensional (2D) gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS) is a versatile instrumental platform capable of collecting highly informative, yet highly complex, chemical data for a variety of samples. Fisher-ratio (F-ratio) analysis applied to the supervised comparison of sample classes algorithmically reduces complex GC × GC-TOFMS data sets to find class distinguishing chemical features. F-ratio analysis, using a tile-based algorithm, significantly reduces the adverse effects of chromatographic misalignment and spurious covariance of the detected signal, enhancing the discovery of true positives while simultaneously reducing the likelihood of detecting false positives. Herein, we report a study using tile-based F-ratio analysis whereby four non-native analytes were spiked into diesel fuel at several concentrations ranging from 0 to 100 ppm. Spike level comparisons were performed in two regimes: comparing the spiked samples to the nonspiked fuel matrix and to each other at relative concentration factors of two. Redundant hits were algorithmically removed by refocusing the tiled results onto the original high resolution pixel level data. To objectively limit the tile-based F-ratio results to only features which are statistically likely to be true positives, we developed a combinatorial technique using null class comparisons, called null distribution analysis, by which we determined a statistically defensible F-ratio cutoff for the analysis of the hit list. After applying null distribution analysis, spiked analytes were reliably discovered at ∼1 to ∼10 ppm (∼5 to ∼50 pg using a 200:1 split), depending upon the degree of mass spectral selectivity and 2D chromatographic resolution, with minimal occurrence of false positives. To place the relevance of this work among other methods in this field, results are compared to those for pixel and peak table-based approaches.

Sorting Out Which Students Have Learning Disabilities.

ERIC Educational Resources Information Center

Zirkel, Perry A.

2001-01-01

Compared to students from affluent public and prep schools, few inner-city students receive extra time or other accommodations when taking high-stakes tests. The growth in "false positives" among affluent youth may partly stem from nonspecific definitions under the Individuals with Disabilities Education Act. Fairness is being…

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

PubMed

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

2015-09-18

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

Effect of the Protein Corona on Antibody-Antigen Binding in Nanoparticle Sandwich Immunoassays.

PubMed

de Puig, Helena; Bosch, Irene; Carré-Camps, Marc; Hamad-Schifferli, Kimberly

2017-01-18

We investigated the effect of the protein corona on the function of nanoparticle (NP) antibody (Ab) conjugates in dipstick sandwich immunoassays. Ab specific for Zika virus nonstructural protein 1 (NS1) were conjugated to gold NPs, and another anti-NS1 Ab was immobilized onto the nitrocellulose membrane. Sandwich immunoassay formation was influenced by whether the strip was run in corona forming conditions, i.e., in human serum. Strips run in buffer or pure solutions of bovine serum albumin exhibited false positives, but those run in human serum did not. Serum pretreatment of the nitrocellulose also eliminated false positives. Corona formation around the NP-Ab in serum was faster than the immunoassay time scale. Langmuir binding analysis determined how the immobilized Ab affinity for the NP-Ab/NS1 was impacted by corona formation conditions, quantified as an effective dissociation constant, K D eff . Results show that corona formation mediates the specificity and sensitivity of the antibody-antigen interaction of Zika biomarkers in immunoassays, and plays a critical but beneficial role.

Comparison of 3 Methods to Assess Urine Specific Gravity in Collegiate Wrestlers.

PubMed

Stuempfle, Kristin J.; Drury, Daniel G.

2003-12-01

OBJECTIVE: To investigate the reliability and validity of refractometry, hydrometry, and reagent strips in assessing urine specific gravity in collegiate wrestlers. DESIGN AND SETTING: We assessed the reliability of refractometry, hydrometry, and reagent strips between 2 trials and among 4 testers. The validity of hydrometry and reagent strips was assessed by comparison with refractometry, the criterion measure for urine specific gravity. SUBJECTS: Twenty-one National Collegiate Athletic Association Division III collegiate wrestlers provided fresh urine samples. MEASUREMENTS: Four testers measured the specific gravity of each urine sample 6 times: twice by refractometry, twice by hydrometry, and twice by reagent strips. RESULTS: Refractometer measurements were consistent between trials (R =.998) and among testers; hydrometer measurements were consistent between trials (R =.987) but not among testers; and reagent-strip measurements were not consistent between trials or among testers. Hydrometer (1.018 +/- 0.006) and reagent-strip (1.017 +/- 0.007) measurements were significantly higher than refractometer (1.015 +/- 0.006) measurements. Intraclass correlation coefficients were moderate between refractometry and hydrometry (R =.869) and low between refractometry and reagent strips (R =.573). The hydrometer produced 28% false positives and 2% false negatives, and reagent strips produced 15% false positives and 9% false negatives. CONCLUSIONS: Only the refractometer should be used to determine urine specific gravity in collegiate wrestlers during the weight-certification process.

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.

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.

Sequencing Needs for Viral Diagnostics

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

Gardner, S N; Lam, M; Mulakken, N J

2004-01-26

We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''nearmore » neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.« less

Late lessons from early warnings: towards precaution and realism in research and policy.

PubMed

Gee, D; Krayer von Krauss, M P

2005-01-01

This paper focuses on the evidentiary aspects of the precautionary principle. Three points are highlighted: (i) the difference between association and causation; (ii) how the strength of scientific evidence can be considered; and (iii) the reasons why regulatory regimes tend to err in the direction of false negatives rather than false positives. The point is made that because obtaining evidence of causation can take many decades of research, the precautionary principle can be invoked to justify action when evidence of causation is not available, but there is good scientific evidence of an association between exposures and impacts. It is argued that the appropriate level of proof is context dependent, as "appropriateness" is based on value judgements about the acceptability of the costs, about the distribution of the costs, and about the consequences of being wrong. A complementary approach to evaluating the strength of scientific evidence is to focus on the level of uncertainty. If decision makers are made aware of the limitations of the knowledge base, they can compensate by adopting measures aimed at providing early warnings of un-anticipated effects and mitigating their impacts. The point is made that it is often disregarded that the Bradford Hill criteria for evaluating evidence are asymmetrical, in that the applicability of a criterion increases the strength of evidence on the presence of an effect, but the inapplicability of a criterion does not increase the strength of evidence on the absence of an effect. The paper discusses the reason why there are so many examples of regulatory "false negatives" as opposed to "false positives". Two main reasons are put forward: (i) the methodological bias within the health and environmental sciences; and (ii) the dominance within decision-making of short term economic and political interests. Sixteen features of methods and culture in the environmental and health sciences are presented. Of these, only three features tend to generate "false positives". It is concluded that although the different features of scientific methods and culture produce robust science, they can lead to poor regulatory decisions on hazard prevention.

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

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

PubMed

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

2015-02-01

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

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...

Hilbertian sine as an absolute measure of Bayesian inference in ISR, homeland security, medicine, and defense

NASA Astrophysics Data System (ADS)

Jannson, Tomasz; Wang, Wenjian; Hodelin, Juan; Forrester, Thomas; Romanov, Volodymyr; Kostrzewski, Andrew

2016-05-01

In this paper, Bayesian Binary Sensing (BBS) is discussed as an effective tool for Bayesian Inference (BI) evaluation in interdisciplinary areas such as ISR (and, C3I), Homeland Security, QC, medicine, defense, and many others. In particular, Hilbertian Sine (HS) as an absolute measure of BI, is introduced, while avoiding relativity of decision threshold identification, as in the case of traditional measures of BI, related to false positives and false negatives.

Nested association mapping for dissecting complex traits using Peanut 58K SNP array

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWAS) and linkage mapping have been the two most predominant strategies to dissect complex traits, but are limited by the occurrence of false positives reported for GWAS, and low resolution in the case of linkage analysis. This has led to the development of a joint a...

Erasure Analyses: Reducing the Number of False Positives

ERIC Educational Resources Information Center

McClintock, Joseph Clair

2015-01-01

Erasure analysis is the study of the pattern or quantity of erasures on multiple-choice paper-and-pencil examinations, to determine whether erasures were made post-testing for the purpose of unfairly increasing students' scores. This study examined the erasure data from over 1.4 million exams, taken by more than 600,000 students. Three…

Laser cutting eliminates nucleic acid cross-contamination in dried-blood-spot processing.

PubMed

Murphy, Sean C; Daza, Glenda; Chang, Ming; Coombs, Robert

2012-12-01

Dried blood spots (DBS) are useful for molecular assays but are prone to false positives from cross-contamination. In our malaria DBS assay, cross-contamination was encountered despite cleaning techniques suitable for HIV-1. We therefore developed a contact-free laser cutting system that effectively eliminated cross-contamination during DBS processing.

Rapid Creation and Quantitative Monitoring of High Coverage shRNA Libraries

PubMed Central

Bassik, Michael C.; Lebbink, Robert Jan; Churchman, L. Stirling; Ingolia, Nicholas T.; Patena, Weronika; LeProust, Emily M.; Schuldiner, Maya; Weissman, Jonathan S.; McManus, Michael T.

2009-01-01

Short hairpin RNA (shRNA) libraries are limited by the low efficacy of many shRNAs, giving false negatives, and off-target effects, giving false positives. Here we present a strategy for rapidly creating expanded shRNA pools (∼30 shRNAs/gene) that are analyzed by deep-sequencing (EXPAND). This approach enables identification of multiple effective target-specific shRNAs from a complex pool, allowing a rigorous statistical evaluation of whether a gene is a true hit. PMID:19448642

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.

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.

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

PubMed

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

2017-04-01

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

Iterative usage of fixed and random effect models for powerful and efficient genome-wide association studies

USDA-ARS?s Scientific Manuscript database

False positives in a Genome-Wide Association Study (GWAS) can be effectively controlled by a fixed effect and random effect Mixed Linear Model (MLM) that incorporates population structure and kinship among individuals to adjust association tests on markers; however, the adjustment also compromises t...

Enhanced HTS hit selection via a local hit rate analysis.

PubMed

Posner, Bruce A; Xi, Hualin; Mills, James E J

2009-10-01

The postprocessing of high-throughput screening (HTS) results is complicated by the occurrence of false positives (inactive compounds misidentified as active by the primary screen) and false negatives (active compounds misidentified as inactive by the primary screen). An activity cutoff is frequently used to select "active" compounds from HTS data; however, this approach is insensitive to both false positives and false negatives. An alternative method that can minimize the occurrence of these artifacts will increase the efficiency of hit selection and therefore lead discovery. In this work, rather than merely using the activity of a given compound, we look at the presence and absence of activity among all compounds in its "chemical space neighborhood" to give a degree of confidence in its activity. We demonstrate that this local hit rate (LHR) analysis method outperforms hit selection based on ranking by primary screen activity values across ten diverse high throughput screens, spanning both cell-based and biochemical assay formats of varying biology and robustness. On average, the local hit rate analysis method was approximately 2.3-fold and approximately 1.3-fold more effective in identifying active compounds and active chemical series, respectively, than selection based on primary activity alone. Moreover, when applied to finding false negatives, this method was 2.3-fold better than ranking by primary activity alone. In most cases, novel hit series were identified that would have otherwise been missed. Additional uses of and observations regarding this HTS analysis approach are also discussed.

Gaps along the HIV care continuum: findings among a population seeking sexual health care services in New York City.

PubMed

Pathela, Preeti; Jamison, Kelly; Braunstein, Sarah L; Schillinger, Julia A; Tymejczyk, Olga; Nash, Denis

2018-03-02

Linkage/re-linkage to HIV care for virally unsuppressed persons with new sexually transmitted infections is critical for ending the HIV epidemic. We quantified HIV care continuum gaps, and viral suppression, among HIV-positive patients attending New York City (NYC) sexual health clinics (SHC). 1,649 HIV-positive patients and a 10% sample of 11,954 patients with unknown HIV status on clinic visit date (DOV) were matched against the NYC HIV registry. Using registry diagnosis dates, we categorized matched HIV-positive patients as "new-positives" (newly diagnosed on DOV), "recent-positives (diagnosed ≤90 days before DOV), "prevalent-positives" (diagnosed >90 days before DOV), and "unknown-positives" (previously diagnosed, but status unknown to clinic on DOV). We assessed HIV care continuum outcomes before and after DOV for new-positives, prevalent-positives, and unknown-positives using registry laboratory data. In addition to 1,626 known HIV-positive patients, 5% of the unknown sample (63/1,196) matched to the registry, signifying that about 630 additional HIV-positive patients attended SHCs. Of new-positives, 65% were linked to care after DOV. Of prevalent-positives, 66% were in care on DOV; 43% of the out-of-care were re-linked after DOV. Of unknown-positives, 40% were in care on DOV; 21% of the out-of-care re-linked after DOV. Viral suppression was achieved by: 88% of in-care unknown-positives, 76% in-care prevalent-positives, 50% new-positives, 42% out-of-care prevalent-positives, and 16% out-of-care unknown-positives. Many HIV-positive persons, including those with uncontrolled HIV infection, attend SHCs and potentially contribute to HIV spread. However, HIV status often is not known to staff, resulting in missed linkage/re-linkage to care opportunities. Better outcomes could be facilitated by real-time ascertainment of HIV status and HIV care status.

Advances in nuclear medicine.

PubMed

Selberg, Kurt; Ross, Michael

2012-12-01

Nuclear scintigraphy is a mainstay of diagnostic imaging and has preserved its relevance in the imaging of acute and chronic trauma. It is particularly useful in the evaluation of athletic injuries. Pitfalls of interpretation, false negatives and false positives exist as with many imaging modalities. Synthesis of physical exam findings, lameness evaluation and, when possible, diagnostic analgesia in combination with nuclear scintigraphy imaging findings, will allow for the most information to be applied to the patient's clinical problem. Published by Elsevier Inc.

Sociopathic Knowledge Bases: Correct Knowledge Can Be Harmful Even Given Unlimited Computation

DTIC Science & Technology

1989-08-01

pobitive, as false positives generated by a medical program can often be caught by a physician upon further testing . False negatives, however, may be...improvement over the knowledge base tested is obtained. Although our work is pretty much theoretical research oriented one example of ex- periments is...knowledge base, improves the performance by about 10%. of tests . First, we divide the cases into a training set and a validation set with 70% vs. 30% each

Accounting for heterogeneous treatment effects in the FDA approval process.

PubMed

Malani, Anup; Bembom, Oliver; van der Laan, Mark

2012-01-01

The FDA employs an average-patient standard when reviewing drugs: it approves a drug only if is safe and effective for the average patient in a clinical trial. It is common, however, for patients to respond differently to a drug. Therefore, the average-patient standard can reject a drug that benefits certain patient subgroups (false negatives) and even approve a drug that harms other patient subgroups (false positives). These errors increase the cost of drug development - and thus health care - by wasting research on unproductive or unapproved drugs. The reason why the FDA sticks with an average patient standard is concern about opportunism by drug companies. With enough data dredging, a drug company can always find some subgroup of patients that appears to benefit from its drug, even if the subgroup truly does not. In this paper we offer alternatives to the average patient standard that reduce the risk of false negatives without increasing false positives from drug company opportunism. These proposals combine changes to institutional design - evaluation of trial data by an independent auditor - with statistical tools to reinforce the new institutional design - specifically, to ensure the auditor is truly independent of drug companies. We illustrate our proposals by applying them to the results of a recent clinical trial of a cancer drug (motexafin gadolinium). Our analysis suggests that the FDA may have made a mistake in rejecting that drug.

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.

A semi-parametric within-subject mixture approach to the analyses of responses and response times.

PubMed

Molenaar, Dylan; Bolsinova, Maria; Vermunt, Jeroen K

2018-05-01

In item response theory, modelling the item response times in addition to the item responses may improve the detection of possible between- and within-subject differences in the process that resulted in the responses. For instance, if respondents rely on rapid guessing on some items but not on all, the joint distribution of the responses and response times will be a multivariate within-subject mixture distribution. Suitable parametric methods to detect these within-subject differences have been proposed. In these approaches, a distribution needs to be assumed for the within-class response times. In this paper, it is demonstrated that these parametric within-subject approaches may produce false positives and biased parameter estimates if the assumption concerning the response time distribution is violated. A semi-parametric approach is proposed which resorts to categorized response times. This approach is shown to hardly produce false positives and parameter bias. In addition, the semi-parametric approach results in approximately the same power as the parametric approach. © 2017 The British Psychological Society.

Spatial-Spectral Approaches to Edge Detection in Hyperspectral Remote Sensing

NASA Astrophysics Data System (ADS)

Cox, Cary M.

This dissertation advances geoinformation science at the intersection of hyperspectral remote sensing and edge detection methods. A relatively new phenomenology among its remote sensing peers, hyperspectral imagery (HSI) comprises only about 7% of all remote sensing research - there are five times as many radar-focused peer reviewed journal articles than hyperspectral-focused peer reviewed journal articles. Similarly, edge detection studies comprise only about 8% of image processing research, most of which is dedicated to image processing techniques most closely associated with end results, such as image classification and feature extraction. Given the centrality of edge detection to mapping, that most important of geographic functions, improving the collective understanding of hyperspectral imagery edge detection methods constitutes a research objective aligned to the heart of geoinformation sciences. Consequently, this dissertation endeavors to narrow the HSI edge detection research gap by advancing three HSI edge detection methods designed to leverage HSI's unique chemical identification capabilities in pursuit of generating accurate, high-quality edge planes. The Di Zenzo-based gradient edge detection algorithm, an innovative version of the Resmini HySPADE edge detection algorithm and a level set-based edge detection algorithm are tested against 15 traditional and non-traditional HSI datasets spanning a range of HSI data configurations, spectral resolutions, spatial resolutions, bandpasses and applications. This study empirically measures algorithm performance against Dr. John Canny's six criteria for a good edge operator: false positives, false negatives, localization, single-point response, robustness to noise and unbroken edges. The end state is a suite of spatial-spectral edge detection algorithms that produce satisfactory edge results against a range of hyperspectral data types applicable to a diverse set of earth remote sensing applications. This work also explores the concept of an edge within hyperspectral space, the relative importance of spatial and spectral resolutions as they pertain to HSI edge detection and how effectively compressed HSI data improves edge detection results. The HSI edge detection experiments yielded valuable insights into the algorithms' strengths, weaknesses and optimal alignment to remote sensing applications. The gradient-based edge operator produced strong edge planes across a range of evaluation measures and applications, particularly with respect to false negatives, unbroken edges, urban mapping, vegetation mapping and oil spill mapping applications. False positives and uncompressed HSI data presented occasional challenges to the algorithm. The HySPADE edge operator produced satisfactory results with respect to localization, single-point response, oil spill mapping and trace chemical detection, and was challenged by false positives, declining spectral resolution and vegetation mapping applications. The level set edge detector produced high-quality edge planes for most tests and demonstrated strong performance with respect to false positives, single-point response, oil spill mapping and mineral mapping. False negatives were a regular challenge for the level set edge detection algorithm. Finally, HSI data optimized for spectral information compression and noise was shown to improve edge detection performance across all three algorithms, while the gradient-based algorithm and HySPADE demonstrated significant robustness to declining spectral and spatial resolutions.

Evaluation of the light scattering and the turbidity microtiter plate-based methods for the detection of the excipient-mediated drug precipitation inhibition.

PubMed

Petruševska, Marija; Urleb, Uroš; Peternel, Luka

2013-11-01

The excipient-mediated precipitation inhibition is classically determined by the quantification of the dissolved compound in the solution. In this study, two alternative approaches were evaluated, one is the light scattering (nephelometer) and other is the turbidity (plate reader) microtiter plate-based methods which are based on the quantification of the compound precipitate. Following the optimization of the nephelometer settings (beam focus, laser gain) and the experimental conditions, the screening of 23 excipients on the precipitation inhibition of poorly soluble fenofibrate and dipyridamole was performed. The light scattering method resulted in excellent correlation (r>0.91) between the calculated precipitation inhibitor parameters (PIPs) and the precipitation inhibition index (PI(classical)) obtained by the classical approach for fenofibrate and dipyridamole. Among the evaluated PIPs AUC100 (nephelometer) resulted in only four false positives and lack of false negatives. In the case of the turbidity-based method a good correlation of the PI(classical) was obtained for the PIP maximal optical density (OD(max), r=0.91), however, only for fenofibrate. In the case of the OD(max) (plate reader) five false positives and two false negatives were identified. In conclusion, the light scattering-based method outperformed the turbidity-based one and could be reliably used for identification of novel precipitation inhibitors. Copyright © 2013 Elsevier B.V. All rights reserved.

An AIS-Based E-mail Classification Method

NASA Astrophysics Data System (ADS)

Qing, Jinjian; Mao, Ruilong; Bie, Rongfang; Gao, Xiao-Zhi

This paper proposes a new e-mail classification method based on the Artificial Immune System (AIS), which is endowed with good diversity and self-adaptive ability by using the immune learning, immune memory, and immune recognition. In our method, the features of spam and non-spam extracted from the training sets are combined together, and the number of false positives (non-spam messages that are incorrectly classified as spam) can be reduced. The experimental results demonstrate that this method is effective in reducing the false rate.

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.

Mixture-Tuned, Clutter Matched Filter for Remote Detection of Subpixel Spectral Signals

NASA Technical Reports Server (NTRS)

Thompson, David R.; Mandrake, Lukas; Green, Robert O.

2013-01-01

Mapping localized spectral features in large images demands sensitive and robust detection algorithms. Two aspects of large images that can harm matched-filter detection performance are addressed simultaneously. First, multimodal backgrounds may thwart the typical Gaussian model. Second, outlier features can trigger false detections from large projections onto the target vector. Two state-of-the-art approaches are combined that independently address outlier false positives and multimodal backgrounds. The background clustering models multimodal backgrounds, and the mixture tuned matched filter (MT-MF) addresses outliers. Combining the two methods captures significant additional performance benefits. The resulting mixture tuned clutter matched filter (MT-CMF) shows effective performance on simulated and airborne datasets. The classical MNF transform was applied, followed by k-means clustering. Then, each cluster s mean, covariance, and the corresponding eigenvalues were estimated. This yields a cluster-specific matched filter estimate as well as a cluster- specific feasibility score to flag outlier false positives. The technology described is a proof of concept that may be employed in future target detection and mapping applications for remote imaging spectrometers. It is of most direct relevance to JPL proposals for airborne and orbital hyperspectral instruments. Applications include subpixel target detection in hyperspectral scenes for military surveillance. Earth science applications include mineralogical mapping, species discrimination for ecosystem health monitoring, and land use classification.

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.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Computerized detection of unruptured aneurysms in MRA images: reduction of false positives using anatomical location features

NASA Astrophysics Data System (ADS)

Uchiyama, Yoshikazu; Gao, Xin; Hara, Takeshi; Fujita, Hiroshi; Ando, Hiromichi; Yamakawa, Hiroyasu; Asano, Takahiko; Kato, Hiroki; Iwama, Toru; Kanematsu, Masayuki; Hoshi, Hiroaki

2008-03-01

The detection of unruptured aneurysms is a major subject in magnetic resonance angiography (MRA). However, their accurate detection is often difficult because of the overlapping between the aneurysm and the adjacent vessels on maximum intensity projection images. The purpose of this study is to develop a computerized method for the detection of unruptured aneurysms in order to assist radiologists in image interpretation. The vessel regions were first segmented using gray-level thresholding and a region growing technique. The gradient concentration (GC) filter was then employed for the enhancement of the aneurysms. The initial candidates were identified in the GC image using a gray-level threshold. For the elimination of false positives (FPs), we determined shape features and an anatomical location feature. Finally, rule-based schemes and quadratic discriminant analysis were employed along with these features for distinguishing between the aneurysms and the FPs. The sensitivity for the detection of unruptured aneurysms was 90.0% with 1.52 FPs per patient. Our computerized scheme can be useful in assisting the radiologists in the detection of unruptured aneurysms in MRA images.

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.

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.

Laser Cutting Eliminates Nucleic Acid Cross-Contamination in Dried-Blood-Spot Processing

PubMed Central

Daza, Glenda; Chang, Ming; Coombs, Robert

2012-01-01

Dried blood spots (DBS) are useful for molecular assays but are prone to false positives from cross-contamination. In our malaria DBS assay, cross-contamination was encountered despite cleaning techniques suitable for HIV-1. We therefore developed a contact-free laser cutting system that effectively eliminated cross-contamination during DBS processing. PMID:23052309

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.

Rejecting Astrophysical False Positives from the TrES Transiting Planet Survey: The Example of GSC 03885-00829

NASA Astrophysics Data System (ADS)

O'Donovan, Francis T.; Charbonneau, David; Torres, Guillermo; Mandushev, Georgi; Dunham, Edward W.; Latham, David W.; Alonso, Roi; Brown, Timothy M.; Esquerdo, Gilbert A.; Everett, Mark E.; Creevey, Orlagh L.

2006-06-01

Ground-based wide-field surveys for nearby transiting gas giants are yielding far fewer true planets than astrophysical false positives, some of which are difficult to reject. Recent experience has highlighted the need for careful analysis to eliminate astronomical systems in which light from a faint eclipsing binary is blended with that from a bright star. During the course of the Transatlantic Exoplanet Survey, we identified a system presenting a transit-like periodic signal. We obtained the proper motion and infrared color of this target (GSC 03885-00829) from publicly available catalogs, which suggested this star is an F dwarf, supporting our transit hypothesis. This spectral classification was confirmed using spectroscopic observations from which we determined the stellar radial velocity. The star did not exhibit any signs of a stellar mass companion. However, subsequent multicolor photometry displayed a color-dependent transit depth, indicating that a blend was the likely source of the eclipse. We successfully modeled our initial photometric observations of GSC 03885-00829 as the light from a K dwarf binary system superimposed on the light from a late F dwarf star. High-dispersion spectroscopy confirmed the presence of light from a cool stellar photosphere in the spectrum of this system. With this candidate, we demonstrate both the difficulty in identifying certain types of false positives in a list of candidate transiting planets and our procedure for rejecting these imposters, which may be useful to other groups performing wide-field transit surveys. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

COLLABORATIVE MODELING OF THE BENEFITS AND HARMS ASSOCIATED WITH DIFFERENT U.S. BREAST CANCER SCREENING STRATEGIES

PubMed Central

Mandelblatt, Jeanne S.; Stout, Natasha K.; Schechter, Clyde B.; van den Broek, Jeroen J.; Miglioretti, Diana; Krapcho, Martin; Trentham-Dietz, Amy; Munoz, Diego; Lee, Sandra J.; Berry, Donald A.; van Ravesteyn, Nicolien T.; Alagoz, Oguzhan; Kerlikowske, Karla; Tosteson, Anna N.A.; Near, Aimee M.; Hoeffken, Amanda; Chang, Yaojen; Heijnsdijk, Eveline A.; Chisholm, Gary; Huang, Xuelin; Huang, Hui; Ergun, Mehmet Ali; Gangnon, Ronald; Sprague, Brian L.; Plevritis, Sylvia; Feuer, Eric; de Koning, Harry J.; Cronin, Kathleen A.

2016-01-01

Background Controversy persists about optimal mammography screening strategies. Objective To evaluate mammography strategies considering screening and treatment advances. Design Collaboration of six simulation models. Data Sources National data on incidence, risk, breast density, digital mammography performance, treatment effects, and other-cause mortality. Target Population An average-risk cohort. Time Horizon Lifetime. Perspective Societal. Interventions Mammograms from age 40, 45 or 50 to 74 at annual or biennial intervals, or annually from 40 or 45 to 49 then biennially to 74, assuming 100% screening and treatment adherence. Outcome Measures Screening benefits (vs. no screening) include percent breast cancer mortality reduction, deaths averted, and life-years gained. Harms include number of mammograms, false-positives, benign biopsies, and overdiagnosis. Results for Average-Risk Women Biennial strategies maintain 79.8%-81.3% (range across strategies and models: 68.3–98.9%) of annual screening benefits with almost half the false-positives and fewer overdiagnoses. Screening biennially from ages 50–74 achieves a median 25.8% (range: 24.1%-31.8%) breast cancer mortality reduction; annual screening from ages 40–74 years reduces mortality an additional 12.0% (range: 5.7%-17.2%) vs. no screening, but yields 1988 more false-positives and 7 more overdiagnoses per 1000 women screened. Annual screening from ages 50–74 had similar benefits as other strategies but more harms, so would not be recommended. Sub-population Results Annual screening starting at age 40 for women who have a two- to four-fold increase in risk has a similar balance of harms and benefits as biennial screening of average-risk women from 50–74. Limitations We do not consider other imaging technologies, polygenic risk, or non-adherence. Conclusion These results suggest that biennial screening is efficient for average-risk groups, but decisions on strategies depend on the weight given to the balance of harms and benefits. Primary Funding Source National Institutes of Health PMID:26756606

Detection of insect damage in almonds

NASA Astrophysics Data System (ADS)

Kim, Soowon; Schatzki, Thomas F.

