Prediction using hierarchical data: Applications for automated detection of cervical cancer.

Although the Papanicolaou smear has been successful in decreasing cervical cancer incidence in the developed world, there exist many challenges for implementation in the developing world. Quantitative cytology, a semi-automated method that quantifies cellular image features, is a promising screening test candidate. The nested structure of its data (measurements of multiple cells within a patient) provides challenges to the usual classification problem. Here we perform a comparative study of three main approaches for problems with this general data structure: a) extract patient-level features from the cell-level data; b) use a statistical model that accounts for the hierarchical data structure; and c) classify at the cellular level and use an ad hoc approach to classify at the patient level. We apply these methods to a dataset of 1,728 patients, with an average of 2,600 cells collected per patient and 133 features measured per cell, predicting whether a patient had a positive biopsy result. The best approach we found was to classify at the cellular level and count the number of cells that had a posterior probability greater than a threshold value, with estimated 61% sensitivity and 89% specificity on independent data. Recent statistical learning developments allowed us to achieve high accuracy.

A statistical model for removing inter-device differences in spectroscopy.

We are investigating spectroscopic devices designed to make in vivo cervical tissue measurements to detect pre-cancerous and cancerous lesions. All devices have the same design and ideally should record identical measurements. However, we observed consistent differences among them. An experiment was designed to study the sources of variation in the measurements recorded. Here we present a log additive statistical model that incorporates the sources of variability we identified. Based on this model, we estimated correction factors from the experimental data needed to eliminate the inter-device variability and other sources of variation. These correction factors are intended to improve the accuracy and repeatability of such devices when making future measurements on patient tissue.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings.

Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training.

An empirical model of diagnostic x-ray attenuation under narrow-beam geometry.

PURPOSE: The purpose of this study was to develop and validate a mathematical model to describe narrow-beam attenuation of kilovoltage x-ray beams for the intended applications of half-value layer (HVL) and quarter-value layer (QVL) estimations, patient organ shielding, and computer modeling. METHODS: An empirical model, which uses the Lambert W function and represents a generalized Lambert-Beer law, was developed. To validate this model, transmission of diagnostic energy x-ray beams was measured over a wide range of attenuator thicknesses [0.49-33.03 mm Al on a computed tomography (CT) scanner, 0.09-1.93 mm Al on two mammography systems, and 0.1-0.45 mm Cu and 0.49-14.87 mm Al using general radiography]. Exposure measurements were acquired under narrow-beam geometry using standard methods, including the appropriate ionization chamber, for each radiographic system. Nonlinear regression was used to find the best-fit curve of the proposed Lambert W model to each measured transmission versus attenuator thickness data set. In addition to validating the Lambert W model, we also assessed the performance of two-point Lambert W interpolation compared to traditional methods for estimating the HVL and QVL [i.e., semi-logarithmic (exponential) and linear interpolation]. RESULTS: The Lambert W model was validated for modeling attenuation versus attenuator thickness with respect to the data collected in this study (R2 > 0.99). Furthermore, Lambert W interpolation was more accurate and less sensitive to the choice of interpolation points used to estimate the HVL and/or QVL than the traditional methods of semilogarithmic and linear interpolation. CONCLUSIONS: The proposed Lambert W model accurately describes attenuation of both monoenergetic radiation and (kilovoltage) polyenergetic beams (under narrow-beam geometry).

Detection of microcalcifications on digital screening mammograms using varying degrees of monitor zooming.

OBJECTIVE: The American College of Radiology recommends that mammogram images be viewed at 100% resolution (also called one-to-one or full resolution). We tested the effect of this and three other levels of zooming on the ability of radiologists to identify malignant calcifications on screening mammographic views. MATERIALS AND METHODS: Seven breast imagers viewed 77 mammographic images, 32 with and 45 without malignant microcalcifications, using four different degrees of monitor zooming. The readers indicated whether they thought a cluster of potentially malignant calcifications was present and where the cluster was located. Tested degrees of zooming included fit screen, a size midway between fit screen and 100%, 100%, and a size slightly larger than 100%. RESULTS: Readers failed to detect 17 clusters of malignant calcifications with fit-screen images, 12 clusters with midway images, 13 clusters with 100% images, and 11 clusters with slightly larger images. When viewing images without malignant microcalcifications, the readers marked false-positive areas on 25 images using fit-screen images, 43 of the midway images, 40 of the 100% images, and 29 of the slightly larger images. CONCLUSION: All four tested levels of zooming functioned well. There was a trend for the fit-screen images to function slightly less well than the others with regard to sensitivity, so it may not be prudent to rely on those images without other levels of zooming. The 100% resolution images did not function noticeably better than the others.

A phase II trial of paclitaxel and carboplatin in women with advanced or recurrent uterine carcinosarcoma.

BACKGROUND: Systemic therapy for advanced uterine carcinosarcoma (CS) has been disappointing. The most widely studied regimen is ifosfamide and cisplatinum. Moderate success has been documented using paclitaxel in ovarian CS. The purpose of this study was to evaluate carboplatin/paclitaxel in advanced and recurrent uterine CS. METHODS: A single-arm, prospective, phase II trial opened in October 2001. Primary end points were time to progression (TTP) and response rate (RR). Quality-of-life data were obtained. Patients treated adjuvantly received 6 cycles of carboplatin/paclitaxel every 21 days. Patients with disease at study entry were treated until response, progression, or toxicity. RESULTS: Of 23 patients enrolled, 9 received adjuvant treatment, 13 had documented disease, 1 was inevaluable. Eight of 13 patients with measurable disease had a complete or partial response (62% RR). Overall, median TTP was 9.5 months. In the adjuvant group, median TTP was 15 months. With measurable disease, median TTP was 7.9 months. Median overall survival was 21.1 months. There was no difference in survival between patients with or without measurable disease. For patients having prior radiation, median TTP with recurrence in the radiated field was 13.3 months, and 14.5 months if outside the field (P = 0.71). Two patients (9%) had treatment-limiting toxicity. Quality-of-life scores improved from baseline over time. CONCLUSIONS: Carboplatin and paclitaxel have improved tolerability and RR (62%) compared with previous reports of ifosfamide/cisplatin or ifosfamide/paclitaxel in treating uterine CS. This regimen seems promising and should be considered in combined therapies with targeted agents.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy.

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

Interpretation time of computer-aided detection at screening mammography.

PURPOSE: To prospectively determine the interpretation time associated with computer-aided detection (CAD) and to analyze how CAD affected radiologists' decisions and their level of confidence in their interpretations of digital screening mammograms. MATERIALS AND METHODS: An Institutional Review Board exemption was obtained, and patient consent was waived in this HIPAA compliant study. The participating radiologists gave informed consent. Five radiologists were prospectively studied as they interpreted 267 clinical digital screening mammograms. Interpretation times, recall decisions, and confidence levels were recorded without CAD and then with CAD. Software was used for linear regression fitting of interpretation times. P values less than .05 were considered to indicate statistically significant differences. RESULTS: Mean interpretation time without CAD was 118 seconds ± 4.2 (standard error of the mean). Mean time for reviewing CAD images was 23 seconds ± 1.5. CAD identified additional findings in five cases, increased confidence in 38 cases, and decreased confidence in 21 cases. Interpretation time without CAD increased with the number of mammographic views (P < .0001). Mean times for interpretation without CAD and review of the CAD images both increased with the number of CAD marks (P < .0001). The interpreting radiologist was a significant variable for all interpretation times (P < .0001). Interpretation time with CAD increased by 3.2 seconds (95% confidence interval: 1.8, 4.6) for each calcification cluster marked and by 7.3 seconds (95% confidence interval: 4.7, 9.9) for each mass marked. CONCLUSION: The additional time required to review CAD images represented a 19% increase in the mean interpretation time without CAD. CAD requires a considerable time investment for digital screening mammography but may provide less measureable benefits in terms of confidence of the radiologists.

Repeatability of tissue fluorescence measurements for the detection of cervical intraepithelial neoplasia.

We examined intensity and shape differences in 378 repeated spectroscopic measures of the cervix. We examined causes of variability such as presence of precancer or cancer, pathologic tissue type, menopausal status, hormone or oral contraceptive use, and age; as well as technology related variables like generation of device and provider making exam. Age, device generation, and provider were statistically significantly related to intensity differences. Provider and device generation were related to shape differences. We examined the order of measurements and found a decreased intensity in the second measurement due to hemoglobin absorption. 96% of repeat measurements had classification concordance of cervical intraepithelial neoplasia.

Why does it take longer to read digital than film-screen screening mammograms? A partial explanation.

Digital screening mammograms (DM) take longer to interpret than film-screen screening mammograms (FSM). We evaluated what part of the process takes long in our reading environment. We selected cases from those for which timed readings had been performed as part of a previous study. Readers were timed as they performed various computer manipulations on groups of DM cases and as they moved the alternator and adjusted lighting and manual shutters for FSM cases. Subtracting manipulation time from the original interpretation times yielded estimated times to reach a decision. Manipulation times for DM ranged from a low of 11 s when four-view DM were simply opened and closed in a 4-on-1 hanging protocol before moving on to the next study to 113.8 s when each view of six-view DM were brought up 1-on-1, enlarged to 100% resolution, and panned through. Manipulation times for groups of FSM ranged from 8.3 to 12.1 s. Estimated decision-making times for DM ranged from 128.0 to 202.2 s, while estimated decision-making time for FSM ranged from 60.9 to 146.3 s. Computer manipulation time partially explains the discrepancy in interaction times between DM and FSM. Radiologists also appear to spend more time looking at DM than at FSM before making a decision.

Conspicuity of microcalcifications on digital screening mammograms using varying degrees of monitor zooming.

RATIONALE AND OBJECTIVES: American College of Radiology guidelines suggest that digital screening mammographic images should be viewed at the full resolution at which they were acquired. This slows interpretation speed. The aim of this study was to examine the effect of various levels of zooming on the detection and conspicuity of microcalcifications. MATERIALS AND METHODS: Six radiologists viewed 40 mammographic images five times in different random orders using five different levels of zooming: full resolution (100%) and 30%, 61%, 88%, and 126% of that size. Thirty-three images contained microcalcifications varying in subtlety, all associated with breast cancer. The clusters were circled. Seven images contained no malignant calcifications but also had randomly placed circles. The radiologists graded the presence or absence and visual conspicuity of any calcifications compared to calcifications in a reference image. They also counted the microcalcifications. RESULTS: The radiologists saw the microcalcifications in 94% of the images at 30% size and in either 99% or 100% of the other tested levels of zooming. Conspicuity ratings were worst for the 30% size and fairly similar for the others. Using the 30% size, two radiologists failed to see the microcalcifications on either the craniocaudal or mediolateral oblique view taken from one patient. Interobserver agreement regarding the number of calcifications was lowest for the 30% images and second lowest for the 100% images. CONCLUSIONS: Images at 30% size should not be relied on alone for systematic scanning for microcalcifications. The other four levels of magnification all performed well enough to warrant further testing.

Timed efficiency of interpretation of digital and film-screen screening mammograms.

OBJECTIVE: Our objective was to compare interpretation speeds for digital and film-screen screening mammograms to test whether other variables might affect interpretation times and thus contribute to the apparent difference in interpretation speed between digital mammograms and film-screen mammograms, and to test whether the use of digital rather than film comparison studies might result in significant time savings. MATERIALS AND METHODS: Four readers were timed in the course of actual clinical interpretation of digital mammograms and film-screen mammograms. Interpretation times were compared for subgroups of studies based on the interpretation of the study by BI-RADS code, the number of images, the presence or absence of comparison studies and the type of comparison study, and whether the radiologist personally selected and hung additional films; the same comparisons were made among individual readers. RESULTS: For all four readers, mean interpretation times were longer for digital mammograms than for film-screen mammograms, with differences ranging from 76 to 202 seconds. The difference in interpretation speed between digital and film-screen mammograms was independent of other variables. Digital mammogram interpretation times were significantly longer than film-screen mammogram interpretation times regardless of whether the digital mammograms were matched with film or digital comparison studies. CONCLUSION: In screening mammography interpretation, digital mammograms take longer to read than film-screen mammograms, independent of other variables. Exclusive use of digital comparison studies may not cause interpretation times to drop enough to approach the interpretation time required for film-screen mammograms.

Results of a survey on digital screening mammography: prevalence, efficiency, and use of ancillary diagnostic AIDS.

OBJECTIVE: As the use of full-field digital screening mammography grows rapidly, this study was conducted to determine the time required to interpret digital soft-copy (filmless) mammography compared with conventional film-screen screening mammography and to evaluate radiologists' use of ancillary diagnostic aids when interpreting digital mammography (DM) and conventional film-screen mammography (FSM). MATERIALS AND METHODS: An 18-question survey was sent to 1,703 members of the Society of Breast Imaging, whose e-mail addresses were provided by the society. After subtracting those from whom out-of-office e-mail responses were received and three who wrote back to exclude themselves, there were 1,659 potential participants. Data from the respondents were collected and analyzed by tabulation and cross-tabulation. RESULTS: In total, 396 members of the Society of Breast Imaging completed and returned surveys, for a 23.9% response rate. Of the respondents, 49.0% said that they had access to and interpreted DM. Their estimated average time to read a single digital mammographic study was 2.6 minutes, compared with 2.0 minutes for reading a single film-screen mammographic study. Therefore, the perceived time difference was 0.6 minutes. Magnification was the main ancillary diagnostic aid used in interpreting both DM and FSM: 74.2% of respondents used computer-based magnification at least half the time in interpreting DM, and 90.9% used optical magnification at least half the time in interpreting FSM. Optical magnification was also used by 28.5% of respondents at least half the time in interpreting DM. The respondents also used computer-aided detection frequently: 91.0% and 76.3% of those who had computer-aided detection available said that they used it at least 75% of the time in interpreting DM and FSM, respectively. CONCLUSION: Digital mammography takes longer to interpret than FSM. Radiologists use various ancillary diagnostic aids, but magnification and computer-aided detection are the two most commonly used aids.

Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer.

PURPOSE: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder. EXPERIMENTAL DESIGN: We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence. RESULTS: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met. CONCLUSIONS: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.

Accuracy of colposcopy in the diagnostic setting compared with the screening setting.

OBJECTIVE: To estimate the accuracy of colposcopy to identify cervical precancer in screening and diagnostic settings. METHODS: As part of a larger clinical trial to evaluate the diagnostic accuracy of optical spectroscopy, we recruited 1,850 patients into a diagnostic or a screening group depending on their history of abnormal findings on Papanicolaou tests. Colposcopic examinations were performed and biopsies specimens obtained from abnormal and normal colposcopic sites for all patients. The criterion standard of test accuracy was the histologic report of biopsies. We calculated sensitivities, specificities, likelihood ratios, receiver operating characteristic curves, and areas under the receiver operating characteristic curves. RESULTS: The prevalence of high-grade squamous intraepithelial lesions (HSIL) or cancer was 29.0% for the diagnostic group and 2.2% for the screening group. Using a disease threshold of HSIL, colposcopy had a sensitivity of 0.983 and a specificity of 0.451 in the diagnostic group when the test threshold was low-grade squamous intraepithelial lesions (LSIL), and a sensitivity of 0.714 and a specificity of 0.813 when the test threshold was HSIL. Using the same HSIL disease threshold, in the screening group, colposcopy had a sensitivity of 0.286 and a specificity of 0.877 when the test threshold was LSIL, and a sensitivity of 0.191 and a specificity of 0.961 when the threshold was HSIL. The colposcopy area under the receiver operating characteristic curve was 0.821 (95% confidence interval 0.79-0.85) in the diagnostic setting compared with 0.587 (95% confidence interval 0.56-0.62) in the screening setting. Changing the disease threshold to LSIL demonstrated similar patterns in the tradeoff of sensitivity and specificity and measure of accuracy. CONCLUSION: Colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used to screen for cervical intraepithelial neoplasia. LEVEL OF EVIDENCE: II.

Model-based analysis of reflectance and fluorescence spectra for in vivo detection of cervical dysplasia and cancer.

Development, validation, and implementation of an analytical model to extract biologically and diagnostically relevant parameters from measured cervical tissue reflectance and fluorescence spectra are presented. Monte Carlo simulations of tissue reflectance are used to determine the relative contribution of the signal from the epithelium and stroma. The results indicate that the clinical probe used collects a majority of its reflectance signal from the stroma; therefore, a one-layer analytical model of reflectance is used. Two analytical approaches to calculate reflectance spectra are compared to Monte Carlo simulations, and a diffusion theory-based model is implemented. The model is validated by fitting spectra generated from Monte Carlo simulations and comparing the input and output parameters. Median agreement between extracted optical properties and input parameters is 10.6%. The reflectance model is used together with an analytical model of tissue fluorescence to extract optical properties and fluorophore concentrations from 748 clinical measurements of cervical tissue. A diagnostic algorithm based on these extracted parameters is developed and evaluated using cross-validation. The sensitivity/specificity of this algorithm relative to the gold standard of histopathology per measurement are 8551%; this is comparable to accuracy reported in other studies of optical technologies for detection of cervical cancer and its precursors.

The clinical effectiveness of optical spectroscopy for the in vivo diagnosis of cervical intraepithelial neoplasia: where are we?

OBJECTIVE: In this review, we evaluate the diagnostic efficacy of optical spectroscopy technologies (fluorescence and reflectance spectroscopy) for the in vivo diagnosis of cervical neoplasia using both point probe and multispectral imaging approaches. METHODS: We searched electronic databases using the following terms: cervical cancer, cervical intraepithelial neoplasia, squamous intraepithelial lesion, and spectroscopy, fluorescence spectroscopy, or reflectance spectroscopy. We included studies that evaluated fluorescence and reflectance spectroscopy devices for in vivo diagnosis, compared those results with biopsy results, and reported on the sensitivity and specificity of the devices tested. RESULTS: Twenty-six studies, including seven phase II trials and one randomized clinical trial, met our acceptability criteria. We found several important differences across the studies including device approach (multispectral versus point probe), study population, disease classification system, and disease threshold. This heterogeneity prevented formal combination of sensitivity and specificity results. CONCLUSION: Optical spectroscopy has similar performance to colposcopy and may help localize lesions and therefore be an effective adjunct to colposcopy. Reports on the diagnostic accuracy of these devices should use common thresholds for the construction of receiver operating characteristic curves to enable comparisons with standard technologies and facilitate their adoption. Optical spectroscopy has also been identified for possible use as ASCUS triage and primary screening, yet neither has been sufficiently evaluated to warrant a conclusion as to their suitability in this role.

Fluorescence and reflectance device variability throughout the progression of a phase II clinical trial to detect and screen for cervical neoplasia using a fiber optic probe.

Large phase II trials of fluorescence and reflectance spectroscopy using a fiber optic probe in the screening and diagnostic settings for detecting cervical neoplasia have been conducted. We present accrual and histopathology data, instrumentation, data processing, and the preliminary results of interdevice consistencies throughout the progression of a trial. Patients were recruited for either a screening trial (no history of abnormal Papanicolaou smears) or a diagnostic trial (a history of abnormal Papanicolaou smears). Colposcopy identified normal and abnormal squamous, columnar, and transformation zone areas that were subsequently measured with the fiber probe and biopsied. In the course of the clinical trial, two generations of spectrometers (FastEEM2 and FastEEM3) were designed and utilized as optical instrumentation for in vivo spectroscopic fluorescence and reflectance measurements. Data processing of fluorescence and reflectance data is explained in detail and a preliminary analysis of the variability across each device and probe combination is explored. One thousand patients were recruited in the screening trial and 850 patients were recruited in the diagnostic trial. Three clinical sites attracted a diverse range of patients of different ages, ethnicities, and menopausal status. The fully processed results clearly show that consistencies exist across all device and probe combinations throughout the diagnostic trial. Based on the stratification of the data, the results also show identifiable differences in mean intensity between normal and high-grade tissue diagnosis, pre- and postmenopausal status, and squamous and columnar tissue type. The mean intensity values of stratified data show consistent separation across each of the device and probe combinations. By analyzing trial spectra, we provide more evidence that biographical variables such as menopausal status as well as tissue type and diagnosis significantly affect the data. Understanding these effects will lead to better modeling parameters when analyzing the performance of fluorescence and reflectance spectroscopy.

Instrumentation as a source of variability in the application of fluorescence spectroscopic devices for detecting cervical neoplasia.

We report on a study designed to assess variability among three different fluorescence spectroscopy devices, four fiber optic probes, and three sets of optical calibration standards to better understand the reproducibility of measurements and interdevice comparisons of fluorescence spectroscopic data intended for clinical diagnostic use. Multiple measurements are acquired from all sets of standards using each combination of spectrometer, fiber optic probe, and optical standard. Data are processed using standard calibration methods to remove instrument-dependant responses. Processed spectra are analyzed using an analysis of variance to assess the percent variance explained by each factor that was statistically significant. Analysis of processed data confirms statistically significant differences among the spectrometers and fiber optic probes. However, no differences are found when varying calibration standards or measurement date and time. The spectrometers and fiber optic probes are significant sources of variability, but appropriate data processing substantially reduces these effects. Studies of inter- and intradevice variability are important methodological issues for optical device trials and must be included in the quality assurance studies for the clinical trial design.

A translational bioengineering course provides substantial gains in civic scientific literacy.

A growing number of essential consumer choices and public policy issues require a basic level of scientific literacy. Recent studies suggest as many as three-quarters of adults are unable to read and understand news accounts of scientific advances and controversies. In response to this challenge, a new course for non-science majors, Bioengineering and World Health, was designed to improve biomedical literacy. The goal of this study was to compare scientific literacy of students enrolled in the course to that of two groups of students who had not taken the course; the first control group included students majoring in Biomedical Engineering (BME), the second included those majoring in Liberal Arts or Natural Sciences. Small group interviews in which students discussed science news accounts from the popular press were used to assess scientific literacy. Students in Bioengineering and World Health showed increasing scientific literacy throughout the course. At the conclusion of Bioengineering and World Health, the mean scientific literacy of students in the course was significantly higher than that in both control groups. Students were stratified by the number of semester credit hours completed in science, math, engineering and technology (SME&T) courses. Regardless of number of SME&T hours completed, the mean scientific literacy of students completing Bioengineering and World Health was equivalent to that of BME majors who had completed more than 60 semester credit hours of SME&T coursework, suggesting that a single introductory course can significantly influence scientific literacy as measured by participant's ability to discuss medical innovations from a common news source.