Elementary Forms of the Metaphorical Life : Tropes at Work in Durkheim’s Theory of the Religious

Peer reviewedPostprin

Prefácio

Prefácio ao Volume XI, Número 2, Ano 201

Prefácio

Prefácio ao Volume XI, Número 1, Ano 201

A Framework for Multi-Omic Prediction of Treatment Response to Biologic Therapy for Psoriasis.

Biologic therapies have shown high efficacy in psoriasis, but individual response varies and is poorly understood. To inform biomarker discovery in the Psoriasis Stratification to Optimise Relevant Therapy (i.e., PSORT) study, we evaluated a comprehensive array of omics platforms across three time points and multiple tissues in a pilot investigation of 10 patients with severe psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used RNA sequencing to analyze mRNA and small RNA transcriptome in blood, lesional and nonlesional skin, and the SOMAscan platform to investigate the serum proteome. Using an integrative systems biology approach, we identified signals of treatment response in genes and pathways associated with TNF signaling, psoriasis pathology, and the major histocompatibility complex region. We found association between clinical response and TNF-regulated genes in blood and skin. Using a combination of differential expression testing, upstream regulator analysis, clustering techniques, and predictive modeling, we show that baseline samples are indicative of patient response to biologic therapies, including signals in blood, which have traditionally been considered unreliable for inference in dermatology. In conclusion, our pilot study provides both an analytical framework and empirical basis to estimate power for larger studies, specifically the ongoing PSORT study, which we show as powered for biomarker discovery and patient stratification

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states

Constitutivism

A brief explanation and overview of constitutivism

Ixazomib-lenalidomide-dexamethasone in routine clinical practice: Effectiveness in relapsed/refractory multiple myeloma

[Aim]: To evaluate the effectiveness and safety of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory multiple myeloma in routine clinical practice. Patients & methods: Patient-level data from the global, observational INSIGHT MM and the Czech Registry of Monoclonal Gammopathies were integrated and analyzed.[Results]: At data cut-off, 263 patients from 13 countries were included. Median time from diagnosis to start of IRd was 35.8 months; median duration of follow-up was 14.8 months. Overall response rate was 73%, median progression-free survival, 21.2 months and time-to-next therapy, 33.0 months. Ixazomib/lenalidomide dose reductions were required in 17%/36% of patients; 32%/30% of patients discontinued ixazomib/lenalidomide due to adverse events.[Conclusion]: The effectiveness and safety of IRd in routine clinical practice are comparable to those reported in TOURMALINE-MM1.This work was supported by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited

Light source selection for a solar simulator for thermal applications: A review

Solar simulators are used to test components and systems under controlled and repeatable conditions, often in locations with unsuitable insolation for outdoor testing. The growth in renewable energy generation has led to an increased need to develop, manufacture and test components and subsystems for solar thermal, photovoltaic (PV), and concentrating optics for both thermal and electrical solar applications. At the heart of any solar simulator is the light source itself. This paper reviews the light sources available for both low and high-flux solar simulators used for thermal applications. Criteria considered include a comparison of the lamp wavelength spectrum with the solar spectrum, lamp intensity, cost, stability, durability, and any hazards associated with use. Four main lamp types are discussed in detail, namely argon arc, the metal halide, tungsten halogen lamp, and xenon arc lamps. In addition to describing the characteristics of each lamp type, the popularity of usage of each type over time is also indicated. This is followed by guidelines for selecting a suitable lamp, depending on the requirements of the user and the criteria applied for selection. The appropriate international standards are also addressed and discussed. The review shows that metal halide and xenon arc lamps predominate, since both provide a good spectral match to the solar output. The xenon lamp provides a more intense and stable output, but has the disadvantages of being a high-pressure component, requiring infrared filtering, and the need of a more complex and expensive power supply. As a result, many new solar simulators prefer metal halide lamps

Pushing the Boundaries of Amnesia and Myopia: A Critical Review of the Literature on Identity in Management and Organization Studies

The aim of this article is to review a selection of the literature on identity at work in Management and Organization Studies (MOS) in order to raise critical questions concerning what we see as the dangers of a certain amnesia and myopia. Insofar as some of the contemporary literature neglects to engage with the historical and multidisciplinary past and present, there is a tendency to leave common-sense understandings of identity unexamined, thereby reproducing everyday preoccupations with securing the self. By contrast with such rational individualism, we seek a more embodied understanding of identity, where it is a means of building our ethical engagements and capacities for community living. By failing to problematize identity, there is little recognition of how attempts to secure the self are invariably self-defeating if only because they are necessarily contingent on the other who is unpredictable and uncontrollable. The main contribution of the article is to show how this failure to interrogate identity is far from benign since it often results in reinforcing everyday preoccupations with the self that can turn into narcissism, and deflect and curtail alternative practices of embodied engagement. We trust that our deliberations will be helpful in advancing the ‘road less travelled’, where studies advance beyond taking identity for granted, and move instead towards more embodied understandings of ethical engagement

A Densely Interconnected Genome-Wide Network of MicroRNAs and Oncogenic Pathways Revealed Using Gene Expression Signatures

MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA–pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA–pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA–pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes (“hubs”), most nodes in the miRNA–pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA–pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available