Menstrual cycle associated changes in hormone-related gene expression in oestrogen receptor positive breast cancer.

The major changes in hormone levels that occur through the menstrual cycle have been postulated to affect the expression of hormone-regulated and proliferation-associated genes (PAGs) in premenopausal ER+ breast cancer. Whilst previous studies have demonstrated differences in gene expression, here, we investigated if there are within patient changes in the expression of oestrogen- and progesterone-regulated genes (ERGs and PRGs) and PAGs in ER+ breast cancer during the menstrual cycle. Samples from 96 patients in two independent prospective studies of the effect of menstrual cycle on ER+ breast cancer were used. Plasma hormone measurements were used to assign tumours to one of three pre-defined menstrual cycle windows: W1 (days 27-35 and 1-6; low oestradiol and low progesterone), W2 (days 7-16; high oestradiol and low progesterone) and W3 (days 17-26; intermediate oestradiol and high progesterone). RNA expression of 50 genes, including 27 ERGs, 11 putative PRGs and seven PAGs was measured. The AvERG (geomean of PGR, GREB1, TFF1 and PDZK1) was used as a composite measure of ERG expression and showed significant changes between the three windows of the menstrual cycle increasing over 2.2-fold between W1 and W2 and decreasing between W2 and W3 and between W3 and W1. Proliferation gene expression also varied significantly, following the same pattern of changes as ERG expression, but the changes were of lower magnitude (1.4-fold increase between W1 and W2). Significant changes in the expression of eight individual ERGs, including GREB1, PGR and TFF1, and two PAGs were observed between W1 and either W2 or W3 with all genes showing higher levels in W2 or W3 (1.3-2.4-fold; FDR 0.016-0.05). The AvProg, a composite measure of PRG expression, increased significantly (1.5-fold) in W3 compared to W1 or W2 but no significant changes were observed for individual PRGs. In conclusion, we observed significant changes in ERG, PRG and PAG expression in ER+ breast tumours during the menstrual cycle that may affect the assessment and interpretation of prominent biomarkers (e.g. PgR) and commonly used multigene prognostic signatures in premenopausal ER+ breast cancer

Renal replacement therapy in Europe : A summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus

Publisher Copyright: © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.Background: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient datawere provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp).Whencompared with the USA, the incidence of patients starting RRTpmpsecondary toDMin Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9-51.2) for patients with DM as the cause of ESRD.publishersversionPeer reviewe

THE PRODUCTION OF PLATELET-ACTIVATING-FACTOR (PAF) DURING HEMODIALYSIS WITH CUPROPHANE MEMBRANE - DOES THE CALCIUM-CONCENTRATION IN THE DIALYSATE PLAY ANY ROLE ON IT

There is evidence that PAF may be produced during hemodialysis (HD) mainly when using cuprophane membrane (CU). It is also known that PAF production is dependent on the amount of extracellular calcium (E(Ca)(2+)). In the present study, we investigated the production of PAF during HD with CU as well as the role of the Ca2+ in the dialysate with respect to PAF production. Five hemodialyzed patients were studied in two consecutive HD sessions (the first performed using dialysate without Ca2+. and the second with a Ca2+ concentration of 3.25 mEq/L) and at different times during the sessions the circulating PAF levels as well as the leukocyte and platelet counts were measured. The results demonstrated that a) PAF was indeed produced during HD with CU, b) the highest PAF levels in blood were observed between 5 and 15 minutes from the beginning of HD, at which time the lowest circulating leukocyte and platelet count were measured and c) PAF levels in blood were inversely proportional to the Ca2+ concentration in the dialysate (with the exceptional case of the 15 minutes), although we expected the opposite results

Understanding the Capability of Future Direct-imaging Observations to Quantify Atmospheric Chemical Effects of Stellar Proton Events

Models developed for Earth are often applied in exoplanet contexts. Validation in extraterrestrial settings can provide an important test of model realism and increase our confidence in model predictions. NASA’s upcoming space-based IROUV telescope will provide unprecedented opportunities to perform such tests. Here, we use the Planetary Spectrum Generator to simulate IROUV reflected-light spectroscopic observations of flare-driven photochemical changes produced by the Whole Atmosphere Community Climate Model, part of the Community Earth System Model framework. We find that NO _2 is the most observable gas to target, and integrating the signal for two days following the flare and comparing to a baseline of preflare data would achieve the highest signal-to-noise ratio. The NO _2 response is much larger for K-star tidally locked planets than G-star rapidly rotating planets and does not depend strongly on O _2 level. The NO _2 response should be observable for planets within 3–4 pc independent of the phase angle since the amount of reflected light is larger at smaller phases, but the NO _2 concentration is low near the substellar point. This work outlines a methodology for validating and ground-truthing atmospheric chemistry models developed for Earth that could be useful for the numerical exploration of exoplanets

Simple Physics and Integrators Accurately Reproduce Mercury Instability Statistics

The long-term stability of the solar system is an issue of significant scientific and philosophical interest. The mechanism leading to instability is Mercury’s eccentricity being pumped up so high that Mercury either collides with Venus or is scattered into the Sun. Previously, only three five-billion-year  N -body ensembles of the solar system with thousands of simulations have been run to assess long-term stability. We generate two additional ensembles, each with 2750 members, and make them publicly available at https://archive.org/details/@dorianabbot . We find that accurate Mercury instability statistics can be obtained by (1) including only the Sun and the eight planets, (2) using a simple Wisdom–Holman scheme without correctors, (3) using a basic representation of general relativity, and (4) using a time step of 3.16 days. By combining our solar system ensembles with previous ensembles, we form a 9601-member ensemble of ensembles. In this ensemble of ensembles, the logarithm of the frequency of a Mercury instability event increases linearly with time between 1.3 and 5 Gyr, suggesting that a single mechanism is responsible for Mercury instabilities in this time range and that this mechanism becomes more active as time progresses. Our work provides a robust estimate of Mercury instability statistics over the next five billion years, outlines methodologies that may be useful for exoplanet system investigations, and provides two large ensembles of publicly available solar system integrations that can serve as test beds for theoretical ideas as well as training sets for artificial intelligence schemes