Diagnostic Test Sets Research Articles

Costs of diagnosing early Alzheimer's disease in three European memory clinic settings: Results from the precision medicine in Alzheimer's disease project.

The implementation of disease-modifying treatments for Alzheimer's Disease (AD) will require cost-effective diagnostic processes. As part of The Precision Medicine In AD consortium (PMI-AD) project, the aim is to analyze the baseline costs of diagnosing early AD at memory clinics in Norway, Slovenia, and the Netherlands. The costs of cognitive testing and a clinical examination, apolipoprotein E, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), positron emission tomography and blood-based biomarkers (BBM), which are used in different combinations in the three countries, were analyzed. Standardized unit costs, adjusted for GDP per capita and based on Swedish conditions were applied. The costs were expressed in euros (€) as of 2019. A diagnostic set comprising clinical examination, cognitive testing, MRI and CSF was defined as the gold standard, with MRI mainly used as an exclusion filter. Cost data were available for 994 persons in Norway, 169 in Slovenia and 1015 in the Netherlands. The mean diagnostic costs were 1478 (95% confidence interval 1433-1523) € in Norway, 851 (731-970) € in Slovenia and 1184 (1135-1232) € in the Netherlands. Norway had the highest unit costs but also the greatest use of tests. With a uniform diagnostic test set applied, the diagnostic costs were 1264 (1238-1291) €, in Norway, 843 (771-914) € in Slovenia and 1184 (1156-1213) € in the Netherlands. There were no major cost differences between the final set of diagnoses. The total costs for setting a diagnosis of AD varied somewhat in the three countries, depending on unit costs and use of tests. These costs are relatively low in comparison to the societal costs of AD.

Salivary biomarkers as pioneering indicators for diagnosis and severity stratification of pediatric long COVID.

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), manifests as persistent and often debilitating symptoms enduring well beyond the initial COVID-19 infection. This disease is especially worrying in children since it can seriously alter their development. Presently, a specific diagnostic test or definitive biomarker set for confirming long COVID is lacking, relying instead on the protracted presence of symptoms post-acute infection. We measured the levels of 13 biomarkers in 105 saliva samples (49 from children with long COVID and 56 controls), and the Pearson correlation coefficient was used to analyse the correlations between the levels of the different salivary biomarkers. Multivariate logistic regression analyses were performed to determine which of the 13 analysed salivary biomarkers were useful to discriminate between children with long COVID and controls, as well as between children with mild and severe long COVID symptoms. Pediatric long COVID exhibited increased oxidant biomarkers and decreased antioxidant, immune response, and stress-related biomarkers. Correlation analyses unveiled distinct patterns between biomarkers in long COVID and controls. Notably, a multivariate logistic regression pinpointed TOS, ADA2, total proteins, and AOPP as pivotal variables, culminating in a remarkably accurate predictive model distinguishing long COVID from controls. Furthermore, total proteins and ADA1 were instrumental in discerning between mild and severe long COVID symptoms. This research sheds light on the potential clinical utility of salivary biomarkers in diagnosing and categorizing the severity of pediatric long COVID. It also lays the groundwork for future investigations aimed at unravelling the prognostic value of these biomarkers in predicting the trajectory of long COVID in affected individuals.

Diagnostic Test Point Insertion and Test Compaction

Test points are inserted into a circuit to improve its testability or diagnosability. The diagnosability goal may be to reduce the number of indistinguished fault pairs, increase the accuracy of logic diagnosis, or reduce the number of diagnostic tests. This article describes a test point insertion procedure, combined with a test compaction procedure, whose goal is to reduce the number of tests in a diagnostic test set, and bring it closer to the number of tests in a fault detection test set. A test point allows a fan-out branch to assume values that are different from those of the fan-out stem. Effectively, the fan-out branch becomes an independent input. The test compaction procedure reduces the number of tests in two ways: 1) by utilizing the extra inputs created when test points are inserted and 2) a diagnostic test set typically consists of a fault detection test set followed by diagnostic tests. The test compaction procedure modifies the diagnostic test set to use all the tests as both fault detection and diagnostic tests. Experimental results for single stuck-at faults in benchmark circuits demonstrate the effectiveness of this approach in producing diagnostic test sets whose numbers of tests are closer to those of compact fault detection test sets while preserving the accuracy of logic diagnosis.

