Cancer risk variation in BRCA1/2 mutation families

BRCA1/2 mutation carriers are at a significantly increased risk for breast and ovarian cancer as compared to women in the general population. The cancer risk estimates for mutation carriers show however considerable variation. More accurate, personal risk estimation would be beneficial for counseling and decision making regarding breast cancer screening and preventive surgery. The aim of this thesis was to improve the breast and ovarian cancer risk estimates for BRCA1/2 carriers and their female relatives, by explaining the risk variation and developing subgroup specific risk estimates. Therefore methodology and population characteristics – i.e. mutation status, mutation spectrum, family history, birth cohort – were assessed in families that were referred for genetic testing. The results showed that the reported variation in cancer risk estimates for BRCA1/2 carriers is mainly due to differences in the applied methodology, whereas differences between women have a smaller effect. Non-carriers in BRCA1/2 families appeared to be at a slightly increased risk for breast cancer in their forties as compared to the general population. Differences in the mutation spectrum only partially explained the regional differences among Dutch carriers, and the breast cancer risk did not depend on whether the mutation was paternally or maternally inherited. The breast cancer risk in mutation carriers above age 60 was still significantly increased, and annual screening detected their tumors in a more favorable stage. Application of the above findings will improve risk counselling of BRCA1/2 mutation carriers, and further evaluation of the breast screening protocols in these families is warranted to optimized surveillance

Resonance Tuning in Professional Operatic Sopranos

Soprano singers are capable of singing at pitches exceeding 1000 Hz, where the spacing of the harmonics means that the vocal tract resonances are not fully utilised. Sopranos therefore move the articulators, to "tune" the resonances of the vocal tract near to harmonics of the voice source, improving the efficiency of sound production. Although resonance tuning has been observed in soprano singers, it is not yet understood how this phenomenon is achieved and which articulators play the most significant roles in altering the vocal tract resonances. A preliminary experiment explored the use of broad band noise excitation of the vocal tract to observe resonance tuning behaviour in girl choristers. A second experiment extended this procedure to include MRI to observe the vocal tracts of 6 professional soprano opera singers and investigate how the articulators affect vocal tract resonances. The effects of MRI measurement conditions on singers were also investigated to establish whether measurements obtained during MRI are representative of normal singing. Finally, a perceptual test was conducted to study the perception of different methods of resonance tuning. As expected, considerable R1:f0 tuning, and some R2:2f0 tuning was observed in both groups. MRI revealed some links between resonances and articulators, however no consistent patterns in production were observed across subjects. The results showed strong differences in resonance production between different vowels and subjects, suggesting that resonance tuning production is not only a complex and context-specific topic, but also highly individual

Resonance Tuning in Three Girl Choristers

Objective The phenomenon of resonance tuning, whereby a singer modifies the shape of their vocal tract to increase the acoustic power output, is commonly exploited across large pitch ranges by professional sopranos and has been observed to a lesser degree in nonexpert adult singers. This study considers the employment of two common resonance tuning techniques in experienced child singers; tuning the first vocal tract resonance to the fundamental (R1: fo) and tuning the second resonance to the second harmonic (R2:2 fo). Methods Wide-band excitation at the subject's mouth during singing was used to measure the vocal tract resonances of three girl choristers, and vowel formant values in speech were extracted from samples of spoken text. Measured resonance values were cross-referenced with first and second harmonics for sung vowels across the subjects' ranges to identify the resonance tuning techniques employed, and these results were compared with those previously observed by others in professional adult classical singers. Results and Conclusions There was clear evidence that the subjects employed resonance tuning techniques comparable with the strategies used by adult singers. The protocol and results presented here pave the way for further studies exploring the development of resonance tuning techniques in young soprano voices, with the potential to impact on approaches to classical singing training in the future

Cancer risk variation in BRCA1/2 mutation families

BRCA1/2 mutation carriers are at a significantly increased risk for breast and ovarian cancer as compared to women in the general population. The cancer risk estimates for mutation carriers show however considerable variation. More accurate, personal risk estimation would be beneficial for counseling and decision making regarding breast cancer screening and preventive surgery. The aim of this thesis was to improve the breast and ovarian cancer risk estimates for BRCA1/2 carriers and their female relatives, by explaining the risk variation and developing subgroup specific risk estimates. Therefore methodology and population characteristics – i.e. mutation status, mutation spectrum, family history, birth cohort – were assessed in families that were referred for genetic testing. The results showed that the reported variation in cancer risk estimates for BRCA1/2 carriers is mainly due to differences in the applied methodology, whereas differences between women have a smaller effect. Non-carriers in BRCA1/2 families appeared to be at a slightly increased risk for breast cancer in their forties as compared to the general population. Differences in the mutation spectrum only partially explained the regional differences among Dutch carriers, and the breast cancer risk did not depend on whether the mutation was paternally or maternally inherited. The breast cancer risk in mutation carriers above age 60 was still significantly increased, and annual screening detected their tumors in a more favorable stage. Application of the above findings will improve risk counselling of BRCA1/2 mutation carriers, and further evaluation of the breast screening protocols in these families is warranted to optimized surveillance

CP violation in multibody B decays from QCD factorization

We test a data-driven approach based on QCD factorization for charmless three-body B-decays by confronting it to measurements of CP violation in B⁻→ π⁻π⁺π⁻. While some of the needed non-perturbative objects can be directly extracted from data, some others can, so far, only be modelled. Although this approach is currently model dependent, we comment on the perspectives to reduce this model dependence. While our model naturally accommodates the gross features of the Dalitz distribution, it cannot quantitatively explain the details seen in the current experimental data on local CP asymmetries. We comment on possible refinements of our simple model and conclude by briefly discussing a possible extension of the model to large invariant masses, where large local CP asymmetries have been measured

Performance of cropping systems designed to reduce nitrate leaching into shallow municipal well aquifers

This on-farm experiment tested five different cropping systems with the potential to improve nitrate N management in the capture zones of community water supplies in the upper Midwest. Residual soil nitrate N concentrations were determined for each system in order to estimate the likelihood of nitrate N leaching from the system. An economic analysis also was conducted