Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials

OBJECTIVES In 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen? METHODS TEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization. RESULTS TEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone (n = 2045). The first reports are anticipated in mid- and late-2014. CONCLUSIONS We present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer. Trial Registration TEXT: Clinicaltrials.govNCT00066703 SOFT: Clinicaltrials.govNCT00066690.

Changing correlation structures of the Northern Hemisphere atmospheric circulation from 1000 to 2100 AD

Atmospheric circulation modes are important concepts in understanding the variability of atmospheric dynamics. Assuming their spatial patterns to be fixed, such modes are often described by simple indices from rather short observational data sets. The increasing length of reanalysis products allows these concepts and assumptions to be scrutinised. Here we investigate the stability of spatial patterns of Northern Hemisphere teleconnections by using the Twentieth Century Reanalysis as well as several control and transient millennium-scale simulations with coupled models. The observed and simulated centre of action of the two major teleconnection patterns, the North Atlantic Oscillation (NAO) and to some extent the Pacific North American (PNA), are not stable in time. The currently observed dipole pattern of the NAO, its centre of action over Iceland and the Azores, split into a north–south dipole pattern in the western Atlantic with a wave train pattern in the eastern part, connecting the British Isles with West Greenland and the eastern Mediterranean during the period 1940–1969 AD. The PNA centres of action over Canada are shifted southwards and over Florida into the Gulf of Mexico during the period 1915–1944 AD. The analysis further shows that shifts in the centres of action of either teleconnection pattern are not related to changes in the external forcing applied in transient simulations of the last millennium. Such shifts in their centres of action are accompanied by changes in the relation of local precipitation and temperature with the overlying atmospheric mode. These findings further undermine the assumption of stationarity between local climate/proxy variability and large-scale dynamics inherent when using proxy-based reconstructions of atmospheric modes, and call for a more robust understanding of atmospheric variability on decadal timescales.

Evaluation of 3-dimensional superimposition techniques on various skeletal structures of the head using surface models.

OBJECTIVES To test the applicability, accuracy, precision, and reproducibility of various 3D superimposition techniques for radiographic data, transformed to triangulated surface data. METHODS Five superimposition techniques (3P: three-point registration; AC: anterior cranial base; AC + F: anterior cranial base + foramen magnum; BZ: both zygomatic arches; 1Z: one zygomatic arch) were tested using eight pairs of pre-existing CT data (pre- and post-treatment). These were obtained from non-growing orthodontic patients treated with rapid maxillary expansion. All datasets were superimposed by three operators independently, who repeated the whole procedure one month later. Accuracy was assessed by the distance (D) between superimposed datasets on three form-stable anatomical areas, located on the anterior cranial base and the foramen magnum. Precision and reproducibility were assessed using the distances between models at four specific landmarks. Non parametric multivariate models and Bland-Altman difference plots were used for analyses. RESULTS There was no difference among operators or between time points on the accuracy of each superimposition technique (p>0.05). The AC + F technique was the most accurate (D<0.17 mm), as expected, followed by AC and BZ superimpositions that presented similar level of accuracy (D<0.5 mm). 3P and 1Z were the least accurate superimpositions (0.79there was no difference among operators or between time points on the precision of each superimposition technique (p>0.05), the detected structural changes differed significantly between different techniques (p<0.05). Bland-Altman difference plots showed that BZ superimposition was comparable to AC, though it presented slightly higher random error. CONCLUSIONS Superimposition of 3D datasets using surface models created from voxel data can provide accurate, precise, and reproducible results, offering also high efficiency and increased post-processing capabilities. In the present study population, the BZ superimposition was comparable to AC, with the added advantage of being applicable to scans with a smaller field of view.

The exhaustive concordance of the Bible : showing every word of the text of the common English version : together with a comparative concordance of the Authorized and Revised versions : also brief dictionaries of the Hebrew and Greek words of the original, with references to the English words /

Mode of access: Internet.

Andromaque : reproduction of the text of 1697--the last printed in the lifetime of Racine.

Mode of access: Internet.

The Targum of Onkelos to Genesis. A critical enquiry into the value of the text exhibited by Yemem Mss. compared with that of the European recension together with some specimen chapters of the Oriental text.

Mode of access: Internet.

A dictionary and glossary of the Kor-ân, with copious grammatical references and explanations of the text: Arabic-English.

Reprint of the ed. published in London, 1873.

The works of William Shakespeare : the plays edited from the folio of MDCXXIII, with various readings from all the editions and all the commentators, notes, introductory remarks, a historical sketch of the text, an account of the rise and progress of the English drama, a memoir of the poet, and an essay upon his genius /

Publisher's advertisement (12 p.) at beginning of v. 2.

The works of William Shakespeare : the plays edited from the folio of MDCXXIII, with various readings from all the editions and all the commentators, notes, introductory remarks, a historical sketch of the text, an account of the rise and progress of the English drama, a memoir of the poet, and an essay upon the genius /

Mode of access: Internet.

The works of William Shakespeare ; the plays edited from the folio of MDCXXIII, with various readings from all the editions and all the commentators, notes, introductory remarks, a historical sketch of the text, an account of the rise and progress of the English drama, a memoir of the poet, and an essay upon his genius /

Mode of access: Internet.

The works of William Shakespeare; the plays ed. from the folio of MDCXXIII, with various readings from all the editions and all the commentators, notes, introductory remarks, a historical sketch of the text, an account of the rise and progress of the English drama, a memoir of the poet, and an essay upon the genius;

Mode of access: Internet.

The exhaustive concordance of the Bible: showing every word of the text of the common English version of the canonical books, and every occurrence of each word in regular order; together with A comparative concordance of the Authorized and Revised versions, including the American variations; also brief dictionaries of the Hebrew and Greek words of the original, with references to the English words:

"First edition printed April 1894...twenty--ninth printing 1970."

The complete works of Michael de Montaigne, comprising his essays, letters, and his journey through Germany and Italy. Together with a comprehensive life, and side and footnotes from all the commentators, fully explanatory of the text; biogaphical and bibliographical notices, etc.,

Mode of access: Internet.

Aischylou Choēphoroi. The Choephoroe of Aeschylus. A new edition of the text with notes, critical, explanatory, and philological, designed for the use of students in the universities.

Mode of access: Internet.