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Locally advanced rectal cancer has traditionally been treated with chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, a new strategy, total neoadjuvant therapy, involves the administration of CRT and neoadjuvant chemotherapy with the aim of eradicating micrometastases earlier and achieving greater control of the disease. The use of total neoadjuvant therapy has shown higher rates of pathological complete response and resectability compared with CRT, including improved survival. Nevertheless, distant relapse is the main cause of morbidity and mortality in locally advanced rectal cancer. To address this, new biomarkers are being developed to predict disease response.

In medical and epidemiological studies, the importance of detecting seasonal patterns in the occurrence of diseases makes testing for seasonality highly relevant. There are different parametric and non-parametric tests for seasonality. One of the most widely used parametric tests in the medical literature is the Edwards test. The Edwards test considers a parametric alternative that is a sinusoidal curve with one peak and one trough. The Cave and Freedman test is an extension of the Edwards test that is also frequently applied and considers a sinusoidal curve with two peaks and two troughs as the alternative hypothesis. The Kuiper, Hewitt and David and Newell are common non-parametric tests. Fernández-Durán (2004) developed a family of univariate circular distributions based on non-negative trigonometric (Fourier) sums (series) (NNTS) that can account for an arbitrary number of peaks and troughs. In this article, this family of distributions is used to construct a likelihood ratio test for seasonality considering parametric alternative hypotheses that are NNTS distributions., (© The Author(s) 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Fernández-Durán, J. J. (2004): "Circular distributions based on nonnegative trigonometric sums," Biometrics, 60, 499-503, developed a family of univariate circular distributions based on nonnegative trigonometric sums. In this work, we extend this family of distributions to the multivariate case by using multiple nonnegative trigonometric sums to model the joint distribution of a vector of angular random variables. Practical examples of vectors of angular random variables include the wind direction at different monitoring stations, the directions taken by an animal on different occasions, the times at which a person performs different daily activities, and the dihedral angles of a protein molecule. We apply the proposed new family of multivariate distributions to three real data-sets: two for the study of protein structure and one for genomics. The first is related to the study of a bivariate vector of dihedral angles in proteins. In the second real data-set, we compare the fit of the proposed multivariate model with the bivariate generalized von Mises model of [Shieh, G. S., S. Zheng, R. A. Johnson, Y.-F. Chang, K. Shimizu, C.-C. Wang, and S.-L. Tang (2011): "Modeling and comparing the organization of circular genomes," Bioinformatics, 27(7), 912-918.] in a problem related to orthologous genes in pairs of circular genomes. The third real data-set consists of observed values of three dihedral angles in γ-turns in a protein and serves as an example of trivariate angular data. In addition, a simulation algorithm is presented to generate realizations from the proposed multivariate angular distribution.

The effect of acidity, squalene, hydroxytyrosol, aldehydic form of oleuropein aglycon, hydroxytyrosyl acetate, tyrosol, homovanillic acid, luteolin, apigenin, alpha-tocopherol, and the mixtures hydroxytyrosol/hydroxytyrosyl acetate, hydroxytyrosol/tyrosol, and hydroxytyrosol/alpha-tocopherol on the oxidative stability of an olive oil matrix was evaluated. A purified olive oil was spiked with several concentrations of these compounds and, then, subjected to an accelerated oxidation in a Rancimat apparatus at 100 degrees C. Acidity, squalene, homovanillic acid, and apigenin showed negligible effect. At the same millimolar concentrations, the different o-diphenolic compounds yielded similar and significant increases of the induction time, alpha-tocopherol a lesser increase, and tyrosol a scarce one. At low concentrations of o-diphenols and alpha-tocopherol, a linear relationship between induction time and concentration was found, but at high concentrations the induction time tended toward constant values. To explain this behavior, a kinetic model was applied. The effect of the mixtures hydroxytyrosol/hydroxytyrosyl acetate was similar to that of a single o-diphenol at millimolar concentration equal to the sum of millimolar concentrations of both compounds. Concentrations of tyrosol >0.3 mmol/kg increase the induction time by 3 h. The mixtures hydroxytyrosol/alpha-tocopherol showed opposite effects depending on the relative concentrations of both antioxidants; so, at hydroxytyrosol concentrations <0.2 mmol/kg, the addition of alpha-tocopherol increased the induction time, whereas at higher hydroxytyrosol concentrations, the alpha-tocopherol diminished the stability.

Steroid concentrations in the fetal fluids of 153 single and 69 twin bovine pregnancies, ranging in age from 35 to 125 d of gestation, were studied to compare gonadal steroid secretions in vitro with the concentrations found in amniotic and allantoic fluids during the early stages of sex differentiation. Among the steroids measured in fetal fluids, only the testosterone level showed a correlation with the amount secreted by the gonads. Significantly higher concentrations of testosterone were associated with male fetuses than with female fetuses. The concentrations of androstenedione, estradiol and estrone in both fetal fluid compartments were generally correlated with age, reflecting the extra-gonadal source of steroids in these fluids. Androstenedione levels in fetal fluids were significantly higher in twins than in singletons, suggesting that this parameter may be useful for the diagnosis of fetal sex and/or type of pregnancy.