Abstract: The research described here builds on our previous work by generalizing the univariate models described there to models for multivariate relations. This family, labelled p*, generalizes the Markov random graphs of Frank and Strauss, which were further developed by them and others, building on Besag's ideas on estimation. These models were first used to model random variables embedded in lattices by Ising, and have been quite common in the study of spatial data. Here, they are applied to the statistical analysis of multigraphs, in general, and the analysis of multivariate social networks, in particular. In this paper, we show how to formulate models for multivariate social networks by considering a range of theoretical claims about social structure. We illustrate the models by developing structural models for several multivariate networks.

Abstract: Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.

Abstract: International statistics indicate that there is a close correlation between the consumption of saturated fats (dairy fats and meat fats) and the mortality from coronary heart disease (CHD), and this conception has been confirmed by many epidemiological studies. Such studies alone, however, cannot prove the existence of a cause-and-effect relationship between these two variables; dietary intervention trials are needed. The Finnish Mental Hospital Study was such a trial, conducted in two hospitals near Helsinki in 1959--1971. Practically total replacement of dairy fats by vegetable oils in the diets of these hospitals was followed by a substantial reduction in the mortality of men from CHD. Total mortality also appeared to be reduced. As to the causes of death other than CHD, none was significantly influenced by dietary change. This was also true for malignant neoplasms. To alleviate the burden of CHD on public health, many investigators have recommended important changes in the quantity and quality of dietary fats.

Abstract: Whereas the way animals perceive human contact has been particularly examined in pet animals, a small amount of investigations has been done in domestic ungulates. It was nevertheless assumed that, as pet animals, non-aggressive forms of tactile contact were as well rewarding or positive for these species, even though the features of intraspecific relationships in pet animals and domestic ungulates may be to some extent different.We test here the hypothesis that horses may not consider physical handling by humans as a positive event. When comparing different early human-foal interactions, we found that early exposure to a motionless human enhanced slightly foals reactions to humans whereas forced stroking or handling in early life did not improve later human-foal relation. Foals that were assisted during their first suckling (e.g., brought to the dam's teat) even tended to avoid human approach at 2 weeks, and physical contact at 1 month of age.We argue that interspecies differences may exist in how tactile stimulation is perceived. It may be important for the establishment of a bond that a young animal is active in the process and able, through its behavioral responses, to help define what is positive for it. This way of investigation may have important general implications in how we consider the development of social relations, both within and between species.