Combustion and pyrolysis reactions of alkylated polycyclic aromatic compounds: The decomposition of 13C methylarenes in relation to diesel engine emissions

The thermal decomposition of methylarenes labelled with 13C in the methyl group was investigated. This was conducted using both a direct injection diesel engine and a pyrolysis flow cell connected to a GC-MS. 2-[13C]methylnaphthalene and 9-[13C]methylphenanthrene were synthesized by means of the Corey-House coupling reaction and their identity and purity confirmed by mass spectrometry and NMR. GC-MS analysis of the aromatic fraction separated from the extract of the exhaust particulate collected from the engine operated with n-hexadecane doped with the labelled methylnaphthalene showed that the 13C was not redistributed among the methyl groups of higher PAH. However, with 9-[13C]methylphenanthrene in the fuel a significant amount was retained in the particulate, even though the principal in-cylinder reaction was dealkylation. Pyrolytic reactions of the 13C-labelled methyl arenes were studied in a micro-pyrolysis-GC-MS-apparatus and confirmed dealkylation as the predominant reaction. The detailed chemical mechanism of the pyrolysis was explained by a scheme involving two alternative radical transfer reactions

Darwinism, organizational evolution and survival: key challenges for future research

How do social organizations evolve? How do they adapt to environmental pressures? What resources and capabilities determine their survival within dynamic competition? Charles Darwin’s seminal work The Origin of Species (1859) has provided a significant impact on the development of the management and organization theory literatures on organizational evolution. This article introduces the JMG Special Issue focused on Darwinism, organizational evolution and survival. We discuss key themes in the organizational evolution research that have emerged in recent years. These include the increasing adoption of the co-evolutionary approach, with a particular focus on the definition of appropriate units of analysis, such as routines, and related challenges associated with exploring the relationship between co-evolution, re-use of knowledge, adaptation, and exaptation processes. We then introduce the three articles that we have finally accepted in this Special Issue after an extensive, multi-round, triple blind-review process. We briefly outline how each of these articles contributes to understanding among scholars, practitioners and policy makers of the continuous evolutionary processes within and among social organizations and systems

The extractive industries and development: The resource curse at the micro, meso and macro levels

The resource curse literature has necessarily evolved in a rather fragmented way. While economists, political economists and political scientists have largely focused on the role of mineral abundance in long-term growth with the analysis largely confined to the country (macro) or regional (meso) level, anthropologists, sociologists and other social scientists have explored the development impacts of extractive industries at the community (micro) level. While this has provided a rigorous and comprehensive exploration of extractive industries and their impacts, causal factors that bridge and/or leap-frog these levels tend not to be accounted for. In this paper we examine the evolution of the literature across disciplinary lines and different levels of scale to assess the current status of resource curse debates. In so doing, we aim to explore how an integration of the various multi-scale approaches can help address the persistent problem of the resource curse

Visual attention and action: How cueing, direct mapping, and social interactions drive orienting

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated

Importance of patient bed pathways and length of stay differences in predicting COVID-19 hospital bed occupancy in England.

Background: Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy. Methods: We obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020. Results: In both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: “Ward, CC, Ward”, “Ward, CC”, “CC” and “CC, Ward”. Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days. For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities. Conclusions: We identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19. Trial registration: The ISARIC WHO CCP-UK study ISRCTN66726260 was retrospectively registered on 21/04/2020 and designated an Urgent Public Health Research Study by NIHR.</p

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease