Climate change impact and adaptation assessment for road drainage systems.

Climate change exhibits a clear trend of escalating frequency and intensity of extreme weather events, posing heightened risks to drainage systems along the existing road networks. However, very few studies to date have investigated the consequences of projected future changes in rainfall on main road drainage and the resulting risk of road flooding. The work presented in this paper builds on the limited research by introducing a probabilistic model for assessing the impact of climate change on road drainage systems, incorporating climate uncertainty and drainage system variation. The probabilistic scenario-based model and associated framework offer a practical and innovative method for estimating the impact of short-duration storms under future climates for 2071-2100, in the absence of fine-resolution spatio-temporal data. The model also facilitates the assessment of the effectiveness of a climate adaptation strategy. An illustrative case-study of a road drainage system located in the south of Ireland is presented. It was found that the probability of road flooding during intense rainfall is projected to surpass the current acceptable limits set by Irish standards. Assessment of a proactive climate adaptation strategy implemented in 2015 indicated it may need to be adjusted to further reduce climate change impacts and optimise adaptation costs.

Global high-resolution growth projections dataset for rooftop area consistent with the shared socioeconomic pathways, 2020-2050.

Assessment of current and future growth in the global rooftop area is important for understanding and planning for a robust and sustainable decentralised energy system. These estimates are also important for urban planning studies and designing sustainable cities thereby forwarding the ethos of the Sustainable Development Goals 7 (clean energy), 11 (sustainable cities), 13 (climate action) and 15 (life on land). Here, we develop a machine learning framework that trains on big data containing ~700 million open-source building footprints, global land cover, road, and population datasets to generate globally harmonised estimates of growth in rooftop area for five different future growth narratives covered by Shared Socioeconomic Pathways. The dataset provides estimates for ~3.5 million fishnet tiles of 1/8 degree spatial resolution with data on gross rooftop area for five growth narratives covering years 2020-2050 in decadal time steps. This single harmonised global dataset can be used for climate change, energy transition, biodiversity, urban planning, and disaster risk management studies covering continental to conurbation geospatial levels.

Circadian Clock and Hypoxia.

The timing of life on Earth is remarkable: between individuals of the same species, a highly similar temporal pattern is observed, with shared periods of activity and inactivity each day. At the individual level, this means that over the course of a single day, a person alternates between two states. They are either upright, active, and communicative or they lie down in a state of (un)consciousness called sleep where even the characteristic of neuronal signals in the brain shows distinctive properties. The circadian clock governs both of these time stamps-activity and (apparent) inactivity-making them come and go consistently at the same approximate time each day. This behavior thus represents the meeting of two pervasive systems: the circadian clock and metabolism. In this article, we will describe what is known about how the circadian clock anticipates daily changes in oxygen usage, how circadian clock regulation may relate to normal physiology, and to hypoxia and ischemia that can result from pathologies such as myocardial infarction and stroke.

Reinventing the Penumbra - the Emerging Clockwork of a Multi-modal Mechanistic Paradigm.

The concept of the ischemic penumbra was originally defined as the area around a necrotic stroke core and seen as the tissue at imminent risk of further damage. Today, the penumbra is generally considered as time-sensitive hypoperfused brain tissue with decreased oxygen and glucose availability, salvageable tissue as treated by intervention, and the potential target for neuroprotection in focal stroke. The original concept entailed electrical failure and potassium release but one short of neuronal cell death and was based on experimental stroke models, later confirmed in clinical imaging studies. However, even though the basic mechanisms have translated well, conferring brain protection, and improving neurological outcome after stroke based on the pathophysiological mechanisms in the penumbra has yet to be achieved. ï»¿Recent findings shape the modern understanding of the penumbra revealing a plethora of molecular and cellular pathophysiological mechanisms. We now propose a new model of the penumbra, one which we hope will lay the foundation for future translational success. We focus on the availability of glucose, the brain's central source of energy, and bioenergetic failure as core pathophysiological concepts. We discuss the relation of mitochondrial function in different cell types to bioenergetics and apoptotic cell death mechanisms, autophagy, and neuroinflammation, to glucose metabolism in what is a dynamic ischemic penumbra.

Keeping an eye on circadian time in clinical research and medicine.

BACKGROUND: Daily rhythms are observed in humans and almost all other organisms. Most of these observed rhythms reflect both underlying endogenous circadian rhythms and evoked responses from behaviours such as sleep/wake, eating/fasting, rest/activity, posture changes and exercise. For many research and clinical purposes, it is important to understand the contribution of the endogenous circadian component to these observed rhythms. CONTENT: The goal of this manuscript is to provide guidance on best practices in measuring metrics of endogenous circadian rhythms in humans and promote the inclusion of circadian rhythms assessments in studies of health and disease. Circadian rhythms affect all aspects of physiology. By specifying minimal experimental conditions for studies, we aim to improve the quality, reliability and interpretability of research into circadian and daily (i.e., time-of-day) rhythms and facilitate the interpretation of clinical and translational findings within the context of human circadian rhythms. We describe protocols, variables and analyses commonly used for studying human daily rhythms, including how to assess the relative contributions of the endogenous circadian system and other daily patterns in behaviours or the environment. We conclude with recommendations for protocols, variables, analyses, definitions and examples of circadian terminology. CONCLUSION: Although circadian rhythms and daily effects on health outcomes can be challenging to distinguish in practice, this distinction may be important in many clinical settings. Identifying and targeting the appropriate underlying (patho)physiology is a medical goal. This review provides methods for identifying circadian effects to aid in the interpretation of published work and the inclusion of circadian factors in clinical research and practice.

Novel, Emerging Chip Models of the Blood-Brain Barrier and Future Directions.

The use of microfluidic chips is now allowing for more advanced modelling of the blood-brain barrier (BBB) in vitro, recapitulating heterotypic interactions, 3D architecture, and physiological flow. This chapter will give an introduction to these new technologies and how they are being applied to model the BBB and neurovascular unit (NVU). A foundational understanding of the fluid dynamics germane to the effective use of these chips will be set and an overview of how physical phenomena at the microscale can be exploited to enable new possibilities to control the cell culture environment. The four main approaches to construct microfluidic blood vessel mimetics will be discussed with examples of how these techniques are being applied to model the BBB and more recently to study specific neurovascular disease processes. Finally, practical guidance will be given for researchers wishing to adopt these new techniques along with a summary of the challenges, limitations faced, and new opportunities opened up by these advanced cell culture systems.

Applications of Uncrewed Aerial Vehicles (UAV) Technology to Support Integrated Coastal Zone Management and the UN Sustainable Development Goals at the Coast.

Data and information obtained from low-cost uncrewed aerial vehicles (UAVs), commonly referred to as 'drones', can be used to support integrated coastal zone management (ICZM) and sustainable development at the coast. Several recent studies in various disciplines, including ecology, engineering, and several branches of physical and human geography, describe the applications of UAV technology with practical coastal management potential, yet the extent to which such data can contribute to these activities remains underexplored. The main objective of this paper is to collate this knowledge to highlight the areas in which UAV technology can contribute to ICZM and can influence the achievement of the UN Sustainable Development Goals (SDGs) at the coast. We focus on applications with practical potential for coastal management activities and assess their accessibility in terms of cost, ease of use, and maturity. We identified ten (out of the 17) SDGs to which UAVs can contribute data and information. Examples of applications include surveillance of illegal fishing and aquaculture activities, seaweed resource assessments, cost-estimation of post-storm damages, and documentation of natural and cultural heritage sites under threat from, for example, erosion and sea-level rise. An awareness of how UAVs can contribute to ICZM, as well as the limitations of the technology, can help coastal practitioners to evaluate their options for future management activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s12237-021-01001-5.

Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study.

OBJECTIVES: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Plasma was obtained from 295 hospitalised people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009-2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples. OUTCOME MEASURES: Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality. RESULTS: Vitamin D insufficiency (total 25(OH)D 25-50 nmol/L) and deficiency (<25 nmol/L) were prevalent in COVID-19 (29.3% and 44.4%, respectively), influenza A (47.3% and 37.6%) and critical illness survivors (30.2% and 56.8%). In COVID-19 and influenza A, total 25(OH)D measured early in illness was lower in patients who received IMV (19.6 vs 31.9 nmol/L (p<0.0001) and 22.9 vs 31.1 nmol/L (p=0.0009), respectively). In COVID-19, biologically active free 25(OH)D correlated with total 25(OH)D and was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators. CONCLUSIONS: Vitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes.

High resolution global spatiotemporal assessment of rooftop solar photovoltaics potential for renewable electricity generation.

Rooftop solar photovoltaics currently account for 40% of the global solar photovoltaics installed capacity and one-fourth of the total renewable capacity additions in 2018. Yet, only limited information is available on its global potential and associated costs at a high spatiotemporal resolution. Here, we present a high-resolution global assessment of rooftop solar photovoltaics potential using big data, machine learning and geospatial analysis. We analyse 130 million km2 of global land surface area to demarcate 0.2 million km2 of rooftop area, which together represent 27 PWh yr-1 of electricity generation potential for costs between 40-280 $ MWh-1. Out of this, 10 PWh yr-1 can be realised below 100 $ MWh-1. The global potential is predominantly spread between Asia (47%), North America (20%) and Europe (13%). The cost of attaining the potential is lowest in India (66 $ MWh-1) and China (68 $ MWh-1), with USA (238 $ MWh-1) and UK (251 $ MWh-1) representing some of the costliest countries.

Droplet Microfluidics with Reagent Micromixing for Investigating Intrinsic Platelet Functionality.

INTRODUCTION: Precision mapping of the functional structure of platelet populations holds great promise for the identification of hyper-reactive subtypes that are likely to be disease drivers, having value in prognostics and as therapeutic targets. However, the ability to measure the intrinsic functional capacity of individual platelets is confounded by potent paracrine cross-talk, resulting in phenotypic remodeling of the entire platelet population, and in doing so obscuring the identity of hyper-reactive platelets. METHODS: To address this we have developed a droplet microfluidics strategy for single platelet confinement to exclude paracrine signaling. Consideration of the Poisson distribution was used for high throughput single platelet encapsulation and the preparation of minimal platelet collectives serving as digital models for understanding the role of hyper-reactive platelets coordinating system-level behavior by paracrine signaling. Platelets are retrieved from the droplets for phenotyping using standard flow cytometry. In addition, we have incorporated a staggered herringbone micromixing element for accurate agonist and antibody dispensing in droplets. RESULTS: The methodology was used for characterizing sensitivity distributions from healthy blood donors in response to convulxin (agonist of the GPVI receptor, the major platelet receptor for collagen). P-selectin exposure and α IIb ß 3 integrin activation were used as analytical end-points to demonstrate the existence of hyper-reactive platelets that direct 20-fold gains in system level sensitivity. CONCLUSIONS: The analytical workflow represents an enabling tool for the accurate classification of platelet subtypes and description of their underlying biology. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12195-020-00665-6) contains supplementary material, which is available to authorized users.

Advances in microfluidic in vitro systems for neurological disease modeling.

Neurological disorders are the leading cause of disability and the second largest cause of death worldwide. Despite significant research efforts, neurology remains one of the most failure-prone areas of drug development. The complexity of the human brain, boundaries to examining the brain directly in vivo, and the significant evolutionary gap between animal models and humans, all serve to hamper translational success. Recent advances in microfluidic in vitro models have provided new opportunities to study human cells with enhanced physiological relevance. The ability to precisely micro-engineer cell-scale architecture, tailoring form and function, has allowed for detailed dissection of cell biology using microphysiological systems (MPS) of varying complexities from single cell systems to "Organ-on-chip" models. Simplified neuronal networks have allowed for unique insights into neuronal transport and neurogenesis, while more complex 3D heterotypic cellular models such as neurovascular unit mimetics and "Organ-on-chip" systems have enabled new understanding of metabolic coupling and blood-brain barrier transport. These systems are now being developed beyond MPS toward disease specific micro-pathophysiological systems, moving from "Organ-on-chip" to "Disease-on-chip." This review gives an outline of current state of the art in microfluidic technologies for neurological disease research, discussing the challenges and limitations while highlighting the benefits and potential of integrating technologies. We provide examples of where such toolsets have enabled novel insights and how these technologies may empower future investigation into neurological diseases.

Full color-tunable vertically stacked quantum dot light emitting diodes for next-generation displays and lighting.

We report solution-processed color tunable vertically stacked electroluminescent red, green, and blue quantum dot light emitting diodes (QLEDs). These QLEDs can be independently driven to produce all primary, secondary, and white lights. We have fabricated the device by chemical and electrical isolation of each QLED with transparent polymers and by the use of transparent electrodes. These stacked QLEDs can be used for next-generation display and lighting applications that need high pixel density along with quantum dots' intrinsic benefits such as low turn-on voltage, color purity, and solution processability.

Monolithically-integrated cytometer for measuring particle diameter in the extracellular vesicle size range using multi-angle scattering.

Size measurement of extracellular vesicles is hampered by the high cost and measurement uncertainty of conventional flow cytometers which is mainly due to the use of non-specialised free space optics. Integrated cytometry, where the optics and fluidics are embedded in a monolithic chip shows promise for the production of low cost, micro-flow cytometers dedicated for extracellular vesicle (EV) analysis with improved size measurement accuracy and precision. This research demonstrates a unique integrated cytometer for sub-micron particle size measurement using multi-angle scattering analysis. A combination of three technologies is used: (i) Dean-based hydrodynamic focussing to deliver a tight sample core stream to the analysis region, (ii) integrated waveguides with multimode interference devices to focus a narrow excitation beam onto the sample stream, and (iii) an angular array of collection waveguides to measure particle scattering distribution and calculate diameter. Low index 200 nm liposomes could be detected and polystyrene size standards as small as 400 nm diameter could be measured with an uncertainty of ±21 nm (1/2 IQR) demonstrating a first step on the path to high performance integrated cytometry of EVs.

Methodological challenges in European ethics approvals for a genetic epidemiology study in critically ill patients: the GenOSept experience.

BACKGROUND: During the set-up phase of an international study of genetic influences on outcomes from sepsis, we aimed to characterise potential differences in ethics approval processes and outcomes in participating European countries. METHODS: Between 2005 and 2007 of the FP6-funded international Genetics Of Sepsis and Septic Shock (GenOSept) project, we asked national coordinators to complete a structured survey of research ethic committee (REC) approval structures and processes in their countries, and linked these data to outcomes. Survey findings were reconfirmed or modified in 2017. RESULTS: Eighteen countries participated in the study, recruiting 2257 patients from 160 ICUs. National practices differed widely in terms of composition of RECs, procedures and duration of the ethics approval process. Eight (44.4%) countries used a single centralised process for approval, seven (38.9%) required approval by an ethics committee in each participating hospital, and three (16.7%) required both. Outcomes of the application process differed widely between countries because of differences in national legislation, and differed within countries because of interpretation of the ethics of conducting research in patients lacking capacity. The RECs in four countries had no lay representation. The median time from submission to final decision was 1.5 (interquartile range 1-7) months; in nine (50%) approval was received within 1 month; six took over 6 months, and in one 24 months; had all countries been able to match the most efficient approvals processes, an additional 74 months of country or institution-level recruitment would have been available. In three countries, rejection of the application by some local RECs resulted in loss of centres; and one country rejected the application outright. CONCLUSIONS: The potential benefits of the single application portal offered by the European Clinical Trials Regulation will not be realised without harmonisation of research ethics committee practices as well as national legislation.

Asymmetric confinement for defining outgrowth directionality.

Directional connectivity is required to develop accurate in vitro models of the nervous system. This research investigated the interaction of murine neuronal outgrowths with asymmetric microstructured geometries to provide insights into the mechanisms governing unidirectional outgrowth bias. The structures were designed using edge-guidance and critical turning angle principles to study different prohibitive to permissive edge-guidance ratios. The different structures enable outgrowth in the permissive direction, while reducing outgrowth in the prohibitive direction. Outgrowth bias was probabilistic in nature, requiring multiple structures for effective unidirectional bias in primary hippocampal cultures at 14 days in vitro. Arrowhead structures with acute posterior corners were optimal, enabling 100% unidirectional outgrowth bias by virtue of re-routing and delay effects.

Serial integration of Dean-structured sample cores with linear inertial focussing for enhanced particle and cell sorting.

In this contribution, a channel aspect ratio of >2 was used to access high velocity regimes to provide confined sample cores by Dean focussing in advance of linear inertial focussing. This produces a singular separation origin with a mirrored transport path for efficient particle and blood cell sorting, while also increasing the spatial resolution for multiscale sorting.

The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction.

BACKGROUND AND PURPOSE: Platelet activation provides a critical link between inflammation and thrombosis. Sulforaphane (SFN), a naturally occurring isothiocyanate, has been shown to display both anti-inflammatory and anti-thrombotic actions in the systemic microvasculature. As inflammation promotes thrombosis and vice versa, in this study we investigated whether SFN is able to reduce inflammatory potentiation of thrombotic events, suppress platelet activation and thrombus formation in the cerebral microvasculature. EXPERIMENTAL APPROACH: Thrombosis was induced in the murine brain using the light/dye-injury model, in conjunction with LPS treatment, with and without SFN treatment. In vitro and in vivo platelet assays (aggregation, flow and other functional tests) were also employed, using both human and murine platelets. KEY RESULTS: SFN was found to reduce LPS-mediated enhancement of thrombus formation in the cerebral microcirculation. In tail-bleed experiments, LPS treatment prolonged bleeding time, and SFN treatment was found to protect against this LPS-induced derangement of platelet function. SFN inhibited collagen-mediated platelet aggregation in vitro and in vivo and the associated adhesion and impaired calcium signalling. Furthermore, glycoprotein VI was shown to be involved in the protective effects observed with SFN treatment. CONCLUSIONS AND IMPLICATIONS: The data presented here provide evidence for the use of SFN in preventing stroke in selected high-risk patient cohorts.

