Global climate change is one of the big challenges society faces today. Warming of the climate system is unequivocal, and evident from observations of increasing global average temperatures. Warming is also observed in the oceans, and is accompanied by a change in salinity, with the high latitudes becoming 'fresher' (i.e., less saline) and the subtropics and tropics becoming more saline - a redistribution of properties that has the potential to affect ocean circulation. There are also clear effects of climate change on the chemistry of the oceans. Whilst increased uptake of more abundant atmospheric carbon dioxide leads to an acidification of the oceans that threatens marine ecosystems, only little is known about the effects of higher concentrations of certain trace metals, as a result of anthropogenic pollution and changing erosion patterns on land. Such changes are very important, however, as the ability of the ocean to take up carbon dioxide from the atmosphere is strongly coupled to the supply of so-called nutrients, elements that are essential for life in the ocean. As part of this project, we will develop a better understanding of such 'biogeochemical cycles'. We picked out three trace metals, neodymium (Nd), cadmium (Cd), and lead (Pb), which together represent the behaviour of many different elements in the ocean. For example, both Cd and Pb are today supplied to the environment by human activity and this may alter their natural cycles. As Cd is an important micronutrient in the ocean, such changes could also affect the global carbon cycle. As part of our project, a PhD student will focus on understanding whether the natural flux of dust from desert areas to the ocean and the anthropogenic particles the dust scavenges in the atmosphere have an important impact on the marine Cd and Pb cycles. The student will furthermore study, how the cycling of these elements in the ocean is altered by changing oxygen concentrations. Oxygen is (next to the nutrients) another important player in biogeochemical cycles, and its solubility in seawater is temperature dependent. Climate models predict that extended zones with low oxygen concentrations will develop in the future oceans. Another important aspect of the ocean system is that ocean currents are the key mechanism for distributing heat, and thus they have a significant impact on regional and local climate. Furthermore, water mass movements (both vertical and lateral) are very important for the carbon cycle, as the deep ocean contains 50-60 times more carbon than the atmosphere. Today we can monitor ocean circulation by measuring the physical properties of seawater. Observations over the past 50 years, however, do not give us any clear indication whether the pattern of ocean circulation is changing. From studies of the past we know, however, that ocean water masses had a different configuration during the ice ages and past periods of extreme warmth. Neodymium isotopes in seawater are often used for such reconstructions, and the results show stunning relationships between past temperatures, carbon dioxide levels, and ocean circulation. A patchy understanding the modern Nd cycle however limits our confidence in such reconstructions, and thus our ability to transfer the inferred mechanisms to future models. In particular, it is generally assumed that away from ocean margins, Nd isotopes are an ideal ocean circulation tracer as they are only modified by mixing between water masses. However, there are many potential marine processes, which may not be in accord with this simplistic view. Such uncertainties will be addressed by the current project, based on a comprehensive suite of new observational data that will be collected for samples from strategic locations in the Atlantic Ocean. In conjunction with modelling efforts, our new data will shed light on the processes governing the marine Nd cycle and the suitability of Nd isotopes as circulation tracer.

The COVID-19 pandemic is having substantial consequences on UK and global food and nutrition security (FNS). This project will undertake world-leading research to provide government, business and decision makers with the evidence that they need to develop a robust FNS response to the current pandemic. The pandemic is causing major shocks to the four pillars of FNS: access; availability; utilisation and stability. Examples include reductions in productivity (labour limitations), breakdown of norms of food systems (distribution, changed demand) and supply chain restrictions (e.g. shortages of agri-chemicals for crop management). Economic impacts are altering both supply, distribution and demand. Collectively these shocks are substantially altering food systems whilst in the longer-term normal processes of trade may not adapt appropriately leading to changes in the balance of traded commodities, reduction in food reserves and price increases. The issue of FNS is relevant to all members of society, particularly for those most vulnerable to shortages or price increases. The food sector is also a major part of the UK economy, as it contributes approximately £111 billion a year and accounts for over 13% of national employment. It is the UK's largest manufacturing sector. The project focusses on UK FNS which is heavily dependent on global markets. Nearly half of the food we consume is imported and UK livestock industries rely heavily on imported feed. Some countries have already restricted exports in order to supply home markets. Normal market forces, transportation and distribution networks may no longer be appropriate to provide national requirements. A priority is to understand how to increase capacity for self-reliance to maintain civic stability, a healthy population and to understand the ramifications for third countries. The aim of this study is to conduct an initial rapid FNS risk assessment and explore options for changes in agricultural production, trade and distribution to protect FNS without jeopardising wider ecological and climate goals. The Research Programme will deliver seven key outputs: 1. Report on rapid risk assessment of the global food system considering how direct and indirect COVID-19 impacts and responses are propagating risks to food and nutrition security. 2. Report on Rapid risk assessment of UK food system responses and vulnerabilities and consequences on access, availability, utilisation and stability. 3. A set of plausible scenarios to explore the cascading risks and consequences of pandemic impacts on food sand nutrition security. 4. Report on alternative land use and management options that will increase resilience. 5. Report and maps of the spatial assessment of the alternative land use and management options. 6. Report including infographics reviewing lessons learned from the pandemic to improve Food and Nutrition Security. 7. Two workshops and other dissemination events and report with recommendations. The knowledge and foresight generated will be applicable to and of value across multiple sectors of the economy. It will inform policy support and development within UK and devolved Governments and help industry and business make informed decisions and plan adaptations. Information generated will support the UK's strong position in global trade. Identifying data gaps now will enable improved monitoring of impacts, both at UK and global scales.

