Extensive sequence-influenced DNA methylation polymorphism in the human genome

Background: Epigenetic polymorphisms are a potential source of human diversity, but their frequency and relationship to genetic polymorphisms are unclear. DNA methylation, an epigenetic mark that is a covalent modification of the DNA itself, plays an important role in the regulation of gene expression. Most studies of DNA methylation in mammalian cells have focused on CpG methylation present in CpG islands (areas of concentrated CpGs often found near promoters), but there are also interesting patterns of CpG methylation found outside of CpG islands. Results: We compared DNA methylation patterns on both alleles between many pairs (and larger groups) of related and unrelated individuals. Direct observation and simulation experiments revealed that around 10% of common single nucleotide polymorphisms (SNPs) reside in regions with differences in the propensity for local DNA methylation between the two alleles. We further showed that for the most common form of SNP, a polymorphism at a CpG dinucleotide, the presence of the CpG at the SNP positively affected local DNA methylation in cis. Conclusions: Taken together with the known effect of DNA methylation on mutation rate, our results suggest an interesting interdependence between genetics and epigenetics underlying diversity in the human genome

Normative Ethics Does Not Need a Foundation: It Needs More Science

The impact of science on ethics forms since long the subject of intense debate. Although there is a growing consensus that science can describe morality and explain its evolutionary origins, there is less consensus about the ability of science to provide input to the normative domain of ethics. Whereas defenders of a scientific normative ethics appeal to naturalism, its critics either see the naturalistic fallacy committed or argue that the relevance of science to normative ethics remains undemonstrated. In this paper, we argue that current scientific normative ethicists commit no fallacy, that criticisms of scientific ethics contradict each other, and that scientific insights are relevant to normative inquiries by informing ethics about the options open to the ethical debate. Moreover, when conceiving normative ethics as being a nonfoundational ethics, science can be used to evaluate every possible norm. This stands in contrast to foundational ethics in which some norms remain beyond scientific inquiry. Finally, we state that a difference in conception of normative ethics underlies the disagreement between proponents and opponents of a scientific ethics. Our argument is based on and preceded by a reconsideration of the notions naturalistic fallacy and foundational ethics. This argument differs from previous work in scientific ethics: whereas before the philosophical project of naturalizing the normative has been stressed, here we focus on concrete consequences of biological findings for normative decisions or on the day-to-day normative relevance of these scientific insights

Inferring Visuomotor Priors for Sensorimotor Learning

Sensorimotor learning has been shown to depend on both prior expectations and sensory evidence in a way that is consistent with Bayesian integration. Thus, prior beliefs play a key role during the learning process, especially when only ambiguous sensory information is available. Here we develop a novel technique to estimate the covariance structure of the prior over visuomotor transformations – the mapping between actual and visual location of the hand – during a learning task. Subjects performed reaching movements under multiple visuomotor transformations in which they received visual feedback of their hand position only at the end of the movement. After experiencing a particular transformation for one reach, subjects have insufficient information to determine the exact transformation, and so their second reach reflects a combination of their prior over visuomotor transformations and the sensory evidence from the first reach. We developed a Bayesian observer model in order to infer the covariance structure of the subjects' prior, which was found to give high probability to parameter settings consistent with visuomotor rotations. Therefore, although the set of visuomotor transformations experienced had little structure, the subjects had a strong tendency to interpret ambiguous sensory evidence as arising from rotation-like transformations. We then exposed the same subjects to a highly-structured set of visuomotor transformations, designed to be very different from the set of visuomotor rotations. During this exposure the prior was found to have changed significantly to have a covariance structure that no longer favored rotation-like transformations. In summary, we have developed a technique which can estimate the full covariance structure of a prior in a sensorimotor task and have shown that the prior over visuomotor transformations favor a rotation-like structure. Moreover, through experience of a novel task structure, participants can appropriately alter the covariance structure of their prior

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Could sound be used as a strategy for reducing symptoms of perceived motion sickness?

<p>Abstract</p> <p>Background</p> <p>Working while exposed to motions, physically and psychologically affects a person. Traditionally, motion sickness symptom reduction has implied use of medication, which can lead to detrimental effects on performance. Non-pharmaceutical strategies, in turn, often require cognitive and perceptual attention. Hence, for people working in high demand environments where it is impossible to reallocate focus of attention, other strategies are called upon. The aim of the study was to investigate possible impact of a mitigation strategy on perceived motion sickness and psychophysiological responses, based on an artificial sound horizon compared with a non-positioned sound source.</p> <p>Methods</p> <p>Twenty-three healthy subjects were seated on a motion platform in an artificial sound horizon or in non-positioned sound, in random order with one week interval between the trials. Perceived motion sickness (Mal), maximum duration of exposure (ST), skin conductance, blood volume pulse, temperature, respiration rate, eye movements and heart rate were measured continuously throughout the trials.</p> <p>Results</p> <p>Mal scores increased over time in both sound conditions, but the artificial sound horizon, applied as a mitigation strategy for perceived motion sickness, showed no significant effect on Mal scores or ST. The number of fixations increased with time in the non-positioned sound condition. Moreover, fixation time was longer in the non-positioned sound condition compared with sound horizon, indicating that the subjects used more time to fixate and, hence, assumingly made fewer saccades.</p> <p>Conclusion</p> <p>A subliminally presented artificial sound horizon did not significantly affect perceived motion sickness, psychophysiological variables or the time the subjects endured the motion sickness triggering stimuli. The number of fixations and fixation times increased over time in the non-positioned sound condition.</p

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

The General Age of Leadership: Older-Looking Presidential Candidates Win Elections during War

As nation-state leaders age they increasingly engage in inter-state militarized disputes yet in industrialized societies a steady decrease in testosterone associated with aging is observed – which suggests a decrease in dominance behavior. The current paper points out that from modern societies to Old World monkeys increasing both in age and social status encourages dominant strategies to maintain acquired rank. Moreover, it is argued this consistency has shaped an implicit prototype causing followers to associate older age with dominance leadership. It is shown that (i) faces of older leaders are preferred during intergroup conflict and (ii) morphing U.S. Presidential candidates to appear older or younger has an overriding effect on actual election outcomes. This indicates that democratic voting can be systematically adjusted by activating innate biases. These findings appear to create a new line of research regarding the biology of leadership and contextual cues of age

Parents' Experiences Discussing Pediatric Vaccination with Healthcare Providers: A Survey of Canadian Naturopathic Patients

Parents who choose to selectively vaccinate or avoid vaccination for their children may do so at risk of compromising relations with their family physician or pediatrician. Groups that are associated with reduced rates of pedicatic vaccination, such as parents who access naturopathic care, may be particularly vulnerable to this issue.In March through September 2010, we administered a 26-item cross-sectional survey to 129 adult patients, all of whom were parents with children ≤ 16 years of age, presenting for naturopathic care in Ontario, Canada. Ninety-five parents completed the survey (response rate 74%), and only 50.5% (48 of 95) reported that their children had received all recommended vaccines. Most parents (50.5%; 48 of 95) reported feeling pressure to vaccinate from their allopathic physician and, of those who discussed vaccination with their physician, 25.9% (21 of 81) were less comfortable continuing care as a result. Five percent (4 of 81) of respondents were advised by their physician that their children would be refused care if they decided against vaccination. In our adjusted generalized linear model, feeling pressure to vaccinate (odds ratio [OR] = 3.07; 95% confidence interval [CI] = 1.14 to 8.26) or endorsing a naturopathic physician as their most trusted source of information regarding vaccination (OR = 3.57; 95% CI = 1.22 to 10.44) were associated with greater odds of having a partially vaccinated or unvaccinated child. The majority (69.6%; 32 of 46) of parent's with partially vaccinated or unvaccinated children reported a willingness to re-consider this decision.Use of naturopathic care should be explored among parents in order to identify this high-risk group and engage them in discussion regarding pediatric vaccination to encourage evidence-based, shared decision making. Physicians should ensure that discussions regarding vaccination are respectful, even if parents are determined not to vaccinate their children

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Stigma and Self-Stigma in Addiction

Addictions are commonly accompanied by a sense of shame or self-stigmatization. Self-stigmatization results from public stigmatization in a process leading to the internalization of the social opprobrium attaching to the negative stereotypes associated with addiction. We offer an account of how this process works in terms of a range of looping effects, and this leads to our main claim that for a significant range of cases public stigma figures in the social construction of addiction. This rests on a social constructivist account in which those affected by public stigmatization internalize its norms. Stigma figures as part-constituent of the dynamic process in which addiction is formed. Our thesis is partly theoretical, partly empirical, as we source our claims about the process of internalization from interviews with people in treatment for substance use problems