Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice

<p>Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice</p

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

The Sloan Digital Sky Survey quasar catalog: Tenth data release â&amp;dagger

We present the Data Release 10 Quasar (DR10Q) catalog from the Baryon Oscillation Spectroscopic Survey (BOSS) of the Sloan Digital Sky Survey III. The catalog includes all BOSS objects that were targeted as quasar candidates during the first 2.5 years of the survey and that are confirmed as quasars via visual inspection of the spectra, have luminosities Mi[z = 2] < −20.5 (in a ΛCDMcosmology with H0 = 70 km s−1 Mpc−1, ΩM = 0.3, and ΩΛ = 0.7), and either display at least one emission line with a full width at half maximum (FWHM) larger than 500 km s−1 or, if not, have interesting/complex absorption features. The catalog also includes known quasars (mostly from SDSS-I and II) that were reobserved by BOSS. The catalog contains 166 583 quasars (74 454 are new discoveries since SDSS-DR9) detected over 6373 deg2 with robust identification and redshift measured by a combination of principal component eigenspectra. The number of quasars with z > 2.15 (117 668) is ∼5 times greater than the number of z > 2.15 quasars known prior to BOSS. Redshifts and FWHMs are provided for the strongest emission lines (C iv, C iii, Mg ii). The catalog identifies 16 461 broad absorption line quasars and gives their characteristics. For each object, the catalog presents five-band (u, g, r, i, z) CCD-based photometry with typical accuracy of 0.03 mag and information on the optical morphology and selection method. The catalog also contains X-ray, ultraviolet, near-infrared, and radio emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra cover the wavelength region 3600−10 500 Å at a spectral resolution in the range 1300 < R < 2500; the spectra can be retrieved from the SDSS Catalog Archive Server. We also provide a supplemental list of an additional 2376 quasars that have been identified among the galaxy targets of the SDSS-III/BOSS.I.P. received partial support from Center of Excellence in Astrophysics and Associated Technologies (PFB 06). The French Participation Group to SDSS-III was supported by the Agence Nationale de la Recherche under contracts ANR-08-BLAN-0222 and ANR-12-BS05-0015. A.D.M. is a research fellow of the Alexander von Humboldt Foundation of Germany and was partially supported through NSF Grant 1211112 and NASA ADAP award NNX12AE38G. Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the US Department of Energy Office of Science.This is the published version. It originally appeared in Astronomy and Astrophysics and is available online at http://www.aanda.org/articles/aa/abs/2014/03/aa22691-13/aa22691-13.html

Dental calculus evidence of Taï Forest Chimpanzee plant consumption and life history transitions

Dental calculus (calcified dental plaque) is a source of multiple types of data on life history. Recent research has targeted the plant microremains preserved in this mineralised deposit as a source of dietary and health information for recent and past populations. However, it is unclear to what extent we can interpret behaviour from microremains. Few studies to date have directly compared the microremain record from dental calculus to dietary records, and none with long-term observation dietary records, thus limiting how we can interpret diet, food acquisition and behaviour. Here we present a high-resolution analysis of calculus microremains from wild chimpanzees (Pan troglodytes verus) of Taï National Park, Côte d"Ivoire. We test microremain assemblages against more tan two decades of field behavioural observations to establish the ability of calculus to capture the composition of diet. Our results show that some microremain classes accumulate as long-lived dietary markers. Phytolith abundance in calculus can reflect the proportions of plants in the diet, yet this pattern is not true for starches. We also report microremains can record information about other dietary behaviours, such as the age of weaning and learned food processing techniques like nutcracking

The Sloan Digital Sky Survey quasar catalog: Tenth data release â&amp;dagger

We present the Data Release 10 Quasar (DR10Q) catalog from the Baryon Oscillation Spectroscopic Survey (BOSS) of the Sloan Digital Sky Survey III. The catalog includes all BOSS objects that were targeted as quasar candidates during the first 2.5 years of the survey and that are confirmed as quasars via visual inspection of the spectra, have luminosities Mi[z = 2] < −20.5 (in a ΛCDMcosmology with H0 = 70 km s−1 Mpc−1, ΩM = 0.3, and ΩΛ = 0.7), and either display at least one emission line with a full width at half maximum (FWHM) larger than 500 km s−1 or, if not, have interesting/complex absorption features. The catalog also includes known quasars (mostly from SDSS-I and II) that were reobserved by BOSS. The catalog contains 166 583 quasars (74 454 are new discoveries since SDSS-DR9) detected over 6373 deg2 with robust identification and redshift measured by a combination of principal component eigenspectra. The number of quasars with z > 2.15 (117 668) is ∼5 times greater than the number of z > 2.15 quasars known prior to BOSS. Redshifts and FWHMs are provided for the strongest emission lines (C iv, C iii, Mg ii). The catalog identifies 16 461 broad absorption line quasars and gives their characteristics. For each object, the catalog presents five-band (u, g, r, i, z) CCD-based photometry with typical accuracy of 0.03 mag and information on the optical morphology and selection method. The catalog also contains X-ray, ultraviolet, near-infrared, and radio emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra cover the wavelength region 3600−10 500 Å at a spectral resolution in the range 1300 < R < 2500; the spectra can be retrieved from the SDSS Catalog Archive Server. We also provide a supplemental list of an additional 2376 quasars that have been identified among the galaxy targets of the SDSS-III/BOSS.I.P. received partial support from Center of Excellence in Astrophysics and Associated Technologies (PFB 06). The French Participation Group to SDSS-III was supported by the Agence Nationale de la Recherche under contracts ANR-08-BLAN-0222 and ANR-12-BS05-0015. A.D.M. is a research fellow of the Alexander von Humboldt Foundation of Germany and was partially supported through NSF Grant 1211112 and NASA ADAP award NNX12AE38G. Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the US Department of Energy Office of Science.This is the published version. It originally appeared in Astronomy and Astrophysics and is available online at http://www.aanda.org/articles/aa/abs/2014/03/aa22691-13/aa22691-13.html

Research in progress: report on the ICAIL 2017 doctoral consortium

This paper arose out of the 2017 international conference on AI and law doctoral consortium. There were five students who presented their Ph.D. work, and each of them has contributed a section to this paper. The paper offers a view of what topics are currently engaging students, and shows the diversity of their interests and influences

Spatiotemporal processing of somatosensory stimuli in schizotypy

Unusual interaction behaviors and perceptual aberrations, like those occurring in schizotypy and schizophrenia, may in part originate from impaired remapping of environmental stimuli in the body space. Such remapping is contributed by the integration of tactile and proprioceptive information about current body posture with other exteroceptive spatial information. Surprisingly, no study has investigated whether alterations in such remapping occur in psychosis-prone individuals. Four hundred eleven students were screened with respect to schizotypal traits using the Schizotypal Personality Questionnaire. A subgroup of them, classified as low, moderate, and high schizotypes were to perform a temporal order judgment task of tactile stimuli delivered on their hands, with both uncrossed and crossed arms. Results revealed marked differences in touch remapping in the high schizotypes as compared to low and moderate schizotypes. For the first time here we reveal that the remapping of environmental stimuli in the body space, an essential function to demarcate the boundaries between self and external world, is altered in schizotypy. Results are discussed in relation to recent models of 'self-disorders' as due to perceptual incoherence

Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

Background We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of “granular biopersistent particles without known specific toxicity” (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK’s human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification. Methods We followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk. Results The MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species. Conclusion Classifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.International Carbon Black Associatio

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry