Training Radiologists to Interpret Contrast-enhanced Mammography: Toward a Standardized Lexicon

Objective Using terms adapted from the BI-RADS Mammography and MRI lexicons, we trained radiologists to interpret contrast-enhanced mammography (CEM) and assessed reliability of their description and assessment. Methods A 60-minute presentation on CEM and terminology was reviewed independently by 21 breast imaging radiologist observers. For 21 CEM exams with 31 marked findings, observers recorded background parenchymal enhancement (BPE) (minimal, mild, moderate, marked), lesion type (oval/round or irregular mass, or non-mass enhancement), intensity of enhancement (none, weak, medium, strong), enhancement quality (none, homogeneous, heterogeneous, rim), and BI-RADS assessment category (2, 3, 4A, 4B, 4C, 5). “Expert” consensus of 3 other radiologists experienced in CEM was developed. Kappa statistic was used to assess agreement between radiologists and expert consensus, and between radiologists themselves, on imaging feature categories and final assessments. Reproducibility of specific feature descriptors was assessed as fraction of consensus-concordant responses. Results Radiologists demonstrated moderate agreement for BPE, (mean kappa, 0.43; range, 0.05–0.69), and lowest reproducibility for “minimal.” Agreement was substantial for lesion type (mean kappa, 0.70; range, 0.47–0.93), moderate for intensity of enhancement (mean kappa, 0.57; range, 0.44–0.76), and moderate for enhancement quality (mean kappa, 0.59; range, 0.20–0.78). Agreement on final assessment was fair (mean kappa, 0.26; range, 0.09–0.44), with BI-RADS category 3 the least reproducible. Decision to biopsy (BI-RADS 2–3 vs 4–5) showed moderate agreement with consensus (mean kappa, 0.54; range, −0.06–0.87). Conclusion With minimal training, agreement for description of CEM findings by breast imaging radiologists was comparable to other BI-RADS lexicons.

Validating curricular competencies in innovation and entrepreneurship for biomedical research trainees: A modified Delphi approach

Introduction:Biomedical researchers need skills in innovation and entrepreneurship (I&E) to efficiently translate scientific discoveries into products and services to be used to improve health.Methods:In 2016, the European Union identified and published 15 entrepreneurial competencies (EntreComp) for the general population. To validate the appropriateness of these competencies for I&E training for biomedical researchers and to identify program content, we conducted six modified Delphi panels of 45 experts (6–9 per panel). Participating experts had diverse experience, representing such fields as entrepreneurship, academic research, venture capital, and industry.Results:The experts agreed that all 15 EntreComp competencies were important for biomedical research trainees and no additional competencies were identified. In a two-round Delphi process, the experts identified 120 topics to be included in a training curriculum. They rated the importance of each topic using a 5-point scale from not at all important (1) to extremely important (5) for two student groups: entrepreneurs (those interested in starting their own ventures) and intrapreneurs (those wanting to be innovative and strategic within academia or industry). Consensus (mean importance score >4) was reached that 85 (71%) topics were of high importance for the curriculum. Four topics were identified by multiple panels for both student groups: resiliency, goal setting, team management, and communication skills.Conclusions:I&E training for biomedical trainees should address all 15 EntreComp competencies, including “soft skills,” and be flexible to accommodate the needs of trainees on different career trajectories.

A pattern of arrests in Iran will intensify

Significance Since the major anti-government protests in January 2018, Tehran has engaged in a gradual but growing campaign of repression against civil society and economic actors, arresting activists and dual nationals on national security charges and businesspeople for corruption and currency manipulation. Increasing activism in outlying provinces has also resulted in an uptick in arrests among minority groups. Impacts Fears of a popular backlash and the lack of elite consensus mean a wholesale social crackdown is improbable. All sides will talk up a tough line on corruption amid popular anger over economic conditions. Tensions with the United States will not be resolved before elections in both countries take place.

Harmonization protocols for thyroid stimulating hormone (TSH) immunoassays: different approaches based on the consensus mean value

The lack of interchangeable laboratory results and consensus in current practices has underpinned greater attention to standardization and harmonization projects. In the area of method standardization and harmonization, there is considerable debate about how best to achieve comparability of measurement for immunoassays, and in particular heterogeneous proteins. The term standardization should be used only when comparable results among measurement procedures are based on calibration traceability to the International System of Units (SI unit) using a reference measurement procedure (RMP). Recently, it has been promoted the harmonization of methods for many immunoassays, and in particular for thyreotropin (TSH), as accepted RMPs are not available. In a recent paper published in this journal, a group of well-recognized authors used a complex statistical approach in order to reduce variability between the results observed with the 14 TSH immunoassay methods tested in their study. Here we provide data demonstrating that data from an external quality assessment (EQA) study allow similar results to those obtained using the reported statistical approach.

Isotope Dilution–LC-MS/MS Reference Method Assessment of Serum Folate Assay Accuracy and Proficiency Testing Consensus Mean

BACKGROUND Current methods for measuring folates in clinical laboratories are competitive folate binding protein assays. These assays show a considerable lack of agreement that has implications for the comparability of data across studies as well as for long-term population studies. The development of isotope dilution–liquid chromatography–tandem mass spectrometry (ID-LC-MS/MS) reference methods permitted the evaluation of method accuracy and consistency over time. METHODS We measured 3 pools of human serum by ID-LC-MS/MS, calculated values for total folate, and distributed the same pools to participants in a national External Quality Assessment scheme. We used linear regression to compare the all-laboratory and method data with reference method values. The exercise was repeated after 18 months to assess the stability of the all-laboratory and method data. RESULTS The distributed serum pools had mass spectrometry values for folate species typical of those found in healthy individuals from populations not receiving dietary folic acid fortification. There was good agreement of the all-laboratory data set with the reference method (y =0.86x + 0.91 μg/L) at both time points. Linear regression demonstrated that the Abbott Architect showed the closest agreement with the reference method. The Roche Elecsys method was nonlinear and showed a calibration offset of 2.6 μg/L (4.57 nmol/L). CONCLUSIONS Calibration of serum folate assays traceable to higher-order reference methods increases method accuracy and improves consistency. The all-laboratory consensus mean proved sufficiently accurate and stable to be used as the target for monitoring laboratory performance.

Proficiency Testing Program for the Determination of Total Arsenic, Cadmium, and Lead in Seawater Shrimp

The proficiency testing (PT) program for 97 worldwide laboratories for determining total arsenic, cadmium, and lead in seawater shrimp under the auspices of the Asia-Pacific Laboratory Accreditation Cooperation (APLAC) is discussed. The program is one of the APLAC PT series whose primary purposes are to establish mutual agreement on the equivalence of the operation of APLAC member laboratories and to take corrective actions if testing deficiencies are identified. Pooled data for Cd and Pb were normally distributed with interlaboratory variations of 21.9 and 34.8, respectively. The corresponding consensus mean values estimated by robust statistics were in good agreement with those obtained in the homogeneity tests. However, a bimodal distribution was observed from the determination of total As, in which 14 out of 74 participants reported much smaller values (0.4826.4 mg/kg) as compared with the mean values of 60.9 mg/kg in the homogeneity test. The use of consensus mean is known to have significant deviation from the true value in bi- or multimodal distribution. Therefore, the mode value, a better estimate of central tendency, was chosen to assess participants' performance for total As. Estimates of the overall uncertainty from participants varied in this program, and some were recommended to acquire more comprehensive exposure toward important criteria as stipulated in ISO/IEC 17025.

ABC of Statistics for Verification and Validation (V&V) of Simulations of High-Consequence Engineering Systems

We begin this expository essay by reviewing, with examples from the materials and fabrication testing literature, what a typical engineer already knows about statistics. We then consider a central question in engineering decision making, i.e., given a computer simulation of high-consequence systems, how do we verify and validate (V & V) and what are the margins of errors of all the important predicted results? To answer this question, we assert that we need three basic tools that already exist in statistical and metrological sciences: (A) Error Analysis. (B) Experimental Design. (C) Uncertainty Analysis. Those three tools, to be known as A B C of statistics, were developed through a powerful linkage between the statistical and metrological sciences. By extending the key concepts of this linkage from physical experiments to numerical simulations, we propose a new approach to answering the V & V question posed earlier. The key concepts are: (1) Uncertainty as defined in ISO Guide to the Expression of Uncertainty in Measurement (1993). (2) Design of experiments prior to data collection in a randomized or orthogonal scheme to evaluate interactions among model variables. (3) Standard reference benchmarks for calibration, and inter-laboratory studies for “weighted” consensus mean. To illustrate the need for and to discuss the plausibility of this metrology-based approach to V & V, two example problems are presented: (a) the verification of 12 simulations of the deformation of a cantilever beam, and (b) the calculation of a mean time to failure for a uniformly loaded 100-column single-floor steel grillage on fire.

Comparison of Serum and Plasma Methylmalonic Acid Measurements in 13 Laboratories: An International Study

Background: Detection of cobalamin deficiency is increasingly important, and methylmalonic acid (MMA) appears to be a useful marker. Information on interlaboratory variation and on methodological differences for MMA in serum and plasma is limited. Methods: Using gas chromatography/mass spectrometry, 13 laboratories participated in a 2-day analysis of 8 serum and 11 EDTA-plasma specimens. Results were analyzed for imprecision, recovery, and differences among laboratories and methods. Results: The mean among-laboratory imprecision (CV) was 19% and 21% for serum and plasma samples, respectively, and 9.3% and 7.8% for serum and plasma samples with added MMA, respectively. The mean within-laboratory (among-run) CV was 13% for both serum and plasma samples and 5.2% and 4.9% for serum and plasma samples with added MMA. Within-method imprecision was the same or higher than among-method imprecision. The mean among-laboratory recovery of MMA was 105% and 95% in serum and plasma, respectively. Most laboratories showed a proportional bias relative to the consensus mean of up to 15%. Two laboratories reported results that on average were almost 30% higher than the consensus mean. Conclusions: No method differences were found, but significant among-laboratory imprecision was found in the present study. Improvements are needed to reduce the analytical imprecision of most laboratories, and attention must be focused on calibration issues. Differences among laboratories can be improved by introducing high-quality reference materials and by instituting external quality assessment programs.