Consequences of selecting technology pathways on cumulative carbon dioxide emissions for the United Kingdom

The UK has an ambitious target of an 80% reduction in carbon dioxide emissions by 2050, to be reached using a series of ‘carbon budgets’ to aid policy development. Current energy systems modelling methods do not explore, or are unable to account for, physical (thermodynamic) limits to the rate of change of infrastructure. The power generation sector has a variety of technological options for this low-carbon transition. We compare physically constrained scenarios that accentuate either carbon capture and storage, fastest plausible nuclear new build, or fastest plausible build rate of offshore wind. We set these in the context of the UK’s legislated fifth carbon budget, which has a comprehensive range of carbon reduction measures with respect to business-as-usual. The framework for our scenario comparison uses our novel system dynamics model to substantiate the policy’s ability to meet 2035 emissions targets while maintaining financial productivity and socially expected employment levels. For an ambitious nuclear new build programme we find that even if it stays on track it is more expensive than offshore wind generation and delays emissions reductions. This affects the cumulative emissions and impacts on the UK’s ability to contribute to international climate change targets. If delays or cancellation occur to the deployment programmes of carbon capture and storage technologies or nuclear new build, we suggest the electricity and decarbonisation targets can by met by a fast growth of offshore wind generation with no change to financial and employment levels.Arup’s internal Design and Technical Fun

Modelling socio-economic and energy data to generate business-as-usual scenarios for carbon emissions

The UK Government is legally committed to achieving an 80% reduction in carbon dioxide emissions compared with 1990 by 2050. The use of scenarios is wide ranging to inform policy development and forming a businessas-usual scenario helps to understand possible effects of different policy interventions. However, the term business-as-usual is frequently misused. We show how econo-physical business-as-usual scenarios can be developed by examining the historical behaviour of coefficients which manifest the relationship between components of an economy. We endogenise economic growth by mimicking national level policies that focus on a target level of unemployment. Our case-study demonstrates the ‘trendability’ of coefficients which for one example coefficient is replicated for Australia, Colombia, Taiwan and the USA. We manifest a gross domestic product growth of 2% falling to 1% which contrasts with an exogenous growth of 2.3% of a comparator business-as-usual scenario. We suggest that it may be possible to achieve a greater reduction in the business-asusual carbon dioxide emissions in the UK fifth carbon budget than currently projected.Arup’s internal Design and Technical Fun

Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn -based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients

System modelling of very low Earth orbit satellites for Earth observation

The operation of satellites in very low Earth orbit (VLEO) has been linked to a variety of benefits to both the spacecraft platform and mission design. Critically, for Earth observation (EO) missions a reduction in altitude can enable smaller and less powerful payloads to achieve the same performance as larger instruments or sensors at higher altitude, with significant benefits to the spacecraft design. As a result, renewed interest in the exploitation of these orbits has spurred the development of new technologies that have the potential to enable sustainable operations in this lower altitude range. In this paper, system models are developed for (i) novel materials that improve aerodynamic performance enabling reduced drag or increased lift production and resistance to atomic oxygen erosion and (ii) atmosphere-breathing electric propulsion (ABEP) for sustained drag compensation or mitigation in VLEO. Attitude and orbit control methods that can take advantage of the aerodynamic forces and torques in VLEO are also discussed. These system models are integrated into a framework for concept-level satellite design and this approach is used to explore the system-level trade-offs for future EO spacecraft enabled by these new technologies. A case-study presented for an optical very-high resolution spacecraft demonstrates the significant potential of reducing orbital altitude using these technologies and indicates possible savings of up to 75% in system mass and over 50% in development and manufacturing costs in comparison to current state-of-the-art missions. For a synthetic aperture radar (SAR) satellite, the reduction in mass and cost with altitude were shown to be smaller, though it was noted that currently available cost models do not capture recent commercial advancements in this segment. These results account for the additional propulsive and power requirements needed to sustain operations in VLEO and indicate that future EO missions could benefit significantly by operating in this altitude range. Furthermore, it is shown that only modest advancements in technologies already under development may begin to enable exploitation of this lower altitude range. In addition to the upstream benefits of reduced capital expense and a faster return on investment, lower costs and increased access to high quality observational data may also be passed to the downstream EO industry, with impact across a wide range of commercial, societal, and environmental application areas

Molecular Mechanism of Action of Antimalarial Benzoisothiazolones: Species-Selective Inhibitors of the Plasmodium spp. MEP Pathway enzyme, IspD

The methylerythritol phosphate (MEP) pathway is an essential metabolic pathway found in malaria parasites, but absent in mammals, making it a highly attractive target for the discovery of novel and selective antimalarial therapies. Using high-throughput screening, we have identified 2-phenyl benzo[d]isothiazol-3(2H)-ones as species-selective inhibitors of Plasmodium spp. 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (IspD), the third catalytic enzyme of the MEP pathway. 2-Phenyl benzo[d]isothiazol-3(2H)-ones display nanomolar inhibitory activity against P. falciparum and P. vivax IspD and prevent the growth of P. falciparum in culture, with EC50 values below 400 nM. In silico modeling, along with enzymatic, genetic and crystallographic studies, have established a mechanism-of-action involving initial non-covalent recognition of inhibitors at the IspD binding site, followed by disulfide bond formation through attack of an active site cysteine residue on the benzo[d]isothiazol-3(2H)-one core. The species-selective inhibitory activity of these small molecules against Plasmodium spp. IspD and cultured parasites suggests they have potential as lead compounds in the pursuit of novel drugs to treat malaria

Economic evaluation alongside pragmatic randomised trials: developing a standard operating procedure for clinical trials units

<p>Abstract</p> <p>Background</p> <p>There is wide recognition that pragmatic randomised trials are the best vehicle for economic evaluation. This is because trials provide the best chance of ensuring internal validity, not least through the rigorous prospective collection of patient-specific data. Furthermore the marginal cost of collecting economic data alongside clinical data is typically modest. UK Clinical Research Collaboration (UKCRC) does not require a standard operating procedure (SOP) for economic evaluation as a prerequisite for trial unit registration. We judge that such a SOP facilitates the integration of health economics into trials.</p> <p>Methods</p> <p>A collaboration between health economists and trialists at Bangor University led to the development of a SOP for economic evaluation alongside pragmatic trials, in addition to the twenty SOPs required by UKCRC for registration, which include randomisation, data management and statistical analysis.</p> <p>Results</p> <p>Our recent telephone survey suggests that no other UKCRC-registered trials unit currently has an economic SOP.</p> <p>Conclusion</p> <p>We argue that UKCRC should require, from all Trials Units undertaking economic evaluation and seeking registration or re-registration, a SOP for economic evaluation as one of their portfolio of supporting SOPs.</p

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits