209 research outputs found

    Clinical Trials Registry - India: Redefining the conduct of clinical trials

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    Autonomous vehicle decision-making: Should we be bio-inspired?

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    © Springer International Publishing AG 2017. On our crowded roads, drivers must compete for space but cooperate to avoid occupying the same space at the same time. Decision-making is strategic and requires mutual understanding of other’s choices. Fully autonomous vehicles (AVs) will need risk management software to make these types strategic decisions without human arbitration. Accidents will occur, and what constitutes rational and ‘safe’ decisions will be scrutinized by the legal system. It is far from clear how AV-Human and AV-AV interactions should be managed. Game Theory provides a framework for analyzing mutual ‘games’ with 2 or more players. It assumes that players mutually optimize their outcomes according to Nash equilibria (NE), but do humans follow Nash equilibria in Human-Human interactions? We implemented simple two-player competitive games to see whether people played rationally according to Nash equilibria. On each of 100 trials, each player was instructed to maximise their reward by pressing one of three buttons labelled “4”, “6”, and “12”, without knowing the other players choice. If players pressed different buttons, they received a reward of 4, 6, or 12 points accordingly. If players pressed the same button, the reward was reduced depending on the game type. Results showed that players did not follow NE, but played a probabilistic game that included the “4” button, even though pressing this button is always suboptimal. We suggest that this may be an evolutionary strategy, but it clearly shows that people do not follow the ‘rational’ Nash strategy. It seems that AV-human interactions will be probabilistic. In AV-AV interactions, software may be playing itself, and may also require probabilistic optimal evolutionary-type strategies. We doubt that the full implications of autonomous decision-making have been fully worked out. Whether probabilistic decisions will tolerated legally and actuarially is doubtful. One way to avoid them would be to allow regulated AV-AV communications, and force software decisions to be deterministic according to some protocol. However, AV-Human interactions seem likely to remain problematic

    Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

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    What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity

    Decomposing Neural Synchrony: Toward an Explanation for Near-Zero Phase-Lag in Cortical Oscillatory Networks

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    Background: Synchronized oscillation in cortical networks has been suggested as a mechanism for diverse functions ranging from perceptual binding to memory formation to sensorimotor integration. Concomitant with synchronization is the occurrence of near-zero phase-lag often observed between network components. Recent theories have considered the importance of this phenomenon in establishing an effective communication framework among neuronal ensembles. Methodology/Principal Findings: Two factors, among possibly others, can be hypothesized to contribute to the near-zero phase-lag relationship: (1) positively correlated common input with no significant relative time delay and (2) bidirectional interaction. Thus far, no empirical test of these hypotheses has been possible for lack of means to tease apart the specific causes underlying the observed synchrony. In this work simulation examples were first used to illustrate the ideas. A quantitative method that decomposes the statistical interdependence between two cortical areas into a feed-forward, a feed-back and a common-input component was then introduced and applied to test the hypotheses on multichannel local field potential recordings from two behaving monkeys. Conclusion/Significance: The near-zero phase-lag phenomenon is important in the study of large-scale oscillatory networks. A rigorous mathematical theorem is used for the first time to empirically examine the factors that contribute to this phenomenon. Given the critical role that oscillatory activity is likely to play in the regulation of biological processes at al

    Poor mental health and sexual risk behaviours in Uganda: A cross-sectional population-based study

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    <p>Abstract</p> <p>Background</p> <p>Poor mental health predicts sexual risk behaviours in high-income countries, but little is known about this association in low-income settings in sub-Saharan Africa where HIV is prevalent. This study investigated whether depression, psychological distress and alcohol use are associated with sexual risk behaviours in young Ugandan adults.</p> <p>Method</p> <p>Household sampling was performed in two Ugandan districts, with 646 men and women aged 18-30 years recruited. Hopkins Symptoms Checklist-25 was used to assess the presence of depression and psychological distress. Alcohol use was assessed using a question about self-reported heavy-episodic drinking. Information on sexual risk behaviour was obtained concerning number of lifetime sexual partners, ongoing concurrent sexual relationships and condom use.</p> <p>Results</p> <p>Depression was associated with a greater number of lifetime partners and with having concurrent partners among women. Psychological distress was associated with a greater number of lifetime partners in both men and women and was marginally associated (p = 0.05) with having concurrent partners among women. Psychological distress was associated with inconsistent condom use among men. Alcohol use was associated with a greater number of lifetime partners and with having concurrent partners in both men and women, with particularly strong associations for both outcome measures found among women.</p> <p>Conclusion</p> <p>Poor mental health is associated with sexual risk behaviours in a low-income sub-Saharan African setting. HIV preventive interventions should consider including mental health and alcohol use reduction components into their intervention packages, in settings where depression, psychological distress and alcohol use are common.</p

    Co-ordinated Role of TLR3, RIG-I and MDA5 in the Innate Response to Rhinovirus in Bronchial Epithelium

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    The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8–12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases

    Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

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    Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size

    Network deconvolution as a general method to distinguish direct dependencies in networks

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    Recognizing direct relationships between variables connected in a network is a pervasive problem in biological, social and information sciences as correlation-based networks contain numerous indirect relationships. Here we present a general method for inferring direct effects from an observed correlation matrix containing both direct and indirect effects. We formulate the problem as the inverse of network convolution, and introduce an algorithm that removes the combined effect of all indirect paths of arbitrary length in a closed-form solution by exploiting eigen-decomposition and infinite-series sums. We demonstrate the effectiveness of our approach in several network applications: distinguishing direct targets in gene expression regulatory networks; recognizing directly interacting amino-acid residues for protein structure prediction from sequence alignments; and distinguishing strong collaborations in co-authorship social networks using connectivity information alone. In addition to its theoretical impact as a foundational graph theoretic tool, our results suggest network deconvolution is widely applicable for computing direct dependencies in network science across diverse disciplines.National Institutes of Health (U.S.) (grant R01 HG004037)National Institutes of Health (U.S.) (grant HG005639)Swiss National Science Foundation (Fellowship)National Science Foundation (U.S.) (NSF CAREER Award 0644282

    Projected changes of rainfall seasonality and dry spells in a high greenhouse gas emissions scenario

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    In this diagnostic study we analyze changes of rainfall seasonality and dry spells by the end of the twenty-first century under the most extreme IPCC5 emission scenario (RCP8.5) as projected by twenty-four coupled climate models contributing to Coupled Model Intercomparison Project 5 (CMIP5). We use estimates of the centroid of the monthly rainfall distribution as an index of the rainfall timing and a threshold-independent, information theory-based quantity such as relative entropy (RE) to quantify the concentration of annual rainfall and the number of dry months and to build a monsoon dimensionless seasonality index (DSI). The RE is projected to increase, with high inter-model agreement over Mediterranean-type regions---southern Europe, northern Africa and southern Australia---and areas of South and Central America, implying an increase in the number of dry days up to 1Â month by the end of the twenty-first century. Positive RE changes are also projected over the monsoon regions of southern Africa and North America, South America. These trends are consistent with a shortening of the wet season associated with a more prolonged pre-monsoonal dry period. The extent of the global monsoon region, characterized by large DSI, is projected to remain substantially unaltered. Centroid analysis shows that most of CMIP5 projections suggest that the monsoonal annual rainfall distribution is expected to change from early to late in the course of the hydrological year by the end of the twenty-first century and particularly after year 2050. This trend is particularly evident over northern Africa, southern Africa and western Mexico, where more than 90% of the models project a delay of the rainfall centroid from a few days up to 2Â weeks. Over the remaining monsoonal regions, there is little inter-model agreement in terms of centroid changes
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