Application Of Diagnostic Tests Research Articles

Ethnic Disparities in Clinical Presentation of Patients with Early‐Onset Alzheimer’s Disease

AbstractBackgroundEarly‐onset Alzheimer’s Disease (EOAD) affects patients under age 65 and may present with non‐amnestic features. Black patients are half as likely as White patients to be diagnosed despite twice as many risk factors. Ethnic disparities in EOAD have not been fully characterized.MethodsWe retrospectively collected data on ethnicity, level of education, Montreal Cognitive Assessment (MoCA) scores on EOAD patients diagnosed between 2017 and 2022 at The University of Chicago Memory Center.ResultsOf 88 total patients, 60 (68.8%) identified as White and 28 (31.8%) identified as Black. Age at diagnosis was 57.3 ± 5.24 years in Black patients compared to 55.9 ± 5.69 years In White patients. Average time to diagnosis was longer in Black patients (5 ± 9.21 yrs.) vs White patients (3.5 ± 6.44 yrs). Black patients had lower MoCA scores than Whites at presentation (12.17 ± 6.91 vs 15.15 ± 5.92), despite similar education levels among Black vs. White patients (14.71 ± 2.30 vs 15.21 ± 3.00).Black patients more commonly displayed an amnestic profile (19 or 67.9%) than a non‐amnestic presentation (9 or 32.1%), although 2 patients (7.14%) presented with visual symptoms suggestive of posterior cortical atrophy (PCA), 5 (17.9%) patients had prominent language symptoms suggestive of logopenic primary progress aphasia (l‐PPA) and 1 (3.6%) patient had an executive presentation, suggestive of executive variant of AD (EAD). In White patients, 11 (18.3%) were diagnosed with PCA, 10 (16.7%) with EAD and 8 (13.3%) with l‐PPA.Differences were noted in the application of diagnostic tests, in that neuropsychological testing (NPT) and CSF testing were less often ordered in Black patients (NPT: 8 (29%) in Blacks vs 45 (75%) Whites, p = 0.001; CSF: 4 (14%) Blacks vs 30 (50%) Whites, p = 0.002).ConclusionIn our cohort, Black patients with EOAD were on average older, more advanced, and experience longer delays and differences in diagnostic management than their White counterparts. Further work is needed to characterize the barriers to diagnosis for Black patients with EOAD and the potential differences in clinical presentations.

Single-Domain Antibody Multimers for Detection of Botulinum Neurotoxin Serotypes C, D, and Their Mosaics in Endopep-MS.

Botulinum neurotoxins (BoNTs) are highly toxic proteins that require high-affinity immunocapture reagents for use in endopeptidase-based assays. Here, 30 novel and 2 earlier published llama single-domain antibodies (VHHs) against the veterinary-relevant BoNT serotypes C and D were yeast-produced. These VHHs recognized 10 independent antigenic sites, and many cross-reacted with the BoNT/DC and CD mosaic variants. As VHHs are highly suitable for genetically linking to increase antigen-binding affinity, 52 VHH multimers were produced and their affinity for BoNT/C, D, DC, and CD was determined. A selection of 15 multimers with high affinity (KD < 0.1 nM) was further shown to be resilient to a high salt wash that is used for samples from complex matrices and bound native BoNTs from culture supernatants as shown by Endopep-MS. High-affinity multimers suitable for further development of a highly sensitive Endopep-MS assay include four multimers that bind both BoNT/D and CD with KD of 14-99 pM, one multimer for BoNT/DC (65 pM) that also binds BoNT/C (75 pM), and seven multimers for BoNT/C (<1-19 pM), six of which also bind BoNT/DC with lower affinity (93-508 pM). In addition to application in diagnostic tests, these VHHs could be used for the development of novel therapeutics for animals or humans.

Climbing the Integration Ladder: A Case Study on an Interdisciplinary and Case-Based Approach to Teaching General Pathology, Parasitology and Microbiology in the Veterinary Curriculum.