1999-01-01

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

PLASMA OXYTOCIN LEVELS PREDICT SOCIAL CUE RECOGNITION IN INDIVIDUALS WITH SCHIZOPHRENIA

PubMed Central

Strauss, Gregory P.; Keller, William R.; Koenig, James I.; Gold, James M.; Frost, Katherine H.; Buchanan, Robert W.

2015-01-01

Lower endogenous levels of the neuropeptide oxytocin may be an important biological predictor of social cognition impairments in schizophrenia (SZ). Prior studies have demonstrated that lower-level social cognitive processes (e.g., facial affect perception) are significantly associated with reduced plasma oxytocin levels in SZ; however, it is unclear whether higher-level social cognition, which requires inferential processes and knowledge not directly presented in the stimulus, is associated with endogenous oxytocin. The current study explored the association between endogenous oxytocin levels and lower- and higher-level social cognition in 40 individuals diagnosed with SZ and 22 demographically matched healthy controls (CN). All participants received the Social Cue Recognition Test (SCRT), which presents participants with videotaped interpersonal vignettes and subsequent true/false questions related to concrete or abstract aspects of social interactions in the vignettes. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ and CN did not differ on SCRT hits, but SZ had more false positives and lower sensitivity scores than CN. Higher plasma oxytocin levels were associated with better sensitivity scores for abstract items in CN and fewer false positives for concrete items in individuals with SZ. Findings indicate that endogenous oxytocin levels predict accurate encoding of lower-level socially relevant information in SZ. PMID:25673435

Vision Screening of School Children by Teachers as a Community Based Strategy to Address the Challenges of Childhood Blindness.

PubMed

Kaur, Gurvinder; Koshy, Jacob; Thomas, Satish; Kapoor, Harpreet; Zachariah, Jiju George; Bedi, Sahiba

2016-04-01

Early detection and treatment of vision problems in children is imperative to meet the challenges of childhood blindness. Considering the problems of inequitable distribution of trained manpower and limited access of quality eye care services to majority of our population, innovative community based strategies like 'Teachers training in vision screening' need to be developed for effective utilization of the available human resources. To evaluate the effectiveness of introducing teachers as the first level vision screeners. Teacher training programs were conducted for school teachers to educate them about childhood ocular disorders and the importance of their early detection. Teachers from government and semi-government schools located in Ludhiana were given training in vision screening. These teachers then conducted vision screening of children in their schools. Subsequently an ophthalmology team visited these schools for re-evaluation of children identified with low vision. Refraction was performed for all children identified with refractive errors and spectacles were prescribed. Children requiring further evaluation were referred to the base hospital. The project was done in two phases. True positives, false positives, true negatives and false negatives were calculated for evaluation. In phase 1, teachers from 166 schools underwent training in vision screening. The teachers screened 30,205 children and reported eye problems in 4523 (14.97%) children. Subsequently, the ophthalmology team examined 4150 children and confirmed eye problems in 2137 children. Thus, the teachers were able to correctly identify eye problems (true positives) in 47.25% children. Also, only 13.69% children had to be examined by the ophthalmology team, thus reducing their work load. Similarly, in phase 2, 46.22% children were correctly identified to have eye problems (true positives) by the teachers. By random sampling, 95.65% children were correctly identified as normal (true negatives) by the teachers. Considering the high true negative rates and reasonably good true positive rates and the wider coverage provided by the program, vision screening in schools by teachers is an effective method of identifying children with low vision. This strategy is also valuable in reducing the workload of the eye care staff.

Can We Legislate Spam?

ERIC Educational Resources Information Center

Wigen, Wendy

2004-01-01

Spam is not just a technology issue. It is a social issue, and it threatens something very dear: the viability of e-mail. Campuses struggle to support solutions that will control the costs of filtering spam, keep "false positives" to a minimum and not diminish their own marketing use of mass e-mails. The openness of the Internet, long touted as…

Data-Driven Significance Estimation for Precise Spike Correlation

PubMed Central

Grün, Sonja

2009-01-01

The mechanisms underlying neuronal coding and, in particular, the role of temporal spike coordination are hotly debated. However, this debate is often confounded by an implicit discussion about the use of appropriate analysis methods. To avoid incorrect interpretation of data, the analysis of simultaneous spike trains for precise spike correlation needs to be properly adjusted to the features of the experimental spike trains. In particular, nonstationarity of the firing of individual neurons in time or across trials, a spike train structure deviating from Poisson, or a co-occurrence of such features in parallel spike trains are potent generators of false positives. Problems can be avoided by including these features in the null hypothesis of the significance test. In this context, the use of surrogate data becomes increasingly important, because the complexity of the data typically prevents analytical solutions. This review provides an overview of the potential obstacles in the correlation analysis of parallel spike data and possible routes to overcome them. The discussion is illustrated at every stage of the argument by referring to a specific analysis tool (the Unitary Events method). The conclusions, however, are of a general nature and hold for other analysis techniques. Thorough testing and calibration of analysis tools and the impact of potentially erroneous preprocessing stages are emphasized. PMID:19129298

Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies.

PubMed

Rahmani, Elior; Zaitlen, Noah; Baran, Yael; Eng, Celeste; Hu, Donglei; Galanter, Joshua; Oh, Sam; Burchard, Esteban G; Eskin, Eleazar; Zou, James; Halperin, Eran

2016-05-01

In epigenome-wide association studies (EWAS), different methylation profiles of distinct cell types may lead to false discoveries. We introduce ReFACTor, a method based on principal component analysis (PCA) and designed for the correction of cell type heterogeneity in EWAS. ReFACTor does not require knowledge of cell counts, and it provides improved estimates of cell type composition, resulting in improved power and control for false positives in EWAS. Corresponding software is available at http://www.cs.tau.ac.il/~heran/cozygene/software/refactor.html.

A biopsymeter to support the diagnostic procedure of skin samples

NASA Astrophysics Data System (ADS)

Fioravanti, Valeria; Chandrashekar, Shailendra; Brandhoff, Lukas; Pucciarelli, Daniela; van den Driesche, Sander; Breiteneder, Heimo; Hafner, Christine; Vellekoop, Michael J.

2015-06-01

We present an infrared biopsymeter to assist pathologists in the diagnosis of melanoma presence in skin biopsies. The designed and realized system combines the features of visual inspection and physical sensing to reduce false positives and false negatives occurring during standard histopathological analyses. The biopsymeter determines the CH2-stretch ratio by infrared absorbance measurements of skin biopsies. Investigations conducted with the biopsymeter shows that malignant melanomas and melanoma metastases have higher CH2-stretch ratio values compared to healthy skin tissues.

miREE: miRNA recognition elements ensemble

PubMed Central

2011-01-01

Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between sensitivity and specificity. miREE obtains a reasonable trade-off between filtering false positives and identifying targets. miREE tool is available online at http://didattica-online.polito.it/eda/miREE/ PMID:22115078

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

Characterization of network structure in stereoEEG data using consensus-based partial coherence.

PubMed

Ter Wal, Marije; Cardellicchio, Pasquale; LoRusso, Giorgio; Pelliccia, Veronica; Avanzini, Pietro; Orban, Guy A; Tiesinga, Paul He

2018-06-06

Coherence is a widely used measure to determine the frequency-resolved functional connectivity between pairs of recording sites, but this measure is confounded by shared inputs to the pair. To remove shared inputs, the 'partial coherence' can be computed by conditioning the spectral matrices of the pair on all other recorded channels, which involves the calculation of a matrix (pseudo-) inverse. It has so far remained a challenge to use the time-resolved partial coherence to analyze intracranial recordings with a large number of recording sites. For instance, calculating the partial coherence using a pseudoinverse method produces a high number of false positives when it is applied to a large number of channels. To address this challenge, we developed a new method that randomly aggregated channels into a smaller number of effective channels on which the calculation of partial coherence was based. We obtained a 'consensus' partial coherence (cPCOH) by repeating this approach for several random aggregations of channels (permutations) and only accepting those activations in time and frequency with a high enough consensus. Using model data we show that the cPCOH method effectively filters out the effect of shared inputs and performs substantially better than the pseudo-inverse. We successfully applied the cPCOH procedure to human stereotactic EEG data and demonstrated three key advantages of this method relative to alternative procedures. First, it reduces the number of false positives relative to the pseudo-inverse method. Second, it allows for titration of the amount of false positives relative to the false negatives by adjusting the consensus threshold, thus allowing the data-analyst to prioritize one over the other to meet specific analysis demands. Third, it substantially reduced the number of identified interactions compared to coherence, providing a sparser network of connections from which clear spatial patterns emerged. These patterns can serve as a starting point of further analyses that provide insight into network dynamics during cognitive processes. These advantages likely generalize to other modalities in which shared inputs introduce confounds, such as electroencephalography (EEG) and magneto-encephalography (MEG). Copyright © 2018. Published by Elsevier Inc.

Assessment of an Optical Flow Field-Based Polyp Detector for CT Colonography

DTIC Science & Technology

2001-10-25

sort true polyps from false positives based on features extracted from the computed OFFs. II. METHODOLOGY A. Pre-processing The 3D CT data was...subvolume and scrolling direction, as follows:      = ∑ Z ZD y)x,( Smoothy )x,( vv (2) The smoothing filter used is a 3×3 rectangular

Identification of Childhood Disability in Jamaica: Evaluation of the Ten Question Screen.

ERIC Educational Resources Information Center

Thorburn, Marigold; And Others

1992-01-01

This study examined the internal validity and reasons for false positives for the Ten Question Screen (with and without probes), used by community workers in developing nations to assess type and severity of disability. Results support the use of the screen but only if paired with measurements of hearing and visual impairments. (DB)

Natural Product Libraries to Accelerate the High Throughput Discovery of Therapeutic Leads±

PubMed Central

Johnson, Tyler A.; Sohn, Johann; Inman, Wayne D.; Estee, Samarkand A.; Loveridge, Steven T.; Vervoort, Helene C.; Tenney, Karen; Liu, Junke; Ang, Kenny Kean-Hooi; Ratnam, Joseline; Bray, Walter M.; Gassner, Nadine C.; Shen, Young Y.; Lokey, R. Scott; McKerrow, James H.; Boundy-Mills, Kyria; Nukanto, Arif; Kanti, Atit; Julistiono, Heddy; Kardono, Leonardus B. S.; Bjeldanes, Leonard F.; Crews, Phillip

2011-01-01

A high throughput (HT) paradigm generating LC-MS-UV-ELSD based natural product libraries to discover compounds with new bioactivities and or molecular structures is presented. To validate this methodology an extract of the Indo Pacific marine sponge Cacospongia mycofijiensis was evaluated using assays involving cytoskeletal profiling, tumor cell lines, and parasites. Twelve known compounds were identified including the latrunculins (1–4, 10), fijianolides (5, 8–9), mycothiazole (11), the aignopsanes (6–7) and sacrotride A (13). Compounds 1–4, 5, 8–11 exhibited bioactivity not previously reported against the parasite T. brucei, while 11 showed selectivity for lymphoma (U937) tumor cell lines. Four new compounds were also discovered including: aignopsanoic acid B (13), apo latrunculin T (14), 20-methoxy-fijianolide A (15) and aignopsane ketal (16). Compounds 13 and 16 represent important derivatives of the aignopsane class, 14 exhibited inhibition of T. brucei without disrupting microfilament assembly and 15 demonstrated modest microtubule stabilizing effects. The use of removable well plate libraries to avoid false positives from extracts enriched with only 1–2 major metabolites is also discussed. Overall, these results highlight the advantages of applying modern methods in natural products-based research to accelerate the HT discovery of therapeutic leads and or new molecular structures using LC-MS-UV-ELSD based libraries. PMID:22129061

A simple method for determining polymeric IgA-containing immune complexes.

PubMed

Sancho, J; Egido, J; González, E

1983-06-10

A simplified assay to measure polymeric IgA-immune complexes in biological fluids is described. The assay is based upon the specific binding of a secretory component for polymeric IgA. In the first step, multimeric IgA (monomeric and polymeric) immune complexes are determined by the standard Raji cell assay. Secondly, labeled secretory component added to the assay is bound to polymeric IgA-immune complexes previously fixed to Raji cells, but not to monomeric IgA immune complexes. To avoid false positives due to possible complement-fixing IgM immune complexes, prior IgM immunoadsorption is performed. Using anti-IgM antiserum coupled to CNBr-activated Sepharose 4B this step is not time-consuming. Polymeric IgA has a low affinity constant and binds weakly to Raji cells, as Scatchard analysis of the data shows. Thus, polymeric IgA immune complexes do not bind to Raji cells directly through Fc receptors, but through complement breakdown products, as with IgG-immune complexes. Using this method, we have been successful in detecting specific polymeric-IgA immune complexes in patients with IgA nephropathy (Berger's disease) and alcoholic liver disease, as well as in normal subjects after meals of high protein content. This new, simple, rapid and reproducible assay might help to study the physiopathological role of polymeric IgA immune complexes in humans and animals.

Overdetection in breast cancer screening: development and preliminary evaluation of a decision aid

PubMed Central

Hersch, Jolyn; Jansen, Jesse; Barratt, Alexandra; Irwig, Les; Houssami, Nehmat; Jacklyn, Gemma; Thornton, Hazel; Dhillon, Haryana; McCaffery, Kirsten

2014-01-01

Objective To develop, pilot and refine a decision aid (ahead of a randomised trial evaluation) for women around age 50 facing their initial decision about whether to undergo mammography screening. Design Two-stage mixed-method pilot study including qualitative interviews (n=15) and a randomised comparison using a quantitative survey (n=34). Setting New South Wales, Australia. Participants Women aged 43–59 years with no personal history of breast cancer. Interventions The decision aid provides evidence-based information about important outcomes of mammography screening over 20 years (breast cancer mortality reduction, overdetection and false positives) compared with no screening. The information is presented in a short booklet for women, combining text and visual formats. A control version produced for the purposes of comparison omits the overdetection-related content. Outcomes Comprehension of key decision aid content and acceptability of the materials. Results Most women considered the decision aid clear and helpful and would recommend it to others. Nonetheless, the piloting process raised important issues that we tried to address in iterative revisions. Some participants found it hard to understand overdetection and why it is of concern, while there was often confusion about the distinction between overdetection and false positives. In a screening context, encountering balanced information rather than persuasion appears to be contrary to people's expectations, but women appreciated the opportunity to become better informed. Conclusions The concept of overdetection is complex and new to the public. This study highlights some key challenges for communicating about this issue. It is important to clarify that overdetection differs from false positives in terms of its more serious consequences (overtreatment and associated harms). Screening decision aids also must clearly explain their purpose of facilitating informed choice. A staged approach to development and piloting of decision aids is recommended to further improve understanding of overdetection and support informed decision-making about screening. PMID:25256188

Maremar, prevalence of chronic kidney disease, how to avoid over-diagnosis and under-diagnosis.

PubMed

De Broe, Marc E; Gharbi, Mohammed Benghanem; Elseviers, Monique

2016-04-01

Chronic kidney disease is considered as a major public health problem. Recent studies mention a prevalence rate between 8%-12%. Several editorials, comments, short reviews described the weaknesses (lack of confirmation of proteinuria, and of chronicity of decreased estimated glomerular filtration rate) of a substantial number of studies and the irrational of using a single arbitrary set point, i.e. diagnosis of chronic kidney disease whenever the estimated glomerular filtration rate is less than 60mL/min/1.73m(2). Maremar (Maladies rénales chroniques au Maroc) is a prevalence study of chronic kidney disease, hypertension, diabetes and obesity in a randomized, representative, high response rate (85%), sample of the adult population of Morocco, strictly applying the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Compared to the vast majority of the available studies, Maremar has a low prevalence of chronic kidney disease (2.9% adjusted to the actual adult population of Morocco). The population pyramid, and particularly the confirmation of proteinuria and "chronicity" of the decreased estimated glomerular filtration rate are the main reasons for this low prevalence of chronic kidney disease. The choice of arbitrary single threshold of estimated glomerular filtration rate for classifying stage 3-5 chronic kidney disease inevitably leads to "over-diagnosis" (false positives) of the disease in the elderly, particularly those without proteinuria, hematuria or hypertension, and to "under-diagnosed" (false negatives) in younger individuals with an estimated glomerular filtration rate above 60mL/min/1.73m(2) and below the 3rd percentile of their age/gender category. There is an urgent need for quality studies using in a correct way the recent KDIGO guidelines when investigating the prevalence of chronic kidney disease, in order to avoid a 50 to 100% overestimation of a disease state with potential dramatic consequences. The combination of the general population screening encompassing four different major health problems in the same screening procedure, using the correct methodologies and procedures, combined with a prevention/follow-up program results in a clinically/scientifically relevant program. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

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.

Silkworm larvae plasma (SLP) assay for detection of bacteria: False positives secondary to inflammation in vivo.

PubMed

Ma, Michelle; Rice, Tyler A; Percopo, Caroline M; Rosenberg, Helene F

2017-01-01

The silkworm larvae plasma (SLP) assay has been developed as a means to detect bacterial peptidoglycan as a surrogate for live bacteria. Here, we present results that indicate that generation of melanin by this assay is not fully reliable as a surrogate marker for bacterial count. Published by Elsevier B.V.

Diagnosing Childhood Thought Disorder: Do Parent Checklists Yield False Positives?

ERIC Educational Resources Information Center

Longeway, K.; Johnson, S.; Garwood, M.; Davis, L.

This study examined the validity of using the Child Behavior Checklist (CBCL) Thought Problem sub-scale with urban low-income children (N=46) referred to a hospital-based mental health clinic. It was hypothesized that cultural, linguistic, or socio-economic status (SES) factors may influence the manner in which parents understand and respond to…

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

PubMed Central

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

2012-01-01

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

Systems pharmacology augments drug safety surveillance

PubMed Central

Lorberbaum, Tal; Nasir, Mavra; Keiser, Michael J.; Vilar, Santiago; Hripcsak, George; Tatonetti, Nicholas P.

2014-01-01

Small molecule drugs are the foundation of modern medical practice yet their use is limited by the onset of unexpected and severe adverse events (AEs). Regulatory agencies rely on post-marketing surveillance to monitor safety once drugs are approved for clinical use. Despite advances in pharmacovigilance methods that address issues of confounding bias, clinical data of AEs are inherently noisy. Systems pharmacology– the integration of systems biology and chemical genomics – can illuminate drug mechanisms of action. We hypothesize that these data can improve drug safety surveillance by highlighting drugs with a mechanistic connection to the target phenotype (enriching true positives) and filtering those that do not (depleting false positives). We present an algorithm, the modular assembly of drug safety subnetworks (MADSS), to combine systems pharmacology and pharmacovigilance data and significantly improve drug safety monitoring for four clinically relevant adverse drug reactions. PMID:25670520

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

Assessment of real-time PCR cycle threshold values in Microsporum canis culture-positive and culture-negative cats in an animal shelter: a field study.

PubMed

Jacobson, Linda S; McIntyre, Lauren; Mykusz, Jenny

2018-02-01

Objectives Real-time PCR provides quantitative information, recorded as the cycle threshold (Ct) value, about the number of organisms detected in a diagnostic sample. The Ct value correlates with the number of copies of the target organism in an inversely proportional and exponential relationship. The aim of the study was to determine whether Ct values could be used to distinguish between culture-positive and culture-negative samples. Methods This was a retrospective analysis of Ct values from dermatophyte PCR results in cats with suspicious skin lesions or suspected exposure to dermatophytosis. Results One hundred and thirty-two samples were included. Using culture as the gold standard, 28 were true positives, 12 were false positives and 92 were true negatives. The area under the curve for the pretreatment time point was 96.8% (95% confidence interval [CI] 94.2-99.5) compared with 74.3% (95% CI 52.6-96.0) for pooled data during treatment. Before treatment, a Ct cut-off of <35.7 (approximate DNA count 300) provided a sensitivity of 92.3% and specificity of 95.2%. There was no reliable cut-off Ct value between culture-positive and culture-negative samples during treatment. Ct values prior to treatment differed significantly between the true-positive and false-positive groups ( P = 0.0056). There was a significant difference between the pretreatment and first and second negative culture time points ( P = 0.0002 and P <0.0001, respectively). However, there was substantial overlap between Ct values for true positives and true negatives, and for pre- and intra-treatment time points. Conclusions and relevance Ct values had limited usefulness for distinguishing between culture-positive and culture-negative cases when field study samples were analyzed. In addition, Ct values were less reliable than fungal culture for determining mycological cure.

Diagnostic Performance of Ultrasonography for Pediatric Appendicitis: A Night and Day Difference?

PubMed

Mangona, Kate Louise M; Guillerman, R Paul; Mangona, Victor S; Carpenter, Jennifer; Zhang, Wei; Lopez, Monica; Orth, Robert C

2017-12-01

For imaging pediatric appendicitis, ultrasonography (US) is preferred because of its lack of ionizing radiation, but is limited by operator dependence. This study investigates the US diagnostic performance during night shifts covered by radiology trainees compared to day shifts covered by attending radiologists. Appy-Scores (1 = completely visualized normal appendix; 2 = partially visualized normal appendix; 3 = nonvisualized appendix with no inflammatory changes in the expected region of the appendix; 4 = equivocal; 5a = nonperforated appendicitis; 5b = perforated appendicitis) from 2935 US examinations (2161:774, day-to-night) from July 2013 to 2014 were correlated with the intraoperative diagnoses and the clinical follow-up. The diagnostic performance of trainees and attendings was compared with Fisher exact test. Interobserver agreement was measured by Cohen kappa coefficient. Appendicitis prevalence was 25.3% (day) and 22.5% (night). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive vale were 94.0%, 93.7%, 93.8%, 97.9%, and 83.4% during the day and 92.0%, 91.2%, 91.3%, 97.5%, and 75.2% at night. Specificity (P = .048) and positive predictive value (P = .011) differed, with more false positives at night (7%) than during the day (4.7%). Trainee and attending agreement was high (k = 0.995), with Appy-Scores of 1, 4, and 5a most frequently discordant. US has a high diagnostic performance and interobserver agreement for pediatric appendicitis when interpreted by radiology trainees during night shifts or attending radiologists during day shifts. However, lower specificity and positive predictive value at night warrants a thorough trainee education to avoid false-positive examinations. Published by Elsevier Inc.

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

PubMed

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

2017-01-01

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

ScreenBEAM: a novel meta-analysis algorithm for functional genomics screens via Bayesian hierarchical modeling | Office of Cancer Genomics

Cancer.gov

Functional genomics (FG) screens, using RNAi or CRISPR technology, have become a standard tool for systematic, genome-wide loss-of-function studies for therapeutic target discovery. As in many large-scale assays, however, off-target effects, variable reagents' potency and experimental noise must be accounted for appropriately control for false positives.

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 ...

Identifying Students' Mathematical Skills from a Multiple-Choice Diagnostic Test Using an Iterative Technique to Minimise False Positives

ERIC Educational Resources Information Center

Manning, S.; Dix, A.

2008-01-01

There is anecdotal evidence that a significant number of students studying computing related courses at degree level have difficulty with sub-GCE mathematics. Testing of students' skills is often performed using diagnostic tests and a number of computer-based diagnostic tests exist, which work, essentially, by testing one specific diagnostic skill…

Evaluation of surveillance case definition in the diagnosis of leptospirosis, using the Microscopic Agglutination Test: a validation study.

PubMed

Dassanayake, Dinesh L B; Wimalaratna, Harith; Agampodi, Suneth B; Liyanapathirana, Veranja C; Piyarathna, Thibbotumunuwe A C L; Goonapienuwala, Bimba L

2009-04-22

Leptospirosis is endemic in both urban and rural areas of Sri Lanka and there had been many out breaks in the recent past. This study was aimed at validating the leptospirosis surveillance case definition, using the Microscopic Agglutination Test (MAT). The study population consisted of patients with undiagnosed acute febrile illness who were admitted to the medical wards of the Teaching Hospital Kandy, from 1st July 2007 to 31st July 2008. The subjects were screened to diagnose leptospirosis according to the leptospirosis case definition. MAT was performed on blood samples taken from each patient on the 7th day of fever. Leptospirosis case definition was evaluated in regard to sensitivity, specificity and predictive values, using a MAT titre >or= 1:800 for confirming leptospirosis. A total of 123 patients were initially recruited of which 73 had clinical features compatible with the surveillance case definition. Out of the 73 only 57 had a positive MAT result (true positives) leaving 16 as false positives. Out of the 50 who didn't have clinical features compatible with the case definition 45 had a negative MAT as well (true negatives), therefore 5 were false negatives. Total number of MAT positives was 62 out of 123. According to these results the test sensitivity was 91.94%, specificity 73.77%, positive predictive value and negative predictive values were 78.08% and 90% respectively. Diagnostic accuracy of the test was 82.93%. This study confirms that the surveillance case definition has a very high sensitivity and negative predictive value with an average specificity in diagnosing leptospirosis, based on a MAT titre of >or= 1: 800.

Bayesian truthing and experimental validation in homeland security and defense

NASA Astrophysics Data System (ADS)

Jannson, Tomasz; Forrester, Thomas; Wang, Wenjian; Kostrzewski, Andrew; Pradhan, Ranjit

2014-05-01

In this paper we discuss relations between Bayesian Truthing (experimental validation), Bayesian statistics, and Binary Sensing in the context of selected Homeland Security and Intelligence, Surveillance, Reconnaissance (ISR) optical and nonoptical application scenarios. The basic Figure of Merit (FoM) is Positive Predictive Value (PPV), as well as false positives and false negatives. By using these simple binary statistics, we can analyze, classify, and evaluate a broad variety of events including: ISR; natural disasters; QC; and terrorism-related, GIS-related, law enforcement-related, and other C3I events.

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

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

Automating concept identification in the electronic medical record: an experiment in extracting dosage information.

PubMed Central

Evans, D. A.; Brownlow, N. D.; Hersh, W. R.; Campbell, E. M.

1996-01-01

We discuss the development and evaluation of an automated procedure for extracting drug-dosage information from clinical narratives. The process was developed rapidly using existing technology and resources, including categories of terms from UMLS96. Evaluations over a large training and smaller test set of medical records demonstrate an approximately 80% rate of exact and partial matches' on target phrases, with few false positives and a modest rate of false negatives. The results suggest a strategy for automating general concept identification in electronic medical records. PMID:8947694

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.

Waterway wide area tactical coverage and homing (WaterWATCH) program overview

NASA Astrophysics Data System (ADS)

Driggers, Gerald; Cleveland, Tammy; Araujo, Lisa; Spohr, Robert; Umansky, Mark

2008-04-01

The Congressional and Army sponsored WaterWATCH TM Program has developed and demonstrated a fully integrated shallow water port and facility monitoring system. It provides fully automated monitoring of domains above and below the surface of the water using primarily off-the-shelf sensors and software. The system is modular, open architecture and IP based, and elements can be mixed and matched to adapt to specific applications. The sensors integrated into the WaterWATCH TM system include cameras, radar, passive and active sonar, and various motion detectors. The sensors were chosen based on extensive requirements analyses and tradeoffs. Descriptions of the system and individual sensors are provided, along with data from modular and system level testing. Camera test results address capabilities and limitations associated with using "smart" image analysis software with stressing environmental issues such as bugs, darkness, rain and snow. Radar issues addressed include achieving range and resolution requirements. The passive sonar capability to provide near 100% true positives with zero false positives is demonstrated. Testing results are also presented to show that inexpensive active sonar can be effective against divers with or without SCUBA gear and that false alarms due to fish can be minimized. A simple operator interface has also been demonstrated.

Comparison of results for morphine urinalyses by radioimmunoassay and thin-layer chromatography in a narcotic clinic setting.

PubMed

Kokoski, R J; Jain, M

1975-03-01

Radioimmunoassay (RIA) and thin-layer chromatography (TLC) were compared for morphine detection in an actual narcotic clinic setting. A choice of urines from all those screened by TLC allowed a critical comparison as to actual use or non-use of narcotic drugs, rather than a sampling at random in which the question of possible false positives or negatives cannot be conclusively answered. Although RIA is more sensitive than TLC, its advantage is apparent only in those cases where urine specimens are difficult to obtain frequently regularly or where the use of morphine is suspected by the positive identification of quinine in urine that was morphine-negative by TLC. In a selected group of negative and positive specimens chosen without conscious bias, the two methods gave consistently similar results, indicating that the modified TLC method provided a few or no false positives or negatives if the negatives were from those cases that were not positive anytime up to 3-4 days before urine collection. We conclude that RIA can be of significant value as a supplement to a TLC screening program, without sacrificing the many advantages that TLC has to offer.

Improving Echo-Guided Procedures Using an Ultrasound-CT Image Fusion System.

PubMed

Diana, Michele; Halvax, Peter; Mertz, Damien; Legner, Andras; Brulé, Jean-Marcel; Robinet, Eric; Mutter, Didier; Pessaux, Patrick; Marescaux, Jacques

2015-06-01

Image fusion between ultrasound (US) and computed tomography (CT) scan or magnetic resonance can increase operator accuracy in targeting liver lesions, particularly when those are undetectable with US alone. We have developed a modular gel to simulate hepatic solid lesions for educational purposes in imaging and minimally invasive ablation techniques. We aimed to assess the impact of image fusion in targeting artificial hepatic lesions during the hands-on part of 2 courses (basic and advanced) in hepatobiliary surgery. Under US guidance, 10 fake tumors of various sizes were created in the livers of 2 pigs, by percutaneous injection of a biocompatible gel engineered to be hyperdense on CT scanning and barely detectable on US. A CT scan was obtained and a CT-US image fusion was performed using the ACUSON S3000 US system (Siemens Healthcare, Germany). A total of 12 blinded course attendants, were asked in turn to perform a 10-minute liver scan with US alone followed by a 10-minute scan using image fusion. Using US alone, the expert managed to identify all lesions successfully. The true positive rate for course attendants with US alone was 14/36 and 2/24 in the advanced and basic courses, respectively. The total number of false positives identified was 26. With image fusion, the rate of true positives significantly increased to 31/36 (P < .001) in the advanced group and 16/24 in the basic group (P < .001). The total number of false positives, considering all participants, decreased to 4 (P < .001). Image fusion significantly increases accuracy in targeting hepatic lesions and might improve echo-guided procedures. © The Author(s) 2015.

Accuracy of ultrasound for the prediction of placenta accreta.

PubMed

Bowman, Zachary S; Eller, Alexandra G; Kennedy, Anne M; Richards, Douglas S; Winter, Thomas C; Woodward, Paula J; Silver, Robert M

2014-08-01

Ultrasound has been reported to be greater than 90% sensitive for the diagnosis of accreta. Prior studies may be subject to bias because of single expert observers, suspicion for accreta, and knowledge of risk factors. We aimed to assess the accuracy of ultrasound for the prediction of accreta. Patients with accreta at a single academic center were matched to patients with placenta previa, but no accreta, by year of delivery. Ultrasound studies with views of the placenta were collected, deidentified, blinded to clinical history, and placed in random sequence. Six investigators prospectively interpreted each study for the presence of accreta and findings reported to be associated with its diagnosis. Sensitivity, specificity, positive predictive, negative predictive value, and accuracy were calculated. Characteristics of accurate findings were compared using univariate and multivariate analyses. Six investigators examined 229 ultrasound studies from 55 patients with accreta and 56 controls for 1374 independent observations. 1205/1374 (87.7% overall, 90% controls, 84.9% cases) studies were given a diagnosis. There were 371 (27.0%) true positives; 81 (5.9%) false positives; 533 (38.8%) true negatives, 220 (16.0%) false negatives, and 169 (12.3%) with uncertain diagnosis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 53.5%, 88.0%, 82.1%, 64.8%, and 64.8%, respectively. In multivariate analysis, true positives were more likely to have placental lacunae (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), loss of retroplacental clear space (OR, 2.4; 95% CI, 1.1-4.9), or abnormalities on color Doppler (OR, 2.1; 95% CI, 1.8-2.4). Ultrasound for the prediction of placenta accreta may not be as sensitive as previously described. Copyright © 2014 Mosby, Inc. All rights reserved.

Evaluating methods of correcting for multiple comparisons implemented in SPM12 in social neuroscience fMRI studies: an example from moral psychology.

PubMed

Han, Hyemin; Glenn, Andrea L

2018-06-01

In fMRI research, the goal of correcting for multiple comparisons is to identify areas of activity that reflect true effects, and thus would be expected to replicate in future studies. Finding an appropriate balance between trying to minimize false positives (Type I error) while not being too stringent and omitting true effects (Type II error) can be challenging. Furthermore, the advantages and disadvantages of these types of errors may differ for different areas of study. In many areas of social neuroscience that involve complex processes and considerable individual differences, such as the study of moral judgment, effects are typically smaller and statistical power weaker, leading to the suggestion that less stringent corrections that allow for more sensitivity may be beneficial and also result in more false positives. Using moral judgment fMRI data, we evaluated four commonly used methods for multiple comparison correction implemented in Statistical Parametric Mapping 12 by examining which method produced the most precise overlap with results from a meta-analysis of relevant studies and with results from nonparametric permutation analyses. We found that voxelwise thresholding with familywise error correction based on Random Field Theory provides a more precise overlap (i.e., without omitting too few regions or encompassing too many additional regions) than either clusterwise thresholding, Bonferroni correction, or false discovery rate correction methods.

Sensitivity and Specificity of Histoplasma Antigen Detection by Enzyme Immunoassay.

PubMed

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

2015-01-01

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

Detection of Spoofed MAC Addresses in 802.11 Wireless Networks

NASA Astrophysics Data System (ADS)

Tao, Kai; Li, Jing; Sampalli, Srinivas

Medium Access Control (MAC) address spoofing is considered as an important first step in a hacker's attempt to launch a variety of attacks on 802.11 wireless networks. Unfortunately, MAC address spoofing is hard to detect. Most current spoofing detection systems mainly use the sequence number (SN) tracking technique, which has drawbacks. Firstly, it may lead to an increase in the number of false positives. Secondly, such techniques cannot be used in systems with wireless cards that do not follow standard 802.11 sequence number patterns. Thirdly, attackers can forge sequence numbers, thereby causing the attacks to go undetected. We present a new architecture called WISE GUARD (Wireless Security Guard) for detection of MAC address spoofing on 802.11 wireless LANs. It integrates three detection techniques - SN tracking, Operating System (OS) fingerprinting & tracking and Received Signal Strength (RSS) fingerprinting & tracking. It also includes the fingerprinting of Access Point (AP) parameters as an extension to the OS fingerprinting for detection of AP address spoofing. We have implemented WISE GUARD on a test bed using off-the-shelf wireless devices and open source drivers. Experimental results show that the new design enhances the detection effectiveness and reduces the number of false positives in comparison with current approaches.

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

PubMed Central

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

2016-01-01

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

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

Rapid Field-Usable Cyanide Sensor Development for Blood and Saliva

DTIC Science & Technology

2013-12-01

fluorescent readings were measured using an Ocean Optics USB2000+ Spectrometer. The spiked plasma gave a signal of approximately 18% of an aqueous...fluorescent readings were measured using an Ocean Optics USB2000+ Spectrometer. The optimization data can be seen in Figure 1.1.1-3. For aqueous...measured using an Ocean Optics USB2000+ Spectrometer. The identification of interferents is important to assess the possibility of false positives for

Detection of Staphylococcus Aureus Enterotoxin A and B Genes with PCR-EIA and a Hand-Held Electrochemical Sensor

DTIC Science & Technology

2004-06-11

Streptococcus pneumoniae 33400 Enterobacter cloaceae 49141 S. pyogenes 19615 E. aerogenes m10822 Vibrio cholerae N16961 Enterococcus durans 6056 Yersinia...identified. Thus the sensitivity for both assays was 100%. Of the 56 samples that lacked sea or seb genes, two false positives ( Enterobacter aerogenes ...Comanonas, Enterobacter , Enterococcus, Escherichia, Francisella, Haemophilus, Klebsiella, Listeria, Moraxella, Neisseria, Proteus, Pseudomonas, Salmonella

Hyperspectral imaging for differentiation of foreign materials from pinto beans

NASA Astrophysics Data System (ADS)

Mehrubeoglu, Mehrube; Zemlan, Michael; Henry, Sam

2015-09-01

Food safety and quality in packaged products are paramount in the food processing industry. To ensure that packaged products are free of foreign materials, such as debris and pests, unwanted materials mixed with the targeted products must be detected before packaging. A portable hyperspectral imaging system in the visible-to-NIR range has been used to acquire hyperspectral data cubes from pinto beans that have been mixed with foreign matter. Bands and band ratios have been identified as effective features to develop a classification scheme for detection of foreign materials in pinto beans. A support vector machine has been implemented with a quadratic kernel to separate pinto beans and background (Class 1) from all other materials (Class 2) in each scene. After creating a binary classification map for the scene, further analysis of these binary images allows separation of false positives from true positives for proper removal action during packaging.

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

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

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

1984-01-01

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

Permutation inference for the general linear model

PubMed Central

Winkler, Anderson M.; Ridgway, Gerard R.; Webster, Matthew A.; Smith, Stephen M.; Nichols, Thomas E.

2014-01-01

Permutation methods can provide exact control of false positives and allow the use of non-standard statistics, making only weak assumptions about the data. With the availability of fast and inexpensive computing, their main limitation would be some lack of flexibility to work with arbitrary experimental designs. In this paper we report on results on approximate permutation methods that are more flexible with respect to the experimental design and nuisance variables, and conduct detailed simulations to identify the best method for settings that are typical for imaging research scenarios. We present a generic framework for permutation inference for complex general linear models (glms) when the errors are exchangeable and/or have a symmetric distribution, and show that, even in the presence of nuisance effects, these permutation inferences are powerful while providing excellent control of false positives in a wide range of common and relevant imaging research scenarios. We also demonstrate how the inference on glm parameters, originally intended for independent data, can be used in certain special but useful cases in which independence is violated. Detailed examples of common neuroimaging applications are provided, as well as a complete algorithm – the “randomise” algorithm – for permutation inference with the glm. PMID:24530839

Missing value imputation strategies for metabolomics data.

PubMed

Armitage, Emily Grace; Godzien, Joanna; Alonso-Herranz, Vanesa; López-Gonzálvez, Ángeles; Barbas, Coral

2015-12-01

The origin of missing values can be caused by different reasons and depending on these origins missing values should be considered differently and dealt with in different ways. In this research, four methods of imputation have been compared with respect to revealing their effects on the normality and variance of data, on statistical significance and on the approximation of a suitable threshold to accept missing data as truly missing. Additionally, the effects of different strategies for controlling familywise error rate or false discovery and how they work with the different strategies for missing value imputation have been evaluated. Missing values were found to affect normality and variance of data and k-means nearest neighbour imputation was the best method tested for restoring this. Bonferroni correction was the best method for maximizing true positives and minimizing false positives and it was observed that as low as 40% missing data could be truly missing. The range between 40 and 70% missing values was defined as a "gray area" and therefore a strategy has been proposed that provides a balance between the optimal imputation strategy that was k-means nearest neighbor and the best approximation of positioning real zeros. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A soft kinetic data structure for lesion border detection.

PubMed

Kockara, Sinan; Mete, Mutlu; Yip, Vincent; Lee, Brendan; Aydin, Kemal

2010-06-15

The medical imaging and image processing techniques, ranging from microscopic to macroscopic, has become one of the main components of diagnostic procedures to assist dermatologists in their medical decision-making processes. Computer-aided segmentation and border detection on dermoscopic images is one of the core components of diagnostic procedures and therapeutic interventions for skin cancer. Automated assessment tools for dermoscopic images have become an important research field mainly because of inter- and intra-observer variations in human interpretations. In this study, a novel approach-graph spanner-for automatic border detection in dermoscopic images is proposed. In this approach, a proximity graph representation of dermoscopic images in order to detect regions and borders in skin lesion is presented. Graph spanner approach is examined on a set of 100 dermoscopic images whose manually drawn borders by a dermatologist are used as the ground truth. Error rates, false positives and false negatives along with true positives and true negatives are quantified by digitally comparing results with manually determined borders from a dermatologist. The results show that the highest precision and recall rates obtained to determine lesion boundaries are 100%. However, accuracy of assessment averages out at 97.72% and borders errors' mean is 2.28% for whole dataset.

Computer-aided detection of pulmonary embolism at CT pulmonary angiography: can it improve performance of inexperienced readers?

PubMed

Blackmon, Kevin N; Florin, Charles; Bogoni, Luca; McCain, Joshua W; Koonce, James D; Lee, Heon; Bastarrika, Gorka; Thilo, Christian; Costello, Philip; Salganicoff, Marcos; Joseph Schoepf, U

2011-06-01

To evaluate the effect of a computer-aided detection (CAD) algorithm on the performance of novice readers for detection of pulmonary embolism (PE) at CT pulmonary angiography (CTPA). We included CTPA examinations of 79 patients (50 female, 52 ± 18 years). Studies were evaluated by two independent inexperienced readers who marked all vessels containing PE. After 3 months all studies were reevaluated by the same two readers, this time aided by CAD prototype. A consensus read by three expert radiologists served as the reference standard. Statistical analysis used χ(2) and McNemar testing. Expert consensus revealed 119 PEs in 32 studies. For PE detection, the sensitivity of CAD alone was 78%. Inexperienced readers' initial interpretations had an average per-PE sensitivity of 50%, which improved to 71% (p < 0.001) with CAD as a second reader. False positives increased from 0.18 to 0.25 per study (p = 0.03). Per-study, the readers initially detected 27/32 positive studies (84%); with CAD this number increased to 29.5 studies (92%; p = 0.125). Our results suggest that CAD significantly improves the sensitivity of PE detection for inexperienced readers with a small but appreciable increase in the rate of false positives.

47 CFR 74.403 - Frequency selection to avoid interference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Frequency selection to avoid interference. 74... Pickup Broadcast Stations § 74.403 Frequency selection to avoid interference. (a) Where two or more... select frequencies or schedule operation in such manner as to avoid mutual interference. If mutual...

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.

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

PubMed

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

2010-07-01

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

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

PubMed

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

2016-07-29

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

Mass Spectrometric Rapid Diagnosis of Infectious Diseases.

DTIC Science & Technology

1980-01-01

the analytical procedures to warrant reporting anew the whole analytical procedure. A. Sample Collection and Storage Procedure Urine samples were...positives or false-negatives. Next we have carried out a longitudinal study on urine samples obtained from groups of volunteer subjects vaccinated with...sterilization and storage procedures. 2. Developed new, simpler sample preparation techniques including one to handle tissue culture media. 3. Improved on the

Short RNA indicator sequences are not completely degraded by autoclaving

PubMed Central

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

2014-01-01

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

47 CFR 74.403 - Frequency selection to avoid interference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Frequency selection to avoid interference. 74... Pickup Broadcast Stations § 74.403 Frequency selection to avoid interference. (a) Where two or more... select frequencies or schedule operation in such manner as to avoid mutual interference. If mutual...

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.

Detecting false positive sequence homology: a machine learning approach.

PubMed

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

2016-02-24

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

Comparison of Screening Dilution and Automated Reading for Antinuclear Antibody Detection on HEP2 Cells in the Monitoring of Connective Tissue Diseases.

PubMed

Depincé-Berger, Anne E; Moreau, Amelie; Bossy, Virginie; Genin, Christian; Rinaudo, Melanie; Paul, Stephane

2016-09-01

Indirect immunofluorescence plays a major role in the detection of antinuclear antibodies (ANAs) and follow-up of their titers in the context of connective tissue diseases. Given the numerous unfavorable features of the conventional manual reading of HEP2 slides (need of time and expert morphologists for the reading, lack of standardization, subjectivity of the interpretation), the biomedical industry has developed automated techniques of slide preparation and microscope reading. We collected 49 sera beforehand analyzed by the conventional reading of slides. They were prepared again by QUANTA-Lyser(®) and reanalyzed in four different conditions: two dilutions of screening (1/40 and 1/80), two different systems of analysis, NOVA View(®) automated reading (INOVA Diagnostics), then confirmation by the operator, and conventional manual reading by two different qualified operators. The analysis was realized in blind of the first interpretation and clinical diagnosis. The sera were classified in four groups, on the basis of the results of the first analysis: negative sera (titer < 1/160; 11 patients), low positives (titer at 1/160; 18 patients), moderated positives (titers between 1/320 and 1/640; 10 patients), and strong positives (titers between 1/1,280 and 1/2,560; 10 patients). Among the 49 patients, 13 presented a connective tissue disease including 4 systemic scleroderma (SS), 3 rheumatoid arthritis (RA), 2 Goujerot-Sjogren (GS), 2 systemic lupus erythematosus (SLE), 1 polymyositis (PM), 1 Raynaud's syndrome (RS), and 1 CREST syndrome. One patient presented both an SLE and an SS. Regarding the screening dilution, the 1/40 dilution is less specific than the 1/80 dilution for both the systems of analysis (5.6% vs. 16.7% for the manual reading, and 27.8% vs. 50% for the automated reading). It also generates statistically more false positives (P = 0.037 for the conventional analysis and P = 0.003 for the automated system). The automated NOVA View(®) reading of slides allows a gain in specificity for both dilutions, and also statistically less false positives (P = 0.002 at the 1/40 and P = 0.0006 at the 1/80), and detriment of the sensitivity at the highest dilution (84.6% vs. 92.3% with manual reading). Thus, according to our analysis of 49 sera, the automated NOVA View(®) system of reading of slides at the dilution 1/80 seems to be a successful condition for the detection of ANAs on HEP2 cells, close to the significance (P = 0.067). The automated NOVA View(®) reading of slides allows saving time, and an improvement in the standardization. Nevertheless, it requires a confirmation by a qualified operator, to interpret mixed patterns in particular. © 2016 Wiley Periodicals, Inc.

Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts.

PubMed

Tynkkynen, Juho; Chouraki, Vincent; van der Lee, Sven J; Hernesniemi, Jussi; Yang, Qiong; Li, Shuo; Beiser, Alexa; Larson, Martin G; Sääksjärvi, Katri; Shipley, Martin J; Singh-Manoux, Archana; Gerszten, Robert E; Wang, Thomas J; Havulinna, Aki S; Würtz, Peter; Fischer, Krista; Demirkan, Ayse; Ikram, M Arfan; Amin, Najaf; Lehtimäki, Terho; Kähönen, Mika; Perola, Markus; Metspalu, Andres; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Vasan, Ramachandran S; Kivimäki, Mika; van Duijn, Cornelia M; Seshadri, Sudha; Salomaa, Veikko

2018-06-01

Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Hoarding versus collecting: where does pathology diverge from play?

PubMed

Nordsletten, Ashley E; Mataix-Cols, David

2012-04-01

A new diagnosis termed Hoarding Disorder has been proposed for inclusion in the upcoming DSM-5 to cover the majority of cases where severe hoarding occurs in the absence of, or independently from other mental disorders. Much effort has been directed to ensuring that the proposed criteria discriminate Hoarding Disorder from other mental disorders, particularly those historically associated with hoarding (e.g. OCD, OCPD). Considerably less attention, however, has been paid to addressing the suitability of the proposed criteria for effectively differentiating pathological hoarding from normative collecting behavior. This is crucial in order to avoid false positives or the overpathologization of this widespread human activity. Collecting behavior mirrors many of the core features of hoarding (e.g. the acquisition of and emotional attachment to a potentially large number of objects), is highly prevalent and is generally considered a normative form of object amassment; as such, it represents a valid population with which to explore the diagnostic boundaries of Hoarding Disorder. Examination of the collecting literature, within the context of the hoarding diagnostic criteria, indicates that, for the majority of collectors, a diagnosis of Hoarding Disorder is likely to be effectively ruled out. For a minority of 'extreme' collectors, a diagnosis may potentially be adequate. This review highlights the similarities and differences between hoarding and collecting and offers suggestions for further research in this group. Copyright © 2012 Elsevier Ltd. All rights reserved.

47 CFR 74.803 - Frequency selection to avoid interference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Frequency selection to avoid interference. 74... Power Auxiliary Stations § 74.803 Frequency selection to avoid interference. (a) Where two or more low... frequencies or schedule operation in such manner as to avoid mutual interference. If a mutually satisfactory...

47 CFR 74.803 - Frequency selection to avoid interference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Frequency selection to avoid interference. 74... Power Auxiliary Stations § 74.803 Frequency selection to avoid interference. (a) Where two or more low... frequencies or schedule operation in such manner as to avoid mutual interference. If a mutually satisfactory...

Robust regression for large-scale neuroimaging studies.

PubMed

Fritsch, Virgile; Da Mota, Benoit; Loth, Eva; Varoquaux, Gaël; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Brühl, Rüdiger; Butzek, Brigitte; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Lemaitre, Hervé; Mann, Karl; Nees, Frauke; Paus, Tomas; Schad, Daniel J; Schümann, Gunter; Frouin, Vincent; Poline, Jean-Baptiste; Thirion, Bertrand

2015-05-01

Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e.g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain-behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhancing the detection of barcoded reads in high throughput DNA sequencing data by controlling the false discovery rate.

PubMed

Buschmann, Tilo; Zhang, Rong; Brash, Douglas E; Bystrykh, Leonid V

2014-08-07

DNA barcodes are short unique sequences used to label DNA or RNA-derived samples in multiplexed deep sequencing experiments. During the demultiplexing step, barcodes must be detected and their position identified. In some cases (e.g., with PacBio SMRT), the position of the barcode and DNA context is not well defined. Many reads start inside the genomic insert so that adjacent primers might be missed. The matter is further complicated by coincidental similarities between barcode sequences and reference DNA. Therefore, a robust strategy is required in order to detect barcoded reads and avoid a large number of false positives or negatives.For mass inference problems such as this one, false discovery rate (FDR) methods are powerful and balanced solutions. Since existing FDR methods cannot be applied to this particular problem, we present an adapted FDR method that is suitable for the detection of barcoded reads as well as suggest possible improvements. In our analysis, barcode sequences showed high rates of coincidental similarities with the Mus musculus reference DNA. This problem became more acute when the length of the barcode sequence decreased and the number of barcodes in the set increased. The method presented in this paper controls the tail area-based false discovery rate to distinguish between barcoded and unbarcoded reads. This method helps to establish the highest acceptable minimal distance between reads and barcode sequences. In a proof of concept experiment we correctly detected barcodes in 83% of the reads with a precision of 89%. Sensitivity improved to 99% at 99% precision when the adjacent primer sequence was incorporated in the analysis. The analysis was further improved using a paired end strategy. Following an analysis of the data for sequence variants induced in the Atp1a1 gene of C57BL/6 murine melanocytes by ultraviolet light and conferring resistance to ouabain, we found no evidence of cross-contamination of DNA material between samples. Our method offers a proper quantitative treatment of the problem of detecting barcoded reads in a noisy sequencing environment. It is based on the false discovery rate statistics that allows a proper trade-off between sensitivity and precision to be chosen.

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.

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

NASA Technical Reports Server (NTRS)

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

TESS Follow-up Observing Program (TFOP) Working Group:A Mission-led Effort to Coordinate Community Resources to Confirm TESS Planets

NASA Astrophysics Data System (ADS)

Collins, Karen; Quinn, Samuel N.; Latham, David W.; Christiansen, Jessie; Ciardi, David; Dragomir, Diana; Crossfield, Ian; Seager, Sara

2018-01-01

The Transiting Exoplanet Survey Satellite (TESS) will observe most of the sky over a period of two years. Observations will be conducted in 26 sectors of sky coverage and each sector will be observed for ~27 days. Data from each sector is expected to produce hundreds of transiting planet candidates (PCs) per month and thousands over the two year nominal mission. The TFOP Working Group (WG) is a mission-led effort organized to efficiently provide follow-up observations to confirm candidates as planets or reject them as false positives. The primary goal of the TFOP WG is to facilitate achievement of the Level One Science Requirement to measure masses for 50 transiting planets smaller than 4 Earth radii. Secondary goals are to serve any science coming out of TESS and to foster communication and coordination both within the TESS Science Team and with the community at large. The TFOP WG is organized as five Sub Groups (SGs). SG1 will provide seeing-limited imaging to measure blending within a candidate's aperture and time-series photometry to identify false positives and in some cases to improve ephemerides, light curves, and/or transit time variation (TTV) measurements. SG2 will provide reconnaissance spectroscopy to identify astrophysical false positives and to contribute to improved host star parameters. SG3 will provide high-resolution imaging with adaptive optics, speckle imaging, and lucky imaging to detect nearby objects. SG4 will provide precise radial velocities to derive orbits of planet(s) and measure their mass(es) relative to the host star. SG5 will provide space-based photometry to confirm and/or improve the TESS photometric ephemerides, and will also provide improved light curves for transit events or TTV measurements. We describe the TFOP WG observing and planet confirmation process, the five SGs that comprise the TFOP WG, ExoFOP-TESS and other web-based tools being developed to support TFOP WG observers, other advantages of joining the TFOP WG, the TFOP WG charter and publication policy, preferred capabilities of SG team members, and the TFOP WG application process.

The use of U.S. Geological Survey digital geospatial data products for science research

USGS Publications Warehouse

Varanka, Dalia E.; Deering, Carol; Caro, Holly

2012-01-01

The development of geographic information system (GIS) transformed the practice of geographic science research. The availability of low-cost, reliable data by the U.S. Geological Survey (USGS) supported the advance of GIS in the early stages of the transition to digital technology. To estimate the extent of the scientific use of USGS digital geospatial data products, a search of science literature databases yielded numbers of articles citing USGS products. Though this method requires careful consideration to avoid false positives, these citation numbers of three types of products (vector, land-use/land-cover, and elevation data) were graphed, and the frequency trends were examined. Trends indicated that the use of several, but not all, products increased with time. The use of some products declined and reasons for these declines are offered. To better understand how these data affected the design and outcomes of research projects, the study begins to build a context for the data by discussing digital cartographic research preceding the production of mass-produced products. The data distribution methods used various media for different system types and were supported by instructional material. The findings are an initial assessment of the affect of USGS products on GIS-enabled science research. A brief examination of the specific papers indicates that USGS data were used for science and GIS conceptual research, advanced education, and problem analysis and solution applications.

Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

PubMed

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR predictions.

VizieR Online Data Catalog: Stellar and planet properties for K2 candidates (Montet+, 2015)

NASA Astrophysics Data System (ADS)

Montet, B. T.; Morton, T. D.; Foreman-Mackey, D.; Johnson, J. A.; Hogg, D. W.; Bowler, B. P.; Latham, D. W.; Bieryla, A.; Mann, A. W.

2017-09-01

In this paper, we present stellar and planetary parameters for each system. We also analyze the false positive probability (FPP) of each system using vespa, a new publicly available, general-purpose implementation of the Morton (2012ApJ...761....6M) procedure to calculate FPPs for transiting planets. Through this analysis, as well as archival imaging, ground-based seeing-limited survey data, and adaptive optics imaging, we are able to confirm 21 of these systems as transiting planets at the 99% confidence level. Additionally, we identify six systems as false positives. (5 data files).

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

PubMed

Ochoa Sangrador, C; Pascual Terrazas, A

2016-02-01

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

Skeletal age and age verification in youth sport.

PubMed

Malina, Robert M

2011-11-01

Problems with accurate chronological age (CA) reporting occur on a more or less regular basis in youth sports. As a result, there is increasing discussion of age verification. Use of 'bone age' or skeletal age (SA) for the purpose of estimating or verifying CA has been used in medicolegal contexts for many years and also in youth sport competitions. This article reviews the concept of SA, and the three most commonly used methods of assessment. Variation in SA within CA groups among male soccer players and female artistic gymnasts is evaluated relative to the use of SA as a tool for verification of CA. Corresponding data for athletes in several other sports are also summarized. Among adolescent males, a significant number of athletes will be identified as older than a CA cutoff because of advanced skeletal maturation when they in fact have a valid CA. SA assessments of soccer players are comparable to MRI assessments of epiphyseal-diaphyseal union of the distal radius in under-17 soccer players. Both protocols indicate a relatively large number of false negatives among youth players aged 15-17 years. Among adolescent females, a significant number of age-eligible artistic gymnasts will be identified as younger than the CA cutoff because of later skeletal maturation when in fact they have a valid CA. There is also the possibility of false positives-identifying gymnasts as younger than the CA cutoff because of late skeletal maturation when they have a valid CA. The risk of false negatives and false positives implies that SA is not a valid indicator of CA.

Final Report: Computer-aided Human Centric Cyber Situation Awareness

DTIC Science & Technology

2016-03-20

logs, OS audit trails, vulnerability reports, and packet dumps ), weeding out the false positives, grouping the related indicators so that different...short time duration of each visual stimulus in an fMRI study, we have designed “network security analysis cards ” that require the subject to...determine whether alerts in the cards indicate malicious events. Two types of visual displays of alerts (i.e., tabular display and node-link display) are

An automated framework for NMR resonance assignment through simultaneous slice picking and spin system forming.

PubMed

Abbas, Ahmed; Guo, Xianrong; Jing, Bing-Yi; Gao, Xin

2014-06-01

Despite significant advances in automated nuclear magnetic resonance-based protein structure determination, the high numbers of false positives and false negatives among the peaks selected by fully automated methods remain a problem. These false positives and negatives impair the performance of resonance assignment methods. One of the main reasons for this problem is that the computational research community often considers peak picking and resonance assignment to be two separate problems, whereas spectroscopists use expert knowledge to pick peaks and assign their resonances at the same time. We propose a novel framework that simultaneously conducts slice picking and spin system forming, an essential step in resonance assignment. Our framework then employs a genetic algorithm, directed by both connectivity information and amino acid typing information from the spin systems, to assign the spin systems to residues. The inputs to our framework can be as few as two commonly used spectra, i.e., CBCA(CO)NH and HNCACB. Different from the existing peak picking and resonance assignment methods that treat peaks as the units, our method is based on 'slices', which are one-dimensional vectors in three-dimensional spectra that correspond to certain ([Formula: see text]) values. Experimental results on both benchmark simulated data sets and four real protein data sets demonstrate that our method significantly outperforms the state-of-the-art methods while using a less number of spectra than those methods. Our method is freely available at http://sfb.kaust.edu.sa/Pages/Software.aspx.

