Spot the difference: Comparing results of analyses from real patient data and synthetic derivatives

BACKGROUND: Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification. OBJECTIVES: To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd., Beer Sheva, Israel) for its ability to produce data that can be used for research purposes while obviating privacy and confidentiality concerns. METHODS: We explored three use cases and tested the robustness of synthetic data by comparing the results of analyses using synthetic derivatives to analyses using the original data using traditional statistics, machine learning approaches, and spatial representations of the data. We designed these use cases with the purpose of conducting analyses at the observation level (Use Case 1), patient cohorts (Use Case 2), and population-level data (Use Case 3). RESULTS: For each use case, the results of the analyses were sufficiently statistically similar ( DISCUSSION AND CONCLUSION: This article presents the results of each use case and outlines key considerations for the use of synthetic data, examining their role in clinical research for faster insights and improved data sharing in support of precision healthcare

A cross dialectal view of the Arabic dative alternation

This paper is concerned with the syntax of ditransitive verbs in Arabic.We concentrate on the vernaculars, focussing in particular on three geographically spread dialects: Egyptian Cairene Arabic, the dominant vernacular in Egypt, Hijazi Arabic, spoken in Western Saudi Arabia and Maltese, a mixed language with a Magrebi/Siculo-Arabic stratum. We show that all three exhibit an alternation (the dative alternation) between a ditransitive ('double object') construction and a corresponding prepositional dative construction, and outline a number of differences between these constructions in the different varieties of Arabic. We consider the distribution of verbs exhibiting the dative alternation in the light of Ryding's (2011) observations concerning Modern Standard Arabic

Critical analysis of information security culture definitions

This article aims to advance the understanding of information security culture through a critical reflection on the wide-ranging definitions of information security culture in the literature. It uses the hermeneutic approach for conducting literature reviews. The review identifies 16 definitions of information security culture in the literature. Based on the analysis of these definitions, four different views of culture are distinguished. The shared values view highlights the set of cultural value patterns that are shared across the organization. An action-based view highlights the behaviors of individuals in the organization. A mental model view relates to the abstract view of the individual’s thinking on how information security culture must work. Finally, a problem-solving view emphasizes a combination of understanding from shared value-based and action-based views. The paper analyzes and presents the limitations of these four views of information security culture definitions

R5-SHIV Induces Multiple Defects in T Cell Function during Early Infection of Rhesus Macaques Including Accumulation of T Reg Cells in Lymph Nodes

Background: HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues. Methods: Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation. Results/Conclusions: We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection

Altering an Artificial Gagpolnef Polyprotein and Mode of ENV Co-Administration Affects the Immunogenicity of a Clade C HIV DNA Vaccine

HIV-1 candidate vaccines expressing an artificial polyprotein comprising Gag, Pol and Nef (GPN) and a secreted envelope protein (Env) were shown in recent Phase I/II clinical trials to induce high levels of polyfunctional T cell responses; however, Env-specific responses clearly exceeded those against Gag. Here, we assess the impact of the GPN immunogen design and variations in the formulation and vaccination regimen of a combined GPN/Env DNA vaccine on the T cell responses against the various HIV proteins. Subtle modifications were introduced into the GPN gene to increase Gag expression, modify the expression ratio of Gag to PolNef and support budding of virus-like particles. I.m. administration of the various DNA constructs into BALB/c mice resulted in an up to 10-fold increase in Gag- and Pol-specific IFNγ+ CD8+ T cells compared to GPN. Co-administering Env with Gag or GPN derivatives largely abrogated Gag-specific responses. Alterations in the molar ratio of the DNA vaccines and spatially or temporally separated administration induced more balanced T cell responses. Whereas forced co-expression of Gag and Env from one plasmid induced predominantly Env-specific T cells responses, deletion of the only H-2d T cell epitope in Env allowed increased levels of Gag-specific T cells, suggesting competition at an epitope level. Our data demonstrate that the biochemical properties of an artificial polyprotein clearly influence the levels of antigen-specific T cells, and variations in formulation and schedule can overcome competition for the induction of these responses. These results are guiding the design of ongoing pre-clinical and clinical trials

Deterrence in Cyberspace: An Interdisciplinary Review of the Empirical Literature

The popularity of the deterrence perspective across multiple scientific disciplines has sparked a lively debate regarding its relevance in influencing both offenders and targets in cyberspace. Unfortunately, due to the invisible borders between academic disciplines, most of the published literature on deterrence in cyberspace is confined within unique scientific disciplines. This chapter therefore provides an interdisciplinary review of the issue of deterrence in cyberspace. It begins with a short overview of the deterrence perspective, presenting the ongoing debates concerning the relevance of deterrence pillars in influencing cybercriminals’ and cyberattackers’ operations in cyberspace. It then reviews the existing scientific evidence assessing various aspects of deterrence in the context of several disciplines: criminology, law, information systems, and political science. This chapter ends with a few policy implications and proposed directions for future interdisciplinary academic research

Representation of the verb's argument-structure in the human brain

<p>Abstract</p> <p>Background</p> <p>A verb's argument structure defines the number and relationships of participants needed for a complete event. One-argument (intransitive) verbs require only a subject to make a complete sentence, while two- and three-argument verbs (transitives and ditransitives) normally take direct and indirect objects. Cortical responses to verbs embedded into sentences (correct or with syntactic violations) indicate the processing of the verb's argument structure in the human brain. The two experiments of the present study examined whether and how this processing is reflected in distinct spatio-temporal cortical response patterns to isolated verbs and/or verbs presented in minimal context.</p> <p>Results</p> <p>The magnetoencephalogram was recorded while 22 native German-speaking adults saw 130 German verbs, presented one at a time for 150 ms each in experiment 1. Verb-evoked electromagnetic responses at 250 – 300 ms after stimulus onset, analyzed in source space, were higher in the left middle temporal gyrus for verbs that take only one argument, relative to two- and three-argument verbs. In experiment 2, the same verbs (presented in different order) were preceded by a proper name specifying the subject of the verb. This produced additional activation between 350 and 450 ms in or near the left inferior frontal gyrus, activity being larger and peaking earlier for one-argument verbs that required no further arguments to form a complete sentence.</p> <p>Conclusion</p> <p>Localization of sources of activity suggests that the activation in temporal and frontal regions varies with the degree by which representations of an event as a part of the verbs' semantics are completed during parsing.</p