PrEP (HIV pre-exposure prophylaxis) and its possibilities for clinical practice

In this article, we reflect on the possibilities that PrEP (HIV pre-exposure prophylaxis) raises for HIV specialist clinicians. Often neglected, yet a direct participant at the intersection of a complex tension within public health debates on how to reduce HIV transmission and the sexual sociability of individuals, we reflect on current thinking of health practitioners involved in the day-to-day practice of prescribing PrEP. Drawing on interviews with practitioners in the context of UK sexual health and HIV specialist medicine, while bearing in mind neoliberal critiques and process studies of medical science, we propose that PrEP invites the possibility for reconstituting approaches to sex and risk

Argumentum ad misericordiam - the critical intimacies of victimhood

This article discusses the widespread use of victim tropes in contemporary Anglo-American culture by using cultural theory to analyse key social media memes circulating on Facebook in 2015. Since the growth of social media, victim stories have been proliferating, and each demands a response. Victim narratives are rhetorical, they are designed to elicit pity and shame the perpetrator. They are deployed to stimulate political debate and activism, as well as to appeal to an all-purpose humanitarianism. Victimology has its origins in Law and Criminology, but this paper opens up the field more broadly to think about the cultural politics of victimhood, to consider how the victim-figure can be appropriated by/for different purposes, particularly racial and gender politics, including in the case of Rachel Dolezal, and racial passing. In formulating an ethical response to the lived experience of victims, we need to think about the different kinds of critical intimacies elicited by such media

Risk, reassurance and routine: a qualitative study of narrative understandings of the potential for HIV self-testing among men who have sex with men in England

BACKGROUND: HIV testing has seen a rapid evolution over the last decade with multiple modalities now in use globally. In recent years HIV self-testing (HIVST) has been legalised in the UK paving the way for further expansion of testing. Interventions are delivered in particular social contexts which shape uptake. It is therefore important to understand how novel interventions are likely to be received by their intended users. This study aims to understand how HIVST compliments existing testing strategies considered or adopted by men who have sex with men (MSM). We do this by analysing normative discourses surrounding HIV testing and their perceptions of HIVST's potential future roles. METHODS: Six focus group discussions (FGDs) were conducted with 47 MSM in London, Manchester and Plymouth. One focus group included only MSM who reported higher risk behaviours and one with those who had never tested for HIV. Data were analysed through a thematic framework analysis. RESULTS: Three main narratives for testing for HIV were identified: (i) testing in response to a specific risk event; (ii) as reassurance when there was a small amount of doubt or anxiety related to HIV; and (iii) in response to social norms perpetuated through peers, HIV community groups and the medical establishment to test regularly for HIV. HIVST had limited utility for men when testing in response to specific risk events except in the case of significant structural barriers to other testing opportunities. HIVST was considered to have utility when seeking reassurance, and was thought to be very useful when testing to satisfy the needs and expectations of others around regular testing. There was some ambivalence about the incursion of a clinical intervention into the home. CONCLUSIONS: HIVST following risk events will likely be limited to those for whom existing service provision is insufficient to meet immediate needs based on structural or personal barriers to testing. Obligations of biological citizenship are central to MSM's understanding of the utility of HIVST. In the context of discourses of biocitizenship, men perceive HIVST to have dual roles: firstly as a tool to manage (mild) anxiety around one's HIV status based on an acknowledgment of HIV vulnerability arising from being homosexually active. Secondly, HIVST is useful in complying with social norms and meeting the perceived demands of biomedicine

Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain

Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro

Loop Interactions during Catalysis by Dihydrofolate Reductase fromMoritella profunda

Dihydrofolate reductase (DHFR) is often used as a model system to study the relation between protein dynamics and catalysis. We have studied a number of variants of the cold-adapted DHFR from Moritella profunda (MpDHFR), in which the catalytically important M20 and FG loops have been altered, and present a comparison with the corresponding variants of the wellstudied DHFR from Escherichia coli (EcDHFR). Mutations in the M20 loop do not affect the actual chemical step of transfer of hydride from reduced nicotinamide adenine dinucleotide phosphate to the substrate 7,8-dihydrofolate in the catalytic cycle in either enzyme; they affect the steady state turnover rate in EcDHFR but not in MpDHFR. Mutations in the FG loop also have different effects on catalysis by the two DHFRs. Despite the two enzymes most likely sharing a common catalytic cycle at pH 7, motions of these loops, known to be important for progression through the catalytic cycle in EcDHFR, appear not to play a significant role in MpDHFR

Geo-Engineering through Internet Informatics (GEMINI)

The program, for development and methodologies, was a 3-year interdisciplinary effort to develop an interactive, integrated Internet Website named GEMINI (Geo-Engineering Modeling through Internet Informatics) that would build real-time geo-engineering reservoir models for the Internet using the latest technology in Web applications

Revision of Stratigraphic Nomenclature and Classification of the Pleasanton, Kansas City, Lansing, and Lower Part of the Douglas Groups (Lower Upper Pennsylvanian, Missourian) in Kansas

Correction of several long-standing miscorrelations within the Missourian succession in Kansas has resulted from recent field work along outcrop and has been substantiated by near-surface drilling. This requires some revision of nomenclature and classification of this succession of rocks so that its stratigraphy is clarified and sufficiently characterized to facilitate its utilization in the interpretation of geologic history and assessment of resources. The revision also is timely for consideration of the succession in the pending selection of international Series/Stage boundary stratotypes. New formations now recognized in Kansas are the Hepler and Shale Hill Formations in the Pleasanton Group; the Elm Branch Shale and Mound Valley Limestone, both essentially reinstated, in the Bronson Subgroup of the Kansas City Group; the Nellie Bly Formation and Dewey Limestone, both newly extended into Kansas (from Oklahoma) in the Linn Subgroup of the Kansas City Group; the Liberty Memorial Shale, reinstated (from Missouri) in the Zarah Subgroup of the Kansas City Group; and the Cass Limestone, newly extended into Kansas (from Nebraska) in the middle of the Douglas Group. In addition, the Coffeyville Group is now recognized in southern Kansas to more adequately characterize the southward facies transition of the upper Pleasanton and lower Kansas City Groups (most of the Bronson Subgroup). Several formations previously recognized in Kansas have been revised (Tacket Formation, Hertha Limestone, Cherryvale Formation, Wyandotte Limestone, Lane Shale, Stanton Limestone), with members shifted from or to adjacent formations. Two members are raised in rank (Rock Lake Shale and South Bend Limestone); four members are extended into Kansas from surrounding areas (Exline Limestone Member of Shale Hill Formation, Gretna Shale Member of South Bend Limestone, Little Pawnee Shale Member and Shoemaker Limestone Member ofCass Limestone); one member is reinstated (Little Kaw Limestone Member of South Bend Limestone); and two members are newly defined in Kansas (Mantey Shale Member and Guthrie Mountain Shale Member of Shale Hill Formation)

Geo-Engineering Modeling Through Internet Informatics (GEMINI)

GEMINI (Geo-Engineering Modeling through Internet Informatics) is a public-domain web application focused on analysis and modeling of petroleum reservoirs and plays (http://www.kgs.ukans.edu/Gemini/index.html). GEMINI creates a virtual project by ''on-the-fly'' assembly and analysis of on-line data either from the Kansas Geological Survey or uploaded from the user. GEMINI's suite of geological and engineering web applications for reservoir analysis include: (1) petrofacies-based core and log modeling using an interactive relational rock catalog and log analysis modules; (2) a well profile module; (3) interactive cross sections to display ''marked'' wireline logs; (4) deterministic gridding and mapping of petrophysical data; (5) calculation and mapping of layer volumetrics; (6) material balance calculations; (7) PVT calculator; (8) DST analyst, (9) automated hydrocarbon association navigator (KHAN) for database mining, and (10) tutorial and help functions. The Kansas Hydrocarbon Association Navigator (KHAN) utilizes petrophysical databases to estimate hydrocarbon pay or other constituent at a play- or field-scale. Databases analyzed and displayed include digital logs, core analysis and photos, DST, and production data. GEMINI accommodates distant collaborations using secure password protection and authorized access. Assembled data, analyses, charts, and maps can readily be moved to other applications. GEMINI's target audience includes small independents and consultants seeking to find, quantitatively characterize, and develop subtle and bypassed pays by leveraging the growing base of digital data resources. Participating companies involved in the testing and evaluation of GEMINI included Anadarko, BP, Conoco-Phillips, Lario, Mull, Murfin, and Pioneer Resources