Showing papers on "False positive paradox published in 1999"

Genomic control for association studies.

Abstract: A dense set of single nucleotide polymorphisms (SNP) covering the genome and an efficient method to assess SNP genotypes are expected to be available in the near future. An outstanding question is how to use these technologies efficiently to identify genes affecting liability to complex disorders. To achieve this goal, we propose a statistical method that has several optimal properties: It can be used with case control data and yet, like family-based designs, controls for population heterogeneity; it is insensitive to the usual violations of model assumptions, such as cases failing to be strictly independent; and, by using Bayesian outlier methods, it circumvents the need for Bonferroni correction for multiple tests, leading to better performance in many settings while still constraining risk for false positives. The performance of our genomic control method is quite good for plausible effects of liability genes, which bodes well for future genetic analyses of complex disorders.

Correspondence between outcomes of brief and extended functional analyses.

Abstract: We compared results obtained from 50 sets of functional analysis data from assessments of self-injurious behavior (SIB), 35 of which showed clear response patterns and 15 of which were undifferentiated, with those obtained from two abbreviated methods of assessment: (a) a brief functional analysis, consisting of the first session of each condition from the full functional analysis, and (b) a within-session analysis, in which data from the brief analysis were regraphed to show minute-by-minute changes in response rates during a session. Results indicated that outcomes of the brief and within-session analyses corresponded with those of the full functional analyses in 66.0% and 68.0% of the cases, respectively. Further examination of results indicated a tendency for the brief analysis to identify a large proportion of positive cases (both true and false positives) and for the within-session analysis to identify a large proportion of negative cases (true and false negatives).

Multiple Approaches to Analyzing Count Data in Studies of Individual Differences: The Propensity for Type I Errors, Illustrated with the Case of Absenteeism Prediction

Abstract: The present study compares eight models for analyzing count data: ordinary least squares (OLS), OLS with a transformed dependent variable, Tobit, Poisson, overdispersed Poisson, negative binomial, ordinal logistic, and ordinal probit regressions. Simulation reveals the extent that each model produces false positives. Results suggest that, despite methodological expectations, OLS regression does not produce more false positives than expected by chance. The Tobit and Poisson models yield too many false positives. The negative binomial models produce fewer than expected false positives.

A wavelet-based algorithm for detecting clustered microcalcifications in digital mammograms.

Abstract: A computerized scheme to detect clustered microcalcifications in digital mammograms has been developed. Detection of individual microcalcifications in regions of interest (ROIs) was also performed. The mammograms were previously classified into fatty and dense, according to their breast tissue. The most appropriate wavelet basis and reconstruction levels were selected. To select the wavelet basis, 40 profiles of microcalcifications were decomposed and reconstructed using different types of wavelet functions and different combinations of wavelet coefficients. The symlets with a basis of length 8 were chosen for fatty tissue. For dense tissue, the Daubechies’ wavelets with a four-element basis were employed. Two methods to detect individual microcalcifications were evaluated: (a) two-dimensional wavelet transform, and (b) one-dimensional wavelet transform. The second technique yielded the best results, and was used to detect clustered microcalcifications in the complete mammogram. When detecting individual microcalcifications by using two-dimensional wavelet transform we have obtained, for fatty ROIs, a sensitivity of 71.11% at a false positive rate of 7.13 per image. For dense ROIs the sensitivity was 60.76% and the false positive rate, 7.33. The areas (A 1 ) under the AFROC curves were 0.33±0.04 and 0.28±0.02, respectively. The one-dimensional wavelet transform method yielded 80.44% of sensitivity and 6.43 false positives per image (A 1 =0.39±0.03) for fatty ROIs, and 62.17% and 5.82 false positives per image (A 1 =0.37±0.02) for dense ROIs. For the detection of clusters of microcalcifications in the entire mammogram, the sensitivity was 80.00% with 0.94 false positives per image (A 1 =0.77±0.09) for fatty mammograms, and 72.85% of sensitivity at a false positive detection rate of 2.21 per image (A 1 =0.64±0.07) for dense mammograms. Globally, a sensitivity of 76.43% at a false positive detection rate of 1.57 per image was obtained.

