Improving precision and reducing bias in biological surveys: estimating false-negative error rates

The use of presence/absence data in wildlife management and biological surveys is widespread. There is a growing interest in quantifying the sources of error associated with these data. We show that false-negative errors (failure to record a species when in fact it is present) can have a significant impact on statistical estimation of habitat models using simulated data. Then we introduce an extension of logistic modeling, the zero-inflated binomial (ZIB) model that permits the estimation of the rate of false-negative errors and the correction of estimates of the probability of occurrence for false-negative errors by using repeated. visits to the same site. Our simulations show that even relatively low rates of false negatives bias statistical estimates of habitat effects. The method with three repeated visits eliminates the bias, but estimates are relatively imprecise. Six repeated visits improve precision of estimates to levels comparable to that achieved with conventional statistics in the absence of false-negative errors In general, when error rates are less than or equal to50% greater efficiency is gained by adding more sites, whereas when error rates are >50% it is better to increase the number of repeated visits. We highlight the flexibility of the method with three case studies, clearly demonstrating the effect of false-negative errors for a range of commonly used survey methods.

Maximum Margin Classifiers with Specified False Positive and False Negative Error Rates

This paper addresses the problem of maximum margin classification given the moments of class conditional densities and the false positive and false negative error rates. Using Chebyshev inequalities, the problem can be posed as a second order cone programming problem. The dual of the formulation leads to a geometric optimization problem, that of computing the distance between two ellipsoids, which is solved by an iterative algorithm. The formulation is extended to non-linear classifiers using kernel methods. The resultant classifiers are applied to the case of classification of unbalanced datasets with asymmetric costs for misclassification. Experimental results on benchmark datasets show the efficacy of the proposed method.

Optimizing the balance between false positive and false negative error probabilities of confirmatory methods for the detection of veterinary drug residues

GC-MS data on veterinary drug residues in bovine urine are used for controlling the illegal practice of fattening cattle. According to current detection criteria, peak patterns of preferably four ions should agree within 10 or 20% from a corresponding standard pattern. These criteria are rigid, rather arbitrary and do not match daily practice. A new model, based on multivariate modeling of log peak abundance ratios, provides a theoretical basis for the identification of analytes and optimizes the balance between the avoidance of false positives and false negatives. The performance of the model is demonstrated on data provided by five laboratories, each supplying GC-MS measurements on the detection of clenbuterol, dienestrol and 19 beta-nortestosterone in urine. The proposed model shows a better performance than confirmation by using the current criteria and provides a statistical basis for inspection criteria in terms of error probabilities.

Clostridium difficile Ribotype 023 Lacks the Ability To Hydrolyze Esculin, Leading to False-Negative Results on Chromogenic Agar

41.Connor, M.C., Fairley, D.J. Marks, N.J. McGrath, J.W. (2016) Clostridium difficile Ribotype 023 lacks the ability to hydrolyse esculin, leading to false negative results on chromogenic agar. Letters in Applied Microbiology

Dengue-4 false negative results by Panbio (R) Dengue Early ELISA assay in Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Screening for carriage of methicillin-resistant Staphylococcus aureus shortly after exposure may lead to false-negative results

We evaluated a double screening strategy for carriage of methicillin-resistant Staphylococcus aureus (MRSA) in patients exposed to a newly detected MRSA carrier. If the first screening of the exposed patient yielded negative results, screening was repeated 4 days later. This strategy detected 12 (28%) of the 43 new MRSA carriers identified during the study period. The results suggest that there is an incubation period before MRSA carriage is detectable.

Is quantitative interpretation likely to increase sensitivity of dobutamine stress echocardiography? A study of false-negative results

Background: False-negative interpretations of do-butamine stress echocardiography (DSE) may be associated with reduced wall stress. using measurements of contraction, we sought whether these segments were actually ischemic but unrecognized or showed normal contraction. Methods. We studied 48 patients (29 men; mean age 60 +/- 10 years) with normal regional function on the basis of standard qualitative interpretation of DSE. At coronary angiography within. 6 months of DSE, 32 were identified as having true-negative and 16 as having false-negative results of DSE. Three apical views were used to measure regional function with color Doppler tissue, integrated backscatter, and strain rate imaging. Cyclic variation of integrated backscatter was measured in 16 segments, and strain rate and peak systolic strain was calculated in 6 walls at rest and peak stress. Results. Segments with false-negative results of DSE were divided into 2 groups with and without low wall stress according to previously published cut-off values. Age, sex, left ventricular mass, left ventricular geometric pattern, and peak workload were not significantly different between patients with true and false-negative results of DSE. Importantly, no significant differences in cyclic variation and strain parameters at rest and peak stress were found among segments with true-and false-negative results of DSE with and without low wall stress. Stenosis severity had no influence on cyclic variation and strain parameters at peak stress. Conclusions: False-negative results of DSE reflect lack of ischemia rather than underinterpretation of regional left ventricular function. Quantitative markers are unlikely to increase the sensitivity of DSE.

