Archives parlementaires de 1787 à 1860 ; 52-61, 63-82. Convention nationale. Série 1 / Tome 81 / impr. par ordre du Sénat et de la Chambre des députés ; fondé par MM. Mavidal et E. Laurent ; continué́ par M. L. Lataste,... M. Louis Claveau,... M. Constant Pionnier,... [et al.]

Collection : Les archives de la Révolution française ; 3.1

Friday Facts, December 3, 2010, Vol. 81

Bureau of Nutrition and Health Promotion part of the Iowa Department of Public Health produces of weekly newsletter about the Iowa WIC Program for the State of Iowa citizen.

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.

CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation.

Previously we determined that S81 is the highest stoichiometric phosphorylation on the androgen receptor (AR) in response to hormone. To explore the role of this phosphorylation on growth, we stably expressed wild-type and S81A mutant AR in LHS and LAPC4 cells. The cells with increased wild-type AR expression grow faster compared with parental cells and S81A mutant-expressing cells, indicating that loss of S81 phosphorylation limits cell growth. To explore how S81 regulates cell growth, we tested whether S81 phosphorylation regulates AR transcriptional activity. LHS cells stably expressing wild-type and S81A mutant AR showed differences in the regulation of endogenous AR target genes, suggesting that S81 phosphorylation regulates promoter selectivity. We next sought to identify the S81 kinase using ion trap mass spectrometry to analyze AR-associated proteins in immunoprecipitates from cells. We observed cyclin-dependent kinase (CDK)9 association with the AR. CDK9 phosphorylates the AR on S81 in vitro. Phosphorylation is specific to S81 because CDK9 did not phosphorylate the AR on other serine phosphorylation sites. Overexpression of CDK9 with its cognate cyclin, Cyclin T, increased S81 phosphorylation levels in cells. Small interfering RNA knockdown of CDK9 protein levels decreased hormone-induced S81 phosphorylation. Additionally, treatment of LNCaP cells with the CDK9 inhibitors, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole and Flavopiridol, reduced S81 phosphorylation further, suggesting that CDK9 regulates S81 phosphorylation. Pharmacological inhibition of CDK9 also resulted in decreased AR transcription in LNCaP cells. Collectively these results suggest that CDK9 phosphorylation of AR S81 is an important step in regulating AR transcriptional activity and prostate cancer cell growth.

Fly Ash Concrete Compressive Strength and Freeze-Thaw Durability, MLR-81-06, 1981

The current study investigated the effect of fly ash class, source and amount on the compressive strength and freeze-thaw durability of fly ash concrete. Concrete aggregates of varying quality were also included as test variables. The current results and those obtained from previous laboratory and field work indicate that compressive strength can·be affected by fly ash class, source and amount while aggregate quality is shown to have no effect on strength. Freeze-thaw durability of fly ash concrete is strongly affected by aggregate quality and to a lesser degree by fly ash class, amount and source.

Evaluation of the Concrete Admixture Gla-Zit, MLR-81-5, 1983

A concrete admixture, Gla-Zit, was evaluated in 1970 by the Iowa State Highway Commission and found to be lacking in providing beneficial effects to concrete. This current evaluation is similar to that conducted in 1970 with slight modifications in the actual concrete mixes studied. At the request of the manufacturer, all concrete mixes containing Gla-Zit were non-air entrained. Concrete properties examined were compressive strength, salt scaling resistance, absorption, resistance to chloride penetration, and freeze-thaw durability. The differences found in the mixes studied are much more attributible to air entrainment, or the lack thereof, than the influence of Gla-Zit. The study re-affirms that it is necessary to have properly air entrained concrete to lessen the detrimental effects of freeze and thaw and scaling caused by salting. There is no data in the study to suggest that Gla-Zit has any significant effect on any of the concrete properties examined.

Report on Fly Ash Variability, MLR-81-2, 1981

The physical-chemical testing of fly ashes indicates that, under normal operating conditions, a low variability of results can be expected from a particular generating plant unit. However, unannounced changes in coal source and/or plant operations do occur and they may result in an ash with undesirable properties. Since these properties can be detected by physical-chemical testing, it is recommended that this testing be performed on a lot-by-lot basis when a plant is supplying fly ash to a construction project.

Polk County, Township 81 North Range 24 West

Des Moines River Plat Maps.

Polk County, Township 81 North Range 25 West

Des Moines River Plat Maps.

Dallas County, Township 81 North Range 26 West

Des Moines River Plat Maps.

Dallas County, Township 81 North Range 27 West

Des Moines River Plat Maps.

Field Evaluation of Electro-Reflective Measuring Apparatus (ERMA), MLR-81-01, 1981

The Electro-Reflective Measuring Apparatus (ERMA) was developed by the Minnesota Department of Highways in 1974 to measure the retro-reflective characteristics of pavement marking materials. Minnesota researchers recommended that due to the increased cost of pavement marking materials and reduced availability of these materials, ERMA can and should be used as a maintenance management tool to determine when painting is necessary rather than according to a fixed time schedule. The Iowa DOT Office of Materials built an ERMA device patterned after Minnesota's design in 1976. Subsequent efforts to calibrate and correlate this ERMA device to District Paint Foremen ratings proved unsuccessful, and ERMA modification or abandonment was recommended in 1979. Lyman Moothart, Materials Lab. Tech. 4, modified the ERMA device in 1980 and correlation attempts to District Paint Foremen ratings conducted in November 1980 have been moderately successful. A Paint/No Paint ERMA value has been established which will identify about 90% of the painting needs but will also include about 40% of the marking lines not needing repainting. The Office of Maintenance should establish a trial ERMA program to study the accuracy and potential cost savings of using ERMA to identify pavement marking needs.

Report on Fly Ash as a Soil Additive, MLR-81-03, 1981

The addition of a selected self-cementing, Class C fly ash to blow sand soils improves their compacted strength greatly as opposed to the minimal strength improvement when fly ash is mixed with loess soil. By varying the percentage of fly ash added, the resulting blow sand-fly ash mixture can function as a low strength stabilized material or as a higher strength sub-base. Low strength stabilized material can also be obtained by mixing loess soils with a selected Class C fly ash. The development of the higher strength values required for subbase materials is very dependent upon compaction delay time and moisture condition of the material. Results at this time indicate that, when compaction delays are involved, excess moisture in the material has the greatest positive effect in achieving minimum strengths. Other added retarding agents, such as borax and gypsum, have less effect.