128 research outputs found
Lifeworld Inc. : and what to do about it
Can we detect changes in the way that the world turns up as they turn up? This paper makes such an attempt. The first part of the paper argues that a wide-ranging change is occurring in the ontological preconditions of Euro-American cultures, based in reworking what and how an event is produced. Driven by the security – entertainment complex, the aim is to mass produce phenomenological encounter: Lifeworld Inc as I call it. Swimming in a sea of data, such an aim requires the construction of just enough authenticity over and over again. In the second part of the paper, I go on to argue that this new world requires a different kind of social science, one that is experimental in its orientation—just as Lifeworld Inc is—but with a mission to provoke awareness in untoward ways in order to produce new means of association. Only thus, or so I argue, can social science add to the world we are now beginning to live in
Biologically inspired simulation of livor mortis
We present a biologically motivated livor mortis simulation that is capable of modelling the colouration changes in skin caused by blood pooling after death. Our approach consists of a simulation of post mortem blood dynamics and a layered skin shader that is controlled by the haemoglobin and oxygen levels in blood. The object is represented by a layered data structure made of a triangle mesh for the skin and a tetrahedral mesh on which the blood dynamics are simulated. This allows us to simulate the skin discolouration caused by livor mortis, including early patchy appearance, fixation of hypostasis and pressure induced blanching. We demonstrate our approach on two different models and scenarios and compare the results to real world livor mortis photographic examples
Exploration of piperidine 3D fragment chemical space : synthesis and 3D shape analysis of fragments derived from 20 regio- and diastereoisomers of methyl substituted pipecolinates
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2D molecules. Herein, we report the synthesis of piperidine-based 3D fragment building blocks - 20 regio- and diastereoisomers of methyl substituted pipecolinates using simple and general synthetic methods. cis-Piperidines, accessed through a pyridine hydrogenation were transformed into their trans-diastereoisomers using conformational control and unified reaction conditions. Additionally, diastereoselective lithiation/trapping was utilised to access trans-piperidines. Analysis of a virtual library of fragments derived from the 20 cis- and trans-disubstituted piperidines showed that it consisted of 3D molecules with suitable molecular properties to be used in fragment-based drug discovery programs
Design and Synthesis of 56 Shape Diverse 3-D Fragments
Fragment-based drug discovery is now widely adopted for lead generation in the pharmaceutical industry. However, fragment screening collections are often predominantly populated with flat, 2-D molecules. Herein, we describe a workflow for the design and synthesis of 56 3-D disubstituted pyrrolidine and piperidine fragments that occupy under-represented areas of fragment space (as demonstrated by a principal moments of inertia (PMI) analysis). A key, and unique, underpinning design feature of this fragment collection is that assessment of fragment shape and conformational diversity (by considering conformations up to 1.5 kcal mol -1 above the energy of the global minimum energy conformer) is carried out prior to synthesis and is also used to select targets for synthesis. The 3-D fragments were designed to contain suitable synthetic handles for future fragment elaboration. Finally, by comparing our 3-D fragments with six commercial libraries, it is clear that our collection has high three-dimensionality and shape diversity
Acute immune signatures and their legacies in severe acute respiratory syndrome coronavirus-2 infected cancer patients
Given the immune system’s importance for cancer surveillance and treatment, we have investigated how it
may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type,
stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2,
apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients.
This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus
shedding. Furthermore, while recovered solid cancer patients’ immunophenotypes resemble those of nonvirus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at
risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer
patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform
their care
Exercising control at the urban scale: Towards a theory of spatial organisation and surveillance
The purpose of this chapter is to explore how urban spaces are implicated in the control and surveillance of users in a culture saturated by the notion of the self as a consuming body or entity. Using the work of Foucault on disciplinary cultures, Lefebvre in relation to the production of space, and other seminal theorists such as Baudrillard, Bauman, Shields, and Walzer, a model for analysing the three dimensions of social spatialisation is proposed and illustrated by reference to contemporary public spaces, and specifically spaces of mundane leisure such as shopping malls and high streets. The chapter deals with how the public realm as a controlling space has been theorised in terms of opposition to such controlling tendencies—from the flaneur, through the self-constructed narratives of De Certeau’s walker to the digitally ‘enhanced’ individual today, appropriating space via technology and their own projects in tinder and so on, and other potentially subversive media
The 'living of time': entangled temporalities of home and the city
This paper explores the entanglements between urban and domestic temporalities in order to understand what it means to live in the city. Inspired by the film Estate: a reverie (Zimmerman, 2015a), and drawing on a series of home-city biographies, this paper explores the ‘living of time’ through the memories, experiences, and narratives of residents
living on different housing estates near Kingsland Road in Hackney, East London. We address two key questions: how are residents' experiences of urban living shaped by multi-layered and entangled temporalities of home and the city? What can an understanding of the urban and domestic 'living of time’ reveal about temporality, home and the city? We explore the ways in which entangled and multi-scalar ‘roots’ and ‘routes’
(Clifford, 1997) chart migration, housing and family histories for urban residents which, in turn, shape and help to articulate narratives of domestic and urban change in terms of stability and instability. We then turn to the overlapping and/or contested temporalities of urban and domestic lives, whereby residents’ home lives – and their wider ideas about the estate, street, neighbourhood or city as home – are affected
by processes of urban change in complex and often contradictory ways. Finally, we investigate the ways in which home-city temporalities have shaped, and are shaped by, people’s hopes and fears for their future homes. Urban dwelling is shaped by multiple and multi-layered temporalities, intertwining the past, present and future, generations and
life courses, and housing, family and migration histories. The urban and domestic ‘living of time’ reveals how residents adapt to, negotiate and at times resist processes of change and continuity at home and in the city
Moving through a dappled world: the aesthetics of shade and shadow in place
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. In addressing geography’s neglect of shade and shadow, this paper explores how the dynamic play of shadow and light constitutes an integral part of everyday affective and sensory attunement to place and guides pedestrian movement. First, we identify how particular shadows are shaped by distinctive kinds of solar radiance, material forms, human visual perception and cultural representations. We then consider the different cultural ways in which shade and shadow have been interpreted across space and time and identify diverse shadowy effects in different geographical contexts. Thereafter, we focus on particular key elements of central Melbourne’s shadow aesthetics, discuss how patterns of shade guide urban choreographies, and explore how architects have imaginatively manipulated shadow
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
Background:
Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings:
Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79).
Interpretation:
In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research
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