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BackgroundPrurigo nodularis is a chronic skin disease characterised by intensely pruritic, hyperkeratotic nodules. Vixarelimab, a human monoclonal antibody, binds to the beta subunit of the oncostatin M receptor, inhibiting signalling of both interleukin 31 and oncostatin M, two cytokine pathways that contribute to pruritus and nodule formation in prurigo nodularis.MethodsThis double-blind, placebo-controlled, phase 2a trial was done at both private and academic dermatology outpatient research clinics across the United States and Canada (n = 40). Patient eligibility criteria included age 18-75 years, physician-documented diagnosis of prurigo nodularis minimum 6 months duration of prurigo nodularis, presence of at least 10 pruritic nodules approximately 0.5-2 cm in size on at least two different anatomical locations (excluding face and scalp) and involving the extremities, and presence of normal-appearing skin between nodules; atopic dermatitis as a comorbidity was exclusionary. Patients were required to have moderate-to-severe pruritus, defined as Worst Itch-Numeric Rating Scale (WI-NRS) score ≥7 at screening and LS-mean weekly WI-NRS score ≥5 for each of the 2 consecutive weeks immediately before randomisation. Participants were randomly assigned (1:1) to receive weekly subcutaneous vixarelimab 360 mg (720 mg loading dose) or placebo using stratification factors (sex and presence of atopy) and block size 4 through the IWRS system. Stratification by atopy status was based on the reported high prevalence of atopy in this population and the potential impact of atopy in the immunopathologic process in prurigo nodularis. Patients, investigators, study sponsor, and site staff were masked to study treatment. The primary efficacy endpoint was least squares (LS)-mean percent change from baseline (PCFB) at Week 8 in weekly average Worst Itch-Numeric Rating Scale (WI-NRS) score. The primary efficacy endpoint was analysed with ANCOVA including treatment as fixed effect, with baseline WI-NRS, and randomisation stratification factor as covariates. All randomised patients who had at least 1 dose of study drug or placebo were included in the Safety Analysis Set. This trial is registered at ClinicalTrials.gov, NCT03816891.FindingsOf 50 patients randomised between March 11, 2019 and January 31, 2020, 23 vixarelimab recipients and 26 placebo recipients comprised the modified intent-to-treat analysis population (baseline LS-mean [SD] WI-NRS score, 8.3 [1.05]). Outcomes at Week 8 for vixarelimab versus placebo included LS-mean PCFB in WI-NRS score, -50.6% versus -29.4% (LS-mean difference [95% CI], -21.2% [-40.82, -1.60]; p = 0.03); ≥4-point reduction in WI-NRS score, 52.2% (12/23) versus 30.8% (8/26) (p = 0.11); PN-IGA score of 0 or 1, 30.4% (7/23) versus 7.7% (2/26) (p = 0.03); LS-mean PCFB in pruritus VAS score, -54.4% versus -32.6% (p = 0.03); and LS-mean PCFB sleep loss reduction (improvement), -56.3% versus -30.0% (p = 0.02). No deaths, serious TEAEs, or TEAEs leading to dose interruption were reported. The percentage of vixarelimab recipients reporting any TEAE was 91.3% (21/23) versus 76.9% (20/26) of placebo recipients; drug-related TEAEs generally were similar between the two groups (vixarelimab, 43.5% [10/23]; placebo, 38.5% [10/26]).InterpretationVixarelimab demonstrated rapid reduction of pruritus and achievement of clear/almost clear skin in one-third of the patients by Week 8. Relief of itch and clearing of skin nodules represent two important potential therapeutic advances in the management of patients suffering from the debilitating disease Prurigo Nodularis.FundingKiniksa Pharmaceuticals, Ltd.

To analyse oil, the world's most traded commodity, we combine Global Production Network (GPN) and Global Financial Network (GFN) approaches into the Global Production and Financial Network (GPFN). The combination offers a dynamic framework, as key actors and geographies in the GPFN change over time. It brings together the production and financial strands of research on oil and overcomes the physical reality v. financial fiction dichotomy in literature. Using a wide range of data on oil networks, prices, historical accounts, as well as industry, media and policy reports, we apply the GPFN to explain the evolution of oil networks, since their inception, as well as the mid- and short-term price anomalies since 2010. Our history of oil GPFN demonstrates the stability of its analytical categories and the stickiness of power wielded by some actors and geographies, while others come and go. Our account of price anomalies shows the inseparability of physical and financial factors in explaining them. As whole the GFPN is an opportunity to understand the evolving broad structures, distribution of power and price formation in markets, and as such represents a way forward for studying other products and sectors. [ABSTRACT FROM AUTHOR]

As the final days of 1 997 tick away and we ready ourselves for the New Year and the approach of the 'millenium, we are struck by the coincidence of two important planning anniversaries. The Department of City and Regional Planning (DCRPI at the University of California, Berkeley, founded in 1948, commemorates its jubilee anniversary this year. DCRP celebrates a proud history of readily evolving and changing with the planning discipline as well as provoking changes to it.

This article surveys the presence of the Unorganized American Militia movement on computer networks and explores how the Militia movement uses computer networks to build an Mimagined network communityw. The transformation of computer networks from a tool of the academic elite to a mass consumption commodity offers new poten tial for social organization. This transformation also allows for new conceptions of community and the way relationships based on shared identities are built. This article argues that computer communications can h elp communities imagine themselves and expand.

Despite the prevalence of transparency discourses in economic life (e.g., postcrisis socioeconomic reforms), scholarship is just beginning to analyze how these discourses produce new relations between market actors in platform economies. In this article, we argue that in the context of financial markets and the political economy of data, transparency functions as a discursive construction that creates suitable conditions for the manufacture and extraction of data as an asset. First, we examine the role of transparency and opacity in various understandings of the 2007–2008 global financial crisis (GFC). In doing so we link the emergence of FinTech firms to a careful ex post facto reconstruction of the GFC as what we term a "crisis of data." Then, through problematizing the idea that transparent economic relations necessarily lead to greater accountability, equity, or public good, we argue that transparency is better understood as a relational practice that is continuously and contingently renegotiated. Taking up the example of debt data, we provide case studies of the data brokerage companies BlackRock and dv01 to analyze how transparency constitutes the material infrastructure of debt markets, which facilitates the construction of data assets for profitable circulation in a financialized political economy. We analyze our case studies with a focus on four transparency practices used to infuse data with value—building relationality, increasing granularity, managing directionality, and creating legibility. [ABSTRACT FROM AUTHOR]

This article presents an overview and initial results of a geoweb analysis designed to provide the foundation for a continued discussion of the potential impacts of 'big data' for the practice of critical human geography. While Haklay's (2012) observation that social media content is generated by a small number of 'outliers' is correct, we explore alternative methods and conceptual frameworks that might allow for one to overcome the limitations of previous analyses of user-generated geographic information. Though more illustrative than explanatory, the results of our analysis suggest a cautious approach toward the use of the geoweb and big data that are as mindful of their shortcomings as their potential. More specifically, we propose five extensions to the typical practice of mapping georeferenced data that we call going 'beyond the geotag': (1) going beyond social media that is explicitly geographic; (2) going beyond spatialities of the 'here and now'; (3) going beyond the proximate; (4) going beyond the human to data produced by bots and automated systems, and (5) going beyond the geoweb itself, by leveraging these sources against ancillary data, such as news reports and census data. We see these extensions of existing methodologies as providing the potential for overcoming existing limitations on the analysis of the geoweb. The principal case study focuses on the widely reported riots following the University of Kentucky men's basketball team's victory in the 2012 NCAA championship and its manifestation within the geoweb. Drawing upon a database of archived Twitter activity including all geotagged tweets since December 2011 we analyze the geography of tweets that used a specific hashtag (#LexingtonPoliceScanner) in order to demonstrate the potential application of our methodological and conceptual program. By tracking the social, spatial, and temporal diffusion of this hashtag, we show how large databases of such spatially referenced internet content can be used in a more systematic way for critical social and spatial analysis. Keywords: geoweb; #LexingtonPoliceScanner; big data; Twitter; geotag, Introduction On 2 April 2012, following the victory of the University of Kentucky Wildcats men's basketball team in the NCAA championship game, a spontaneous celebration of fans spilled into the [...]