‘The Production of Space’, in: Frans Jacobi, Imagine, Space Poetry, Copenhagen, 1996, unpaginated.

The Production of Space

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

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A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

Genetics and analysis of quantitative traits

Transactions of the Institute of British Geographers

The spatial syntax of urban segregation

This paper summarises the latest theories in the field of space syntax. It opens with a discussion of the relationship between the form of urban grids and the process of how cities are formed by human activity; this is done by a comprehensive review of space syntax theory from its starting point in the1970s. The paper goes on to present research into how cities balance the micro-economic factors which shape the spatial structure of cities with the cultural factors that shape the underlying form of residential areas. It goes on to discuss the relationship between activity and space and how this relationship is formed by the way different activities make different demands on movement and co-presence. The paper ends with a discussion regarding the manner in which patterns of spatial integration influence the location of different classes and social groups in the city and contribute to the pathology of housing estates. The paper concludes that spatial form needs to be understood as a contributing factor in forming the patterns of integration and segregation in cities.

The city as one thing

As the pace of organisational change accelerates and as new technologies demand more rapid responses from organisations to changing conditions in their business environment, buildings are being called on to play an active role in helping to generate new organisational structures and in facilitating individual communication. This raises questions not only of the nature of organisational structure and of how communication technologies will affect that, but also of the possible mechanisms by which spatial structure can affect patterns of interaction in the work organisation. In this paper we will review two recent research-led design projects in which space syntax techniques were used to help define the building brief for an organisation which depends for its market lead on its ability to innovate. Building on research into the design of research laboratories, we found that patterns of space use and movement generated by spatial configuration have a direct impact on the frequency of contact between workers in office-based organisations. The frequency of contact is shown in turn to have an impact on work-related communications cited as 'useful' by questionnaire. These patterns are found to be 'system effects' in that they cannot be attributed to an individual worker's desk location but appear to result from the configuration of the whole system of spaces through which people move in their daily work, and have detectable effects on the mean 'usefulness' to others of all workers in a part of a building. The analysis suggests, however, that spatial integration alone may be insufficient to support flexible working and that spatial differentiation is necessary to provide the range of environments needed by different types of work activity.

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The space of innovation: interaction and communication in the work environment

Previous reports have implicated an induction of genes in IFN/STAT1 (Interferon/STAT1) signaling in radiation resistant and prosurvival tumor phenotypes in a number of cancer cell lines, and we have hypothesized that upregulation of these genes may be predictive of poor survival outcome and/or treatment response in Glioblastoma Multiforme (GBM) patients. We have developed a list of 8 genes related to IFN/STAT1 that we hypothesize to be predictive of poor survival in GBM patients. Our working hypothesis that over-expression of this gene signature predicts poor survival outcome in GBM patients was confirmed, and in addition, it was demonstrated that the survival model was highly subtype-dependent, with strong dependence in the Proneural subtype and no detected dependence in the Classical and Mesenchymal subtypes. We developed a specific multi-gene survival model for the Proneural subtype in the TCGA (the Cancer Genome Atlas) discovery set which we have validated in the TCGA validation set. In addition, we have performed network analysis in the form of Bayesian Network discovery and Ingenuity Pathway Analysis to further dissect the underlying biology of this gene signature in the etiology of GBM. We theorize that the strong predictive value of the IFN/STAT1 gene signature in the Proneural subtype may be due to chemotherapy and/or radiation resistance induced through prolonged constitutive signaling of these genes during the course of the illness. The results of this study have implications both for better prediction models for survival outcome in GBM and for improved understanding of the underlying subtype-specific molecular mechanisms for GBM tumor progression and treatment response.

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Expression signature of IFN/STAT1 signaling genes predicts poor survival outcome in glioblastoma multiforme in a subtype-specific manner.

In their News Focus article “Closing the net on common disease genes” (11 May, p. [820][1]), J. Couzin and J. Kaiser present an optimistic appraisal of genome-wide association (GWA) studies. Within the past year, Science has published results from seven GWA studies for obesity, cardiovascular

Laura Vaughan

Papers

The spatial syntax of urban segregation

The city as one thing

The space of innovation: interaction and communication in the work environment

Expression signature of IFN/STAT1 signaling genes predicts poor survival outcome in glioblastoma multiforme in a subtype-specific manner.

Problems with Genome-Wide Association Studies