Computerized detection of lung nodules using energy-subtracted soft-tissue and standard chest images

Abstract: A method, system and computer readable medium configured for computerized detection of lung abnormalities, including obtaining a standard digital chest image and a soft-tissue digital chest image; generating a first difference image from the standard digital chest image and a second difference image from the soft-tissue digital chest image; identifying candidate abnormalities in the first and second difference images; extracting from the standard digital chest image and the first difference image predetermined first features of each of the candidate abnormalities identified in the first difference image; extracting from the soft-tissue digital chest image and the second difference images predetermined second features of each of the candidate abnormalities identified in the second difference image; analyzing the extracted first features and the extracted second features to identify and eliminate false positive candidate abnormalities respectively corresponding thereto; applying extracted features from remaining candidate abnormalities derived respectively from the first and second difference images and remaining after the elimination of the false positive candidate abnormalities to respective artificial neural networks to eliminate further false positive candidate abnormalities; performing a logical OR operation of the candidate abnormalities derived respectively from the first and second difference images and remaining after the elimination of the false positive candidate abnormalities; and outputting a signal indicative of a result of performing the logical OR operation. The logical OR combination, of locations of the candidate abnormalities detected in the first difference image and the second difference image, yields an improved detection sensitivity (over 90%) and only slightly increased false positives rate (3.2 false positives per chest image).

Comparison of mammography and breast infrared imaging: sensitivity, specificity, false negatives, false positives, positive predictive value and negative predictive value

Abstract: Breast infrared imaging (IRI) for detection of breast cancer has been unfairly maligned as having unacceptably high false positive and false negative rates. IRI actually has statistical performance characteristics that are similar to mammography. The false positive rate of 14% is about twice as high as mammography but surgical intervention is not possible (no increase in invasive procedures). Also, the false negatives of IRI do not hinder the detection of breast cancer by physical exam, mammography and ultrasound. Finally, the ability of IRI to predict who will develop breast cancer is not appreciated and IRI results should be used to select patients for prevention trials.

Method of unsupervised cell nuclei segmentation

Abstract: A method of segmentation of cell nuclei is described that uses an active contours approach based on a Viterbi search algorithm. Also disclosed is an initialisation technique that maximises the probability of a correct segmentation. The invention also includes a method to classify cell nuclei according to the difficulty of correct segmentation. Nuclei that are difficult to segment can be rejected to minimise the probability of false positives. The probability of false positives can be driven close to 0%.

Reduction of False Positives in Prokaryotic mRNA Differential Display

Abstract: inverse PCR primers, P1 and P2, can be used to delete the same internal region from a series of DNA constructs containing the target region. Similarly, an internal deletion can be made by a PCR-ligation-PCR approach as described by Ali and Steinkasserer (1). According to this method, for example, the first-round PCR can be performed in two seperate reactions by primers V1/P2 and P1/V2, followed by ligation of the two PCR products and reamplification of the desired PCR product from the ligation mixture by primers V1/V2. The final PCR product will be equivalent to our PCR product after the second round of PCR. Compared with the method of Ali and Steinkasserer, our method has the following advantages. First, our procedure is completed by merely two PCRs instead of three. Second, our ligation is mostly a self-ligation with only a single ligated product with one orientation, while the method of Ali and Steinkasserer generates multiple products with different orientations, which can cause difficulty with identifying the correct PCR product in the end. Thus, our two-step PCR method is a useful alternative for generating an internal deletion.

Evaluation of replication studies, combined data analysis, and analytical methods in complex diseases.

Abstract: Due to genetic heterogeneity, phenocopies, incomplete penetrance, misdiagnosis, and unknown mode of inheritance, linkage studies of most complex diseases are unlikely to provide conclusive findings with unambiguously high lod scores. Typically, several marginally significant lod scores or elevated lod scores are observed in a genome-wide screen. However, it is usually difficult to differentiate these findings from false positives (type I errors). Two approaches are commonly used to guard against false positives: replication studies in independent samples and combined data analysis. In the current paper, we evaluated these two common approaches using simulated data where data from multiple groups were available and locations of disease genes were known. We found replication studies and combined data analysis performed similarly in terms of their ability to identify true and false positive linkages. Both approaches confirmed two true linkages and did not confirm any false positive linkages. The results also indicated that it is not appropriate to apply the criteria proposed for confirming significant evidence for linkage to confirm regions with only suggestive evidence for linkage. The current results support previous findings that parametric analysis using an incorrect genetic model can still identify a true linkage.

