Bayesian P-Splines to investigate the impact of covariates on Multiple Sclerosis clinical course

This paper aims at proposing suitable statistical tools to address heterogeneity in repeated measures, within a Multiple Sclerosis (MS) longitudinal study. Indeed, due to unobservable sources of heterogeneity, modelling the effect of covariates on MS severity evolves as a very difficult feature. Bayesian P-Splines are suggested for modelling non linear smooth effects of covariates within generalized additive models. Thus, based on a pooled MS data set, we show how extending Bayesian P-splines to mixed effects models (Lang and Brezger, 2001), represents an attractive statistical approach to investigate the role of prognostic factors in affecting individual change in disability

Graphical chain models for the analysis of complex genetic diseases: an application to hypertension

A crucial task in modern genetic medicine is the understanding of complex genetic diseases. The main complicating features are that a combination of genetic and environmental risk factors is involved, and the phenotype of interest may be complex. Traditional statistical techniques based on lod-scores fail when the disease is no longer monogenic and the underlying disease transmission model is not defined. Different kinds of association tests have been proved to be an appropriate and powerful statistical tool to detect a candidate gene for a complex disorder. However, statistical techniques able to investigate direct and indirect influences among phenotypes, genotypes and environmental risk factors, are required to analyse the association structure of complex diseases. In this paper we propose graphical models as a natural tool to analyse the multifactorial structure of complex genetic diseases. An application of this model to primary hypertension data set is illustrated

Simpson’s Paradox for the Cox Model

In the context of survival analysis, we define a covariate X as protective (detrimental) for the failure time T if the conditional distribution of [T | X = x] is stochastically increasing (decreasing) as a function of x. In the presence of another covariate Y, there exist situations where [T | X = x, Y = y] is stochastically decreasing in x for each fixed y, but [T | X = x] is stochastically increasing. When studying causal effects and influence of covariates on a failure time, this state of affairs appears paradoxical and raises the question of whether X should be considered protective or detrimental. In a biomedical framework, for instance when X is a treatment dose, such a question has obvious practical importance. Situations of this kind may be seen as a version of Simpson’s paradox. In this paper we study this phenomenon in terms of the well-known Cox model. More specifically, we analyze conditions on the parameters of the model and the type of dependence between X and Y required for the paradox to hold. Among other things, we show that the paradox may hold for residual failure times conditioned on T > t even when the covariates X and Y are independent. This is due to the fact that independent covariates may become dependent when conditioned on the failure time being larger than t.In the context of survival analysis, we define a covariate X as protective (detrimental) for the failure time T if the conditional distribution of [T | X = x] is stochastically increasing (decreasing) as a function of x. In the presence of another covariate Y, there exist situations where [T | X = x, Y = y] is stochastically decreasing in x for each fixed y, but [T | X = x] is stochastically increasing. When studying causal effects and influence of covariates on a failure time, this state of affairs appears paradoxical and raises the question of whether X should be considered protective or detrimental. In a biomedical framework, for instance when X is a treatment dose, such a question has obvious practical importance. Situations of this kind may be seen as a version of Simpson’s paradox. In this paper we study this phenomenon in terms of the well-known Cox model. More specifically, we analyze conditions on the parameters of the model and the type of dependence between X and Y required for the paradox to hold. Among other things, we show that the paradox may hold for residual failure times conditioned on T > t even when the covariates X and Y are independent. This is due to the fact that independent covariates may become dependent when conditioned on the failure time being larger than t.Non-Refereed Working Papers / of national relevance onl

Mythological References in Ausonius’ Epistolary

Ausonius’ letters constitute a specimen of the way he employs references to Greek mythology. The process by which Ausonius reworks mythological material fol- lows patterns that were already well established in the Latin literary tradition of re-working Greek sources. The recycling of such material is not only proof of his technical prowess, but also demonstrates his ability to perform precise thematic choices. Frequently, the use of mythology is part of the metaliterary and metapoetic discourses tackled by Ausonius while addressing his friends as recipients of letters. The analysis of individual letters reveals how the poet used mythological references for two main purposes. The first is to elevate the tone and content of the discourse, employing a series of artificial comparisons with mythical characters and events. Brief mythological references used to formulate playful numerical periphrases are also worth noting here. The second aim is encomiastic, namely the celebration of his friends, the recipients of his letters, who are transferred from everyday reality to the higher level of the mythical dimension and the superhuman sphere

The Pr.O.F. project: orienting late High School students to University methodology in Chemistry and other Sciences

The P.r.O.F. project has been presented at the ECTN meeting and positively evaluated. The project aims to help high school students in the transition to University. It covers the areas of Chemistry, Physics, Biology and Mathematics. In the Chemistry section, methodological issues were emphasized. The specific subject, selected jointly by University and School teachers, was Solutions and Solubility. Short and long-time tests were performed to check the effectiveness of the intervention

Investigating Determinants of Multiple Sclerosis in Longitunal Studies: A Bayesian Approach

Modelling data from Multiple Sclerosis longitudinal studies is a challenging topic since the phenotype of interest is typically ordinal; time intervals between two consecutive measurements are nonconstant and they can vary among individuals. Due to these unobservable sources of heterogeneity statistical models for analysis of Multiple Sclerosis severity evolve as a difficult feature. A few proposals have been provided in the biostatistical literature (Heijtan (1991); Albert, (1994)) to address the issue of investigating Multiple Sclerosis course. In this paper Bayesian P-Splines (Brezger and Lang, (2006); Fahrmeir and Lang (2001)) are indicated as an appropriate tool since they account for nonlinear smooth effects of covariates on the change in Multiple Sclerosis disability. By means of Bayesian P-Spline model we investigate both the randomness affecting Multiple Sclerosis data as well as the ordinal nature of the response variable

Sustainable Synthesis of Epoxidized Cynara C. Seed Oil

The use of non-edible vegetable oils to produce oleochemicals has been attracting more attention in recent years. Cardoon seed oil, derived from the Cynara C. plant, growing in marginal and contaminated lands, represents a non-edible alternative to soybean oil to obtain plasticizers through epoxidation reaction. The use of hydrogen peroxide as oxidant and in the presence of a heterogeneous catalyst allows overcoming the limits of epoxidation with peracids. γ-alumina has been shown to have an active catalyst epoxidation reaction with hydrogen peroxide, mainly using acetonitrile as solvent. However, the use of acetonitrile as solvent is widely debated due to its hazardous character and health issues. For these reasons, the influence of solvent on the reaction was studied in this work to find a more environmentally friendly and stable solvent. The study showed that the epoxidation reaction takes place also in the absence of solvent although with lower selectivity. The type of solvent influences both the epoxidation and decomposition reactions of hydrogen peroxide. γ-valerolactone was found to be the most promising solvent for cardoon oil epoxidation reaction. This finding represents a noteworthy novelty in the field of epoxidation of vegetable oils with hydrogen peroxide, opening the way to greener and cleaner process. Finally, an optimization study showed that the most effective molar ratio between hydrogen peroxide and double bonds for better selectivity was 4.5 and the need to use the highest possible initial concentration of hydrogen peroxide (approximately 60 wt. %)

THE SIXTH WAVE OF INNOVATION: ARE WE READY?

Organizations faced different development paths over the centuries, caused by changes in the competitive environment and the ability to respond to these changes. Such changes and choices can be analyzed from the perspective of innovation waves, responsible for changing the current competition structure and present a new competitive format for organizations. By observing the existing five waves of innovation, we can see a significant jump in development for companies that well understood the context of the new wave and competitive problems for other companies, even leaders in their market were “swept” off the competitive landscape. There are indications that a sixth wave of innovation is coming and who is guided by the sustainability, since the depletion of resources can cause many companies and countries conquer higher competitive performance to seek innovative solutions to the problem and those that fail to do so may have a loss of competitiveness. Given the aforementioned context, this theoretical essay aims to discuss sustainability as the sixth wave of innovation and how it can affect organizations. It is expected that the article raises a reflection about this phenomenon and serve as a starting point for future discussions

Viroid Intercellular Trafficking: RNA Motifs, Cellular Factors and Broad Impacts

Viroids are noncoding RNAs that infect plants. In order to establish systemic infection, these RNAs must traffic from an initially infected host cell into neighboring cells and ultimately throughout a whole plant. Recent studies have identified structural motifs in a viroid that are required for trafficking, enabling further studies on the mechanisms of their function. Some cellular proteins interact with viroids in vivo and may play a role in viroid trafficking, which can now be directly tested by using a virus-induced gene silencing system that functions efficiently in plant species from which these factors were identified. This review discusses these recent advances, unanswered questions and the use of viroid infection as an highly productive model to elucidate mechanisms of RNA trafficking that is of broad biological significance