Diagnostic test set for osteoarthritis of the hip and the knee in people with an intellectual disability

Purpose: People with intellectual disabilities (ID) nowadays live longer due to improved medical care. However, they have many health problems at a relatively young age, like poor fitness, high frailty levels and mental health problems, compared to the general population. We also expect that osteoarthritis is a problem in people with ID, not only because of their increasing age, but also because of the high prevalence of risk factors such as obesity and joint loading problems through spasticity and laxity.

New Targets for Diagnostic Test Generation

A logic diagnosis procedure provides information about the defects that are present in a faulty unit as a set of candidate faults. To obtain smaller, and more accurate, sets of candidate faults, a diagnostic test generation procedure produces a test set that distinguishes fault pairs. This paper observes that large sets of candidate faults are obtained when multiple defects are present in a faulty unit, even if a diagnostic test set is used for logic diagnosis. This points to the possibility that fault pairs do not provide a complete set of targets for diagnostic test generation. This paper analyzes the conditions that cause a large set of candidate faults to be formed under a particular logic diagnosis procedure and suggests new targets for diagnostic test generation. The experimental results for benchmark circuits demonstrate that a diagnostic test set can be improved by adding diagnostic tests for the new targets.

COMEDI: Combinatorial Election of Diagnostic Vectors From Detection Test Sets for Logic Circuits

Although the modern automatic test pattern generation (ATPG) tools can efficiently produce near-optimal test sets with high fault-coverage for a circuit-under-test, a diagnostic test set (DTS), which is needed for fault localization, is much more challenging to construct. The DTS is used to analyze the responses of failing chips during manufacturing test for the purpose of identifying the root cause of observed errors. In this paper, a novel technique for selecting a powerful DTS for stuck-at faults from a pool of ATPG detection vectors is proposed. Unlike existing methods, this technique does not use any diagnostic test generation, circuit modification, or miter-based approach. It constructs a combinatorial cover of the pool to determine a test set with high diagnostic coverage (DC). Two variants of the covering algorithm are proposed based on this technique. The experimental results on several combinational and scan-based benchmark circuits demonstrate the effectiveness of our method in terms of the size of the DTS, DC, and CPU time.

Low-Power Diagnostic Test Sets for Transition Faults Based on Functional Broadside Tests

Functional broadside tests address overtesting due to high-power dissipation by creating functional operation conditions during the clock cycles where delay faults are detected. Guided by their switching activity, it is possible to generate a low-power test set whose switching activity does not exceed the switching activity possible during functional operation. This brief applies the same approach to the generation of a low-power diagnostic test set. Excessively high switching activity can cause unexpected fault effects to appear, which will reduce the accuracy of fault diagnosis. This is avoided with a low-power diagnostic test set. Functional broadside tests are also used for avoiding diagnostic tests with unnecessarily low switching activity. The procedure described in this brief is the first to generate low-power diagnostic tests under functional constraints on switching activity as given by functional broadside tests.

Comparison of the serological tests ICT and ELISA for the diagnosis of alveolar echinococcosis in France.

Serological diagnosis of alveolar echinococcosis (AE) is a key element for efficient patient treatment management. A rapid immunochromatography test kit (ICT) using the recombinant Em18 antigen (rEm18) was recently developed. The aim of our study was to assess this test on a panel of sera from French patients with alveolar echinococcosis and control patients. In a blind test, a total of 112 serum samples were tested including samples of AE (n = 30), cystic echinococcosis [CE] (n = 15), and polycystic echinococcosis [PE] (n = 1). For the comparison, 66 sera from patients with hepatocarcinoma, fascioliasis, toxocariasis, Caroli’s disease, or autoimmune chronic active hepatitis were used. The diagnostic test sets we used were the rEm18-ICT and two validated ELISAs with rEm18 and Em2-Em18 antigens, respectively. For the ICT, 27/30 sera from AE patients, 4/15 sera from CE patients and the PE patient serum were positive. One serum from the control panel (toxocariasis) was positive for the ICT. The rEm18-ICT sensitivity (90.0%) and specificity (92.7%) for detection of Em18-specific antibodies confirmed it as a relevant tool for AE diagnosis. The rEm18-ELISA had a sensitivity of 86.7% and specificity of 91.5%, and the Em2-Em18-ELISA had a sensitivity of 96.7% and specificity of 87.8%. However, when AE patient sera are recorded as weak in intensity with the ICT, we recommend a double reading and use of a reference sample if the ICT is used for patient follow-up.

