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A dynamic model of the body gas stores for carbon dioxide, oxygen and inert gases that incorporates circulatory transport delays to and from the lung
No full textMany models of the body’s gas stores have been generated for specific purposes. Here, we seek to produce a more general purpose model that: 1) is relevant for both respiratory (CO2 and O2) and inert gases; 2) is based firmly on anatomy and not arbitrary compartments; 3) can be scaled to individuals; and 4) incorporates arterial and venous circulatory delays as well as tissue volumes so that it can reflect rapid transients with greater precision. First, a “standard man” of 11 compartments was produced, based on data compiled by the International Radiation Protection Commission. Each compartment was supplied via its own parallel circulation, the arterial and venous volumes of which were based on reported tissue blood volumes together with data from a detailed anatomical model for the large arteries and veins. A previously published model was used for the blood gas chemistry of CO2 and O2. It was not permissible ethically to insert pulmonary artery catheters into healthy volunteers for model validation. Therefore, validation was undertaken by comparing model predictions with previously published data and by comparing model predictions with experimental data for transients in gas exchange at the mouth following changes in alveolar gas composition. Overall, model transients were fastest for O2, intermediate for CO2, and slowest for N2. There was good agreement between model estimates and experimentally measured data. Potential applications of the model include estimation of closed-loop gain for the ventilatory chemoreflexes and improving the precision associated with multibreath washout testing and respiratory measurement of cardiac output
Standardisation of clinical assessment, management and follow-up of acute hospitalised exacerbation of COPD: a Europe-wide consensus
No full textBackground: Despite hospitalization for exacerbation being a high-risk event for morbidity and mortality, there is little consensus globally regarding the assessment and management of hospitalised exacerbations of COPD. We aimed to establish a consensus list of symptoms, physiological measures, clinical scores, patient questionnaires and investigations to be obtained at time of hospitalised COPD exacerbation and follow-up.
Methods: A modified Delphi online survey with pre-defined consensus of importance, feasibility and frequency of measures at hospitalisation and follow-up of a COPD exacerbation was undertaken.
Findings: A total of 25 COPD experts from 18 countries contributed to all 3 rounds of the survey. Experts agreed that a detailed history and examination were needed. Experts also agreed on which treatments are needed and how soon these should be delivered. Experts recommended that a full blood count, renal function, C-reactive protein and cardiac blood biomarkers (BNP and troponin) should be measured within 4 hours of admission and that the modified Medical Research Council dyspnoea scale (mMRC) and COPD assessment test (CAT) should be performed at time of exacerbation and follow-up. Experts encouraged COPD clinicians to strongly consider discussing palliative care, if indicated, at time of hospitalisation.
Interpretation: This Europe-wide consensus document is the first attempt to standardise the assessment and care of patients hospitalised for COPD exacerbations. This should be regarded as the starting point to build knowledge and evidence on patients hospitalised for COPD exacerbations
80 questions for UK biological security
No full textMultiple national and international trends and drivers are radically changing what biological security means for the United Kingdom (UK). New technologies present novel opportunities and challenges, and globalisation has created new pathways and increased the speed, volume and routes by which organisms can spread. The UK Biological Security Strategy (2018) acknowledges the importance of research on biological security in the UK. Given the breadth of potential research, a targeted agenda identifying the questions most critical to effective and coordinated progress in different disciplines of biological security is required. We used expert elicitation to generate 80 policy-relevant research questions considered by participants to have the greatest impact on UK biological security. Drawing on a collaboratively-developed set of 450 questions, proposed by 41 experts from academia, industry and the UK government (consulting 168 additional experts) we subdivided the final 80 questions into six categories: bioengineering; communication and behaviour; disease threats (including pandemics); governance and policy; invasive alien species; and securing biological materials and securing against misuse. Initially, the questions were ranked through a voting process and then reduced and refined to 80 during a one-day workshop with 35 participants from a variety of disciplines. Consistently emerging themes included: the nature of current and potential biological security threats, the efficacy of existing management actions, and the most appropriate future options. The resulting questions offer a research agenda for biological security in the UK that can assist the targeting of research resources and inform the implementation of the UK Biological Security Strategy. These questions include research that could aid with the mitigation of Covid-19, and preparation for the next pandemic. We hope that our structured and rigorous approach to creating a biological security research agenda will be replicated in other countries and regions. The world, not just the UK, is in need of a thoughtful approach to directing biological security research to tackle the emerging issues