Eclipsing Binaries From the CSTAR Project at Dome A, Antarctica

NASA Astrophysics Data System (ADS)

Yang, Ming; Zhang, Hui; Wang, Songhu; Zhou, Ji-Lin; Zhou, Xu; Wang, Lingzhi; Wang, Lifan; Wittenmyer, R. A.; Liu, Hui-Gen; Meng, Zeyang; Ashley, M. C. B.; Storey, J. W. V.; Bayliss, D.; Tinney, Chris; Wang, Ying; Wu, Donghong; Liang, Ensi; Yu, Zhouyi; Fan, Zhou; Feng, Long-Long; Gong, Xuefei; Lawrence, J. S.; Liu, Qiang; Luong-Van, D. M.; Ma, Jun; Wu, Zhenyu; Yan, Jun; Yang, Huigen; Yang, Ji; Yuan, Xiangyan; Zhang, Tianmeng; Zhu, Zhenxi; Zou, Hu

2015-04-01

The Chinese Small Telescope ARray (CSTAR) has observed an area around the Celestial South Pole at Dome A since 2008. About 20,000 light curves in the i band were obtained during the observation season lasting from 2008 March to July. The photometric precision achieves about 4 mmag at i = 7.5 and 20 mmag at i = 12 within a 30 s exposure time. These light curves are analyzed using Lomb-Scargle, Phase Dispersion Minimization, and Box Least Squares methods to search for periodic signals. False positives may appear as a variable signature caused by contaminating stars and the observation mode of CSTAR. Therefore, the period and position of each variable candidate are checked to eliminate false positives. Eclipsing binaries are removed by visual inspection, frequency spectrum analysis, and a locally linear embedding technique. We identify 53 eclipsing binaries in the field of view of CSTAR, containing 24 detached binaries, 8 semi-detached binaries, 18 contact binaries, and 3 ellipsoidal variables. To derive the parameters of these binaries, we use the Eclipsing Binaries via Artificial Intelligence method. The primary and secondary eclipse timing variations (ETVs) for semi-detached and contact systems are analyzed. Correlated primary and secondary ETVs confirmed by false alarm tests may indicate an unseen perturbing companion. Through ETV analysis, we identify two triple systems (CSTAR J084612.64-883342.9 and CSTAR J220502.55-895206.7). The orbital parameters of the third body in CSTAR J220502.55-895206.7 are derived using a simple dynamical model.

Sequence and structural analyses of nuclear export signals in the NESdb database

PubMed Central

Xu, Darui; Farmer, Alicia; Collett, Garen; Grishin, Nick V.; Chook, Yuh Min

2012-01-01

We compiled >200 nuclear export signal (NES)–containing CRM1 cargoes in a database named NESdb. We analyzed the sequences and three-dimensional structures of natural, experimentally identified NESs and of false-positive NESs that were generated from the database in order to identify properties that might distinguish the two groups of sequences. Analyses of amino acid frequencies, sequence logos, and agreement with existing NES consensus sequences revealed strong preferences for the Φ1-X3-Φ2-X2-Φ3-X-Φ4 pattern and for negatively charged amino acids in the nonhydrophobic positions of experimentally identified NESs but not of false positives. Strong preferences against certain hydrophobic amino acids in the hydrophobic positions were also revealed. These findings led to a new and more precise NES consensus. More important, three-dimensional structures are now available for 68 NESs within 56 different cargo proteins. Analyses of these structures showed that experimentally identified NESs are more likely than the false positives to adopt α-helical conformations that transition to loops at their C-termini and more likely to be surface accessible within their protein domains or be present in disordered or unobserved parts of the structures. Such distinguishing features for real NESs might be useful in future NES prediction efforts. Finally, we also tested CRM1-binding of 40 NESs that were found in the 56 structures. We found that 16 of the NES peptides did not bind CRM1, hence illustrating how NESs are easily misidentified. PMID:22833565

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.

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

Plans for Follow-Up Observations of Kepler Planet Candidates

NASA Astrophysics Data System (ADS)

Gautier, Thomas N., III

2009-05-01

Ground based follow-up observations of transiting planet candidates identified by Kepler are pursued to identify false positives and to search for non-transiting planets in the systems of true transiting planets. I will describe the observational protocols developed by the Kepler team and the web based infrastructure we are using to support the observations. The current state of the Kepler follow-up observations will be reported.

How Accurately Can Your Wrist Device Recognize Daily Activities and Detect Falls?

PubMed Central

Gjoreski, Martin; Gjoreski, Hristijan; Luštrek, Mitja; Gams, Matjaž

2016-01-01

Although wearable accelerometers can successfully recognize activities and detect falls, their adoption in real life is low because users do not want to wear additional devices. A possible solution is an accelerometer inside a wrist device/smartwatch. However, wrist placement might perform poorly in terms of accuracy due to frequent random movements of the hand. In this paper we perform a thorough, large-scale evaluation of methods for activity recognition and fall detection on four datasets. On the first two we showed that the left wrist performs better compared to the dominant right one, and also better compared to the elbow and the chest, but worse compared to the ankle, knee and belt. On the third (Opportunity) dataset, our method outperformed the related work, indicating that our feature-preprocessing creates better input data. And finally, on a real-life unlabeled dataset the recognized activities captured the subject’s daily rhythm and activities. Our fall-detection method detected all of the fast falls and minimized the false positives, achieving 85% accuracy on the first dataset. Because the other datasets did not contain fall events, only false positives were evaluated, resulting in 9 for the second, 1 for the third and 15 for the real-life dataset (57 days data). PMID:27258282

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.

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

PubMed

Grandjean, P

2015-12-01

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

What are the core ideas behind the Precautionary Principle?

PubMed

Persson, Erik

2016-07-01

The Precautionary Principle is both celebrated and criticized. It has become an important principle for decision making, but it is also subject to criticism. One problem that is often pointed out with the principle is that is not clear what it actually says and how to use it. I have taken on this problem by performing an analysis of some of the most influential formulations of the principle in an attempt to identify the core ideas behind it, with the purpose of producing a formulation of the principle that is clear and practically applicable. It was found that what is called the Precautionary Principle is not a principle that tells us what do to achieve extra precaution or how to handle situations when extra precaution is called for. Instead, it was found to be a list of circumstances that each justify extra precaution. An analysis of some of the most common and influential formulations of the Precautionary Principle identified four such circumstances: (1) When we deal with important values that tend to be systematically downplayed by traditional decision methods - such as human health and the environment. (2) When we suspect that the decision might lead to irreversible and severe consequences and the values at stake are also irreplaceable, (3) When timing is at least as important as being right. (4) When it is more important to avoid false negatives than false positives. This interpretation of the Precautionary Principle does not say anything about what kind of actions to take when extra precaution is called for, but it does provide a clear and practically useful list of circumstances that call for extra precaution and that is not subject to the most common objections to the Precautionary Principle. Copyright © 2016 Elsevier B.V. All rights reserved.

High-sensitivity, high-selectivity detection of chemical warfare agents

NASA Astrophysics Data System (ADS)

Pushkarsky, Michael B.; Webber, Michael E.; Macdonald, Tyson; Patel, C. Kumar N.

2006-01-01

We report high-sensitivity detection of chemical warfare agents (nerve gases) with very low probability of false positives (PFP). We demonstrate a detection threshold of 1.2ppb (7.7μg/m3 equivalent of Sarin) with a PFP of <1:106 in the presence of many interfering gases present in an urban environment through the detection of diisopropyl methylphosphonate, an accepted relatively harmless surrogate for the nerve agents. For the current measurement time of ˜60s, a PFP of 1:106 corresponds to one false alarm approximately every 23months. The demonstrated performance satisfies most current homeland and military security requirements.

Amplicon-based semiconductor sequencing of human exomes: performance evaluation and optimization strategies.

PubMed

Damiati, E; Borsani, G; Giacopuzzi, Edoardo

2016-05-01

The Ion Proton platform allows to perform whole exome sequencing (WES) at low cost, providing rapid turnaround time and great flexibility. Products for WES on Ion Proton system include the AmpliSeq Exome kit and the recently introduced HiQ sequencing chemistry. Here, we used gold standard variants from GIAB consortium to assess the performances in variants identification, characterize the erroneous calls and develop a filtering strategy to reduce false positives. The AmpliSeq Exome kit captures a large fraction of bases (>94 %) in human CDS, ClinVar genes and ACMG genes, but with 2,041 (7 %), 449 (13 %) and 11 (19 %) genes not fully represented, respectively. Overall, 515 protein coding genes contain hard-to-sequence regions, including 90 genes from ClinVar. Performance in variants detection was maximum at mean coverage >120×, while at 90× and 70× we measured a loss of variants of 3.2 and 4.5 %, respectively. WES using HiQ chemistry showed ~71/97.5 % sensitivity, ~37/2 % FDR and ~0.66/0.98 F1 score for indels and SNPs, respectively. The proposed low, medium or high-stringency filters reduced the amount of false positives by 10.2, 21.2 and 40.4 % for indels and 21.2, 41.9 and 68.2 % for SNP, respectively. Amplicon-based WES on Ion Proton platform using HiQ chemistry emerged as a competitive approach, with improved accuracy in variants identification. False-positive variants remain an issue for the Ion Torrent technology, but our filtering strategy can be applied to reduce erroneous variants.

CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

PubMed Central

Hestand, Matthew S; van Galen, Michiel; Villerius, Michel P; van Ommen, Gert-Jan B; den Dunnen, Johan T; 't Hoen, Peter AC

2008-01-01

Background The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments. Results We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACR database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool. Conclusion The program CORE_TF is accessible in a user friendly web interface at . It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites. PMID:19036135

Automatic Fall Detection System Based on the Combined Use of a Smartphone and a Smartwatch.

PubMed

Casilari, Eduardo; Oviedo-Jiménez, Miguel A

2015-01-01

Due to their widespread popularity, decreasing costs, built-in sensors, computing power and communication capabilities, Android-based personal devices are being seen as an appealing technology for the deployment of wearable fall detection systems. In contrast with previous solutions in the existing literature, which are based on the performance of a single element (a smartphone), this paper proposes and evaluates a fall detection system that benefits from the detection performed by two popular personal devices: a smartphone and a smartwatch (both provided with an embedded accelerometer and a gyroscope). In the proposed architecture, a specific application in each component permanently tracks and analyses the patient's movements. Diverse fall detection algorithms (commonly employed in the literature) were implemented in the developed Android apps to discriminate falls from the conventional activities of daily living of the patient. As a novelty, a fall is only assumed to have occurred if it is simultaneously and independently detected by the two Android devices (which can interact via Bluetooth communication). The system was systematically evaluated in an experimental testbed with actual test subjects simulating a set of falls and conventional movements associated with activities of daily living. The tests were repeated by varying the detection algorithm as well as the pre-defined mobility patterns executed by the subjects (i.e., the typology of the falls and non-fall movements). The proposed system was compared with the cases where only one device (the smartphone or the smartwatch) is considered to recognize and discriminate the falls. The obtained results show that the joint use of the two detection devices clearly increases the system's capability to avoid false alarms or 'false positives' (those conventional movements misidentified as falls) while maintaining the effectiveness of the detection decisions (that is to say, without increasing the ratio of 'false negatives' or actual falls that remain undetected).

Binary Code Extraction and Interface Identification for Security Applications

DTIC Science & Technology

2009-10-02

the functions extracted during the end-to-end applications and at the bottom some additional functions extracted from the OpenSSL library. fact that as...mentioned in Section 5.1 through Section 5.3 and some additional functions that we extract from the OpenSSL library for evaluation purposes. The... OpenSSL functions, the false positives and negatives are measured by comparison with the original C source code. For the malware samples, no source is

Utility of minimal preparation ct colonography in detecting colorectal cancer in elderly and frail patients.

PubMed

Meiklejohn, D J; Ridley, L J; Ngu, M C; Cowlishaw, J L; Duller, A; Ridley, W

2018-06-11

Colorectal cancers result in substantial morbidity and mortality to Australian society each year. The usual investigation for bowel malignancyis optical colonoscopy (OC), withcomputed tomographic colonography (CTC) used as an alternative investigation. The catharsis and colon insufflation associated with these investigations pose a higher risk in the elderly and frail. Risks include perforation, serum electrolyte disturbance, and anaesthesia/sedation risks.Minimal preparation computed tomographic colonography (MPCTC) eliminates these risks. This paper audits a 6-year period ofMPCTC in an Australian tertiary referral hospital. 145 patients underwent MPCTC during the study period. There were 7 true positives, 2 false positives and 2 false negatives. Analysis of this population indicates a sensitivity of 0.78 (95% CI 0.51 - 1.05), specificity of 0.99 (95% CI 0.97 - 1.01), positive predictive value (PPV) of 0.78 (95% CI 0.51 - 1.05) and negative predictive value (NPV) of 0.99 (95% CI 0.97 - 1.01). These findings are concordant with other published studies. The auditconfirmsthatminimal preparation CT colonography is a reasonable alternative to OC and CTC in detecting colorectal cancer in symptomatic elderly and frail patients, without the procedural risks inherent inmore invasive investigations. For most patients MPCTC ruled out significant colorectal carcinoma with a high negative predictive value. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants.

PubMed

Almawazini, Abdulmajid M; Hanafi, Hamdi K; Madkhali, Hasan A; Majrashi, Noura B

2017-10-01

To evaluate the effectiveness of critical congenital heart disease (CCHD) screening program for early diagnosis of cardiac anomalies in newborn infants.  Methods: This is a hospital-based prospective cross-sectional study conducted in the Pediatric and Neonatology Department, King Fahad Hospital at  Albaha, Saudi Arabia, between February 2016 and February 2017. Results: We screened 2961 (95.4%) of 3103 patients in a nursery unit; 142 (4.6%) patients were not screened. The test was positive in 114 (3.9%) patients and negative in 2847 (96.1%). There were 94 (3.2%) false positives and 20 (0.7%) true positives. Critical cardiac defects were diagnosed in 7 (0.2%) patients of all screened infants, and severe pulmonary hypertension was diagnosed in 13 (0.4%) patients. True negative results were found in 2841(96%) patients, and no cardiac defect was diagnosed, whereas false negative results were seen in 6 (0.2%) patients diagnosed with ventricular septal defect. The sensitivity was 77%, and the specificity was very high at 97%, with a positive predictive value of 18%, and a negative predictive value of 99.8% (95% confidence interval 13.78-19.18, p=0.0001). Conclusion: Pulse oximetry was found to be easy, safe, sensitive, and highly specific for diagnosis of CCHD.

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

PubMed Central

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

2009-01-01

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

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).

A new approach for low-cost noninvasive detection of asymptomatic heart disease at rest.

PubMed

DeMarzo, Arthur P; Calvin, James E

2007-01-01

It would be useful to have an inexpensive, noninvasive point-of-care test for early detection of asymptomatic heart disease. This study used impedance cardiography (ICG) in a new way to assess heart function that did not use stroke volume or cardiac output. There is a model of the ICG dZ/dt waveform that may be used as a template to represent normal heart function. The hypothesis was that a dZ/dt waveform which deviates from that template should indicate heart dysfunction and therefore heart disease. The objective was to assess the accuracy of this new ICG approach, using echocardiography as the standard. Thirty-four outpatients undergoing echocardiographic testing were tested by ICG while sitting upright and supine. All patients had no symptoms or history of a structural or functional heart disorder. Echocardiographic testing showed 17 patients with abnormalities and 17 as normal. ICG testing yielded 16 true positives for heart dysfunction with 1 false negative (sensitivity = 94%) and 17 true negatives with no false positives (specificity = 100%). Considering that the cost, technical skill, and time required for this ICG test are comparable to those of an electrocardiograph, this new approach has potential as a point-of-care screening test for asymptomatic heart disease.

Lorazepam induces multiple disturbances in selective attention: attentional overload, decrement in target processing efficiency, and shifts in perceptual discrimination and response bias.

PubMed

Michael, George Andrew; Bacon, Elisabeth; Offerlin-Meyer, Isabelle

2007-09-01

There is a general consensus that benzodiazepines affect attentional processes, yet only few studies have tried to investigate these impairments in detail. The purpose of the present study was to investigate the effects of a single dose of Lorazepam on performance in a target cancellation task with important time constraints. We measured correct target detections and correct distractor rejections, misses and false positives. The results show that Lorazepam produces multiple kinds of shifts in performance, which suggests that it impairs multipLe processes: (a) the evolution of performance over time was not the same between the placebo and the Lorazepam groups, with the Lorazepam affecting performance quite early after the beginning of the test. This is suggestive of a depletion of attentional resources during sequential attentional processing; (b) Lorazepam affected differently target and distractor processing, with target detection being the most impaired; (c) misses were more frequent under Lorazepam than under placebo, but no such difference was observed as far as false positives were concerned. Signal detection analyses showed that Lorazepam (d) decreased perceptual discrimination, and (e) reliably increased response bias. Our results bring new insights on the multiple effects of Lorazepam on selective attention which, when combined, may have deleterious effects on human performance.

Performance of species occurrence estimators when basic assumptions are not met: a test using field data where true occupancy status is known

USGS Publications Warehouse

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

2015-01-01

Our results demonstrate that even small probabilities of misidentification and among-site detection heterogeneity can have severe effects on estimator reliability if ignored. We challenge researchers to place greater attention on both heterogeneity and false positives when designing and analysing occupancy studies. We provide 9 specific recommendations for the design, implementation and analysis of occupancy studies to better meet this challenge.

Basic Research at the University of Washington to Counter Improvised Explosive Devices

DTIC Science & Technology

2011-01-31

elements and fluorescent sensor elements can be co-located on the fiber. Having sensors with different sensing mechanisms would help reduce false...detection positives. The results of this research have been published in several peer-reviewed journal papers and a book chapter, and presented at a...project is to understand the fundamental mechanisms of the sensing properties of the semiconducting metal oxide nanowires in order to further improve

Evaluation of a system for automatic detection of diabetic retinopathy from color fundus photographs in a large population of patients with diabetes.

PubMed

Abràmoff, Michael D; Niemeijer, Meindert; Suttorp-Schulten, Maria S A; Viergever, Max A; Russell, Stephen R; van Ginneken, Bram

2008-02-01

To evaluate the performance of a system for automated detection of diabetic retinopathy in digital retinal photographs, built from published algorithms, in a large, representative, screening population. We conducted a retrospective analysis of 10,000 consecutive patient visits, specifically exams (four retinal photographs, two left and two right) from 5,692 unique patients from the EyeCheck diabetic retinopathy screening project imaged with three types of cameras at 10 centers. Inclusion criteria included no previous diagnosis of diabetic retinopathy, no previous visit to ophthalmologist for dilated eye exam, and both eyes photographed. One of three retinal specialists evaluated each exam as unacceptable quality, no referable retinopathy, or referable retinopathy. We then selected exams with sufficient image quality and determined presence or absence of referable retinopathy. Outcome measures included area under the receiver operating characteristic curve (number needed to miss one case [NNM]) and type of false negative. Total area under the receiver operating characteristic curve was 0.84, and NNM was 80 at a sensitivity of 0.84 and a specificity of 0.64. At this point, 7,689 of 10,000 exams had sufficient image quality, 4,648 of 7,689 (60%) were true negatives, 59 of 7,689 (0.8%) were false negatives, 319 of 7,689 (4%) were true positives, and 2,581 of 7,689 (33%) were false positives. Twenty-seven percent of false negatives contained large hemorrhages and/or neovascularizations. Automated detection of diabetic retinopathy using published algorithms cannot yet be recommended for clinical practice. However, performance is such that evaluation on validated, publicly available datasets should be pursued. If algorithms can be improved, such a system may in the future lead to improved prevention of blindness and vision loss in patients with diabetes.

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

NASA Technical Reports Server (NTRS)

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

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

PubMed

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

2018-04-20

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

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

PubMed

Zyout, Imad; Czajkowska, Joanna; Grzegorzek, Marcin

2015-12-01

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

Genetic Factors that Affect Tumorigenesis in NF1

DTIC Science & Technology

2004-11-01

Genetica Medica, Universita di Padova, Padova, Italy, 4Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14... conditions as described. We do not know the frequency of false results in a 1.5 Mb rearrangement, yet the NF1REP is over positives nor how it might be...affected by minor alterations in twice the length of the CMT1A-REP. Both rearrangements assay conditions . It is possible that this recombination is a low

Science of Cyber-Security

DTIC Science & Technology

2010-11-01

that a program is bug free. Also, and this is an important issue in getting people 29 to use them, static checkers tend to have false positives...enormous variety of non-standard dialects took a huge amount of work to get what they describe as full version-specific bug compatibility.) Model...coincident detection by T-cells. In- cidentally, this is why it is enough to get rid of T-cells that bind self-peptides without similarly culling B-cells

In-111 WBC imaging in musculoskeletal sepsis

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

Thompson, L.; Ouzounian, T.J.; Webber, M.M.

This study evaluated the accuracy and utility of the In-111 labeled WBC imaging in a series of patients who were suspected of having musculoskeletal sepsis. The labeling of the WBCs was patterned after a method previously described, in which the WBCs are labeled with In-111 oxine in plasma. The WBCs from 100 ml of blood are separated and incubated with In-111 oxine complex, and then 500 ..mu..Ci. of the labeled cells were reinjected into the patient. Images of the areas in question were obtained at 24 hrs. In some instances, 48 hour images were also obtained. Images were interpreted usingmore » consistent criteria. Forty imaging procedures were done on 39 patients. These included 39 total joint protheses, and 17 other images to evaluate possible osteomyelitis, septic arthritis or deep abscesses. Of these studies, 15 were positive, and 42 negative. The findings were then correlated with operative culture and pathology in 21, aspiration cultures and gram stains in 14, and with clinical findings in the remaining 21. This correlation showed 41 true negatives, 12 true positives, 1 false negative, and 2 false positives. The sensitivity was 92.9% and the specificity was 95.2%l. The false negative occurred in a patient on chronic suppressive antibiotic therapy for an infected total hip replacement. The false positive images occurred in a patient with active rheumatoid arthritis and in a patient imaged one month post operative placement of the prosthesis. These images were very useful in several septic patients who had many possible sites of infection. The authors conclude that In-III imaging is an accurate and useful non-invasive method of evaluating musculoskeletal sepsis.« less

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

Identifying seizure clusters in patients with epilepsy

PubMed Central

Lipton, R. B.; LeValley, A. J.; Hall, C. B.; Shinnar, S.

2006-01-01

Clinicians often encounter patients whose neurologic attacks appear to cluster. In a daily diary study, the authors explored whether clustering is a true phenomenon in epilepsy and can be identified in the clinical setting. Nearly half the subjects experienced at least one episode of three or more seizures in 24 hours; 20% also met a statistical clustering criterion. Utilizing the clinical definition of clustering should identify all seizure clusterers, and false positives can be determined with diary data. PMID:16247068

Statistical evaluation of synchronous spike patterns extracted by frequent item set mining

PubMed Central

Torre, Emiliano; Picado-Muiño, David; Denker, Michael; Borgelt, Christian; Grün, Sonja

2013-01-01

We recently proposed frequent itemset mining (FIM) as a method to perform an optimized search for patterns of synchronous spikes (item sets) in massively parallel spike trains. This search outputs the occurrence count (support) of individual patterns that are not trivially explained by the counts of any superset (closed frequent item sets). The number of patterns found by FIM makes direct statistical tests infeasible due to severe multiple testing. To overcome this issue, we proposed to test the significance not of individual patterns, but instead of their signatures, defined as the pairs of pattern size z and support c. Here, we derive in detail a statistical test for the significance of the signatures under the null hypothesis of full independence (pattern spectrum filtering, PSF) by means of surrogate data. As a result, injected spike patterns that mimic assembly activity are well detected, yielding a low false negative rate. However, this approach is prone to additionally classify patterns resulting from chance overlap of real assembly activity and background spiking as significant. These patterns represent false positives with respect to the null hypothesis of having one assembly of given signature embedded in otherwise independent spiking activity. We propose the additional method of pattern set reduction (PSR) to remove these false positives by conditional filtering. By employing stochastic simulations of parallel spike trains with correlated activity in form of injected spike synchrony in subsets of the neurons, we demonstrate for a range of parameter settings that the analysis scheme composed of FIM, PSF and PSR allows to reliably detect active assemblies in massively parallel spike trains. PMID:24167487

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

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.

Observer performance in semi-automated microbleed detection

NASA Astrophysics Data System (ADS)

Kuijf, Hugo J.; Brundel, Manon; de Bresser, Jeroen; Viergever, Max A.; Biessels, Geert Jan; Geerlings, Mirjam I.; Vincken, Koen L.

2013-03-01

Cerebral microbleeds are small bleedings in the human brain, detectable with MRI. Microbleeds are associated with vascular disease and dementia. The number of studies involving microbleed detection is increasing rapidly. Visual rating is the current standard for detection, but is a time-consuming process, especially at high-resolution 7.0 T MR images, has limited reproducibility and is highly observer dependent. Recently, multiple techniques have been published for the semi-automated detection of microbleeds, attempting to overcome these problems. In the present study, a 7.0 T dual-echo gradient echo MR image was acquired in 18 participants with microbleeds from the SMART study. Two experienced observers identified 54 microbleeds in these participants, using a validated visual rating scale. The radial symmetry transform (RST) can be used for semi-automated detection of microbleeds in 7.0 T MR images. In the present study, the results of the RST were assessed by two observers and 47 microbleeds were identified: 35 true positives and 12 extra positives (microbleeds that were missed during visual rating). Hence, after scoring a total number of 66 microbleeds could be identified in the 18 participants. The use of the RST increased the average sensitivity of observers from 59% to 69%. More importantly, inter-observer agreement (ICC and Dice's coefficient) increased from 0.85 and 0.64 to 0.98 and 0.96, respectively. Furthermore, the required rating time was reduced from 30 to 2 minutes per participant. By fine-tuning the RST, sensitivities up to 90% can be achieved, at the cost of extra false positives.

Cancer diagnostics using neural network sorting of processed images

NASA Astrophysics Data System (ADS)

Wyman, Charles L.; Schreeder, Marshall; Grundy, Walt; Kinser, Jason M.

1996-03-01

A combination of image processing with neural network sorting was conducted to demonstrate feasibility of automated cervical smear screening. Nuclei were isolated to generate a series of data points relating to the density and size of individual nuclei. This was followed by segmentation to isolate entire cells for subsequent generation of data points to bound the size of the cytoplasm. Data points were taken on as many as ten cells per image frame and included correlation against a series of filters providing size and density readings on nuclei. Additional point data was taken on nuclei images to refine size information and on whole cells to bound the size of the cytoplasm, twenty data points per assessed cell were generated. These data point sets, designated as neural tensors, comprise the inputs for training and use of a unique neural network to sort the images and identify those indicating evidence of disease. The neural network, named the Fast Analog Associative Memory, accumulates data and establishes lookup tables for comparison against images to be assessed. Six networks were trained to differentiate normal cells from those evidencing various levels abnormality that may lead to cancer. A blind test was conducted on 77 images to evaluate system performance. The image set included 31 positives (diseased) and 46 negatives (normal). Our system correctly identified all 31 positives and 41 of the negatives with 5 false positives. We believe this technology can lead to more efficient automated screening of cervical smears.

Early Detection of Breast Cancer via Multi-plane Correlation Breast Imaging

DTIC Science & Technology

2008-04-01

pathology that the radiologists are looking for, leading to high rate of false positives. An imaging technique which may alleviate the limiting factor of...received on 07/24/06. Five mastectomy specimens were subsequently obtained from the pathology laboratory at the Duke hospital and imaged for this... pathology , thus providing a 2D contour map of the possible locations of the lesion. To evaluate the performance of MCI, the 2D contour map was compared

25 CFR 11.438 - Flight to avoid prosecution or judicial process.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Flight to avoid prosecution or judicial process. 11.438... OFFENSES AND LAW AND ORDER CODE Criminal Offenses § 11.438 Flight to avoid prosecution or judicial process... Offenses exercises jurisdiction for the purpose of avoiding arrest, prosecution or other judicial process...

Sensitivity and specificity of intrathecal fluorescein and white light excitation for detecting intraoperative cerebrospinal fluid leak in endoscopic skull base surgery: a prospective study.

PubMed

Raza, Shaan M; Banu, Matei A; Donaldson, Angela; Patel, Kunal S; Anand, Vijay K; Schwartz, Theodore H

2016-03-01

The intraoperative detection of CSF leaks during endonasal endoscopic skull base surgery is critical to preventing postoperative CSF leaks. Intrathecal fluorescein (ITF) has been used at varying doses to aid in the detection of intraoperative CSF leaks. However, the sensitivity and specificity of ITF at certain dosages is unknown. A prospective database of all endoscopic endonasal procedures was reviewed. All patients received 25 mg ITF diluted in 10 ml CSF and were pretreated with dexamethasone and Benadryl. Immediately after surgery, the operating surgeon prospectively noted if there was an intraoperative CSF leak and fluorescein was identified. The sensitivity, specificity, and positive and negative predictive power of ITF for detecting intraoperative CSF leak were calculated. Factors correlating with postoperative CSF leak were determined. Of 419 patients, 35.8% of patients did not show a CSF leak. Fluorescein-tinted CSF (true positive) was noted in 59.7% of patients and 0 false positives were encountered. CSF without fluorescein staining (false negative) was noted in 4.5% of patients. The sensitivity and specificity of ITF were 92.9% and 100%, respectively. The negative and positive predictive values were 88.8% and 100%, respectively. Postoperative CSF leaks only occurred in true positives at a rate of 2.8%. ITF is extremely specific and very sensitive for detecting intraoperative CSF leaks. Although false negatives can occur, these patients do not appear to be at risk for postoperative CSF leak. The use of ITF may help surgeons prevent postoperative CSF leaks by intraoperatively detecting and confirming a watertight repair.

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.

HacDivSel: Two new methods (haplotype-based and outlier-based) for the detection of divergent selection in pairs of populations

PubMed Central

2017-01-01

The detection of genomic regions involved in local adaptation is an important topic in current population genetics. There are several detection strategies available depending on the kind of genetic and demographic information at hand. A common drawback is the high risk of false positives. In this study we introduce two complementary methods for the detection of divergent selection from populations connected by migration. Both methods have been developed with the aim of being robust to false positives. The first method combines haplotype information with inter-population differentiation (FST). Evidence of divergent selection is concluded only when both the haplotype pattern and the FST value support it. The second method is developed for independently segregating markers i.e. there is no haplotype information. In this case, the power to detect selection is attained by developing a new outlier test based on detecting a bimodal distribution. The test computes the FST outliers and then assumes that those of interest would have a different mode. We demonstrate the utility of the two methods through simulations and the analysis of real data. The simulation results showed power ranging from 60–95% in several of the scenarios whilst the false positive rate was controlled below the nominal level. The analysis of real samples consisted of phased data from the HapMap project and unphased data from intertidal marine snail ecotypes. The results illustrate that the proposed methods could be useful for detecting locally adapted polymorphisms. The software HacDivSel implements the methods explained in this manuscript. PMID:28423003

FDG-PET/CT can rule out malignancy in patients with vocal cord palsy.

PubMed

Thomassen, Anders; Nielsen, Anne Lerberg; Lauridsen, Jeppe Kiilerich; Blomberg, Björn Alexander; Hess, Søren; Petersen, Henrik; Johansen, Allan; Asmussen, Jon Thor; Sørensen, Jesper Roed; Johansen, Jørgen; Godballe, Christian; Høilund-Carlsen, Poul Flemming

2014-01-01

The aim was to investigate the performance of (18)F-fluorodeoxyglucose PET/CT to rule out malignancy in patients with confirmed vocal cord palsy (VCP). Between January 2011 and June 2013, we retrospectively included consecutive patients referred to PET/CT with paresis or paralysis of one or both vocal cords. PET/CT results were compared to clinical workup and histopathology. The study comprised 65 patients (32 females) with a mean age of 66±12 years (range 37-89). Eleven patients (17%) had antecedent cancer. Twenty-seven (42%) were diagnosed with cancer during follow-up. The palsy was right-sided in 24 patients, left-sided in 37, and bilateral in 4. Median follow-up was 7 months (interquartile range 4-11 months). Patients without cancer were followed for at least three months. PET/CT suggested a malignancy in 35 patients (27 true positives, 8 false positives) and showed none in 30 (30 true negatives, 0 false negatives). Thus, the sensitivity, specificity, positive and negative predictive values, and accuracy were (95% confidence intervals in parenthesis): 100% (88%-100%), 79% (64%-89%), 77% (61%-88%), 100% (89%-100%), and 88% (78%-94%), respectively. Sixteen patients had palliative treatment, while 11 were treated with curative intent, emphasising the severity of VCP and the need for a rapid and accurate diagnostic work-up. In this retrospective survey, biopsy proven malignancy (whether newly diagnosed or relapsed) was the cause of VCP in almost half of patients (42%). PET/CT had a high sensitivity (100%) with a relatively high false positive rate, but was excellent in ruling out malignancy (negative predictive value 100%).

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

PubMed Central

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

1993-01-01

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

Metabarcoding for the parallel identification of several hundred predators and their prey: Application to bat species diet analysis.

PubMed

Galan, Maxime; Pons, Jean-Baptiste; Tournayre, Orianne; Pierre, Éric; Leuchtmann, Maxime; Pontier, Dominique; Charbonnel, Nathalie

2018-05-01

Assessing diet variability is of main importance to better understand the biology of bats and design conservation strategies. Although the advent of metabarcoding has facilitated such analyses, this approach does not come without challenges. Biases may occur throughout the whole experiment, from fieldwork to biostatistics, resulting in the detection of false negatives, false positives or low taxonomic resolution. We detail a rigorous metabarcoding approach based on a short COI minibarcode and two-step PCR protocol enabling the "all at once" taxonomic identification of bats and their arthropod prey for several hundreds of samples. Our study includes faecal pellets collected in France from 357 bats representing 16 species, as well as insect mock communities that mimic bat meals of known composition, negative and positive controls. All samples were analysed using three replicates. We compare the efficiency of DNA extraction methods, and we evaluate the effectiveness of our protocol using identification success, taxonomic resolution, sensitivity and amplification biases. Our parallel identification strategy of predators and prey reduces the risk of mis-assigning prey to wrong predators and decreases the number of molecular steps. Controls and replicates enable to filter the data and limit the risk of false positives, hence guaranteeing high confidence results for both prey occurrence and bat species identification. We validate 551 COI variants from arthropod including 18 orders, 117 family, 282 genus and 290 species. Our method therefore provides a rapid, resolutive and cost-effective screening tool for addressing evolutionary ecological issues or developing "chirosurveillance" and conservation strategies. © 2017 John Wiley & Sons Ltd.

Resampling-Based Empirical Bayes Multiple Testing Procedures for Controlling Generalized Tail Probability and Expected Value Error Rates: Focus on the False Discovery Rate and Simulation Study

PubMed Central

Dudoit, Sandrine; Gilbert, Houston N.; van der Laan, Mark J.

2014-01-01

Summary This article proposes resampling-based empirical Bayes multiple testing procedures for controlling a broad class of Type I error rates, defined as generalized tail probability (gTP) error rates, gTP(q, g) = Pr(g(Vn, Sn) > q), and generalized expected value (gEV) error rates, gEV(g) = E[g(Vn, Sn)], for arbitrary functions g(Vn, Sn) of the numbers of false positives Vn and true positives Sn. Of particular interest are error rates based on the proportion g(Vn, Sn) = Vn/(Vn + Sn) of Type I errors among the rejected hypotheses, such as the false discovery rate (FDR), FDR = E[Vn/(Vn + Sn)]. The proposed procedures offer several advantages over existing methods. They provide Type I error control for general data generating distributions, with arbitrary dependence structures among variables. Gains in power are achieved by deriving rejection regions based on guessed sets of true null hypotheses and null test statistics randomly sampled from joint distributions that account for the dependence structure of the data. The Type I error and power properties of an FDR-controlling version of the resampling-based empirical Bayes approach are investigated and compared to those of widely-used FDR-controlling linear step-up procedures in a simulation study. The Type I error and power trade-off achieved by the empirical Bayes procedures under a variety of testing scenarios allows this approach to be competitive with or outperform the Storey and Tibshirani (2003) linear step-up procedure, as an alternative to the classical Benjamini and Hochberg (1995) procedure. PMID:18932138

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

Comparison of Positron Emission Tomography Scanning and Sentinel Node Biopsy in the Detection of Inguinal Node Metastases in Patients With Anal Cancer

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

Mistrangelo, Massimiliano, E-mail: mistrangelo@katamail.co; Centre of Minimally Invasive Surgery, University of Turin; Pelosi, Ettore

2010-05-01

Background: Inguinal lymph node metastases in patients with anal cancer are an independent prognostic factor for local failure and overall mortality. Inguinal lymph node status can be adequately assessed with sentinel node biopsy, and the radiotherapy strategy can subsequently be changed. We compared this technique vs. dedicated 18F-fluorodeoxyglucose positron emission tomography (PET) to determine which was the better tool for staging inguinal lymph nodes. Methods and Materials: In our department, 27 patients (9 men and 18 women) underwent both inguinal sentinel node biopsy and PET-CT. PET-CT was performed before treatment and then at 1 and 3 months after treatment. Results:more » PET-CT scans detected no inguinal metastases in 20 of 27 patients and metastases in the remaining 7. Histologic analysis of the sentinel lymph node detected metastases in only three patients (four PET-CT false positives). HIV status was not found to influence the results. None of the patients negative at sentinel node biopsy developed metastases during the follow-up period. PET-CT had a sensitivity of 100%, with a negative predictive value of 100%. Owing to the high number of false positives, PET-CT specificity was 83%, and positive predictive value was 43%. Conclusions: In this series of patients with anal cancer, inguinal sentinel node biopsy was superior to PET-CT for staging inguinal lymph nodes.« less

High-sensitivity high-selectivity detection of CWAs and TICs using tunable laser photoacoustic spectroscopy

NASA Astrophysics Data System (ADS)

Pushkarsky, Michael; Webber, Michael; Patel, C. Kumar N.

2005-03-01

We provide a general technique for evaluating the performance of an optical sensor for the detection of chemical warfare agents (CWAs) in realistic environments and present data from a simulation model based on a field deployed discretely tunable 13CO2 laser photoacoustic spectrometer (L-PAS). Results of our calculations show the sensor performance in terms of usable sensor sensitivity as a function of probability of false positives (PFP). The false positives arise from the presence of many other gases in the ambient air that could be interferents. Using the L-PAS as it exists today, we can achieve a detection threshold of about 4 ppb for the CWAs while maintaining a PFP of less than 1:106. Our simulation permits us to vary a number of parameters in the model to provide guidance for performance improvement. We find that by using a larger density of laser lines (such as those obtained through the use of tunable semiconductor lasers), improving the detector noise and maintaining the accuracy of laser frequency determination, optical detection schemes can make possible CWA sensors having sub-ppb detection capability with <1:108 PFP. We also describe the results of a preliminary experiment that verifies the results of the simulation model. Finally, we discuss the use of continuously tunable quantum cascade lasers in L-PAS for CWA and TIC detection.

Comprehensive benchmarking and ensemble approaches for metagenomic classifiers.

PubMed

McIntyre, Alexa B R; Ounit, Rachid; Afshinnekoo, Ebrahim; Prill, Robert J; Hénaff, Elizabeth; Alexander, Noah; Minot, Samuel S; Danko, David; Foox, Jonathan; Ahsanuddin, Sofia; Tighe, Scott; Hasan, Nur A; Subramanian, Poorani; Moffat, Kelly; Levy, Shawn; Lonardi, Stefano; Greenfield, Nick; Colwell, Rita R; Rosen, Gail L; Mason, Christopher E

2017-09-21

One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited. In this study, we use the largest-to-date set of laboratory-generated and simulated controls across 846 species to evaluate the performance of 11 metagenomic classifiers. Tools were characterized on the basis of their ability to identify taxa at the genus, species, and strain levels, quantify relative abundances of taxa, and classify individual reads to the species level. Strikingly, the number of species identified by the 11 tools can differ by over three orders of magnitude on the same datasets. Various strategies can ameliorate taxonomic misclassification, including abundance filtering, ensemble approaches, and tool intersection. Nevertheless, these strategies were often insufficient to completely eliminate false positives from environmental samples, which are especially important where they concern medically relevant species. Overall, pairing tools with different classification strategies (k-mer, alignment, marker) can combine their respective advantages. This study provides positive and negative controls, titrated standards, and a guide for selecting tools for metagenomic analyses by comparing ranges of precision, accuracy, and recall. We show that proper experimental design and analysis parameters can reduce false positives, provide greater resolution of species in complex metagenomic samples, and improve the interpretation of results.

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.

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.

[Child psychiatric assessment and the debate regarding the abuse of abuse].

PubMed

Fegert, J M

1995-03-01

The current discussion on false allegations in sexual abuse cases has led to a polarization in the views expressed about the credibility of children. Some authors even speak of a "child sexual accuse syndrome" or of a "sexual abuse allegation in divorce" (SAID) syndrome. A phenomenological analysis of the multiple reasons for misinterpretations is presented. Instead of stressing the importance only of false positives in child sexual abuse questions, an attempt is made to describe reasons for false negatives. Based on a retrospective analysis of 50 consecutive child psychiatric experts in connection with court cases, there does not appear to be an increase in false accusations. Rather, only about one third of the cases even involved suspected sexual abuse. Sexual abuse allegations were much more frequent in girls than in boys. Of 20 abuse allegations we judge four to be false allegations. In only one of these cases, that of an adolescent girl who had been abused in childhood, was the false allegation intended.

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

Ultra-deep sequencing enables high-fidelity recovery of biodiversity for bulk arthropod samples without PCR amplification

PubMed Central

2013-01-01

Background Next-generation-sequencing (NGS) technologies combined with a classic DNA barcoding approach have enabled fast and credible measurement for biodiversity of mixed environmental samples. However, the PCR amplification involved in nearly all existing NGS protocols inevitably introduces taxonomic biases. In the present study, we developed new Illumina pipelines without PCR amplifications to analyze terrestrial arthropod communities. Results Mitochondrial enrichment directly followed by Illumina shotgun sequencing, at an ultra-high sequence volume, enabled the recovery of Cytochrome c Oxidase subunit 1 (COI) barcode sequences, which allowed for the estimation of species composition at high fidelity for a terrestrial insect community. With 15.5 Gbp Illumina data, approximately 97% and 92% were detected out of the 37 input Operational Taxonomic Units (OTUs), whether the reference barcode library was used or not, respectively, while only 1 novel OTU was found for the latter. Additionally, relatively strong correlation between the sequencing volume and the total biomass was observed for species from the bulk sample, suggesting a potential solution to reveal relative abundance. Conclusions The ability of the new Illumina PCR-free pipeline for DNA metabarcoding to detect small arthropod specimens and its tendency to avoid most, if not all, false positives suggests its great potential in biodiversity-related surveillance, such as in biomonitoring programs. However, further improvement for mitochondrial enrichment is likely needed for the application of the new pipeline in analyzing arthropod communities at higher diversity. PMID:23587339

SNaPshot and StripAssay as Valuable Alternatives to Direct Sequencing for KRAS Mutation Detection in Colon Cancer Routine Diagnostics

PubMed Central

Fariña Sarasqueta, Arantza; Moerland, Elna; de Bruyne, Hanneke; de Graaf, Henk; Vrancken, Tamara; van Lijnschoten, Gesina; van den Brule, Adriaan J.C.

2011-01-01

Although direct sequencing is the gold standard for KRAS mutation detection in routine diagnostics, it remains laborious, time consuming, and not very sensitive. Our objective was to evaluate SNaPshot and the KRAS StripAssay as alternatives to sequencing for KRAS mutation detection in daily practice. KRAS exon 2–specific PCR followed by sequencing or by a SNaPshot reaction was performed. For the StripAssay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. To test sensitivities, dilution series of mutated DNA in wild-type DNA were made. Additionally, direct sequencing and SNaPshot were evaluated in 296 colon cancer samples. Detection limits of direct sequencing, SNaPshot, and StripAssay were 20%, 10%, and 1% tumor cells, respectively. Direct sequencing and SNaPshot can detect all 12 mutations in KRAS codons 12 and 13, whereas the StripAssay detects 10 of the most frequent ones. Workload and time to results are comparable for SNaPshot and direct sequencing. SNaPshot is flexible and easy to multiplex. The StripAssay is less time consuming for daily laboratory practice. SNaPshot is more flexible and slightly more sensitive than direct sequencing. The clinical evaluation showed comparable performances between direct sequencing and SNaPshot. The StripAssay is rapid and an extremely sensitive assay that could be considered when few tumor cells are available. However, found mutants should be confirmed to avoid risk of false positives. PMID:21354055

Detection of human papillomavirus 16, 18, and 45 in women with ASC-US cytology and the risk of cervical precancer: results from the CLEAR HPV study.

PubMed

Castle, Phillip E; Cuzick, Jack; Stoler, Mark H; Wright, Thomas C; Reid, Jennifer L; Dockter, Janel; Giachetti, Cristina; Getman, Damon

2015-02-01

The Aptima human papillomavirus (HPV) 16 18/45 Genotype (GT) assay (AHPV-GT) is a qualitative E6/ E7 oncogene messenger RNA test that detects HPV 16 and a pool of HPV 18 and 45. The CLEAR (Clinical Evaluation of APTIMA mRNA) study was the pivotal, prospective, multicenter US clinical study to validate the Aptima HPV (AHPV) assays. In this analysis, we evaluated the clinical performance of AHPV and AHPV-GT assays for detection of cervical intraepithelial neoplasia grade 2 or more severe (CIN2 +) and grade 3 (CIN3) or adenocarcinoma in situ in 912 women with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou result. The AHPV-GT assay was performed on high-risk HPV (hrHPV) positives as determined by the AHPV assay. Overall, the percent positive for hrHPV was 38.8% (354/912), of which 34.2% (121/354) were GT positive. Among hrHPV-positive women, the risks of CIN2 + were 37.0% for HPV 16 positives, 15.9% for HPV 18/45 positives, 14.3% for other hrHPV positives, and 2.2% for AHPV negatives. The risks of CIN3 + were 20.5% for HPV 16 positives, 9.1% for HPV 18/45 positives, 4.3% for other hrHPV positives, and 0.7% for HPV negatives. We demonstrated that AHPV-GT is a reliable and effective test for cervical cancer risk stratification in women with an ASC-US cytology diagnosis. Copyright© by the American Society for Clinical Pathology.

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.

Breast mass detection in tomosynthesis projection images using information-theoretic similarity measures

NASA Astrophysics Data System (ADS)

Singh, Swatee; Tourassi, Georgia D.; Lo, Joseph Y.

2007-03-01

The purpose of this project is to study Computer Aided Detection (CADe) of breast masses for digital tomosynthesis. It is believed that tomosynthesis will show improvement over conventional mammography in detection and characterization of breast masses by removing overlapping dense fibroglandular tissue. This study used the 60 human subject cases collected as part of on-going clinical trials at Duke University. Raw projections images were used to identify suspicious regions in the algorithm's high-sensitivity, low-specificity stage using a Difference of Gaussian (DoG) filter. The filtered images were thresholded to yield initial CADe hits that were then shifted and added to yield a 3D distribution of suspicious regions. These were further summed in the depth direction to yield a flattened probability map of suspicious hits for ease of scoring. To reduce false positives, we developed an algorithm based on information theory where similarity metrics were calculated using knowledge databases consisting of tomosynthesis regions of interest (ROIs) obtained from projection images. We evaluated 5 similarity metrics to test the false positive reduction performance of our algorithm, specifically joint entropy, mutual information, Jensen difference divergence, symmetric Kullback-Liebler divergence, and conditional entropy. The best performance was achieved using the joint entropy similarity metric, resulting in ROC A z of 0.87 +/- 0.01. As a whole, the CADe system can detect breast masses in this data set with 79% sensitivity and 6.8 false positives per scan. In comparison, the original radiologists performed with only 65% sensitivity when using mammography alone, and 91% sensitivity when using tomosynthesis alone.

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.

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.

Facing the problem of "false positives": re-assessment and improvement of a multiplex RT-PCR procedure for the diagnosis of A. flavus mycotoxin producers.

PubMed

Degola, F; Berni, E; Spotti, E; Ferrero, I; Restivo, F M

2009-02-28

The aim of our research project was to consolidate a multiplex RT-PCR protocol to detect aflatoxigenic strains of Aspergillus flavus. Several independent A. flavus strains were isolated from corn and flour samples from the North of Italy and from three European countries. Aflatoxin producing/not producing phenotype was assessed by qualitative and quantitative assays at day five of growth in aflatoxin inducing conditions. Expression of 16 genes belonging to the aflatoxin cluster was assayed by multiplex or monomeric RT-PCR. There is a good correlation between gene expression and aflatoxin production. Strains that apparently transcribed all the relevant genes but did not release aflatoxin in the medium ("false positives") were re-assessed for mycotoxin production after extended growth in inducing condition. All the "false positive" strains in actual fact were positive when aflatoxin determination was performed after 10 days of growth. These strains should then be re-classified as "slow aflatoxin accumulators". To optimise the diagnostic procedure, a quintuplex RT-PCR procedure was designed consisting of a primer set directed against four informative aflatoxin cluster genes and the beta-tubulin gene as an internal amplification control. In conclusion we have provided evidence for the robustness and reliability of our RT-PCR protocol in discriminating mycotoxin producer from non-producer strains of A. flavus. and the molecular procedure we devised is a promising tool with which to screen and control the endemic population of A. flavus colonising different areas of the World.

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.

Recent human evolution has shaped geographical differences in susceptibility to disease

PubMed Central

2011-01-01

Background Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. Results We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations. PMID:21261943

False discovery rates in spectral identification.

PubMed

Jeong, Kyowon; Kim, Sangtae; Bandeira, Nuno

2012-01-01

Automated database search engines are one of the fundamental engines of high-throughput proteomics enabling daily identifications of hundreds of thousands of peptides and proteins from tandem mass (MS/MS) spectrometry data. Nevertheless, this automation also makes it humanly impossible to manually validate the vast lists of resulting identifications from such high-throughput searches. This challenge is usually addressed by using a Target-Decoy Approach (TDA) to impose an empirical False Discovery Rate (FDR) at a pre-determined threshold x% with the expectation that at most x% of the returned identifications would be false positives. But despite the fundamental importance of FDR estimates in ensuring the utility of large lists of identifications, there is surprisingly little consensus on exactly how TDA should be applied to minimize the chances of biased FDR estimates. In fact, since less rigorous TDA/FDR estimates tend to result in more identifications (at higher 'true' FDR), there is often little incentive to enforce strict TDA/FDR procedures in studies where the major metric of success is the size of the list of identifications and there are no follow up studies imposing hard cost constraints on the number of reported false positives. Here we address the problem of the accuracy of TDA estimates of empirical FDR. Using MS/MS spectra from samples where we were able to define a factual FDR estimator of 'true' FDR we evaluate several popular variants of the TDA procedure in a variety of database search contexts. We show that the fraction of false identifications can sometimes be over 10× higher than reported and may be unavoidably high for certain types of searches. In addition, we further report that the two-pass search strategy seems the most promising database search strategy. While unavoidably constrained by the particulars of any specific evaluation dataset, our observations support a series of recommendations towards maximizing the number of resulting identifications while controlling database searches with robust and reproducible TDA estimation of empirical FDR.

Appropriate use of D-dimer testing can minimize over-utilization of venous duplex ultrasound in a contemporary high-volume hospital.

PubMed

Mousa, Albeir Y; Broce, Mike; Gill, Gurpreet; Kali, Maher; Yacoub, Michael; AbuRahma, Ali F

2015-02-01

The sensitivity of d-dimer (DD) in detecting deep venous thrombosis (DVT) is remarkably high; however, many institutions send patients immediately for a venous duplex ultrasound (VDU). This study was designed to examine the appropriate utilization of DD and VDU in a high-volume hospital. A retrospective study was conducted on consecutive patients who presented to a high-volume emergency department (ED) with lower extremity limb swelling/pain over a 30-day period, who were sent for VDU during an evaluation for DVT. VDU data were merged with electronic DD laboratory results. The enzyme-linked immunosorbent assay method was used to provide DD values and thresholds. Values above 0.60 mg/fibrinogen equivalent unit (FEU) were considered abnormal. We reviewed the medical records of 517 ED patients in the month of June 2013. After applying the Wells criteria, 157 patients (30.4%) were excluded because of a history of DVT or pulmonary embolism, having been screened for shortness of breath, or sent for surveillance-leaving 360 for analysis. The average age was 59.3 ± 16.5 years with more women (210, 58.3%) and the majority reported limb pain or swelling (73.9%). DD was performed on 51 patients with an average value of 3.6 ± 5.4 mg/FEU, of which 43 (84.3%) were positive. DD identified all positive and negative DVT patients (100% sensitivity and negative predictive value), but also included 40 false positives (16.7% specificity). On the other hand, 309 patients were sent directly to VDU without DD; of those, 43 (13.9%) were positive for DVT. However, 266 (86.1%) patients were negative for DVT by VDU without DD and these were deemed improper by our current study protocol. Potential charge savings were calculated as VDU for all (360 × $1000 = $360,000), DD for all (360 × $145 = $52,200), and VDU for both true and false positives (estimated to be about 25% of the cases; 90 × $1000 = $90,000); this equals a charge savings of $217,800 and would avoid unnecessary VDUs. Based on the results of our study, we suggest that the DD test be utilized during the initial work-up for patients with limb swelling/pain in the emergency room. Appropriate utilization of DD, as well as other clinical criteria, may limit the over-utilization and added cost of VDU, without a negative impact on patient care. The results of DD tests should be utilized to limit the number of patients sent for VDU to only those patients with a positive DD or other significant underlying concerns. Copyright © 2015 Elsevier Inc. All rights reserved.

Women's perceptions of breast cancer screening. Spanish screening programme survey.

PubMed

Baena-Cañada, José M; Rosado-Varela, Petra; Expósito-Álvarez, Inmaculada; González-Guerrero, Macarena; Nieto-Vera, Juan; Benítez-Rodríguez, Encarnación

2014-12-01

Participants in breast cancer screening programmes may benefit from early detection but may also be exposed to the risks of overdiagnosis and false positives. We surveyed a sample of Spanish women to assess knowledge, information sources, attitudes and psychosocial impact. A total of 434 breast cancer screening programme participants aged 45-69 years were administered questionnaires regarding knowledge, information sources, attitudes and psychosocial impact. Scores of 5 or more (out of 10) and 12 or less (out of 24) were established as indicating adequate knowledge and a positive attitude, respectively. Psychosocial impact was measured using the Hospital Anxiety and Depression Scale and the Cancer Worry Scale. Only 42 women (9.7%) had adequate knowledge. The mean (SD) knowledge score was 2.97 (1.16). Better educated women and women without previous false positives had higher scores. The main sources of information were television, press, Andalusian Health Service documentation and family and friends. Most participants (99.1%) had a positive attitude, with a mean (SD) score of 3.21 (2.66). Mean (SD) scores for anxiety, depression and cancer worry were 1.86 (3.26), 0.72 (1.99) and 9.4 (3.04), respectively. Women have a very positive attitude to breast cancer screening, but are poorly informed and use television as their main information source. They experience no negative psychosocial impact from participation in such programmes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reduction of lymph tissue false positives in pulmonary embolism detection

NASA Astrophysics Data System (ADS)

Ghanem, Bernard; Liang, Jianming; Bi, Jinbo; Salganicoff, Marcos; Krishnan, Arun

2008-03-01

Pulmonary embolism (PE) is a serious medical condition, characterized by the partial/complete blockage of an artery within the lungs. We have previously developed a fast yet effective approach for computer aided detection of PE in computed topographic pulmonary angiography (CTPA),1 which is capable of detecting both acute and chronic PEs, achieving a benchmark performance of 78% sensitivity at 4 false positives (FPs) per volume. By reviewing the FPs generated by this system, we found the most dominant type of FP, roughly one third of all FPs, to be lymph/connective tissue. In this paper, we propose a novel approach that specifically aims at reducing this FP type. Our idea is to explicitly exploit the anatomical context configuration of PE and lymph tissue in the lungs: a lymph FP connects to the airway and is located outside the artery, while a true PE should not connect to the airway and must be inside the artery. To realize this idea, given a detected candidate (i.e. a cluster of suspicious voxels), we compute a set of contextual features, including its distance to the airway based on local distance transform and its relative position to the artery based on fast tensor voting and Hessian "vesselness" scores. Our tests on unseen cases show that these features can reduce the lymph FPs by 59%, while improving the overall sensitivity by 3.4%.

Transit shapes and self-organizing maps as a tool for ranking planetary candidates: application to Kepler and K2

NASA Astrophysics Data System (ADS)

Armstrong, D. J.; Pollacco, D.; Santerne, A.

2017-03-01

A crucial step in planet hunting surveys is to select the best candidates for follow-up observations, given limited telescope resources. This is often performed by human 'eyeballing', a time consuming and statistically awkward process. Here, we present a new, fast machine learning technique to separate true planet signals from astrophysical false positives. We use self-organizing maps (SOMs) to study the transit shapes of Kepler and K2 known and candidate planets. We find that SOMs are capable of distinguishing known planets from known false positives with a success rate of 87.0 per cent, using the transit shape alone. Furthermore, they do not require any candidate to be dispositioned prior to use, meaning that they can be used early in a mission's lifetime. A method for classifying candidates using a SOM is developed, and applied to previously unclassified members of the Kepler Objects of Interest (KOI) list as well as candidates from the K2 mission. The method is extremely fast, taking minutes to run the entire KOI list on a typical laptop. We make PYTHON code for performing classifications publicly available, using either new SOMs or those created in this work. The SOM technique represents a novel method for ranking planetary candidate lists, and can be used both alone or as part of a larger autovetting code.

Pepper, chili (Capsicum annuum).

PubMed

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

2015-01-01

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

Just How Much Does That Cost, Anyway? An Analysis of the Financial Costs and Benefits of the No-Fly List

DTIC Science & Technology

2009-01-01

easier and more streamlined airport security checkpoint experience. Having outlined the key aspects of the no-fly list, the article will now turn...attempts to fly, he/she is stopped at the airport by local law enforcement and airport security . Having identified how many false positives there are in a...activities: the cost of the passenger being detained at the airport and missing his/her flight; the cost of airport security /personnel detaining the

MR-Guided Near Infrared Spectroscopy for Reducing Breast Cancer False Positives

DTIC Science & Technology

2009-09-01

an Invivo breast coil in a (b) Philips scanner , and (b) a USA Instruments coil in a (d) GE scanner . 8 Quantitative accuracy in optical imaging...reconstruction [7], which includes a weighting term to account for the accuracy of the MR scanner in determining water and fat images. The advantage of... scanner used in this study. These methods were tested in a 86mm diameter gelatin phantom, shown in Figure 6, with porcine blood added to mimic the

Performance of two strategies for urgent ANCA and anti-GBM analysis in vasculitis.

PubMed

de Joode, Anoek A E; Roozendaal, Caroline; van der Leij, Marcel J; Bungener, Laura B; Sanders, Jan Stephan F; Stegeman, Coen A

2014-02-01

In anti-neutrophil cytoplasmic antibodies (ANCA) associated small vessel vasculitis (AAV), rapid testing for ANCA and anti-glomerular basement membrane (GBM) antibodies may be beneficial for therapeutic purpose. We analysed the diagnostic performance of two rapid ANCA and anti-GBM test methods in 260 patients with suspected AAV. Between January 2004 and November 2010, we analysed 260 samples by qualitative Dotblot (Biomedical Diagnostics); retrospective analysis followed with directly coated highly sensitive automated Phadia ELiA and ELiA anti-GBM. Results were related to the final clinical diagnosis and compared with routine capture ELISA. Seventy-four patients had a final diagnosis of AAV (n=62) or anti-GBM disease (n=12). Both Dotblot and ELiA detected all 12 cases of anti-GBM disease; 2 false positive results were found. Dotblot detected ANCA in 56 of 62 AAV patients (sensitivity 90%, NPV 97%), and showed 5 false positives (specificity 97%, PPV 90%). The Phadia ELiA anti-PR3(s) or anti-MPO(s) was positive in 57 of 62 AAV patients (sensitivity 92%, NPV 97%), and had 5 false positives (specificity 97%, PPV 88%). Routine capture ELISA was equally accurate (sensitivity 94%, specificity 97%, PPV 88%, NPV 98%). The Dotblot and Phadia ELiA on anti-GBM, anti-PR3(s) and anti-MPO(s) performed excellently; results were almost identical to routine ELISA. When suspicion of AAV or anti-GBM disease is high and diagnosis is urgently needed, both tests are very powerful for rapid serological diagnosis. Further studies have to confirm the test performances in samples routinely presented for ANCA testing and in follow-up of positive patients. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma.

PubMed

Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

2015-01-01

Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation.

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.

A spectroscopic tool for identifying sources of origin for materials of military interest

NASA Astrophysics Data System (ADS)

Miziolek, Andrzej W.; De Lucia, Frank C.

2014-05-01

There is a need to identify the source of origin for many items of military interest, including ammunition and weapons that may be circulated and traded in illicit markets. Both fieldable systems (man-portable or handheld) as well as benchtop systems in field and home base laboratories are desired for screening and attribution purposes. Laser Induced Breakdown Spectroscopy (LIBS) continues to show significant capability as a promising new tool for materials identification, matching, and provenance. With the use of the broadband, high resolution spectrometer systems, the LIBS devices can not only determine the elemental inventory of the sample, but they are also capable of elemental fingerprinting to signify sources of origin of various materials. We present the results of an initial study to differentiate and match spent cartridges from different manufacturers and countries. We have found that using Partial Least Squares Discriminant Analysis (PLS-DA) we are able to achieve on average 93.3% True Positives and 5.3% False Positives. These results add to the large body of publications that have demonstrated that LIBS is a particularly suitable tool for source of origin determinations.

Modeling HIV-1 Drug Resistance as Episodic Directional Selection

PubMed Central

Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L.; Scheffler, Konrad

2012-01-01

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance. PMID:22589711

Applying a new computer-aided detection scheme generated imaging marker to predict short-term breast cancer risk

NASA Astrophysics Data System (ADS)

Mirniaharikandehei, Seyedehnafiseh; Hollingsworth, Alan B.; Patel, Bhavika; Heidari, Morteza; Liu, Hong; Zheng, Bin

2018-05-01

This study aims to investigate the feasibility of identifying a new quantitative imaging marker based on false-positives generated by a computer-aided detection (CAD) scheme to help predict short-term breast cancer risk. An image dataset including four view mammograms acquired from 1044 women was retrospectively assembled. All mammograms were originally interpreted as negative by radiologists. In the next subsequent mammography screening, 402 women were diagnosed with breast cancer and 642 remained negative. An existing CAD scheme was applied ‘as is’ to process each image. From CAD-generated results, four detection features including the total number of (1) initial detection seeds and (2) the final detected false-positive regions, (3) average and (4) sum of detection scores, were computed from each image. Then, by combining the features computed from two bilateral images of left and right breasts from either craniocaudal or mediolateral oblique view, two logistic regression models were trained and tested using a leave-one-case-out cross-validation method to predict the likelihood of each testing case being positive in the next subsequent screening. The new prediction model yielded 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 showed an increasing trend in the adjusted odds ratio and risk prediction scores (p  <  0.01). Thus, this study demonstrated that CAD-generated false-positives might include valuable information, which needs to be further explored for identifying and/or developing more effective imaging markers for predicting short-term breast cancer risk.

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.

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

PubMed

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

2015-01-01

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

Sensitivity and Specificity of Interictal EEG-fMRI for Detecting the Ictal Onset Zone at Different Statistical Thresholds

PubMed Central

Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim

2014-01-01

There is currently a lack of knowledge about electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) specificity. Our aim was to define sensitivity and specificity of blood oxygen level dependent (BOLD) responses to interictal epileptic spikes during EEG-fMRI for detecting the ictal onset zone (IOZ). We studied 21 refractory focal epilepsy patients who had a well-defined IOZ after a full presurgical evaluation and interictal spikes during EEG-fMRI. Areas of spike-related BOLD changes overlapping the IOZ in patients were considered as true positives; if no overlap was found, they were treated as false-negatives. Matched healthy case-controls had undergone similar EEG-fMRI in order to determine true-negative and false-positive fractions. The spike-related regressor of the patient was used in the design matrix of the healthy case-control. Suprathreshold BOLD changes in the brain of controls were considered as false positives, absence of these changes as true negatives. Sensitivity and specificity were calculated for different statistical thresholds at the voxel level combined with different cluster size thresholds and represented in receiver operating characteristic (ROC)-curves. Additionally, we calculated the ROC-curves based on the cluster containing the maximal significant activation. We achieved a combination of 100% specificity and 62% sensitivity, using a Z-threshold in the interval 3.4–3.5 and cluster size threshold of 350 voxels. We could obtain higher sensitivity at the expense of specificity. Similar performance was found when using the cluster containing the maximal significant activation. Our data provide a guideline for different EEG-fMRI settings with their respective sensitivity and specificity for detecting the IOZ. The unique cluster containing the maximal significant BOLD activation was a sensitive and specific marker of the IOZ. PMID:25101049

Computer-aided detection of artificial pulmonary nodules using an ex vivo lung phantom: influence of exposure parameters and iterative reconstruction.

PubMed

Wielpütz, Mark O; Wroblewski, Jacek; Lederlin, Mathieu; Dinkel, Julien; Eichinger, Monika; Koenigkam-Santos, M; Biederer, Jürgen; Kauczor, Hans-Ulrich; Puderbach, Michael U; Jobst, Bertram J

2015-05-01

To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the performance of computer-aided detection (CAD) of pulmonary nodules on chest multidetector computed tomography (MDCT). Seven porcine lung explants were inflated in a dedicated ex vivo phantom shell and prepared with n=162 artificial nodules of a clinically relevant volume and maximum diameter (46-1063 μl, and 6.2-21.5 mm). n=118 nodules were solid and n=44 part-solid. MDCT was performed with different combinations of 120 and 80 kV with 120, 60, 30 and 12 mA*s, and reconstructed with both filtered back projection (FBP) and IR. Subsequently, 16 datasets per lung were subjected to dedicated CAD software. The rate of true positive, false negative and false positive CAD marks was measured for each reconstruction. The rate of true positive findings ranged between 88.9-91.4% for FBP and 88.3-90.1% for IR (n.s.) with most exposure settings, but was significantly lower with the combination of 80 kV and 12 mA*s (80.9% and 81.5%, respectively, p<0.05). False positive findings ranged between 2.3-8.1 annotations per lung. For nodule volumes <200 μl the rate of true positives was significantly lower than for >300 μl (p<0.05). Similarly, it was significantly lower for diameters <12 mm compared to ≥12 mm (p<0.05). The rate of true positives for solid and part-solid nodules was similar. Nodule CAD on chest MDCT is robust over a wide range of exposure settings. Noise reduction by IR is not detrimental for CAD, and may be used to improve image quality in the setting of low-dose MDCT for lung cancer screening. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Testing new methodologies for short -term earthquake forecasting: Multi-parameters precursors

NASA Astrophysics Data System (ADS)

Ouzounov, Dimitar; Pulinets, Sergey; Tramutoli, Valerio; Lee, Lou; Liu, Tiger; Hattori, Katsumi; Kafatos, Menas

2014-05-01

We are conducting real-time tests involving multi-parameter observations over different seismo-tectonics regions in our investigation of phenomena preceding major earthquakes. Our approach is based on a systematic analysis of several selected parameters, namely: gas discharge; thermal infrared radiation; ionospheric electron density; and atmospheric temperature and humidity, which we believe are all associated with the earthquake preparation phase. We are testing a methodology capable to produce alerts in advance of major earthquakes (M > 5.5) in different regions of active earthquakes and volcanoes. During 2012-2013 we established a collaborative framework with PRE-EARTHQUAKE (EU) and iSTEP3 (Taiwan) projects for coordinated measurements and prospective validation over seven testing regions: Southern California (USA), Eastern Honshu (Japan), Italy, Greece, Turkey, Taiwan (ROC), Kamchatka and Sakhalin (Russia). The current experiment provided a "stress test" opportunity to validate the physical based earthquake precursor approach over regions of high seismicity. Our initial results are: (1) Real-time tests have shown the presence of anomalies in the atmosphere and ionosphere before most of the significant (M>5.5) earthquakes; (2) False positives exist and ratios are different for each region, varying between 50% for (Southern Italy), 35% (California) down to 25% (Taiwan, Kamchatka and Japan) with a significant reduction of false positives as soon as at least two geophysical parameters are contemporarily used; (3) Main problems remain related to the systematic collection and real-time integration of pre-earthquake observations. Our findings suggest that real-time testing of physically based pre-earthquake signals provides a short-term predictive power (in all three important parameters, namely location, time and magnitude) for the occurrence of major earthquakes in the tested regions and this result encourages testing to continue with a more detailed analysis of false alarm ratios and understanding of the overall physics of earthquake preparation.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Modeling HIV-1 drug resistance as episodic directional selection.

PubMed

Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

2012-01-01

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

Collective intelligence meets medical decision-making: the collective outperforms the best radiologist.

PubMed

Wolf, Max; Krause, Jens; Carney, Patricia A; Bogart, Andy; Kurvers, Ralf H J M

2015-01-01

While collective intelligence (CI) is a powerful approach to increase decision accuracy, few attempts have been made to unlock its potential in medical decision-making. Here we investigated the performance of three well-known collective intelligence rules ("majority", "quorum", and "weighted quorum") when applied to mammography screening. For any particular mammogram, these rules aggregate the independent assessments of multiple radiologists into a single decision (recall the patient for additional workup or not). We found that, compared to single radiologists, any of these CI-rules both increases true positives (i.e., recalls of patients with cancer) and decreases false positives (i.e., recalls of patients without cancer), thereby overcoming one of the fundamental limitations to decision accuracy that individual radiologists face. Importantly, we find that all CI-rules systematically outperform even the best-performing individual radiologist in the respective group. Our findings demonstrate that CI can be employed to improve mammography screening; similarly, CI may have the potential to improve medical decision-making in a much wider range of contexts, including many areas of diagnostic imaging and, more generally, diagnostic decisions that are based on the subjective interpretation of evidence.

Changes of TSH-Stimulation Blocking Antibody (TSBAb) and Thyroid Stimulating Antibody (TSAb) Over 10 Years in 34 TSBAb-Positive Patients with Hypothyroidism and in 98 TSAb-Positive Graves' Patients with Hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-Receptor-Antibody (TRAb)-Positive Patients

PubMed Central

Takasu, Nobuyuki; Matsushita, Mina

2012-01-01

Two TRAbs: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves' hyperthyroidism. TSBAb and TSAb block TSH-binding to cells as TRAb, measured as TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb. We studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34 TSBAb-positives with hypothyroidism continued to have persistently positive TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism. Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34 TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive Graves' hyperthyroidism. Two of the 98 TSAb-positive Graves' patients with hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are TRAbs. TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic and 10 goitrous) over 10 years. All of the 10 TSBAb-positive goitrous patients recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic patients continued to have hypothyroidism. PMID:22655217

InstantLabs Listeria species food safety kit. Performance tested methods 041304.

PubMed

Sharma, Neil; Bambusch, Lauren; Le, Thu; Morey, Amit

2014-01-01

The InstantLabs Listeria Species Food SafetyKitwas validated against the International Organization for Standardization (ISO) reference method 11290-1 for the detection of Listeria monocytogenes and other Listeria species. The matrixes (stainless steel, sealed concrete, cheddar cheese, raw shrimp, and hot dogs) were inoculated with approximately 1 CFU/test portion of various Listeria species to generate fractional positives (5-15) in 20 inoculated samples. Enrichments were also fractionally inoculated with L. monocytogenes for side-by-side testing of the InstantLabs Listeria monocytogenes Food Safety Kit. Stainless steel and sealed concrete samples were validated using 4 x 4" and 1 x 1" test areas, respectively, and enriched in Buffered Listeria Enrichment Broth (BLEB) at 35 +/- 1 degrees C for 22-28 h. All food samples were tested at 25 g or 25 mL and enriched in BLEB at 35 +/- 1 degrees C for 24-28 h. All samples were confirmed using the ISO reference method, regardless of initial screen result. The InstantLabs test method performed as well as or better than the reference method for the detection of Listeria species on stainless steel, sealed concrete, cheddar cheese, raw shrimp, and hot dogs. Inclusivity and exclusivity testing revealed no false negatives and no false positives among the 80 Listeria species and 30 non-Listeria species examined. The method was shown to be robust when variations were introduced to the enrichment time, the volume for DNA extraction, and the heat block time (data not shown).

Detection of white matter lesion regions in MRI using SLIC0 and convolutional neural network.

PubMed

Diniz, Pedro Henrique Bandeira; Valente, Thales Levi Azevedo; Diniz, João Otávio Bandeira; Silva, Aristófanes Corrêa; Gattass, Marcelo; Ventura, Nina; Muniz, Bernardo Carvalho; Gasparetto, Emerson Leandro

2018-04-19

White matter lesions are non-static brain lesions that have a prevalence rate up to 98% in the elderly population. Because they may be associated with several brain diseases, it is important that they are detected as soon as possible. Magnetic Resonance Imaging (MRI) provides three-dimensional data with the possibility to detect and emphasize contrast differences in soft tissues, providing rich information about the human soft tissue anatomy. However, the amount of data provided for these images is far too much for manual analysis/interpretation, representing a difficult and time-consuming task for specialists. This work presents a computational methodology capable of detecting regions of white matter lesions of the brain in MRI of FLAIR modality. The techniques highlighted in this methodology are SLIC0 clustering for candidate segmentation and convolutional neural networks for candidate classification. The methodology proposed here consists of four steps: (1) images acquisition, (2) images preprocessing, (3) candidates segmentation and (4) candidates classification. The methodology was applied on 91 magnetic resonance images provided by DASA, and achieved an accuracy of 98.73%, specificity of 98.77% and sensitivity of 78.79% with 0.005 of false positives, without any false positives reduction technique, in detection of white matter lesion regions. It is demonstrated the feasibility of the analysis of brain MRI using SLIC0 and convolutional neural network techniques to achieve success in detection of white matter lesions regions. Copyright © 2018. Published by Elsevier B.V.

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

PubMed Central

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

2011-01-01

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

Characterization of Exoplanet Atmospheres and Kepler Planet Candidates with Multi-Color Photometry from the Gran Telescopio Canarias

NASA Astrophysics Data System (ADS)

Colon, Knicole; Ford, E. B.

2012-01-01

With over 180 confirmed transiting exoplanets and NASA's Kepler mission's recent discovery of over 1200 transiting exoplanet candidates, we can conduct detailed investigations into the (i) properties of exoplanet atmospheres and (ii) false positive rates for planet search surveys. To aid these investigations, we developed a novel technique of using the Optical System for Imaging and low Resolution Integrated Spectroscopy (OSIRIS) installed on the 10.4-meter Gran Telescopio Canarias (GTC) to acquire near-simultaneous multi-color photometry of (i) HD 80606b in bandpasses around the potassium (K I) absorption feature, (ii) GJ 1214b in bandpasses around a possible methane absorption feature and (iii) several Kepler planet candidates. For HD 80606b, we measure a significant color change during transit between wavelengths that probe the K I line core and the K I wing, equivalent to a 4.2% change in the apparent planetary radius. We hypothesize that the excess absorption may be due to K I in a high-speed wind being driven from the exoplanet's exosphere. This is one of the first detections of K I in an exoplanet atmosphere. For GJ 1214b, we compare the transit depths measured "on” and "off” a possible methane absorption feature and use our results to help resolve conflicting results from other studies regarding the composition of this super-Earth-size planet's atmosphere. For Kepler candidates, we use the color change during transit to reject candidates that are false positives (e.g., a blend with an eclipsing binary either in the background/foreground or bound to the target star). We target small planets (<6 Earth radii) with short orbital periods (<6 days), since eclipsing binaries can mimic planets in this regime. Our results include identification of two false positives and test recent predictions of the false positive rates for the Kepler sample. This research demonstrates the value of the GTC for exoplanet follow-up.

Kepler Reliability and Occurrence Rates

NASA Astrophysics Data System (ADS)

Bryson, Steve

2016-10-01

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

A novel approach to describing and detecting performance anti-patterns

NASA Astrophysics Data System (ADS)

Sheng, Jinfang; Wang, Yihan; Hu, Peipei; Wang, Bin

2017-08-01

Anti-pattern, as an extension to pattern, describes a widely used poor solution which can bring negative influence to application systems. Aiming at the shortcomings of the existing anti-pattern descriptions, an anti-pattern description method based on first order predicate is proposed. This method synthesizes anti-pattern forms and symptoms, which makes the description more accurate and has good scalability and versatility as well. In order to improve the accuracy of anti-pattern detection, a Bayesian classification method is applied in validation for detection results, which can reduce false negatives and false positives of anti-pattern detection. Finally, the proposed approach in this paper is applied to a small e-commerce system, the feasibility and effectiveness of the approach is demonstrated further through experiments.

Computing the binding affinity of a ligand buried deep inside a protein with the hybrid steered molecular dynamics

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

Villarreal, Oscar D.; Yu, Lili; Department of Laboratory Medicine, Yancheng Vocational Institute of Health Sciences, Yancheng, Jiangsu 224006

Computing the ligand-protein binding affinity (or the Gibbs free energy) with chemical accuracy has long been a challenge for which many methods/approaches have been developed and refined with various successful applications. False positives and, even more harmful, false negatives have been and still are a common occurrence in practical applications. Inevitable in all approaches are the errors in the force field parameters we obtain from quantum mechanical computation and/or empirical fittings for the intra- and inter-molecular interactions. These errors propagate to the final results of the computed binding affinities even if we were able to perfectly implement the statistical mechanicsmore » of all the processes relevant to a given problem. And they are actually amplified to various degrees even in the mature, sophisticated computational approaches. In particular, the free energy perturbation (alchemical) approaches amplify the errors in the force field parameters because they rely on extracting the small differences between similarly large numbers. In this paper, we develop a hybrid steered molecular dynamics (hSMD) approach to the difficult binding problems of a ligand buried deep inside a protein. Sampling the transition along a physical (not alchemical) dissociation path of opening up the binding cavity- -pulling out the ligand- -closing back the cavity, we can avoid the problem of error amplifications by not relying on small differences between similar numbers. We tested this new form of hSMD on retinol inside cellular retinol-binding protein 1 and three cases of a ligand (a benzylacetate, a 2-nitrothiophene, and a benzene) inside a T4 lysozyme L99A/M102Q(H) double mutant. In all cases, we obtained binding free energies in close agreement with the experimentally measured values. This indicates that the force field parameters we employed are accurate and that hSMD (a brute force, unsophisticated approach) is free from the problem of error amplification suffered by many sophisticated approaches in the literature.« less

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

NCLscan: accurate identification of non-co-linear transcripts (fusion, trans-splicing and circular RNA) with a good balance between sensitivity and precision.

PubMed

Chuang, Trees-Juen; Wu, Chan-Shuo; Chen, Chia-Ying; Hung, Li-Yuan; Chiang, Tai-Wei; Yang, Min-Yu

2016-02-18

Analysis of RNA-seq data often detects numerous 'non-co-linear' (NCL) transcripts, which comprised sequence segments that are topologically inconsistent with their corresponding DNA sequences in the reference genome. However, detection of NCL transcripts involves two major challenges: removal of false positives arising from alignment artifacts and discrimination between different types of NCL transcripts (trans-spliced, circular or fusion transcripts). Here, we developed a new NCL-transcript-detecting method ('NCLscan'), which utilized a stepwise alignment strategy to almost completely eliminate false calls (>98% precision) without sacrificing true positives, enabling NCLscan outperform 18 other publicly-available tools (including fusion- and circular-RNA-detecting tools) in terms of sensitivity and precision, regardless of the generation strategy of simulated dataset, type of intragenic or intergenic NCL event, read depth of coverage, read length or expression level of NCL transcript. With the high accuracy, NCLscan was applied to distinguishing between trans-spliced, circular and fusion transcripts on the basis of poly(A)- and nonpoly(A)-selected RNA-seq data. We showed that circular RNAs were expressed more ubiquitously, more abundantly and less cell type-specifically than trans-spliced and fusion transcripts. Our study thus describes a robust pipeline for the discovery of NCL transcripts, and sheds light on the fundamental biology of these non-canonical RNA events in human transcriptome. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

What is the best strategy for investigating abnormal liver function tests in primary care? Implications from a prospective study.

PubMed

Lilford, Richard J; Bentham, Louise M; Armstrong, Matthew J; Neuberger, James; Girling, Alan J

2013-06-20

Evaluation of predictive value of liver function tests (LFTs) for the detection of liver-related disease in primary care. A prospective observational study. 11 UK primary care practices. Patients (n=1290) with an abnormal eight-panel LFT (but no previously diagnosed liver disease). Patients were investigated by recording clinical features, and repeating LFTs, specific tests for individual liver diseases, and abdominal ultrasound scan. Patients were characterised as having: hepatocellular disease; biliary disease; tumours of the hepato-biliary system and none of the above. The relationship between LFT results and disease categories was evaluated by stepwise regression and logistic discrimination, with adjustment for demographic and clinical factors. True and False Positives generated by all possible LFT combinations were compared with a view towards optimising the choice of analytes in the routine LFT panel. Regression methods showed that alanine aminotransferase (ALT) was associated with hepatocellular disease (32 patients), while alkaline phosphatase (ALP) was associated with biliary disease (12 patients) and tumours of the hepatobiliary system (9 patients). A restricted panel of ALT and ALP was an efficient choice of analytes, comparing favourably with the complete panel of eight analytes, provided that 48 False Positives can be tolerated to obtain one additional True Positive. Repeating a complete panel in response to an abnormal reading is not the optimal strategy. The LFT panel can be restricted to ALT and ALP when the purpose of testing is to exclude liver disease in primary care.

InstantLabs Listeria monocytogenes food safety kit. Performance tested method 051304.

PubMed

Sharma, Neil; Bambusch, Lauren; Le, Thu; Morey, Amit

2014-01-01

The InstantLabs Listeria monocytogenes Food Safety Kit was validated against the International Organization for Standardization (ISO) reference method 11290-1 for the detection of Listeria monocytogenes and other Listeria species. The matrixes (stainless steel, sealed concrete, ice cream, whole milk, cheddar cheese, raw shrimp, hot dogs, deli turkey, and lettuce) were inoculated with approximately 1 CFU/test portion of L. monocytogenes to generate fractional positives (5-15) in 20 inoculated samples. Enrichments were also fractionally inoculated with L. grayii for side-by-side testing of the Listeria Species Food Safety Kit. Stainless steel and sealed concrete samples were validated using 4 x 4" and 1 x 1 " test areas, respectively, and enriched in Buffered Listeria Enrichment Broth (BLEB) at 35 +/- 1degreesC for 22-28 h. All food samples were tested at 25 g and enriched in BLEB at 35 +/- 1 degreesC for 24-28 h. All samples were confirmed using the ISO reference method, regardless of initial screen result. The InstantLabs test method performed as well as or better than the reference method for the detection of L. monocytogenes on stainless steel and sealed concrete and in ice cream, whole milk, cheddar cheese, raw shrimp, hot dogs, deli turkey, and lettuce. Inclusivity and exclusivity testing revealed no false negatives and no false positives among the 50 L. monocytogenes serovars and 30 non-L. monocytogenes species examined. The method was shown to be robust when the enrichment times, volumes for DNA extraction, and heat block times were varied.

Emergency ultrasound in the acute assessment of haemothorax

PubMed Central

Brooks, A; Davies, B; Smethhurst, M; Connolly, J

2004-01-01

Aims: To evaluate thoracic ultrasound for the detection of haemothorax in patients with thoracic trauma against established investigations. Methods: Thoracic ultrasound was performed as an extension of the standard focused assessment with sonography for trauma (FAST) protocol used at the Queen's Medical Centre for the assessment of adult patients with torso trauma. Fluid was sought in both pleural cavities using a hand portable ultrasound system by one of two non-radiologists trained in FAST. Findings were compared against subsequent investigations/procedures performed at the discretion of the attending emergency physician—supine chest radiography, intercostal drain, computed tomography, or thoracotomy. The sensitivity of the technique and the time taken to diagnosis for each investigation were recorded. Results: Sixty one patients, 54 (89%) after blunt trauma, underwent thoracic ultrasound evaluation during the study. Twelve patients had a haemothorax detected by ultrasound and confirmed by computed tomography or by tube thoracostomy. Four haemothoraces detected on ultrasound were not apparent on trauma chest radiography. There were 12 true positives, 48 true negatives, no false positives, and one false negative scan. The sensitivity of ultrasound was 92% and specificity 100% with a positive predictive value of 100% and negative predictive value 98% for the detection of haemothorax after trauma. Conclusions: Emergency ultrasound of the chest performed as part of the primary survey of the traumatised patient can rapidly and accurately diagnose haemothorax and is a valuable tool to augment the immediate clinical assessment of these patients. PMID:14734374

Face detection assisted auto exposure: supporting evidence from a psychophysical study

NASA Astrophysics Data System (ADS)

Jin, Elaine W.; Lin, Sheng; Dharumalingam, Dhandapani

2010-01-01

Face detection has been implemented in many digital still cameras and camera phones with the promise of enhancing existing camera functions (e.g. auto exposure) and adding new features to cameras (e.g. blink detection). In this study we examined the use of face detection algorithms in assisting auto exposure (AE). The set of 706 images, used in this study, was captured using Canon Digital Single Lens Reflex cameras and subsequently processed with an image processing pipeline. A psychophysical study was performed to obtain optimal exposure along with the upper and lower bounds of exposure for all 706 images. Three methods of marking faces were utilized: manual marking, face detection algorithm A (FD-A), and face detection algorithm B (FD-B). The manual marking method found 751 faces in 426 images, which served as the ground-truth for face regions of interest. The remaining images do not have any faces or the faces are too small to be considered detectable. The two face detection algorithms are different in resource requirements and in performance. FD-A uses less memory and gate counts compared to FD-B, but FD-B detects more faces and has less false positives. A face detection assisted auto exposure algorithm was developed and tested against the evaluation results from the psychophysical study. The AE test results showed noticeable improvement when faces were detected and used in auto exposure. However, the presence of false positives would negatively impact the added benefit.

