| 1. |
- Demenais, F, et al.
(author)
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Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study.
- 2010
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 1568-1583
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Journal article (peer-reviewed)abstract
- Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
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| 2. |
- Van Holsbeke, C., et al.
(author)
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Acoustic streaming cannot discriminate reliably between endometriomas and other types of adnexal lesion: a multicenter study of 633 adnexal masses
- 2010
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 35:3, s. 349-353
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Journal article (peer-reviewed)abstract
- Objective To determine the ability of acoustic streaming to discriminate between endometriomas and other adnexal masses. Methods We used data from 1938 patients with an adnexal mass included in Phase 2 of the International Ovarian Tumor Analysis (IOTA) study. All patients had been examined by transvaginal gray-scale and Doppler ultrasound following a standardized research protocol. Assessment of acoustic streaming was voluntary and was carried out only in lesions containing echogenic cyst fluid. Acoustic streaming was defined as movement of particles inside the cyst fluid during gray-scale and/or color Doppler examination provided that the probe had been held still for two seconds to ensure that the movement of the particles was not caused by movement of the probe or the patient. Only centers where acoustic streaming had been evaluated in > 90% of cases were included. Sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), and positive and negative predictive values (PPV and NPV) of acoustic streaming with regard to endometrioma were calculated. Results 460 (24%) masses were excluded because they were examined in centers where <= 90% of the masses with echogenic cyst fluid had been evaluated for the presence of acoustic streaming. Acoustic streaming was evaluated in 633 of 646 lesions containing echogenic cyst fluid. It was present in 19 (9%) of 209 endometriomas and in 55 (13%) of 424 other lesions. This corresponds to a sensitivity of absent acoustic streaming with regard to endometrioma of 91% (190/209), a specificity of 13% (55/424), LR+ of 1.04, LR- of 0.69, PPV of 34% (190/559) and NPV of 74% (55/74). Conclusions Acoustic streaming cannot discriminate reliably between endometrioinas and other adnexal lesions, and the presence of acoustic streaming does not exclude an endometrioma. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
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| 3. |
- Van Holsbeke, C., et al.
(author)
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Prospective external validation of the 'ovarian crescent sign' as a single ultrasound parameter to distinguish between benign and malignant adnexal pathology
- 2010
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 36:1, s. 81-87
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Journal article (peer-reviewed)abstract
- Objective To determine the sensitivity and specificity of the 'ovarian crescent sign' (OCS) - a rim of normal ovarian tissue seen adjacent to an ipsilateral adnexal mass as a sonographic feature to discriminate between benign and malignant adnexal masses. Methods The patients included were a subgroup of patients participating in the International Ovarian Tumor Analysis (IOTA) Phase 2 study, which is an international multicenter study. The subgroup comprised 1938 patients, with an adnexal mass, recruited from 19 ultrasound centers in different countries. All patients were scanned using the same standardized ultrasound protocol. Information on more than 40 demographic and ultrasound variables were collected, but the evaluation of the OCS was optional. Only patients from centers that had evaluated the OCS in >= 90% of their cases were included. The gold standard was the histological diagnosis of the adnexal mass. The ability of the OCS to discriminate between borderline or invasively malignant vs. benign adnexal masses, as well as between invasively malignant vs. other (benign and borderline) tumors, was determined and compared with the performance of subjective evaluation of ultrasound findings by the ultrasound examiner. Results The OCS was evaluated in 1377 adnexal masses from 12 centers, 938 (68%) masses being benign, 86 (6%) borderline, 305 (22%) primary invasive and 48 (3%) metastases. The OCS was present in 398 (42%) of 938 benign masses, in 14 (16%) of 86 borderline tumors, in 18 (6%) of 305 primary invasive tumors (one malignant struma ovarii, one uterine clear cell adenocarcinoma and 16 epithelial carcinomas, i.e. four Stage I and 12 Stage II-IV) and in two (4%) of 48 ovarian metastases. Hence, the sensitivity and specificity for absent OCS to identify a malignancy was 92% and 42%, respectively, and the positive and negative likelihood ratios (LR+ and LR-, respectively) were 1.60 and 0.18. Subjective impression performed significantly better than the OCS. Sensitivity and specificity were 90% and 92%, respectively, LR+ was 11.0 and LR- was 0.10. For discrimination between invasive vs. benign or borderline tumors, the sensitivity for absent OCS was 94%, the specificity was 40%, the LR+ was 1.58 and the LR- was 0.14. Conclusion This study confirms previous reports that the presence of the OCS decreases the likelihood of invasive malignancy in adnexal masses. However it is a poor discriminator between benign and malignant adnexal masses. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
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| 4. |
- Creevey, O. L., et al.
(author)
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Fundamental properties of the Population II fiducial stars HD 122563 and Gmb 1830 from CHARA interferometric observations
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A17-
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Journal article (peer-reviewed)abstract
- We have determined the angular diameters of two metal-poor stars, HD 122563 and Gmb 1830, using CHARA and Palomar Testbed Interferometer observations. For the giant star HD 122563, we derive an angular diameter theta(3D) = 0.940 +/- 0.011 milliarcseconds (mas) using limb-darkening from 3D convection simulations and for the dwarf star Gmb 1830 (HD 103095) we obtain a 1D limb-darkened angular diameter theta(1D) = 0.679 +/- 0.007 mas. Coupling the angular diameters with photometry yields effective temperatures with precisions better than 55 K (T-eff = 4598 +/- 41 K and 4818 +/- 54 K - for the giant and the dwarf star, respectively). Including their distances results in very well-determined luminosities and radii (L = 230 +/- 7 L-circle dot, R = 24.1 +/- 1.1 R-circle dot and L = 0.213 +/- 0.002 L-circle dot, R = 0.665 +/- 0.014 R-circle dot, respectively). We used the CESAM2k stellar structure and evolution code in order to produce models that fit the observational data. We found values of the mixing-length parameter alpha (which describes 1D convection) that depend on the mass of the star. The masses were determined from the models with precisions of < 3% and with the well-measured radii excellent constraints on the surface gravity are obtained (log g = 1.60 +/- 0.04, 4.59 +/- 0.02 dex, respectively). The very small errors on both log g and T-eff provide stringent constraints for spectroscopic analyses given the sensitivity of abundances to both of these values. The precise determination of T-eff for the two stars brings into question the photometric scales for metal-poor stars.
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