Novel method for quantifying AhR-ligand binding affinities using microscale thermophoresis
No full textThe aryl hydrocarbon receptor (AhR) is a highly conserved cellular sensor of a variety of environmental pollutants and dietary-, cell- and microbiota-derived metabolites with important roles in fundamental biological processes. Deregulation of the AhR pathway is implicated in several diseases, including autoimmune diseases and cancer, rendering AhR a promising target for drug development and host-directed therapy. The pharmacological intervention of AhR processes requires detailed information about the ligand binding properties to allow specific targeting of a particular signaling process without affecting the remaining. Here, we present a novel microscale thermophoresis-based approach to monitoring the binding of purified recombinant human AhR to its natural ligands in a cell-free system. This approach facilitates a precise identification and characterization of unknown AhR ligands and represents a screening strategy for the discovery of potential selective AhR modulators
Folgen des harten Brexit im Internationalen Privat- und Zivilverfahrensrecht
No full textDurch den Brexit ist die Lage für grenzüberschreitende Gerichtsverfahren und
Rechtsverhältnisse zwischen Deutschland und dem Vereinigten Königreich deutlich komplizierter geworden. Das Internationale Privat- und Zivilverfahrensrecht blieb nämlich letztlich im Handels- und Kooperationsabkommen für die künftigen Beziehungen der EU und des Vereinigten Königreichs völlig ungeregelt. Der vorliegende Beitrag behandelt die Herausforderungen dieses „harten Brexits“, denen sich deutsche Rechtspraktiker in alten und künftigen Fällen stellen müssen
Cost effective assessment of human and habitat factors essential for critically endangered lions in West Africa
No full textConflict with humans and habitat fragmentation are major threats to large carnivores in Africa, and transboundary protected areas may ease some of the space requirements for individual countries. The W-Arly-Pendjari complex (WAP) in West Africa sits across Benin, Burkina Faso, and Niger and is the last regional stronghold for many species, including the regionally critically endangered lion (Panthera leo). However, variation in monitoring efforts, limited resources, and imperfect coordination confound their conservation. We demonstrate a cost-effective and scalable design to effectively identify the landscape-level factors that limit the distribution and abundance of large carnivores and their preferred prey. We used an occupancy framework for a combination of spoor and line transect data. We found a high degree of variation in prey density, strongly related to evapotranspiration. Lion occupancy increased in areas of high riparian forest cover, far from hunting concessions and with more pastoralist activities. Hyaena occupancy was inversely related to anthropogenic pressures, and positively related to dense vegetation and overall prey density. We discuss conservation challenges such as illegal hunting and grazing in the context of transboundary management
Hidden water in magma ocean exoplanets
No full textWe demonstrate that the deep volatile storage capacity of magma oceans has significant implications for the bulk composition, interior, and climate state inferred from exoplanet mass and radius data. Experimental petrology provides the fundamental properties of the ability of water and melt to mix. So far, these data have been largely neglected for exoplanet mass–radius modeling. Here we present an advanced interior model for water-rich rocky exoplanets. The new model allows us to test the effects of rock melting and the redistribution of water between magma ocean and atmosphere on calculated planet radii. Models with and without rock melting and water partitioning lead to deviations in planet radius of up to 16% for a fixed bulk composition and planet mass. This is within the current accuracy limits for individual systems and statistically testable on a population level. Unrecognized mantle melting and volatile redistribution in retrievals may thus underestimate the inferred planetary bulk water content by up to 1 order of magnitude
Associations between touchscreen exposure and hot and cool inhibitory control in 10-month-old infants
