Laser Capture Microscopy RNA Sequencing for Topological Mapping of Synovial Pathology During Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease in which the joint lining or synovium becomes highly inflamed and majorly contributes to disease progression. Understanding pathogenic processes in RA synovium is critical for identifying therapeutic targets. We performed laser capture microscopy (LCM) followed by RNA sequencing (LCM-RNAseq) to study regional transcriptomes throughout RA synovium. METHODS: Synovial lining, sublining, and vessel samples were captured by LCM from seven patients with RA and seven patients with osteoarthritis (OA). RNAseq was performed on RNA extracted from captured tissue. Principal component analysis was performed on the sample set by disease state. Differential expression analysis was performed between disease states based on log2 fold change and q value parameters. Pathway analysis was performed using the Reactome Pathway Database on differentially expressed genes among disease states. Significantly enriched pathways in each synovial region were selected based on the false discovery rate. RESULTS: RA and OA transcriptomes were distinguishable by principal component analysis. Pairwise comparisons of synovial lining, sublining, and vessel samples between RA and OA revealed substantial differences in transcriptional patterns throughout the synovium. Hierarchical clustering of pathways based on significance revealed a pattern of association between biologic function and synovial topology. Analysis of pathways uniquely enriched in each region revealed distinct phenotypic abnormalities. As examples, RA lining samples were marked by anomalous immune cell signaling, RA sublining samples were marked by aberrant cell cycle, and RA vessel samples were marked by alterations in heme scavenging. CONCLUSION: LCM-RNAseq confirms reported transcriptional differences between the RA synovium and the OA synovium and provides evidence supporting a relationship between synovial topology and molecular anomalies in RA.

Implementing life cycle sustainability assessment for improved space mission design.

Within the space sector, the application of Environmental Life Cycle Assessment (E-LCA) is beginning to emerge as a credible and compelling method for scientifically quantifying environmental impacts of space missions. However, E-LCA does not fully align with the concept of triple-bottom-line sustainability, while the combination of all three sustainability dimensions (environment, society, and economy) within a single life cycle study has thus far never been attempted within the space industry. Moving toward a Life Cycle Sustainability Assessment (LCSA) is, therefore, a logical next step for the space sector to allow these three sustainability dimensions to be addressed. Consequently, this article presents the underlying principles of a new LCSA framework for space missions and demonstrates its applicability for improving system-level design concepts based on the interaction between sustainability dimensions. The framework was formed based on a systematic literature review to analyze the background, issues, and knowledge gaps related to life cycle methodologies, as well as context-specific sustainability aspects. The framework has been implemented within a life cycle database called the Strathclyde Space Systems Database (SSSD). Using the SSSD, the framework was tested on a mission concept called Moon Ice Observation Satellite to demonstrate how changes in the design for a circular economy and other sustainability-based principles will affect the functionality of the mission at the system level. It is envisaged that this framework will enable engineers to create sustainable space systems, technologies, and products that are not only cost-efficient, eco-efficient, and socially responsible, but also ones that can easily justify and evidence their sustainability. Integr Environ Assess Manag 2023;19:1002-1022. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Employment of Young Adult Cancer Caregivers, Other Disease Caregivers, and Non-Caregiving Adults.

Young adults are increasingly taking on caregiving roles in the United States, and cancer caregivers often experience a greater burden than other caregivers. An unexpected caregiving role may disrupt caregiver employment, leading to lost earning potential and workforce re-entry challenges. We examined caregiving employment among young adult caregivers (i.e., family or friends) using the 2015 Behavioral Risk Factor Surveillance System (BRFSS), which included caregiving, employment, and sociodemographic variables. Respondents' ages varied between 18 and 39, and they were categorized as non-caregivers (n = 16,009), other caregivers (n = 3512), and cancer caregivers (n = 325). Current employment was compared using Poisson regressions to estimate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI), including gender-stratified models. We estimated employment by cancer caregiving intensity (low, moderate, high). Cancer caregivers at all other income levels were more likely to be employed than those earning below USD 20,000 (aIRR ranged: 1.88-2.10, all p< 0.015). Female cancer caregivers who were 25-29 (aIRR = 0.71, 95% CI = 0.51-1.00) and single (aIRR = 0.70, 95% CI = 0.52-0.95) were less likely to be employed than their counterparts. College-educated males were 19% less likely to be employed than high school-educated caregivers (95% CI = 0.68-0.98). Evaluating caregiver employment goals and personal financial situations may help identify those at risk for employment detriments, especially among females, those with lower educational attainment, and those earning below USD 20,000 annually.

