Geospatial analysis and living urban geometry

This essay outlines how to incorporate morphological rules within the exigencies of our technological age. We propose using the current evolution of GIS (Geographical Information Systems) technologies beyond their original representational domain, towards predictive and dynamic spatial models that help in constructing the new discipline of "urban seeding". We condemn the high-rise tower block as an unsuitable typology for a living city, and propose to re-establish human-scale urban fabric that resembles the traditional city. Pedestrian presence, density, and movement all reveal that open space between modernist buildings is not urban at all, but neither is the open space found in today's sprawling suburbs. True urban space contains and encourages pedestrian interactions, and has to be designed and built according to specific rules. The opposition between traditional self-organized versus modernist planned cities challenges the very core of the urban planning discipline. Planning has to be re-framed from being a tool creating a fixed future to become a visionary adaptive tool of dynamic states in evolution

Phosphoryl Transfers of the Phospholipase D Superfamily: A Quantum Mechanical Theoretical Study

The HKD-containing Phospholipase D superfamily catalyzes the cleavage of the headgroup of phosphatidylcholine to produce phosphatidic acid and choline. The mechanism of this cleavage process is studied theoretically. The geometric basis of our models is the X-ray crystal structure of the five-coordinate phosphohistidine intermediate from Streptomyces sp. Strain PMF (PDB Code = 1V0Y). Hybrid ONIOM QM:QM methodology with Density Functional Theory (DFT) and semiempirical PM6 (DFT:PM6) is used to acquire thermodynamic and kinetic data for the initial phosphoryl transfer, subsequent hydrolysis, and finally, the formation of the experimentally observed ″dead-end″ phosphohistidine product (PDB Code = 1V0W). The model contains nineteen amino acid residues (including the two highly conserved HKD-motifs), four explicit water molecules, and the substrate. Via computations, the persistence of the short-lived five-coordinate phosphorane intermediate on the minutes times scale is rationalized. This five-coordinate phosphohistidine intermediate energetically exists between the hydrolysis event and ″substrate reorganization″ (the reorganization of the in vitro model substrate within the active site). Computations directly support the thermodynamic favorability of the in vitro four-coordinate phosphohistidine product. In vivo, the activation energy of substrate reorganization is too high, perhaps due to a combination of substrate immobility when embedded in the lipid bilayer, as well as its larger steric bulk compared to the compound used in the in vitro substrate soaks. On this longer time scale, the enzyme will migrate along the lipid membrane toward its next substrate target, rather than promote the formation of the dead-end product. © 2013 American Chemical Society

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. Methods: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic—from March 1 to Sept 13, 2020—at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. Findings: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46–60]) were included in the study. Median ECMO duration was 15 days (IQR 8–27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. Interpretation: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. Funding: None