United States

Clinical trials are research studies involving patients or healthy volunteers which aim to test whether a new treatment is safe and 'better' than current treatment. Clinical trials are grouped into stages (or phases) and researchers aim to answer different questions at each of the phases. The earliest of these, Phase I, aims to test whether a treatment is safe, to investigate side effects and to and to recommend a dose of the treatment for further testing. Phase I trials involve small numbers of participants who may be healthy volunteers or patients. The first group of participants in a phase I trial are given a low dose of treatment and if shown to be safe and without many side effects, the next group of participants are given a higher dose. Further groups of participants are enrolled; with the dose, being raised for each successive group until a dose is reached that has too many negative side effects. The decision whether to give patients the same, a higher, or lower dose of treatment is carefully made before the treatment is given. These trials are called "dose-escalation" or "dose-finding" trials. Once a clinical trial is complete, the results are reported to the clinical research community and to the public. To make sure that these reports are reliable and helpful for further research, a set of guidelines of the important items to be reported, Consolidated Standards of Reporting Trials (or CONSORT for short) have been published. It sets out a standard way for authors to report how the trial is designed, analysed and interpreted and has been instrumental in promoting transparent reporting. The original CONSORT guidelines were developed for specific types of trials and their design features often differ from dose-finding trials. This is important as currently trial reports of Phase I trials often miss out important information about how they were designed and conducted, which can make it difficult for the reader to interpret and gauge the validity of the trials. This wastes time and resources, but more importantly, may unethically expose participants to ineffective or even harmful interventions. Making the best decisions in a Phase I trial, on whether to give a patient the same dose, or a higher or lower dose, is key to the success of the trial. The statistical methods used to guide these decisions have advanced significantly over the past 25 years, so that safer trials with more reliable results can be conducted. But these methods are often complex, and have additional transparency and reporting demands. To address these problems, we will develop an 'extension' to the CONSORT guidelines, which is relevant to all early phase dose-finding designs in different diseases. The main CONSORT Statement has now been extended in 7 other design areas, primarily in later phase trials (www.consort-statement.org/extensions). A CONSORT extension for dose-finding trials is long overdue. To develop an internationally agreed way to report such trials, we have brought together a multi-disciplinary, international team of experts in the design, running and reporting of early phase trials who work in academic institutions or pharmaceutical industry, and those with expertise in developing reporting guidelines of trials. Finally, to ensure that the developed CONSORT extension will be widely adopted, we will involve key groups throughout this research: the trial community, journal editors (who publish articles on dose-finding trials), peer reviewers (who assess research papers), regulators, patients and the public. We will publicise our outputs at relevant meetings and to local/national Patient and Pubic Involvement (PPI) groups, and will use social media to raise awareness. We will conduct practical workshops, highlighting common reporting flaws and how to use the new guideline. We will co-produce two lay papers with our PPI representative to effectively involve, engage and inform patients and the public about the importance of this work.

In Asia and West Africa the majority of rain falls during the summer monsoon season. Monsoon rain is vital for agriculture, and a late or weak monsoon can mean disaster for crops, to the point where the Indian finance minister once described the monsoon as the country's 'real finance minister'. However, while we have a strong conceptual understanding of climatic changes controlled by thermodynamics (e.g. temperature, sea level), changes controlled by wind patterns (e.g. regional precipitation) are far less intuitive. State-of-the-art models struggle to correctly simulate patterns of monsoon rainfall in the present day, and predict a range of future changes. Without basic understanding of the wind circulations controlling the monsoons it is impossible to judge which predictions we can trust, both seasonally and under global warming. Recently, major advances have been made in our understanding of the mechanisms controlling the monsoons by using very abstract model configurations: aquaplanets (planets covered only in water) and simulations including simple continents. By stripping back the complexity of the real world, these models have at last given us basic theories for the controls on when and where zonal-mean tropical rain falls. However, these successful theories have in general not yet been adapted to the regional scale, and this presents an enormous opportunity for a step-change in our fundamental understanding of regional monsoons, their variability and response to climate change. To address the challenge of connecting theory to reality, we have identified a novel approach combining machine learning methods with a hierarchy of model simulations and data. The model hierarchy will allow us to study how monsoon circulations behave and theory performs as complexity increases. In particular, we will make use of a new, highly-configurable idealised climate model, Isca, which allows us to run simulations ranging from very simple aquaplanets up to a simplified model of Earth within a single, consistent framework. A major challenge in understanding regional monsoons is that the mathematics underpinning theory becomes highly complex at a local scale. However, machine learning has recently been applied to similar problems in oceanic science to identify regions governed by different key processes. We will use these techniques to simplify the mathematics and develop regional theories for monsoon rainfall. Theories appropriate to each region will be used to interpret the behaviour of the latest state-of-the-art climate models. We will use both simulations of past and future climate, and more idealised simulations targeted at identifying differences between models in simulating processes contributing to climate change (e.g. sea ice, plant physiology). This should help in understanding biases in simulations of historical climate and constraining intermodel differences in projections of climate under global warming. By identifying which models can be trusted to simulate the monsoons and the drivers of future changes, it should be possible to produce more robust and useable projections for these key regions. The final phase of the project will test whether different theories are needed to understand monsoon behaviour on different timescales. Do theories for climatological rainfall also explain rainfall variations week-to-week, or decade-to-decade? Do these processes have a lead time which could provide information for subseasonal-to-seasonal or decadal forecasting? Can theoretical insight help us untangle how decadal variations in sea surface temperature modulate the processes governing interannual variability in monsoon rain? By approaching these complex problems from a new perspective, Bridge aims to at last build the same level of confidence in our predictions of circulation-governed monsoon rainfall as we have in thermodynamically controlled climate features.