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.

DeepMitosis: Mitosis detection via deep detection, verification and segmentation networks.

PubMed

Li, Chao; Wang, Xinggang; Liu, Wenyu; Latecki, Longin Jan

2018-04-01

Mitotic count is a critical predictor of tumor aggressiveness in the breast cancer diagnosis. Nowadays mitosis counting is mainly performed by pathologists manually, which is extremely arduous and time-consuming. In this paper, we propose an accurate method for detecting the mitotic cells from histopathological slides using a novel multi-stage deep learning framework. Our method consists of a deep segmentation network for generating mitosis region when only a weak label is given (i.e., only the centroid pixel of mitosis is annotated), an elaborately designed deep detection network for localizing mitosis by using contextual region information, and a deep verification network for improving detection accuracy by removing false positives. We validate the proposed deep learning method on two widely used Mitosis Detection in Breast Cancer Histological Images (MITOSIS) datasets. Experimental results show that we can achieve the highest F-score on the MITOSIS dataset from ICPR 2012 grand challenge merely using the deep detection network. For the ICPR 2014 MITOSIS dataset that only provides the centroid location of mitosis, we employ the segmentation model to estimate the bounding box annotation for training the deep detection network. We also apply the verification model to eliminate some false positives produced from the detection model. By fusing scores of the detection and verification models, we achieve the state-of-the-art results. Moreover, our method is very fast with GPU computing, which makes it feasible for clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Improving cervical region of interest by eliminating vaginal walls and cotton-swabs for automated image analysis

NASA Astrophysics Data System (ADS)

Venkataraman, Sankar; Li, Wenjing

2008-03-01

Image analysis for automated diagnosis of cervical cancer has attained high prominence in the last decade. Automated image analysis at all levels requires a basic segmentation of the region of interest (ROI) within a given image. The precision of the diagnosis is often reflected by the precision in detecting the initial region of interest, especially when some features outside the ROI mimic the ones within the same. Work described here discusses algorithms that are used to improve the cervical region of interest as a part of automated cervical image diagnosis. A vital visual aid in diagnosing cervical cancer is the aceto-whitening of the cervix after the application of acetic acid. Color and texture are used to segment acetowhite regions within the cervical ROI. Vaginal walls along with cottonswabs sometimes mimic these essential features leading to several false positives. Work presented here is focused towards detecting in-focus vaginal wall boundaries and then extrapolating them to exclude vaginal walls from the cervical ROI. In addition, discussed here is a marker-controlled watershed segmentation that is used to detect cottonswabs from the cervical ROI. A dataset comprising 50 high resolution images of the cervix acquired after 60 seconds of acetic acid application were used to test the algorithm. Out of the 50 images, 27 benefited from a new cervical ROI. Significant improvement in overall diagnosis was observed in these images as false positives caused by features outside the actual ROI mimicking acetowhite region were eliminated.

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

Comparison of Assays for Sensitive and Reproducible Detection of Cell Culture-Infectious Cryptosporidium parvum and Cryptosporidium hominis in Drinking Water

PubMed Central

Di Giovanni, George D.; Rochelle, Paul A.

2012-01-01

This study compared the three most commonly used assays for detecting Cryptosporidium sp. infections in cell culture: immunofluorescent antibody and microscopy assay (IFA), PCR targeting Cryptosporidium sp.-specific DNA, and reverse transcriptase PCR (RT-PCR) targeting Cryptosporidium sp.-specific mRNA. Monolayers of HCT-8 cells, grown in 8-well chamber slides or 96-well plates, were inoculated with a variety of viable and inactivated oocysts to assess assay performance. All assays detected infection with low doses of flow cytometry-enumerated Cryptosporidium parvum oocysts, including infection with one oocyst and three oocysts. All methods also detected infection with Cryptosporidium hominis. The RT-PCR assay, IFA, and PCR assay detected infection in 23%, 25%, and 51% of monolayers inoculated with three C. parvum oocysts and 10%, 9%, and 16% of monolayers inoculated with one oocyst, respectively. The PCR assay was the most sensitive, but it had the highest frequency of false positives with mock-infected cells and inactivated oocysts. IFA was the only infection detection assay that did not produce false positives with mock-infected monolayers. IFA was also the only assay that detected infections in all experiments with spiked oocysts recovered from Envirochek capsules following filtration of 1,000 liters of treated water. Consequently, cell culture with IFA detection is the most appropriate method for routine and sensitive detection of infectious Cryptosporidium parvum and Cryptosporidium hominis in drinking water. PMID:22038611

Resampling procedures to identify important SNPs using a consensus approach.

PubMed

Pardy, Christopher; Motyer, Allan; Wilson, Susan

2011-11-29

Our goal is to identify common single-nucleotide polymorphisms (SNPs) (minor allele frequency > 1%) that add predictive accuracy above that gained by knowledge of easily measured clinical variables. We take an algorithmic approach to predict each phenotypic variable using a combination of phenotypic and genotypic predictors. We perform our procedure on the first simulated replicate and then validate against the others. Our procedure performs well when predicting Q1 but is less successful for the other outcomes. We use resampling procedures where possible to guard against false positives and to improve generalizability. The approach is based on finding a consensus regarding important SNPs by applying random forests and the least absolute shrinkage and selection operator (LASSO) on multiple subsamples. Random forests are used first to discard unimportant predictors, narrowing our focus to roughly 100 important SNPs. A cross-validation LASSO is then used to further select variables. We combine these procedures to guarantee that cross-validation can be used to choose a shrinkage parameter for the LASSO. If the clinical variables were unavailable, this prefiltering step would be essential. We perform the SNP-based analyses simultaneously rather than one at a time to estimate SNP effects in the presence of other causal variants. We analyzed the first simulated replicate of Genetic Analysis Workshop 17 without knowledge of the true model. Post-conference knowledge of the simulation parameters allowed us to investigate the limitations of our approach. We found that many of the false positives we identified were substantially correlated with genuine causal SNPs.

Combustion Safety Simplified Test Protocol Field Study

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

Brand, L; Cautley, D.; Bohac, D.

2015-11-05

"9Combustions safety is an important step in the process of upgrading homes for energy efficiency. There are several approaches used by field practitioners, but researchers have indicated that the test procedures in use are complex to implement and provide too many false positives. Field failures often mean that the house is not upgraded until after remediation or not at all, if not include in the program. In this report the PARR and NorthernSTAR DOE Building America Teams provide a simplified test procedure that is easier to implement and should produce fewer false positives. A survey of state weatherization agencies onmore » combustion safety issues, details of a field data collection instrumentation package, summary of data collected over seven months, data analysis and results are included. The project provides several key results. State weatherization agencies do not generally track combustion safety failures, the data from those that do suggest that there is little actual evidence that combustion safety failures due to spillage from non-dryer exhaust are common and that only a very small number of homes are subject to the failures. The project team collected field data on 11 houses in 2015. Of these homes, two houses that demonstrated prolonged and excessive spillage were also the only two with venting systems out of compliance with the National Fuel Gas Code. The remaining homes experienced spillage that only occasionally extended beyond the first minute of operation. Combustion zone depressurization, outdoor temperature, and operation of individual fans all provide statistically significant predictors of spillage.« less

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

"9Combustion safety is an important step in the process of upgrading homes for energy efficiency. There are several approaches used by field practitioners, but researchers have indicated that the test procedures in use are complex to implement and provide too many false positives. Field failures often mean that the house is not upgraded until after remediation or not at all, if not include in the program. In this report the PARR and NorthernSTAR DOE Building America Teams provide a simplified test procedure that is easier to implement and should produce fewer false positives. A survey of state weatherization agencies onmore » combustion safety issues, details of a field data collection instrumentation package, summary of data collected over seven months, data analysis and results are included. The project provides several key results. State weatherization agencies do not generally track combustion safety failures, the data from those that do suggest that there is little actual evidence that combustion safety failures due to spillage from non-dryer exhaust are common and that only a very small number of homes are subject to the failures. The project team collected field data on 11 houses in 2015. Of these homes, two houses that demonstrated prolonged and excessive spillage were also the only two with venting systems out of compliance with the National Fuel Gas Code. The remaining homes experienced spillage that only occasionally extended beyond the first minute of operation. Combustion zone depressurization, outdoor temperature, and operation of individual fans all provide statistically significant predictors of spillage.« less

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

Kepler

NASA Technical Reports Server (NTRS)

Howell, Steve B.

2011-01-01

The NASA Kepler mission recently announced over 1200 exoplanet candidates. While some are common Hot Jupiters, a large number are Neptune size and smaller, transit depths suggest sizes down to the radius of Earth. The Kepler project has a fairly high confidence that most of these candidates are real exoplanets. Many analysis steps and lessons learned from Kepler light curves are used during the vetting process. This talk will cover some new results in the areas of stellar variability, solar systems with multiple planets, and how transit-like signatures are vetted for false positives, especially those indicative of small planets.

Radioiodine therapy for thyroid cancer depicted uterine leiomyoma.

PubMed

Hirata, Kenji; Shiga, Tohru; Kubota, Kanako C; Okamoto, Shozo; Kamibayashi, Tomohito; Tamaki, Nagara

2009-03-01

A 55-year-old woman underwent radioiodine therapy for papillary carcinoma of the thyroid. Post-therapeutic I-131 scan revealed radioiodine uptake in the pelvic region and in the thyroid bed. CT revealed a huge mass connected to the uterus. The tumor was operated on and histologically proven to be a leiomyoma of the uterus. Some physiological conditions or nonthyroidal diseases can cause false positives in patients with postoperative thyroid cancer. We suggest that uterine leiomyoma might be added to the pitfall list, although the mechanism of I-131 uptake remains unclear.

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

DTIC Science & Technology

2011-01-20

of 2009, was de- signed to address the important question of the frequency of Earth -size planets around Sun -like stars, and to characterize ex...physically associated with the candidate (hierarchical triple systems) and in a long-period orbit around their common center of mass would often be spatially...positive scenar- ios that is complementary to other diagnostics, and should play an important role in the discovery of Earth -size planets around other

One-day fluorescent-antibody procedure for detecting salmonellae in frozen and dried foods.

PubMed

Goepfert, J M; Mann, M E; Hicks, R

1970-12-01

The indirect fluorescent-antibody technique was used to examine 422 food samples for the presence of salmonellae. A cultural phase involving a 16-hr preenrichment in buffered nutrient broth-milk medium followed by a 4- to 5-hr subculture into fresh medium of the same composition was evaluated. This procedure yielded a sufficient population of salmonellae so that no false-negative results were obtained. Of the 31 false-positives obtained, 12 samples yielded positive cultural results upon extensive subculture of the original enrichment broths. Yeast cells and both vegetative and spore forms of bacilli were observed to fluoresce when stained with anti-Salmonella serum. Efforts to ascertain the cause of these cross-reactions and several alternate explanations are discussed.

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.

The neuropsychological differentiation of patients with very mild Alzheimer's disease and/or major depression.

PubMed

desRosiers, G; Hodges, J R; Berrios, G

1995-11-01

To evaluate the usefulness of standardized neuropsychological tests in the psychometric differentiation of patients with very mild or mild Alzheimer's Disease (AD) and/or major depression presenting in a tertiary clinic with memory/attention complaints. Controlled prospective clinicoexperimental design. Multidisciplinary Memory Clinic at Addenbroke's Hospital, Cambridge, England. Twenty-four patients with a clinical diagnosis of Alzheimer's disease (12 with major depression and 12 without), 12 patients with major depressive illness but without AD, and 12 healthy control subjects, all matched for age, sex, education levels, and estimates of premorbid intellectual potential. Mini-Mental State Examination (MMSE), Wechsler's Logical Memory (WLM) and Visual Reproduction (WVR), immediate and delayed reproduction, Wechsler's paired Associate Learning (WPAL), including the Easy and Hard subsets. Warrington's Recognition Memory for Faces (WRMF), Kendrick's Object Learning (KOLT) and Digit Copying (KDCT) Tests. Minimum 2-year follow-up diagnosis. Statistically, patients with very mild AD were distinguished clearly from those without AD on most tests of memory functions. Psychometrically, only KOLT and an index of retention on WLM and WVR were specific enough to avoid false positives, a requirement for second-stage tools. They also proved sensitive enough to suggest their role as first-stage instruments when screening for primary dementia in high-functioning patients scoring above the cut-point on MMSE. As efforts intensify to develop more powerful means to identify patients with Alzheimer's disease in its earliest stages, inclusion of specialist tests posing greater cognitive challenge than standard mental status scales has been one strategy. Our study explored how some of these neuropsychological tools behave psychometrically when analyzed on a single-case basis, and the results suggest a few are sensitive enough to boost detection above base rates alone while also being specific enough to reduce false alarms. Retention on Wechsler's Logical Memory and Visual Reproduction tasks and scores on Kendrick's Object Learning Test helped decrease the degree of ambiguity when cognitive profiles were used to distinguish depressed patients with Alzheimer disease from those without.

IMPAIRED FERTILITY AND PERCEIVED DIFFICULTIES CONCEIVING IN GHANA: MEASUREMENT PROBLEMS AND PROSPECTS.

PubMed

Fledderjohann, Jasmine; Johnson, David R

2016-08-01

What is the most appropriate measure of impaired fertility for understanding its social consequences in sub-Saharan Africa? The dearth of subjective measures in surveys in the region has prevented comparisons of subjective and objective measures. Perceived difficulties conceiving may have a greater impact than objective measures for social outcomes such as divorce, stigmatization and distress. This study compares 12- (clinical) and 24- (epidemiological) month measures from biomedicine and 5- and 7-year measures from demography with a subjective measure of impaired fertility using correlations, random effects models and test-retest models to assess relationships between measures, their association with sociodemographic characteristics and the stability of measures across time. Secondary panel data (1998-2004) from 1350 Ghanaian women aged 15-49 of all marital statuses are used. Longer waiting times to identification of impaired fertility required by demographic measures result in more stable measures, but perceived difficulties conceiving are most closely aligned with clinical infertility (r=0.61; p<0.05). Epidemiological infertility is also closely aligned with the subjective measure. A large proportion of those identified as having impaired fertility based purely on waiting times are successful contraceptors. Where subjective measures are not available, epidemiological (24-month) measures may be most appropriate for studies of the social consequences of impaired fertility. Accounting for contraceptive use is important in order to avoid false positives. Future research should consider a variety of measures of perceived difficulties conceiving and self-identified infertility to assess which is most valid; in order to accomplish this, it is imperative that subjective measures of infertility be included in social surveys in sub-Saharan Africa.

A minimal standardization setting for language mapping tests: an Italian example.

PubMed

Rofes, Adrià; de Aguiar, Vânia; Miceli, Gabriele

2015-07-01

During awake surgery, picture-naming tests are administered to identify brain structures related to language function (language mapping), and to avoid iatrogenic damage. Before and after surgery, naming tests and other neuropsychological procedures aim at charting naming abilities, and at detecting which items the subject can respond to correctly. To achieve this goal, sufficiently large samples of normed and standardized stimuli must be available for preoperative and postoperative testing, and to prepare intraoperative tasks, the latter only including items named flawlessly preoperatively. To discuss design, norming and presentation of stimuli, and to describe the minimal standardization setting used to develop two sets of Italian stimuli, one for object naming and one for verb naming, respectively. The setting includes a naming study (to obtain picture-name agreement ratings), two on-line questionnaires (to acquire age-of-acquisition and imageability ratings for all test items), and the norming of other relevant language variables. The two sets of stimuli have >80 % picture-name agreement, high levels of internal consistency and reliability for imageability and age of acquisition ratings. They are normed for psycholinguistic variables known to affect lexical access and retrieval, and are validated in a clinical population. This framework can be used to increase the probability of reliably detecting language impairments before and after surgery, to prepare intraoperative tests based on sufficient knowledge of pre-surgical language abilities in each patient, and to decrease the probability of false positives during surgery. Examples of data usage are provided. Normative data can be found in the supplementary materials.

Selecting accurate post-elimination monitoring tools to prevent reemergence of urogenital schistosomiasis in Morocco: a pilot study.

PubMed

Balahbib, Abdelaali; Amarir, Fatima; Corstjens, Paul L A M; de Dood, Claudia J; van Dam, Govert J; Hajli, Amina; Belhaddad, Meryem; El Mansouri, Bouchra; Sadak, Abderrahim; Rhajaoui, Mohamed; Adlaoui, El Bachir

2017-04-06

After alleged stop of transmission of schistosomiasis and further down the line in post elimination settings, sensitive tools are required to monitor infection status to prevent potential re-emergence. In Rahala, where transmission cycle of Schistosoma haematobium is interrupted since 2004 but where 30% of snails are still infected by S. bovis, potential human S. bovis infection can't be excluded. As methods based on egg-counts do not provide the required sensitivity, antibody or antigen assays are envisaged as the most appropriate tools for this type of monitoring. In this pilot study, the performances of three assays were compared: two commercially available antibody tests (ELISA and haemagglutination format) indicating exposure, and an antigen test (lateral flow strip format) demonstrating active infection. All 37 recruited study participants resided in Rahala (Akka, province Tata, Morocco). Participants had been diagnosed and cured from schistosomiasis in the period between 1983 and 2003. In 2015 these asymptomatic participants provided fresh clinical samples (blood and urine) for analysis with the aforementioned diagnostics tests. No eggs were identified in the urine of the 37 participants. The haemagglutination test indicated 6 antibody positives whereas the ELISA indicated 28 antibody positives, one indecisive and one false positive. ELISA and haemagglutination results matched for 18 individuals, amongst which 5 out of 6 haemagglutination positives. With the antigen test (performed on paired serum and urine samples), serum from two participants (cured 21 and 32 years ago) indicated the presence of low levels of the highly specific Schistosoma circulating anodic antigen (CAA), demonstrating low worm level infections (less than 5 pg/ml corresponding to probably single worm pair). One tested also CAA positive with urine. ELISA indicated the presence of human anti-Schistosoma antibodies in these two CAA positive cases, haemagglutination results were negative. To prevent reemergence of schistosomiasis in Morocco current monitoring programs require specific protocols that include testing of antibody positives for active infection by the UCP-LF CAA test, the appropriate diagnostic tool to identify Schistosoma low grade infections in travelers, immigrants and assumed cured cases. The test is genus specific will also identify infections related to S. bovis.

Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus

PubMed Central

Rezaie, Ali; Buresi, Michelle; Lembo, Anthony; Lin, Henry; McCallum, Richard; Rao, Satish; Schmulson, Max; Valdovinos, Miguel; Zakko, Salam; Pimentel, Mark

2017-01-01

Objectives: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Methods: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Results: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. Conclusions: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research. PMID:28323273

Data-driven region-of-interest selection without inflating Type I error rate.

PubMed

Brooks, Joseph L; Zoumpoulaki, Alexia; Bowman, Howard

2017-01-01

In ERP and other large multidimensional neuroscience data sets, researchers often select regions of interest (ROIs) for analysis. The method of ROI selection can critically affect the conclusions of a study by causing the researcher to miss effects in the data or to detect spurious effects. In practice, to avoid inflating Type I error rate (i.e., false positives), ROIs are often based on a priori hypotheses or independent information. However, this can be insensitive to experiment-specific variations in effect location (e.g., latency shifts) reducing power to detect effects. Data-driven ROI selection, in contrast, is nonindependent and uses the data under analysis to determine ROI positions. Therefore, it has potential to select ROIs based on experiment-specific information and increase power for detecting effects. However, data-driven methods have been criticized because they can substantially inflate Type I error rate. Here, we demonstrate, using simulations of simple ERP experiments, that data-driven ROI selection can indeed be more powerful than a priori hypotheses or independent information. Furthermore, we show that data-driven ROI selection using the aggregate grand average from trials (AGAT), despite being based on the data at hand, can be safely used for ROI selection under many circumstances. However, when there is a noise difference between conditions, using the AGAT can inflate Type I error and should be avoided. We identify critical assumptions for use of the AGAT and provide a basis for researchers to use, and reviewers to assess, data-driven methods of ROI localization in ERP and other studies. © 2016 Society for Psychophysiological Research.

Kepler Mission Discovers Trove of Extrasolar Planet Candidates

NASA Astrophysics Data System (ADS)

Showstack, Randy

2011-02-01

NASA's Kepler discovery mission is collecting more than just pennies from heaven. Results from the first 4 months of science operations of the Kepler space telescope, announced on 2 February, include the discovery of 1235 candidate planets orbiting 997 stars in a small portion of the Milky Way galaxy examined by the telescope. Follow-up observations likely could confirm about 80% of the candidates as actual planets rather than false positives, according to researchers. This new trove of possible exoplanets could greatly expand the number of known planets outside of our solar system.

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

PubMed

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

2015-02-01

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

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

PubMed

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

2015-08-01

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

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

PubMed

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

2009-02-01

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

Breast cancer mammographic diagnosis performance in a public health institution: a retrospective cohort study.

PubMed

Mello, Juliana M R B; Bittelbrunn, Fernando P; Rockenbach, Marcio A B C; May, Guilherme G; Vedolin, Leonardo M; Kruger, Marilia S; Soldatelli, Matheus D; Zwetsch, Guilherme; de Miranda, Gabriel T F; Teixeira, Saone I P; Arruda, Bruna S

2017-12-01

To evaluate the quality assurance of mammography results at a reference institution for the diagnosis and treatment of breast cancer in southern Brazil, based on the BIRADS (Breast Imaging Reporting and Data System) 5th edition recommendations for auditing purposes. Retrospective cohort and cross-sectional study with 4502 patients (9668 mammographies)) who underwent at least one or both breast mammographies throughout 2013 at a regional public hospital, linked to a federal public university. The results were followed until 31 December 2014, including true positives (TPs), true negatives (TNs), false positives (FPs), false negatives (FNs), positive predictive values (PPVs), negative predictive value (NPV), sensitivity and specificity, with a confidence interval of 95%. The study showed high quality assurance, particularly regarding sensitivity (90.22%) and specificity (92.31%). The overall positive predictive value (PPV) was 65.35%, and the negative predictive value (NPV) was 98.32%. The abnormal interpretation rate (recall rate) was 12.26%. The results are appropriate when compared to the values proposed by the BIRADS 5th edition. Additionally, the study provided self-reflection considering our radiological practice, which is essential for improvements and collaboration regarding breast cancer detection. It may stimulate better radiological practice performance and continuing education, despite possible infrastructure and facility limitations. • Accurate quality performance rates are possible despite financial and governmental limitations. • Low-income institutions should develop standardised teamwork to improve radiological practice. • Regular mammography audits may help to increase the quality of public health systems.

Automation of a flocculation test for syphilis on Groupamatic equipment.

PubMed Central

Garretta, M; Paris-Hamelin, A; Gener, J; Muller, A; Matte, C; Vaisman, A

1975-01-01

A flocculation reaction employing a cardiolipid antigen was used for syphilis screening on Groupamatic equipment in parallel with conventional screening reactions: Kolmer CF, RPCF, Kahn, Kline, and RPR. The positive samples were confirmed by FTA-200, FTA-ABS, TPI, and in some cases by TPHA. There were 5,212 known samples which had already been tested by all methods and of which 1,648 were positive, and 58,636 screened samples including 65 positives. Half of the samples in the first series were taken without anticoagulant; the remainder were collected in potassium EDTA. The percentage of false positives with the Groupamatic was about 1-4 per cent. The percentage of false negatives among positve (greater than or equal+) samples varied from 0-18 to 1-3 per cent.; on the other hand the sensitivity was less good for samples giving doubtful and/or dissociated reactions in conventional screening reactions. The specificity and sensitivity of this technique are acceptable for a blood transfusion centre. The reproducibility is excellent and the automatic reading of results accurate. Additional advantages are rapidity (340 samples processed per hour); simultaneous performance of eleven other immunohaematological reactions; no contamination between samples; automatic reading, interpretation, and print-out of results; and saving of time because samples are not filed sequentially and are automatically identified when the results are obtained. Although the importance of syphilis in blood transfusion seems small, estimates of the risk are difficult and further investigations are planned. Images PMID:1098731

Real-time processing of EMG signals for bionic arm purposes

NASA Astrophysics Data System (ADS)

Olid Dominguez, Ferran; Wawrzyniak, Zbigniew M.

2016-09-01

This paper is connected with the problem of prostheses, that have always been a necessity for the human being. Bio-physiological signals from muscles, electromyographic signals have been collected, analyzed and processed in order to implement a real-time algorithm which is capable of differentiation of two different states of a bionic hand: open and closed. An algorithm for real-time electromyographic signal processing with almost no false positives is presented and it is explained that in bio-physiological experiments proper signal processing is of great importance.

[A quickly methodology for drug intelligence using profiling of illicit heroin samples].

PubMed

Zhang, Jianxin; Chen, Cunyi

2012-07-01

The aim of the paper was to evaluate a link between two heroin seizures using a descriptive method. The system involved the derivation and gas chromatographic separation of samples followed by a fully automatic data analysis and transfer to a database. Comparisons used the square cosine function between two chromatograms assimilated to vectors. The method showed good discriminatory capabilities. The probability of false positives was extremely slight. In conclusion, this method proved to be efficient and reliable, which appeared suitable for estimating the links between illicit heroin samples.

Source detection at 100 meter standoff with a time-encoded imaging system

NASA Astrophysics Data System (ADS)

Brennan, J.; Brubaker, E.; Gerling, M.; Marleau, P.; Monterial, M.; Nowack, A.; Schuster, P.; Sturm, B.; Sweany, M.

2018-01-01

We present the design, characterization, and testing of a laboratory prototype radiological search and localization system. The system, based on time-encoded imaging, uses the attenuation signature of neutrons in time, induced by the geometrical layout and motion of the system. We have demonstrated the ability to detect a ∼ 1mCi252Cf radiological source at 100m standoff with 90% detection efficiency and 10% false positives against background in 12min. This same detection efficiency is met at 15s for a 40m standoff, and 1 . 2s for a 20m standoff.

Statistical behavior of ten million experimental detection limits

NASA Astrophysics Data System (ADS)

Voigtman, Edward; Abraham, Kevin T.

2011-02-01

Using a lab-constructed laser-excited fluorimeter, together with bootstrapping methodology, the authors have generated many millions of experimental linear calibration curves for the detection of rhodamine 6G tetrafluoroborate in ethanol solutions. The detection limits computed from them are in excellent agreement with both previously published theory and with comprehensive Monte Carlo computer simulations. Currie decision levels and Currie detection limits, each in the theoretical, chemical content domain, were found to be simply scaled reciprocals of the non-centrality parameter of the non-central t distribution that characterizes univariate linear calibration curves that have homoscedastic, additive Gaussian white noise. Accurate and precise estimates of the theoretical, content domain Currie detection limit for the experimental system, with 5% (each) probabilities of false positives and false negatives, are presented.

Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus.

PubMed

Rezaie, Ali; Buresi, Michelle; Lembo, Anthony; Lin, Henry; McCallum, Richard; Rao, Satish; Schmulson, Max; Valdovinos, Miguel; Zakko, Salam; Pimentel, Mark

2017-05-01

Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

Predicting the severity of motor neuron disease progression using electronic health record data with a cloud computing Big Data approach.

PubMed

Ko, Kyung Dae; El-Ghazawi, Tarek; Kim, Dongkyu; Morizono, Hiroki

2014-05-01

Motor neuron diseases (MNDs) are a class of progressive neurological diseases that damage the motor neurons. An accurate diagnosis is important for the treatment of patients with MNDs because there is no standard cure for the MNDs. However, the rates of false positive and false negative diagnoses are still very high in this class of diseases. In the case of Amyotrophic Lateral Sclerosis (ALS), current estimates indicate 10% of diagnoses are false-positives, while 44% appear to be false negatives. In this study, we developed a new methodology to profile specific medical information from patient medical records for predicting the progression of motor neuron diseases. We implemented a system using Hbase and the Random forest classifier of Apache Mahout to profile medical records provided by the Pooled Resource Open-Access ALS Clinical Trials Database (PRO-ACT) site, and we achieved 66% accuracy in the prediction of ALS progress.

Processing demands in belief-desire reasoning: inhibition or general difficulty?

PubMed

Friedman, Ori; Leslie, Alan M

2005-05-01

Most 4-year-olds can predict the behavior of a person who wants an object but is mistaken about its location. More difficult is predicting behavior when the person is mistaken about location and wants to avoid the object. We tested between two explanations for children's difficulties with avoidance false belief: the Selection Processing model of inhibitory processing and a General Difficulty account. Children were presented with a false belief task and a control task, in which belief attribution was as difficult as in the false belief task. Predicting behavior in light of the character's desire to avoid the object added more difficulty in the false belief task. This finding is consistent with the Selection Processing model, but not with the General Difficulty account.

Affective SSVEP BCI to effectively control 3D objects by using a prism array-based display

NASA Astrophysics Data System (ADS)

Mun, Sungchul; Park, Min-Chul

2014-06-01

3D objects with depth information can provide many benefits to users in education, surgery, and interactions. In particular, many studies have been done to enhance sense of reality in 3D interaction. Viewing and controlling stereoscopic 3D objects with crossed or uncrossed disparities, however, can cause visual fatigue due to the vergenceaccommodation conflict generally accepted in 3D research fields. In order to avoid the vergence-accommodation mismatch and provide a strong sense of presence to users, we apply a prism array-based display to presenting 3D objects. Emotional pictures were used as visual stimuli in control panels to increase information transfer rate and reduce false positives in controlling 3D objects. Involuntarily motivated selective attention by affective mechanism can enhance steady-state visually evoked potential (SSVEP) amplitude and lead to increased interaction efficiency. More attentional resources are allocated to affective pictures with high valence and arousal levels than to normal visual stimuli such as white-and-black oscillating squares and checkerboards. Among representative BCI control components (i.e., eventrelated potentials (ERP), event-related (de)synchronization (ERD/ERS), and SSVEP), SSVEP-based BCI was chosen in the following reasons. It shows high information transfer rates and takes a few minutes for users to control BCI system while few electrodes are required for obtaining reliable brainwave signals enough to capture users' intention. The proposed BCI methods are expected to enhance sense of reality in 3D space without causing critical visual fatigue to occur. In addition, people who are very susceptible to (auto) stereoscopic 3D may be able to use the affective BCI.

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

Deducing the Milky Way's Massive Cluster Population

NASA Astrophysics Data System (ADS)

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

2010-11-01

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

Biased lineup instructions and face identification from video images.

PubMed

Thompson, W Burt; Johnson, Jaime

2008-01-01

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

Evaluation of DNA extraction protocols for Brucella abortus pcr detection in aborted fetuses or calves born from cows experimentally infected with strain 2308

PubMed Central

Matrone, M.; Keid, L.B.; Rocha, V.C.M.; Vejarano, M.P.; Ikuta, C.Y.; Rodriguez, C.A.R.; Ferreira, F.; Dias, R.A.; Ferreira Neto, J.S

2009-01-01

The objective of the present study was to improve the detection of B. abortus by PCR in organs of aborted fetuses from infected cows, an important mechanism to find infected herds on the eradication phase of the program. So, different DNA extraction protocols were compared, focusing the PCR detection of B. abortus in clinical samples collected from aborted fetuses or calves born from cows challenged with the 2308 B. abortus strain. Therefore, two gold standard groups were built based on classical bacteriology, formed from: 32 lungs (17 positives), 26 spleens (11 positives), 23 livers (8 positives) and 22 bronchial lymph nodes (7 positives). All samples were submitted to three DNA extraction protocols, followed by the same amplification process with the primers B4 and B5. From the accumulated results for organ, the proportion of positives for the lungs was higher than the livers (p=0.04) or bronchial lymph nodes (p=0.004) and equal to the spleens (p=0.18). From the accumulated results for DNA extraction protocol, the proportion of positives for the Boom protocol was bigger than the PK (p< 0.0001) and GT (p=0.0004). There was no difference between the PK and GT protocols (p=0.5). Some positive samples from the classical bacteriology were negative to the PCR and vice-versa. Therefore, the best strategy for B. abortus detection in the organs of aborted fetuses or calves born from infected cows is the use, in parallel, of isolation by classical bacteriology and the PCR, with the DNA extraction performed by the Boom protocol. PMID:24031391

Ankle-Brachial index by oscillometry: A very useful method to assess peripheral arterial disease in diabetes

PubMed Central

Premanath, M.; Raghunath, M.

2010-01-01

Background: Peripheral Arterial Disease (PAD) remains the least recognized form of atherosclerosis. The Ankle-Brachial Index (ABI) has emerged as one of the potent markers of diffuse atherosclerosis, cardiovascular (CV) risk, and overall survival in general public, especially in diabetics. The important reason for the lack of early diagnosis is the non-availability of a test that is easy to perform and less expensive, with no training required. Objectives: To evaluate the osillometric method of performing ABI with regard to its usefulness in detecting PAD cases and to correlate the signs and symptoms with ABI. Materials and Methods: Two hundred diabetics of varying duration attending the clinic for a period of eight months, from August 2006 to April 2007, were evaluated for signs, symptoms, and risk factors. ABI was performed using the oscillometric method. The positives were confirmed by Doppler evaluation. An equal number of age- and sex-matched controls, which were ABI negative, were also assessed by Doppler. Sensitivity and Specificity were determined. Results: There were 120 males and 80 females. Twelve males (10%) and six females (7.5%) were ABI positive. On Doppler, eleven males (91.5%) and three females (50%) were true positives. There were six false negatives from the controls (three each). The Sensitivity was 70% and Specificity was 75%. Symptoms and signs correlated well with ABI positives. Hypertension was the most important risk factor. Conclusions: In spite of the limitations, the oscillometric method of performing ABI is a simple procedure, easy to perform, does not require training and can be performed as an outpatient procedure not only by doctors, but also by the paramedical staff to detect more PAD cases. PMID:20535314

Network Compression as a Quality Measure for Protein Interaction Networks

PubMed Central

Royer, Loic; Reimann, Matthias; Stewart, A. Francis; Schroeder, Michael

2012-01-01

With the advent of large-scale protein interaction studies, there is much debate about data quality. Can different noise levels in the measurements be assessed by analyzing network structure? Because proteomic regulation is inherently co-operative, modular and redundant, it is inherently compressible when represented as a network. Here we propose that network compression can be used to compare false positive and false negative noise levels in protein interaction networks. We validate this hypothesis by first confirming the detrimental effect of false positives and false negatives. Second, we show that gold standard networks are more compressible. Third, we show that compressibility correlates with co-expression, co-localization, and shared function. Fourth, we also observe correlation with better protein tagging methods, physiological expression in contrast to over-expression of tagged proteins, and smart pooling approaches for yeast two-hybrid screens. Overall, this new measure is a proxy for both sensitivity and specificity and gives complementary information to standard measures such as average degree and clustering coefficients. PMID:22719828

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.

When species matches are unavailable are DNA barcodes correctly assigned to higher taxa? An assessment using sphingid moths

PubMed Central

2011-01-01

Background When a specimen belongs to a species not yet represented in DNA barcode reference libraries there is disagreement over the effectiveness of using sequence comparisons to assign the query accurately to a higher taxon. Library completeness and the assignment criteria used have been proposed as critical factors affecting the accuracy of such assignments but have not been thoroughly investigated. We explored the accuracy of assignments to genus, tribe and subfamily in the Sphingidae, using the almost complete global DNA barcode reference library (1095 species) available for this family. Costa Rican sphingids (118 species), a well-documented, diverse subset of the family, with each of the tribes and subfamilies represented were used as queries. We simulated libraries with different levels of completeness (10-100% of the available species), and recorded assignments (positive or ambiguous) and their accuracy (true or false) under six criteria. Results A liberal tree-based criterion assigned 83% of queries accurately to genus, 74% to tribe and 90% to subfamily, compared to a strict tree-based criterion, which assigned 75% of queries accurately to genus, 66% to tribe and 84% to subfamily, with a library containing 100% of available species (but excluding the species of the query). The greater number of true positives delivered by more relaxed criteria was negatively balanced by the occurrence of more false positives. This effect was most sharply observed with libraries of the lowest completeness where, for example at the genus level, 32% of assignments were false positives with the liberal criterion versus < 1% when using the strict. We observed little difference (< 8% using the liberal criterion) however, in the overall accuracy of the assignments between the lowest and highest levels of library completeness at the tribe and subfamily level. Conclusions Our results suggest that when using a strict tree-based criterion for higher taxon assignment with DNA barcodes, the likelihood of assigning a query a genus name incorrectly is very low, if a genus name is provided it has a high likelihood of being accurate, and if no genus match is available the query can nevertheless be assigned to a subfamily with high accuracy regardless of library completeness. DNA barcoding often correctly assigned sphingid moths to higher taxa when species matches were unavailable, suggesting that barcode reference libraries can be useful for higher taxon assignments long before they achieve complete species coverage. PMID:21806794

Neural network for photoplethysmographic respiratory rate monitoring

NASA Astrophysics Data System (ADS)

Johansson, Anders

2001-10-01

The photoplethysmographic signal (PPG) includes respiratory components seen as frequency modulation of the heart rate (respiratory sinus arrhythmia, RSA), amplitude modulation of the cardiac pulse, and respiratory induced intensity variations (RIIV) in the PPG baseline. The aim of this study was to evaluate the accuracy of these components in determining respiratory rate, and to combine the components in a neural network for improved accuracy. The primary goal is to design a PPG ventilation monitoring system. PPG signals were recorded from 15 healthy subjects. From these signals, the systolic waveform, diastolic waveform, respiratory sinus arrhythmia, pulse amplitude and RIIV were extracted. By using simple algorithms, the rates of false positive and false negative detection of breaths were calculated for each of the five components in a separate analysis. Furthermore, a simple neural network (NN) was tried out in a combined pattern recognition approach. In the separate analysis, the error rates (sum of false positives and false negatives) ranged from 9.7% (pulse amplitude) to 14.5% (systolic waveform). The corresponding value of the NN analysis was 9.5-9.6%.

Texture analysis applied to second harmonic generation image data for ovarian cancer classification

NASA Astrophysics Data System (ADS)

Wen, Bruce L.; Brewer, Molly A.; Nadiarnykh, Oleg; Hocker, James; Singh, Vikas; Mackie, Thomas R.; Campagnola, Paul J.

2014-09-01

Remodeling of the extracellular matrix has been implicated in ovarian cancer. To quantitate the remodeling, we implement a form of texture analysis to delineate the collagen fibrillar morphology observed in second harmonic generation microscopy images of human normal and high grade malignant ovarian tissues. In the learning stage, a dictionary of "textons"-frequently occurring texture features that are identified by measuring the image response to a filter bank of various shapes, sizes, and orientations-is created. By calculating a representative model based on the texton distribution for each tissue type using a training set of respective second harmonic generation images, we then perform classification between images of normal and high grade malignant ovarian tissues. By optimizing the number of textons and nearest neighbors, we achieved classification accuracy up to 97% based on the area under receiver operating characteristic curves (true positives versus false positives). The local analysis algorithm is a more general method to probe rapidly changing fibrillar morphologies than global analyses such as FFT. It is also more versatile than other texture approaches as the filter bank can be highly tailored to specific applications (e.g., different disease states) by creating customized libraries based on common image features.

Isolating "Unknown" Bacteria in the Introductory Microbiology Laboratory: A New Selective Medium for Gram-Positives.

ERIC Educational Resources Information Center

McKillip, John L.; Drake, MaryAnne

1999-01-01

Describes the development, preparation, and use of a medium that can select against a wide variety of Gram-negative bacteria while still allowing growth and differentiation of a wide range of Gram-positives. (WRM)

Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates.

PubMed

Bodian, Dale L; Klein, Elisabeth; Iyer, Ramaswamy K; Wong, Wendy S W; Kothiyal, Prachi; Stauffer, Daniel; Huddleston, Kathi C; Gaither, Amber D; Remsburg, Irina; Khromykh, Alina; Baker, Robin L; Maxwell, George L; Vockley, Joseph G; Niederhuber, John E; Solomon, Benjamin D

2016-03-01

To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing. NBS genes are generally well covered by WGS. There is a median of one (range: 0-6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays.

A framework for automatic information quality ranking of diabetes websites.

PubMed

Belen Sağlam, Rahime; Taskaya Temizel, Tugba

2015-01-01

Objective: When searching for particular medical information on the internet the challenge lies in distinguishing the websites that are relevant to the topic, and contain accurate information. In this article, we propose a framework that automatically identifies and ranks diabetes websites according to their relevance and information quality based on the website content. Design: The proposed framework ranks diabetes websites according to their content quality, relevance and evidence based medicine. The framework combines information retrieval techniques with a lexical resource based on Sentiwordnet making it possible to work with biased and untrusted websites while, at the same time, ensuring the content relevance. Measurement: The evaluation measurements used were Pearson-correlation, true positives, false positives and accuracy. We tested the framework with a benchmark data set consisting of 55 websites with varying degrees of information quality problems. Results: The proposed framework gives good results that are comparable with the non-automated information quality measuring approaches in the literature. The correlation between the results of the proposed automated framework and ground-truth is 0.68 on an average with p < 0.001 which is greater than the other proposed automated methods in the literature (r score in average is 0.33).

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

PubMed

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

2016-08-01

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

Identifying insects with incomplete DNA barcode libraries, African fruit flies (Diptera: Tephritidae) as a test case.

PubMed

Virgilio, Massimiliano; Jordaens, Kurt; Breman, Floris C; Backeljau, Thierry; De Meyer, Marc

2012-01-01

We propose a general working strategy to deal with incomplete reference libraries in the DNA barcoding identification of species. Considering that (1) queries with a large genetic distance with their best DNA barcode match are more likely to be misidentified and (2) imposing a distance threshold profitably reduces identification errors, we modelled relationships between identification performances and distance thresholds in four DNA barcode libraries of Diptera (n = 4270), Lepidoptera (n = 7577), Hymenoptera (n = 2067) and Tephritidae (n = 602 DNA barcodes). In all cases, more restrictive distance thresholds produced a gradual increase in the proportion of true negatives, a gradual decrease of false positives and more abrupt variations in the proportions of true positives and false negatives. More restrictive distance thresholds improved precision, yet negatively affected accuracy due to the higher proportions of queries discarded (viz. having a distance query-best match above the threshold). Using a simple linear regression we calculated an ad hoc distance threshold for the tephritid library producing an estimated relative identification error <0.05. According to the expectations, when we used this threshold for the identification of 188 independently collected tephritids, less than 5% of queries with a distance query-best match below the threshold were misidentified. Ad hoc thresholds can be calculated for each particular reference library of DNA barcodes and should be used as cut-off mark defining whether we can proceed identifying the query with a known estimated error probability (e.g. 5%) or whether we should discard the query and consider alternative/complementary identification methods.

Magnetic resonance imaging for detecting root avulsions in traumatic adult brachial plexus injuries: protocol for a systematic review of diagnostic accuracy.

PubMed

Wade, Ryckie G; Takwoingi, Yemisi; Wormald, Justin C R; Ridgway, John P; Tanner, Steven; Rankine, James J; Bourke, Grainne

2018-05-19

Adult brachial plexus injuries (BPI) are becoming more common. The reconstruction and prognosis of pre-ganglionic injuries (root avulsions) are different to other types of BPI injury. Preoperative magnetic resonance imaging (MRI) is being used to identify root avulsions, but the evidence from studies of its diagnostic accuracy are conflicting. Therefore, a systematic review is needed to address uncertainty about the accuracy of MRI and to guide future research. We will conduct a systematic search of electronic databases alongside reference tracking. We will include studies of adults with traumatic BPI which report the accuracy of preoperative MRI (index test) against surgical exploration of the roots of the brachial plexus (reference standard) for detecting either of the two target conditions (any root avulsion or any pseudomeningocoele as a surrogate marker of root avulsion). We will exclude case reports, articles considering bilateral injuries and studies where the number of true positives, false positives, false negatives and true negatives cannot be derived. The methodological quality of the included studies will be assessed using a tailored version of the QUADAS-2 tool. Where possible, a bivariate model will be used for meta-analysis to obtain summary sensitivities and specificities for both target conditions. We will investigate heterogeneity in the performance of MRI according to field strength and the risk of bias if data permits. This review will summarise the current diagnostic accuracy of MRI for adult BPI, identify shortcomings and gaps in the literature and so help to guide future research. PROSPERO CRD42016049702 .

Assay based on electrical impedance spectroscopy to discriminate between normal and cancerous mammalian cells.

PubMed

Giana, Fabián Eduardo; Bonetto, Fabián José; Bellotti, Mariela Inés

2018-03-01

In this work we present an assay to discriminate between normal and cancerous cells. The method is based on the measurement of electrical impedance spectra of in vitro cell cultures. We developed a protocol consisting on four consecutive measurement phases, each of them designed to obtain different information about the cell cultures. Through the analysis of the measured data, 26 characteristic features were obtained for both cell types. From the complete set of features, we selected the most relevant in terms of their discriminant capacity by means of conventional statistical tests. A linear discriminant analysis was then carried out on the selected features, allowing the classification of the samples in normal or cancerous with 4.5% of false positives and no false negatives.

Assay based on electrical impedance spectroscopy to discriminate between normal and cancerous mammalian cells

NASA Astrophysics Data System (ADS)

Giana, Fabián Eduardo; Bonetto, Fabián José; Bellotti, Mariela Inés

2018-03-01

In this work we present an assay to discriminate between normal and cancerous cells. The method is based on the measurement of electrical impedance spectra of in vitro cell cultures. We developed a protocol consisting on four consecutive measurement phases, each of them designed to obtain different information about the cell cultures. Through the analysis of the measured data, 26 characteristic features were obtained for both cell types. From the complete set of features, we selected the most relevant in terms of their discriminant capacity by means of conventional statistical tests. A linear discriminant analysis was then carried out on the selected features, allowing the classification of the samples in normal or cancerous with 4.5% of false positives and no false negatives.

33 CFR 83.08 - Action to avoid collision (Rule 8).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Action to avoid collision (Rule 8). 83.08 Section 83.08 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INLAND NAVIGATION RULES RULES Steering and Sailing Rules Conduct of Vessels in Any Condition of...

A new condition for assessing the clinical efficiency of a diagnostic test.

PubMed

Bokhari, Ehsan; Hubert, Lawrence

2015-09-01

When prediction using a diagnostic test outperforms simple prediction using base rates, the test is said to be "clinically efficient," a term first introduced into the literature by Meehl and Rosen (1955) in Psychological Bulletin. This article provides three equivalent conditions for determining the clinical efficiency of a diagnostic test: (a) Meehl-Rosen (Meehl & Rosen, 1955); (b) Dawes (Dawes, 1962); and (c) the Bokhari-Hubert condition, introduced here for the first time. Clinical efficiency is then generalized to situations where misclassification costs are considered unequal (for example, false negatives are more costly than false positives). As an illustration, the clinical efficiency of an actuarial device for predicting violent and dangerous behavior is examined that was developed as part of the MacArthur Violence Risk Assessment Study. (c) 2015 APA, all rights reserved.

33 CFR 83.08 - Action to avoid collision (Rule 8).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Action to avoid collision (Rule 8). 83.08 Section 83.08 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INLAND NAVIGATION RULES RULES Steering and Sailing Rules Conduct of Vessels in Any Condition of...

33 CFR 83.08 - Action to avoid collision (Rule 8).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Action to avoid collision (Rule 8). 83.08 Section 83.08 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INLAND NAVIGATION RULES RULES Steering and Sailing Rules Conduct of Vessels in Any Condition of...

Evaluation of a Cordia-IC enzyme-linked immunosorbent assay kit for the detection of circulating immune complexes.

PubMed Central

Landoy, Z; West, T E; Vladutiu, A O; Fitzpatrick, J E

1985-01-01

A commercial kit (Cordia-IC) from Cordis Laboratory, Miami, Fla., was compared with the Raji cell radioimmunoassay for its ability to detect circulating immune complexes (CIC) in sera from 30 control subjects and 118 patients with infectious diseases. The 118 patients were categorized into the following groups: (i) 23 patients with bacterial endocarditis, (ii) 41 patients with bacteremia from an infected intravascular catheter or access device, and (iii) 54 patients with Staphylococcus aureus bacteremia related to a deep tissue infection. The Cordia-IC was comparable to the Raji cell radioimmunoassay in intraassay variability (4.0 versus 8.0%) and interassay reproducibility (8.7 versus 20.0%). Neither assay found CIC amounts above 12.5 micrograms equivalents (eq) of aggregated human gamma globulin (AHG) per ml in any of the 30 control individuals. In group 1, Cordia-IC detected 19 of 23 positives (mean, 73.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 23 positives (mean, 54.8 micrograms eq of AHG per ml). In group 2, Cordia-IC detected 19 of 41 positives (mean, 20.6 micrograms eq of AHG per ml), whereas the Raji cell detected 16 of 41 positives (mean, 15.1 micrograms eq of AHG per ml). In group 3, Cordia-IC found 38 of 54 positives (mean, 28.0 micrograms eq of AHG per ml), whereas the Raji cell found 32 of 54 positives (mean, 23.9 micrograms eq of AHG per ml). Statistically, these findings were not significantly different in any of the three patient groups (P> 0.15), and there was an overall good correlation between the results obtained by the two assays (r+0.64, P<0.001). The Cordia-IC provided a suitable assay for the detection of CIC and might find application in routine clinical laboratories. PMID:3897269

33 CFR 83.08 - Action to avoid collision (Rule 8).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Action to avoid collision (Rule 8). 83.08 Section 83.08 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INLAND NAVIGATION RULES RULES Steering and Sailing Rules Conduct of Vessels in Any Condition of...

33 CFR 83.08 - Action to avoid collision (Rule 8).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Action to avoid collision (Rule 8). 83.08 Section 83.08 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INLAND NAVIGATION RULES RULES Steering and Sailing Rules Conduct of Vessels in Any Condition of...

Experimental investigation of observation error in anuran call surveys

USGS Publications Warehouse

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

2010-01-01

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

Identifying Insects with Incomplete DNA Barcode Libraries, African Fruit Flies (Diptera: Tephritidae) as a Test Case

PubMed Central

Virgilio, Massimiliano; Jordaens, Kurt; Breman, Floris C.; Backeljau, Thierry; De Meyer, Marc

2012-01-01

We propose a general working strategy to deal with incomplete reference libraries in the DNA barcoding identification of species. Considering that (1) queries with a large genetic distance with their best DNA barcode match are more likely to be misidentified and (2) imposing a distance threshold profitably reduces identification errors, we modelled relationships between identification performances and distance thresholds in four DNA barcode libraries of Diptera (n = 4270), Lepidoptera (n = 7577), Hymenoptera (n = 2067) and Tephritidae (n = 602 DNA barcodes). In all cases, more restrictive distance thresholds produced a gradual increase in the proportion of true negatives, a gradual decrease of false positives and more abrupt variations in the proportions of true positives and false negatives. More restrictive distance thresholds improved precision, yet negatively affected accuracy due to the higher proportions of queries discarded (viz. having a distance query-best match above the threshold). Using a simple linear regression we calculated an ad hoc distance threshold for the tephritid library producing an estimated relative identification error <0.05. According to the expectations, when we used this threshold for the identification of 188 independently collected tephritids, less than 5% of queries with a distance query-best match below the threshold were misidentified. Ad hoc thresholds can be calculated for each particular reference library of DNA barcodes and should be used as cut-off mark defining whether we can proceed identifying the query with a known estimated error probability (e.g. 5%) or whether we should discard the query and consider alternative/complementary identification methods. PMID:22359600

Using micropower impulse radar technology to screen for pneumothorax: an international bi-institutional study.

PubMed

van der Wilden, Gwendolyn M; Van der Wilden, Gwen; Albers, Christoph E; Albers, Christof; Haefeli, Pascal C; Haefeli, Peter; Zimmermann, Heinz; Zimmerman, Heinz; Exadaktylos, Aristomenis; Exadaktylos, Aris; Levy, Phillip; Birkhan, Oscar; Birkham, Oscar; Michaildou, Maria; Michailidou, Maria; Sideris, Antonios; Velmahos, George C; Velmahos, George; Alam, Hasan B; Alam, Hasan; King, David R; King, David; Fagenholz, Peter J; Fagenholz, Peter; Yeh, D Dante; Yeh, Dante; de Moya, Marc A

2012-12-01

Pneumothoraces (PTXs) are a common entity in thoracic trauma. Micropower impulse radar (MIR) has been able to detect PTXs in surgical patients. However, this technology has not been tested previously on trauma patients. The purpose of this study was to determine the sensitivity and specificity of MIR to detect clinically significant PTXs. We hypothesized that MIR technology can effectively screen trauma patients for clinically significant PTXs. This was a prospective observational study in Level I trauma centers in Boston, Massachusetts, and Bern, Switzerland. All trauma patients undergoing a chest computed tomographic (CT) scan were eligible for the study. Consent was obtained, and readings were performed within 30 minutes before or after the CT scan. The patients had eight lung fields tested (four on each side). The qualitative and quantitative MIR results were blinded and stored on the device. We then compared the results of the MIR to the CT scan and the need for chest tube drainage. We defined PTXs as clinically significant if they required a chest tube. Seventy-five patients were enrolled, with a mean age of 46 ± 16 years. Eighty-four percent were male. The screening test took approximately 1 minute. All but two patients had blunt chest trauma. Six true-positives, 6 false-positives, 63 true-negatives, and 0 false-negatives resulted in an overall sensitivity of 100%. MIR is an easy to use handheld technology that effectively screened patients for clinically significant PTXs, with a sensitivity and negative predictive value of 100%. MIR may be used for rapid, repeatable, and ongoing surveillance of trauma patients. Diagnostic study, level III.

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.

Development of the 7-Item Binge-Eating Disorder Screener (BEDS-7).

PubMed

Herman, Barry K; Deal, Linda S; DiBenedetti, Dana B; Nelson, Lauren; Fehnel, Sheri E; Brown, T Michelle

2016-01-01

Develop a brief, patient-reported screening tool designed to identify individuals with probable binge-eating disorder (BED) for further evaluation or referral to specialists. Items were developed on the basis of the DSM-5 diagnostic criteria, existing tools, and input from 3 clinical experts (January 2014). Items were then refined in cognitive debriefing interviews with participants self-reporting BED characteristics (March 2014) and piloted in a multisite, cross-sectional, prospective, noninterventional study consisting of a semistructured diagnostic interview (to diagnose BED) and administration of the pilot Binge-Eating Disorder Screener (BEDS), Binge Eating Scale (BES), and RAND 36-Item Short-Form Health Survey (RAND-36) (June 2014-July 2014). The sensitivity and specificity of classification algorithms (formed from the pilot BEDS item-level responses) in predicting BED diagnosis were evaluated. The final algorithm was selected to minimize false negatives and false positives, while utilizing the fewest number of BEDS items. Starting with the initial BEDS item pool (20 items), the 13-item pilot BEDS resulted from the cognitive debriefing interviews (n = 13). Of the 97 participants in the noninterventional study, 16 were diagnosed with BED (10/62 female, 16%; 6/35 male, 17%). Seven BEDS items (BEDS-7) yielded 100% sensitivity and 38.7% specificity. Participants correctly identified (true positives) had poorer BES scores and RAND-36 scores than participants identified as true negatives. Implementation of the brief, patient-reported BEDS-7 in real-world clinical practice is expected to promote better understanding of BED characteristics and help physicians identify patients who may have BED.

Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention.

PubMed

Mandelblatt, Jeanne; van Ravesteyn, Nicolien; Schechter, Clyde; Chang, Yaojen; Huang, An-Tsun; Near, Aimee M; de Koning, Harry; Jemal, Ahmedin

2013-07-15

US breast cancer mortality is declining, but thousands of women still die each year. Two established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI  ≥  30 kg/m(2) ). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer. If current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels. Maximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. © 2013 American Cancer Society.

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

PubMed

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

2014-06-01

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

Development of an improved CAD scheme for automated detection of lung nodules in digital chest images.

PubMed

Xu, X W; Doi, K; Kobayashi, T; MacMahon, H; Giger, M L

1997-09-01

Lung cancer is the leading cause of cancer deaths in men and women in the United States, with a 5-year survival rate of only about 13%. However, this survival rate can be improved to 47% if the disease is diagnosed and treated at an early stage. In this study, we developed an improved computer-aided diagnosis (CAD) scheme for the automated detection of lung nodules in digital chest images to assist radiologists, who could miss up to 30% of the actually positive cases in their daily practice. Two hundred PA chest radiographs, 100 normals and 100 abnormals, were used as the database for our study. The presence of nodules in the 100 abnormal cases was confirmed by two experienced radiologists on the basis of CT scans or radiographic follow-up. In our CAD scheme, nodule candidates were selected initially by multiple gray-level thresholding of the difference image (which corresponds to the subtraction of a signal-enhanced image and a signal-suppressed image) and then classified into six groups. A large number of false positives were eliminated by adaptive rule-based tests and an artificial neural network (ANN). The CAD scheme achieved, on average, a sensitivity of 70% with 1.7 false positives per chest image, a performance which was substantially better as compared with other studies. The CPU time for the processing of one chest image was about 20 seconds on an IBM RISC/6000 Powerstation 590. We believe that the CAD scheme with the current performance is ready for initial clinical evaluation.