3,493 research outputs found

    Medical ovariectomy in menopausal breast cancer patients with high testosterone levels : a further step toward tailored therapy

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    Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrine resistance suggesting the involvement of androgens as activators of the androgen receptor pathway and as stimulators of epidermal growth factor synthesis and function. Data from a series of prospective studies on operable breast cancer patients, showing high serum testosterone levels are associated to increased risk of recurrence, provide further support to a role for androgens in breast cancer progression. According to the above reported evidence, we proposed to counteract excessive androgen production in the adjuvant setting of estrogen receptor-positive patients and suggested selecting postmenopausal patients with elevated levels of serum testosterone, marker of ovarian hyperandrogenemia, for adjuvant treatment with a gonadotropins-releasing hormone analogue (medical oophorectomy) in addition to standard therapy with anti-estrogens. The proposed approach provides an attempt of personalized medicine that needs to be further investigated in clinical trials

    Usual energy and macronutrient intakes in 2-9-year-old European children

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    OBJECTIVE: Valid estimates of population intakes are essential for monitoring trends as well as for nutritional interventions, but such data are rare in young children. In particular, the problem of misreporting in dietary data is usually not accounted for. Therefore, this study aims to provide accurate estimates of intake distributions in European children. DESIGN: Cross-sectional setting-based multi-centre study. SUBJECTS: A total of 9560 children aged 2-9 years from eight European countries with at least one 24-h dietary recall (24-HDR). METHODS: The 24-HDRs were classified in three reporting groups based on age- and sex-specific Goldberg cutoffs (underreports, plausible reports, overreports). Only plausible reports were considered in the final analysis (N=8611 children). The National Cancer Institute (NCI)-Method was applied to estimate population distributions of usual intakes correcting for the variance inflation in short-term dietary data. RESULTS: The prevalence of underreporting (9.5%) was higher compared with overreporting (3.4%). Exclusion of misreports resulted in a shift of the energy and absolute macronutrient intake distributions to the right, and further led to the exclusion of extreme values, that is, mean values and lower percentiles increased, whereas upper percentiles decreased. The distributions of relative macronutrient intakes (% energy intake from fat/carbohydrates/proteins) remained almost unchanged when excluding misreports. Application of the NCI-Method resulted in markedly narrower intake distributions compared with estimates based on single 24-HDRs. Mean percentages of usual energy intake from fat, carbohydrates and proteins were 32.2, 52.1 and 15.7%, respectively, suggesting the majority of European children are complying with common macronutrient intake recommendations. In contrast, total water intake (mean: 1216.7 ml per day) lay below the recommended value for >90% of the children. CONCLUSION: This study provides recent estimates of intake distributions of European children correcting for misreporting as well as for the daily variation in dietary data. These data may help to assess the adequacy of young children's diets in Europe

    Gastrointestinal motility during sleep assessed by tracking of telemetric capsules combined with polysomnography - a pilot study.

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    Studies of gastrointestinal function during sleep are hampered by lack of applicable techniques. Recent development of a novel ambulatory telemetric capsule system, which can be used in conjunction with polysomnography, offers a solution to this problem. The 3D-Transit system consists of ingestible electromagnetic capsules traceable through a portable extracorporeal receiver while traversing the gut. During sleep monitored by polysomnography, gastrointestinal motility was concurrently investigated using 3D-Transit in nine healthy subjects. Overall, the amplitude of gastric contractions decreased with depth of sleep (light sleep, N2 versus deep sleep, N3; P<0.05). Progression through the small intestine did not change with depth of sleep (Kruskal-Wallis probability =0.1), and there was no association between nocturnal awakenings or arousals and the occurrence of colonic or small intestinal propagating movements. Basal colonic activity was suppressed during both deep sleep (P<0.05) and light sleep (P<0.05) when compared with nocturnal wake periods. In conclusion, the novel ambulatory 3D-Transit system combined with polysomnography allows minimally invasive and completely ambulatory investigation of associations between sleep patterns and gastrointestinal motility