The School of Veterinary Medicine, University College Dublin, Ireland, restructured the teaching of general pathology, parasitology, and microbiology in third year in 2018 as part of the development of an outcome-based curriculum. A new integrated teaching module was created, called Veterinary Pathobiology, which encompassed the three paraclinical subjects, worth 20 ECTS credits. Subject integration was driven and supported by case-based learning (CBL) activities, and practical classes, which were aimed at facilitating the understanding of basic disease processes, infectious agents, and the application of diagnostic tests. The disciplines maintained their identities within lectures which were aligned by content. The restructuring led to a reduction of contact hours by 20% and of assessment time by 40%. The examinations included integrated questions with an emphasis on the material students had covered in their CBL. Despite positive outcomes, which included equivalent examination scores and positive written feedback by students on teaching and learning, understanding, assessment, relevance, CBL, group work, and generic skills, the average scores for overall student satisfaction dropped dramatically in the second academic year of implementation. This followed the introduction of new regulations by the University relating to student progression, which was capped at "carrying" 10 ECTS credits, thus preventing students that failed the new module from progressing. Other criticisms of the new module by students included too little communication on the changes implemented in its first iteration and a workload perceived to be too heavy. Further restructuring is therefore necessary. This study highlights the process/pitfalls of integration/curricular innovation.

Synthetic Phenolic Glycolipids for Application in Diagnostic Tests for Leprosy.

Point‐of‐care (POC) diagnostic tests for the rapid detection of individuals infected with Mycobacterium leprae, the causative pathogen of leprosy, represent efficient tools to guide therapeutic and prophylactic treatment strategies in leprosy control programs, thus positively contributing to clinical outcome and reducing transmission of this infectious disease. Levels of antibodies directed against the M. leprae‐specific phenolic glycolipid I (PGL−I) closely correlate with an individual's bacterial load and a higher risk of developing leprosy. We describe herein the assembly of a set of PGL glycans carrying the characteristic phenol aglycon and featuring different methylation patterns. The PGL trisaccharides were applied to construct neoglycoproteins that were used to detect anti‐PGL IgM antibodies in leprosy patients. ELISAs and quantitative lateral‐flow assays based on up‐converting nanoparticles (UCP‐LFAs) showed that the generated PGL−I and PGL‐II trisaccharide neoglycoconjugates can be applied for the detection of anti M. leprae IgM antibodies in POC tests.

Automatic detection and characterization of quantitative phase images of thalassemic red blood cells using a mask region-based convolutional neural network.

.Significance: Label-free quantitative phase imaging is a promising technique for the automatic detection of abnormal red blood cells (RBCs) in real time. Although deep-learning techniques can accurately detect abnormal RBCs from quantitative phase images efficiently, their applications in diagnostic testing are limited by the lack of transparency. More interpretable results such as morphological and biochemical characteristics of individual RBCs are highly desirable.Aim: An end-to-end deep-learning model was developed to efficiently discriminate thalassemic RBCs (tRBCs) from healthy RBCs (hRBCs) in quantitative phase images and segment RBCs for single-cell characterization.Approach: Two-dimensional quantitative phase images of hRBCs and tRBCs were acquired using digital holographic microscopy. A mask region-based convolutional neural network (Mask R-CNN) model was trained to discriminate tRBCs and segment individual RBCs. Characterization of tRBCs was achieved utilizing SHapley Additive exPlanation analysis and canonical correlation analysis on automatically segmented RBC phase images.Results: The implemented model achieved 97.8% accuracy in detecting tRBCs. Phase-shift statistics showed the highest influence on the correct classification of tRBCs. Associations between the phase-shift features and three-dimensional morphological features were revealed.Conclusions: The implemented Mask R-CNN model accurately identified tRBCs and segmented RBCs to provide single-RBC characterization, which has the potential to aid clinical decision-making.

One-step wettability patterning of PDMS microchannels for generation of monodisperse alginate microbeads by in Situ external gelation in double emulsion microdroplets

Droplet-based microfluidic systems are promising tools for many biological applications from digitalized analysis to drug delivery and biomolecules synthesis. Among these, fabrication of microgels, particularly alginate microbeads, has substantial importance due to their capability for three-dimensional (3D) encapsulation of cells, drugs and other bioactive materials. However, biocompatible generation of monodisperse alginate microbeads is still challenging. In this study, a new droplet-based microfluidic strategy is developed for cell and chip friendly fabrication of monodispersed alginate microbeads. The polydimethylsiloxane (PDMS) microfluidic device is first treated using on-chip plasma-assisted deposition of polyvinyl alcohol, to selectively modify the hydrophobicity of microchannels. The proposed wettability patterning approach is permanent, simple, reliable, and time-effective, which makes the resulting microfluidic device highly stable and controllable for generation of double emulsions (DEs). The device is then used for fabrication of monodisperse alginate microbeads using external gelation in DE microdroplets. The reported microbead fabrication method offers both biocompatibility as a result of external gelation and rapid recovery of beads from processing solutions, as well as chip-compatibility due to clog-free gelation. This simple and robust DE strategy provides new opportunities not only for 3D micro-encapsulation but also for other droplet-based microfluidic applications in diagnostic testing and drug delivery.

Helicobacter pylori and some aspects of gut microbiota in children.

Helicobacter pylori infection in children differs from infection in adults in many aspects. The rate of infection, epidemiology, clinical presentations and complications, the applicability of diagnostic tests, antibiotic resistance, treatment options, and success rates differ significantly. Due to all these differences, management guidelines for children and adults differ also substantially. In 2017, the Updated ESPGHAN and NASPGHAN Guidelines on the management of H.pylori infection in children were published, emphasizing the differences in clinical presentation and indications for treatment, stating that the primary goal of clinical investigation in children is to identify the cause of upper gastrointestinal symptoms rather than the presence of H.pylori infection. Therefore, the diagnosis should be based on upper endoscopy, and the "test and treat strategy" should not be used in children. Due to an increasing rate of antibiotic resistance worldwide, the updated guidelines recommend broader use of antimicrobial susceptibility testing for H.pylori strains in order to tailor eradication treatment accordingly. Moreover, treatment in children should be prescribed only when indicated and should be based on the rate of eradication in local populations aiming for treatment success above 90%. During the last two decades there has been a steady decrease in the rate of H.pylori infection in both children and adults in the Western world. Two recent publications studying the incidence of H.pylori infection confirmed that early childhood is a time for acquisition of infection both in industrialized and nonindustrialized countries. In addition, they showed that H.pylori could be acquired outside the family. In respect to the inverse association between H.pylori and allergy, a longitudinal study demonstrated that early exposure to H.pylori at any age was inversely associated with atopy and allergic conditions.

Polymer nanoliter well arrays for liquid storage and rapid on-demand electrochemical release

Polymer microfluidic systems are of increasing importance in several applications in biomedicine and biosensing. The integrated encapsulation, storage, and controlled release of small amounts of liquid in such systems remains an unresolved technical challenge. Here, we report two methods for the room-temperature and adhesive-free sealing of 1–330 nanoliter volumes of liquid in off-stoichiometry thiol-ene polymer well arrays by spontaneous bonding to 200 nm thin gold films. Sealed well arrays were stored for more than one month in a liquid environment with <10% liquid loss, and for more than one week in air with minimal loss. We demonstrated that controlling the electrical potential and polarity over encapsulated wells allowed for selecting one of two well opening mechanisms: slow anodic electrochemical etching, or rapid electrolytic gas pressure-induced bursting of the gold film. The results may find potential applications in diagnostic testing, in vivo drug delivery, or in spatio-temporal release of chemical compounds in biological assays.

Pruebas diagnósticas: aspectos básicos de lo que el endoscopista debe saber

Choosing a test on a patient and its interpretation is a daily occurrence that the specialist is faced with, and the endoscopist is no stranger to this. It is common when talking of a diagnostic test (laboratory or imaging) to hear the mention of parameters such as sensitivity, specificity and predictive values. The parameters mentioned (sensitivity, specificity) establish the characteristics of a diagnostic test and are useful to decide when we should use them or the meaning that a test result has in a particular patient.The aim of the study is to present the basic statistical concepts for the understanding and application of diagnostic tests.

A preface on advances in diagnostics for infectious and parasitic diseases: detecting parasites of medical and veterinary importance.

There are many reasons why detection of parasites of medical and veterinary importance is vital and where novel diagnostic and surveillance tools are required. From a medical perspective alone, these originate from a desire for better clinical management and rational use of medications. Diagnosis can be at the individual-level, at close to patient settings in testing a clinical suspicion or at the community-level, perhaps in front of a computer screen, in classification of endemic areas and devising appropriate control interventions. Thus diagnostics for parasitic diseases has a broad remit as parasites are not only tied with their definitive hosts but also in some cases with their vectors/intermediate hosts. Application of current diagnostic tools and decision algorithms in sustaining control programmes, or in elimination settings, can be problematic and even ill-fitting. For example in resource-limited settings, are current diagnostic tools sufficiently robust for operational use at scale or are they confounded by on-the-ground realities; are the diagnostic algorithms underlying public health interventions always understood and well-received within communities which are targeted for control? Within this Special Issue (SI) covering a variety of diseases and diagnostic settings some answers are forthcoming. An important theme, however, throughout the SI is to acknowledge that cross-talk and continuous feedback between development and application of diagnostic tests is crucial if they are to be used effectively and appropriately.

Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis

Clinical Scenario A man was referred to liver transplantation clinic for the evaluation of enlarging abdominal girth and welling of feet during the preceding 2 months. The patient was Cambodian native who immigrated to the United States 5 ears ago. The patient was first diagnosed with chronic hepatitis virus (HBV) infection shortly after his entry into the United tates. However, he was not further evaluated, treated, or folowed. He had no personal or family history of liver disease or iver cancer. Physical examination of the abdomen showed mild epatosplenomegaly with positive shifting dullness from a oderate amount of ascites. There was no abdominal tenderess. Laboratory results included platelet count, 95,000/ L; spartate aminotransferase, 100 U/L; alanine aminotransferase, 5 U/L; and Model for End-Stage Liver Disease score, 13. Viral erology showed hepatitis B surface antigen–positive and entigen–positive and HBV DNA of 5 million IU/mL. Serum lpha-fetoprotein (AFP) was normal at 4 ng/mL. An abdominal ltrasound (US) showed cirrhotic liver contour and evidence of ortal hypertension. An esophagogastroduodenoscopy showed arge esophageal varices. The patient was started on the followng medications: spironolactone and furosemide for the ascites, ropranolol for the varices, and entecavir for HBV. Patient was urther assessed and then listed for liver transplantation. During the ensuing 12 months, the patient had substantial linical improvement including resolution of ascites as well as epatitis B e seroconversion. He also underwent abdominal US nd serum AFP measurement on a 6-month interval. An abominal US performed 18 months after his presentation howed a new 2.1-cm hyperechoic nodule in the right lobe of he liver along with mild elevation of serum AFP at 22 ng/mL. subsequent triphasic abdominal computed tomography (CT) can showed a 2.2-cm well-circumscribed vascular mass that ad arterial enhancement and venous washout, thus meeting he radiographic diagnosis criteria for hepatocellular carcinoma HCC) of the American Association for the Study of Liver isease (AASLD). The patient underwent transarterial chemombolization and subsequently received a liver transplant. Four ears later, the patient is doing well with satisfactory liver unction with no evidence of recurrent HBV or HCC.

A Review of Probiotic Therapy in Preventive Dental Practice.

Probiotics have been widely publicized in the general press and the consumer media. Knowledge of the existence of "probiotics" is commonplace, and the effectiveness of probiotic therapy has been well reported in the medical literature. However, even though most published dental studies have reported positive results, the dental profession has not yet accepted the use of probiotic therapy as an adjunct for preventive dental care. This review article discusses published and current research into the applications of probiotics along with diagnostic testing of the oral biofilm. Probiotic therapy appears to be generally safe and effective in modifying with beneficial bacteria the oral biofilm and thereby reducing the effects of pathogenic oral bacteria. In this review, some examples of current oral probiotic research are discussed along with reference to the potential application of diagnostic testing of the oral biofilm for the presence of oral pathogens as a precursor to initiation of specific probiotic therapy. Dental professionals should be actively investigating this potentially very useful therapeutic measure for the benefit of their patients.

Guidelines for Diagnostic Tests and Diagnostic Accuracy in Surgical Research

ABSTRACTObjective: This is a guideline review of the application of diagnostic tests and diagnostic accuracy in surgical research. Summary Background Data: There is an increasing use of diagnostic tests in surgery, and an understanding of the accuracy for each test is important for surgeons. Methods: This methodological review outlines the basic concepts of diagnostic test accuracy, including sensitivity, specificity, diagnostic odds ratio, likelihood ratios, and predictive values. Sources of bias in diagnostic accuracy studies are explained in simplified terms. The graphical methods used to present diagnostic accuracy are demonstrated. Study quality issues are outlined using published guidelines. Finally, the principles of diagnostic meta-analysis, including more advanced approaches such as bivariate and hierarchical summary receiver operating characteristic methods are explained. Conclusion: In the era of evidence-based surgery, the ability to understand and interpret the fundamental principles of diagnostic accuracy literature is vital to improve patient care and reduce the confusion in clinical practice over the most appropriate diagnostic test.

Diagnosing Coronary Artery Disease in Women

Coronary heart disease (CHD) remains the leading cause of death in women. However, there are multiple challenges to the diagnosis of CHD in women, including: 1) women perceive their risk of CHD to be lower than it truly is, 2) women frequently present with atypical cardiac symptoms, 3) traditional stress tests have lower accuracy in women than in men, 4) women have a lower frequency of obstructive CHD detected at angiography than do men, and 5) a high percentage of women without obstructive CHD by invasive angiography have recurrent chest pain. Given the increasing number of options and complexity of noninvasive testing for CHD, it is important for women's health care providers to select the best test for a given patient. Newer imaging modalities such as cardiac computed tomography and magnetic resonance imaging offer speed, convenience, and high diagnostic accuracy in women. The goal of this article is to provide practitioners with an overview of the conventional diagnostic tests and to compare these with the newer imaging modalities. The appropriate application of diagnostic tests should allow practitioners to identify accurately and reassure those patients who are at low risk while targeting those who have preclinical or symptomatic atherosclerosis so that they can receive aggressive medical therapy, referral to cardiovascular specialists, or both.

La efectividad de la detección precoz de las enfermedades

Secondary prevention through the early detection of diseases and their resulting early intervention and management, within an individual strategy for the prevention of diseases, has become a widespread practice in the last decade in both primary and specialist care. Similarly, there are demands by professionals and citizens for the health systems to offer prevention programmes and activities. In the application of diagnostic tests in asymptomatic persons, known as disease screening, different consequences are implied that involve both technical and care issues, and work and economic overload on the health services, both if the practice of early detection is due to selective individual indication or due to a public health decision. It is necessary to reflect on the need and opportuneness of such preventive practices, discerning which activities combine conditions in accordance with technical principles and scientific evidence, or if, on the contrary, they are carried out due to routine, simple complacency or pure empiricism. That is why the different prior phases and verifications that the health professional must consider before the broad diagnostic and therapeutic arsenal is applied with preventive aims are discussed.

Genital ulcer disease in central Australia: predictors of testing and outcomes

To identify factors associated with the uptake and outcome of testing for infectious causes of genital ulcer disease (GUD) in central Australia. Prospective investigation of GUD cases in central Australia from February 2002 to August 2003. Data were collected from primary health care clinics in remote indigenous communities of Central Australia. During the study period, 134 cases of GUD were reported and investigated. Of these cases, 71 (53%) were in women (age range 14-75, median 28) and 63 (47%) in men (14-63, median 28). Testing for syphilis was undertaken for 111 (82.8%) cases, 75 (56%) were tested for herpes simplex virus infection, and 82 (61.2%) for donovanosis. Testing for at least one of the three sexually transmissible pathogens of interest was undertaken in 128 (95.5%) cases, while 99 (73.9%) were tested for two pathogens and 41 (30.6%) for all three agents. Of subjects tested, 19.8% had new syphilis infection, 51% had herpes simplex virus infection and 7% had donovanosis. In 19 of 41 (46.3%) subjects fully investigated no cause for genital ulceration was found. This study provides the first quantitative description of GUD diagnosis in central Australia. Logistic constraints limited the systematic application of diagnostic tests. Current treatment protocols may need to be reassessed in light of the higher than expected detection of genital herpes as a cause of GUD.

A simple, bead-based approach for multi-SNP molecular haplotyping

Single nucleotide polymorphisms (SNPs) within a gene region have often been studied to determine their effect on phenotype. Although a single base pair change can produce a phenotypic change, phenotype is often influenced by the presence of multiple polymorphisms and their relative positions within a given region. For example, if multiple changes occur in a promoter region, how they influence gene expression will depend on their cis/trans configuration. As such, it is essential to consider the haplotype, or the alignment of multiple SNP alleles on each chromosome when attempting to associate genomic changes with phenotype. Unfortunately, no method of high-throughput molecular haplotyping of multiple SNPs currently exists. In response to this unmet need, we have developed an inexpensive, reliable bead-based capture-based haplotyping (CBH) assay to determine the phase, or haplotype, of multiple SNP alleles in a high-throughput manner. The CBH assay requires minimal setup and handling, requires no centrifugation steps and can be performed in <1 h. Data collection is performed via flow cytometry and the assay yields plus/minus results allowing for automated calling by a simple computer application. We will present data demonstrating the molecular haplotyping of 11 SNPs within exon 2 of the N-acetyltransferase-2 (NAT2) gene, which expresses an important drug-metabolizing enzyme. This assay has applications in diagnostic testing, promoter analysis, association studies and pharmacogenetic analysis.

Characterization of an immunologic polymorphism (D79H) in the heavy chain of factor V

During the study of a family with hereditary factor (F)V deficiency (FV Amersfoort, 1102 A > T in exon 7) we identified an individual with 5% FV heavy chain antigen (FV(HC)) and 50% FV light chain antigen (FV(LC)). Further testing revealed that apart from the FV Amersfoort allele a second variant FV allele was segregating in this family, which encodes for a FV molecule with a reduced affinity for mAb V-23 used in the FV heavy chain ELISA (ELISA(HC)). Identification and characterization of the molecular basis responsible for the reduced affinity of the variant FV for mAb V-23. Family members of the proband were screened for mutations in the exons coding for the heavy chain of FV, after which the recombinant variant FV could be generated and characterized. Next, the cases and controls of the Leiden Thrombophilia Study (LETS) were genotyped for carriership of the variant FV. In the variant FV allele a polymorphism in exon 3 (409G > C) was identified, which predicts the replacement of aspartic acid 79 by histidin (D79H). Introduction of this mutation in recombinant FV confirmed that it reduces the affinity for binding to mAb V-23. The substitution has no effect on FV(a) stability and Xa-cofactor activity. In Caucasians the frequency of the FV-79H allele is approximately 5%. Analysis of the LETS revealed that the FV-79H allele is not associated with FV levels (FV(LC)), activated protein C sensitivity (using an activated partial thromboplastin time-based test) or risk of venous thrombosis (OR 1.07, CI 95: 0.7-1.7). The D79H substitution in FV should be considered as a neutral polymorphism. The monoclonal antibody V-23, which has a strongly reduced affinity for FV-79H, is not suitable for application in diagnostic tests.

Application of diagnostic tests in veterinary epidemiologic studies

Important applications of diagnostic tests in non-clinical areas of veterinary medicine include surveillance, monitoring or screening for disease, prevalence estimation, and risk-factor studies. In this review, we address the processing and analysis of diagnostic data with special emphasis on serological data from enzyme-linked immunosorbent assays (ELISAs). We describe methods that are used to adjust for misclassification (imperfect sensitivity and specificity) in the different applications of diagnostic tests. These methods often have limitations attributable to the uncertainty of sensitivity and specificity estimates. We review descriptive and analytical statistical methods that allow adequate presentation of non-clinical diagnostic data.

Analysis of Correlated ROC Areas in Diagnostic Testing

This paper focuses on methods of analysis of areas under receiver operating characteristic (ROC) curves. Analysis of ROC areas should incorporate the correlation structure of repeated measurements taken on the same set of cases and the paucity of measurements per treatment resulting from an effective summarization of cases into a few area measures of diagnostic accuracy. The repeated nature of ROC data has been taken into consideration in the analysis methods previously suggested by Swets and Pickett (1982, Evaluation of Diagnostic Systems: Methods from Signal Detection Theory), Hanley and McNeil (1983, Radiology 148, 839-843), and DeLong, DeLong, and Clarke-Pearson (1988, Biometrics 44, 837-845). DeLong et al.'s procedure is extended to a Wald test for general situations of diagnostic testing. The method of analyzing jackknife pseudovalues by treating them as data is extremely useful when the number of area measures to be tested is quite small. The Wald test based on covariances of multivariate multisample U-statistics is compared with two approaches of analyzing pseudovalues, the univariate mixed-model analysis of variance (ANOVA) for repeated measurements and the three-way factorial ANOVA. Monte Carlo simulations demonstrate that the three tests give good approximation to the nominal size at the 5% levels for large sample sizes, but the paired t-test using ROC areas as data lacks the power of the other three tests and Hanley and McNeil's method is inappropriate for testing diagnostic accuracies. The Wald statistic performs better than the ANOVAs of pseudovalues. Jackknifing schemes of multiple deletion where different structures of normal and diseased distributions are accounted for appear to perform slightly better than simple multiple-deletion schemes but no appreciable power difference is apparent, and deletion of too many cases at a time may sacrifice power. These methods have important applications in diagnostic testing in ROC studies of radiology and of medicine in general.