The Fueling and Evolution of AGN: Internal and External Triggers

In this chapter, I review the fueling and evolution of active galactic nuclei (AGN) under the influence of internal and external triggers, namely intrinsic properties of host galaxies (morphological or Hubble type, color, presence of bars and other non-axisymmetric features, etc) and external factors such as environment and interactions. The most daunting challenge in fueling AGN is arguably the angular momentum problem as even matter located at a radius of a few hundred pc must lose more than 99.99 % of its specific angular momentum before it is fit for consumption by a BH. I review mass accretion rates, angular momentum requirements, the effectiveness of different fueling mechanisms, and the growth and mass density of black BHs at different epochs. I discuss connections between the nuclear and larger-scale properties of AGN, both locally and at intermediate redshifts, outlining some recent results from the GEMS and GOODS HST surveys.Comment: Invited Review Chapter to appear in LNP Volume on "AGN Physics on All Scales", Chapter 6, in press. 40 pages, 12 figures. Typo in Eq 5 correcte

Systematic Reviews of Animal Experiments Demonstrate Poor Human Clinical and Toxicological Utility

The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive Scopus biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one of which was contentious. These included reviews of the clinical utility of experiments expected by ethics committees to lead to medical advances, of highly-cited experiments published in major journals, and of chimpanzee experiments — those involving the species considered most likely to be predictive of human outcomes. Seven additional reviews failed to clearly demonstrate utility in predicting human toxicological outcomes, such as carcinogenicity and teratogenicity. Consequently, animal data may not generally be assumed to be substantially useful for these purposes. Possible causes include interspecies differences, the distortion of outcomes arising from experimental environments and protocols, and the poor methodological quality of many animal experiments, which was evident in at least 11 reviews. No reviews existed in which the majority of animal experiments were of good methodological quality. Whilst the effects of some of these problems might be minimised with concerted effort (given their widespread prevalence), the limitations resulting from interspecies differences are likely to be technically and theoretically impossible to overcome. Non-animal models are generally required to pass formal scientific validation prior to their regulatory acceptance. In contrast, animal models are simply assumed to be predictive of human outcomes. These results demonstrate the invalidity of such assumptions. The consistent application of formal validation studies to all test models is clearly warranted, regardless of their animal, non-animal, historical, contemporary or possible future status. Likely benefits would include, the greater selection of models truly predictive of human outcomes, increased safety of people exposed to chemicals that have passed toxicity tests, increased efficiency during the development of human pharmaceuticals and other therapeutic interventions, and decreased wastage of animal, personnel and financial resources. The poor human clinical and toxicological utility of most animal models for which data exists, in conjunction with their generally substantial animal welfare and economic costs, justify a ban on animal models lacking scientific data clearly establishing their human predictivity or utility