No full textTouchscreen use amongst young children has proliferated in recent years, yet little is known about the association between daily touchscreen exposure and inhibitory control in the first year of life. Previous research has found a negative association between the amount of television viewing and inhibitory control in early childhood, but it is unclear whether negative associations with screen use extend to touchscreens. The current study presents an exploratory analysis of the cross-sectional associations between inhibitory control and the amount of touchscreen use amongst 10-month-olds (n = 128–156). Touchscreen exposure was assessed via parent-report. In order to include a range of “hot” and “cool” aspects of inhibitory control, these skills were assessed using lab-based response inhibition and prohibition tasks as well as parent-reported observations of infants’ inhibitory control abilities and broader regulatory behaviors. A “Cognitive Executive Function (EEFQ-CEF)” score (encompassing Inhibitory Control, Flexibility, and Working Memory items) was included as a secondary broader executive function construct to examine whether effects showed specificity to inhibitory control rather than executive functions more generally. Correlation analyses indicated no association between touchscreen exposure and the four indices of IC. However, a positive association was found for the amount of touchscreen exposure and EEFQ-CEF once accounting for sociodemographic variables. The implications of these findings and future directions are discussed
The role of L1 typology and L2 proficiency in null subject transfer
No full textThis dissertation is a large-scale investigation on the omission of subject pronouns by learners of null-subject languages. A null-subject language is one where pronouns are either optional or unnecessary to make reference to a primary subject. In these languages, (which includes, Spanish, Italian, Arabic, Mandarin Chinese, Russian, Swahili, and many others) dropping a pronoun does not result in ambiguity. However, English is a non-null-subject language and a subject pronoun is always required in referring expressions. The aim of the present study is to determine if this difference in subject parameters means that learners are more prone to omit pronouns in second language (L2) English production. The first research question of the present study asks, ‘do null subjects in the L1 transfer to L2 English?’ This question becomes more complex when we consider that there are more than one type of null-subject language. How null subjects are licensed is in ‘canonical’ null-subject languages like Spanish is quite different from ‘radical’ null subject languages like Japanese. Typological classification, then, becomes an additional consideration and the basis of research question two. The literature has suggested, however, that regardless of L1, the effects of language transfer are still persistent at advanced levels of L2 proficiency. This means, that learners are still omitting pronouns in L2 English—beyond the B2 level—just as they would in their null-subject first language (L1). Research question three queries whether proficiency, rather than L1, is the key factor in accurate L2 grammatical production.
The majority of the research on these questions has focused on smaller-scale studies of L1 Spanish or Italian learners of English. To address this, I use data from the EFCAMDAT learner corpus to sample a large and typologically diverse set of learners. This corpus contains over a million writing samples from 174,000 learners representing 198 nationalities. For this study, writing samples from learners with L1 Arabic, L1 Chinese (Mandarin), and L1 Russian were selected and analysed for their accuracy in pronoun production and omission. The results of chi-square and logistic regression analysis indicate that null-subject transfer is limited. There was a clear effect of L1, but not typology. L1 Arabic and L1 Chinese learners had nearly identical rates of accuracy (
Transcription initiation at a consensus bacterial promoter proceeds via a 'bind-unwind-load-and-lock' mechanism
No full textTranscription initiation starts with unwinding of promoter DNA by RNA polymerase (RNAP) to form a catalytically competent RNAP-promoter complex (RPO). Despite extensive study, the mechanism of promoter unwinding has remained unclear, in part due to the transient nature of intermediates on path to RPo. Here, using single-molecule unwinding-induced fluorescence enhancement to monitor promoter unwinding, and single-molecule fluorescence resonance energy transfer to monitor RNAP clamp conformation, we analyze RPo formation at a consensus bacterial core promoter. We find that the RNAP clamp is closed during promoter binding, remains closed during promoter unwinding, and then closes further, locking the unwound DNA in the RNAP active-centre cleft. Our work defines a new, 'bind-unwind-load-and-lock' model for the series of conformational changes occurring during promoter unwinding at a consensus bacterial promoter and provides the tools needed to examine the process in other organisms and at other promoters