Optical mammography combined with fluorescence imaging: lesion detection using scatterplots

Using scatterplots of 2 or 3 parameters, diffuse optical tomography and fluorescence imaging are combined to improve detectability of breast lesions. Small or low contrast phantom-lesions that were missed in the optical and fluorescence images were detected in the scatterplots. In patient measurements, all tumors were visible and easily differentiated from artifacts and areolas in the scatterplots. The different rate of intake and wash out of the fluorescent contrast agent in the healthy versus malignant tissues was also observed in the scatterplot: this information can be used to discriminate malignant lesion from normal structures

Computer-aided detection (CAD) for breast MRI: evaluation of efficacy at 3.0 T

OBJECTIVE: The purpose of the study was to evaluate the accuracy of 3.0-T breast MRI interpretation using manual and fully automated kinetic analyses. MATERIAL AND METHODS: Manual MRI interpretation was done on an Advantage Workstation. Retrospectively, all examinations were processed with a computer-aided detection (CAD) system. CAD data sets were interpreted by two experienced breast radiologists and two residents. For each lesion automated analysis of enhancement kinetics was evaluated at 50% and 100% thresholds. Forty-nine malignant and 22 benign lesions were evaluated. RESULTS: Using threshold enhancement alone, the sensitivity and specificity of CAD were 97.9% and 86.4%, respectively, for the 50% threshold, and 97.9% and 90%, respectively, for the 100% threshold. Manual interpretation by two breast radiologists showed a sensitivity of 84.6% and a specificity of 68.8%. For the same two radiologists the mean sensitivity and specificity for CAD-based interpretation was 90.4% (not significant) and 81.3% (significant at p < 0.05), respectively. With one-way ANOVA no significant differences were found between the two breast radiologists and the two residents together, or between any two readers separately. CONCLUSION: CAD-based analysis improved the specificity compared with manual analysis of enhancement. Automated analysis at 50% and 100% thresholds showed a high sensitivity and specificity for readers with varying levels of experience

A Novel Fluorescent Imaging Agent for Diffuse Optical Tomography of the Breast: First Clinical Experience in Patients

Purpose: This is the first clinical evaluation of a novel fluorescent imaging agent (Omocianine) for breast cancer detection with diffuse optical tomography (DOT). Procedures: Eleven women suspected of breast cancer were imaged with DOT at multiple time points (up to 24 h) after receiving an intravenous injection of Omocianine (doses 0.01 to 0.1 mg/kg bodyweight). Breast MRI was obtained for comparison. Results: Histopathology showed invasive cancer in ten patients and fibroadenoma in one patient. With the lowest dose of Omocianine, two of three lesions were detected; with the second dose, three of three lesions were detected; with the two highest doses, none of five lesions were detected. Lesion location on DOT showed excellent agreement with MRI. Optimal lesion-tobackground signals were obtained after 8 h. No adverse events occurred. Conclusions: Lowest doses of Omocianine performed best in lesion detection; DOT using a lowdose fluorescent agent is feasible and safe for breast cancer visualization in patients

Research strategies for organizational history:a dialogue between historical theory and organization theory

If history matters for organization theory, then we need greater reflexivity regarding the epistemological problem of representing the past; otherwise, history might be seen as merely a repository of ready-made data. To facilitate this reflexivity, we set out three epistemological dualisms derived from historical theory to explain the relationship between history and organization theory: (1) in the dualism of explanation, historians are preoccupied with narrative construction, whereas organization theorists subordinate narrative to analysis; (2) in the dualism of evidence, historians use verifiable documentary sources, whereas organization theorists prefer constructed data; and (3) in the dualism of temporality, historians construct their own periodization, whereas organization theorists treat time as constant for chronology. These three dualisms underpin our explication of four alternative research strategies for organizational history: corporate history, consisting of a holistic, objectivist narrative of a corporate entity; analytically structured history, narrating theoretically conceptualized structures and events; serial history, using replicable techniques to analyze repeatable facts; and ethnographic history, reading documentary sources "against the grain." Ultimately, we argue that our epistemological dualisms will enable organization theorists to justify their theoretical stance in relation to a range of strategies in organizational history, including narratives constructed from documentary sources found in organizational archives. Copyright of the Academy of Management, all rights reserved

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P &lt;.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes