Search

Transitions are processes of systemic change where niches peripheral to a sociotechnical regime accumulate momentum, scale up and eventually transform its core. In contrast to this dominant narrative in transitions research, infrastructure systems exhibit the reverse process as change propagates from the regime core to its periphery. We explore this under-researched process in the case of digitalization in UK construction. We analyse six UK megaprojects that span more than 30 years as a single longitudinal embedded case, and show how the adoption of digital technologies driven by regime incumbents, seeds the processes of technology adaptation, aggregation, and system transformation. The adoption of digital technologies by incumbents is necessary to cope with megaproject scale and scope. Their adaptation to technology instigates organizational level change that starts at the regime core, accumulates with each project and makes these changes ripple across the industry and transform it.

Through a systematic literature review we explore how digital technologies reshape and catalyze digital innovations in the built environment—a highly project-based setting. We analyzed circa 3,000 titles, further narrowed down to 87 articles. We synthesized an original framework for data analysis. The article presents implications for the deployment of digital technologies on three levels: individuals, organizations, and projects. Whereas most of these studies examined the impact of digital innovation in projects, recommendations focused on organizations, suggesting future directions for performance measurement, developing capabilities of firms to manage changes in dynamic environments and interorganizational settings.

Enzymatically oxygenated phospholipids (eoxPL) formed by lipoxygenases (LOX) and cyclooxygenase (COX) in platelets and leukocytes are pro-coagulant in multiple model systems. However, their generation in arterial thrombotic disease, and how their levels are modulated by common therapies is unknown. Here, eoxPL were first characterized in isolated platelets and leukocytes from an arterial vascular disease cohort, a healthy cohort administered low dose aspirin, and from retrieved human arterial thrombi. In both cohorts, aspirin reduced platelet COX-1-derived eoxPL, while elevating diacyl 12-LOX-derived eoxPL in males, through enhanced Lands’ cycle esterification. Conversely, P2Y12 inhibition reduced 12-LOX-derived eoxPL in leukocytes. Complex aspirin-dependent gender and seasonal effects on platelet eoxPL were seen in healthy subjects. Limb or coronary (STEMI) thrombi showed a platelet eoxPL signature while carotid thrombi had a white cell profile. Mice genetically lacking leukocyte 12/15-LOX, which are deficient in eoxPL, generated smaller carotid thrombi in vivo. In summary, pro-coagulant eoxPL generation is altered in human arterial vascular disease by commonly used cardiovascular therapies. These changes to the phospholipid composition of blood cells in humans at risk of thrombotic events may be clinically significant where the pro-coagulant membrane plays a central but poorly understood role in driving elevated thrombotic risk.Key PointseoxPL generation is altered in health and arterial vascular disease by aspirin or P2Y12 inhibitors, and shows gender and seasonal variation.Aspirin regulates eoxPL by inhibiting cyclooxygenase and modulating Lands’ cycle.The eoxPL profile of human arterial thrombi identifies platelet and leukocyte involvement.Mice deficient in LOX-derived eoxPL form smaller arterial thrombiin vivo.

Our case study explored a Local Resilience Forum's (LRF) civil contingency response to COVID-19 in the United Kingdom. We undertook 19 semistructured ethnographic longitudinal interviews, between March 25, 2020 and February 17, 2021, with a Director of a Civil Contingencies Unit and a Chief Fire Officer who both played key roles within their LRF. Within these interviews, we focused on their strategic level decision-making and how their relationship with national government impacted on local processes and outcomes. Using a form of grounded theory, our data describe the chronological evolution of an increasingly effective localized approach toward outbreak control and a growing resilience in dealing with concurrent emergency incidents. However, we also highlight how national government organizations imposed central control on aspects of the response in ways that undermined or misaligned with local preparedness. Thus, during emergencies, central governments can undermine the principle of subsidiarity and damage the ways in which LRFs can help scaffold local resilience. Our work contributes to the theoretical understanding of the social psychological factors that can shape the behaviour of responder agencies during a prolonged crisis. In particular, the implications of our analysis for advancing our conceptual understanding of strategic decision-making during emergencies are discussed.

Thrombosis is a leading contributor to death and disability, carrying high social and healthcare costs. Current treatment protocols in patients presenting with blood clots (such as those with ischemic stroke) recommend the administration of thrombolytic drugs; however, this option is associated with severe haemorrhagic side effects. Clinicians currently have access to a wide range of fibrinolytic biomarkers; however, these either rely on monitoring a single component of the fibrinolytic system or use arbitrary definitions of lysis, and thus have limited value.This thesis presents the development and validation of a novel haemorhe-ological biomarker, utilising advanced rheological techniques that measure fibrinol-ysis through the detection of a gel and de-gel point. This provides a global marker of coagulation and lysis based on the period of haemostatic functionality, i.e. the clots lifetime as a viscoelastic solid. This biomarker was evaluated in samples of blood and plasma, and the results demonstrate its potential use as a tool for the monitoring and development of thrombolytic therapies.The work herein also investigates the influence of shear induced modifi-cation of clot structure on clot lysis through the use of controlled stress parallel superposition rheometry. Clots formed under increasing levels of shear stress were found to have increased resistance to lysis, a finding which has significance in-vivo when considering pathophysiologically relevant changes to flow, due to high blood pressure and narrowing of blood vessels. Finally, the effects of platelet mediated contraction were shown to have a negligible impact on the rheological measurements and the associated biomarker. This represents a significant advan-tage over current mechanical based techniques, such as thromboelastometry and thromboelastography.

AimPaleoclimate reconstructions have enhanced our understanding of how past climates may have shaped present-day biodiversity. We hypothesize that habitat stability in historical Afrotropical refugia played a major role in the habitat suitability and persistence of chimpanzees (Pan troglodytes) during the late Quaternary. We aimed to build a dynamic model of changing habitat suitability for chimpanzees at fine spatio-temporal scales to provide a new resource for understanding their ecology, behaviour and evolution.LocationAfrotropics.TaxonChimpanzee (Pan troglodytes), including all four subspecies (P. t. verus, P. t. ellioti, P. t. troglodytes, P. t. schweinfurthii).MethodsWe used downscaled bioclimatic variables representing monthly temperature and precipitation estimates, historical human population density data and an extensive database of georeferenced presence points to infer chimpanzee habitat suitability at 62 paleoclimatic time periods across the Afrotropics based on ensemble species distribution models. We mapped habitat stability over time using an approach that accounts for dispersal between time periods, and compared our modelled stability estimates to existing knowledge of Afrotropical refugia. Our models cover a spatial resolution of 0.0467 degrees (approximately 5.19 km2 grid cells) and a temporal resolution of every 1,000–4,000 years dating back to the Last Interglacial (120,000 BP).ResultsOur results show high habitat stability concordant with known historical forest refugia across Africa, but suggest that their extents are underestimated for chimpanzees. We provide the first fine-grained dynamic map of historical chimpanzee habitat suitability since the Last Interglacial which is suspected to have influenced a number of ecological-evolutionary processes, such as the emergence of complex patterns of behavioural and genetic diversity.Main ConclusionsWe provide a novel resource that can be used to reveal spatio-temporally explicit insights into the role of refugia in determining chimpanzee behavioural, ecological and genetic diversity. This methodology can be applied to other taxonomic groups and geographic areas where sufficient data are available.

Background Delirium is a common severe neuropsychiatric condition secondary to physical illness, which predominantly affects older adults in hospital. Prior to this study, the UK point prevalence of delirium was unknown. We set out to ascertain the point prevalence of delirium across UK hospitals and how this relates to adverse outcomes. Methods We conducted a prospective observational study across 45 UK acute care hospitals. Older adults aged 65 years and older were screened and assessed for evidence of delirium on World Delirium Awareness Day (14th March 2018). We included patients admitted within the previous 48 h, excluding critical care admissions. Results The point prevalence of Diagnostic and Statistical Manual on Mental Disorders, Fifth Edition (DSM-5) delirium diagnosis was 14.7% (222/1507). Delirium presence was associated with higher Clinical Frailty Scale (CFS): CFS 4–6 (frail) (OR 4.80, CI 2.63–8.74), 7–9 (very frail) (OR 9.33, CI 4.79–18.17), compared to 1–3 (fit). However, higher CFS was associated with reduced delirium recognition (7–9 compared to 1–3; OR 0.16, CI 0.04–0.77). In multivariable analyses, delirium was associated with increased length of stay (+ 3.45 days, CI 1.75–5.07) and increased mortality (OR 2.43, CI 1.44–4.09) at 1 month. Screening for delirium was associated with an increased chance of recognition (OR 5.47, CI 2.67–11.21). Conclusions Delirium is prevalent in older adults in UK hospitals but remains under-recognised. Frailty is strongly associated with the development of delirium, but delirium is less likely to be recognised in frail patients. The presence of delirium is associated with increased mortality and length of stay at one month. A national programme to increase screening has the potential to improve recognition.

Protein glycosylation contributes to critical biological function of glycoproteins. Glycan analysis is essential for the production of biopharmaceuticals as well as for the identification of disease biomarkers. However, glycans are highly heterogeneous, which has considerably hampered the progress of glycomics. Here, we present an improved 96-well plate format platform for streamlined glycan profiling that takes advantage of rapid glycoprotein denaturation, deglycosylation, fluorescent derivatization, and on-matrix glycan clean-up. This approach offers high sensitivity with consistent identification and quantification of diverse N-glycans across multiple samples on a high-throughput scale. We demonstrate its capability for N-glycan profiling of glycoproteins from various sources, including two recombinant monoclonal antibodies produced from Chinese Hamster Ovary cells, EG2-hFc and rituximab, polyclonal antibodies purified from human serum, and total glycoproteins from human serum. Combined with the complementary information obtained by sequential digestion from exoglycosidase arrays, this approach allows the detection and identification of multiple N-glycans in these complex biological samples. The reagents, workflow, and Hydrophilic interaction liquid chromatography with fluorescence detection (HILIC-FLD), are simple enough to be implemented into a straightforward user-friendly setup. This improved technology provides a powerful tool in support of rapid advancement of glycan analysis for biopharmaceutical development and biomarker discovery for clinical disease diagnosis.