Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

BACKGROUND: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. METHODS: BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205. FINDINGS: 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI. INTERPRETATION: For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. FUNDING: Novartis, United States National Cancer Institute, International Breast Cancer Study Group.

[Illustrations du Quart livre des faictz et dictz héroïques du noble Pantagruel.] / François Rabelais, aut. du texte

Comprend : [Livre IV. Fig. au Prologue : François Rabelais rédigeant les aventures de Pantagruel.] [Cote : microfilm R 28836] ; [Livre IV. Chap. Ier. Fig. au titre :] Comment Pantagruel monta sur mer pour visiter l'Oracle de la divine bouteille [Cote : microfilm R 28836] ; [Livre IV. Chap. II. Fig. au titre :] Comment Pantagruel rencontra un navire de voyageurs retournans du pays Lanternois. [Cote : microfilm R 28836] ; [Livre IV. Chap. III. Fig. au titre :] Comment Panurge feit noyer en mer les moutons et le marchant qui les conduisoit [Cote : microfilm R 28836] ; [Livre IV. Chap. IV. Fig. au titre :] Comment Pantagruel arriva en l'Isle Eunasin, et des estranges alliances du pays. [Cote : microfilm R 28836] ; [Livre IV. Chap. V. Fig. au titre :] Comment Pantagruel descendit en l'Isle de Chely, en laquelle regnoit Panigon [Cote : microfilm R 28836] ; [Livre IV. Chap. VI. Fig. au titre :] Comment nous passasmes Procuration et de l'estrange maniere de vivre entre les Chicquanoux. [Cote : microfilm R 28836] ; [Livre IV. Chap. VII. Fig. au titre :] Comment Pantagruel passa les Isles de Tohu et Bohu et de l'estrange mort de Bringuenaril les avaleurs de moulins à vent [Cote : microfilm R 28836] ; [Livre IV. Chap. IX. Fig. au titre :] Quelles contenances eurent Panurge et frere Jean durant la tempeste [Cote : microfilm R 28836]

High-density collagen gel tubes as a matrix for primary human bladder smooth muscle cells.

Tissue-engineered grafts for the urinary tract are being investigated for the potential treatment of several urologic diseases. These grafts, predominantly tubular-shaped, usually require in vitro culture prior to implantation to allow cell engraftment on initially cell-free scaffolds. We have developed a method to produce tubular-shaped collagen scaffolds based on plastic compression. Our approach produces a ready cell-seeded graft that does not need further in vitro culture prior to implantation. The tubular collagen scaffolds were in particular investigated for their structural, mechanical and biological properties. The resulting construct showed an especially high collagen density, and was characterized by favorable mechanical properties assessed by axial extension and radial dilation. Young modulus in particular was greater than non-compressed collagen tubes. Seeding densities affected proliferation rate of primary human bladder smooth muscle cells. An optimal seeding density of 10(6) cells per construct resulted in a 25-fold increase in Alamar blue-based fluorescence after 2 wk in culture. These high-density collagen gel tubes, ready seeded with smooth muscle cells could be further seeded with urothelial cells, drastically shortening the production time of graft for urinary tract regeneration.

Reliure de : Poemata

Numérisation partielle de reliure

Brain glucose sensing, counterregulation, and energy homeostasis.

Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

Los conceptos de espacio y tiempo en la teoría de la relatividad

Algunos filósofos no han vacilado en afirmar que la teoria de la relatividad era el relativismo aplicado a la Física. Para probar su apreciación han aducido algunas expresiones de EINSTEIN -de otros físicosno nos ocuparemos aquí-, que pueden inducir a confusión: así, por ejemplo, la afirmación de que no se puede hablar de la trayectoria deun móvil, de que en la realidad no es válida la ley de composición de ve locidades, etc. Con su acostumbrada brillantez ha dicho ORTEGA YGASSET frases como la siguiente: "Para la física de EINSTEIN, nuestro conocimiento es absoluto, la realidad es la relativa".Para ver si aquellas aprensiones son justificadas y, sobre todo, para ver si se puede admitir lo filosófico que hay en la teoría de la relatividad,vamos a someter a ésta a una dura prueba: a ser examinada por la filosofía que mejor ha sabido armonizar, a nuestro parecer, lo sensible y loideal: la filosofía escolástica, que al no apoyarse en teorías científicas, sino en la observación cierta de las cosas, podemos considerarla comoadecuado instrumento de trabajo. Entre los filósofos escolásticos nos ha parecido muy digno de tenerse en cuenta SUAREZ. El llega, efectivamente,al campo escolástico en una época de intenso renacimiento. Las grandes aportaciones medievales son sometidas por él a una aguda críticay sin integrarse en ninguna escuela, tiene la suficiente libertad de espíritu para seguir sus propios derroteros. Además, en este problema, nose aparta SUAREZ en lo esencial del sentir común de los filósofos escolásticos.

Efficient targeted transcript discovery via array-based normalization of RACE libraries.

Rapid amplification of cDNA ends (RACE) is a widely used approach for transcript identification. Random clone selection from the RACE mixture, however, is an ineffective sampling strategy if the dynamic range of transcript abundances is large. To improve sampling efficiency of human transcripts, we hybridized the products of the RACE reaction onto tiling arrays and used the detected exons to delineate a series of reverse-transcriptase (RT)-PCRs, through which the original RACE transcript population was segregated into simpler transcript populations. We independently cloned the products and sequenced randomly selected clones. This approach, RACEarray, is superior to direct cloning and sequencing of RACE products because it specifically targets new transcripts and often results in overall normalization of transcript abundance. We show theoretically and experimentally that this strategy leads indeed to efficient sampling of new transcripts, and we investigated multiplexing the strategy by pooling RACE reactions from multiple interrogated loci before hybridization.

Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images.

This paper presents a validation study on statistical nonsupervised brain tissue classification techniques in magnetic resonance (MR) images. Several image models assuming different hypotheses regarding the intensity distribution model, the spatial model and the number of classes are assessed. The methods are tested on simulated data for which the classification ground truth is known. Different noise and intensity nonuniformities are added to simulate real imaging conditions. No enhancement of the image quality is considered either before or during the classification process. This way, the accuracy of the methods and their robustness against image artifacts are tested. Classification is also performed on real data where a quantitative validation compares the methods' results with an estimated ground truth from manual segmentations by experts. Validity of the various classification methods in the labeling of the image as well as in the tissue volume is estimated with different local and global measures. Results demonstrate that methods relying on both intensity and spatial information are more robust to noise and field inhomogeneities. We also demonstrate that partial volume is not perfectly modeled, even though methods that account for mixture classes outperform methods that only consider pure Gaussian classes. Finally, we show that simulated data results can also be extended to real data.

The IST METRA Project

This article summarizes the main achievementsof the Multi-Element Transmit andReceive Antennas (METRA) Project, an ISTresearch and technological development project carried out between January 2000 and June 2001 by Universitat Politècnica de Catalunya, the Center for Personkommunikation of Aalborg University, Nokia Networks, Nokia Mobile Phones, and Vodafone Group Research and Development.The main objective of METRA was the performanceevaluation of multi-antenna terminals incombination with adaptive antennas at the basestation in UMTS communication systems. 1 AMIMO channel sounder was developed that providedrealistic multi-antenna channel measurements.Using these measured data, stochasticchannel models were developed and properly validated.These models were also evaluated inorder to estimate their corresponding channelcapacity. Different MIMO configurations andprocessing schemes were developed for both theFDD and TDD modes of UTRA, and their linkperformance was assessed. Performance evaluationwas completed by system simulations thatillustrated the benefits of MIMO configurationsto the network operator. Implementation cost vs.performance improvement was also covered bythe project, including the base station and terminalmanufacturer and network operator viewpoints.Finally, significant standards contributionswere generated by the project and presented to the pertinent 3GPP working groups.