Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n=144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(β)=1.20, p=0.060] and decreased levels of reduced glutathione (GSH) [exp(β)=0.55, p=0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(β)=0.83, exp(β)=0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(β)=1.73, p-value=0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.This research was supported in part by research grants from the European Union Commission (H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), from the Institute of Health Carlos III, supported by European Regional Development Fund/FEDER (FIS-PI13/02406, FISPI14/ 00067, FIS-PI16/01820, FIS-PI16/01812, FIS-PI16/01858 and FIS-PI17/01743), and from the Consejería de Salud, Junta de Andalucía (PS-0506-2016). Funding for the equipment used was provided by Velux Fonden, Augustinus Fonden and Svend Andersen Fonden. The authors thank Kirsten og Freddy Johansens Fond and the International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC, Rigshospitalet, Copenhagen University) for economic support. Dr. Juan Pedro Arrebola is under contract within Ramón y Cajal Program (Ministerio de Economía, Industria y Competitividad de España, RYC-2016-20155)

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Transitions of cardio-metabolic risk factors in the Americas between 1980 and 2014

Describing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014

Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

High-dimensional maximum marginal likelihood item factor analysis by adaptive quadrature

Although the Bock–Aitkin likelihood-based estimation method for factor analysis of dichotomous item response data has important advantages over classical analysis of item tetrachoric correlations, a serious limitation of the method is its reliance on fixed-point Gauss-Hermite (G-H) quadrature in the solution of the likelihood equations and likelihood-ratio tests. When the number of latent dimensions is large, computational considerations require that the number of quadrature points per dimension be few. But with large numbers of items, the dispersion of the likelihood, given the response pattern, becomes so small that the likelihood cannot be accurately evaluated with the sparse fixed points in the latent space. In this paper, we demonstrate that substantial improvement in accuracy can be obtained by adapting the quadrature points to the location and dispersion of the likelihood surfaces corresponding to each distinct pattern in the data. In particular, we show that adaptive G-H quadrature, combined with mean and covariance adjustments at each iteration of an EM algorithm, produces an accurate fast-converging solution with as few as two points per dimension. Evaluations of this method with simulated data are shown to yield accurate recovery of the generating factor loadings for models of upto eight dimensions. Unlike an earlier application of adaptive Gibbs sampling to this problem by Meng and Schilling, the simulations also confirm the validity of the present method in calculating likelihood-ratio chi-square statistics for determining the number of factors required in the model. Finally, we apply the method to a sample of real data from a test of teacher qualifications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43596/1/11336_2003_Article_1141.pd

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe