Net neutrality discourses: comparing advocacy and regulatory arguments in the United States and the United Kingdom

Telecommunications policy issues rarely make news, much less mobilize thousands of people. Yet this has been occurring in the United States around efforts to introduce "Net neutrality" regulation. A similar grassroots mobilization has not developed in the United Kingdom or elsewhere in Europe. We develop a comparative analysis of U.S. and UK Net neutrality debates with an eye toward identifying the arguments for and against regulation, how those arguments differ between the countries, and what the implications of those differences are for the Internet. Drawing on mass media, advocacy, and regulatory discourses, we find that local regulatory precedents as well as cultural factors contribute to both agenda setting and framing of Net neutrality. The differences between national discourses provide a way to understand both the structural differences between regulatory cultures and the substantive differences between policy interpretations, both of which must be reconciled for the Internet to continue to thrive as a global medium

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

A theoretical framework informing research about the role of stress in the pathophysiology of bipolar disorder

Background: the staggering illness burden associated with Bipolar Disorder (BD) invites the need for primary prevention strategies. Before preventative strategies can be considered in individuals during a pre-symptomatic period (i.e., at risk), unraveling the mechanistic steps wherein external stress is transduced and interacts with genetic vulnerability in the early stages of BD will be a critical conceptual necessity.Methods: Herein we comprehensively review extant studies reporting on stress and bipolar disorder. the over-arching aim is to propose a conceptual framework to inform research about the role of stress in the pathophysiology of BD. Computerized databases i.e. PubMed, PsychInfo, Cochrane Library and Scielo were searched using the following terms: bipolar disorder cross-referenced with stress, general reaction to stress, resilience, resistance, recovery stress-diathesis, allostasis, and hormesis.Results: Data from literature indicate the existence of some theoretical models to understand the influence of stress in the pathophysiology of BD, including classical stress-diathesis model and new models such as allostasis and hormesis. in addition, molecular mechanisms involved in stress adaptation (resistance, resilience and recovery) can also be translated in research strategies to investigate the impact of stress in the pathophysiology of BD.Limitations: Most studies are retrospective and/or cross sectional, do not consider the period of development, assess brain function with only one or few methodologies, and use animal models which are not always similar to human phenotypes.Conclusion: the interaction between stress and brain development is dynamic and complex. in this article we proposed a theoretical model for investigation about the role of stress in the pathophysiology of BD, based on the different kinds of stress adaptation response and their putative neurobiological underpinnings. (c) 2012 Elsevier Inc. All rights reserved.Universidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilUniv Toronto, Univ Hlth Network, Mood Disorders Psychophamacol Unit, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilWeb of Scienc

Novel therapeutic targets in depression: Minocycline as a candidate treatment

Mood disorders are marked by high rates of non-recovery, recurrence, and chronicity, which are insufficiently addressed by current therapies. Several patho-etiological models have been proposed that are not mutually exclusive and include but are not limited to the monoamine, inflammatory, neurotrophic, gliotrophic, excitatory, and oxidative stress systems. A derivative of these observations is that treatment(s) which target one or more of these mechanistic steps may be capable of mitigating, or preventing, disparate psychopathological features. Minocycline is an agent with pleiotropic properties that targets multiple proteins and cellular processes implicated in the patho-etiology of mood disorders. Moreover, preclinical and preliminary clinical evidence suggests that minocycline possesses antidepressant properties. Herein, we provide the rationale for conducting a randomized, controlled trial to test the antidepressant properties of minocycline. (C) 2012 Elsevier B.V. All rights reserved.Eli LillyJanssen-OrthoAstra ZenecaBristol-Meyers SquibbClera, Inc.Glaxo Smith KlineLundbeckPfizerServierSt. Jude MedicalConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Toronto Rehabilitation InstituteHeart and Stroke Foundation Centre for Stroke RecoveryStanley Medical Research InstituteNational Alliance for Research on Schizophrenia and Depression (NARSAD)National Institutes of Mental HealthShireAstra-ZenecaForestSepracorUniv Toronto, Mood Disorders Psychopharmacol Unit, Univ Hlth Network, Dept Psychiat, Toronto, ON M5T 2S8, CanadaUniv Toronto, Inst Med Sci, Toronto, ON M5T 2S8, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilUniv Toronto, Dept Pharmacol, Toronto, ON M5T 2S8, CanadaUniv Toronto, Dept Toxicol, Toronto, ON M5T 2S8, CanadaSunnybrook Hlth Sci Ctr, Neuropsychopharrnacol Res Grp, Toronto, ON M4N 3M5, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals Risk Men, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci LINC, São Paulo, BrazilWeb of Scienc