An optimal design for screening trials

Yao, Begg, and Livingston (1996, Biometrics 52, 992-1001) considered the optimal group size for testing a series of potentially therapeutic agents to identify a promising one as soon as possible for given error rates. The number of patients to be tested with each agent was fixed as the group size. We consider a sequential design that allows early acceptance and rejection, and we provide an optimal strategy to minimize the sample sizes (patients) required using Markov decision processes. The minimization is under the constraints of the two types (false positive and false negative) of error probabilities, with the Lagrangian multipliers corresponding to the cost parameters for the two types of errors. Numerical studies indicate that there can be a substantial reduction in the number of patients required.

Early diagnosis of breast cancer

The greatest effect on reducing mortality in breast cancer comes from the detection and treatment of invasive cancer when it is as small as possible. Although mammography screening is known to be effective, observer errors are frequent and false-negative cancers can be found in retrospective studies of prior mammograms. In the year 2001, 67 women with 69 surgically proven cancers detected at screening in the Mammography Centre of Helsinki University Hospital had previous mammograms as well. These mammograms were analyzed by an experienced screening radiologist, who found that 36 lesions were already visible in previous screening rounds. CAD (Second Look v. 4.01) detected 23 of these missed lesions. Eight readers with different kinds of experience with mammography screening read the films of 200 women with and without CAD. These films included 35 of those missed lesions and 16 screen-detected cancers. CAD sensitivity was 70.6% and specificity 15.8%. Use of CAD lengthened the mean time spent for readings but did not significantly affect readers sensitivities or specificities. Therefore the use of applied version of CAD (Second Look v. 4.01) is questionable. Because none of those eight readers found exactly same cancers, two reading methods were compared: summarized independent reading (at least a single cancer-positive opinion within the group considered decisive) and conference consensus reading (the cancer-positive opinion of the reader majority was considered decisive). The greatest sensitivity of 74.5% was achieved when the independent readings of 4 best-performing readers were summarized. Overall the summarized independent readings were more sensitive than conference consensus readings (64.7% vs. 43.1%) while there was far less difference in mean specificities (92.4% vs. 97.7%). After detecting suspicious lesion, the radiologist has to decide what is the most accurate, fast, and cost-effective means of further work-up. The feasibility of FNAC and CNB in the diagnosis of breast lesions was compared in non-randomised, retrospective study of 580 (503 malignant) breast lesions of 572 patients. The absolute sensitivity for CNB was better than for FNAC, 96% (206/214) vs. 67% (194/289) (p < 0.0001). An additional needle biopsy or surgical biopsy was performed for 93 and 62 patients with FNAC, but for only 2 and 33 patients with CNB. The frequent need of supplement biopsies and unnecessary axillary operations due to false-positive findings made FNAC (294 ) more expensive than CNB (223 ), and because the advantage of quick analysis vanishes during the overall diagnostic and referral process, it is recommendable to use CNB as initial biopsy method.

Negative and positive predictive values of nerve monitoring in thyroidectomy

Background Recurrent nerve injury is 1 of the most important complications of thyroidectomy. During the last decade, nerve monitoring has gained increasing acceptance in several centers as a method to predict and to document nerve function at the end of the operation. We evaluated the efficacy of a nerve monitoring system in a series of patients who underwent thyroidectomy and critically analyzed the negative predictive value (NPV) and positive predictive value (PPV) of the method. Methods. NIM System efficacy was prospectively analyzed in 447 patients who underwent thyroidectomy between 2001 and 2008 (366 female/81 male; 420 white/47 nonwhite; 11 to 82 years of age; median, 43 years old). There were 421 total thyroidectomies and 26 partial thyroidectomies, leading to 868 nerves at risk. The gold standard to evaluate inferior laryngeal nerve function was early postoperative videolaryngoscopy, which was repeated after 4 to 6 months in all patients with abnormal endoscopic findings. Results. At the early evaluation, 858 nerves (98.8%) presented normal videolaryngoscopic features after surgery. Ten paretic/paralyzed nerves (1.2%) were detected (2 unexpected unilateral paresis, 2 unexpected bilateral paresis, 1 unexpected unilateral paralysis, 1 unexpected bilateral paralyses, and 1 expected unilateral paralysis). At the late videolaryngoscopy, only 2 permanent nerve paralyses were noted (0.2%), with an ultimate result of 99.8% functioning nerves. Nerve monitoring showed absent or markedly reduced electrical activity at the end of the operations in 25/868 nerves (2.9%), including all 10 endoscopically compromised nerves, with 15 false-positive results. There were no false-negative results. Therefore, the PPV was 40.0%, and the NPV was 100%. Conclusions. In the present series, nerve monitoring had a very high PPV but a low NPV for the detection of recurrent nerve injury. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 175-179, 2012

Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data. MSforID'

A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30,000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their Setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS.

Biomarker-guided personalised emergency medicine for all - hope for another hype?

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and consecutive defensive medicine, second, delayed and sub-optimal therapeutic decisions, and third, prognostic uncertainty with misguided triage and site-of-care decisions all contributing to the waste of our limited health care resources. A multifaceted approach for a more targeted management of medical patients from emergency admission to discharge including biomarkers, will translate into better resource use, shorter length of hospital stay, reduced overall costs, improved patients satisfaction and outcomes in terms of mortality and re-hospitalisation. Hopefully, the concepts outlined in this review will help the reader to improve their diagnostic skills and become more parsimonious laboratory test requesters.

THE USE OF ARM CIRCUMFERENCE FOR SIMPLIFIED SCREENING FOR MALNUTRITION BY MINIMALLY TRAINED HEALTH WORKERS

Because of its simplicity and low cost, arm circumference (AC) is being used increasingly in screening for protein energy malnutrition among pre-school children in many parts of the developing world, especially where minimally trained health workers are employed. The objectives of this study were as follows: (1) To determine the relationship of the AC measure with weight for age and weight for height in the detection of malnutrition among pre-school children in a Guatemalan Indian village. (2) To determine the performance of minimally trained promoters under field conditions in measuring AC, weight and height. (3) To describe the practical aspects of taking AC measures versus weight, age and height.^ The study was conducted in San Pablo La Laguna, one of four villages situated on the shores of Lake Atitlan, Guatemala, in which a program of simplified medical care was implemented by the Institute for Nutrition for Central America and Panama (INCAP). Weight, height, AC and age data were collected for 144 chronically malnourished children. The measurements obtained by the trained investigator under the controlled conditions of the health post were correlated against one another and AC was found to have a correlation with weight for age of 0.7127 and with weight for height of 0.7911, both well within the 0.65 to 0.80 range reported in the literature. False positive and false negative analysis showed that AC was more sensitive when compared with weight for height than with weight for age. This was fortunate since, especially in areas with widespread chronic malnutrition, weight for height detects those acute cases in immediate danger of complicating illness or death. Moreover, most of the cases identified as malnourished by AC, but not by weight for height (false positives), were either young or very stunted which made their selection by AC better than weight for height. The large number of cases detected by weight for age, but not by AC (false negative rate--40%) were, however, mostly beyond the critical age period and had normal weight for heights.^ The performance of AC, weight for height and weight for age under field conditions in the hands of minimally trained health workers was also analyzed by correlating these measurements against the same criterion measurements taken under ideally controlled conditions of the health post. AC had the highest correlation with itself indicating that it deteriorated the least in the move to the field. Moreover, there was a high correlation between AC in the field and criterion weight for height (0.7509); this correlation was almost as high as that for field weight for height versus the same measure in the health post (0.7588). The implication is that field errors are so great for the compounded weight for height variable that, in the field, AC is about as good a predictor of the ideal weight for height measure.^ Minimally trained health workers made more errors than the investigator as exemplified by their lower intra-observer correlation coefficients. They consistently measured larger than the investigator for all measures. Also there was a great deal of variability between these minimally trained workers indicating that careful training and followup is necessary for the success of the AC measure.^ AC has many practical advantages compared to the other anthropometric tools. It does not require age data, which are often unreliable in these settings, and does not require sophisticated subtraction and two dimensional table-handling skills that weight for age and weight for height require. The measure is also more easily applied with less disturbance to the child and the community. The AC tape is cheap and not easily damaged or jarred out of calibration while being transported in rugged settings, as is often the case with weight scales. Moreover, it can be kept in a health worker's pocket at all times for continual use in a widespread range of settings. ^