Diagnostic Test Sets with Increased Switching Activity for Transition Faults

Diagnostic Test Sets with Increased Switching Activity for Transition Faults

Development of a diagnostic test set to assess agreement in breast pathology: practical application of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS)

BackgroundDiagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods.MethodsBreast tissue biopsies were selected from the National Cancer Institute-funded Breast Cancer Surveillance Consortium sites. We used a random sampling stratified according to woman’s age (40–49 vs. ≥50), parenchymal breast density (low vs. high) and interpretation of the original pathologist. A 3-member panel of expert breast pathologists first independently interpreted each case using five primary diagnostic categories (non-proliferative changes, proliferative changes without atypia, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma). When the experts did not unanimously agree on a case diagnosis a modified Delphi method was used to determine the reference standard consensus diagnosis. The final test cases were stratified and randomly assigned into one of four unique test sets.ConclusionsWe found GRRAS recommendations to be very useful in reporting diagnostic test set development and recommend inclusion of two additional criteria: 1) characterizing the study population and 2) describing the methods for reference diagnosis, when applicable.

Gradual Diagnostic Test Generation and Observation Point Insertion Based on the Structural Distance Between Indistinguished Fault Pairs

The size of a diagnostic test set is significantly larger than the size of a fault detection test set. As a result, fault detection test sets may be used for initial defect diagnosis, and diagnostic tests may be added as needed to narrow down a set of candidate defect sites. Between a fault detection test set and a full diagnostic test set there is a large range of test sets that can be used for improved (initial) diagnosis. This paper describes a diagnostic test generation process that produces such a range of test sets. The process is based on a ranking of the indistinguished fault pairs according to the importance of distinguishing them. The ranking is based on the structural distance between faults. This allows failure analysis to explore fewer and more localized areas of the circuit as the size of the diagnostic test set is increased. This paper also discusses the insertion of observation points to distinguish fault pairs that remain indistinguished by a diagnostic test set. Observation point insertion uses the ranked list of indistinguished fault pairs to ensure that a limited number of observation points will address the fault pairs that are the most important to distinguish.

Diagnostic Test Set Minimization and Full-Response Fault Dictionary

We minimize a given test set without loss of diagnostic resolution in full-response fault dictionary. An integer linear program (ILP), formulated from fault simulation data, provides ultimate reduction of test vectors while preserving fault coverage and pair-wise distinguishability of faults. The complexity of the ILP is made manageable by two innovations. First, we define a generalized independence relation between pairs of faults to reduce the number of fault pairs that need to be distinguished. This significantly reduces the number of ILP constraints. Second, we propose a two-phase ILP approach. In the first phase, using an existing procedure, we select a minimal detection test set. In the second phase, additional tests are selected for the undiagnosed faults using a newly formulated diagnostic ILP. The overall minimized test set may be only slightly longer than a one-step ILP optimization, but has advantages of reducing the minimization problem complexity and the test time required by the minimized tests. Benchmark results show potential for significantly smaller diagnostic test sets.

Test vector chains for increased resolution and reduced storage of diagnostic tests

The use of diagnostic test sets improves the accuracy of defect diagnosis by allowing smaller sets of candidate defect sites to be obtained. However, diagnostic test sets are significantly larger than fault detection test sets, and the complexity of deterministic diagnostic test generation is higher because of the need to consider pairs of faults. This work studies a solution that addresses both the size of a diagnostic test set and the complexity of deterministic diagnostic test generation through the use of what are called test vector chains. Test vector chains provide a specific algorithm for obtaining new tests from existing ones through single-bit changes. They allow smaller test sets to be stored, and additional tests to be obtained by computing test vector chains or subsets thereof. Experimental results demonstrate that tests obtained through test vector chains are effective as diagnostic tests, and that the resulting storage requirements are close to those of fault detection test sets.

Static test compaction for diagnostic test sets of full-scan circuits

The authors describe a static test compaction procedure for diagnostic test sets of full-scan circuits. Similar to reverse order and random order fault simulation procedures applied to fault detection test sets, the procedure simulates the test set in different orders in order to identify unnecessary tests. Two features distinguish the procedure from earlier ones. (i) It uses a diagnostic fault simulation process based on equivalence classes to identify tests that are not necessary for distinguishing fault pairs. (ii) It includes an iterative reordering process whose goal is to increase the number of tests that will be identified as unnecessary. Experimental results are presented to demonstrate the ability of the procedure to compact diagnostic test sets and the effectiveness of the iterative reordering process.

On the Use of Functional Test Generation in Diagnostic Test Generation for Synchronous Sequential Circuits

We study the relationship between diagnostic test generation for a gate-level fault model, which is used for generating diagnostic test sets for manufacturing defects, and functional test generation for a high-level fault model. In general, a functional fault may partially represent some of the effects of one gate-level fault but not another. Generating a test sequence for the functional fault is then likely to detect one gate-level fault but not the other, thus distinguishing the two faults. This relationship points to the ability to use a functional test generation procedure (that targets functional fault detection) as a way of generating diagnostic test sequences for gate-level faults. We use this observation in two ways. The more direct way is to define functional faults that correspond to the differences between pairs of gate-level faults. The second way is to use functional test sequences as diagnostic test sequences without explicitly considering gate-level faults. We support the use of the resulting procedures with experimental results.

Correlation of Radiologist Rank as a Measure of Skill in Screening and Diagnostic Interpretation of Mammograms

To determine whether skill in the interpretation of screening mammograms is correlated with skill in the interpretation of diagnostic mammograms. The institutional review board of the University of South Florida approved this study. This study was determined to be exempt from informed consent requirements because of the retrospective use of images and was conducted before HIPPA requirements were implemented. A total of 59 radiologists interpreted screening and diagnostic performance test sets of mammograms with a 1-year interval. Interpretations were recorded with modifications of the Breast Imaging and Reporting Data System. Radiologist skill was measured as the radiologist's ranking among his or her cohort in each of several measures of performance (ie, performance test receiver operating characteristic curve area, performance test screening sensitivity, performance test diagnostic sensitivity, and associated specificities). Correlations between radiologist rank in screening and rank in the diagnostic performance test measures were analyzed with the Spearman rank correlation statistical test. Radiologist rank in screening interpretations and in diagnostic interpretations was found to be significantly correlated in all measurements (P < .05). However, only two measurments (ie, receiver operating characteristic curve area rank correlation of 0.327 and sensitivity rank correlation of 0.402) remained significant after adjusting for multiple testing. The correlation between ranked screening specificity and ranked diagnostic specificity (0.296) was significant at only the .05 level. The interpretive performance of radiologists among their peers is moderately correlated between screening and diagnostic interpretations. Thus, proficiency in one area does not guarantee proficiency in the other area for some radiologists.

An efficient structural approach to board interconnect diagnosis

In this paper we present an efficient structural approach for diagnosing board interconnects using boundary-scan. Whereas existing diagnosis approaches assume only wired-AND or wired-OR bridging fault model, we consider a more complex bridging short fault model in a CMOS circuit environment. The diagnostic test set is generated on the basis of graph theoretic technique and the adjacency fault model is adopted. By using the structural information of the wiring layout, the test length can be reduced. Both one-step and two-step diagnosis algorithms are given. They guarantee the complete diagnosis of multiple interconnect faults with no aliasing or confounding. The algorithms have been evaluated by simulation on several benchmark layouts and randomly generated layouts. Simulation results show that more than 50% reduction in the number of tests can be achieved for two-step diagnosis when the fault rate is very small, such as in a matured product line. This can significantly save the diagnosis cost for boundary-scan testing.

Diagnosis of Boards for Realistic Interconnect Shorts

Original algorithms and tools for generating diagnostic test sets for board interconnect shorts, and assessing their diagnostic resolution are proposed. The test sets are derived from a representation of realistic shorts, extracted from the board layout. Diagnostic resolution is statistically evaluated by simulating diagnosis of a sample of realistic shorts. The overall methodology is based on a new theoretical framework that accounts for the probabilities of shorts, according to their multiplicity and possible logic behaviour. Results on real board layouts show that, compared to the traditional schemes, our test sets have higher diagnostic resolution, shorter test vectors, and can be produced efficiently.

A Design for Testability of Undetectable Crosspoint Faults in Programmable Logic Arrays

In this paper, the validity of single fault assumption in deriving diagnostic test sets is examined with respect to crosspoint faults in programmable logic arrays (PLA's). The control input procedure developed here can be used to convert PLA's having undetectable crosspoint faults to crosspoint-irredundant PLA's for testing purposes. All crosspoints will be testable in crosspoint-irredundant PLA's. The control inputs are used as extra variables during testing. They are maintained at logic 1 during normal operation. A useful heuristic for obtaining a near-minimal number of control inputs is suggested. Expressions for calculating bounds on the number of control inputs have also been obtained.