    Inference of structure ensembles of flexible biomolecules from sparse, averaged data

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    We present the theoretical foundations of a general principle to infer structure ensembles of flexible biomolecules from spatially and temporally averaged data obtained in biophysical experiments. The central idea is to compute the Kullback-Leibler optimal modification of a given prior distribution [Image: see text] with respect to the experimental data and its uncertainty. This principle generalizes the successful inferential structure determination method and recently proposed maximum entropy methods. Tractability of the protocol is demonstrated through the analysis of simulated nuclear magnetic resonance spectroscopy data of a small peptide

    String Junctions and Bound States of Intersecting Branes

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    We study four-dimensional black hole configurations which result from wrapping M5-branes on a Calabi-Yau manifold, as well as U-dual realizations. Our aim is to understand the microscopic degrees of freedom responsible for the existence of bound states of multiple branes. The details depend on the chosen U-frame; in some cases, they are massless string junctions. We also identify a perturbative description in which these states correspond to twisted strings of intersecting D3-branes at an orbifold singularity. In each case, these are the preponderant states of the spacetime infrared conformal field theory and account for the entropy of the blackhole.Comment: 14 pages; 2 figures; uses latex with epsf and hyperref package

    Mars and frame-dragging: study for a dedicated mission

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    In this paper we preliminarily explore the possibility of designing a dedicated satellite-based mission to measure the general relativistic gravitomagnetic Lense-Thirring effect in the gravitational field of Mars. The focus is on the systematic error induced by the multipolar expansion of the areopotential and on possible strategies to reduce it. It turns out that the major sources of bias are the Mars'equatorial radius R and the even zonal harmonics J_L, L = 2,4,6... of the areopotential. An optimal solution, in principle, consists of using two probes at high-altitudes (a\approx 9500-9600 km) and different inclinations, and suitably combining their nodes in order to entirely cancel out the bias due to \delta R. The remaining uncancelled mismodelled terms due to \delta J_L, L = 2,4,6,... would induce a bias \lesssim 1%, according to the present-day MGS95J gravity model, over a wide range of admissible values of the inclinations. The Lense-Thirring out-of-plane shifts of the two probes would amount to about 10 cm yr^-1.Comment: LaTex2e, 16 pages, 5 figures, no tables. To appear in General Relativity and Gravitatio

    Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort : a nested case-control study

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    Background and aims: The increase in breast cancer incidence over recent decades has been accompanied by an increase in the frequency of metabolic syndrome. Several studies suggest that breast cancer risk is associated with the components of metabolic syndrome (high serum glucose and triglycerides, low HDL-cholesterol, high blood pressure, and abdominal obesity), but no prospective study has investigated risk in relation to the presence of explicitly defined metabolic syndrome. We investigated associations between metabolic syndrome, its components, and breast cancer risk in a nested case-control study on postmenopausal women of the ORDET cohort. Methods and results: After a median follow-up of 13.5 years, 163 women developed breast cancer; metabolic syndrome was present in 29.8%. Four matched controls per case were selected by incidence density sampling, and rate ratios were estimated by conditional logistic regression. Metabolic syndrome (i.e. presence of three or more metabolic syndrome components) was significantly associated with breast cancer risk (rate ratio 1.58 [95% confidence interval 1.07-2.33]), with a significant risk increase for increasing number of components (P for trend 0.004). Among individual metabolic syndrome components, only low serum HDL-cholesterol and high triglycerides were significantly associated with increased risk. Conclusions: This prospective study indicates that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women. Although serum HDL-cholesterol and triglycerides had the strongest association with breast cancer, all components may contribute to increased risk by multiple interacting mechanisms. Prevention or reversal of metabolic syndrome by life-style changes may be effective in preventing breast cancer in postmenopausal women
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