Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover

Background: The Ovarian Protection Trial In Premenopausal Breast Cancer Patients “OPTION” trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6–8 cycles of (neo)adjuvant chemotherapy (CT) þ/ goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CTþ/-G on markers of bone turnover. Methods: Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (r40 vs 440 years) and with exploratory analysis according to POI rates at 12 months. Results: In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CTþG (40.81 vs 57.82 p¼0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CTþG, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CTþG 5.845 vs CT 8.5 p¼0.0006). These changes were predominantly seen in women 440 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses. Conclusion: Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI

Inhomogeneous Neutrino Degeneracy and Big Bang Nucleosynthesis

We examine Big Bang nucleosynthesis (BBN) in the case of inhomogenous neutrino degeneracy, in the limit where the fluctuations are sufficiently small on large length scales that the present-day element abundances are homogeneous. We consider two representive cases: degeneracy of the electron neutrino alone, and equal chemical potentials for all three neutrinos. We use a linear programming method to constrain an arbitrary distribution of the chemical potentials. For the current set of (highly-restrictive) limits on the primordial element abundances, homogeneous neutrino degeneracy barely changes the allowed range of the baryon-to-photon ratio. Inhomogeneous degeneracy allows for little change in the lower bound on the baryon-to-photon ratio, but the upper bound in this case can be as large as 1.1 \times 10^{-8} (only electron neutrino degeneracy) or 1.0 \times 10^{-9} (equal degeneracies for all three neutrinos). For the case of inhomogeneous neutrino degeneracy, we show that there is no BBN upper bound on the neutrino energy density, which is bounded in this case only by limits from structure formation and the cosmic microwave background.Comment: 6 pages, no figure

An analysis of navigation algorithms for smartphones using J2ME

Embedded systems are considered one of the most potentialareas for future innovations. Two embedded fields that will mostcertainly take a primary role in future innovations are mobile roboticsand mobile computing. Mobile robots and smartphones are growing innumber and functionalities, becoming a presence in our daily life. In thispaper, we study the current feasibility of a smartphone to execute navigationalgorithms. As a test case, we use a smartphone to control anautonomous mobile robot. We tested three navigation problems: Mapping,Localization and Path Planning. For each of these problems, analgorithm has been chosen, developed in J2ME, and tested on the field.Results show the current mobile Java capacity for executing computationallydemanding algorithms and reveal the real possibility of usingsmartphones for autonomous navigation

Blue Straggler Stars: Early Observations that Failed to Solve the Problem

In this chapter, I describe early ideas on blue stragglers, and various observations (some published, some not) that promised but failed to resolve the question of their origin. I review the data and ideas that were circulating from Allan Sandage's original discovery in 1953 of "anomalous blue stars" in the globular cluster M3, up until about 1992, when what seems to have been the only previous meeting devoted to Blue Straggler Stars (BSSs) was held at the Space Telescope Science Institute.Comment: Chapter 2, in Ecology of Blue Straggler Stars, H.M.J. Boffin, G. Carraro & G. Beccari (Eds), Astrophysics and Space Science Library, Springe

Tenure, gender and household structure

Starting with a review of recent literature on gender and housing, this paper goes on to develop a new theory of household structure, in which concepts of gender and generation play a key role. The utility of this theory is then demonstrated in the analysis of data from a survey of households in the City of Salford

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in <5 % of cases and showed no association wit

Carbamide peroxide gel stability under different temperature conditions: is manipulated formulation an option?

Nowadays the use of gel containing carbamide peroxide (CP) prepared in Pharmacy is a normal practice in the population. However, the quality of this product is questionable concerning its stability. The aim of this study is was to synthesize and to analyze this drug alone or associated to Carbopol gel through analytical methodology compatible with the routine of the Pharmacies. The reaction between urea and hydrogen peroxide was carried out at different resting times: 24 hours (CP 24 powder) and 48 hours (CP48 powder) after the mixture. Both products were associated with Carbopol 940® gel 1.5% (G) generating G24 and G48 samples. The stability of powders (CP24 e CP48) and the formulations (G24 and G48) were evaluated as a function of time (15, 40 and 45 days) and thermal variation (refrigeration: 8 °C±1; thermal shock 32 °C±1 /8 °C±1; stove: 32 °C±1), using a standard titration method. As a result, only under refrigeration the CP24 and CP48 contents remained stable during the period of 45 days. An interesting finding was that G24 and G48 presented greater stability for at least 45-days under refrigeration and thermal shock conditions, and up to 30 days under stove conditions. The results for the G24 and G48 were slightly higher than those obtained for the control. Therefore, we were able to conclude that association with Carbopol 940® Gel 1.5 % provided greater CP stability and that manipulated formulations containing CP may be viable for use in a period of 45 days under refrigeration conditions. The titration proved to be an effective technique for the analysis of CP with or without Carbopol 940® gel 1.5%.Atualmente, a utilização de gel contendo peróxido de carbamida manipulado em Farmácia é uma prática comum na população. No entanto, a qualidade deste produto é questionada, sobretudo no que se refere à estabilidade deste fármaco. O objetivo deste trabalho consiste na avaliação da viabilidade de sintetizar e analisar quantitativamente este fármaco associado ou não a um gel de Carbopol através de metodologia analítica compatível com a rotina das Farmácias. A reação entre a uréia e o peróxido de hidrogênio foi realizada em tempos diferentes de repouso após a mistura, 24 h para sintetizar o pó PC 24 e 48 h para o pó CP 48. Estes pós foram associados a um gel (G) de Carbopol 940® 1,5 %, originando as amostras G24 e G48. A estabilidade dos pós (PC 24 e PC 48) e das formulações (G 24 e G 48) foi avaliada em função do tempo (15, 40 e 45 dias) e da variação térmica (refrigeração: 8 °C±1; choque térmico: 32 °C±1/8 °C±1 e estufa: 32 °C±1), através da técnica de titulometria. Os resultados indicam que unicamente sob refrigeração o CP24 e o CP 48 mantiveram-se estáveis no período de 45 dias. O G24 e o G48 apresentaram estáveis por pelo menos 45 dias nas condições de refrigeração e choque térmico e por 30 dias na condição estufa. Os resultados obtidos para o G24 e G48 foram ligeiramente superiores aos obtidos para o controle. Além disso, é possível concluir que a associação do PC com o gel de Carbopol 940® 1,5 % promoveu um aumento na estabilidade do PC e que as preparações manipuladas contendo PC são viáveis para uso durante um período de 45 sob refrigeração. A titulometria mostrou-se uma técnica eficaz para a análise do PC associado ou não ao gel de Carbopol 940® 1,5%

WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene

Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother’s, and, to a lesser extent, with father’s TL having the strongest influence on the offspring. In this cohort, mother’s, but not father’s age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait