Based on investigation of the earliest colonic tissue alteration in familial adenomatous polyposis (FAP) patients, we present the hypothesis that initiation of colorectal cancer by adenomatous polyposis coli (APC) mutation is mediated by dysregulation of two cellular mechanisms. One involves differentiation, which normally decreases the proportion (proliferative fraction) of colonic crypt cells that can proliferate; the other is a cell cycle mechanism that simultaneously increases the probability that proliferative cells are in S phase. In normal crypts, stem cells (SC) at the crypt bottom generate rapidly proliferating cells, which undergo differentiation while migrating up the crypt. Our modeling of normal crypts suggests that these transitions are mediated by mechanisms that regulate proliferative fraction and S-phase probability. In FAP crypts, the population of rapidly proliferating cells is shifted upwards, as indicated by the labeling index (LI; i.e., crypt distribution of cells in S phase). Our analysis of FAP indicates that these transitions are delayed because the proliferative fraction and S-phase probability change more slowly as a function of crypt level. This leads to expansion of the proliferative cell population, including a subpopulation that has a low frequency of S-phase cells. We previously reported that crypt SC overpopulation explains the LI shift. Here, we determine that SCs (or cells having high stemness) are proliferative cells with a low probability of being in S phase. Thus, dysregulation of mechanisms that control proliferative fraction and S-phase probability explains how APC mutations induce SC overpopulation at the crypt bottom, shift the rapidly proliferating cell population upwards, and initiate colon tumorigenesis. [Cancer Res 2008;68(9):3304-13]

No abstract

No abstract

Many conceptions of field-effects of consciousness have been proposed. The most well-developed of these is Maharishi Mahesh Yogi’s, which holds that every individual in society, whether stressed or coherent, contributes to collective consciousness. Collective consciousness in turn impacts the life of every individual, guiding the trends of life in the nation. Over 600 studies have documented that the Transcendental Meditation® and advanced TM-Sidhi® program increase coherence in the individual, as indicated by improved brain integration, health, cognitive abilities, and behavior. Fifty additional studies indicate that these more coherent individuals radiate an influence of coherence throughout society, as reflected in reductions of conflicts and improvements in quality of life. In the present study, interrupted time series analysis was used to evaluate the effectiveness of this population-level health intervention that was implemented at a clearly defined point in time. It found that during the Demonstration period of 2007-2011, compared to the Baseline period of 2000 to 2006, when a group practicing the Transcendental Meditation and TM-Sidhi techniques reached or exceeded a predicted required threshold of √1% of the U.S. population (1725) there were significant and meaningful trend reductions in indicators of national stress: homicides, rape, aggravated assault, robbery, infant mortality, drug-related deaths, motor vehicle fatalities, fatalities due to injuries in youths ages 10-19, and in a composite index of all eight variables (p’s < .0001). Moreover, from 2007 to 2016, when the size of the group decreased to below the required threshold, all stress indicators increased again. Potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies could not explain the results. The results support a new highly practical field-theoretic understanding of social dynamics.

This study outlines and empirically tests a field-theoretic view of consciousness and positive social change based on the ancient Vedic tradition of knowledge from India (Veda means “knowledge” in Sanskrit) as brought to light by the Vedic scholar and scientist of consciousness, Maharishi Mahesh Yogi. In contrast to most contemporary theories of mind and consciousness originating in the West, Maharishi’s Vedic science of consciousness posits the existence of an interpersonal, nonlocalized dimension of consciousness that underlies both individual consciousness and the “collective consciousness” of society, or “national consciousness.” We review previous empirical tests in Cambodia, India, the Philippines (and other countries) of hypotheses derived from this field-theoretic view of consciousness. We then present new empirical results, which together with prior research, provide evidence for an interpersonal dimension to consciousness. Segmented-trend regression analysis of data from a prospective, 15-year U.S. national social experiment found support for the hypothesis that “field effects of consciousness” created by group practice of Transcendental Meditation® and its advanced technique, the TM-Sidhi® program, by a theoretically predicted number of participants contributed to a reduction in social stress in national consciousness as indicated by improved monthly homicide trends during the study’s experimental period 2007-2011 (p < .0001). These results are consistent with significant reductions in crime and violence associated with group practice of the TM® and TM-Sidhi® program as reported in previous peer-reviewed research. This reduction was followed by a predicted subsequent increase in homicide trends 2012-2016 (p < .0001) after the group fell below the required size (approximately the √1% of the U.S. population).