Improving Charge Injection via a Blade-Coating Molybdenum Oxide Layer: Toward High-Performance Large-Area Quantum-Dot Light-Emitting Diodes.

A solution-processed molybdenum oxide (MoO x) as the hole injection layer (HIL) by doctor-blade coating was developed to improve the efficiency and lifetime of red-emitting quantum-dot light-emitting diodes (QD-LEDs). It has been demonstrated that by adding isopropyl alcohol into the MoO x precursor during the doctor-blade coating process, the morphology, composition, and the surface electronic structure of the MoO x HIL could be tailored. A high-quality MoO x film with optimized charge injection was obtained, based on which all-solution-processed highly efficient red-emitting QD-LEDs were realized by using a low-cost doctor-blade coating technique under ambient conditions. The red QD-LEDs exhibited the maximum current efficiency and external quantum efficiency of 16 cd/A and 15.1%, respectively. Moreover, the lifetime of red devices initializing at 100 cd/m2 was 3236 h under ambient conditions, which is about twice as long as those with a conventional poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) HIL. Large-area QD-LEDs with 4 in. emitting areas were fabricated with blade coating as well, which exhibit a high efficiency of 12.1 cd/A for red emissions. Our work paves a new way to the realization of efficient large-area QD-LEDs, and the processing and findings from this work can be expanded into next-generation lighting and flat-panel displays.

High efficiency quantum dot light emitting diodes from positive aging.

Colloidal quantum dot-polymer hybrid light emitting diodes (QLEDs) that exhibit external quantum efficiencies >12% for all three primary colors (21% from green) have been demonstrated. These high efficiencies result in part from a positive aging effect reported here for the first time, where positive aging means the efficiency of the QLED increased with time. We have achieved 470 h operational life time (T90) at 2550 nits for red QLEDs. At longer times, negative aging phenomena lead to lower luminance and limit the lifetime of the QLEDs. It is concluded that we have reasonable control over the efficiency of QLEDs. The next challenge is to achieve lifetimes sufficiently long for all three primary colors for applications such as in television and illumination.

Derivation and validation of a prognostic model for postoperative risk stratification of critically ill patients with faecal peritonitis.

BACKGROUND: Prognostic scores and models of illness severity are useful both clinically and for research. The aim of this study was to develop two prognostic models for the prediction of long-term (6 months) and 28-day mortality of postoperative critically ill patients with faecal peritonitis (FP). METHODS: Patients admitted to intensive care units with faecal peritonitis and recruited to the European GenOSept study were divided into a derivation and a geographical validation subset; patients subsequently recruited to the UK GAinS study were used for temporal validation. Using all 50 clinical and laboratory variables available on day 1 of critical care admission, Cox proportional hazards regression was fitted to select variables for inclusion in two prognostic models, using stepwise selection and nonparametric bootstrapping sampling techniques. Using Area under the receiver operating characteristic curve (AuROC) analysis, the performance of the models was compared to SOFA and APACHE II. RESULTS: Five variables (age, SOFA score, lowest temperature, highest heart rate, haematocrit) were entered into the prognostic models. The discriminatory performance of the 6-month prognostic model yielded an AuROC 0.81 (95% CI 0.76-0.86), 0.73 (95% CI 0.69-0.78) and 0.76 (95% CI 0.69-0.83) for the derivation, geographic and temporal external validation cohorts, respectively. The 28-day prognostic tool yielded an AuROC 0.82 (95% CI 0.77-0.88), 0.75 (95% CI 0.69-0.80) and 0.79 (95% CI 0.71-0.87) for the same cohorts. These AuROCs appeared consistently superior to those obtained with the SOFA and APACHE II scores alone. CONCLUSIONS: The two prognostic models developed for 6-month and 28-day mortality prediction in critically ill septic patients with FP, in the postoperative phase, enhanced the day one SOFA score's predictive utility by adding a few key variables: age, lowest recorded temperature, highest recorded heart rate and haematocrit. External validation of their predictive capability in larger cohorts is needed, before introduction of the proposed scores into clinical practice to inform decision making and the design of clinical trials.