Method for decreasing false positives in frame synchronization of code division multiple access

Abstract: A solution to a problem of false positives in frame synchronization in telecommunication systems involves generating a separate channel estimate based only on the non-SW (all −1) bits of a pilot sequence. This non-SW channel estimate is used to correct received pilot SW symbols. These specially corrected symbols are rake combined separately from other symbols. The result is used exclusively for the frame synchronization detector. Normal channel estimate calculations and rake combining proceeds as usual. This method of frame synchronization only refers to SW bit matches. False positives are decreased using the invention.

Diagnostic performance of two antigen capture tests for the diagnosis of Plasmodium falciparum malaria in Zimbabwe.

Abstract: Objective The objective was to compare the diagnostic performance of two antigen capture tests, ParaSight-F test and Immunochromatographic test (ICT), for the diagnosis of Plasmodium falciparum malaria. Design A comparative study. Setting Burma Valley, Mutare District, Manicaland in Zimbabwe. Subjects Patients attending the local clinic with clinical signs and symptoms associated with malaria infection. A blood film was collected from the patient and at the same time blood for the ParaSight-F test and the ICT was collected too. A total of 123 patients were diagnosed using the ICT test, the ParaSight-F test and microscopy which was used as a "gold" standard. Main outcome measures True positives and negatives, false positives and negatives with reference to microscopy. Results The results indicate that ICT had a higher sensitivity (100%) than the ParaSight-F test (93.94%) but showing a lower specificity. The specificity for ICT (75%) is lower than the ParaSight-F test (81.2%) because of the presence of circulating P. falciparum histidine-rich protein-2 (PfHRP-2) in blood even after two weeks post treatment. Two slides that were negative for ParaSight-F tests showed positive on microscopy. However, 21 and 12 slides which were negative on microscopy, showed positive with ICT and ParaSight-F respectively. The fact that ICT detects very low quantities of PfHRP-2 puts it at a comparative advantage because it detects positives even at very low parasite rates. Conclusion The availability of these two antigen capture tests, which are easy to perform, will reduce the number of severe cases by providing early diagnosis. The tests will also reduce the number of unnecessary treatments and irrational use of antimalarials.

L'impiego delle dpoae negli screenings neonatali

Abstract: The purpose of the work was to determine the feasibility of direct nursery DPOAE testing in a universal hearing screening, evaluate the results and calculate the reliability of this test vs. Auditory Brainstem Responses (ABR). To this purpose DPOAE (sweep and I/O test) were performed on 500 children born between January and August 1996 at the Civil Hospital of Mestre, Italy. All the children were examined in the nursery, no matter what the risk factors or specific motivations. Besides determining whether the examination could be performed, its specificity and sensitivity, the time required and any variation depending on the day of testing were also evaluated. In a high percentage of cases (11.2%) it proved impossible to perform the test. In addition, when compared to ABR, the percentage of false positives was rather high (16.2%) and specificity was 84%. As conceived, the test requires 6'09" per ear. Comparison of the differences in results according to day of execution did not appear significant although there was a lower percentage of false positive after the third day of life. DPOAE can be measured in the nursery. The high number of false positives and the frequent need to repeat the measurements, however, increase the amount of time required for this test, thus voiding any time savings over an ABR screening: a test which is rather lengthy by provides a high degree of specificity.

[The clinical evaluation of MTD false-positive & false-negative results].

Abstract: The usefulness of MTD (Amplified Mycobacterium Tuberculosis Direct Test) for a rapid diagnosis of tuberculosis was evaluated. A total of 400 clinical samples obtained from July, 1995 to June, 1997 were tested by MTD, direct microscopy and culture. The results of MTD and smear/culture were coincident in 387 out of 400 samples. Eight samples (2%) were MTD false-positive (i.e. they were MTD positive but smear and culture negative), and 5 (1.25%) were MTD false-negative (i.e. MTD negative but smear and/or culture positive). Despite a careful review of the clinical data of those patients whose samples showed discrepant results, the reasons of discrepancy were not clear in 2 (0.5%) of the 8 false positives and 3 (0.75%) of the 5 false negatives. In the other cases, the MTD false positives may be accounted for the presence of previous M. tuberculosis infection, the influence of anti-tuberculous medication and so on, and the MTD false negatives are most likely due to the presence of inhibitors (blood, for example) or to the small number of organisms in the specimens. It can be concluded that adequate samples should be obtained, and that MTD should be repeated in case of discrepant results.