182 research outputs found

    Rise of the Machines: The Legal Implications for Investor Protection with the Rise of Robo-Advisors

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    This note examines the complex state of financial innovation and preexisting investor protection regimes, mainly the Investment Advisers Act of 1940, which do not properly address the question of whether a robo-advisor platform serving as registered investment advisers satisfies the fiduciary standard elements laid out in the Act. This article examines the current regulation from the Department of Labor, the Financial Industry Regulatory Authority, and the Securities and Exchange Commission and addresses the inadequacies in each regulatory entity’s policy prescription. This article contends that robo-advisors can not act as a fiduciary for several reasons – primarily because these platforms do not provide the type of individualized portfolio analysis that traditional fiduciary agents provide

    Studies on Actinomycetes from Soils of Baffin Island

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    Investigations were made of the abundance and relative incidence of different types of actinomycetes in soil samples from Baffin Island, Northwest Territories. Numbers were relatively low in all samples examined, and no specific group predominated. Cultures grown at 26°C. showed greater metabolic activity than when grown at 10°C., and isolates from different soils varied in degree of activity. Ammonium nitrogen proved to be the best nitrogen source. A comparatively wide range of carbon compounds was utilized; glucose, fructose, mannitol, raffinose and sucrose were the best sources. Moderate growth of a large number of isolates was also obtained with acetate, fumarate, pyruvate and succinate. With one exception the incidence of actinomycetes antagonistic toward bacteria, yeasts and fungi was remarkably high in the soils studied. The samples did, however, differ in proportion of antagonistic types.Études sur les actionmycètes des sols de l'île de Baffin. On a mené des enquêtes sur l'abondance et l'incidence relative des différents types d'actionmycètes dans des échantillons de sols de l'île de Baffin, Territoires du Nord-Ouest. Tous les échantillons examinés ont donné des comptages relativement bas et aucun groupe spécifique ne dominait. Les cultures venues à 26ºC montraient une plus grande activité métabolique que celles venues à 10ºC, et des isolats de sols différents avaient des degrés d'activité variables. L'azote de l'ammonium s'est révélé être la meilleure source de cet élément. On a utilisé une gamme étendue de composés carbonés : glucose, fructose, mannitol, raffinose et sucrose étaient les meilleures sources de carbone. On a aussi obtenu avec l'acétate, le fumarate, le pyruvate et le succinate une croissance modérée d'un grand nombre d'isolats. A une exception près, l'incidence des actinomycètes antagonistes des bactéries, levures et champignons était remarquablement élevée. Cependant, ces échantillons différaient entre eux dans leurs proportions de types antagonistes

    Growth and electronic and magnetic structure of iron oxide films on Pt(111)

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    Ultrathin (111)-oriented polar iron oxide films were grown on a Pt(111) single crystal either by the reactive deposition of iron or oxidation of metallic iron monolayers. These films were characterized using low energy electron diffraction, scanning tunneling microscopy and conversion electron Mossbauer spectroscopy. The reactive deposition of Fe led to the island growth of Fe3O4, in which the electronic and magnetic properties of the bulk material were modulated by superparamagnetic size effects for thicknesses below 2 nm, revealing specific surface and interface features. In contrast, the oxide films with FeO stoichiometry, which could be stabilized as thick as 4 nm under special preparation conditions, had electronic and magnetic properties that were very different from their bulk counterpart, w\"ustite. Unusual long range magnetic order appeared at room temperature for thicknesses between three and ten monolayers, the appearance of which requires severe structural modification from the rock-salt structure.Comment: 17 pages, 6 figures, 50 reference

    Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

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    IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p &amp;lt; 0.001), focal seizures (65.0% vs. 36.8%; p &amp;lt; 0.001) and GTCS (83.7% vs. 67.2%; p &amp;lt; 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p &amp;lt; 0.001]; focal seizures, 29.4% vs. 8.7% [p &amp;lt; 0.001]; GTCS, 69.0% vs. 48.1% [p &amp;lt; 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p &amp;lt; 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.</jats:sec

    Staged treatment response in status epilepticus: Lessons from the SENSE registry.

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    Although in epilepsy patients the likelihood of becoming seizure-free decreases substantially with each unsuccessful treatment, to our knowledge this has been poorly investigated in status epilepticus (SE). We aimed to evaluate the proportion of SE cessation and functional outcome after successive treatment steps. We conducted a post hoc analysis of a prospective, observational, multicenter cohort (Sustained Effort Network for treatment of Status Epilepticus [SENSE]), in which 1049 incident adult SE episodes were prospectively recorded at nine European centers. We analyzed 996 SE episodes without coma induction before the third treatment step. Rates of SE cessation, mortality (in ongoing SE or after SE control), and favorable functional outcome (assessed with modified Rankin scale) were evaluated after each step. SE was treated successfully in 838 patients (84.1%), 147 (14.8%) had a fatal outcome (36% of them died while still in SE), and 11 patients were transferred to palliative care while still in SE. Patients were treated with a median of three treatment steps (range 1-13), with 540 (54.2%) receiving more than two steps (refractory SE [RSE]) and 95 (9.5%) more than five steps. SE was controlled after the first two steps in 45%, with an additional 21% treated after the third, and 14% after the fourth step. Likelihood of SE cessation (p &lt; 0.001), survival (p = 0.003), and reaching good functional outcome (p &lt; 0.001) decreased significantly between the first two treatment lines and the third, especially in patients not experiencing generalized convulsive SE, but remained relatively stable afterwards. The significant worsening of SE prognosis after the second step clinically supports the concept of RSE. However, and differing from findings in human epilepsy, RSE remains treatable in about one third of patients, even after several failed treatment steps. Clinical judgment remains essential to determine the aggressiveness and duration of SE treatment, and to avoid premature treatment cessation in patients with SE

    Synthetic light-activated ion channels for optogenetic activation and inhibition

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    Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca22+^{2+}) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca2+^{2+} might be desirable. Moreover, there is need for an efficient light-gated potassium (K+^{+}) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca2+^{2+} and K+^{+} in cell physiology, light-activated Ca2+^{2+}-permeant and K+^{+}-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca2+^{2+}-permeant and K+^{+}-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca2+^{2+} or for K+^{+}, respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca2+^{2+}-permeant channel, and to body extension when expressing the light-sensitive K+^{+} channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons

    Cellular Radiosensitivity: How much better do we understand it?

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    Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

    Synthetic Light-Activated Ion Channels for Optogenetic Activation and Inhibition

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    Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2+) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca2+ might be desirable. Moreover, there is need for an efficient light-gated potassium (K+) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca2+ and K+ in cell physiology, light-activated Ca2+-permeant and K+-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca2+-permeant and K+-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca2+ or for K+, respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca2+-permeant channel, and to body extension when expressing the light-sensitive K+ channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons

    Peer navigation improves diagnostic follow-up after breast cancer screening among Korean American women: results of a randomized trial

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    To test an intervention to increase adherence to diagnostic follow-up tests among Asian American women. Korean American women who were referred for a diagnostic follow-up test (mainly diagnostic mammograms) and who had missed their follow-up appointment were eligible to participate in the study. Women from two clinics (n&nbsp;=&nbsp;176) were randomly allocated to a usual care control arm or a peer navigator intervention arm. A 20-min telephone survey was administered to women in both study arms six&nbsp;months after they were identified to assess demographic and socio-economic characteristics and the primary outcome, self-reported completion of the recommended follow-up exam. Among women who completed the survey at six-month follow-up, self-reported completion of follow-up procedures was 97% in the intervention arm and 67% in the control arm (p&nbsp;&lt;&nbsp;0.001). Based on an intent-to-treat analysis of all women who were randomized and an assumption of no completion of follow-up exam for women with missing outcome data, self-reported completion of follow-up was 61% in the intervention arm and 46% in the usual care control arm (p&nbsp;&lt;&nbsp;0.069). Our results suggest that a peer navigator intervention to assist Korean American women to obtain follow-up diagnostic tests after an abnormal breast cancer screening test is efficacious
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