Advancing biomarker research: utilizing 'Big Data' approaches for the characterization and prevention of bipolar disorder

Objective: To provide a strategic framework for the prevention of bipolar disorder (BD) that incorporates a 'Big Data' approach to risk assessment for BD.Methods: Computerized databases (e. g., Pubmed, PsychInfo, and MedlinePlus) were used to access English-language articles published between 1966 and 2012 with the search terms bipolar disorder, prodrome, 'Big Data', and biomarkers cross-referenced with genomics/genetics, transcriptomics, proteomics, metabolomics, inflammation, oxidative stress, neurotrophic factors, cytokines, cognition, neurocognition, and neuroimaging. Papers were selected from the initial search if the primary outcome(s) of interest was (were) categorized in any of the following domains: (i) 'omics' (e. g., genomics), (ii) molecular, (iii) neuroimaging, and (iv) neurocognitive.Results: the current strategic approach to identifying individuals at risk for BD, with an emphasis on phenotypic information and family history, has insufficient predictive validity and is clinically inadequate. the heterogeneous clinical presentation of BD, as well as its pathoetiological complexity, suggests that it is unlikely that a single biomarker (or an exclusive biomarker approach) will sufficiently augment currently inadequate phenotypic-centric prediction models. We propose a 'Big Data'-bioinformatics approach that integrates vast and complex phenotypic, anamnestic, behavioral, family, and personal 'omics' profiling. Bioinformatic processing approaches, utilizing cloud-and grid-enabled computing, are now capable of analyzing data on the order of tera-, peta-, and exabytes, providing hitherto unheard of opportunities to fundamentally revolutionize how psychiatric disorders are predicted, prevented, and treated. High-throughput networks dedicated to research on, and the treatment of, BD, integrating both adult and younger populations, will be essential to sufficiently enroll adequate samples of individuals across the neurodevelopmental trajectory in studies to enable the characterization and prevention of this heterogeneous disorder.Conclusions: Advances in bioinformatics using a 'Big Data' approach provide an opportunity for novel insights regarding the pathoetiology of BD. the coordinated integration of research centers, inclusive of mixed-age populations, is a promising strategic direction for advancing this line of neuropsychiatric research.Stanley Medical Research InstituteNational Alliance for Research on Schizophrenia and DepressionNational Institute of Mental HealthAstraZenecaBristol-Myers SquibbEli Lilly Co.ForestJanssen-OrthoLundbeckPfizerSepracorShireNational Institute of HealthNeuropsychopharmacology Research GroupSunnybrook Research InstituteToronto Rehabilitation InstituteHeart and Stroke Foundation Centre for Stroke RecoveryEli Lilly Fellowship AwardConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Toronto, Dept Psychiat, Toronto, ON M5T 2S8, CanadaUniv Toronto, Dept Pharmacol, Toronto, ON M5T 2S8, CanadaUniv Hlth Network, Mood Disorders Psychopharmacol Unit, Toronto, ON, CanadaUniv Toronto, Inst Med Sci, Toronto, ON M5T 2S8, CanadaUniv S Carolina, Sch Med, Dept Neuropsychiat, Columbia, SC USASunnybrook Res Inst, Toronto, ON, CanadaUniv Fed Rio Grande do Sul, Psychiat Residents Hosp Clin Porto Alegre, Porto Alegre, RS, BrazilQueens Univ, Ctr Neurosci Studies, Kingston, ON, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals At Risk, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci, São Paulo, BrazilMt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, CanadaUniversidade Federal de São Paulo, Dept Psychiat, Program Recognit & Intervent Individuals At Risk, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, Interdisciplinary Lab Clin Neurosci, São Paulo, BrazilWeb of Scienc

Correction to: DNA copy number evolution in Drosophila cell lines

Following publication of the original article [1], the authors reported the following errors