Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

Effect of ethanol intoxication on the levels of dolichols in rat liver Golgi apparatus

none4D. COTTALASSO;M. A. PRONZATO;U. M. MARINARI;G. NANNICottalasso, Damiano; Pronzato, MARIA ADELAIDE; Marinari, Umberto; Nanni, Giorgi

Plasma advanced glycosylation end products in maintenance haemodialysis patients

Pentosidine is a useful marker of advanced glycation end-products (AGE) which form cross-links between proteins and have been found elevated in plasma and tissues of uraemic and haemodialysed subjects. The origin and fate of these molecules are not clearly understood, but they might play a role in the cardiovascular complications of end stage renal failure. The aim of this study was to evaluate the effect of different types of substitutive therapy on the removal of pentosidine. Methods. Pentosidine was measured by a two-step HPLC methodology. Its concentration was evaluated in plasma before and after dialysis session, in 24-h urine, and in dialysate of subjects treated with three types of chronic substitutive therapy: bicarbonate haemodialysis, acetate-free biofiltration, and haemofiltration. Pentosidine levels were compared among the three therapy modalities and correlated with clinical and biochemical parameters. Results. Plasma pentosidine level was extremely high (23.7 \ub1 2.0 pmol/mg protein) in the patients treated with the different dialysis modalities. The dialysis session had no significant effect on its plasma concentration, but haemofiltration seemed to be the most efficient method (300-2000 nmol of pentosidine removed per session versus 250-700 nmol per session with the two other approaches). An interesting correlation was found between pentosidine and blood urea nitrogen (r = 0.58, P < 0.01) and pentosidine with uric acid (r = 0.48, P < 0.05). Conclusions. These results suggest that none of the methodology showed a good removal of pentosidine, but among them haemofiltration has the best efficiency. The statistical relationships between pentosidine and urea and uric acid respectively might provide insight into the origin of pentosidine. The accumulation of reactive AGE in uraemic patients may be implicated in the organ and tissue damage observed in uraemia

Development of in vitro testing strategies for toxicity evaluation of mixtures derived from discarded laboratory chemicals

Our complementary methods can represent an high content sensitive tool to assess the safety of chemical mixtures, that can act on skin, as well on eye and neural functions. Aim of this study was to assess the toxic potential of two mixtures (Cat. EWC160506, one inorganic and one organic), by different in vitro approaches