Complex diseases demand novel treatment strategies: understanding drug combination

For many multigene or multifactorial diseases,the one-drug therapy for inhibiting a defined molecular target is often less effective than combined treatments.Typically,drug combination therapies are multitargeted,so the mechanisms or even interactions are often complementary.These drug-drug interactions may promote alteration of pharmacokinetic or pharmacodynamic activities of one drug by another drug.Other interactions may change the expected effect of medications through polymorphisms that alter the expression or activity of the drug-mediated enzyme and the cell signaling cascade,such as drug-gene interactions and drug-drug-gene interactions.The number of possible existing interactions requires appropriate methods of study.In this review,we summarized combination therapies for cancer,as well as for viral,cardiovascular,and neurological diseases.Here,we also highlight known methodologies,such as in vitro methods based on Loewe’s and Bliss’s pioneer models and in silico methods based on online available data.With more elaborate methods and reliable results,multitarget therapies through drug combinations may increasingly benefit patients suffering from complex diseases.

Transport Costs in the Automotive Supply Chain

The study, carried out within the LogNet research project financed by Calabria region, deals with the analysis of the automotive supply chain. In particular, after a first examination of the characteristics of the whole automotive supply chain, attention was focussed on its final part, that is, on transport and end-market distribution. The paper proposes specific models, which are differentiated by the transport mode （road, rail, sea） they are involved, to estimate the temporal and monetary costs related to the activity of goods distribution to the compounds/end-clients. The proposed mode/ling formulations concern two different areas of investigation： the network segment and interchange nodes. Each cost item is also calculated through aggregate formulations （where the cost is function of a single significant variable in relation to a unit cost parameter） and disaggregate formulations （where each cost item is separately considered）. The models have been applied to a study carried out for the modal transfer of vehicles in the port of Gioia Tauro, south of Italy. The analysis has allowed, on the one hand, to calibrate certain models and, on the other, to simulate certain scenario hypotheses to verify the technical feasibility of a different structure for the automotive supply chain in Italy.

Hypothesis testing and statistical analysis of microbiome

After the initiation of Human Microbiome Project in 2008,various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies.In this review and perspective,we discuss the research and statistical hypotheses in gut microbiome studies,focusing on mechanistic concepts that underlie the complex relationships among host,microbiome,and environment.We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models.Given the current challenges and limitations in biostatistic approaches and tools,we discuss the future direction in developing statistical methods and models for the microbiome studies.