Statistical Programs for High Speed Computers

Two objectives of much experimentation in science and engineering are (i) to establish the form of an adequate mathematical model for the system being investigated and (ii) to obtain precise estimates of the model parameters. In the past, statistical design procedures have been proposed for tackling either one of these problems separately. Investigators, however, frequently want to perform experiments which will shed light on both questions simultaneously. In this paper, therefore, we present a design criterion which takes both objectives into account. The basic design strategy is to emphasize model discrimination when there is considerable doubt as to which model is best and gradually shifting the emphasis to parameter estimation as experimentation progresses and discrimination is accomplished. It is assumed that experiments can be performed sequentially. The use of the design criterion is illustrated with an example.     

Zwitterionic‐Coated “Stealth” Nanoparticles for Biomedical Applications: Recent Advances in Countering Biomolecular Corona Formation and Uptake by the Mononuclear Phagocyte System

Nanoparticles represent highly promising platforms for the development of imaging and therapeutic agents, including those that can either be detected via more than one imaging technique (multi‐modal imaging agents) or used for both diagnosis and therapy (theranostics). A major obstacle to their medical application and translation to the clinic, however, is the fact that many accumulate in the liver and spleen as a result of opsonization and scavenging by the mononuclear phagocyte system. This focused review summarizes recent efforts to develop zwitterionic‐coatings to counter this issue and render nanoparticles more biocompatible. Such coatings have been found to greatly reduce the rate and/or extent of non‐specific adsorption of proteins and lipids to the nanoparticle surface, thereby inhibiting production of the “biomolecular corona” that is proposed to be a universal feature of nanoparticles within a biological environment. Additionally, in vivo studies have demonstrated that larger‐sized nanoparticles with a zwitterionic coating have extended circulatory lifetimes, while those with hydrodynamic diameters of ≤5 nm exhibit small‐molecule‐like pharmacokinetics, remaining sufficiently small to pass through the fenestrae and slit pores during glomerular filtration within the kidneys, and enabling efficient excretion via the urine. The larger particles represent ideal candidates for use as blood pool imaging agents, whilst the small ones provide a highly promising platform for the future development of theranostics with reduced side effect profiles and superior dose delivery and image contrast capabilities.     

Statistical Programs for High Speed Computers

It is pointed out that the inferential theory of the segmented regression model depends strongly on whether or not continuity at the change-point is assumed. In particular, if it is not, the likelihood ratio test for the presence of two segments tends to infinity.     

Statistical Programs for High Speed Computers

Eight-run two level factorial and fractional factorial designs are examined from two points of view: (1) the number of levels which must be changed in performing the design, (2) the effect of a first order time trend on the main effects. It is found that only a few run orders are desirable from these viewpoints and thus randomization of the runs is likely, in general, to lead to an unfavorable sequence.