Anemia Management in Rural Haitian Children: A Mixed Methods Study.

INTRODUCTION: We examined factors influencing anemia outcomes in rural children following implementation of a prevention program. METHOD: Mixed methods study of children, parents, and clinicians utilized statistical modeling and content/ethnographic analysis. Retrospective chart abstraction evaluated treatments administered and measured hemoglobin in children aged 6 to 59 months (n = 161). Prospective interviews/questionnaires examined parent (n = 51) and clinician (n = 19) perceptions. RESULTS: Anemia prevalence decreased by 21.2%. Predictors of increased hemoglobin were clinic visit number and age at first visit. Once anemia improved, children were likely to remain improved (P = .65). Despite favorable program perceptions, stakeholders emphasized ecological barriers, including social disadvantage and local practices. DISCUSSION: Socioeconomic factors prevented guideline concordant behaviors. Persistent attention to intrapersonal, interpersonal, and community social determinants is a sine qua non for successfully managing the epidemic. The first step to provide culturally congruent care is to explicitly acknowledge that guideline-concordant behaviors are often complex.

Galactose-1-Phosphate Uridyltransferase Activities in Different Genotypes: A Retrospective Analysis of 927 Samples.

BACKGROUND: Classic galactosemia is an inherited disorder of galactose metabolism caused by the impaired activity of galactose-1-phosphate uridyltransferase (GALT). Untreated galactosemia is life-threatening; however, early dietary intervention prevents mortality and reduces morbidity associated with this disease. The diagnosis of galactosemia includes the measurement of GALT activity in red blood cells (RBC) and GALT gene analysis. In this study, we evaluate GALT activity in different genotypes using the results of combined biochemical and molecular testing in 927 samples. METHODS: GALT activity in RBC was measured by LC-MS/MS. The analysis of the GALT gene was performed by targeted gene analysis and/or full gene sequencing. Samples were assigned based on the presence of pathogenic (G) or Duarte 2 (D) variants, or their absence (Neg), to G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes. Finite mixture models were applied to investigate distributions of GALT activities in these genotypes. The reference ranges were determined using the central 95% of values of GALT activities. RESULTS: The ranges of GALT activity in G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes are 0.0 to 0.7 µmol·h-1 gHb-1, 3.1 to 7.8 µmol·h-1 gHb-1, 6.5 to 16.2 µmol·h-1 gHb-1, 6.4 to 16.5 µmol·h-1 gHb-1, 12.0 to 24.0 µmol·h-1 gHb-1, and 19.4 to 33.4 µmol·h-1 gHb-1, respectively. CONCLUSIONS: The GALT activity ranges established in this study are in agreement with the expected impact of the genotype on the enzymatic activity. Molecular findings should be interpreted in view of biochemical results to confirm genotype-phenotype correlation.

Organizational Benchmarks for Test Utilization Performance: An Example Based on Positivity Rates for Genetic Tests.

OBJECTIVES: Health care organizations are under increasing pressure to deliver value by improving test utilization management. Many factors, including organizational factors, could affect utilization performance. Past research has focused on the impact of specific interventions in single organizations. The impact of organizational factors is unknown. The objective of this study is to determine whether testing patterns are subject to organizational effects, ie, are utilization patterns for individual tests correlated within organizations. METHODS: Comparative analysis of ordering patterns (positivity rates for three genetic tests) across 659 organizations. Hierarchical regression was used to assess the impact of organizational factors after controlling for test-level factors (mutation prevalence) and hospital bed size. RESULTS: Test positivity rates were correlated within organizations. CONCLUSIONS: Organizations have a statistically significant impact on the positivity rate of three genetic tests.

Statistical Literacy Among Academic Pathologists: A Survey Study to Gauge Knowledge of Frequently Used Statistical Tests Among Trainees and Faculty.

