There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological ...studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases.
During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62-0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC.
Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.
We have used femtosecond x-ray diffraction to study laser-shocked fiber-textured polycrystalline tantalum targets as the 37-253 GPa shock waves break out from the free surface. We extract the time ...and depth-dependent strain profiles within the Ta target as the rarefaction wave travels back into the bulk of the sample. In agreement with molecular dynamics simulations, the lattice rotation and the twins that are formed under shock compression are observed to be almost fully eliminated by the rarefaction process.
Key insights into the behavior of materials can be gained by observing their structure as they undergo lattice distortion. Laser pulses on the femtosecond time scale can be used to induce disorder in ...a "pump-probe" experiment with the ensuing transients being probed stroboscopically with femtosecond pulses of visible light, x-rays, or electrons. Here we report three-dimensional imaging of the generation and subsequent evolution of coherent acoustic phonons on the picosecond time scale within a single gold nanocrystal by means of an x-ray free-electron laser, providing insights into the physics of this phenomenon. Our results allow comparison and confirmation of predictive models based on continuum elasticity theory and molecular dynamics simulations.
Objective: The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods: The ...associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort n = 2948) were performed. Results: Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96-2.71, p-trend = 0.04 and 1.58, 95% CI 1.10-2.25, p-trend = 0.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10-2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression. Conclusions: Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour.
Alcohol is a probable risk factor with regard to colorectal neoplasm and is metabolized to the carcinogen acetaldehyde by the genetically polymorphic alcohol dehydrogenase 3 (ADH3) enzyme. We ...evaluated whether the association between alcohol and colorectal adenomas is modified by ADH3 polymorphism. We recruited 433 cases with adenomatous polyps and 436 polyp-free controls among Caucasians undergoing endoscopy between 1995 and 2000. Frequency and amount of habitual alcohol consumption were assessed by beverage type, using a validated self-administered food frequency questionnaire. All participants provided blood for genotyping of ADH3. Multivariate analyses adjusting for gender, age, and indication for endoscopy showed that alcohol increased the risk of colorectal adenomas among women odds ratio (OR), 1.8; 95% confidence interval (CI), 1.0-3.2, >/=10 versus <1 drink/week. Among men, the risk of adenomas was increased only for those consuming > 21 drinks/week (OR, 1.8; 95% CI, 0.9-3.8, compared with men drinking < 1 drink/week). Among subjects in the highest tertile of alcohol consumption, those with the ADH3*1/*1 genotype were at higher risk (OR, 1.8; 95% CI, 1.0-3.1) than those with other ADH3 genotypes (OR, 1.2; 95% CI, 0.7-1.9) when compared with those in the lowest tertile with ADH3*1/*2 or ADH3*2/*2 genotypes. In conclusion, our findings are consistent with results of other studies, suggesting that alcohol consumption elevates the risk of adenomatous colorectal polyps. ADH3 polymorphism may modify the association between alcohol consumption and colorectal adenomas.
The kinetics of the ribonuclease H (RNase H) surface hydrolysis of RNA−DNA heteroduplexes formed on DNA microarrays was studied using a combination of real-time surface plasmon resonance imaging ...(SPRI) and surface plasmon fluorescence spectroscopy (SPFS). Time-dependent SPRI and SPFS data at various enzyme concentrations were quantitatively analyzed using a simple model that couples diffusion, enzyme adsorption, and surface enzyme kinetics. This model is characterized by a set of three rate constants, enzyme adsorption (k a), enzyme desorption (k d), enzyme catalysis (k cat), and one dimensionless diffusion parameter (β ). Values of k a = 3.15 (±0.20) × 106 M-1·s-1, k d = 0.10 (±0.05) s-1, and k cat = 0.95 (±0.10) s-1 were determined from fitting all of the SPRI and SPFS data sets. One of the most interesting kinetic parameters is the surface RNase H hydrolysis reaction rate constant (k cat), which was found to be ∼10 times slower than that observed in solution, but ∼100 times faster than that recently observed for the exonuclease III surface hydrolysis of double-stranded DNA microarrays (k cat = 0.009 s-1). Moreover, the surface coverage of the intermediate enzyme−substrate complex (ES) was found to be extremely small during the course of the reaction because k cat is much larger than the product of k a and the bulk enzyme concentration.
