2015-hall.pdf: “Genetics and the placebo effect: the placebome”, (2015-05-01; ):
- Predisposition to respond to placebo treatment may be in part a stable heritable trait.
- Candidate placebo response pathways may interact with drugs to modify outcomes in both the placebo and drug treatment arms of clinical trials.
- Genomic analysis of randomized placebo and no-treatment controlled trials are needed to fully realize the potential of the placebome.
Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses statistically-significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in design. The study of genomic effects on placebo response, ‘the placebome’, is in its infancy. Here, we review evidence from placebo studies and to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for and clinical care.
Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear(3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenousβ-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR / Cas9 platform, a prerequisite for any clinical applications of -mediated editing.
2012-bakker.pdf: “The Last Magic Show: A Blind Brain Theory of the Appearance of Consciousness”, (2012-04-17; ):
According to the latest estimates, the human brain performs some 38 000 trillion operations per second. When you compare this to the amount of information that reaches conscious awareness, the disproportion becomes nothing short of remarkable. What are the consequences of this radical informatic asymmetry?
The Blind Brain Theory of the Appearance of Consciousness (BBT) represents an attempt to ‘explain away’ several of the most perplexing features of consciousness in terms of information loss and depletion. The first-person perspective, it argues, is the expression of the kinds and quantities of information that, for a variety of structural and developmental reasons, cannot be accessed by the ‘conscious brain.’ Puzzles as profound and persistent as the now, personal identity, conscious unity, and most troubling of all, intentionality, could very well be kinds of illusions foisted on conscious awareness by different versions of the informatic limitation expressed, for instance, in the boundary of your visual field.
By explaining away these phenomena, BBT separates the question of consciousness from the question of how consciousness appears, and so drastically narrows the so-called explanatory gap. If true, it solves the hard problem. But at what cost?
1995-mackenzie.pdf: “Tacit Knowledge, Weapons Design, and the Uninvention of Nuclear Weapons”, (1995; ):
Tacit Knowledge, embodied in people rather than words, equations, or diagrams, plays a vital role in science. The historical record of the development and spread of nuclear weapons and the recollections of their designers suggest that tacit knowledge is also crucial to nuclear weapons development. Therefore, if design ceases, and if there is no new generation of designers to whom that tacit knowledge can be passed, then in an important (though qualified) sense nuclear weapons will have been uninvented. Their renewed development would thus have some of the characteristics of reinvention rather than simply copying. In addition, knowledge may be lost not only as a result of complete disarmament, but also as a consequence of likely measures such as a nuclear test ban.
2007-doran.pdf: “So You Discovered an Anomaly … Gonna Publish It? An Investigation Into the Rationality of Publishing a Market Anomaly”, (2007-01-11; ):
If publishing an anomaly leads to the dissipation of its profitability, a notion that has mounting empirical support, then publishing a highly profitable market anomaly seems to be irrational behavior. This paper explores the issue by developing and empirically testing a theory that argues that publishing a market anomaly may, in fact, be rational behavior. The theory predicts that researchers with few (many) publications and lesser (stronger) reputations have the highest (lowest) incentive to publish market anomalies. Employing probit models, simple OLS regressions, and principal component analysis, we show that (a) market anomalies are more likely to be published by researchers with fewer previous publications and who have been in the field for a shorter period of time and (b) the profitability of published market anomalies is inversely related to the common factor spanning the number of publications the author has and the number of years that have elapsed since the professor earned his Ph.D. The empirical results suggest that the probability of publishing an anomaly and the profitability of anomalies that are published are inversely related to the reputation of the authors. These results corroborate the theory that publishing an anomaly is rational behavior for an author trying to establish his or her reputation.