CONTEXT: -Statistical literacy can be defined as understanding the statistical tests and terminology needed for the design, analysis, and conclusions of original research or laboratory testing. Little is known about the statistical literacy of clinical or anatomic pathologists. OBJECTIVE: -To determine the statistical methods most commonly used in pathology studies from the literature and to assess familiarity and knowledge level of these statistical tests by pathology residents and practicing pathologists. DESIGN: -The most frequently used statistical methods were determined by a review of 1100 research articles published in 11 pathology journals during 2015. Familiarity with statistical methods was determined by a survey of pathology trainees and practicing pathologists at 9 academic institutions in which pathologists were asked to rate their knowledge of the methods identified by the focused review of the literature. RESULTS: -We identified 18 statistical tests that appear frequently in published pathology studies. On average, pathologists reported a knowledge level between "no knowledge" and "basic knowledge" of most statistical tests. Knowledge of tests was higher for more frequently used tests. Greater statistical knowledge was associated with a focus on clinical pathology versus anatomic pathology, having had a statistics course, having an advanced degree other than an MD degree, and publishing research. Statistical knowledge was not associated with length of pathology practice. CONCLUSIONS: -An audit of pathology literature reveals that knowledge of about 12 statistical tests would be sufficient to provide statistical literacy for pathologists. On average, most pathologists report they can interpret commonly used tests but are unable to perform them. Most pathologists indicated that they would benefit from additional statistical training.

Factors related to HPV vaccine uptake and 3-dose completion among women in a low vaccination region of the USA: an observational study.

BACKGROUND: To assess the demographic and attitudinal factors associated with HPV vaccine initiation and completion among 18-26 year old women in Utah. METHOD: Between January 2013 and December 2013, we surveyed 325 women from the University of Utah Community Clinics about their HPV vaccine related beliefs and behaviors. Odds ratios (ORs) were estimated from logistic regression models to identify variables related to HPV vaccine initiation and series completion. RESULTS: Of the 325 participants, 204 (62.8 %) had initiated the vaccine and 159 (48.9 %) had completed the 3-dose series. The variables associated with HPV vaccine initiation were lower age (OR = 1.18 per year); being unmarried (OR = 3.62); not practicing organized religion (OR = 2.40); knowing how HPV spreads (OR = 6.29); knowing the connection between HPV and cervical cancer (OR = 3.90); a belief in the importance of preventive vaccination (OR = 2.45 per scale unit); strength of doctor recommendation (OR = 1.86 per scale unit); and whether a doctor's recommendation was influential (OR = 1.70 per scale unit). These variables were also significantly associated with HPV vaccine completion. CONCLUSION: The implications of these findings may help inform policies and interventions focused on increasing HPV vaccination rates among young women. For example, without this information, programs might focus on HPV awareness; however, the results of this study illustrate that awareness is already high (near saturation) in target populations and other factors, such as strong and consistent physician recommendations, are more pivotal in increasing likelihood of vaccination. Additionally, our findings indicate the need for discussions of risk assessment be tailored to the young adult population.

Publication outcome of abstracts presented at the AACC annual meeting.

BACKGROUND: Failure to publish study results causes duplication of effort and is a significant source of waste. It also can lead to distortions in the evidence base that can lead to misallocation of resources and medical harm. Failure to publish is commonly studied by comparing the conversion rate of meeting abstracts or publication rate of registered trials and has not been studied in clinical chemistry. The objective of this study was to determine the abstract conversion rate in clinical chemistry. METHODS: For the set of abstracts published from the 2011 annual meeting of the American Association for Clinical Chemistry, we determined which converted to full publications and which had not. We used 3 methods to match publications to abstracts: 1) a survey sent to corresponding authors of abstracts, 2) a web scrape of Google Scholar, and PubMed, and 3) a manual search using Scopus. Publication rates were compared by topic, country of corresponding author, institution type, and award recognition. RESULTS: Matching publications were found for 38% (95% CI: 34-42%) of the abstracts. The acceptance rate for submitted manuscripts was 34% (95% CI: 28-43%) among those who responded to the survey. Publication rates varied by topic (range 13% to 59%); rates from academic institutions were higher than commercial institutions (42% vs 16%, p<0.001). The publication rate of abstracts recognized "with distinction" was significantly greater than the publication rate of non-winners (68% vs 37%, p=0.001). CONCLUSION: A significant proportion of abstracts presented at the AACC national meeting are not followed by full publication.

Population-based analysis of Alzheimer's disease risk alleles implicates genetic interactions.

BACKGROUND: Reported odds ratios and population attributable fractions (PAF) for late-onset Alzheimer's disease (LOAD) risk loci (BIN1, ABCA7, CR1, MS4A4E, CD2AP, PICALM, MS4A6A, CD33, and CLU) come from clinically ascertained samples. Little is known about the combined PAF for these LOAD risk alleles and the utility of these combined markers for case-control prediction. Here we evaluate these loci in a large population-based sample to estimate PAF and explore the effects of additive and nonadditive interactions on LOAD status prediction performance. METHODS: 2419 samples from the Cache County Memory Study were genotyped for APOE and nine LOAD risk loci from AlzGene.org. We used logistic regression and receiver operator characteristic analysis to assess the LOAD status prediction performance of these loci using additive and nonadditive models and compared odds ratios and PAFs between AlzGene.org and Cache County. RESULTS: Odds ratios were comparable between Cache County and AlzGene.org when identical single nucleotide polymorphisms were genotyped. PAFs from AlzGene.org ranged from 2.25% to 37%; those from Cache County ranged from .05% to 20%. Including non-APOE alleles significantly improved LOAD status prediction performance (area under the curve = .80) over APOE alone (area under the curve = .78) when not constrained to an additive relationship (p < .03). We identified potential allelic interactions (p values uncorrected): CD33-MS4A4E (synergy factor = 5.31; p < .003) and CLU-MS4A4E (synergy factor = 3.81; p < .016). CONCLUSIONS: Although nonadditive interactions between loci significantly improve diagnostic ability, the improvement does not reach the desired sensitivity or specificity for clinical use. Nevertheless, these results suggest that understanding gene-gene interactions may be important in resolving Alzheimer's disease etiology.

Surveillance of human papilloma virus using reference laboratory data for the purpose of evaluating vaccine impact.

Nationwide positivity rates of high-risk human papillomavirus for the United States before and since the introduction of a Human Papillomavirus (HPV) vaccine in 2006 would provide insight into the population impact of HPV vaccination. Data for high-risk HPV testing results from January 1, 2004 to June 1, 2013 at a national reference laboratory were retrospectively analyzed to produce 757,761 patient records of women between the ages of 14 and 59. Generalized linear models and finite mixture models were utilized to eliminate sources of bias and establish a population undergoing standard gynecological screening. Unadjusted positivity rates for high-risk HPV were 27.2% for all age groups combined. Highest rates occurred in women aged 14 to 19. While the positivity rates decreased for all age groups from 2004 to 2013, the higher age categories showed less downward trend following vaccine introduction, and the two age categories 20 to 24 and 25 to 29 showed a significantly different downward trend between pre- and post-vaccine time periods (-0.1% per year to -1.5% per year, and 0.4% per year to -1.5% per year, respectively). All other age groups had rates of change that became less negative, indicating a slower rate of decline.

Elevated factor IX activity is associated with an increased odds ratio for both arterial and venous thrombotic events.

OBJECTIVES: Elevations of factor IX (FIX) are thought to contribute to thrombotic risk, but this has not been well characterized. We retrospectively sought to determine whether elevated FIX levels are a risk factor for thrombosis in 81 adult subjects younger than 65 years (mean, 47 years) who were referred for evaluation of a hypercoagulable state. METHODS: Patients were classified by arterial transient ischemic attack/stroke (TIA/stroke, n = 62) or venous thromboembolism (VTE, n = 19) events. FIX activity testing was performed on all 81 subjects and a reference group of 40 healthy individuals. RESULTS: Thirteen (21%) of 62 subjects with TIA/stroke and 5 (26%) of 19 subjects with VTE had elevated FIX activity. Odds ratios for TIA/stroke and VTE in subjects with elevated FIX activity were 3.7 (95% confidence interval [CI], 0.76-17.65) and 6.8 (95% CI, 1.18-39.07), respectively. CONCLUSIONS: Our findings suggest an association between elevated FIX levels and both arterial and venous thrombotic events.

Evaluation of CCR3 as a basophil activation marker.

OBJECTIVES: Recent reports have provided conflicting evidence on the stability of CCR3 expression on the surface of basophils. Hence we wanted to independently evaluate the diagnostic usefulness of CCR3 as a surrogate marker of basophil activation and function. METHODS: We examined the correlative relationship between CCR3 expression on the surface of donor basophils and histamine release after donor basophils were treated with agonistic antibodies directed against the high-affinity IgE-Fc receptor and serum samples from 80 individuals displaying symptoms of chronic urticaria (CU). RESULTS: We observed that CCR3 was significantly downregulated on donor basophils treated with the agonistic antibody and CU-patient serum that demonstrated positive "histamine-releasing activity" (HRA scores >10). However, CCR3 downregulation was also observed on donor basophils incubated with more than 40% of CU-patient serum samples with HRA scores less than or equal to 10. CONCLUSIONS: Overall our data show that CCR3 demonstrates adequate sensitivity (83%) but weak specificity (59%) in its ability to reliably identify histamine-releasing activated basophils.

Application of a new informatics tool for contamination screening in the HIV sequencing laboratory.

BACKGROUND: Current HIV-1 sequencing-based methods for detecting drug resistance-associated mutations are open and susceptible to contamination. Informatic identification of clinical sequences that are nearly identical to one another may indicate specimen-to-specimen contamination or another laboratory-associated issue. OBJECTIVES: To design an informatic tool to rapidly identify potential contamination in the clinical laboratory using sequence analysis and to establish reference ranges for sequence variation in the HIV-1 protease and reverse transcriptase regions among a U.S. patient population. STUDY DESIGN: We developed an open-source tool named HIV Contamination Detection (HIVCD). HIVCD was utilized to make pairwise comparisons of nearly 8000 partial HIV-1 pol gene sequences from patients across the United States and to calculate percent identities (PIDs) for each pair. ROC analysis and standard deviations of PID data were used to determine reference ranges for between-patient and within-patient comparisons and to guide selection of a threshold for identifying abnormally high PID between two unrelated sequences. RESULTS: The PID reference range for between-patient comparisons ranged from 83.8 to 95.7% while within-patient comparisons ranged from 96 to 100%. Interestingly, 48% of between-patient sequence pairs with a PID>96.5 were geographically related. The selected threshold for abnormally high PIDs was 96 (AUC=0.993, sensitivity=0.980, specificity=0.999). During routine use, HIVCD identified a specimen mix-up and the source of contamination of a negative control. CONCLUSIONS: In our experience, HIVCD is easily incorporated into laboratory workflow, useful for identifying potential laboratory errors, and contributes to quality testing. This type of analysis should be incorporated into routine laboratory practice.

Diagnostic utility of microsatellite genotyping for molar pregnancy testing.

CONTEXT: Molecular genotyping by analysis of DNA microsatellites, also known as short tandem repeats (STRs), is an established method for diagnosing and classifying hydatidiform mole. Distinction of both complete hydatidiform mole and partial hydatidiform mole from nonmolar specimens is relevant for clinical management owing to differences in risk for persistent gestational trophoblastic disease. OBJECTIVE: To determine the technical performance of microsatellite genotyping by using a commercially available multiplex assay, and to describe the application of additional methods to confirm other genetic abnormalities detected by the genotyping assay. DESIGN: Microsatellite genotyping data on 102 cases referred for molar pregnancy testing are presented. A separate panel of mini STR markers, flow cytometry, fluorescence in situ hybridization, and p57 immunohistochemistry were used to characterize cases with other incidental genetic abnormalities. RESULTS: Forty-eight cases were classified as hydatidiform mole (31, complete hydatidiform mole; 17, partial hydatidiform mole). Genotyping also revealed 11 cases of suspected trisomy and 1 case of androgenetic/biparental mosaicism. Trisomy for selected chromosomes (13, 16, 18, and 21) was confirmed in all cases by using a panel of mini STR markers. CONCLUSIONS: This series illustrates the utility of microsatellite genotyping as a stand-alone method for accurate classification of hydatidiform mole. Other genetic abnormalities may be detected by genotyping; confirmation of the suspected abnormality requires additional testing.

Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome.

Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high associated mortality. Numerous studies have attempted to define characteristics to more accurately predict outcome. Two recent studies have demonstrated that Merkel cell polyomavirus (MCPyV) seropositivity correlated with a better prognosis, while a third study revealed no difference. Expression of p63 by tumor cell nuclei has been shown to be associated with a worse prognosis in a European cohort. To better understand the relationship between prognosis and MCPyV or p63 status, we used immunohistochemistry to evaluate both attributes in 36 US patients with MCC. Our results show that when considered as a binary variable, p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) = ∞) for shortened survival. In addition, our results show that MCPyV status does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates the European observation that p63 immunoexpression is useful as a prognostic tool. Larger studies will need to be performed in order to determine whether p63 status should be included in MCC staging, since our study is limited by its relative small size.

Cerebrospinal fluid myelin basic protein is frequently ordered but has little value: a test utilization study.

Diagnosis of multiple sclerosis (MS) is facilitated by analyzing biochemical properties of cerebrospinal fluid (CSF). Oligoclonal bands (OCBs) and immunoglobulin G (IgG) index are well-established markers for evaluating patients suspected of having MS. Myelin basic protein (MBP) is also ordered frequently, but its usefulness remains questionable. OCB, IgG index, and MBP were measured in 16,690 consecutive CSF samples. Samples were divided into 2 groups based on MS status known (n = 71) or unknown (n = 16,118). Medical charts of the MS status known group were reviewed to determine their MS status. OCBs have a stronger association to IgG index results than does MBP. Importantly, MBP does not add a statistically significant increase in diagnostic sensitivity or specificity when used in combination with OCB and/or IgG index. The data indicate that MBP is an unnecessary and overused test.

Consensus: a framework for evaluation of uncertain gene variants in laboratory test reporting.

Accurate interpretation of gene testing is a key component in customizing patient therapy. Where confirming evidence for a gene variant is lacking, computational prediction may be employed. A standardized framework, however, does not yet exist for quantitative evaluation of disease association for uncertain or novel gene variants in an objective manner. Here, complementary predictors for missense gene variants were incorporated into a weighted Consensus framework that includes calculated reference intervals from known disease outcomes. Data visualization for clinical reporting is also discussed.

Reference interval computation: which method (not) to choose?

BACKGROUND: When different methods are applied to reference interval (RI) calculation the results can sometimes be substantially different, especially for small reference groups. If there are no reliable RI data available, there is no way to confirm which method generates results closest to the true RI. METHODS: We randomly drawn samples obtained from a public database for 33 markers. For each sample, RIs were calculated by bootstrapping, parametric, and Box-Cox transformed parametric methods. Results were compared to the values of the population RI. RESULTS: For approximately half of the 33 markers, results of all 3 methods were within 3% of the true reference value. For other markers, parametric results were either unavailable or deviated considerably from the true values. The transformed parametric method was more accurate than bootstrapping for sample size of 60, very close to bootstrapping for sample size 120, but in some cases unavailable. CONCLUSIONS: We recommend against using parametric calculations to determine RIs. The transformed parametric method utilizing Box-Cox transformation would be preferable way of RI calculation, if it satisfies normality test. If not, the bootstrapping is always available, and is almost as accurate and precise as the transformed parametric method.

Methods specification for diagnostic test accuracy studies in fine-needle aspiration cytology: a survey of reporting practice.

Diagnostic test accuracy (DTA) studies on fine-needle aspiration cytology (FNAC) often show considerable variability in diagnostic accuracy between study centers. Many factors affect the accuracy of FNAC. A complete description of the testing parameters would help make valid comparisons between studies and determine causes of performance variation. We investigated the manner in which test conditions are specified in FNAC DTA studies to determine which parameters are most commonly specified and the frequency with which they are specified and to see whether there is significant variability in reporting practice. We identified 17 frequently reported test parameters and found significant variation in the reporting of these test specifications across studies. On average, studies reported 5 of the 17 items that would be required to specify the test conditions completely. A more complete and standardized reporting of methods, perhaps by means of a checklist, would improve the interpretation of FNAC DTA studies.