Matter with a high energy density (>10(5) joules per cm(3)) is prevalent throughout the Universe, being present in all types of stars and towards the centre of the giant planets; it is also relevant ...for inertial confinement fusion. Its thermodynamic and transport properties are challenging to measure, requiring the creation of sufficiently long-lived samples at homogeneous temperatures and densities. With the advent of the Linac Coherent Light Source (LCLS) X-ray laser, high-intensity radiation (>10(17) watts per cm(2), previously the domain of optical lasers) can be produced at X-ray wavelengths. The interaction of single atoms with such intense X-rays has recently been investigated. An understanding of the contrasting case of intense X-ray interaction with dense systems is important from a fundamental viewpoint and for applications. Here we report the experimental creation of a solid-density plasma at temperatures in excess of 10(6) kelvin on inertial-confinement timescales using an X-ray free-electron laser. We discuss the pertinent physics of the intense X-ray-matter interactions, and illustrate the importance of electron-ion collisions. Detailed simulations of the interaction process conducted with a radiative-collisional code show good qualitative agreement with the experimental results. We obtain insights into the evolution of the charge state distribution of the system, the electron density and temperature, and the timescales of collisional processes. Our results should inform future high-intensity X-ray experiments involving dense samples, such as X-ray diffractive imaging of biological systems, material science investigations, and the study of matter in extreme conditions.
A search for Formula omitted violation in charmless four-body decays of Formula omitted and Formula omitted baryons with a proton and three charged mesons in the final state is performed. To cancel ...out production and detection charge-asymmetry effects, the search is carried out by measuring the difference between the Formula omitted asymmetries in a charmless decay and in a decay with an intermediate charmed baryon with the same particles in the final state. The data sample used was recorded in 2011 and 2012 with the LHCb detector and corresponds to an integrated luminosity of Formula omitted. A total of 18 Formula omitted asymmetries are considered, either accounting for the full phase space of the decays or exploring specific regions of the decay kinematics. No significant Formula omitted-violation effect is observed in any of the measurements.
Abstract Denosumab has been shown to reduce new vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis. In subjects who were treatment-naïve or previously treated with ...alendronate, denosumab was associated with greater gains in bone mineral density (BMD) and decreases in bone turnover markers when compared with alendronate-treated subjects. This trial was designed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy. In this randomized, open-label study, postmenopausal women aged ≥ 55 years received denosumab 60 mg subcutaneously every 6 months or risedronate 150 mg orally every month for 12 months. Endpoints included percentage change from baseline in total hip BMD (primary endpoint), femoral neck, and lumbar spine BMD at month 12, and percentage change from baseline in sCTX-1 at months 1 and 6. Safety was also assessed. A total of 870 subjects were randomized (435, risedronate; 435, denosumab) who had a mean (SD) age of 67.7 (6.9) years, mean (SD) BMD T-scores of − 1.6 (0.9), − 1.9 (0.7), and − 2.2 (1.2) at the total hip, femoral neck, and lumbar spine, respectively, and median sCTX-1 of 0.3 ng/mL at baseline. At month 12, denosumab significantly increased BMD compared with risedronate at the total hip (2.0% vs 0.5%), femoral neck (1.4% vs 0%), and lumbar spine (3.4% vs 1.1%; p < 0.0001 at all sites). Denosumab significantly decreased sCTX-1 compared with risedronate at month 1 (median change from baseline of − 78% vs − 17%; p < 0.0001) and month 6 (− 61% vs − 23%; p < 0.0001). Overall and serious adverse events were similar between groups. In postmenopausal women who were suboptimally adherent to alendronate therapy, transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover.
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