Pubertal timing and breast density in young women: a prospective cohort study.

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk

Aldosterone modulates the association between NCC and ENAC

Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption

Defect configurations and dynamical behavior in a Gay-Berne nematic emulsion

To model a nematic emulsion consisting of a surfactant-coated water droplet dispersed in a nematic host, we performed a molecular dynamics simulation of a droplet immersed in a system of 2048 Gay-Berne ellipsoids in a nematic phase. Strong radial anchoring at the surface of the droplet induced a Saturn ring defect configuration, consistent with theoretical predictions for very small droplets. A surface ring configuration was observed for lower radial anchoring strengths, and a pair of point defects was found near the poles of the droplet for tangential anchoring. We also simulated the falling ball experiment and measured the drag force anisotropy, in the presence of strong radial anchoring as well as zero anchoring strength.Comment: 17 pages, 15 figure

Viscosities of the Gay-Berne nematic liquid crystal

We present molecular dynamics simulation measurements of the viscosities of the Gay-Berne phenomenological model of liquid crystals in the nematic and isotropic phases. The temperature dependence of the rotational and shear viscosities, including the nonmonotonic behavior of one shear viscosity are in good agreement with experimental data. The bulk viscosities are significantly larger than the shear viscosities, again in agreement with experiment.Comment: 11 pages, 4 Postscript figures, Revte

The GLAST Burst Monitor

The next large NASA mission in the field of gamma-ray astronomy, GLAST, is scheduled for launch in 2007. Aside from the main instrument LAT (Large-Area Telescope), a gamma-ray telescope for the energy range between 20 MeV and > 100 GeV, a secondary instrument, the GLAST burst monitor (GBM), is foreseen. With this monitor one of the key scientific objectives of the mission, the determination of the high-energy behaviour of gamma-ray bursts and transients can be ensured. Its task is to increase the detection rate of gamma-ray bursts for the LAT and to extend the energy range to lower energies (from ~10 keV to \~30 MeV). It will provide real-time burst locations over a wide FoV with sufficient accuracy to allow repointing the GLAST spacecraft. Time-resolved spectra of many bursts recorded with LAT and the burst monitor will allow the investigation of the relation between the keV and the MeV-GeV emission from GRBs over unprecedented seven decades of energy. This will help to advance our understanding of the mechanisms by which gamma-rays are generated in gamma-ray bursts.Comment: 8 pages, 7 figures, to appear in SPIE conference proceedings vol 5488, "UV-Gamma Ray Space Telescope Systems," Glasgow UK, 21-24 June 200

Dynamic Modulation of Thymic MicroRNAs in Response to Stress

thymocyte subsets. Several of the differentially regulated murine thymic miRs are also stress responsive in the heart, kidney, liver, brain, and/or spleen. The most dramatic thymic microRNA down modulated is miR-181d, exhibiting a 15-fold reduction following stress. This miR has both similar and distinct gene targets as miR-181a, another member of miR-181 family. Many of the differentially regulated microRNAs have known functions in thymopoiesis, indicating that their dysregulation will alter T cell repertoire selection and the formation of naïve T cells. This data has implications for clinical treatments involving anti-inflammatory steroids, ablation therapies, and provides mechanistic insights into the consequences of infections

The Methodology of Modern Macroeconomics and the Descriptive Approach to Discounting

Critics of modern macroeconomics often raise concerns about unwarranted welfare conclusions and data mining. This paper illustrates these concerns with a thought experiment, based on the debate in environmental economics about the appropriate discount rate in climate change analyses: I set up an economy where a social evaluator wants to determine the optimal time path of emission levels, and seeks advice for this from an old-style neo-classical macroeconomist and a new neo-classical (modern) macroeconomist; I then describe how both economists analyze the economy, their policy advice, and their mistakes. I then use the insights from this thought experiment to point out some pitfalls of the modern macroeconomic methodology

The Fermi Gamma-Ray Burst Monitor

The Gamma-Ray Burst Monitor (GBM) will significantly augment the science return from the Fermi Observatory in the study of Gamma-Ray Bursts (GRBs). The primary objective of GBM is to extend the energy range over which bursts are observed downward from the energy range of the Large Area Telescope (LAT) on Fermi into the hard X-ray range where extensive previous data exist. A secondary objective is to compute burst locations on-board to allow re-orientiong the spacecraft so that the LAT can observe delayed emission from bright bursts. GBM uses an array of twelve sodium iodide scintillators and two bismuth germanate scintillators to detect gamma rays from ~8 keV to ~40 MeV over the full unocculted sky. The on-board trigger threshold is ~0.7 photons/cm2/s (50-300 keV, 1 s peak). GBM generates on-board triggers for ~250 GRBs per year.Comment: 36 pages, 18 figures, to be published in Astrophysical Journa